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Introduction: Golden pompano (Trachinotus ovatus) is economically significant important for offshore cage aquaculture in China and Southeast Asian countries. Lack of high-quality genomic data and accurate gene annotations greatly restricts its genetic breeding progress. Objectives: To decode the mechanisms of sex determination and rapid growth in golden pompano and facilitate the sex- and growth-aimed genetic breeding. Methods: Genome assemblies of male and female golden pompano were generated using Illumina, PacBio, BioNano, genetic maps and Hi-C sequencing data. Genomic comparisons, whole genome re-sequencing of 202 F1 individuals, QTL mapping and gonadal transcriptomes were used to analyze the sex determining region, sex chromosome evolution, SNP loci, and growth candidate genes. Zebrafish model was used to investigate the functions of growth candidate gene. Results: Female (644.45 Mb) and male (652.12 Mb) genomes of golden pompano were assembled and annotated at the chromosome level. Both genomes are highly conserved and no new or highly differentiated sex chromosomes occur. A 3.5 Mb sex determining region on LG15 was identified, where Hsd17b1, Micall2 and Lmx1a were putative candidates for sex determination. Three SNP loci significantly linked to growth were pinpointed, and a growth-linked gene gpsstr1 was identified by locus BSNP1369 (G → C, 17489695, Chr23). Loss of sstr1a (homologue of gpsstr1) in zebrafish caused growth retardation. Conclusion: This study provides insights into sex chromosome evolution, sex determination and rapid growth of golden pompano.

Abstract Objective This study aims to present a case of persistent mycetoma caused by Scedosporium boydii and undertake a systematic literature overview to elucidate the clinical characteristics and antifungal treatment exhibited by such patients. Methods We report the case of a 24-year-old female who sustained a Scedosporium boydii infection in her right foot over a decade ago following a nail puncture. Concurrently, a comprehensive literature overview was conducted on PubMed, focusing on documented cases of Scedosporium boydii infections with the intent of extracting relevant clinical data. Results Our analysis revealed that post-transplantation, trauma, near drowning, corticosteroid administration, and prior surgical history were the main risk factors for Scedosporium boydii infection. Prevalent infection sites included skin/bone tissues, the central nervous system, and ocular regions. Among the 49 patients identified, 24 received itraconazole therapy and 25 received voriconazole, with no significant difference in patient outcomes (P = 0.158). Of these, 12 patients experienced treatment failure. Notably, prolonged antifungal treatment duration was identified as a protective factor against mortality in Scedosporium boydii infections [P = 0.022, OR(95%CI): 0.972(0.949–0.996)]. Conversely, a history of post-transplantation emerged as a potential risk factor for mortality[P = 0.046, OR(95%CI): 7.017(1.034–47.636)]. Conclusion While uncommon, Scedosporium boydii infections carry a significant burden of morbidity and adverse outcomes. Heightened clinical vigilance is warranted in individuals presenting with risk factors for this pathogen. Timely and effective antifungal intervention is crucial, with both voriconazole and itraconazole demonstrating positive treatment outcomes for Scedosporium boydii infection. Therefore, prioritizing these antifungal agents should be considered a key therapeutic strategy in the management of this patient population.

Abstract Wild germplasm resources are crucial for gene mining and molecular breeding because of their special trait performance. Haplotype-resolved genome is an ideal solution for fully understanding the biology of subgenomes in highly heterozygous species. Here, we surveyed the genome of a wild walnut tree from Gongliu County, Xinjiang, China, and generated a haplotype-resolved reference genome of 562.99 Mb (contig N50 = 34.10 Mb) for one haplotype (hap1) and 561.07 Mb (contig N50 = 33.91 Mb) for another haplotype (hap2) using PacBio high-fidelity (HiFi) reads and Hi-C technology. Approximately 527.20 Mb (93.64%) of hap1 and 526.40 Mb (93.82%) of hap2 were assigned to 16 pseudochromosomes. A total of 41039 and 39744 protein-coding gene models were predicted for hap1 and hap2, respectively. Moreover, 123 structural variations (SVs) were identified between the two haplotype genomes. Allele-specific expression genes (ASEGs) that respond to cold stress were ultimately identified. These datasets can be used to study subgenome evolution, for functional elite gene mining and to discover the transcriptional basis of specific traits related to environmental adaptation in wild walnut.

ObjectiveThe effect of atrial fibrillation (AF) patterns on outcomes remains controversial. This study aims to evaluate the influence of AF type on the risk of cardiocerebrovascular events after left atrial appendage closure (LAAC) at long-term follow-up.MethodsAF was categorized as paroxysmal AF (PAF) and non-PAF (NPAF). The baseline characteristics, procedural data, peri-procedural complications, and long-term outcomes between patients with PAF and NPAF after LAAC were compared.ResultsWe analyzed 410 AF patients (mean age 74.8 ± 8.2 years; 271 male; 144 with PAF, 266 NPAF). The NPAF group tended to be older (≥75 years), male, and have chronic kidney disease (CKD) compared with the PAF group. The procedural data and peri-procedural complications were comparable. During 2.2 ± 1.5 years of follow-up, the incidences of thromboembolism, major bleeding, and device-related thrombus (DRT) did not differ between the two groups. The observed risk of thromboembolism and major bleeding was significantly lower than the estimated risk based on the CHA2DS2-VASc and HAS-BLED scores, respectively, in patients who underwent LAAC, regardless of the AF type. NPAF patients were associated with a higher risk of all-cause mortality, non-cardiovascular mortality, and combined efficacy endpoints. This association disappeared after propensity score matching (PSM) analysis.ConclusionsThe risk of thromboembolism and major bleeding was lower in patients who underwent LAAC, regardless of the AF type. Although NPAF often coexists with multiple risk factors, it was not associated with worse long-term outcomes after LAAC when compared with PAF.

Nangqian grey yak (Bos grunniens) is a unique yak population in Qinghai Province, China. In this study, the whole mitogenome sequences of 18 Nangqian grey yaks were sequenced based on the next-generation sequencing (NGS) technology and annotated. The total length of whole mitogenome sequence is between 16.323 bp and 16.325 bp, including a non-coding control region (D-loop region), 22 tRNA genes, 13 protein-coding genes and two rRNA genes (12S rRNA and 16S rRNA). Maternal genetic diversity based on the mitogenome variations was analyzed. A total of 12 haplotypes were identified among 18 complete mitogenome sequences, the haplotype diversity and nucleotide diversity of Nangqian grey yak were 0.948±0.033 and 0.001±0.001, respectively. Compared with the wild yak population and six other domestic yak breeds/populations in China, the haplotype diversity of Nangqian grey yak population was higher, indicating abundant maternal genetic diversity in Nangqian grey yak. The phylogenetic tree showed that Nangqian grey yak was most closely related to Tibet alpine, Xueduo, Changtai, Sibu, Zhongdian, Tianzhu white, Ashdan, Jinchuan, Jiulong, Pamir, Pali, Qinghai plateau, Huanhu, Datong, Bazhou and wild yak breeds/populations, closer to Chawula, Muli, Gannan, Niangya and Yushu yak breeds, but far away from other yak breeds (i.e. Leiwuqi and Maiwa yak).

Abstract Background Mesenchymal stem cell (MSC) therapy is an attractive treatment option for various cancers. Whether MSCs can be used to treat well-differentiated endometrial cancer (EC) remains unclear. The aim of this study is to explore the potential therapeutic effects of MSCs on EC and the underlying mechanisms. Methods The effects of adipose-derived MSCs (AD-MSCs), umbilical-cord-derived MSCs (UC-MSCs), and endometrium-derived MSCs (eMSCs) on the malignant behaviors of EC cells were explored via in vitro and in vivo experiments. Three EC models, including patient-derived EC organoid lines, EC cell lines, and EC xenograft model in female BALB/C nude mice, were used for this study. The effects of MSCs on EC cell proliferation, apoptosis, migration, and the growth of xenograft tumors were evaluated. The potential mechanisms by which eMSCs inhibit EC cell proliferation and stemness were explored by regulating DKK1 expression in eMSCs or Wnt signaling in EC cells. Results Our results showed that eMSCs had the highest inhibitory effect on EC cell viability, and EC xenograft tumor growth in mice compared to AD-MSCs and UC-MSCs. Conditioned medium (CM) obtained from eMSCs significantly suppressed the sphere-forming ability and stemness-related gene expression of EC cells. In comparison to AD-MSCs and UC-MSCs, eMSCs had the highest level of Dickkopf-related protein 1 (DKK1) secretion. Mechanistically, eMSCs inhibited Wnt/β-catenin signaling in EC cells via secretion of DKK1, and eMSCs suppressed EC cell viability and stemness through DKK1-Wnt/β-catenin signaling. Additionally, the combination of eMSCs and medroxyprogesterone acetate (MPA) significantly inhibited the viability of EC organoids and EC cells compared with eMSCs or MPA alone. Conclusions The eMSCs, but not AD-MSCs or UC-MSCs, could suppress the malignant behaviors of EC both in vivo and in vitro via inhibiting the Wnt/β-catenin signaling pathway by secreting DKK1. The combination of eMSCs and MPA effectively inhibited EC growth, indicating that eMSCs may potentially be a new therapeutic strategy for young EC patients desiring for fertility preservation.

Asherman’s syndrome is an endometrial regeneration disorder resulting from injury to the endometrial basal layer, causing the formation of scar tissue in the uterus and cervix. This usually leads to uterine infertility, menstrual disorders, and placental abnormalities. While stem cell therapy has shown extensive progress in repairing the damaged endometrium and preventing intrauterine adhesion, issues of low engraftment rates, rapid senescence, and the risk of tumorigenesis remain to be resolved for efficient and effective application of this technology in endometrial repair. This study addressed these challenges by developing a co-culture system to generate multi-lineage endometrial organoids (MLEOs) comprising endometrial epithelium organoids (EEOs) and endometrial mesenchymal stem cells (eMSCs). The efficacy of these MLEOs was investigated by seeding them on a biocompatible scaffold, the human acellular amniotic membrane (HAAM), to create a biological graft patch, which was subsequently transplanted into an injury model of the endometrium in rats. The results indicated that the MLEOs on the HAAM patch facilitated endometrial angiogenesis, regeneration, and improved pregnancy outcomes. The MLEOs on the HAAM patch could serve as a promising strategy for treating endometrial injury and preventing Asherman’s syndrome.

BackgroundStudies investigating the cardioprotective effect of volatile anesthetics on cardiac troponins in off-pump coronary artery bypass grafting (OPCAB) surgery remain controversial. This current study was conducted to systematically evaluate the impact of volatile anesthetics and propofol on patients undergoing OPCAB surgery.MethodsA computerized search of electronic databases was conducted up to July 21, 2023, to identify relevant studies using appropriate search terms. The primary outcomes of interest were the levels of myocardial injury biomarkers (e.g., cTnI, cTnT), while secondary outcomes included extubation time, length of ICU stay, 30-day mortality, transfusion and thrombosis, and postoperative recovery, which were compared between two anesthesia techniques.ResultsA search of databases produced 14 relevant studies with a combined total of 703 patients. Among them, 355 were allocated to the volatile anesthetics group and 348 to the propofol group. Our study reveals a statistically significant reduction in myocardial injury biomarkers among patients who received volatile anesthetics compared to those who received propofol (P 0.05). There was no significant difference in postoperative mechanical ventilation time, length of ICU stay, and mortality between the two groups (all P > 0.05).ConclusionsThis study suggested that volatile anesthetics, specifically sevoflurane, in adult OPCAB surgery provide a better cardioprotective effect than propofol.Systematic Review RegistrationPROSPERO (CRD42023444277).

Abstract Exercise recommendation is an integral part of enabling personalized learning. Giving appropriate exercises can facilitate learning for learners. The programming problem recommendation is a specific application of the exercise recommendation. Therefore, an innovative recommendation framework for programming problems that integrate learners’ learning styles is proposed. In addition, there are some difficulties to be solved in this framework, such as quantifying learning behavior, representing programming problems, and quantifying learning strategies. For the difficulties in quantifying learning behavior and quantifying learning strategies, a programming problem recommendation algorithm based on deep reinforcement learning (DRLP) is proposed. DRLP includes the specific design of action space, action-value Q-network, and reward function. Learning style is embedded into DRLP through action space to make recommendations more personalized. To represent the programming problem in DRLP, a multi-dimensional integrated programming problem representation model is proposed to quantify the difficulty feature, knowledge point feature, text description, input description, and output description of programming problems. In particular, Bi-GRU is introduced to learn texts’ contextual semantic association information from both positive and negative directions. Finally, a simulation experiment is carried out with the actual learning behavior data of 47,147 learners in the LUOGU Online Judge system. Compared with the optimal baseline model, the recommendation effect of DRLP has improved (HR, MRR, and Novelty have increased by 4.35%, 1.15%, and 1.1%), which proves the rationality of the programming problem representation model and action-value Q-network.

Many aspects of the tumourigenesis of endometrioid endometrial cancers (EEC) are still poorly understood. Here, the authors use single-cell transcriptomics to characterise EEC tumours and their microenvironment across different stages, and reveal potential cells of origin for EEC.

Comparisons of genomic and methylomic changes during the conservation of indigenous chicken breeds in China provide insight into conservation programmes for these breeds and their adaptations to unique environments.

BackgroundPatient portals not only provide patients with access to electronic health records (EHRs) and other digital health services, such as prescription renewals, but they can also improve patients’ self-management, engagement with health care professionals (HCPs), and care processes. However, these benefits depend on patients’ willingness to use patient portals and, ultimately, their experiences with the usefulness and ease of use of the portals. ObjectiveThis study aimed to investigate the perceived usability of a national patient portal and the relationship of patients’ very positive and very negative experiences with perceived usability. The study was aimed to be the first step in developing an approach for benchmarking the usability of patient portals in different countries. MethodsData were collected through a web-based survey of the My Kanta patient portal’s logged-in patient users in Finland from January 24, 2022, to February 14, 2022. Respondents were asked to rate the usability of the patient portal, and the ratings were used to calculate approximations of the System Usability Scale (SUS) score. Open-ended questions asked the patients about their positive and negative experiences with the patient portal. The statistical analysis included multivariate regression, and the experience narratives were analyzed using inductive content analysis. ResultsOf the 1,262,708 logged-in patient users, 4719 responded to the survey, giving a response rate of 0.37%. The patient portal’s usability was rated as good, with a mean SUS score of 74.3 (SD 14.0). Reporting a very positive experience with the portal was positively associated with perceived usability (β=.51; P

The design of a reasonable heterostructure electrode to achieve enhanced areal performance for supercapacitors remains a great challenge. Here, we constructed hierarchical porous NiCoP/NiO nanocomposites anchored on Ni foam with tunable electronic and structural properties, as well as robust interfacial interaction. In NiCoP/NiO, the interconnected NiO nanosheets serve as a carrier with enriched anchoring sites to confine the NiCoP and improve its stability. Meanwhile, the ultrathin NiCoP nanosheets with bimetallic centers are connected with porous NiO nanosheets to form a reliable heterojunction, enhancing the electrochemical reaction kinetics. Taking advantage of the synergistic contribution of bimetallic centers, phosphides and unique structure, the NiCoP/NiO delivers a high areal specific capacitance (1860 mF cm−2 at 5 mA cm−2), good rate performance of 78.5% at six times the increased current density, and remarkable durability (11.0% decrease after 10,000 cycles). Furthermore, the assembled hybrid supercapacitor NiCoP/NiO//porous-activated carbon (PAC) delivers a high areal energy density of 173.7 μWh cm−2 (116.4 μWh cm−2) at 1.6 mW cm−2 (32 mW cm−2). The results indicate that the design of the heterostructure interface with strong chemical interface and tunable electronic structure is an effective and promising approach to boost the electrochemical performance for advanced supercapacitors.

Abstract Background The rapid emergence and global spread of COVID-19 have caused substantial global disruptions that have impacted malaria programs worldwide. Innovative strategies to enable countries aiming to eliminate malaria as well as those that are already certified as malaria-free, are needed to address malaria importation in the context of the COVID-19 pandemic. China was certified as malaria-free in 2021 and now aims to prevent the malaria re-establishment. Nonpharmaceutical interventions such as entry screening, quarantining, and health education for individuals returning from international travel during the COVID-19 pandemic present both opportunities and challenges to the management of imported malaria. This study aimed to describe and analyze the operational challenges associated with an integrated surveillance and case management program in which malaria re-establishment prevention measures were incorporated into the COVID-19 program in China. Methods After the integration of malaria re-establishment prevention activities into the COVID-19 program for 10 months in Jiangsu Province, China, a focus-group discussion of public health workers working on preventing malaria re-establishment and controlling COVID-19 was held in June 2021, aiming to explore the operational challenges and lessons learned from the integrated approach. Results From 01 August 2020 to 31 May 2021, 8,947 overseas travelers with Yangzhou as the final destination underwent 14-day managed quarantine and 14-day home isolation. Of these travelers, 5,562 were from malaria-endemic regions. A total of 26,026 education booklets and materials were distributed to expand malaria-related knowledge. Twenty-two patients with unknown fever were screened for malaria with rapid diagnostic tests, and one patient was confirmed to have imported malaria. The challenges associated with the implementation of the integrated malaria surveillance and case management program include neglect of malaria due to COVID-19, lack of a standard operating procedure for malaria screening, mobility of public health providers, and difficulties in respecting the timeline of the “1–3-7” surveillance strategy. Conclusions China’s experience highlights the feasibility of integrated case surveillance and management of existing infectious diseases and new emerging infections. It also demonstrates the importance of a sound public health infrastructure with adequate, trained field staff for screening, testing, contact tracing, and providing health education, all of which are crucial for the success of both malaria re-establishment prevention program and the effective control of COVID-19.

FCS-like zinc finger (FLZ) is a plant-specific gene family that plays an important regulatory role in plant growth and development and its response to stress. However, studies on the characteristics and functions of cotton FLZ family genes are still lacking. This study systematically identified members of the cotton FLZ gene family based on cotton genome data. The cotton FLZ family genes were systematically analyzed by bioinformatics, and their expression patterns in different tissues and under low-temperature stress were analyzed by transcriptome and qRT–PCR. The G. hirsutum genome contains 56 FLZ genes distributed on 20 chromosomes, and most of them are located in the nucleus. According to the number and evolution analysis of FLZ family genes, FLZ family genes can be divided into five subgroups in cotton. The G. hirsutum FLZ gene has a wide range of tissue expression types, among which the expression is generally higher in roots, stems, leaves, receptacles and calyx. Through promoter analysis, it was found that it contained the most cis-acting elements related to methyl jasmonate (MeJA) and abscisic acid (ABA). Combined with the promoter and qRT–PCR results, it was speculated that GhFLZ11, GhFLZ25, GhFLZ44 and GhFLZ55 were involved in the response of cotton to low-temperature stress. Taken together, our findings suggest an important role for the FLZ gene family in the cotton response to cold stress. This study provides an important theoretical basis for further research on the function of the FLZ gene family and the molecular mechanism of the cotton response to low temperature.

Abstract Temperature tolerance is an important trait from both an economic and evolutionary perspective in fish. Because of difficulties with measurements, genome-wide selection using quantitative trait loci (QTLs) affecting Upper temperature tolerance may be an alternative for genetic improvement. Turbot Scophthalmus maximus (L.) is a cold-water marine fish with high economic value in Europe and Asia. The genetic bases of upper temperature tolerance (UTTs) traits have been rarely studied. In this study, we constructed a genetic linkage map of turbot using simple sequence repeats (SSRs) and single nucleotide polymorphism (SNP) markers. A total of 190 SSR and 8,123 SNP were assigned to 22 linkage groups (LGs) of a consensus map, which spanned 3,648.29 cM of the turbot genome, with an average interval of 0.44 cM. Moreover, we re-anchored genome sequences, allowing 93.8% physical sequences to be clustered into 22 turbot pseudo-chromosomes. A high synteny was observed between two assemblies from the literature. QTL mapping and validation analysis identified thirteen QLTs which are major effect QTLs, of these, 206 linked SNP loci, and two linked SSR loci were considered to have significant QTL effects. Association analysis for UTTs with 129 QTL markers was performed for different families, results showed that eight SNP loci were significantly correlated with UTT, which markers could be helpful in selecting thermal tolerant breeds of turbot. 1,363 gene sequences were genomically annotated, and 26 QTL markers were annotated. We believe these genes could be valuable candidates affecting high temperatures, providing valuable genomic resources for the study of genetic mechanisms regulating thermal stress. Similarly, they may be used in marker-assisted selection (MAS) programs to improve turbot performance.

Abstract Background Early recurrence is the major cause of poor prognosis in hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are deeply involved in HCC prognosis. In this study, we aimed to establish a prognostic lncRNA signature for HCC early recurrence. Methods The lncRNA expression profile and corresponding clinical data were retrieved from total 299 HCC patients in TCGA database. LncRNA candidates correlated to early recurrence were selected by differentially expressed gene (DEG), univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. A 25-lncRNA prognostic signature was constructed according to receiver operating characteristic curve (ROC). Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the performance of this signature. ROC and nomogram were used to evaluate the integrated models based on this signature with other independent clinical risk factors. Gene set enrichment analysis (GSEA) was used to reveal enriched gene sets in the high-risk group. Tumor infiltrating lymphocytes (TILs) levels were analyzed with single sample Gene Set Enrichment Analysis (ssGSEA). Immune therapy response prediction was performed with TIDE and SubMap. Chemotherapeutic response prediction was conducted by using Genomics of Drug Sensitivity in Cancer (GDSC) pharmacogenomics database. Results Compared to low-risk group, patients in high-risk group showed reduced disease-free survival (DFS) in the training (p

Abstract Background Lycium Linn. (Solanaceae) is a genus of economically important plants producing fruits and leaves with high nutritional value and medicinal benefits. However, genetic analysis of this plant and molecular breeding for quality improvement are limited by the lack of sufficient molecular markers. Results In this study, two parental strains, ‘Ningqi No. 1’ (Lycium barbarum L.) and ‘Yunnan Gouqi’ (Lycium yunnanense Kuang et A.M. Lu), and 200 F1 hybrid individuals were resequenced for genetic analysis. In total, 8,507 well-selected SNPs were developed, and a high-density genetic map (NY map) was constructed with a total genetic distance of 2,122.24 cM. A consensus genetic map was established by integrating the NY map and a previously published genetic map (NC map) containing 15,240 SNPs, with a total genetic distance of 3,058.19 cM and an average map distance of 0.21 cM. The 12 pseudochromosomes of the Lycium reference genome were anchored using this consensus genetic map, with an anchoring rate of 64.3%. Moreover, weak collinearities between the consensus map and the pepper, potato, and tomato genomes were observed. Twenty-five stable QTLs were identified for leaf- and fruit-related phenotypes, including fruit weight, fruit longitude, leaf length, the fruit index, and the leaf index; these stable QTLs were mapped to four different linkage groups, with LOD scores ranging from 2.51 to 19.37 and amounts of phenotypic variance explained from 6.2% to 51.9%. Finally, 82 out of 188 predicted genes underlying stable QTLs for fruit-related traits were differentially expressed according to RNA-seq analysis. Conclusions A chromosome-level assembly can provide a foundation for further functional genomics research for wolfberry. The genomic regions of these stably expressed QTLs could be used as targets for further fine mapping and development of molecular markers for marker-assisted selection (MAS). The present study provided valuable information on saturated SNP markers and reliable QTLs for map-based cloning of functional genes related to yield and morphological traits in Lycium spp.

Melatonin widely mediates multiple developmental dynamics in plants as a vital growth stimulator, stress protector, and developmental regulator. N-acetylserotonin methyltransferase (ASMT) is the key enzyme that catalyzes the final step of melatonin biosynthesis in plants and plays an essential role in the plant melatonin regulatory network. Studies of ASMT have contributed to understanding the mechanism of melatonin biosynthesis in plants. However, AMST gene is currently uncharacterized in most plants. In this study, we characterized the JrASMT gene family using bioinformatics in a melatonin-rich plant, walnut. Phylogenetic, gene structure, conserved motifs, promoter elements, interacting proteins and miRNA analyses were also performed. The expansion and differentiation of the ASMT family occurred before the onset of the plant terrestrialization. ASMT genes were more differentiated in dicotyledonous plants. Forty-six ASMT genes were distributed in clusters on 10 chromosomes of walnut. Four JrASMT genes had homologous relationships both within walnut and between species. Cis-regulatory elements showed that JrASMT was mainly induced by light and hormones, and targeted cleavage of miRNA172 and miR399 may be an important pathway to suppress JrASMT expression. Transcriptome data showed that 13 JrASMT were differentially expressed at different periods of walnut bud development. WGCNA showed that JrASMT1/10/13/23 were coexpressed with genes regulating cell fate and epigenetic modifications during early physiological differentiation of walnut female flower buds. JrASMT12/28/37/40 were highly expressed during morphological differentiation of flower buds, associated with altered stress capacity of walnut flower buds, and predicted to be involved in the regulatory network of abscisic acid, salicylic acid, and cytokinin in walnut. The qRT-PCR validated the results of differential expression analysis and further provided three JrASMT genes with different expression profiles in walnut flower bud development. Our study explored the evolutionary relationships of the plant ASMT gene family and the functional characteristics of walnut JrASMT. It provides a valuable perspective for further understanding the complex melatonin mechanisms in plant developmental regulation.

Sugarcane is one of the most important industrial crops globally. It is the second largest source of bioethanol, and a major crop for biomass-derived electricity and sugar worldwide. Smut, caused by Sporisorium scitamineum, is a major sugarcane disease in many countries, and is managed by smut-resistant varieties. In China, smut remains the single largest constraint for sugarcane production, and consequently it impacts the value of sugarcane as an energy feedstock. Quantitative trait loci (QTLs) associated with smut resistance and linked diagnostic markers are valuable tools for smut resistance breeding. Here, we developed an F1 population (192 progeny) by crossing two sugarcane varieties with contrasting smut resistance and used for genome-wide single nucleotide polymorphism (SNP) discovery and mapping, using a high-throughput genotyping method called “specific locus amplified fragment sequencing (SLAF-seq) and bulked-segregant RNA sequencing (BSR-seq). SLAF-seq generated 148,500 polymorphic SNP markers. Using SNP and previously identified SSR markers, an integrated genetic map with an average 1.96 cM marker interval was produced. With this genetic map and smut resistance scores of the F1 individuals from four crop years, 21 major QTLs were mapped, with a phenotypic variance explanation (PVE) > 8.0%. Among them, 10 QTLs were stable (repeatable) with PVEs ranging from 8.0 to 81.7%. Further, four QTLs were detected based on BSR-seq analysis. aligning major QTLs with the genome of a sugarcane progenitor Saccharum spontaneum, six markers were found co-localized. Markers located in QTLs and functional annotation of BSR-seq-derived unigenes helped identify four disease resistance candidate genes located in major QTLs. 77 SNPs from major QTLs were then converted to Kompetitive Allele-Specific PCR (KASP) markers, of which five were highly significantly linked to smut resistance. The co-localized QTLs, candidate resistance genes, and KASP markers identified in this study provide practically useful tools for marker-assisted sugarcane smut resistance breeding.

The gardenia is a traditional medicinal horticultural plant in China, but its molecular genetic research has been largely hysteretic. Here, we constructed an F1 population with 200 true hybrid individuals. Using the genotyping-by-sequencing method, a high-density sex-average genetic map was generated that contained 4,249 SNPs with a total length of 1956.28 cM and an average genetic distance of 0.46 cM. We developed 17 SNP-based Kompetitive Allele-Specific PCR markers and found that 15 SNPs were successfully genotyped, of which 13 single-nucleotide polymorphism genotypings of 96 F1 individuals showed genotypes consistent with GBS-mined genotypes. A genomic collinearity analysis between gardenia and the Rubiaceae species Coffea arabica, Coffea canephora and Ophiorrhiza pumila showed the relativity strong conservation of LG11 with NC_039,919.1, HG974438.1 and Bliw01000011.1, respectively. Lastly, a quantitative trait loci analysis at three phenotyping time points (2019, 2020, and 2021) yielded 18 QTLs for growth-related traits and 31 QTLs for leaf-related traits, of which qBSBN7-1, qCD8 and qLNP2-1 could be repeatably detected. Five QTL regions (qCD8 and qSBD8, qBSBN7 and qSI7, qCD4-1 and qLLLS4, qLNP10 and qSLWS10-2, qSBD10 and qLLLS10) with potential pleiotropic effects were also observed. This study provides novel insight into molecular genetic research and could be helpful for further gene cloning and marker-assisted selection for early growth and development traits in the gardenia.

Currently, studies on the energy efficiency of manufacturing systems usually lack synthetic and systematic techniques. In this paper, a holistic framework is demonstrated in order to achieve more sustainable manufacturing, which covers machine-level, system-level and life-cycle-level energy efficiency techniques. Based on these, the mechanism of how energy consumption is affected by machining processes and system operation is analyzed to achieve a comprehensive decision on energy efficiency optimization. Four main topics are included in this paper: (1) Hierarchical sustainability goals and metrics for energy-efficient manufacturing; (2) Machine-level machining processes optimization for energy efficiency enhancement; (3) System-level innovations for efficient consumption management; (4) Life-cycle level energy flow modeling and energy recycling strategy. An automotive engine manufacturing system is taken as an example to build a concrete understanding of the application of the framework. Moreover, this holistic framework establishes the theoretical basis for promoting the energy efficiency of automotive engine manufacturing systems. Furthermore, the proposed techniques can provide decision-making support for achieving sustainable manufacturing in a wider scope of mechanical manufacturing.

Urate oxidase (uricase, Uox) is a big obstacle for scientists to establish stable animal models for studying hyperuricemia and associated disorders. Due to the low survival rate of uricase-deficient mice, we generated a Uox-knockout model animal from Sprague Dawley (SD) rats using the CRISPR/Cas9 technique by deleting exons 2 to 4 of the Uox gene. The uricase-deficient rats were named “Kunming-DY rats”, and were apparently healthy with more than a 95% survival up to one year. The male rats’ serum uric acid (SUA) increased to 48.3 ± 19.1 µg/ml, significantly higher than those of wild-type rats. Some indexes of the blood fat like total triglyceride, low density lipoprotein, and renal function indexes including blood urea nitrogen and serum creatinine were significantly different from those of wild-type rats, however, all the indexes were close to or in normal ranges. Histological renal changes including mild glomerular/tubular lesions were observed in these uricase-deficient rats. Thus, “Kunming-DY rats” with stable uricase-deficiency were successfully established and are an alternative model animal to study hyperuricemia and associated diseases mimicking human conditions.

According to the 3GPP specification,a new self-organization network of smart pipe in mobile internet was addressed.By introducing integrated policy control function,the external signals were supervised periodically,and the best optimized network strategies were predicted by the recurrent neural network algorithm,delivered by PCRF,and updated automatically with feedback of the regulations.This solution was effectively applied in scenarios such as speed limit of large traffic users,network protection under high load,and online advertisement recommendation etc.

Abstract Background In the current scenario, the drug-resistant tuberculosis is a significant challenge in the control of tuberculosis worldwide. In order to investigate the in vivo evolution of drug-resistant M. tuberculosis, the present study envisaged sequencing of the draft genomes of 18 serial isolates from four pre-extensively drug-resistant (pre-XDR) tuberculosis patients for continuous genetic alterations. Results All of the isolates harbored single nucleotide polymorphisms (SNPs) ranging from 1303 to 1309 with M. tuberculosis H37Rv as the reference. SNPs ranged from 0 to 12 within patients. The evolution rates were higher than the reported SNPs of 0.5 in the four patients. All the isolates exhibited mutations at sites of known drug targets, while some contained mutations in uncertain drug targets including folC, proZ, and pyrG. The compensatory substitutions for rescuing these deleterious mutations during evolution were only found in RpoC I491T in one patient. Many loci with microheterogeneity showed transient mutations in different isolates. Ninety three SNPs exhibited significant association with refractory pre-XDR TB isolates. Conclusions Our results showed evolutionary changes in the serial genetic characteristics of the pre-XDR TB patients due to accumulation of the fixed drug-resistant related mutations, and the transient mutations under continuous antibiotics pressure over several years.

Trust-based celebrity user identification is the key to the industry's reputation for electronic word of mouth. However, trust and mistrust are independent and coexistent concepts. In this context, we need to consider the existence of the two kinds of user relations brought about by the impact. This paper analyzes the characteristics of trust and distrust in social networks, and gives formal descriptions of trust networks, untrusted networks, and mixed trust networks. Based on the indicators such as degree distribution, correlation coefficient, and matching coefficient, the structural properties of mixed trust networks are studied. Based on the PageRank algorithm, the HTMM metrics affecting users under the mixed trust network environment are proposed. Finally, the validity of HTMM is verified through a real data set containing trust and distrust. Experimental results show that the results of HTMM's celebrity user identification method still have a low level of trust.

As the causative bacteria of tuberculosis, Mycobacteriumtuberculosis (M. tb) is aggravated by the emergence of its multidrug-resistant isolates in China. Mutations of six of the most frequently reported resistant genes (rpoB, katG, inhA, embB, gyrA, and rpsL) were detected for rifampicin (RIF), isoniazid (INH), ethambutol (EMB), ofloxacin (OFX), and streptomycin (STR) in this study. The amino acid missense mutations (MMs) and their corresponding single nucleotide polymorphism mutations for all drug-resistant (DR) isolates are described in detail. All isolates were divided into non-extensively drug-resistant (Non-XDR) and preXDR/XDR groups. No statistical differences were detected among MMs and linked MMs (LMs) between the two groups, except for rpsL 88 (p = 0.037). In the preXDR/XDR group, the occurrence of MMs in rpoB, katG, and inhA developed phenotypic resistance and MMs of rpoB 531, katG 315, rpsL 43, and rpsL 88 could develop high levels of DR. It is necessary to carry out epidemiological investigations of DR gene mutations in the local region, and thus provide necessary data to support the design of new technologies for rapid detection of resistant M. tb and the optimization of detection targets.

Abstract Tuberculosis (TB) is considered as one of the most serious threats to public health in many parts of the world. The threat is even more severe in the developing countries where there is a lack of advanced medical amenities and contemporary anti-TB drugs. In such situations, dosage optimization of existing medication regimens seems to be the only viable option. Therapeutic drug monitoring study results suggest that high-dose treatment regimens can compensate the low serum concentration of anti-TB drugs and shorten the therapy duration. The article presents a critical review on the possible changes that occur in the host and the pathogen upon the administration of standard and high-dose regimens. Some of the most common factors that are responsible for low anti-TB drug concentrations in the serum are differences in hosts’ body weight, metabolic processing of the drug, malabsorption and/or drug–drug interaction. Furthermore, failure to reach the cavitary pulmonary and extrapulmonary tissues also contributes to the therapeutic inefficiency of the drugs. In such conditions, administration of higher doses can help in compensating the pathogenic outcomes of enhancement of the pathogen’s physical barriers, efflux pumps and genetic mutations. The present article also presents a summary of the recorded treatment outcomes of clinical trials that were conducted to test the efficacy of administration of high dose of anti-tuberculosis drugs. This review will help physicians across the globe to understand the underlying pathophysiological changes (including side effects) that dictate the clinical outcomes in patients administered with standard and/or high dose anti-TB drugs.

Purpose: Whole brain radiation therapy (WBRT) remains the standard of care for patients with multiple brain metastases, but more than half of treated patients will develop intracranial progression. Because there is no clear consensus on the optimal therapeutic approach, a prognostic index would be helpful to guide treatment options at progression. We explored whether the recursive partitioning analysis (RPA) score prior to repeat WBRT is predictive of survival. Methods and materials: This multi-institutional pooled analysis included patients with 2 or more brain metastases from any solid primary tumor that was treated with 2 courses of WBRT. Information on demographics, disease characteristics, and intervals between courses was collected. RPA class was abstracted or retrospectively assigned, and descriptive statistics calculated. Median survival (MS) was determined using the Kaplan-Meier method and compared using log rank tests. Univariate and multivariate analyses were performed via Cox regression analysis. Results: For 205 patients, the median age was 55 years (range, 25-83 years), 68% were female, 40.5% had non-small cell lung cancer, and 31.2% had small cell lung cancer. Prior to the second WBRT, 4.9% of patients were RPA class 1, 36.6% were RPA2, and 58.5% were RPA3, with an MS of 7.5 months (95% confidence interval [CI], 4.7-10.3), 5.2 months (95% CI, 3.7-6.7 months), and 2.9 months (95% CI, 2.2-2.9 months), respectively (P = .001). On univariate and multivariate analyses, a Karnofsky Performance Status of

Abstract Obesity is crucially involved in many metabolic diseases, such as type 2 diabetes, cardiovascular disease and cancer. Regulating the number or size of adipocytes has been suggested to be a potential treatment for obesity. In this study, we investigated the effect of pyrocincholic acid 3β-O-β-d-quinovopyranosyl-28-O-β-d-glucopyranoside (PAQG), a 27-nor-oleanolic acid saponin extracted from Metadina trichotoma, on adipogenesis and lipid metabolism in 3T3-L1 adipocytes. The 3T3-L1 pre-adipocytes were incubated with vehicle or PAQG for 6 days in differentiation process. PAQG significantly reduced the adipogenesis, adiponectin secretion and the expression level of key transcription factors related to adipogenesis, such as PPARγ, C/EBPβ, C/EBPα, and FABP4. Moreover, PAQG increased the levels of FFA and glycerol in medium and reduced TG level in mature adipocytes. Interestingly, PAQG not only promoted the activation of AMPK and genes involved in fatty oxidation including PDK4 and CPT1a, but also inhibited those genes involved in fatty acid biosynthesis, such as SREBP1c, FAS, ACCα and SCD1. In conclusion, PAQG inhibits the differentiation and regulates lipid metabolism of 3T3-L1 cells via AMPK pathway, suggesting that PAQG may be a novel and promising natural product for the treatment of obesity and hyperlipidemia. Graphical Abstract

Wolfberry (Lycium Linn. 2n = 24) fruit, Gouqizi, is a perennial shrub, traditional food and medicinal plant resource in China. Leaf and fruit related characteristics are economically important traits that are the focus for genetic improvement, but few studies into the molecular genetics of this crop have been reported to date. Here, an F1 population (302 individuals) derived from a cross between “NO.1 Ningqi” (Lycium barbarum L.) and “Chinese gouqi” (Lycium chinese Mill.) was constructed. We recorded fruit weight, longitude, diameter and index along with leaf length, width and index for three consecutive years from 2015 to 2017. Based on this population and these phenotypic data, we constructed the first high-density genetic map of Lycium using specific length amplified fragment sequencing (SLAF-seq) and analyzed quantitative trait loci (QTLs). The map contains 6733 single nucleotide polymorphisms and 12 linkage groups (LG) with a total map distance of 1702.45 cM and an average map distance of 0.253 cM. A total of 55 QTLs were mapped for more than 2 years, of which 18 stable QTLs for fruit index on LG 11, spanning an interval of 73.492–90.945 cM, were detected. qFI11-15 for fruit index was an impressive QTL with logarithm of odds (LOD) and proportion of variance explained (PEV) values reaching 11.07 and 19.7%, respectively. The QTLs on LG 11 were gathered tightly, having an average interval of less than 1 cM per QTL, suggesting that there might be a cluster region controlling fruit index. Remarkably, qLI10-2 and qLI11-2 for leaf index were detectable for 3 years. These results give novel insight into the genetic control of leaf and fruit related traits in Lycium and provide robust support for undertaking further positional cloning studies and implementing marker-assisted selection in seedlings.

Cross talk occurs between the human gut and the lung through a gut-lung axis involving the gut microbiota. However, the signatures of the human gut microbiota after active Mycobacterium tuberculosis infection have not been fully understood. Here, we investigated changes in the gut microbiota in tuberculosis (TB) patients by shotgun sequencing the gut microbiomes of 31 healthy controls and 46 patients. We observed a dramatic changes in gut microbiota in tuberculosis patients as reflected by significant decreases in species number and microbial diversity. The gut microbiota of TB patients were mostly featured by the striking decrease of short-chain fatty acids (SCFAs)-producingbacteria as well as associated metabolic pathways. A classification model based on the abundance of three species, Haemophilus parainfluenzae, Roseburia inulinivorans, and Roseburia hominis, performed well for discriminating between healthy and diseased patients. Additionally, the healthy and diseased states can be distinguished by SNPs in the species of B. vulgatus. We present a comprehensive profile of changes in the microbiota in clinical TB patients. Our findings will shed light on the design of future diagnoses and treatments for M. tuberculosis infections.

Learning style recognition is an indispensable part of achieving personalized learning in online learning systems. The traditional inventory method for learning style identification faces the limitations such as subject and static characteristics. Therefore, an automatic and reliable learning style recognition mechanism is designed in this article. First, a learning style labeling framework (LSDFA) based on multilabel fusion is proposed, which can obtain learning style labels by mining the potential information of two sets of inventories. Furthermore, a two-layer ensemble model (SRGSML) based on learners' online learning behaviors data to recognize learners' learning styles is proposed, which combines the resampling technology (SMOTE) to solve the unreliable prediction problem caused by class imbalance. The superiority of the proposed mechanism is verified on learning behavior data of 2056 learners during the online teaching period of Shanghai Normal University. Experimental results show that the recognition accuracy of SRGSML reaches 0.977, as well as prove the effectiveness of the LSDFA for labeling learning style.

A non-dispersive infrared (NDIR) methane gas sensor prototype has achieved a minimum detection limit of 1 parts per million by volume (ppm). The central idea of the design of the sensor is to decrease the detection limit by increasing the signal to noise ratio (SNR) of the system. In order to decrease the noise level, a single frequency filter algorithm based on fast Fourier transform (FFT) is adopted for signal processing. Through simulation and experiment, it is found that the full width at half maximum (FWHM) of the filter narrows with the extension of sampling period and the increase of lamp modulation frequency, and at some optimum sampling period and modulation frequency, the filtered signal maintains a noise to signal ratio of below 1/10,000. The sensor prototype provides the key techniques for a hand-held methane detector that has a low cost and a high resolution. Such a detector may facilitate the detection of leakage of city natural gas pipelines buried underground, the monitoring of landfill gas, the monitoring of air quality and so on.

Tuberculosis (TB) remains a significant human health issue. More effective biomarkers for use in tuberculosis prevention, diagnosis, and treatment, including markers that can discriminate between healthy individuals and those with latent infection, are urgently needed. To identify a set of such markers, we used Solexa sequencing to examine microRNA expression in the serum of patients with active disease, healthy individuals with latent TB, and those with or without prior BCG inoculation. We identified 24 microRNAs that are up-regulated (2.85-1285.93 fold) and 6 microRNAs that are down-regulated (0.003-0.11 fold) (P

Cytokines are important in the cell-mediated response to Schistosoma mansoni eggs. We have found that Th2 cytokine responses (e.G. IL-4 and IL-5) are argumented after egg laying begins while the response (IL-2 and IFN-*) are down regulated in S. mansoni infected mice. Treatment of mice with anti-IL-5 monoclonal antibodies (Mab) suppressed the eosinophil response almost completley but did not affect granuloma size and slightly increased hepatic fibrosis. Anti-IL-4 treatment abolished IgE responses in infected mice and decreased hepatic fibrosis slightly. Anti-IFN-* treatment had no effect on hepatic pathology. Anti-IL-2 treatment decreased granuloma size significantly and decreased hepatic fibrosis markedly. Anti-IL-2 treatment dramatically decreased IL-5 secretion by splenic cells in vitro and decreased peripheral blood and tissue eosinophilia. In contrast IL-4 secretion was unaffected and serum IgE was normal or increased. IL-2 and IFN-* secretion by splenic cells of treated mice were slightly but not significantly increased suggesting that anti-IL-2 treatment affecting Th2 rather than Th1 responses.