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Abstract The hallmarks of stem cells, such as proliferation, self-renewal, development, differentiation, and regeneration, are critical to maintain stem cell identity which is sustained by genetic and epigenetic factors. Super-enhancers (SEs), which consist of clusters of active enhancers, play a central role in maintaining stemness hallmarks by specifically transcriptional model. The SE-navigated transcriptional complex, including SEs, non-coding RNAs, master transcriptional factors, Mediators and other co-activators, forms phase-separated condensates, which offers a toggle for directing diverse stem cell fate. With the burgeoning technologies of multiple-omics applied to examine different aspects of SE, we firstly raise the concept of “super-enhancer omics”, inextricably linking to Pan-omics. In the review, we discuss the spatiotemporal organization and concepts of SEs, and describe links between SE-navigated transcriptional complex and stem cell features, such as stem cell identity, self-renewal, pluripotency, differentiation and development. We also elucidate the mechanism of stemness and oncogenic SEs modulating cancer stem cells via genomic and epigenetic alterations hijack in cancer stem cell. Additionally, we discuss the potential of targeting components of the SE complex using small molecule compounds, genome editing, and antisense oligonucleotides to treat SE-associated organ dysfunction and diseases, including cancer. This review also provides insights into the future of stem cell research through the paradigm of SEs.

Abstract The accuracy of short‐term photovoltaic (PV) power prediction is crucial for maintaining power system stability and grid scheduling. Here, a short‐term PV power prediction framework is proposed considering combined weather similarity day screening, signal decomposition noise reduction and hybrid deep learning to realize PV power prediction. First, a combined meteorological similar day screening model is constructed to screen out historical days similar to the day, which reduces the number of training sets; Second, Synchrosqueezing Wavelet Transform is utilized to eliminate data noise. Third, a Convolution Neural Network‐Gate Recurrent Unit (CNN‐GRU) network is constructed to extract periodic and nonlinear features in the PV power generation data series and to capture the relationship features between PV power generation and meteorological factors to improve the prediction accuracy. Fourth, the Sparrow Search Algorithm is introduced to perform hyper‐parameter optimization of the CNN‐GRU network to accelerate the model convergence and improve the model training efficiency. Finally, this paper conducts simulation experiments and the experimental results show that the prediction method proposed in this paper can effectively improve the prediction accuracy of short‐term PV power compared to the baseline model, and the method proposed in this paper is superior to other conventional methods.

Abstract The Japanese sawyer beetle Monochamus alternatus (Coleoptera: Cerambycidae) is a pest in pine forests and acts as a vector for the pine wood nematode Bursaphelenchus xylophilus, which causes the pine wilt disease. We assembled a high-quality genome of M. alternatus at the chromosomal level using Illumina, Nanopore, and Hi-C sequencing technologies. The assembled genome is 767.12 Mb, with a scaffold N50 of 82.0 Mb. All contigs were assembled into ten pseudo-chromosomes. The genome contains 63.95% repeat sequences. We identify 16, 284 protein-coding genes in the genome, of which 11,244 were functionally annotated. The high-quality genome of M. alternatus provides an invaluable resource for the biological, ecological, and genetic study of this beetle and opens new avenues for understanding the transmission of pine wood nematode by insect vectors.

Legionella, one of the main pathogens that causes community-acquired pneumonia, can lead to Legionella pneumonia, a condition characterized predominantly by severe pneumonia. This disease, caused by the bacterium Legionella pneumophila, can quickly progress to critical pneumonia and is often associated with damage to multiple organs. As a result, it requires close attention in terms of clinical diagnosis and treatment. Omadacycline, a new type of tetracycline derivative belonging to the aminomethylcycline class of antibiotics, is a semi-synthetic compound derived from minocycline. Its key structural feature, the aminomethyl modification, allows omadacycline to overcome bacterial resistance and broadens its range of effectiveness against bacteria. Clinical studies have demonstrated that omadacycline is not metabolized in the body, and patients with hepatic and renal dysfunction do not need to adjust their dosage. This paper reports a case of successful treatment of Legionella pneumonia with omadacycline in a patient who initially did not respond to empirical treatment with moxifloxacin. The patient also experienced electrolyte disturbance, as well as dysfunction in the liver and kidneys, delirium, and other related psychiatric symptoms.

Objectives: Limited data on clinical and microbiological efficacy, patient mortality, and other associated factors are available for ceftazidime/avibactam (CAZ/AVI)-based regimens for carbapenem-resistant Gram-negative bacteria (CR-GNB). This study aimed to assess these issues retrospectively using multicenter data. Methods: This multicenter study included CR-GNB infected patients treated with CAZ/AVI-based regimens for more than three days. Patient characteristics, bacterial culture reports, drug-sensitivity test results, and antibiotic use, including CAZ/AVI use, were extracted from the patient's clinical records. The clinical and microbiological efficacy of the combined drug regimen and patient mortality were evaluated according to corresponding definitions. Univariate and multivariate logistic regressions were performed to explore the efficacy and mortality-related factors. Results: A total of 183 patients with CR-GNB infection were considered for the analysis according to the inclusion and exclusion criteria. After the treatment of CAZ/AVI-based regimens, the clinical efficacy was 75.4 %. The 7-day microbial efficacy and clearance rate after treatment were 43.7 % and 66.0 %, respectively. Moreover, 30-day all-cause and in-hospital mortality were 11.5 % and 14.2 %, respectively. Harboring renal dysfunction (creatinine clearance rate (CCR) of

Brain cancer: opportunities to block “super-enhanced” tumor growth “Superenhancer” regions within the genome help coordinate the malignant growth of brain tumors, and could offer a target for the development of therapies and prognostic biomarkers. These regions contain a dense accumulation of gene regulatory sequences, which operate in collaboration to establish cellular identity. A review by Jian Qu and colleagues at Central South University, Changsha, China, shows how these regulatory sequences get hijacked in various brain cancers and can facilitate tumor cell proliferation and invasion. Many tumor cells acquire mutations that lead to the formation of superenhancers that are absent in healthy cells. However, this process also offers therapeutic opportunities, and researchers have identified numerous drug candidates that can potentially block tumorigenesis by selectively interfering with superenhancer function. Superenhancer activity could also provide a potentially useful clinical signature for assessing tumor aggressiveness.

Abstract We have developed a microscale hydraulic soft gripper and demonstrated the handling of an insect without damage. This gripper is built on Polydimethylsiloxane (PDMS) with the soft material casting technique to form three finger-like columns, which are placed on a circular membrane. The fingers have a length of 1.5 mm and a diameter of 300 µm each; the distance between the two fingers is 600 µm of center-to-center distance. A membrane as a 150 µm soft film is built on top of a cylindrical hollow space. Applying pressure to the interior space can bend the membrane. Bending the membrane causes the motion of opening/closing of the gripper, and as a result, the three fingers can grip an object or release it. The PDMS was characterized, and the experimental results were used later in Abaqus software to simulate the gripping motion. The range of deformation of the gripper was investigated by simulation and experiment. The result of the simulation agrees with the experiments. The maximum 543 µN force was measured for this microfluidic-compatible microgripper and it could lift a ball that weighs 168.4 mg and has a 0.5 mm diameter. Using this microgripper, an ant was manipulated successfully without any damage. Results showed fabricated device has great a potential as micro/bio manipulator.

Identifying fraudulent campaigns or messages remains a difficult task in the field of natural language processing. We proposed a hypothesis that if the well-known brands in the same category as the crowdfunding project can implement similar technology as crowdfunding projects, the project is considered to be more feasible. The opposite is considered more likely to be fraudulent. This research proposed a novel BNB-NO-BK method to detect fraudulent crowdfunding projects. A novel method called BNB, which was constructed by key-BERT, NLTK, and fine-tuned QA model for BERT, was proposed to extract the characteristics of crowdfunding projects. We proposed a novel NO (Nice Classification & Ontology) method for classifying the categories of projects, which constructed ontology trees based on the characteristics of the crowdfunding projects and our modified Nice Classification. Furthermore, we proposed a novel BK (Brand Knowledge) cross-checking method to extract the features of crowdfunding projects. Finally, we compared the performances of different machine learning methods for identifying fraudulent crowdfunding projects. Furthermore, to address the problem of possible bias caused by unbalanced data, we used data augmentation to process the dataset. Our proposed method achieved an accuracy of 95.71% in detecting fraudulent crowdfunding projects, which was superior to existing methods.

Introduction: In the past decade, super-enhancer (SE) has become a research hotspot with increasing attention on cancer occurrence, development, and prognosis. To illustrate the hotspots of SE in cancer research and its evolutionary tendency, bibliometric analysis was carried out for this topic.Methods: Literature published before Dec 31, 2022, in WOSCC, was systematically classified, and Citespace, bibliometric.com/app, and GraphPad Prism analyzed the data.Results: After screening out inappropriate documents and duplicate data, 911 publications were selected for further bibliometric analysis. The top five research areas were Oncology (257, 28.211%), Cell Biology (210, 23.052%), Biochemistry Molecular Biology (209, 22.942%), Science Technology Other Topics (138, 15.148%), and Genetics Heredity (132, 14.490%). The United States of America (United States) has the highest number of documents (462, 50.71%), followed by China (303, 33.26%). Among the most productive institutions, four of which are from the United States and one from Singapore, the National University of Singapore. Harvard Medical School (7.68%) has the highest percentage of articles. Young, Richard A, with 32 publications, ranks first in the number of articles. The top three authors came from Whitehead Institute for Biomedical Research as a research team. More than two-thirds of the research are supported by the National Institutes of Health of the United States (337, 37.654%) and the United States Department of Health Human Services (337, 37.654%). And “super enhancer” (525), “cell identity” (258), “expression” (223), “cancer” (205), and “transcription factor” (193) account for the top 5 occurrence keywords.Discussion: Since 2013, SE and cancer related publications have shown a rapid growth trend. The United States continues to play a leading role in this field, as the top literature numbers, affiliations, funding agencies, and authors were all from the United States, followed by China and European countries. A high degree of active cooperation is evident among a multitude of countries. The role of SEs in cell identity, gene transcription, expression, and inhibition, as well as the relationship between SEs and TFs, and the selective inhibition of SEs, have received much attention, suggesting that they are hot issues for research.

Objectives: Augmented renal clearance (ARC) is a state of enhanced renal function commonly observed in 30%–65% of critically ill patients despite normal serum creatinine levels. Using unadjusted standard dosing regimens of renally eliminated drugs in ARC patients often leads to subtherapeutic concentrations, poor clinical outcomes, and the emergence of multidrug-resistant bacteria. We summarized pharmaceutical, pharmacokinetic, and pharmacodynamic research on the definition, underlying mechanisms, and risk factors of ARC to guide individualized dosing of antibiotics and various strategies for optimizing outcomes.Methods: We searched for articles between 2010 and 2022 in the MEDLINE database about ARC patients and antibiotics and further provided individualized antibiotic dosage regimens for patients with ARC.Results: 25 antibiotic dosage regimens for patients with ARC and various strategies for optimization of outcomes, such as extended infusion time, continuous infusion, increased dosage, and combination regimens, were summarized according to previous research.Conclusion: ARC patients, especially critically ill patients, need to make individualized adjustments to antibiotics, including dose, frequency, and method of administration. Further comprehensive research is required to determine ARC staging, expand the range of recommended antibiotics, and establish individualized dosing guidelines for ARC patients.

Abstract Background Viola philippica Cav. is the only source plant of “Zi Hua Di Ding”, which is a Traditional Chinese Medicine (TCM) that is utilized as an antifebrile and detoxicant agent for the treatment of acute pyogenic infections. Historically, many Viola species with violet flowers have been misused in “Zi Hua Di Ding”. Viola have been recognized as a taxonomically difficult genera due to their highly similar morphological characteristics. Here, all common V. philippica adulterants were sampled. A total of 24 complete chloroplast (cp) genomes were analyzed, among these 5 cp genome sequences were downloaded from GenBank and 19 cp genomes, including 2 “Zi Hua Di Ding” purchased from a local TCM pharmacy, were newly sequenced. Results The Viola cp genomes ranged from 156,483 bp to 158,940 bp in length. A total of 110 unique genes were annotated, including 76 protein-coding genes, 30 tRNAs, and four rRNAs. Sequence divergence analysis screening identified 16 highly diverged sequences; these could be used as markers for the identification of Viola species. The morphological, maximum likelihood and Bayesian inference trees of whole cp genome sequences and highly diverged sequences were divided into five monophyletic clades. The species in each of the five clades were identical in their positions within the morphological and cp genome tree. The shared morphological characters belonging to each clade was summarized. Interestingly, unique variable sites were found in ndhF, rpl22, and ycf1 of V. philippica, and these sites can be selected to distinguish V. philippica from samples all other Viola species, including its most closely related species. In addition, important morphological characteristics were proposed to assist the identification of V. philippica. We applied these methods to examine 2 “Zi Hua Di Ding” randomly purchased from the local TCM pharmacy, and this analysis revealed that the morphological and molecular characteristics were valid for the identification of V. philippica. Conclusions This study provides invaluable data for the improvement of species identification and germplasm of V. philippica that may facilitate the application of a super-barcode in TCM identification and enable future studies on phylogenetic evolution and safe medical applications.

Abstract Background Seizures are a common symptom in glioma patients, and they can cause brain dysfunction. However, the mechanism by which glioma-related epilepsy (GRE) causes alterations in brain networks remains elusive. Objective To investigate the potential pathogenic mechanism of GRE by analyzing the dynamic expression profiles of microRNA/ mRNA/ lncRNA in brain tissues of glioma patients. Methods Brain tissues of 16 patients with GRE and 9 patients with glioma without epilepsy (GNE) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60 K. The cDNA was labeled and hybridized to the Agilent LncRNA + mRNA Human Gene Expression Microarray V3.0, 4 × 180 K. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value 2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor. Results We found that 3 differentially expressed miRNAs (miR-10a-5p, miR-10b-5p, miR-629-3p), 6 differentially expressed lncRNAs (TTN-AS1, LINC00641, SNHG14, LINC00894, SNHG1, OIP5-AS1), and 49 differentially expressed mRNAs play a vitally critical role in developing GRE. The expression of GABARAPL1, GRAMD1B, and IQSEC3 were validated more than twofold higher in the GRE group than in the GNE group in the validation cohort. Pathways including ECM receptor interaction and long-term potentiation (LTP) may contribute to the disease’s progression. Meanwhile, We built a lncRNA-microRNA-Gene regulatory network with structural and functional significance. Conclusion These findings can offer a fresh perspective on GRE-induced brain network changes.

The plastome (plastid genome) represents an indispensable molecular data source for studying phylogeny and evolution in plants. Although the plastome size is much smaller than that of nuclear genome, and multiple plastome annotation tools have been specifically developed, accurate annotation of plastomes is still a challenging task. Different plastome annotation tools apply different principles and workflows, and annotation errors frequently occur in published plastomes and those issued in GenBank. It is therefore timely to compare available annotation tools and establish standards for plastome annotation. In this review, we review the basic characteristics of plastomes, trends in the publication of new plastomes, the annotation principles and application of major plastome annotation tools, and common errors in plastome annotation. We propose possible methods to judge pseudogenes and RNA-editing genes, jointly consider sequence similarity, customed algorithms, conserved domain or protein structure. We also propose the necessity of establishing a database of reference plastomes with standardized annotations, and put forward a set of quantitative standards for evaluating plastome annotation quality for the scientific community. In addition, we discuss how to generate standardized GenBank annotation flatfiles for submission and downstream analysis. Finally, we prospect future technologies for plastome annotation integrating plastome annotation approaches with diverse evidences and algorithms of nuclear genome annotation tools. This review will help researchers more efficiently use available tools to achieve high-quality plastome annotation, and promote the process of standardized annotation of the plastome.

Southwestern China, adjacent to the Qinghai-Tibetan Plateau (QTP), is known as a hotspot for plant diversity and endemism, and it is the origin and diversification center of Persicarieae. As one of the major lineages in Polygonaceae, Persicarieae represents a diverse adaptation to various habitats. As a result of morphological plasticity and poorly resolving molecular markers, phylogenetic relationships and infrageneric classification within Persicarieae have long been controversial. In addition, neither plastome phylogenomic studies nor divergence time estimates on a larger sample of Persicarieae species have been made thus far. We sequenced and assembled 74 complete plastomes, including all of the recognized genera within Persicarieae and their relatives. We conducted a comprehensive phylogenetic study of the major clades within Persicarieae and, based on the thus obtained robust phylogeny, also estimated divergence time and the evolution of diagnostic morphological traits. Major relationships found in previous phylogenetic studies were confirmed, including those of the backbone of the tree, which had been a major problem in previous phylogenies of the tribe. Phylogenetic analysis revealed strong support for Koenigia as sister to Bistorta, and together they were sister to the robustly supported Persicaria. Based on the phylogenetic and morphological evidence, we recognize five sections in Persicaria: Persicaria, Amphibia, Tovara, Echinocaulon, and Cephalophilon. It is estimated that the divergence of the Persicarieae began around the late Paleocene, with diversification concentrated in the Eocene and Miocene. In addition, it is suggested that the increasing westerly and monsoon winds in conjunction with the uplift of the QTP may be the driving force for origin and diversification of Persicarieae species. These results provide a valuable evolutionary framework for the study of adaptation in Polygonaceae and insights into plant diversification on the QTP and adjacent areas.

Chloridoideae is one of the largest subfamilies of Poaceae, containing many species of great economic and ecological value; however, phylogenetic relationships among the subtribes and genera of Cynodonteae are controversial. In the present study, we combined 111 plastomes representing all five tribes, including 25 newly sequenced plastomes that are mostly from Cynodonteae. Phylogenetic analyses supported the five monophyletic tribes of Chloridoideae, including Centropodieae, Triraphideae, Eragrostideae, Zoysieae and Cynodonteae. Simultaneously, nine monophyletic lineages were revealed in Cynodonteae: supersubtribe Boutelouodinae, subtribes Tripogoninae, Aeluropodinae, Eleusininae, Dactylocteniinae, supersubtribe Gouiniodinae, Cleistogenes and Orinus, and subtribe Triodiinae. Within the tribe of Cynodonteae, the basal lineage is supersubtribe Boutelouodinae and Tripogoninae is sister to the remaining lineages. The clade formed of Aeluropodinae and Eleusininae is sister to the clade composed of Dactylocteniinae, supersubtribe Gouiniodinae, Cleistogenes and Orinus, and subtribe Triodiinae. The clade comprising Dactylocteniinae and supersubtribe Gouiniodinae is sister to the clade comprising Cleistogenes, Orinus, and Triodiinae. Acrachne is a genus within Eleusininae but not within Dactylocteniinae. Molecular evidence determined that Diplachne is not clustered with Leptochloa, which indicated that Diplachne should not be combined into Leptochloa. Cleistogenes is sister to a clade composed of Orinus and Triodia, whereas the recently proposed subtribe Orininae was not supported. Cynodonteae was estimated to have experienced rapid divergence within a short period, which could be a major obstacle in resolving its phylogenetic relationships. Ancestral state reconstructions of morphological characters showed that the most recent common ancestor (MRCA) of Chloridoideae has a panicle, multiple florets in each spikelet, the peaked type of stomatal subsidiary cells, and a saddle-shaped phytoliths, while the ancestral morphological characters of Cynodonteae are the panicle, peaked type of stomatal subsidiary cells, sharp-cap cell typed and equal-base-cell microhair, and square-shaped phytoliths. Overall, plastome phylogenomics provides new insights into the phylogenetic relationships and morphological character evolution of Chloridoideae.

Gliomas are central nervous system tumors originating from glial cells, whose incidence and mortality rise in coming years. The current treatment of gliomas is surgery combined with chemotherapy or radiotherapy. However, developing therapeutic resistance is one of the significant challenges. Recent research suggested that small interfering RNA (siRNA) has excellent potential as a therapeutic to silence genes that are significantly involved in the manipulation of gliomas’ malignant phenotypes, including proliferation, invasion, metastasis, therapy resistance, and immune escape. However, it is challenging to deliver the naked siRNA to the action site in the cells of target tissues. Therefore, it is urgent to develop delivery strategies to transport siRNA to achieve the optimal silencing effect of the target gene. However, there is no systematic discussion about siRNAs’ clinical potential and delivery strategies in gliomas. This review mainly discusses siRNAs’ delivery strategies, especially nanotechnology-based delivery systems, as a potential glioma therapy. Moreover, we envisage the future orientation and challenges in translating these findings into clinical applications.

Aims: Carbapenem-resistant K. pneumoniae (CRKP) is the most common carbapenem-resistant Enterobacteriaceae with high mortality. Ceftazidime-avibactam (CAZ-AVI) has exhibited excellent in vitro activity in vivo against CRKP. However, the efficacy of CAZ-AVI in KPC-producing CRKP-infected patients with different kidney statuses varies, such as renal insufficiency, normal renal function, and augmented renal clearance (ARC). We explored the use of therapeutic drug monitoring (TDM) to evaluate the concentration and efficacy of CAZ-AVI in CRKP-infected patients with different kidney statuses.Methods: Serum concentrations for CAZ and AVI were determined by the high-performance liquid chromatography method. Bacterial identification, routine susceptibility testing, renal function index, and others were performed in standard protocols in the hospital’s clinical laboratories.Results: In the two patients with ARC, in case 1, CAZ-AVI 2.5g q6h was used with good efficacy, and the concentrations were up to the pharmacokinetics/pharmacodynamics targets. In Case 2, 2.5 g q8h was used with invalid effectiveness, and AVI Cmin was only 0.797 mg/l, which is lower than the PK/PD target. Case 3 was renal insufficiency using CAZ-AVI 1.25 q8h, and case 4 was normal renal function using 2.5 g q8h. Their concentrations were both up to the PK/PD targets.Conclusion: TDM results demonstrated that CAZ-AVI steady-state plasma concentration varies among patients with different kidney statuses, providing evidence for the utility of TDM of CAZ-AVI in individualized drug dose adjustment. ARC patients may need more CAZ-AVI daily doses than the standard dose.

ObjectiveTo investigate the potential pathogenic mechanism of temporal lobe epilepsy with hippocampal sclerosis (TLE+HS) by analyzing the expression profiles of microRNA/ mRNA/ lncRNA/ DNA methylation in brain tissues.MethodsBrain tissues of six patients with TLE+HS and nine of normal temporal or parietal cortices (NTP) of patients undergoing internal decompression for traumatic brain injury (TBI) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60K. The cDNA was labeled and hybridized to the Agilent LncRNA+mRNA Human Gene Expression Microarray V3.0,4 × 180K. For methylation detection, the DNA was labeled and hybridized to the Illumina 450K Infinium Methylation BeadChip. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value < 0.05 and absolute fold change >2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor. BrainSpan database was used to screen for signatures that were not differentially expressed in normal human hippocampus and cortex (data from BrainSpan), but differentially expressed in TLE+HS’ hippocampus and NTP’ cortex (data from our cohort). The strategy “Guilt by association” was used to predict the prospective roles of each important hub mRNA, miRNA, or lncRNA.ResultsA significantly negative correlation (r < −0.5) was found between 116 pairs of microRNA/mRNA, differentially expressed in six patients with TLE+HS and nine of NTP. We examined this regulation network’s intersection with target gene prediction results and built a lncRNA-microRNA-Gene regulatory network with structural, and functional significance. Meanwhile, we found that the disorder of FGFR3, hsa-miR-486-5p, and lnc-KCNH5-1 plays a key vital role in developing TLE+HS.

Abstract Although new developments of surgery, chemotherapy, radiotherapy, and immunotherapy treatments for cancer have improved patient survival, the emergence of chemoresistance in cancer has significant impacts on treatment effects. The development of chemoresistance involves several polygenic, progressive mechanisms at the molecular and cellular levels, as well as both genetic and epigenetic heterogeneities. Chemotherapeutics induce epigenetic reprogramming in cancer cells, converting a transient transcriptional state into a stably resistant one. Super-enhancers (SEs) are central to the maintenance of identity of cancer cells and promote SE-driven-oncogenic transcriptions to which cancer cells become highly addicted. This dependence on SE-driven transcription to maintain chemoresistance offers an Achilles’ heel for chemoresistance. Indeed, the inhibition of SE components dampens oncogenic transcription and inhibits tumor growth to ultimately achieve combined sensitization and reverse the effects of drug resistance. No reviews have been published on SE-related mechanisms in the cancer chemoresistance. In this review, we investigated the structure, function, and regulation of chemoresistance-related SEs and their contributions to the chemotherapy via regulation of the formation of cancer stem cells, cellular plasticity, the microenvironment, genes associated with chemoresistance, noncoding RNAs, and tumor immunity. The discovery of these mechanisms may aid in the development of new drugs to improve the sensitivity and specificity of cancer cells to chemotherapy drugs.

Polymyxin B (PMB), a kind of polymyxin, was widely used in carbapenem-resistant Gram-negative bacterial (CR-GNB) infections. However, adverse reactions such as nephrotoxicity and neurotoxicity limit its use in clinical practice. The aim of this study was to explore PMB associated with nephrotoxicity and its predictors. Patients who received PMB intravenous drip for more than 72 h were eligible for the study. Characteristics of patients, concomitant nephrotoxic agents, underlying disease, and antimicrobial susceptibility were submitted for descriptive analysis. Univariate analysis and binary logistic regression were used to assess the factors leading to acute kidney injury (AKI). AKI was assessed with serum creatinine variations according to the classification of risk (stage R), injury (stage I), failure (stage F), loss, and end-stage of kidney disease. Among 234 patients with CR-GNB infections who used PMB in our study, 67 (28.63%) patients developed AKI, including 31 (14.25%) patients in stage R, 15 (6.41%) patients in stage I, and 21 (8.97%) patients in stage F. The incident rate of PMB-related nephrotoxicity in patients with normal renal function was 32.82% (43/131). The higher risk factors of AKI include males [odds ratio (OR) = 3.237; 95% confidence interval (95%CI) = 1.426–7.350], digestive system diseases [OR = 2.481 (1.127–5.463)], using furosemide (>20 mg/day) [OR = 2.473 (1.102–5.551)], and baseline serum creatinine [OR = 0.994 (0.990–0.999)]. Nonparametric tests of K-independent samples showed that baseline serum creatinine and the PMB maintenance dose were associated with the severity of nephrotoxicity (both p < 0.05). Male, digestive system diseases, using furosemide (>20 mg/day), and high baseline serum creatinine were the independent risk factors of PMB-associated AKI development. The maintenance dose of PMB may be related to the severity of AKI. These risk factors should be taken into consideration when initiating PMB-based therapy. The serum creatinine value should be closely monitored when using PMB.

Vancomycin is a hydrophilic antibiotic widely used in severe infections, including bacteremia and central nervous system (CNS) infections caused by Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci and enterococci. Appropriate antimicrobial dosage regimens can help achieve the target exposure and improve clinical outcomes. However, vancomycin exposure in serum and cerebrospinal fluid (CSF) is challenging to predict due to rapidly changing pathophysiological processes and patient-specific factors. Vancomycin concentrations may be decreased for peripheral infections due to augmented renal clearance (ARC) and increased distribution caused by systemic inflammatory response syndrome (SIRS), increased capillary permeability, and aggressive fluid resuscitation. Additionally, few studies on vancomycin’s pharmacokinetics (PK) in CSF for CNS infections. The relationship between exposure and clinical response is unclear, challenging for adequate antimicrobial therapy. Accurate prediction of vancomycin pharmacokinetics/pharmacodynamics (PK/PD) in patients with high interindividual variation is critical to increase the likelihood of achieving therapeutic targets. In this review, we describe the interaction between ARC and vancomycin PK/PD, patient-specific factors that influence the achievement of target exposure, and recent advances in optimizing vancomycin dosing schedules for severe infective patients with ARC.

Abstract To improve personalized diagnosis and prognosis for oral squamous cell carcinoma (OSCC) by identification of hub methylated‐CpG sites and associated genes, weighted gene comethylation network analysis (WGCNA) was performed to examine and identify hub modules and CpG sites correlated with OSCC. Here, WGCNA modeling yielded blue and brown comethylation modules that were significantly associated with OSCC status. Following screening of the differentially expressed genes (DEGs) from gene expression microarrays and differentially methylated‐CpG sites (DCGs), integrated multiomics analysis of the DEGs, DCGs, and hub CpG sites from the modules was performed to investigate their correlations. Expression levels of 16 CpG sites‐associated genes were negatively correlated with methylation patterns of promoter. Moreover, Kaplan‐Meier survival analysis of the hub CpG sites and associated genes was carried out using 2 public databases, MethSurv and GEPIA. Only 5 genes, ACTA1, ACTN2, OSR1, SYNGR1, and ZNF677, had significant overall survival using GEPIA. Hypermethylated‐CpG sites ACTN2‐cg21376883 and OSR1‐cg06509239 were found to be associated with poor survival by MethSurv. Methylation status of specific site and expression levels of associated genes were determined using clinical samples by quantitative methylation‐specific PCR and real‐time PCR. Pearson's correlation analysis showed that methylation levels of cg06509239 and cg18335068 were negatively related to OSR1 and ZNF677 expression levels, respectively. Our classification schema using multiomics analysis represents a screening framework for identification of hub CpG sites and associated genes.

Monitoring the properties of fluids in microfluidic chips often requires complex open-space optics technology and expensive equipment. In this work, we introduce dual-parameter optical sensors with fiber tips into the microfluidic chip. Multiple sensors were distributed in each channel of the chip, which enabled the real-time monitoring of the concentration and temperature of the microfluidics. The temperature sensitivity and glucose concentration sensitivity could reach 314 pm/°C and −0.678 dB/(g/L), respectively. The hemispherical probe hardly affected the microfluidic flow field. The integrated technology combined the optical fiber sensor with the microfluidic chip and was low cost with high performance. Therefore, we believe that the proposed microfluidic chip integrated with the optical sensor is beneficial for drug discovery, pathological research and material science investigation. The integrated technology has great application potential for micro total analysis systems (μ-TAS).

This paper presents an experimental study to investigate the heat transfer limit of a micro-grooved OHP at the vertical bottom heat mode. The internal hydraulic diameter of the micro-grooved OHP is about 2.0 mm, and deionized water was used as a working fluid at volumetric filling ratios (FRs) ranging from 30% to 60%. Experimental results demonstrated that the micro-grooved OHP could significantly enhance the allowable maximum input heat flux before the occurrence of dry-out owing to the capillary action provided by micro-grooved structures to facilitate condensate backflow to the evaporator. The OHP obtained a maximum effective thermal conductivity of 41.8 kW/(m·°C) at 40% FR, corresponding to a dry-out heat flux of 36.9 W/cm2 with respect to the heat transfer limit. The allowable maximum input heat flux was found to be greater than 80 W/cm2 for 50% and 60% FRs, and could be further increased by increasing the OHP turn number. This study provides a promising option to address thermal management demand for high-density power devices.

Objectives: Dendrobium officinale polysaccharide (DOP) is the main active ingredient in a valuable traditional Chinese medicine, which exerts several pharmacological activities including hepatoprotection and hypoglycemic effects. However, the effects of DOP on obesity-associated insulin resistance (IR) and lipid metabolism remain unknown. This study aimed to investigate the role of DOP in IR and abnormal lipid metabolism in obese mice.Methods: IR models were established using 3T3-L1 adipocytes, C2C12 myocytes, and primary cultured hepatocytes exposed to palmitate acid. After treatment with DOP, insulin-stimulated glucose uptake, glucose release, and AKT phosphorylation was detected. Fasting blood glucose, fasting serum insulin, the glucose tolerance test (GTT), and the insulin tolerance test (ITT) were measured to evaluate IR of obese mice. Lipid analysis was conducted to evaluate the effects of DOP on lipid metabolism in obese mice.Results:In vitro, DOP treatment ameliorated palmitic acid-induced IR in adipocytes, myocytes, and hepatocytes. DOP regulated cellular insulin sensitivity via the peroxisome proliferator-activated receptor-γ (PPAR-γ). Furthermore, administration of DOP significantly reduced the IR and visceral adipose tissue (VAT) inflammation of diet-induced obese (DIO) and the genetically-induced obesity mice (ob/ob) mouse models. In addition, DOP treatment attenuated the high-fat diet (HFD)-induced liver lipid accumulation by reducing liver triglycerides (TG), plasma free fatty acid (FFA), serum cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels, while increasing HDL-C levels.Conclusion: DOP could improve obesity-associated IR and abnormal lipid metabolism through its activities on PPAR-γ, and may serve as a potential therapeutic agent for obesity-associated insulin resistance and lipid metabolism disorder.

Abstract Background Plastome (plastid genome) sequences provide valuable information for understanding the phylogenetic relationships and evolutionary history of plants. Although the rapid development of high-throughput sequencing technology has led to an explosion of plastome sequences, annotation remains a significant bottleneck for plastomes. User-friendly batch annotation of multiple plastomes is an urgent need. Results We introduce Plastid Genome Annotator (PGA), a standalone command line tool that can perform rapid, accurate, and flexible batch annotation of newly generated target plastomes based on well-annotated reference plastomes. In contrast to current existing tools, PGA uses reference plastomes as the query and unannotated target plastomes as the subject to locate genes, which we refer to as the reverse query-subject BLAST search approach. PGA accurately identifies gene and intron boundaries as well as intron loss. The program outputs GenBank-formatted files as well as a log file to assist users in verifying annotations. Comparisons against other available plastome annotation tools demonstrated the high annotation accuracy of PGA, with little or no post-annotation verification necessary. Likewise, we demonstrated the flexibility of reference plastomes within PGA by annotating the plastome of Rosa roxburghii using that of Amborella trichopoda as a reference. The program, user manual and example data sets are freely available at https://github.com/quxiaojian/PGA. Conclusions PGA facilitates rapid, accurate, and flexible batch annotation of plastomes across plants. For projects in which multiple plastomes are generated, the time savings for high-quality plastome annotation are especially significant.

WaDang recognition can provide valuable information for digital protection of cultural relics. However, WaDang recognition is challenging due to a great number of variations, such as different characters, different background pattern, and different scale and rotation. In this paper, we try to solve these problems by using hand-crafted and deep features and integrate them into multiple instance learning, in which the features of instances are divided into two parts and their similarity is computed by multiple kernel learning. The experiments on our collected WaDang images, MUSK, and COREL datasets show that the proposed algorithm is effective and its performance is compared with other state-of-art algorithms.

Osteoporosis is a chronic age-related disease. During aging, bone marrow-derived mesenchymal stem cells (BMSCs) display increased adipogenic, along with decreased osteogenic, differentiation capacity. The aim of the present study was to investigate the effect of calcitonin gene-related peptide (CGRP) on the osteogenic and adipogenic differentiation potential of BMSC-derived osteoblasts. Here, we found that the level of CGRP was markedly lower in bone marrow supernatant from aged mice compared with that in young mice. In vitro experiments indicated that CGRP promoted the osteogenic differentiation of BMSCs while inhibiting their adipogenic differentiation. Compared with vehicle-treated controls, aged mice treated with CGRP showed a substantial promotion of bone formation and a reduction in fat accumulation in the bone marrow. Similarly, we found that CGRP could significantly enhance bone formation in ovariectomized (OVX) mice in vivo. Together, our results suggested that CGRP may be a key regulator of the age-related switch between osteogenesis and adipogenesis in BMSCs and may represent a potential therapeutic strategy for the treatment of age-related bone loss.

Cleistogenes (Orininae, Cynodonteae, Chloridoideae, Poaceae) is an ecologically important genus. The phylogenetic placement of Cleistogenes and phylogenetic relationships among Cleistogenes taxa remain controversial for a long time. To resolve the intra- and inter-generic relationships of Cleistogenes, the plastomes of 12 Cleistogenes taxa (including 8 species and 4 varieties), one Orinus species, 15 Triodia species, two Tripogon species, and two Aeluropus species were included in the present study. All the taxa showed a similar pattern in plastome structure, gene order, gene content, and IR boundaries. The number of simple sequence repeats ranged from 145 (O. kokonorica) to 161 (T. plurinervata and T. schinzii). Moreover, 1,687 repeats were identified in these taxa, including 1,012 forward, 650 palindromic, 24 reverse, and one complement. Codon usage analysis revealed that these plastomes contained 16,633 (T. stipoides) to 16,678 (T. tomentosa) codons. Sequence divergence analysis among Cleistogenes and closely related genera identified five non-coding regions (trnS-UGA-psbZ, rpl32-trnL-UAG, trnQ-UUG-psbK, trnD-GUC-psbM, trnT-GGU-trnE-UUC). Phylogenetic analysis of complete plastomes indicated that Cleistogenes is sister to a clade composed of Orinus and Triodia, whereas it did not support the sister relationship between the recently proposed subtribe Orininae (Cleistogenes and Orinus) and Triodia. The subtribe Orininae was not supported by our complete plastome data. The split between Cleistogenes and Orinus-Triodia clade go back to 14.01 Ma. Besides, our findings suggested that C. squarrosa and C. songorica are the successive early diverging groups in the phylogenetic analysis. The other 10 taxa are divided into two groups: a monophyletic group composed of Cleistogenes sp. nov. and C. caespitosa var. ramosa is sister to other eight Cleistogenes taxa. Cleistogenes was estimated to have experienced rapid divergence within a short period, which could be a major obstacle in resolving phylogenetic relationships within Cleistogenes. Collectively, our results provided valuable insights into the phylogenetic study of grass species.

Meige syndrome (MS) is cranial dystonia characterized by the combination of upper and lower cranial involvement and including binocular eyelid spasms (blepharospasm; BSP) and involuntary movements of the jaw muscles (oromandibular dystonia; OMD). The etiology and pathogenesis of this disorder of the extrapyramidal system are not well-understood. Neurologic and ophthalmic examinations often reveal no abnormalities, making diagnosis difficult and often resulting in misdiagnosis. A small proportion of patients have a family history of the disease, but to date no causative genes have been identified to date and no cure is available, although botulinum toxin A therapy effectively mitigates the symptoms and deep brain stimulation is gaining increasing attention as a viable alternative treatment option. Here we review the history and progress of research on MS, BSP, and OMD, as well as the etiology, pathology, diagnosis, and treatment.

Objective: The emergence of carbapenem-resistant gram-negative bacteria (CR-GNB) has brought great challenges to clinical anti-infection treatment around the world. Polymyxins are often considered as the last line of defense in the treatment of CR-GNB infections. In this study, we explored the microbiological efficacy of Polymyxin B (PMB) on different CR-GNB infections as well as the factors influencing microbiological efficacy.Methods: CR-GNB infected patients with PMB-based regimens were enrolled. Clinical and microbiological data were collected from the medical electronic record system of the Second Xiangya hospital. The efficacy of PMB on different CR-GNB was evaluated by the clearance rate at 7-days and within the course of treatment, as well as the 30-day mortality rate.Results: A total of 294 CR-GNB infected patients were enrolled: 154 CR-Acinetobacter baumannii (CRAB), 55 CR-Klebsiella pneumoniae (CRKP), and 85 CR-Pseudomonas aeruginosa (CRPA). The CRAB group had the highest 7-day bacterial clearance rate [(CRAB: 39.0%) vs. (CRKP: 29.4%) vs. (CRPA: 14.5%), P = 0.003] and total bacterial clearance rate [(CRAB: 49.0%) vs. (CRKP: 39.8%) vs. (CRPA: 18.2%), P < 0.001] among the three groups, while the bacterial clearance rate of the CRPA group was the lowest. Multivariate logistic regression showed that the differences among the three groups were multiple CR-GNB infections (P = 0.004), respiratory infections (P = 0.001), PMB resistance (P < 0.001), and the combination of tigecycline (P < 0.001). Binary logistic regression showed that multiple CR-GNB infection [(7-day bacterial clearance: P = 0.004) & (total bacterial clearance: P = 0.011)] and bacterial species [(7-day bacterial clearance: P < 0.001) & (total bacterial clearance: P < 0.001)] were independent risk factors for microbiological efficacy.Conclusion: PMB exhibited differential microbiological efficacy on different types of CR-GNB infections; it had the best effect on CRAB, followed by CRKP and CRPA. Multiple CR-GNB infections and bacterial species were independent risk factors for microbiological efficacy.

Multiple myeloma (MM) is a malignant plasma cell tumor with high heterogeneity, characterized by anemia, hypercalcemia, renal failure, and lytic bone lesions. Although various powerful prognostic factors and models have been exploited, the development of more accurate prognosis and treatment for MM patients is still facing many challenges. Given the essential roles of super-enhancer (SE) associated genes in the tumorigenesis of MM, we tried to initially screen and identify the significant prognostic factors from SE associated genes in MM by the least absolute shrinkage and selection operator (Lasso) penalized Cox regression, univariate and multivariate Cox regression analysis using GSE24080 and GSE9782 datasets. Risk score model of five genes including CSGALNACT1, FAM53B, TAPBPL, REPIN1, and DDX11, was further constructed and the Kaplan-Meier (K-M) curves showed that the low-risk group seems to have better clinical outcome of survival compared to the high-risk group. Time-dependent receiver operating characteristic (ROC) curves presented the favorable performance of the model. An interactive nomogram consisting of the five-gene risk group and eleven clinical traits was established and identified by calibration curves. Therefore, the risk score model of SE associated five genes developed here could be used to predict the prognosis of MM patients, which may assist the clinical treatment of MM patients in the future.

In this paper, TGPs with thickness of around 0.53–0.6 mm are developed with copper plate as the casing material, nanostructured copper foam as the wick and electroplated copper pillar as the support of vapor core. The effects of charge amount of water, nanostructured wick, the number of copper foam layers and vapor core thickness on the thermal performance of the developed TGP are experimentally studied. It is found that increasing the number of copper foam layers or vapor core thickness can greatly lower the TGP thermal resistance. Specifically, a TGP with a double layers copper foam wick has a much better thermal performance than that with single layer even though the total wick thickness and porosity remain unchanged. Experimental results also show that the multiscale micro/nanostructured wick is beneficial for improving the TGP thermal performance. Small change of vapor core thickness can lead to great change of TGP thermal performance. The ultrathin TGP can reach an effective thermal conductivity of 2207 W/(m·K) at an input power of 22.66 W over a heating area of 8 mm × 8 mm.

Osteosarcoma is a malignant tumor most commonly arising in children and adolescents and associated with poor prognosis. In recent years, some prognostic models have been constructed to assist clinicians in the treatment of osteosarcoma. However, the prognosis and treatment of patients with osteosarcoma remain unsatisfactory. Notably, super-enhancer (SE)-associated genes strongly promote the progression of osteosarcoma. In the present study, we constructed a novel effective prognostic model using SE-associated genes from osteosarcoma. Five SE-associated genes were initially screened through the least absolute shrinkage and selection operator (Lasso) penalized Cox regression, as well as univariate and multivariate Cox regression analyses. Meanwhile, a risk score model was constructed using the expression of these five genes. The excellent performance of the five-SE-associated-gene-based prognostic model was determined via time-dependent receiver operating characteristic (ROC) curves and Kaplan–Meier curves. Inferior outcome of overall survival (OS) was predicted in the high-risk group. A nomogram based on the polygenic risk score model was further established to validate the performance of the prognostic model. It showed that our prognostic model performed outstandingly in predicting 1-, 3-, and 5-year OS of patients with osteosarcoma. Meanwhile, these five genes also belonged to the hub genes associated with survival and necrosis of osteosarcoma according to the result of weighted gene co-expression network analysis based on the dataset of GSE39058. Therefore, we believe that the five-SE-associated-gene-based prognostic model established in this study can accurately predict the prognosis of patients with osteosarcoma and effectively assist clinicians in treating osteosarcoma in the future.