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AIM: To figure out whether various atropine dosages may slow the progression of myopia in Chinese kids and teenagers and to determine the optimal atropine concentration for effectively slowing the progression of myopia. METHODS: A systematic search was conducted across the Cochrane Library, PubMed, Web of Science, EMBASE, CNKI, CBM, VIP, and Wanfang database, encompassing literature on slowing progression of myopia with varying atropine concentrations from database inception to January 17, 2024. Data extraction and quality assessment were performed, and a network Meta-analysis was executed using Stata version 14.0 Software. Results were visually represented through graphs. RESULTS: Fourteen papers comprising 2475 cases were included; five different concentrations of atropine solution were used. The network Meta-analysis, along with the surface under the cumulative ranking curve (SUCRA), showed that 1% atropine (100%)>0.05% atropine (74.9%) >0.025% atropine (51.6%)>0.02% atropine (47.9%)>0.01% atropine (25.6%)>control in refraction change and 1% atropine (98.7%)>0.05% atropine (70.4%)>0.02% atropine (61.4%)>0.025% atropine (42%)>0.01% atropine (27.4%)>control in axial length (AL) change. CONCLUSION: In Chinese children and teenagers, the five various concentrations of atropine can reduce the progression of myopia. Although the network Meta-analysis showed that 1% atropine is the best one for controlling refraction and AL change, there is a high incidence of adverse effects with the use of 1% atropine. Therefore, we suggest that 0.05% atropine is optimal for Chinese children to slow myopia progression.

ObjectivesThe application of artificial intelligence (AI) in healthcare is an important public health issue. However, few studies have investigated the perceptions and attitudes of healthcare professionals toward its applications in nursing. This study aimed to explore the knowledge, attitudes, and concerns of healthcare professionals, AI-related professionals, and others in China toward AI in nursing.MethodsWe conducted an online cross-sectional study on nursing students, nurses, other healthcare professionals, AI-related professionals, and others in China between March and April 2024. They were invited to complete a questionnaire containing 21 questions with four sections. The survey followed the principle of voluntary participation and was conducted anonymously. The participants could withdraw from the survey at any time during the study.ResultsThis study obtained 1,243 valid questionnaires. The participants came from 25 provinces and municipalities in seven regions of China. Regarding knowledge of AI in nursing, 57% of the participants knew only a little about AI, 4.7% did not know anything about AI, 64.7% knew only a little about AI in nursing, and 13.4% did not know anything about AI in nursing. For attitudes toward AI in nursing, participants were positive about AI in nursing, with more than 50% agreeing and strongly agreeing with each question on attitudes toward AI in nursing. Differences in the numbers of participants with various categories of professionals regarding knowledge and attitudes toward AI in nursing were statistically significant (p

Abstract Sepsis‐associated acute lung injury (ALI) is a life‐threatening condition in intensive care units with high mortality. LncRNAs have been confirmed to participate in the underlying pathogenesis of septic ALI. This study investigated the biological functions of lncRNA CDKN2B‐AS1 in septic ALI and its potential mechanism.BEAS‐2B cells were challenged with lipopolysaccharide (LPS) and mice were subjected to caecal ligation and puncture (CLP) to induce septic ALI in vitro and in vivo. The expression levels of CDKN2B‐AS1, LIN28B, HIF‐1α, and pyroptosis‐related molecules were assessed by qRT–PCR or Western blotting. The production of IL‐1β and IL‐18 was detected by ELISA. BEAS‐2B cell pyroptosis was examined by flow cytometry. The interaction between LIN28B and CDKN2B‐AS1/HIF‐1α was validated by RIP and RNA pull‐down assays. Colocalization of CDKN2B‐AS1 and LIN28B was observed by FISH. ALI was determined by HE staining, the lung wet‐to‐dry (W/D) weight ratio, inflammatory cell numbers, and total protein concentration in bronchoalveolar lavage fluid (BALF). Caspase‐1 expression in the lung tissues was examined by immunohistochemical staining.CDKN2B‐AS1 was upregulated in BEAS‐2B cells after LPS stimulation. CDKN2B‐AS1 knockdown inhibited pyroptosis in LPS‐exposed BEAS‐2B cells in vitro and the lung tissues of septic mice in vivo. Mechanistically, CDKN2B‐AS1 interacted with LIN28B to enhance HIF‐1α stability. Rescue experiments showed that HIF‐1α overexpression counteracted the inhibitory effect of sh‐CDKN2B‐AS1 on LPS‐induced pyroptosis. CDKN2B‐AS1 bound to LIN28B to trigger NLRP3‐mediated pyroptosis by stabilizing HIF‐1α, which promoted sepsis‐induced ALI. CDKN2B‐AS1 might be a novel therapeutic target for this disease.

Abstract Background The base editors can introduce point mutations accurately without causing double-stranded DNA breaks or requiring donor DNA templates. Previously, cytosine base editors (CBEs) containing different deaminases are reported for precise and accurate base editing in plants. However, the knowledge of CBEs in polyploid plants is inadequate and needs further exploration. Results In the present study, we constructed three polycistronic tRNA-gRNA expression cassettes CBEs containing A3A, A3A (Y130F), and rAPOBEC1(R33A) to compare their base editing efficiency in allotetraploid N. benthamiana (n = 4x). We used 14 target sites to compare their editing efficiency using transient transformation in tobacco plants. The sanger sequencing and deep sequencing results showed that A3A-CBE was the most efficient base editor. In addition, the results showed that A3A-CBE provided most comprehensive editing window (C1 ~ C17 could be edited) and had a better editing efficiency under the base background of TC. The target sites (T2 and T6) analysis in transformed N. benthamiana showed that only A3A-CBE can have C-to-T editing events and the editing efficiency of T2 was higher than T6. Additionally, no off-target events were found in transformed N. benthamiana. Conclusions All in all, we conclude that A3A-CBE is the most suitable vector for specific C to T conversion in N. benthamiana. Current findings will provide valuable insights into selecting an appropriate base editor for breeding polyploid plants.

It is currently a challenge to perform noninvasive molecular biological analysis of in vitro fertilized embryos. In this issue of Cell Genomics, Wu et al.1 developed a non-invasive method to evaluate human pre-implantation embryos by characterizing the extracellular RNAs in spent media from the culture of in vitro fertilization embryos.

Abstract As biological macromolecules, proteins are involved in important cellular functions ranging from DNA replication and biosynthesis to metabolic signalling and environmental sensing. Protein sequencing can help understand the relationship between protein function and structure, and provide key information for disease diagnosis and new drug design. Nanopore sensors are a novel technology to achieve the goal of label‐free and high‐throughput protein sequencing. In recent years, nanopore‐based biosensors have been widely used in the detection and analysis of biomolecules such as DNA, RNA, and proteins. At the same time, computer simulations can describe the transport of proteins through nanopores at the atomic level. This paper reviews the applications of nanopore sensors in protein sequencing over the past decade and the solutions to key problems from a computer simulation perspective, with the aim of pointing the way to the future of nanopore protein sequencing.

AIM: To investigate the influence of the duration of orthokeratology lens cessation on patients' refractive status and corneal endothelial cells.METHODS: Adolescent myopia patients who wore orthokeratology lens from July 2019 to July 2020 and recently planned to stop wearing the lens were divided into mild group and severe group according to spherical equivalent. Refractive status, corneal morphology, corneal endothelial cells, and visual quality were measured at cessation and 1, 2 and 3mo after cessation.RESULTS: The corneal flat K values, steep K values and mean K values in the two groups were lower at cessation than those before wearing lenses. These values returned to the level before wearing lenses at 2mo after cessation(P>0.05). The corneal astigmatism, surface regularity index and surface asymmetry index in each group showed no statistically significant difference before wearing lenses and at 1, 2 and 3mo after cessation(P>0.05). There was no significant change in corneal endothelial cell density of the two groups at 1, 2 and 3mo after cessation compared with those before wearing lenses(P>0.05). The proportion of hexagonal cells in the two groups was lower at cessation than that before wearing lenses, and it returned to the level before wearing lenses at 1mo after cessation(P>0.05).CONCLUSION: Corneal morphology and corneal endothelial cells can be restored to the level before wearing orthokeratology lens at 3mo after cessation.

Abstract Background Fibromuscular dysplasia (FMD) has a high prevalence of associated nontraumatic carotid artery dissection, which could further result in transient ischaemic attack (TIA) or stroke. Limb shaking TIA is an unusual form of TIA that is commonly discribed in elderly patients with atherosclerotic backgrounds, while there are limited data about it in patients with FMD. Furthermore, discussions of limb shaking TIA in nonelderly patients are scarce. Case presentation An Asian 47-year-old female presented with intermittent involuntary movement of the left upper limb accompanied by neck torsion. The episode stopped soon after changing to the supine position. On native source images of time-of-flight magnetic resonance angiography (TOF-MRA), the right internal carotid artery showed a "dual lumen sign" with an intimal flap. On contrast-enhanced magnetic resonance angiography and sagittal black-blood T1WI, an intravascular haematoma with irregular lumen stenosis was observed, which overall indicated right internal carotid artery dissection. Digital subtraction angiography showed the characteristic “string-of-beads” appearance in the left internal carotid artery, and the presence of this sign pointed to the diagnosis of FMD. The patient was finally diagnosed with limb shaking TIA due to internal carotid dissection with fibromuscular dysplasia. The patient was prescribed dual anti-platelet therapy. The limb shaking vanished soon after admission with no reoccurrence in the three-month follow-up. Conclusions This case demonstrates that limb shaking TIA can present in patients with FMD. Limb shaking TIA in nonelderly patients can be caused by multiple diseases, and more detailed patient guidance is required in clinical practice.

High temperatures have a significant impact on plant growth and metabolism. In recent years, the fruit industry has faced a serious threat due to high-temperature stress on fruit plants caused by global warming. In the present study, we explored the molecular regulatory mechanisms that contribute to high-temperature tolerance in kiwifruit. A total of 36 Hsf genes were identified in the A. chinensis (Ac) genome, while 41 Hsf genes were found in the A. eriantha (Ae) genome. Phylogenetic analysis revealed the clustering of kiwifruit Hsfs into three distinct groups (groups A, B, and C). Synteny analysis indicated that the expansion of the Hsf gene family in the Ac and Ae genomes was primarily driven by whole genome duplication (WGD). Analysis of the gene expression profiles revealed a close relationship between the expression levels of Hsf genes and various plant tissues and stress treatments throughout fruit ripening. Subcellular localization analysis demonstrated that GFP-AcHsfA2a/AcHsfA7b and AcHsfA2a/AcHsfA7b -GFP were localized in the nucleus, while GFP-AcHsfA2a was also observed in the cytoplasm of Arabidopsis protoplasts. The results of real-time quantitative polymerase chain reaction (RT-qPCR) and dual-luciferase reporter assay revealed that the majority of Hsf genes, especially AcHsfA2a, were expressed under high-temperature conditions. In conclusion, our findings establish a theoretical foundation for analyzing the potential role of Hsfs in high-temperature stress tolerance in kiwifruit. This study also offers valuable information to aid plant breeders in the development of heat-stress-resistant plant materials.

Multiple displacement amplification (MDA) based on isothermal random priming and high fidelity phi29 DNA polymerase-mediated processive extension has revolutionized the field of whole genome amplification by enabling the amplification of minute amounts of DNA, such as from a single cell, generating vast amounts of DNA with high genome coverage. Despite its advantages, MDA has its own challenges, one of the grandest being the formation of chimeric sequences (chimeras), which presents in all MDA products and seriously disturbs the downstream analysis. In this review, we provide a comprehensive overview of current research on MDA chimeras. We first reviewed the mechanisms of chimera formation and chimera detection methods. We then systematically summarized the characteristics of chimeras, including overlap, chimeric distance, chimeric density, and chimeric rate, as found in independently published sequencing data. Finally, we reviewed the methods used to process chimeric sequences and their impacts on the improvement of data utilization efficiency. The information presented in this review will be useful for those interested in understanding the challenges with MDA and in improving its performance.

ObjectiveTo investigate the effect of transrectal multimodal ultrasound combined with serum prostate-specific antigen (PSA)-related indicators and machine learning for the diagnosis of clinically significant prostate cancer.MethodsBased on Gleason score of postoperative pathological results, the subjects were divided into clinically significant prostate cancer groups(GS>6)and non-clinically significant prostate cancer groups(GS ≤ 6). The independent risk factors were obtained by univariate logistic analysis. Artificial neural network (ANN), logistic regression (LR), support vector machine (SVM), decision tree (DT), random forest (RF), and K-nearest neighbor (KNN) machine learning models were combined with clinically significant prostate cancer risk factors to establish the machine learning model, calculate the model evaluation indicators, construct the receiver operating characteristic curve (ROC), and calculate the area under the curve (AUC).ResultsIndependent risk factor items (P< 0.05) were entered into the machine learning model. A comparison of the evaluation indicators of the model and the area under the ROC curve showed the ANN model to be best at predicting clinically significant prostate cancer, with a sensitivity of 80%, specificity of 88.6%, F1 score of 0.897, and the AUC was 0.855.ConclusionEstablishing a machine learning model by rectal multimodal ultrasound and combining it with PSA-related indicators has definite application value in predicting clinically significant prostate cancer.

Current methods to identify G-quadruplex structures in DNA require specialized protocols and multiple rounds of sequencing. Here, the authors develop a method to detect G-quadruplex structures in DNA based on fluctuations in sequencing quality in a standard sequencing experiment.

Background: Previous studies have shown that a large number of valuable and functional cell-free RNAs (cfRNAs) were found in follicular fluid. However, the species and characteristics of follicular fluid cfRNAs have not been reported. Furthermore, their implications are still barely understood in the evaluation of follicular fluid from follicles of different sizes, which warrants further studies.Objective: This study investigated the landscape and characteristics of follicular fluid cfRNAs, the source of organization, and the potential for distinguishing between follicles of different sizes.Methods: Twenty-four follicular fluid samples were collected from 20 patients who received in vitro fertilization (n = 9) or ICSI (n = 11), including 16 large follicular fluid and 8 small follicular fluid samples. Also, the cfRNA profile of follicular fluid samples was analyzed by RNA sequencing.Results: This result indicated that the concentration of follicular fluid cfRNAs ranged from 0.78 to 8.76 ng/ml, and fragment length was 20–200 nucleotides. The concentration and fragment length of large follicular fluid and small follicular fluid samples were not significantly different (p > 0.05). The technical replica correlation of follicular fluid samples ranged from 0.3 to 0.9, and the correlation of small follicular fluid samples was remarkably (p < 0.001) lower than that of large follicular fluid samples. Moreover, this study found that cfRNAs of the follicular fluid could be divided into 37 Ensembl RNA biotypes, and a large number of mRNAs, circRNAs, and lncRNAs were observed in the follicular fluid. The number of cfRNAs in large follicular fluid was remarkably (p < 0.05) higher than that of small follicular fluid. Furthermore, the follicular fluid contained a large amount of intact mRNA and splice junctions and a large number of tissue-derived RNAs, which are at a balanced state of supply and elimination in the follicular fluid. KEGG pathway analysis showed that differentially expressed cfRNAs were enriched in several pathways, including thyroid hormone synthesis, the cGMP-PKG signaling pathway, and inflammatory mediator regulation of TRP channels. In addition, we further showed that four cfRNAs (TK2, AHDC1, PHF21A, and TTYH1) serve as a potential indicator to distinguish the follicles of different sizes. The ROC curve shows great potential to predict follicular fluid from follicles of different sizes [area under the curve (AUC) > 0.88].Conclusion: Overall, our study revealed that a large number of cfRNAs could be detected in follicular fluid and could serve as a potential non-invasive biomarker in distinguishing between follicles of different sizes. These results may inform the study of the utility and implementation of cfRNAs in clinical practice.

PurposeThe purpose of this study was to define whether mild cognitive impairment (MCI) is associated with iron deposition in rich-club nodes distant from cerebral microbleeds (CMBs) in patients with cerebral small vessel disease (CSVD).MethodsA total of 64 participants underwent magnetic resonance imaging (MRI) scanning and were separated into three groups, namely, CMB(+), CMB(–), and healthy controls (HCs). We compared their characteristics and susceptibility values of rich-club nodes [e.g., superior frontal gyrus (SFG), precuneus, superior occipital gyrus (SOG), thalamus, and putamen]. We then divided the CMB(+) and CMB(–) groups into subgroups of patients with or without MCI. Then, we analyzed the relationship between iron deposition and MCI by comparing the susceptibility values of rich-club nodes. We assessed cognitive functions using the Montreal Cognitive Assessment (MoCA) and quantified iron content using quantitative susceptibility mapping (QSM).ResultsIn the putamen, the CMB(+) and CMB(–) groups had significantly different susceptibility values. Compared with the HCs, the CMB(+) and CMB(–) groups had significantly different susceptibility values for the SFG and SOG. In addition, we found significant differences in the putamen susceptibility values of the CMB(+)MCI(+) group and the two CMB(–) groups. The CMB(+)MCI(+) and CMB(+)MCI(–) groups had significantly different precuneus susceptibility values. The binary logistic regression analysis revealed that only higher susceptibility values of precuneus were associated with a cognitive decline in patients with CMBs, and it indicated statistical significance.ConclusionIron deposition in the precuneus is an independent risk factor for MCI in patients with CMBs. CMBs might influence iron content in remote rich-club nodes and be relevant to MCI.

ObjectiveTo build a machine learning (ML) prediction model for prostate cancer (PCa) from transrectal ultrasound video clips of the whole prostate gland, diagnostic performance was compared with magnetic resonance imaging (MRI).MethodsWe systematically collated data from 501 patients—276 with prostate cancer and 225 with benign lesions. From a final selection of 231 patients (118 with prostate cancer and 113 with benign lesions), we randomly chose 170 for the purpose of training and validating a machine learning model, while using the remaining 61 to test a derived model. We extracted 851 features from ultrasound video clips. After dimensionality reduction with the least absolute shrinkage and selection operator (LASSO) regression, 14 features were finally selected and the support vector machine (SVM) and random forest (RF) algorithms were used to establish radiomics models based on those features. In addition, we creatively proposed a machine learning models aided diagnosis algorithm (MLAD) composed of SVM, RF, and radiologists’ diagnosis based on MRI to evaluate the performance of ML models in computer-aided diagnosis (CAD). We evaluated the area under the curve (AUC) as well as the sensitivity, specificity, and precision of the ML models and radiologists’ diagnosis based on MRI by employing receiver operator characteristic curve (ROC) analysis.ResultsThe AUC, sensitivity, specificity, and precision of the SVM in the diagnosis of PCa in the validation set and the test set were 0.78, 63%, 80%; 0.75, 65%, and 67%, respectively. Additionally, the SVM model was found to be superior to senior radiologists’ (SR, more than 10 years of experience) diagnosis based on MRI (AUC, 0.78 vs. 0.75 in the validation set and 0.75 vs. 0.72 in the test set), and the difference was statistically significant (p< 0.05).ConclusionThe prediction model constructed by the ML algorithm has good diagnostic efficiency for prostate cancer. The SVM model’s diagnostic efficiency is superior to that of MRI, as it has a more focused application value. Overall, these prediction models can aid radiologists in making better diagnoses.

Lily Fusarium wilt disease caused by Fusarium spp. spreads rapidly and is highly destructive, leading to a severe reduction in yield. In this study, lily (Lilium brownii var. viridulum) bulbs were irrigated after planting with suspensions of two Bacillus strains that effectively control lily Fusarium wilt disease to assess their effects on the rhizosphere soil properties and microbial community. A high-throughput sequencing of microorganisms in the rhizosphere soil was performed and the soil physicochemical properties were measured. The FunGuild and Tax4Fun tools were used for a functional profile prediction. The results showed that Bacillus amyloliquefaciens BF1 and B. subtilis Y37 controlled lily Fusarium wilt disease with control efficacies of 58.74% and 68.93%, respectively, and effectively colonized the rhizosphere soil. BF1 and Y37 increased the bacterial diversity and richness of the rhizosphere soil and improved the physicochemical properties of the soil, thereby favoring the proliferation of beneficial microbes. The relative abundance of beneficial bacteria was increased and that of pathogenic bacteria was decreased. Bacillus abundance in the rhizosphere was positively correlated with most soil physicochemical properties, whereas Fusarium abundance was negatively correlated with most physicochemical properties. Functional prediction revealed that irrigation with BF1 and Y37 significantly upregulated glycolysis/gluconeogenesis among metabolism and absorption pathways. This study provides insights into the mechanism by which two Bacillus strains with antifungal activity, BF1 and Y37, antagonize plant pathogenic fungi and lays the foundation for their effective application as biocontrol agents.

Sub-millimeter thick phase change material (PCM) composites have been utilized in the thermal management of micro-electronics serving as a novel thermal interfacial material. However, there is a lack of appropriate measuring methods and precise data for the thin-film PCM composites' intrinsic thermal conductivity, as well as the thermal contact resistance (TCR) at interfaces between those thin-films and metal. In this work, the out-of-plane thermal conductivity of thin-film PCM35, which is a paraffin composite showing the melting point of 35 °C, was first gauged through the commercialized transient plane source (TPS) method, followed by a correction process to deduct the TCR between thin films/temperature sensor interfaces. The direct TPS readings were corrected based on the proportional relation between samples’ thickness and inherent thermal resistance. An improved steady-state heat flow apparatus designed for thin-walled samples was then utilized to examine the reliability of the corrected TPS technique, with a relative deviation between them being only ∼7%. In order to test the applicability of the corrected TPS method, the thermal conductivities of thin polytetrafluoroethylene films were also determined. Furthermore, the TCR between thin PCM35 film and thin 1060Al plate was identified by performing the improved steady-state apparatus. The contribution of overheated PCM35 film on fitting the interfacial voids and reducing the TCR were elucidated, which can guide the thermal design with the use of such thin-film PCMs.

Single-cell genome sequencing has become a useful tool in medicine and biology studies. However, an independent library is required for each cell in single-cell genome sequencing, so that the cost grows with the number of cells. In this study, we report a study which efficiently analyses single-cell copy number variation (CNV) using overlapping pooling strategy and branch and bound (B&B) algorithm. Single cells were overlapped pooled before sequencing, and later were assorted into specific types by estimating their CNV patterns by B&B algorithm. Instead of constructing libraries for each cell, a library is required only for each pool. As the number of pools is smaller than the cells, fewer libraries are required, which means lower cost. Through computer simulations, we overlapped pooled 80 cells into 40 or 27 pools and classified them into cell types based on CNV pattern. The results showed that 84% cells in 40 pools and 76.5% cells in 27 pools were correctly classified on average, while only half or one-third of the sequencing libraries were required. Combining with traditional approaches, our method is expected to significantly improve the efficiency of single-cell genome sequencing.

Polymer-derived ceramic (PDC) thin films are promising wear-resistant coatings for protecting metals and carbon–carbon composites from corrosion and oxidation. However, the high pyrolysis temperature hinders the applications on substrate materials with low melting points. We report a new synthesis route for PDC coatings using initiated chemical vapor deposited poly(1,3,5-trivinyl-1,3,5-trimethylcyclotrisiloxane) (pV _3 D _3 ) as the precursor. We investigated the changes in siloxane moieties and the network topology, and proposed a three-stage mechanism for the thermal annealing process. The rise of the connectivity number for the structures obtained at increased annealing temperatures was found with strong correlation to the enhanced mechanical properties and thermal conductivity. Our PDC films obtained via annealing at 850 °C exhibit at least 14.6% higher hardness than prior reports for PDCs synthesized below 1100 °C. Furthermore, thermal conductivity up to 1.02 W (mK) ^−1 was achieved at the annealing temperature as low as 700 °C, which is on the same order of magnitude as PDCs obtained above 1100 °C. Using minimum thermal conductivity models, we found that the thermal transport is dominated by diffusons in the films below the percolation of rigidity, while ultra-short mean-free path phonons contribute to the thermal conductivity of the films above the percolation threshold. The findings of this work provide new insights for the development of wear-resistant and thermally conductive PDC thin films for durable protection coatings.

In HV cable fault location technology, line parameter uncertainty has an impact on the location criterion and affects the fault location result. Therefore, it is of great significance to study the uncertainty quantification of line parameters. In this paper, an impedance-based fault location criterion was used for an uncertainty study. Three kinds of uncertainty factors, namely the sheath resistivity per unit length, the equivalent grounding resistance on both sides, and the length of the cable section, were taken as random input variables without interaction. They were subject to random uniform distribution within a 50% amplitude variation. The relevant statistical information, such as the mean value, standard deviation and probability distribution, of the normal operation and fault state were calculated using the Monte Carlo simulation (MCS) method, the polynomial chaos expansion (PCE) method, and the univariate dimension reduction method (UDRM), respectively. Thus, the influence of uncertain factors on fault location was analyzed, and the calculation results of the three uncertainty quantification methods compared. The results indicate that: (1) UQ methods are effective for simulation analysis of fault locations, and UDRM has certain application prospects for HV fault location in practice; (2) the quantification results of the MCS, PCE, and UDRM were very close, while the mean convergence rate was significantly higher for the UDRM; (3) compared with the MCS, PCE, and UDRM, the PCE and UDRM had higher accuracy, and MCS and UDRM required less running time.

The popularity of smart applications enables the large-scale integration of flexible loads to power systems, which poses a considerable challenge to system scheduling. Focusing on scheduling optimization with large-scale flexible loads, this paper proposes the equivalent aggregated method for flexible loads, which converts a large number of flexible loads into a few equivalent models to participate in system scheduling. In order to establish the equivalent model, flexible loads are grouped based on their parameters such that loads with the same or similar parameters are clustered into the same group. Then, the equivalent model for each group is established, a proof of the equivalence relationship between the original model and the equivalent model is provided, and the upper bound of equivalence deviations is estimated. The whole equivalent aggregated model is expressed as the sum of equivalent models of all groups. Afterwards, a new approach of applying the equivalent aggregated model to system scheduling is proposed. Case studies show that the equivalent aggregated model can effectively schedule large-scale flexible loads to shave the peak and fill the valley, with small equivalent deviations and fast calculation speed. This validates the proposed model and demonstrates its promising applications to large-scale load scheduling.

Intestinal mycobiome dysbiosis plays an important role in the advancement of HIV- and HCV-infected patients. Co-infection with HCV is an important risk factor for exacerbating immune activation in HIV-infected patients, and gut fungal microbial dysbiosis plays an important role. However, no systematic study has been conducted on the intestinal fungal microbiome of HIV/HCV co-infected patients to date. Patients infected with HIV and HCV, either alone or in combination, and healthy volunteers were included. Stool samples were collected for fungal ITS sequencing and for further mycobiome statistical analysis. We found that the abundance of fungal species significantly decreased in the HIV/HCV co-infection group compared to in the healthy control group, while no significant differences were found in the mono-infection groups. Low-CD4 + T-cell patients in the HIV group and high-ALT-level patients in the HCV group were discovered to have a more chaotic fungal community. Furthermore, the opportunistic pathogenic fungal profiles and fungal inter-correlations in the co-infection group became less characteristic but more complicated than those in the mono-infection groups. Intestinal fungal dysregulation occurs in HIV- and HCV-infected patients, and this dysregulation is further complicated in HIV/HCV co-infected patients.

Our study aimed to determine the impact of HIV coinfection on the natural progression of liver disease in treatment-naive HCV-infected patients. From 2009 to 2017, we tracked non-invasive markers of liver fibrosis and end-stage liver disease (ESLD)-associated mortality among HCV mono-infected and HIV/HCV coinfected patients in an impoverished village in China. The study cohort consisted of 355 HBsAg-negative and anti-HCV (+) or anti-HIV (+) patients recruited in July 2009, 164 of whom were diagnosed with HIV-1 infection. The surviving patients were re-evaluated in August 2017. During the follow-up, the disease status, liver biochemical, and non-invasive indicators of liver fibrosis (APRI and FIB-4) were measured. The transaminases ALT and AST were significantly higher in HIV-positive HCV resolvers (HIV+ HCVr) than in HIV-negative HCV resolvers (HCVr) (p = 0.019 and p < 0.0001, respectively). APRI and FIB-4 scores of HIV-positive chronic HCV carriers (HIV+ HCVc) were significantly higher than in HIV-negative chronic HCV carriers (HCVc) (p < 0.001). Similarly, APRI and FIB-4 scores were higher in the HIV+ HCVr group than in the HCVr group (ps < 0.001). From 2009 to 2017, the levels of ALT (p = 0.006), AST (p = 0.003), APRI (p = 0.015), and FIB-4 (p = 0.025) were significantly elevated in the HIV/HCV coinfected patients with CD4+ T counts below 500 cells/l. ESLD-related mortality was significantly greater in HIV/HCV-infected cases than in HCV mono-infected patients (73.3% vs. 31.3%, p = 0.009) among patients (n = 45) who died between 2009 and 2017 during follow-up. These findings suggest a higher risk of ESLD-related death and rapid progression of liver fibrosis in HIV/HCV coinfected individuals compared with HCV mono-infected patients. During HIV/HCV coinfection, HIV infection may aggravate HCV-associated liver injury.

Growth-regulating factors (GRFs) encode plant-specific transcription factors that play a vital role in regulation of plant growth, development, and stress response. Although GRFs have been identified in various plants, there is no reported work available in Actinidia (commonly known as kiwifruit) so far. In the present study, we identified 22 GRF genes on A. chinensis (hereafter A. chinensis is referred to as Ac, and GRF genes in A. chinensis are referred to as AcGRF) distributed on 17 chromosomes and one contig, and 26 GRF genes in A. eriantha (hereafter A. eriantha is referred to as Ae, and GRF genes in A. eriantha are referred to as AeGRF) distributed on 21 chromosomes. Phylogenetic analysis showed that kiwifruit GRF proteins were clustered into five distinct groups. Additionally, kiwifruit GRFs showed motif composition and gene structure similarities within the same group. Synteny analysis showed that whole-genome duplication played a key role in the expansion of the GRF family in kiwifruit. The higher expression levels of kiwifruit GRFs in young tissues and under stress conditions indicated their regulatory role in kiwifruit growth and development. We observed two genes in Ae (AeGRF6.1, AeGRF 6.2) and two genes in Ac (AcGRF 6.1, AeGRF 6.2) significantly upregulated in different RNA-seq datasets. The presence of conserved protein structures and cis-regulatory elements caused functional divergence in duplicated gene pairs. The subcellular localization indicated the presence of kiwifruit GRFs in the nucleus of the plant cell. Protein-protein interaction analysis predicted AtGIF protein orthologs for AcGRFs and AeGRFs. Taken together, we systematically analyzed the characterization of kiwifruit GRF family members for their potential role in kiwifruit development and Pseudomonas syringae pv. actinidiae (Psa.) invasion response. Further functional studies of kiwifruit GRFs in plant growth, development, and stress response will provide valuable insights for kiwifruit breeders.

Background: Antibody-dependent cellular cytotoxicity (ADCC), which mainly mediated by natural killer (NK) cells, may play a critical role in human immunodeficiency virus type-1 (HIV-1) disease progression. However, the potential mechanisms that affecting NK-mediated ADCC response are still not well-elucidated.Methods: Antigen-antibody complex model of Ab-opsonized P815 cells was adopted to induce a typical non-specific ADCC response. The capacities of HIV-1 specific NK-ADCC were measured by using the combination model of gp120 protein and plasma of HIV-1 elite controllers. The levels of plasma cytokine were measured by ELISA. Anti-IL-2 blocking antibody was used to analyze the impact of activated CD56+ T cells on NK-ADCC response.Results: IL-2, IL-15, IFN-α, and IFN-β could effectively enhance the non-specific and HIV-1-specific NK-ADCC responses. Compared with healthy controls, HIV-1-infected patients showed decreased plasma IL-2 levels, while no differences of plasma IFN-α, IL-15, and IFN-β were presented. IL-2 production was detected from CD56+ T cells activated through antibody-dependent manner. The capability of NK-ADCC could be weakened by blocking IL-2 secretion from activated CD56+ T cells. Although no difference of frequencies of CD56+ T cells was found between HIV-1-infected patients and healthy controls, deficient IL-2 secretion from activated CD56+ T were found in chronic HIV-1 infection.Conclusions: The impaired ability of activated CD56+ T cells to secreting IL-2 might contribute to the attenuated NK cell-mediated ADCC function in HIV-1 infection.

Single-molecule Förster resonance energy transfer (smFRET) inherits the strategy of measurement from the effective “spectroscopic ruler” FRET and can be utilized to observe molecular behaviors with relatively high throughput at nanometer scale. The simplicity in principle and configuration of smFRET make it easy to apply and couple with other technologies to comprehensively understand single-molecule dynamics in various application scenarios. Despite its widespread application, smFRET is continuously developing and novel studies based on the advanced platforms have been done. Here, we summarize some representative examples of smFRET research of recent years to exhibit the versatility and note typical strategies to further improve the performance of smFRET measurement on different biomolecules.

Microfluidic system, as a kind of miniature integrated operating platform, has been applied to solid-state nanopore sensors after many years of experimental study. In the process of introducing microfluidic into solid-state nanopore sensors, many novel device structures are designed due to the abundance of analytes and the diversity of detection methods. Here we review the fundamental setup of nanopore-based microfluidic systems and the developments and advancements that have been taking place in the field. The microfluidic systems with a multichannel strategy to elevate the throughput and efficiency of nanopore sensors are then presented. Multifunctional detection represented by optical-electrical detection, which is realized by microfluidic integration, is also described. A high integration microfluidic system with nanopore is further discussed, which shows the prototype of commercialization.

The growing interest in cell sorting and trapping is driving the demand for high performance technologies. Using labeling techniques or external forces, cells can be identified by a series of methods. However, all of these methods require complicated systems with expensive devices. Based on inherent differences in cellular morphology, cells can be sorted by specific structures in microfluidic devices. The weir filter is a basic and efficient cell sorting and trapping structure. However, in some existing weir devices, because of cell deformability and high flow velocity in gaps, trapped cells may become stuck or even pass through the gaps. Here, we designed and fabricated a microfluidic device with interdigital channels for cell sorting and trapping. The chip consisted of a sheet of silicone elastomer polydimethylsiloxane and a sheet of glass. A square-wave-like weir was designed in the middle of the channel, comprising the interdigital channels. The square-wave pattern extended the weir length by three times with the channel width remaining constant. Compared with a straight weir, this structure exhibited a notably higher trapping capacity. Interdigital channels provided more space to slow down the rate of the pressure decrease, which prevented the cells from becoming stuck in the gaps. Sorting a mixture K562 and blood cells to trap cells demonstrated the efficiency of the chip with the interdigital channel to sort and trap large and less deformable cells. With stable and efficient cell sorting and trapping abilities, the chip with an interdigital channel may be widely applied in scientific research fields.

Boechera stricta (B. stricta) is a wild relative of Arabidopsis, occurring in mostly montane regions of western North America. In this article, we assembled the complete mitochondrial (mt) DNA sequence of B. stricta into a circular genome of length 271,601 bp, including 31 protein-coding genes, 21 tRNA genes, and 3 rRNA genes. From the neighbour-joining phylogenetic tree was constructed, based on the 23 conserved protein-coding genes of B. stricta and other 23 plant species, and the phylogenic relationship and evolution position of B. stricta were determined. The complete mt genome would be useful for further investigation of the genotype-by-environment interactions in mitochondria of Boechera.

Cell-free DNA (cfDNA), which promotes precision oncology, has received extensive concern because of its abilities to inform genomic mutations, tumor burden and drug resistance. The absolute quantification of cfDNA concentration has been proved as an independent prognostic biomarker of overall survival. However, the properties of low abundance and high fragmentation hinder the isolation and further analysis of cfDNA. Microfluidic technologies and lab-on-a-chip (LOC) devices provide an opportunity to deal with cfDNA sample at a micrometer scale, which reduces required sample volume and makes rapid isolation possible. Microfluidic platform also allow for high degree of automation and high-throughput screening without liquid transfer, where rapid and precise examination and quantification could be performed at the same time. Microfluidic technologies applied in cfDNA isolation and analysis are limited and remains to be further explored. This paper reviewed the existing and potential applications of microfluidic technologies in collection and enrichment of cfDNA, quantification, mutation detection and sequencing library construction, followed by discussion of future perspectives.

The co-existence of wild-type and mutated mitochondrial DNA (mtDNA) molecules termed heteroplasmy becomes a research hot point of mitochondria. In this review, we listed several methods of mtDNA heteroplasmy research, including the enrichment of mtDNA and the way of calling heteroplasmic variations. At the present, while calling the novel ultra-low level heteroplasmy, high-throughput sequencing method is dominant while the detection limit of recorded mutations is accurate to 0.01% using the other quantitative approaches. In the future, the studies of mtDNA heteroplasmy may pay more attention to the single-cell level and focus on the linkage of mutations.

MiRNAs have been widely studied due to their important post-transcriptional regulatory roles in gene expression. Many reports have demonstrated the evidence of miRNA isoform products (isomiRs) in high-throughput small RNA sequencing data. However, the biological function involved in these molecules is still not well investigated. Here, we developed a Shannon entropy-based model to estimate isomiR expression profiles of high-throughput small RNA sequencing data extracted from miRBase webserver. By using the Kolmogorov-Smirnov statistical test (KS test), we demonstrated that the 5p and 3p miRNAs present more variants than the single arm miRNAs. We also found that the isomiR variant, except the 3' isomiR variant, is strongly correlated with Minimum Free Energy (MFE) of pre-miRNA, suggesting the intrinsic feature of pre-miRNA should be one of the important factors for the miRNA regulation. The functional enrichment analysis showed that the miRNAs with high variation, particularly the 5' end variation, are enriched in a set of critical functions, supporting these molecules should not be randomly produced. Our results provide a probabilistic framework for miRNA isoforms analysis, and give functional insights into pre-miRNA processing.

The chimeric sequences produced by phi29 DNA polymerase, which are named as chimeras, influence the performance of the multiple displacement amplification (MDA) and also increase the difficulty of sequence data process. Despite several articles have reported the existence of chimeric sequence, there was only one research focusing on the structure and generation mechanism of chimeras, and it was merely based on hundreds of chimeras found in the sequence data of E. coli genome.We finished data mining towards a series of Next Generation Sequencing (NGS) reads which were used for whole genome haplotype assembling in a primary study. We established a bioinformatics pipeline based on subsection alignment strategy to discover all the chimeras inside and achieve their structural visualization. Then, we artificially defined two statistical indexes (the chimeric distance and the overlap length), and their regular abundance distribution helped illustrate of the structural characteristics of the chimeras. Finally we analyzed the relationship between the chimera type and the average insertion size, so that illustrate a method to decrease the proportion of wasted data in the procedure of DNA library construction.131.4 Gb pair-end (PE) sequence data was reanalyzed for the chimeras. Totally, 40,259,438 read pairs (6.19%) with chimerism were discovered among 650,430,811 read pairs. The chimeric sequences are consisted of two or more parts which locate inconsecutively but adjacently on the chromosome. The chimeric distance between the locations of adjacent parts on the chromosome followed an approximate bimodal distribution ranging from 0 to over 5,000 nt, whose peak was at about 250 to 300 nt. The overlap length of adjacent parts followed an approximate Poisson distribution and revealed a peak at 6 nt. Moreover, unmapped chimeras, which were classified as the wasted data, could be reduced by properly increasing the length of the insertion segment size through a linear correlation analysis.This study exhibited the profile of the phi29MDA chimeras by tens of millions of chimeric sequences, and helped understand the amplification mechanism of the phi29 DNA polymerase. Our work also illustrated the importance of NGS data reanalysis, not only for the improvement of data utilization efficiency, but also for more potential genomic information.

Riemerella anatipestifer causes epizootics of infectious disease in poultry that result in serious economic losses to the duck industry. Our previous studies have shown that some strains of R. anatipestifer can form a biofilm, and this may explain the intriguing persistence of R. anatipestifer on duck farms post infection. In this study we used strain CH3, a strong producer of biofilm, to construct a library of random Tn4351 transposon mutants in order to investigate the genetic basis of biofilm formation by R. anatipestifer on abiotic surfaces. A total of 2,520 mutants were obtained and 39 of them showed a reduction in biofilm formation of 47%-98% using crystal violet staining. Genetic characterization of the mutants led to the identification of 33 genes. Of these, 29 genes are associated with information storage and processing, as well as basic cellular processes and metabolism; the function of the other four genes is currently unknown. In addition, a mutant strain BF19, in which biofilm formation was reduced by 98% following insertion of the Tn4351 transposon at the dihydrodipicolinate synthase (dhdps) gene, was complemented with a shuttle plasmid pCP-dhdps. The complemented mutant strain was restored to give 92.6% of the biofilm formation of the wild-type strain CH3, which indicates that the dhdp gene is associated with biofilm formation. It is inferred that such complementation applies also to other mutant strains. Furthermore, some biological characteristics of biofilm-defective mutants were investigated, indicating that the genes deleted in the mutant strains function in the biofilm formation of R. anatipestifer. Deletion of either gene will stall the biofilm formation at a specific stage thus preventing further biofilm development. In addition, the tested biofilm-defective mutants had different adherence capacity to Vero cells. This study will help us to understand the molecular mechanisms of biofilm development by R. anatipestifer and to study the pathogenesis of R. anatipestifer further.

Background: For adults with inflammatory bowel disease (IBD), they experience many challenges in dietary decision‐making. Thus, this study examined the perspective and experiences of adults with IBD in dietary decision‐making. Objective: This study aimed to explore the perception and consideration of people with IBD in their daily dietary decisions through monitoring, interpretation and action during the decision‐making process. Design: A qualitative study of individuals affected by IBD was conducted through semistructured interviews. Results: Twenty patients were recruited from four tertiary hospitals in Nanjing, China, and each participant completed a semistructured interview. The majority of participants reported on the process and experience of dietary decision‐making. Key themes were categorised into three stages: (1) assessing needs, preferences and food cues (monitor); (2) moving from experience to expertise (interpret) and (3) balancing expectations amidst limitations (act). The majority of participants reported that their decisions were shaped by assessing current disease status and food cues. Those interviewed with IBD were willing to make tradeoffs for bowel stability, but their decisions were also influenced by past dietary experiences and traditional Chinese beliefs. The lack of awareness of dietary guidelines was a significant barrier to healthy eating decisions. Positive or negative feelings accompanied dietary decisions. Conclusion: Although most people with IBD change their diet after diagnosis, the changes made are often inconsistent with existing dietary recommendations. Several factors can influence the dietary decision‐making process. This study will help assess the experiences of people with IBD in dietary decision‐making to encourage the formation of targeted dietary health and well‐being interventions. Knowledge of nutrition and diet should be provided in education and training programmes for IBD management. Patient or Public Contribution: The first three authors of this paper were the lead researchers in this study's design. These authors were mentored by patient researchers who also contributed to the manuscript, and the research process was co‐lead and directed by other patient participants and consultants. The results of this paper were directly obtained from patient participants. [ABSTRACT FROM AUTHOR]