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This review introduces various in vitro and in vivo CTC enrichment technologies based on the characteristics of CTC and nanostructures and provides detailed information about the clinical applications of CTC.

The synthesis and biological assessment of neutral or cationic platinum group metal-based anticancer complexes have been extremely studied, whereas there are few reports on the corresponding zwitterionic complexes. Herein, the synthesis, characterization, and bioactivity of zwitterionic half-sandwich phosphine-imine iridium(III), rhodium(III), and ruthenium(II) complexes were presented. The sulfonated phosphine-imine ligand and a group of zwitterionic half-sandwich

Microfluidic devices have developed a wide range of applications in the fields of biomedicine, chemistry, and analytical science. But it is easy to form and accumulate bubbles in microfluidic devices. These bubbles could decrease the detection sensitivity, cause inaccurate analysis results, and even damage the functional region of the device. Inspired by the embolism repair mechanism of angiosperms and the permeability of gas permeable materials, this work proposes a bioinspired permeation-enhanced degassing method. Bionic redundant pits are used in this method to keep bubbles from spreading between microchannels and maintain the continuity of the flow. A hydrophobic gas permeable material is used to enhance the bubble capture capability and accelerate the degassing process. This method can eliminate bubbles automatically and continuously in real time without auxiliary equipment. Compared to the bubble removal only depending on solution in water, the degassing effect of the permeation-enhanced degassing method shows about 1.6 times improvement in the same conditions, and the capability of trapping bubbles is improved by 1.33 times. In this paper, this method was integrated into a concentration gradient generator and a cell culture device. The results show that the concentration gradient generator with degassing structures can dissolve bubbles in a rapid way and reach the stability of the concentration gradient within 5-15 min. The degassing method can run for a long time and improve the cell density and cell viability of HeLa cells up to 2.64 and 1.12 times, respectively. The method has a broad application prospect in microfluidic fields including biomedical fluid processing, virus detection, and microscale reactor operation.

BackgroundGrowing evidence has reported an association between multimorbidity and falls and fear of falling (FOF) in older adults, however, the results regarding this association from China are limited. Our study aimed to investigate the association between multimorbidity and falls and FOF in older adults in eastern China.MethodsWe conducted a cross-sectional study in Zhejiang Province, Eastern China, which recruited a provincial representative sample of adults aged ≥ 60 years. A structured questionnaire including demographic characteristics, chronic diseases, history of falls in the past 12 months, and FOF, was administered by all participants. The exposure variable was multimorbidity, which was defined as the presence of two or more chronic diseases and medical conditions in the same individual. The outcomes included a history of falls and FOF. Multivariate logistic regression was used to evaluate the association between multimorbidity and falls and FOF in older adults.ResultsIn total of 7,774 participants were included in the analysis, among whom 3,898 (50.1%) were female, with a mean ± standard deviation age is 72.9 ± 8.4 years. Multimorbidity was associated with the increased risk of falling in older adults [adjusted odds ratio (OR), 1.99; 95% confidence interval (CI):1.55–2.36]. The ORs for having experienced single fall and repeated falls were 1.85 (95% CI: 1.42–2.42) and 3.45 (95% CI: 1.47–6.97), respectively, with multimorbidity compared with those without chronic diseases. The older adults with multimorbidity were more likely to report FOF compared with those without chronic diseases (adjusted OR, 1.49; 95%CI:1.30–1.70). Moreover, the association between multimorbidity and FOF remained significant in the older adults with a history of fall (OR, 1.57; 95%CI:1.04–2.38).ConclusionThe association between multimorbidity and falls and FOF is significant in the Chinese population and the effects of multimorbidity on falls and FOF do not vary according to the frequency and history of falls in older adults.

A novel negative-stranded RNA mycovirus was isolated from the phytopathogenic fungus Fusarium sibiricum strain AH32. This virus, tentatively named Fusarium sibiricum coguvirus 1 (FsCV1), has a bipartite genome consisting of two RNA segments (RNA1 and RNA2). The negative-sense RNA1 is 6737 nt in length, encoding the RNA-dependent RNA polymerase (RdRp, p251) in the viral complementary (vc) strand. The ambisense RNA2 (1232 nt long) encodes two overlapping proteins: the nucleocapsid protein (NP, p38) in the vc strand and an unknown function protein (UFP, p36) in the viral (v) strand, different from the typical features of Bunyavirales members: the two open reading frames are separated by a long AU-rich intergenic region (IR). Phylogenetic analysis based on the RdRp demonstrated that FsCV1 belongs to the genus Coguvirus, family Phenuiviridae, order Bunyavirales. This is the first report of a coguvirus infecting a fungus.

Carbapenemase-producing Enterobacteriaceae (CPE) isolates are recognized as one of the most severe threats to public health. However, the population structure and genetic characteristics of CPE isolates among bloodstream infections (BSIs) are largely unknown. To address this knowledge gap, in this study, we included patients with clinically significant BSIs due to Enterobacterales isolates, recruited from 26 sentinel hospitals in China (2014–2015). CPE isolates were microbiologically and genomically characterized, including their susceptibility profiles, molecular typing, phylogenetic features, and genetic context analysis of carbapenemase-encoding genes. Of the 2569 BSI Enterobacterales isolates enrolled, 42 (1.6%) were carbapenemase-positive. Moreover, among the 2242 investigated isolates, 1111 (49.6%) extended-spectrum β-lactamase (ESBL)-producing isolates were identified in Escherichia (E.) coli, Klebsiella (K.) pneumoniae, Proteus (P.) mirabilis, and K. oxytoca. Whole genome sequencing analysis showed the clonal spread of K. pneumoniae carbapenemase (KPC)-2-producing K. pneumoniae sequence type 11 (ST11) and New Delhi metallo-β-lactamase (NDM)-5-producing E. coli ST167 in our collection. Plasmid analysis revealed that carbapenemase-encoding genes were located on multiple plasmids. A high prevalence of biofilm-encoding type 3 fimbriae clusters and yesiniabactin-associated genes was observed in K. pneumoniae isolates. This work demonstrates the high prevalence of ESBLs and the wide dissemination of CPE among BSI isolates in China, which represent real clinical threats. Moreover, our findings first illustrate a more comprehensive genome scenario of CPE isolates among BSIs. The clonal spread of KPC-2-producing K. pneumoniae ST11 and NDM-5-producing E. coli ST167 needs to be closely monitored.

Here, we describe the complete genome sequence and molecular characterization of a novel ourmia-like virus, tentatively named “Botryosphaeria dothidea ourmia-like virus 3” (BdOLV3), isolated from the phytopathogenic fungus Botryosphaeria dothidea strain ZM190712-1, associated with branch dieback of walnut in Henan Province, China. The complete BdOLV3 genome is 2247 nucleotides (nt) in length, with a content of 31.55% G, 16.11% A, 23.54% U, and 28.79% C. The BdOLV3 genome contains a single large open reading frame (ORF) encoding an RNA-dependent RNA polymerase (RdRp) of 612 amino acids (aa) with a molecular mass of 67.68 kDa. This RdRp protein contains a catalytic core domain associated with ourmia-like virus in the family Botourmiaviridae. A phylogenetic tree revealed that the novel ourmia-like virus clustered with members of the genus Magoulivirus and was separate from members of the other eleven genera of the family Botourmiaviridae.

Here, we describe a novel ourmia-like virus, Botryosphaeria dothidea ourmia-like virus 2 (BdOLV2), derived from phytopathogenic fungus Botryosphaeria dothidea strain ZM180192-1, infecting maize in Henan province of China. The complete genome sequence of BdOLV2 consists of a positive-sense single-stranded RNA (+ ssRNA) segment with a length of 2,532 nucleotides (nt). The sequence contains a large open reading frame (ORF), encoding a putative RNA-dependent RNA polymerase (RdRp) including 605 amino acids (aa) with a molecular mass of 68.59 kDa. This RdRp protein contains eight typical conserved domain motifs associated with ourmia-like virus. BLASTp analysis revealed that the RdRp protein of BdOLV2 had the highest similarity (62.10%, 58.15%, and 55.75% identity, respectively) with Botourmiaviridae sp., Macrophomina phaseolina ourmia-like virus 2 and Macrophomina phaseolina ourmia-like virus 2-A. Phylogenetic analysis based on the RdRp aa sequence indicated that BdOLV2 is a new member of the genus Magoulivirus with in the family Botourmiaviridae.

Nematodes are abundant, but little is known about their viruses. In this study, we report a novel partitivirus isolated from the entomopathogenic nematode species Steinernema ceratophorum, named "Steinernema ceratophorum partitivirus 1" (ScPV-1). The complete genome of ScPV-1 comprises two dsRNA segments, dsRNA1 (2352 bp) and dsRNA2 (2196 bp). Each dsRNA contains a single open reading frame (ORF), encoding a putative RNA-dependent RNA polymerase (RdRp) and a coat protein (CP), respectively. The sequences of the RdRp and CP showed the highest similarity (47% and 33% identity, respectively) to Plasmopara viticola associated partitivirus 7 (PvAP-7). A multiple sequence alignment and phylogenetic analysis of the RdRp of ScPV-1 and other selected viruses indicated that ScPV-1 is a new member of the genus Betapartitivirus in the family Partitiviridae.

Geological hazards can cause significant harm to the construction and maintenance of reef infrastructure projects in the Xisha Sea area. This study uses high-resolution multichannel earthquake data, single-channel seismic profiles, and multi-beam survey data to identify and analyze the geological hazards in the Xisha Sea area since the Miocene. Based on the geophysical data interpretation, the destructive geological disaster factors that are active, such as active faults, shallow gas, diapers, landslides, multistage scarps (steps), scouring troughs, and canyons, as well as the restrictive geological disaster factors without activity ability, such as buried paleochannels, pockmarks, reefs, and undersea volcanoes, are identified and analyzed. This paper discusses the causes and hazards of geological hazards and, for the first time, draws a comprehensive plane layout of the geological hazards. The above analysis demonstrates that the scarps are mainly located around the atolls or platforms, and the slope of the southeast seabed topography is significantly higher than that of the northwest. There are seven medium and large landslides, mainly located around Yongxing Plateau and Yongle Plateau, caused by gravity and faulting. Shallow gas is mainly developed in the southern part of the North Reef and is indicated by diaper structures, faults, and gas chimneys. A series of shallow faults are developed in the study area, mainly steep normal faults. The scouring troughs are primarily distributed near the Yongxing Platform, Zhongjian North Platform, and Huaguang Platform. Submarine canyons are primarily located in the northern and southern parts of the Shidao Platform. Affected by multiple factors such as hydrodynamic conditions, the stability of sedimentary layers, and sediment supply, the scour degree varies, with the general depth ranging from several meters to several hundred meters. Underwater infrastructure in the study area should not be constructed in areas with active and destructive geological hazards. The results of this study can serve as a guide for further exploration in the Xisha area and disaster prevention and mitigation during construction activity in the area.

Canker and dieback are serious fungal diseases of woody plants, which can cause huge economic losses to orchards. The purpose of this study was to classify and assess pathogenicity of fungal species associated with canker and dieback on fruit trees growing in Henan Province, China. In total, 150 isolates of Botryosphaeriaceae were obtained from six different fruit trees exhibiting typical symptoms of stem canker, branch dieback, and gummosis. Morphological examinations and phylogenetic analysis of ITS, tef1, tub2, and rpb2 revealed two Botryosphaeriaceae species, which are Botryosphaeria dothidea and a novel species, Lasiodiplodia regiae, respectively. Using Koch’s postulates, we confirmed that the different isolates of L. regiae can cause disease in their original hosts. The pathogenicity tests showed that L. regiae can cause canker, dieback, and gummosis symptoms in four different hosts, indicating a relatively wider host range. Moreover, 10 L. regiae isolates exhibited similar symptoms but different levels of virulence on shoots of peach trees under field conditions. This study demonstrated that L. regiae was a new causal agent of canker and dieback of six fruit tree species, which could be a serious risk to the orchard industry in China. Furthermore, the findings also provided a foundation for further epidemiological studies and the development of management strategies.

Determining the mechanism that effects embolism repair in the xylem vessels of plants is of great significance in predicting plant distribution and the screening of drought-resistant plants. However, the mechanism of perforation plates of xylem vessels in the acceleration of embolism repair is still not clear by using conventional methods of anatomy and visualization technology. Microfluidic devices have shown their ability to simulate physiological environments and conduct quantitative experiments. This work proposes a biomimetic microfluidic device to study the mechanism of perforation plates of xylem vessels in the acceleration of embolism repair. The results proffered that the perforation plates increase the rate of embolism removal by increasing the pressure differential through the vessel, and the rate of embolism removal is related to the structural parameters of the perforation plate. A combination of the perforation size, the vessel diameter and the perforation plate angle can be optimised to generate higher pressure differentials, which can accelerate the process of embolism repair. This work provides a new method for studying the mechanism of microstructures of natural plants. Furthermore, the mechanism that perforation plates accelerate embolism repair was applied to an electrochemical flow sensor for online determination of heavy metal ions. Test results of this application indicate that the mechanism can be applied in the engineering field to solve the problems of reduced sensitivity of devices, inaccuracy of analysis results and poor reaction performance caused by bubbles that are generated or introduced easily in microdevices, which paves the way for applying the theory to engineering.

Electronic noses, or e-noses, refer to systems powered by chemical gas sensors, signal processing, and machine learning algorithms for realizing artificial olfaction. They play a crucial role in various applications for decoding chemical environmental information. Despite decades of advances in gas-sensing technology and artificial intelligence, the reliability and stability of e-nose systems remain challenging, which is also one of the major obstacles that prevent e-noses from large-scale deployment. This paper presents a wide-ranging and structured review of the methods and algorithms developed in the e-nose literature over the past few decades. The review adopts a problem-oriented taxonomy aimed at clarifying the motivations and challenges of different methods and algorithms and their pros and cons. Moreover, several promising research directions in this field have been presented.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants threatening ecosystems and human health. Here, we isolated and characterized a new strain, Hydrogenibacillus sp. N12, which is a thermophilic PAH-degrader. Strain N12 utilizes naphthalene as a sole carbon and energy source above 60°C and co-metabolizes many other PAHs as well. The metabolites were identified in the catabolism of naphthalene by gas chromatography-mass spectrometry (GC-MS) and stable isotopic analysis. Based on the identified metabolites, we proposed two possible metabolic pathways, one via salicylic acid and the other via phthalic acid. Whole-genome sequencing reveals that strain N12 possesses a small chromosome of 2.6 Mb. Combining genetic and transcriptional information, we reveal a new gene cluster for the naphthalene degradation. The genes, designated as narAaAb that are predicted to encode the alpha and beta subunits of naphthalene dioxygenase, were subsequently subcloned into Escherichia coli and the enzyme activity was detected by whole-cell transformation. Capacity to degrade several other tricyclic-PAHs was also characterized, suggesting co-existence of other constitutively expressed enzyme systems in strain N12 in addition to the naphthalene degradation gene cluster. Our study provides insights into the potential of the thermophilic PAH-degrader in biotechnology and environmental management applications.

Small RNA (sRNA) plays a central role in RNA silencing in fungi. The genome of Fusarium graminearum gemytripvirus 1 (FgGMTV1) is comprised of three DNA segments: DNA-A, DNA-B, and DNA-C. DNA-A and DNA-B are associated with fungal growth and virulence reduction. To elucidate the role of RNA silencing during the interactions of fungi and viruses, the sRNA profiles of

Trichomonas vaginalis (T. vaginalis) infection is the most common non-viral sexually transmitted disease (STD) in the world. It can cause male reproductive dysfunction and infertility. However, the pathogenic mechanism is not clear. In this study, the excretory secretory proteins of T. vaginalis (TvESPs) were collected, concentrated, and sterilized. After sperm co-cultured with TvESPs, the survival rate and motility of sperms were analyzed by seminal routine examination, and the results showed that the TvESPs could significantly reduce the survival rate and motility of sperms. Fluorescence staining displayed that TvESPs could destroy the integrity of sperm acrosomes. Flow cytometry indicated that TvESPs induced sperm apoptosis. By mouse in vitro fertilization, we confirmed that TvESPs could significantly reduce the fertilization ability of sperms and negatively affect the development of the fertilized ovum. Via semi-quantitative analysis, we found that the apoptosis-related p27, SMAC, p53, BAX, BCL-2, XIAP, and BCL-W molecules were down-regulated in mouse sperm cells after interaction between the sperms and TvESPs, which played an important role in regulating sperm apoptosis. In conclusion, our study showed that T. vaginalis degraded semen quality and negatively affected male fertility by TvESPs. TvESPs may damage sperms by breaking the balance between sperm pro-apoptotic and anti-apoptotic molecules. This study proves that T. vaginalis infection is a risk factor for infertility.

SiCw is expected to be candidate material for Accident Tolerant Fuel (ATF). Nevertheless, the distribution, morphology and size of SiCw have impacts on the thermal conductivity of composite fuels. An analysis model for UO2-SiCw was established using finite element method (FEM), and the effects of whisker orientation, size, volume fraction and aspect ratio on thermal conductivity were analyzed. The generation algorithm of SiCw was improved, and the results of thermal conductivity calculations showed that the improved model is closer to the experimental value. The effect of whisker orientation on thermal conductivity can be calculated by the cosine law of zenith angle and azimuth angle, and deriving a model for calculating thermal conductivity with specific whisker orientation. With the decrease of whisker size, the influence of Kapitza thermal resistance is significant. The formula used to calculate the whisker threshold diameter was deduced, and the results are in good agreement with the FEM results. With the increase of volume fraction of whiskers, the thermal conductivity increases linearly. For morphology, whiskers with high aspect ratio can achieve higher thermal conductivity. There is a value for the ratio of whisker length to matrix size, above which increasing whisker length will slow the increase in thermal conductivity (0.3 for whiskers along the direction of thermal conduction). The thermal conductivity of UO2-SiCw was optimized using the above conclusions, and the radial temperature distribution of pellet was analyzed. The results show that taking full advantage of the anisotropy of whisker heat transfer can significantly improve the thermal conductivity of composites and improve the operation condition of the pellet. The results can provide a good theoretical basis for designing whisker-doped composites with high thermal conductivity.

Trichomonas vaginalis (T. vaginalis) is an extracellular flagellated protozoan parasitizing the human genital and urinary tracts. T. vaginalis infection impacts human reproductive function, but whether it causes infertility is still a matter of debate.In this work, we consulted 205 relevant articles, which were classified into three categories: epidemiological investigations (100), review articles (43), and research articles (62). RevMan 5.4 was used to conduct a meta-analysis of the articles reporting epidemiological investigations comparing the incidence of T. vaginalis infection between infertile and fertile groups. Review and research articles were used to summarize the pathogenesis of infertility caused by T. vaginalis.The results indicated that rate of T. vaginalis infection in the infertile group was significantly higher than that in the fertile group. Moreover, the epidemiological surveys showed that the infertility rates of population infected with T. vaginalis were significantly higher than that of population without T. vaginalis infection. Nine out of ten (90%) related review articles stated that T. vaginalis infection causes infertility, and the review and research articles indicated the main pathogenic mechanisms of infertility caused by T. vaginalis were as follows: T. vaginalis impairs sperm quality, resulting in infertility; the immune response triggered by T. vaginalis infection impacts human reproductive function.Our results confirm that there is a correlation between T. vaginalis infection and infertility, and T. vaginalis infection can lead to infertility. The study provides a foundation for further investigations into its pathogenesis.

Herein, we present the different coordination modes of half-sandwich iridium(III) and rhodium(III) complexes based on pyridine-amine ligands. The pyridyl-amine iridium(III) and rhodium(III) complexes, the corresponding oxidation pyridyl-imine products, and 16-electron pyridyl-amido complexes can be obtained through the change in reaction conditions (nitrogen/adventitious oxygen atmosphere, reaction time, and solvents) and structural variations in the metal and ligand. Overall, the reaction of pyridine-amine ligands with [(η

To investigate the clinical value of modified skin expansion in peripherally inserted central venous catheter (PICC) catheterization under the guidance of B-ultrasound in gastrointestinal cancer patients with chemotherapy.In this retrospective study, 60 gastrointestinal cancer patients with chemotherapy were included and divided into an experimental group (treated with modified skin expansion in PICC catheterization under the guidance of B-ultrasound) and a control group (treated with the longitudinal skin expansion in PICC catheterization under the guidance of B-ultrasound). The bleeding volume, pain score, success rate of one-time PICC catheterization and the incidence of complication were compared between the two groups.The modified skin expansion in PICC catheterization under the guidance of B-ultrasound had obvious effect on gastrointestinal cancer patients with chemotherapy. The VAS scores were significantly lower after PICC catheterization in the experimental group compared with the control group (P0.05). The success rate of one-time PICC catheterization in the experimental group was significantly higher than that in the control group. Moreover, the incidence of complication and massive bleeding during puncture and 24 hours after puncture was significantly lower in the observation group compared with that in the control group.Modified skin expansion in PICC catheterization under the guidance of B-ultrasound in gastrointestinal cancer patients with chemotherapy can improve the success rate of one-time sheath delivery, effectively reduce the amount of blood leakage after catheterization, reduce patients' pain and reduce the incidence of complications.

The artificial lateral line is a bionic sensor developed in recent years to detect physical parameters of gas and liquid flow field, which has great application prospects in underwater target detection, microfluidic velocity detection and smart skin. However, these sensors generally have only one kinocilium, resulting in inability to identify directions. Moreover, the kinocilium exposed directly in fluid shows performance of low sensitivity. This paper presents a flexible, lightweight, and sensitive piezoresistive sensor inspired by lateral line. The sensor presented comprises a cluster of micropillars arranged in stepwise distribution to detect fluid direction and a hydrogel cap to realize high-sensitive and low-speed threshold detection. The experiment of direction detection shows that the output signal in inhibitory direction of the sensor is smaller than the signal in excitatory direction and lagging behind, which can be used in orientation identification. The results show that the sensitivity of the sensor without hydrogel cap is 0.57 mV/(mm/s), while the sensor with hydrogel cap is 1.18 mV/(mm/s), which indicates that the hydrogel cap can increase the sensitivity by 107%. The sensor developed in this paper has a broad application prospect in biomedicine devices and micro-fluid equipment.

It is difficult to remove and eliminate bubbles in microchannels in many devices used in various biomedical fields, such as those needed for microfluidic immunoassays, point-of-care testing, and cell biology evaluations. Accumulated bubbles are associated with a number of negative outcomes, including a decrease in device sensitivity, inaccuracy of analysis results, and even functional failure. Xylem conduits of angiosperm have the ability to remove bubbles in obstructed conduits. Inspired by such an embolism repair mechanism, this paper proposes a bioinspired bubble removal method, which exhibits a prominent ability to dissolve bubbles continuously within a large range of flow rates (2 µL/min–850 µL/min) while retaining the stability and continuity of the flow without auxiliary equipment. Such a method also shows significant bubble removal stability in dealing with Newtonian liquids and non-Newtonian fluids, especially with high viscosity (6.76 Pa s) and low velocity (152 nL/min). Such advantages associated with the proposed bioinspired method reveal promising application prospects in macro/microfluidic fields ranging from 3D printing, implantable devices, virus detection, and biomedical fluid processing to microscale reactor operation and beyond.

BackgroundCarbapenem-resistant Acinetobacter baumannii (CRAB) is a common cause of ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients, but its infection and colonization state are difficult to distinguish. If the judgment is wrong, it may aggravate the abuse of antibiotics and further accelerate the evolution of drug resistance. We sought to provide new clues for the diagnosis, pathogenesis and treatment of CRAB VAP based on lower respiratory tract (LRT) microbiota.MethodsA prospective study was conducted on patients with mechanical ventilation from July 2018 to December 2019 in a tertiary hospital. Multi-genomics studies (16S rRNA amplicon, metagenomics, and whole-genome sequencing [WGS]) of endotracheal deep aspirate (ETA) were performed.ResultsFifty-two ICU patients were enrolled, including 24 with CRAB VAP (CRAB-I), 22 with CRAB colonization (CRAB-C), and six CRAB-negative patients (infection-free) (CRAB-N). Diversity of pulmonary microbiota was significantly lower in CRAB-I than in CRAB-C or CRAB-N (mean Shannon index, 1.79 vs. 2.73 vs. 4.81, P < 0.05). Abundances of 11 key genera differed between the groups. Acinetobacter was most abundant in CRAB-I (76.19%), moderately abundant in CRAB-C (59.14%), and least abundant in CRAB-N (11.25%), but its interactions with other genera increased in turn. Metagenomics and WGS analysis showed that virulence genes were more abundant in CRAB-I than in CRAB-C. Multi-locus sequence typing (MLST) of 46 CRAB isolates revealed that the main types were ST208 (30.43%) and ST938 (15.22%), with no difference between CRAB-I and CRAB-C.ConclusionLower respiratory tract microbiota dysbiosis including elevated relative abundance of Acinetobacter and reduced bacterial interactions, and virulence enrichment may lead to CRAB VAP.

Recent success in identifying gene-regulatory elements in the context of recombinant adeno-associated virus vectors has enabled cell-type-restricted gene expression. However, within the cerebral cortex these tools are largely limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple new enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we discovered enhancers selective for parvalbumin (PV) and vasoactive intestinal peptide-expressing interneurons. Demonstrating the functional utility of these elements, we show that the PV-specific enhancer allowed for the selective targeting and manipulation of these neurons across vertebrate species, including humans. Finally, we demonstrate that our selection method is generalizable and characterizes additional PV-specific enhancers with exquisite specificity within distinct brain regions. Altogether, these viral tools can be used for cell-type-specific circuit manipulation and hold considerable promise for use in therapeutic interventions.

Background Bacteria undergo adaptive mutation in the host. However, the specific effect of antimicrobial use on bacterial evolution and genome mutations related to bacterial survival within a patient is unclear. Materials and methods Three S. capitis strains were sequentially isolated from cerebrospinal fluid of a clinical inpatient. Antimicrobial susceptibility, growth rate, biofilm formation and whole blood survival of these strains were measured. Relative fitness was calculated. The virulence was examined in the Galleria mellonella model. Whole-genome sequencing and in silico analysis were performed to explore the genetic mechanisms of the changes in antimicrobial resistance phenotype. Hypothetical proteins are cloned, expressed and characterized by detection the susceptibility to gentamycin. Results The first isolate was susceptible to rifampin (MIC=0.25 μg/mL), resistant to gentamicin (MIC=16 μg/mL), while the later two isolates were resistant to rifampin (MIC >64 μg/mL), susceptible to gentamicin (MIC=4 μg/mL). For the latter two strains, compared to the first, frameshift mutation in a hypothetical protein encoding gene and base substitutions (in genes saeR, moaA and rpoB) were discovered. The mutation of rpoB gene caused rifampicin resistance. Mutations in saeR, moaA and hypothetical gene are associated with changes in other biological traits. Amino acid sequence-based structure and function identification of the hypothetical protein indicated that a mutation in the encoding gene might be associated with altered aminoglycoside susceptibility. Growth curve showed that the later two isolates grew faster than the first isolate with a positive fitness advantage of 13.5%, and 14.8%, accordingly. Biofilm form ability and whole blood survival of the derivative mutants were also enhanced. No significant differences of virulence in the G. mellonella model were observed. Conclusion We report here for the first time that short-term clinical antibiotic use was associated with resistance mutations, collateral sensitivity, and positive in vivo fitness advantages to S. capitis during infection.

Purpose To investigate the occurrence and genetic characteristics of the bla IMP-26-positive plasmid from a multidrug-resistant clinical isolate, Enterobacter hormaechei L51. Methods Species identification was determined by MALDI-TOF MS and Sanger sequencing. Antimicrobial susceptibility testing was performed by the agar dilution and broth microdilution. Whole-genome sequencing was conducted using Illumina HiSeq 4000-PE150 and PacBio Sequel platforms, and the genome was annotated by the RAST annotation server. The ANI analysis of genomes was performed using OAT. Phylogenetic reconstruction and analyses were performed using the Harvest suite based on the core-genome SNPs of 61 publicly available E. hormaechei genomes. Results The E. hormaechei L51 genome consists of a 5,018,729 bp circular chromosome and a 343,918 bp conjugative IncHI2/2A plasmid pEHZJ1 encoding bla IMP-26 which surrounding genetic context was intI1-bla IMP-26-ltrA-qacE∆1-sul1. A new sequence type (ST1103) was assigned for the isolate L51 which was resistant to cephalosporins, carbapenems, but sensitive to piperacillin-tazobactam, amikacin, tigecycline, trimethoprim-sulfamethoxazole and colistin. Phylogenetic analysis demonstrated that E. hormaechei L51 belonged to the same subspecies as the reference strain E. hormaechei SCEH020042, however 18,248 divergent SNP were identified. Resistance genes in pEHZJ1 including aac(3)-IIc, aac(6') -IIc, bla SHV-178, bla DHA-1, bla TEM-1, bla IMP-26, ereA2, catII, fosA5, qnrB4, tet(D), sul1 and dfrA19. Conclusion In our study, we identified a conjugative IncHI2/2A plasmid carrying bla IMP-26 and bla SHV-178 in E. hormaechei ST1103, a novel multidrug-resistant strain isolated from China, and describe the underlying resistance mechanisms of the strain and detailed genetic context of mega plasmid pEHZJ1.

The solid-liquid phase equilibrium for the ternary system of L-Pyroglutamic acid + L-Glutamic acid + water was determined experimentally by the isothermal solution saturation method at temperatures of 298.15, 308.15, 318.15, and 328.15K under normal atmosphere. According to the obtained solubility data, four ternary phase diagrams and the variable-temperature phase diagram were constructed. Two pure solids, pure L-Pyroglutamic acid and pure L-Glutamic acid, were generated in the L-Pyroglutamic acid + L-Glutamic acid + water system. In the phase diagrams, there were in all three crystallization zones, two cosaturated solubility curves, and one cosaturated point. The variable-temperature phase diagram for the ternary system of L-Pyroglutamic acid + L-Glutamic acid + water could be used for separation and purification L-Pyroglutamic acid and L-Glutamic acid from its mixture. The data of solid-liquid phase equilibrium were correlated and computed with the NRTL model and Wilson model. The RMSD (root mean squar...

The investigation of the relationship between the structure of the catalyst and the microstructure of the obtained polymer has attracted much attention and broad interest in the field of transition metal-catalyzed olefin polymerization. Cycloalkyls, especially cyclohexyl, are known for their rich conformational change. In this contribution, we described the synthesis and characterization of a series of bulky yet flexible cycloalkyl substituted α-diimine ligands and the corresponding nickel and palladium catalysts. The thermostable nickel complexes in this system show high activity (up to 4.89 × 106 g mol−1 h−1) and can generate highly branched polyethylene (up to 112/1000C) with a high molecular weight (up to 54.4 × 104 g mol−1). The obtained polyethylene displays good elastic properties (SR value up to 77%) characteristic of thermoplastic elastomers. The flexible cycloalkyl substituted palladium complexes exhibit low to moderate catalytic activities (0.6–43.9 × 106 g mol−1 h−1), low to moderate molecular weights (0.93–31.23 × 104 g mol−1), and high branching density (87–122/1000C) for ethylene polymerization, while allowing appreciable comonomer incorporation (1.0–7.7%) for ethylene/MA copolymerization. Most interestingly, compared to the flexible cyclohexyl substituted α-diimine nickel and palladium catalysts, the rigid phenyl substituted catalysts generated polyethylene with much lower branching density in ethylene polymerization.

The natural α-amino acid derivate N-dodecanoyl leucinate was synthesized via Schotten–Baumann reaction and alkali treatment, and was applied to the dispersion of arc-discharged single-walled carbon nanotubes (SWNTs). Optical absorption and Raman scattering spectra as well as AFM observation confirmed the effective individualization and selective dispersion of SWNTs. Moreover, charge transfer from N-dodecanoyl leucinate to SWNTs was evidenced by FT-IR and Raman scattering spectroscopic analyses. We believe that the formation of a charge transfer complex between dispersants and SWNTs is responsible for the effective individualization of SWNTs, and that the charge transfer from dispersants to SWNTs (or from SWNTs to dispersants) is crucial for selective dispersion of semiconducting (or metallic) SWNTs.

Herein, a new class of iridium(III)-based metal complexes with phosphine-imine (P^N) ligands are synthesized and authenticated. These complexes show high cytotoxicities against seven cancer cells in vitro. Simultaneously, antitumor mechanism studies show that complex Ir3 induces apoptosis by depolarization of mitochondrial membrane potential, ROS overproduction and ROS-mediated DNA damage. Importantly, BIX01294, a G9a histone methyltransferase inhibitor, could markedly sensitize Ir3-induced cytotoxicity, cell cycle arrest, apoptosis and inhibition of migration in HCT116 cancer cells in vitro. Finally, we show that combined treatment with Ir3 and BIX01294 potently inhibits tumour growth and lung metastasis in vivo. Taken together, we demonstrate that BIX01294 could potently sensitize iridium(III)-based metal complex-induced inhibition of tumour progression and provide the basis for developing new metal-based anticancer agents and therapeutic strategies in vivo for effective cancer therapy.

The rational design by the introduction of fluorine into a compound has achieved success in the development of organic anticancer drugs. However, the fluorine effect in metal-based anticancer complexes has rarely been reported. In this contribution, we report the synthesis, characterization, chemical reactivity, and biological activity of a series of half-sandwich zwitterionic iridium(III) complexes containing different substituents in the η5-CpR ring. The molecular structures for complexes Ir1-Ir4 and Ir7 were determined by single-crystal X-ray crystallography techniques. Notably, the asymmetrically substituted fluoro complexes Ir4 and Ir6 in solution show two conformational isomers. These complexes have sufficient stability, exhibit fluorescence emission, and show potent catalytic activity in converting NADH to NAD+. The effect of the substituents in the η5-CpR ring for these zwitterionic complexes on their anticancer activity was systematically investigated. Surprisingly, the presence of fluorinated substituents gives rise to a significant increase in the anticancer activity. The lipophilicity and cellular uptake levels of these complexes appeared to be the primary factors for their cytotoxicity in this system. A microscopic mechanism study showed that the typical complex Ir4 entered A549 cancer cells through an energy-dependent pathway and was mainly located in lysosomes. Furthermore, an increase in ROS level, apoptosis induction, and cell-cycle perturbation together contribute to the anticancer potency of these zwitterionic complexes.

Small RNA (sRNA) plays a central role in RNA silencing in fungi. The genome of Fusarium graminearum gemytripvirus 1 (FgGMTV1) is comprised of three DNA segments: DNA-A, DNA-B, and DNA-C. DNA-A and DNA-B are associated with fungal growth and virulence reduction. To elucidate the role of RNA silencing during the interactions of fungi and viruses, the sRNA profiles of F. graminearum in association with FgGMTV1 were established, using an FgGMTV1-free library (S-S), a library for infection with the DNA-A and DNA-B segments (S-AB), and a library for infection with the DNA-A, DNA-B, and DNA-C segments (S-ABC). A large amount of virus-derived sRNA (vsiRNA) was detected in the S-AB and S-ABC libraries, accounting for 9.9% and 13.8% of the total sRNA, respectively, indicating that FgGMTV1 triggers host RNA silencing. The total numbers of sRNA reads differed among the three libraries, suggesting that FgGMTV1 infection interferes with host RNA silencing. In addition, the relative proportions of the different sRNA lengths were altered in the S-AB and S-ABC libraries. The genome distribution patterns of the mapping of vsiRNA to DNA-A and DNA-B in the S-AB and S-ABC libraries were also different. These results suggest the influence of DNA-C on host RNA silencing. Transcripts targeted by vsiRNAs were enriched in pathways that included flavin adenine dinucleotide binding, protein folding, and filamentous growth.

Background: Trichomonas vaginalis (T. vaginalis) is an extracellular flagellated protozoan parasitizing the human genital and urinary tracts. T. vaginalis infection impacts human reproductive function, but whether it causes infertility is still a matter of debate.Methods: In this work, we consulted 237 relevant articles, which were classified into three categories: epidemiological investigations (104), review articles (40), and research articles (62). RevMan 5.4 was used to conduct a meta-analysis of the articles reporting epidemiological investigations comparing the incidence of T. vaginalis infection between infertile and fertile groups.Results: The results indicated that rate of T. vaginalis infection in the infertile group was lower than that in the fertile group. However, an epidemiological survey showed that the infertility rate of population infected with T. vaginalis was significantly higher than that of population without T. vaginalis infection. Most review articles stated that T. vaginalis infection causes infertility, while a small fraction of these articles were inconclusive. The conclusion that T. vaginalis infection can lead to infertility is supported by the research articles, which indicated the main pathogenic mechanisms are as follows: T. vaginalis impairs sperm quality, resulting in infertility; the immune response triggered by T. vaginalis infection impacts human reproductive function; and T. vaginalis impairs ovum quality, resulting in infertility.Conclusion: Our study confirmed that T. vaginalis infection can lead to infertility and provides a foundation for further investigations into its pathogenesis.

Nematodes are abundant, yet little is known about their viruses. In this study, we report a novel partitivirus isolated from Entomopathogenic nematode specie “Steinernema ceratophorum, named as Steinernema ceratophorum Partiti-like Virus 1 (ScPV1). The complete genome of ScPV1 is comprised of two dsRNA segments, dsRNA1 (2352 bp) and dsRNA2 (2196 bp) in length. Both dsRNAs contained a single open reading frame (ORF), encoding a putative RNA-dependent RNA polymerase (RdRp) and a coat protein (CP), respectively. The sequences of the RdRp and CP showed the highest similarity (47% and 33% identity, respectively) to Plasmopara viticola associated Partitivirus 7. Multiple sequence alignments and phylogenetic analysis of RdRp of ScPV1 with other selected viruses indicated that ScPV1 is the new member of genus Betapartitivirus in the family Partitiviridae.

Carbapenem-resistantA prospective study was conducted on patients with mechanical ventilation from July 2018 to December 2019 in a tertiary hospital. Multi-genomics studies (16S rRNA amplicon, metagenomics, and whole-genome sequencing [WGS]) of endotracheal deep aspirate (ETA) were performed.Fifty-two ICU patients were enrolled, including 24 with CRAB VAP (CRAB-I), 22 with CRAB colonization (CRAB-C), and six CRAB-negative patients (infection-free) (CRAB-N). Diversity of pulmonary microbiota was significantly lower in CRAB-I than in CRAB-C or CRAB-N (mean Shannon index, 1.79 vs. 2.73 vs. 4.81,Lower respiratory tract microbiota dysbiosis including elevated relative abundance of

Aristolochic acids (AAs), which is commonly found in Aristolochia and Asarum plants, has been widely used in several traditional medicine practices due to their anti-inflammatory, anti-malarial, and anti-hyperglycemic activities. Recently, researchers have found a “decisive link” between liver cancer and aristolochic acid after analyzing a large number of liver cancer samples around the world. Therefore, a highly sensitive and selective method is required for the analysis of AAs in traditional Chinese medicines (TCM). For the determination of AAs in TCM, pretreatment is indispensable because in actual TCM samples, AAs is present in trace amounts and the complex matrix exerts interference. In the past decades, molecularly imprinted polymers (MIPs) have attracted considerable attention as an alternative for the trace analysis in complicated matrices. In this study, MIP-coated SiO2 nanoparticles (SiO2@MIP NPs) was prepared for the determination of aristolochic acid by surface molecular imprinting using aristolochic acid Ⅰ (AAI ) as the template molecule, 2-vinylpyridine (VPY) as the functional monomer, and ethyleneglycol dimethacrylate (EGDMA) as the cross-linking agent. Core-shell-structure SiO2@MIP NPs were obtained by modifying vinyl groups on the surface of SiO2 NPs, coating MIPs films onto the silica surface via selective polymerization, and final extraction of template AAI and generation of the recognition site. To find a suitable functional monomer for the best imprinting effect, the interaction between the template and the functional monomers, including acrylic acid (AA), methyl acrylic acid (MAA), 2-vinyl pyridine (VPY), acrylamide (AM), and methylacrylamide (MAM) was investigated. Electrostatic interaction between AAI and VPY resulted in the maximum decrease in absorbance of AAI at 250 nm. Therefore, VPY was chosen for the preparation of MIP. The morphological and physical properties of the MIPs were characterized by transmission electron microscopy (TEM), Fourier-transform infrared (FT-IR) spectroscopy, thermogravimetric analysis, and N2 adsorption and desorption surface analysis. TEM images showed that SiO2 NPs were monodispersed with diameter of about 200 nm. The clear core-shell structure of SiO2@MIP NPs was observed, and the thickness of MIPs coating was about 35 nm. The FT-IR spectra of SiO2 NPs, vinyl group modified SiO2 and SiO2@MIP NPs revealed that the vinyl group and organic MIP layer were successfully modified at SiO2 sequentially. The results of thermogravimetric analysis were consistent with the FT-IR data for different SiO2 NPs. The nitrogen gas adsorption-desorption experiments showed that SiO2@MIP NPs and non-imprinted polymer (SiO2@NIP NPs) have the same pore volumes, while the surface area and pore size of MIPs were slightly larger than those of NIPs. Therefore, the difference in adsorption between SiO2@MIP NPs and SiO2@NIP NPs resulted from the imprinted sites on the MIP surface, rather than the difference in their surface areas. The adsorption properties of SiO2@MIP NPs were demonstrated by kinetic, isothermal, and selective adsorption experiments. The results of these experiments displayed that SiO2@MIP NPs reached adsorption equilibrium within a short period (120 s) and possessed a much higher rebinding ability than SiO2@NIP NPs. To verify the selectivity of SiO2@MIP NPs for AAI, three structural analogues (viz. tanshinone ⅡA, 2-methoxy-5-nitrophenol, and benzoic acid) were selected. The results showed that the binding capacity of SiO2@MIP NPs was much higher than those of these analogues. SiO2@MIP NPs have high adsorption capacity (5.74 mg/g), high imprinting factor (4.9), good selectivity coefficient (2.3-6.6) towards the structural analogues. SiO2@MIP NPs was used as an adsorbent and combined with HPLC for the selective separation of AAI in TCM. The recoveries of Kebia trifoliate samples spiked with three levels of AAI (0.3, 0.5, and 1.0 μg/mL) ranged from 73% to 83%. The results suggested that the proposed SiO2@MIP NPs could be used for selective enrichment of AAI from real complex TCM samples.

The piezoelectric valveless micropump with the characteristics of precise liquid delivery is widely utilized in the field of biomedicine. However, the improvement of the flow rate of the piezoelectric micropump relies on the increase in size and driving voltage, which hinders its application in the implantable medical field. This article proposes a double-layer chamber valveless piezoelectric micropump, which has the obvious advantages of small size and adjustable flow rate, and is expected to be applied to the treatment of implantable hydrocephalus. The overall size of the micropump is 10 mm × 10 mm × 4 mm, which can be implanted in the cerebral cortex. Combined with polydimethylsiloxane-polyethylene glycol terephthalate bonding technology, the double-layer chamber micropump solves the contradiction between miniaturization and large flow range. The flow rate generated by micropump under low voltage can be adjusted according to the amount of hydrocephalus. In order to reveal the mechanism of increasing the flow rate, the working efficiencies of the microvalve and micropump are studied in this article. The electric-solid-fluid coupling simulation and experimental tests obtained the optimal structural parameters: the divergence angle is 30°, the throat width is 300 μm, and the upper chamber depth is 100 μm. The proposed micropump can achieve the tunable flow rate of 2.16–51.74 μl min−1.