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Abstract Background Using event-related potentials (ERPs), we aimed to investigate audiovisual integration neural mechanisms during a letter identification task in the left and right sides. Unimodal (A,V) and bimodal (AV) stimuli were presented on either side, with ERPs from unimodal (A,V) stimuli on the same side being compared to those from simultaneous bimodal stimuli (AV). Non-zero results of the AV-(A + V) difference waveforms indicated audiovisual integration on the left/right side. Results When spatially coherent AV stimuli were presented on the right side, two significant ERP components in the integrated differential wave were noted. The N134 and N262, present in the first 300 ms of the AV-(A + V) integration difference wave, indicated significant audiovisual integration effects. However, when these stimuli were presented on the left side, there were no significant integration components. This audiovisual integration difference may stem from left/right asymmetry of cerebral hemisphere language processing. Conclusions Audiovisual letter information presented on the right side was easier to integrate, process, and represent. Additionally, only one significant integrative component peaked at 140 ms in the parietal cortex for spatially non-coherent AV stimuli and provided audiovisual multisensory integration, which could be attributed to some integrative neural processes that depend on the spatial congruity of the auditory and visual stimuli.

Abstract 3D printing of liquid metal remains a big challenge due to its low viscosity and large surface tension. In this study, we use Carbopol hydrogel and liquid gallium-indium alloy to prepare a liquid metal high internal phase emulsion gel ink, which can be used for direct-ink-writing 3D printing. The high volume fraction (up to 82.5%) of the liquid metal dispersed phase gives the ink excellent elastic properties, while the Carbopol hydrogel, as the continuous phase, provides lubrication for the liquid metal droplets, ensuring smooth flow of the ink during shear extrusion. These enable high-resolution and shape-stable 3D printing of three-dimensional structures. Moreover, the liquid metal droplets exhibit an electrocapillary phenomenon in the Carbopol hydrogel, which allows for demulsification by an electric field and enables electrical connectivity between droplets. We have also achieved the printing of ink on flexible, non-planar structures, and demonstrated the potential for alternating printing with various materials.

Abstract To screen characteristic genes related to sarcopenia by bioinformatics and machine learning, and to verify the accuracy of characteristic genes in the diagnosis of sarcopenia. Download myopia-related data sets from geo public database, find the differential genes through R language limma package after merging, STRING database to build protein interaction network, and do Go analysis and GSEA analysis to understand the functions and molecular signal pathways that may be affected by the differential genes. Further screen the characteristic genes through LASSO and SVM-RFE machine algorithms, make the ROC curve of the characteristic genes, and obtain the AUC value. 10 differential genes were obtained from the data set, including 7 upregulated genes and 3 downregulated genes. Eight characteristic genes were screened by a machine learning algorithm, and the AUC value of characteristic genes exceeded 0.7. In patients with sarcopenia, the expression of TPPP3, C1QA, LGR5, MYH8, and CDKN1A genes are upregulated, and the expression of SLC38A1, SERPINA5, and HOXB2 genes are downregulated. The above genes have high accuracy in the diagnosis of sarcopenia. The research results provide new ideas for the diagnosis and mechanism research of sarcopenia.

In this study, a one-pot aryl diazonium reaction was used as a simple and mild method to graft graphene onto the smooth and inert surface of T1100-grade carbon fiber (CF) through covalent bonding without any damage on CF, to refine the interface performance of CF/bismaleimide (BMI) composites. XPS, SEM, AFM, and dynamic contact angle testing (DCAT) were used to characterize chemical activity, morphologies, and wettability on untreated and grafted CF surfaces. Meanwhile, the impact of the graft method on the tensile strength of CF was also examined using the monofilament tensile test. IFSS between CF grafted with graphene and BMI resin achieved 104.2 MPa after modification, increasing from 85.5 MPa by 21.8%, while the tensile strength did not decrease compared to the pristine CF. The mechanism of this interface enhancement might be better chemical bonding and mechanical interlock between CF grafted with graphene and BMI resin, which is generated from the high surface chemical activity and rough structure of graphene. This study may propose a simple and mild method to functionalize the CF surface and enhance the interface performance of composites without compromising the tensile properties of T1100-grade CF.

Abstract Background In the domain of forensic science, the application of kinship identification and mixture deconvolution techniques are of critical importance, providing robust scientific evidence for the resolution of complex cases. Microhaplotypes, as the emerging class of genetic markers, have been widely studied in forensics due to their high polymorphisms and excellent stability. Results and discussion In this research, a novel and high-efficient panel integrating 33 microhaplotype loci along with a sex-determining locus was developed by the next generation sequencing technology. In addition, we also assessed its forensic utility and delved into its capacity for kinship analysis and mixture deconvolution. The average effective number of alleles (Ae) of the 33 microhaplotype loci in the Guizhou Han population was 6.06, and the Ae values of 30 loci were greater than 5. The cumulative power of discrimination and cumulative power of exclusion values of the novel panel in the Guizhou Han population were 1-5.6 × 10− 43 and 1-1.6 × 10− 15, respectively. In the simulated kinship analysis, the panel could effectively distinguish between parent-child, full-sibling, half-sibling, grandfather-grandson, aunt-nephew and unrelated individuals, but uncertainty rates clearly increased when distinguishing between first cousins and unrelated individuals. For the mixtures, the novel panel had demonstrated excellent performance in estimating the number of contributors of mixtures with 1 to 5 contributors in combination with the machine learning methods. Conclusions In summary, we have developed a small and high-efficient panel for forensic genetics, which could provide novel insights into forensic complex kinships testing and mixture deconvolution.

Abstract Background Monoamine oxidases (MAOs) is an enzyme that catalyzes the deamination of monoamines. The current research on this enzyme is focused on its role in neuropsychiatric, neurodevelopmental, and neurodegenerative diseases. Indeed, MAOs with two isoforms, namely, A and B, are located on the outer mitochondrial membrane and are widely distributed in the central nervous system and peripheral tissues. Several reports have described periodic changes in the levels of this enzyme in the human endometrial tissue. Results The novel role of MAOs in endometrial receptivity establishment and embryonic development by maintaining monoamine homeostasis was investigated in this study. MAOs activity was observed to be enhanced during the first trimester in both humans and mice under normal conditions. However, under pathological conditions, MAOs activity was reduced and was linked to early pregnancy failure. During the secretory phase, the endometrial stromal cells differentiated into decidual cells with a stronger metabolism of monoamines by MAOs. Excessive monoamine levels cause monoamine imbalance in decidual cells, which results in the activation of the AKT signal, decreased FOXO1 expression, and decidual dysfunction. Conclusions The findings suggest that endometrial receptivity depends on the maintenance of monoamine homeostasis via MAOs activity and that this enzyme participates in embryo implantation and development.

This study investigated the effects of three common thermal processing methods (boiling, steaming, and frying) on the color, nutritional composition, fatty acid profile, volatile base nitrogen (TVB-N), and fat oxidation of crayfish hepatopancreas. Electronic tongue, electronic nose, and gas chromatography-ion mobility spectrometry (GC-IMS) techniques combined with sensory evaluation were applied to evaluate the effects of different thermal processing methods on the physicochemical properties, volatile flavor substances, and sensory quality of crayfish hepatopancreas. The results revealed that, in comparison to fresh hepatopancreas, significant changes in physicochemical properties and volatile flavor compounds were observed after undergoing these three distinct thermal processing methods, with notable variations among the groups. The redness (a*), yellowness (b*), and brightness (L*) values of crayfish hepatopancreas in thermal processing groups were increased, and the frying group was the most significant. Total fatty acids and major fatty acid components decreased, most prominently in the frying group. The steaming group demonstrated better preservation of EPA+DHA. TVB-N and thiobarbituric acid reactive substances (TBARS) were increased, especially in the frying group. Electronic tongue analysis revealed that a prominent umami taste with a hint of saltiness was prevalent in all thermally processed hepatopancreas. Electronic nose analysis showed noticeable differences in aroma characteristics before and after thermal processing, with the frying group displaying the most significant changes. A total of 28 volatile substances were identified by GC-IMS. The number and content of substances were mainly aldehydes and esters. The content of volatile substances in the frying group was the highest, followed by the steaming group, and the boiling group was the least. Sensory evaluations indicated that the frying group with higher aroma, color, and taste scores got the highest overall rating score, and the boiling and steaming groups scored slightly lower and were close. Therefore, the boiling group exhibited the lowest degree of oxidative changes due to heat treatment and retained more characteristics of fresh samples, and the frying group experienced the highest level of heat-induced oxidative changes, resulting in the richest flavor profile and a higher degree of popularity. This research provides valuable insights for optimizing crayfish processing in the industry.

Abstract We present the first formal network analysis of curricular networks for public institutions, focusing around five midwestern universities. As a first such study of public institutions, our analyses are primarily macroscopic in nature, observing patterns in the overall course prerequisite networks (CPNs) and Curriculum Graphs (CGs). An overarching objective is to better understand CPN variability and patterns across different institutions and how these patterns relate to curricular outcomes. In addition to computing well known network centrality measures to capture courses of importance in the CPNs studied, we have also formulated some newer methods with specific relevance to the curricular domains and corresponding graph types at hand. We have discovered that a new graph theoretic measure of node importance which we call reach, based on the well-known concept of reachability, is needed to more accurately express the critical nature of some introductory courses in a university. Another analytical novelty that we introduce and apply to the subject of CPNs is the Longest Paths Induced sub-Graph (LPIG) of the CPN, which yields information on relatively constrained programs and pathways. Finally, we have established a new connection between clustering of the CG and meta-majors at Southern Illinois University Edwardsville (SIUE), providing clusterings of the other public institution CGs as useful heuristics of major groupings as well. This work is borne from collaboration between academic units and academic advising with hopes of practical benefits towards aiding student advising.

Moraxella catarrhalis (M. catarrhalis), once considered as a harmless commensal bacterium, is now recognized as a significant pathogen associated with human mucosal infection. Hence, development of rapid, accurate, and user-friendly detection method is crucial for effective control and management of M. catarrhalis infections. Here, we introduce the M. catarrhalis MCDA-FRT assay, a novel diagnostic approach based on multiple cross displacement amplification (MCDA) for the visual and fluorescent (FRT) detection of M. catarrhalis. This innovative method amplifies the target sequence through MCDA reaction and provides results through the visual observation of a fluorescent signal when exposed to blue light. The generation of the fluorescent signal is facilitated by the cleavage of the restriction endonuclease Nb.BsrDⅠ. The M. catarrhalis MCDA-FRT assay can efficiently detect M. catarrhalis at a temperature of 65 °C in 40 min. It exhibits a remarkable sensitivity of 35 fg of M. catarrhalis genomic DNA, with a specificity of 100%. Furthermore, the assay accurately identified all M. catarrhalis-infected clinical samples tested. In conclusion, the M. catarrhalis MCDA-FRT assay showcases outstanding performance in terms of simplicity, sensitivity, and specificity, which can be used as a promising diagnostic tool for the swift and reliable detection of M. catarrhalis in both field and basic medical settings.

Apostichopus japonicus (A. japonicus) is known as one of the most popular varieties in aquaculture due to its rich nourishment and potential medicinal value. In recent years, with the abnormal change of marine environment and global climate, new challenges are arising continually in the culture process of A. japonicus. Intestinal flora plays an important role in host health and growth, and a lot of studies confirmed the close relationship between the composition change of intestinal flora and the growth of sea cucumbers. In this study, polypeptidin belonging to bacteriocins, was as an additive ingredient in sea cucumber feed. The growth of A. japonicus increased significantly after polypeptidin feeding, and the growth rate reached the highest with 1 % polypeptidin especially. Subsequently 16 S rRNA of gut microbiota from 1 % polypeptidin group was sequenced and analyzed for richness and diversity index, but the results showed that polypeptidin supplement did not markedly change the diversity and main composition of gut microbiota compared to the control. So the further analyze was performed by dependent t-test for paired samples, and found that the abundance of only a few of species at the class level changed significantly, including Alphaproteobacteria, Desulfotomaculia and Chlamydiae, but many species at the genus level changed significantly. Some important metabolic pathways were identified through function prediction, like TCA cycle, streptomycin biosynthesis and phenylalanine metabolism. At this basis, the analysis combined with the genuses and the metabolic pathways demonstrated that polypeptidin might regulate the richness of some bacteria, which could be involved in enzyme degradation, antibacterial substances secreting or underlying pathogenic tendency of gut microbiota ecosystem. These fine-tunings instead of main community structure change were probably more beneficial to the intestinal flora health, and finally contributed to the growth of A. japonicus. Thus, polypeptidin serves as a mild, non-stimulating feed supplement for A. japonicus, and has good prospects for application.

Mycoplasma pneumoniae is a significant pathogen responsible for community-acquired pneumonia, predominantly affecting children and adolescents. Here, we devised a rapid method for M. pneumoniae that combined multiple cross displacement amplification (MCDA) with real-time fluorescence technology. A set of ten primers, which were specifically designed for M. pneumoniae detection, were employed in a real-time fluorescence MCDA reaction. Of these, one primer incorporated a restriction endonuclease recognition sequence, a fluorophore, and a quencher, facilitating real-time fluorescence detection. The real-time (RT)-MCDA reactions were monitored in a simple real-time fluorescence instrument and conducted under optimised conditions (64°C for 40 min). The detection limit of the M. pneumoniae RT-MCDA assay for genomic DNA extracted from M. pneumoniae culture was down to 43 fg/µl. This assay accurately identified M. pneumoniae strains without cross-reacting with other bacteria. To validate its practical application, we tested the M. pneumoniae RT-MCDA assay using genomic DNA extracted from clinical samples. The assay’s detection capability proved comparable with real-time PCR, MCDA-based biosensor detection, and visual inspection under blue light. The entire process, including rapid DNA extraction and real-time MCDA detection, was completed within 1 h. Overall, the M. pneumoniae RT-MCDA assay reported here is a simple and effective diagnostic tool for rapid M. pneumoniae detection, which holds significant potential for point-of-care testing and in resource-limited regions.

Abstract Background Cognitive-Behavior Therapy (CBT) is the validated non-pharmacological treatment for chronic pain in pediatric patients. While some suggested CBT were comparable to the usual care in reducing children’s functional abdominal pain. This meta-analysis was designed to systematically review the literature for RCTs that investigated the efficacy of CBT in children with functional abdominal pain (FAP). Methods PubMed, Embase, and the Cochrane library were searched for papers published up to October 2022. Studies applying different CBT delivery methods (in-person, web-based, phone-based) were included in this meta-analysis to evaluate the comprehensive effectiveness of CBT compared with usual care. Weighted and standardized mean difference with the 95% confidence intervals were used for the synthesis of the results. Primary outcome was the decrease of functional disability inventory (FDI) and the secondary outcomes were the decrease of severity in pain intensity, depression, anxiety, gastrointestinal symptoms, and improvement in physical quality of life (QoL). Results A total of 10 RCTs with 1187 children were included in the final analysis. The results showed that CBT resulted in better effect in reducing functional disability inventory (SMD=-2.282, 95%CI: -4.537 to -0.027, P = 0.047), pain intensity (SMD=-0.594, 95%CI: -1.147 to -0.040, P = 0.036), and improving QoL (SMD = 14.097, 95%CI: 0.901 to 27.292, P = 0.036) compared with the control groups. Comparable effects were observed in the severity of depression (SMD=-0.493, 95%CI: -1.594 to 0.608, P = 0.380), anxiety (SMD=-0.062, 95%CI: -0.640 to 0.517, P = 0.835), and gastrointestinal symptoms (SMD=-1.096 95%CI: -2.243 to 0.050, P = 0.061) between CBT and usual treatment. Conclusions We observed the differences in post-treatment FAP and pain intensity for children receiving CBT compared with children receiving treatment as usual. CBT in the setting of FAP demonstrates promising developments and highlights the need for future research.

Objective: To investigate the effect of Tremella fuciformis polysaccharides (TFP) on oxidative damage induced by exhaustive exercise in mice and analyze its mechanism. Methods: L6 cells were treated with TFP for 48 hours, and the activity of L6 was detected by CCK-8 method. L6 cells were divided into three groups, including the control, H2O2, and H2O2+TFP groups, and incubated for 48 hours. LA levels were measured by a biochemical analyzer, and Nrf2, NQO1, and HO-1 protein levels were detected by Western blot assay. C57BL/6 mice were randomly divided into four groups (n=10 for each group), including model group and model+TFP group (50, 100, 200 mg/kg). The model+TFP groups were continuously gavaged with TFP, while the model group was gavaged with the same dose of distilled water once a day for two consecutive weeks. Exhaustive exercise was performed 30 minutes after the last administration, the duration of exhaustive swimming exercise was recorded, and enzyme-linked immunosorbent assay (ELISA) was used to detect liver glycogen (LG) and skeletal muscle glycogen (MG). ELISA was used to detect blood urea nitrogen (BUN), lactic acid (LA), ROS, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), TNF-α, IL-6 and NF-κBp65 levels. Western blot assay was used to detect the levels of Nrf2, NQO1, and HO-1 proteins. Results: The LA levels of L6 cells in the H2O2 group were significantly (P

The accurate estimation of the postmortem interval has been one of the crucial issues to be solved in forensic research, and it is influenced by various factors in the process of decay. With the development of high-throughput sequencing technology, forensic microbiology has become the major hot topic in forensic science, which provides new research options for postmortem interval estimation. The oral microbial community is one of the most diverse of microbiomes, ranking as the second most abundant microbiota following the gastrointestinal tract. It is remarkable that oral microorganisms have a significant function in the decay process of cadavers. Therefore, we collected outdoor soil to simulate the death environment and focused on the relationship between oral microbial community succession and PMI in rats above the soil. In addition, linear regression models and random forest regression models were developed for the relationship between the relative abundance of oral microbes and PMI. We also identified a number of microorganisms that may be important to estimate PMI, including: Ignatzschineria, Morganella, Proteus, Lysinibacillus, Pseudomonas, Globicatella, Corynebacterium, Streptococcus, Rothia, Aerococcus, Staphylococcus, and so on.

Molecular techniques of nucleic acid testing recommended by the World Health Organization (WHO) for the Mycobacterium tuberculosis (MTB) detection were considered to have the potential access to the accurate tuberculosis (TB) notifications. In this study, a new method, which coupled real-time (rt) fluorescence technique with multiple cross displacement amplification (MCDA), was developed for the rapid, sensitive and specific detection of MTB (termed MTB-rt-MCDA). According to the principle of the rt-MCDA test, a set of ten primers were designed for the MCDA reaction, of which one was engineered with a restrictive endonuclease recognition site, a fluorophore and a quencher for achieving the real-time fluorescence detection. MTB-rt-MCDA test was conducted under the optimized conditions (67 °C, 40 min) on the real-time fluorescence platform. The MTB-rt-MCDA assay accurately identified the MTB strains with no cross reaction with other bacteria. The lowest detectable genomic DNA concentration of the MTB-rt-MCDA assay was 25 fg/μl. We employed the genomic DNA templates extracted from sputum of clinical cases for validating the practical applicability of this assay, and the detection power of the MTB-rt-MCDA assay was comparable to that of the Xpert method and MCDA-based biosensor detection and superior to smear microscope method. The complete process of the MTB-rt-MCDA assay, including rapid extraction of DNA and rt-MCDA test, takes less than 1 h. In conclusion, the presented MTB-rt-MCDA assay provided an effective and simple option for the rapid screening of MTB infection.

ABSTRACTThe type VI secretion system (T6SS) serves as a crucial molecular weapon in interbacterial competition and significantly influences the adaptability of bacteria in their ecological niche. However, the distribution and function of T6SS in clinical Klebsiella pneumoniae, a common opportunistic nosocomial pathogen, have not been fully elucidated. Here, we conducted a genomic analysis of 65 clinical K. pneumoniae isolates obtained from patients with varying infections. Genes encoding a T6SS cluster present in all analyzed strains of K. pneumoniae, and strains with identical sequence type carried structurally and numerically identical T6SS. Our study also highlights the importance of selecting conserved regions within essential T6SS genes for PCR-based identification of T6SS in bacteria. Afterward, we utilized the predominant sequence type 11 (ST11) K. pneumoniae HS11286 to investigate the effect of knocking out T6SS marker genes hcp or vgrG. Transcriptome analysis identified a total of 1,298 co-upregulated and 1,752 co-downregulated differentially expressed genes in both mutants. Pathway analysis showed that only Δhcp mutant exhibited alterations in transport, establishment of localization, localization, and cell processes. The absence of hcp or vgrG gene suppressed the expression of other T6SS-related genes within the locus I cluster. Additionally, interbacterial competition experiments showed that hcp and vgrG are essential for competitive ability of ST11 K. pneumoniae HS11286. This study furthers our understanding of the genomic characteristics of T6SS in clinical K. pneumoniae and suggests the involvement of multiple genes in T6SS of strain HS11286.IMPORTANCEGram-negative bacteria use type VI secretion system (T6SS) to deliver effectors that interact with neighboring cells for niche advantage. Klebsiella pneumoniae is an opportunistic nosocomial pathogen that often carries multiple T6SS loci, the function of which has not yet been elucidated. We performed a genomic analysis of 65 clinical K. pneumoniae strains isolated from various sources, confirming that all strains contained T6SS. We then used transcriptomics to further study changes in gene expression and its effect on interbacterial competition following the knockout of key T6SS genes in sequence type 11 (ST11) K. pneumoniae HS11286. Our findings revealed the distribution and genomic characteristics of T6SS in clinical K. pneumoniae. This study also described the overall transcriptional changes in the predominant Chinese ST11 strain HS11286 upon deletion of crucial T6SS genes. Additionally, this work provides a reference for future research on the identification of T6SS in bacteria.

RNA pseudoknots play a crucial role in various cellular functions. Established pseudoknots show significant variation in both size and structural complexity. Specifically, three-stemmed pseudoknots are characterized by an additional stem-loop embedded in their structure. Recent findings highlight these pseudoknots as bacterial riboswitches and potent stimulators for programmed ribosomal frameshifting in RNA viruses like SARS-CoV2. To investigate the possible presence of functional three-stemmed pseudoknots in human mRNAs, we employed in-house developed computational methods to detect such structures within a dataset comprising 21,780 full-length human mRNA sequences. Numerous three-stemmed pseudoknots were identified. A selected set of 14 potential instances are presented, in which the start codon of the mRNA is found in close proximity either upstream, downstream, or within the identified three-stemmed pseudoknot. These pseudoknots likely play a role in translational initiation regulation. The probability of their existence gains support from their ranking as the most stable pseudoknot identified in the entire mRNA sequence, structural conservation across homologous mRNAs, stereochemical feasibility as demonstrated by structural modeling, and classification as members of the CPK-1 pseudoknot family, which includes many well-established pseudoknots. Furthermore, in four of the mRNAs, two or three closely spaced or tandem three-stemmed pseudoknots were identified. These findings suggest the frequent occurrence of three-stemmed pseudoknots in human mRNAs. A stepwise co-transcriptional folding mechanism is proposed for the formation of a three-stemmed pseudoknot structure. Our results not only provide fresh insights into the structures and functions of pseudoknots but also unveil the potential to target pseudoknots for treating human diseases.

Moraxella catarrhalis (M. catarrhalis) was an important pathogen closely associated with respiratory tract infections. We employed the loop-mediated isothermal amplification (LAMP) coupled with nanoparticle-based lateral flow biosensor (LFB) and fluorescence testing technique for formulating two diagnostic methods for M. catarrhalis detection, termed M. catarrhalis-LAMP-LFB assay and M. catarrhalis-LAMP-FRT, respectively. The M. catarrhalis-LAMP-LFB system incorporated the use of biotin-14-dCTP and a forward loop primer (LF) with a hapten at the 5′ end. This design in LAMP reaction enabled the production of double-labeled products that could be effectively analyzed using the lateral flow biosensor (LFB). For the M. catarrhalis-LAMP-FRT assay, the LF was modified with a sequence at 5′ end, and a fluorophore, as well as a black hole quencher, were strategically labeled at the 5′ end and within the middle of the new LF. The restriction endonuclease Nb.BsrDI could accurately recognize and cleave the newly synthesized double-strand terminal sequences, resulting in the separation of the fluorophore from the black hole quencher and releasing fluorescence signals. Both assays have been proven to be highly sensitive and specific, capable of detecting genomic DNA of M. catarrhalis at concentrations as low as 70 fg, with no cross-reactivity observed with non-M. catarrhalis pathogens. Furthermore, both methods successfully identified M. catarrhalis in all clinical samples within 1 h that were confirmed positive by real-time PCR, exhibiting superior sensitivity than conventional culture methods. Herein, the newly developed two LAMP-based assays were rapid and reliable for M. catarrhalis detection and hold significant promise for deployment in point-of-care (POC) settings.

IntroductionEpstein-Barr virus (EBV) is a highly dangerous virus that is globally prevalent and closely linked to the development of nasopharyngeal cancer (NPC). Plasma EBV DNA analysis is an effective strategy for early detection, prognostication and monitoring of treatment response of NPC.MethodsHere, we present a novel molecular diagnostic technique termed EBV-MCDA-LFB, which integrates multiple cross displacement amplification (MCDA) with nanoparticle-based lateral flow (LFB) to enable simple, rapid and specific detection of EBV. In the EBV-MCDA-LFB system, a set of 10 primers was designed for rapidly amplifying the highly conserved tandem repeat BamHI-W region of the EBV genome. Subsequently, the LFB facilitate direct assay reading, eliminating the use of extra instruments and reagents.ResultsThe outcomes showed that the 65°C within 40 minutes was the optimal reaction setting for the EBV-MCDA system. The sensitivity of EBV-MCDA-LFB assay reached 7 copies per reaction when using EBV recombinant plasmid, and it showed 100% specificity without any cross-reactivity with other pathogens. The feasibility of the EBV-MCDA-LFB method for EBV detection was successfully validated by 49 clinical plasma samples. The complete detection process, consisting of rapid template extraction (15 minutes), MCDA reaction (65°C for 40 minutes), and LFB result reading (2 minutes), can be finalized within a 60-minutes duration.DiscussionEBV-MCDA-LFB assay designed here is a fast, extremely sensitive and specific technique for detecting EBV in field and at the point-of-care (PoC), which is especially beneficial for countries and regions with a high prevalence of the disease and limited economic resources.

Elderly patients (age ≥ 65 years) are susceptible to methicillin-resistant Staphylococcus aureus (MRSA) infections, with potential for more adverse treatment outcomes or complications compared to younger adults (18–64 years). This study compared vancomycin-associated nephrotoxicity and efficacy in elderly and adult patients and investigated the correlation between vancomycin pharmacokinetic/pharmacodynamic (PK/PD) indices and clinical outcomes. A prospective study was conducted in 10 hospitals in Shanghai from October 2012 to November 2019. A total of 164 patients with MRSA infections were enrolled, including 83 elderly and 81 adult patients. Vancomycin therapeutic drug monitoring (TDM) was performed in all patients, indicating significantly higher vancomycin trough concentrations (Ctrough), 24-h area under the curve (AUC24) values, and AUC24/minimum inhibitory concentration (AUC24/MIC) values in elderly patients compared to adult patients. The incidence of vancomycin-associated nephrotoxicity was nearly three times higher in elderly patients (18.1% vs. 6.2%, p = 0.020), despite similar clinical and microbiological efficacy. Of particular importance, a Ctrough > 20 mg/L was found as an independent factor of nephrotoxicity in elderly patients. Further analysis of patients with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 also revealed that elderly patients had significantly higher vancomycin-related PK/PD indices and more nephrotoxicity than adult patients. In conclusion, elderly patients receiving vancomycin therapy face a higher risk of nephrotoxicity, which requires close vancomycin TDM, especially when the Ctrough exceeds 20 mg/L.