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This work developed DNA amplifier logic gates (AND-OR, OR-AND, FAN-IN, FAN-OUT, and 4-bit square-root circuits) using a flap endonuclease 1 (FEN1)-catalyzed signal amplification reaction, for the fastest and compact DNA computing. Moreover, the logic circuit can use input strands with concentrations of less than 1 nM, which is more than 100 times lower than the input concentration of other DNA logic circuits, providing a promising methodology for constructing fast and compact DNA computations. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphism (SNP) typing is crucial for drug dosage and disease progression. Therefore, a simple and convenient genotyping assay is essential for personalised medicine. Herein, we developed a non‐invasive, closed‐tube, and visualised method for genotyping. In this method, oral swabs were lysed to directly perform PCR coupled with nested invasive reaction and visualisation based on gold nanoparticle probes in a closed tube. The strategy for genotyping assay depends on the single base recognition property of invasive reaction. This assay allowed quick and simple sample preparation and the detection of 25 copies/μL of CYP2C19*2 and 100 copies/μL of CYP2C19*3 within 90 min. Further, 20 oral swab samples for CYP2C19*2 and CYP2C19*3 were correctly typed, which agreed with pyrosequencing, indicating that this method has great potential for SNP typing in source‐limited regions to guide personalised medicine. [ABSTRACT FROM AUTHOR]

Currently, organic solvents are necessary for the preparation of anionic liposomes for siRNA delivery. The removal of organic solvent is time‐consuming and the residual organic solvent is not only a hidden danger, but also affects the stability of anionic liposomes. Glycerol, which is physiologically compatible and does not need to be removed, is used to promote the dispersion of lipids and the formation of anionic liposomes. Additionally, the preparation process is simple and not time‐consuming. The results showed that anionic liposomes, which were typically spherical with a particle size of 188.9 nm were successfully prepared with glycerol. And with the help of Ca2+, siRNA was encapsulated in anionic liposomes. The highest encapsulation efficiency at 2.4 mM Ca2+ reached 91%. And the formation of calcium phosphate could promote the endosomal escape of siRNA effectively. The results from cell viability showed that the anionic liposomes had no obvious cytotoxicity. It was also verified that anionic liposomes could improve the resistance of siRNA against degradation. Additionally, siRNA delivered by anionic liposomes could play an effective role in knockout. Therefore, anionic liposomes prepared with glycerol will be a safe and effective delivery platform for siRNA and even other nucleic acid drugs. [ABSTRACT FROM AUTHOR]

Plasmonic nanostructures, functioning as nano-antenna reactors to highly focus light and efficiently convert it into thermal/chemical energy, have a significant potential for sustainable solar water disinfection (SODIS). A high-density plasmonic nanogap-based reactor array opens a way of maximizing the photothermal effect, but achieving uniformity and large density in such a technology while scaling up remains challenging. In this study, we provide an integrative plasmonic dimer array (hPDA) that is uniform and has high density ensuring significantly enhanced SODIS performance. The hPDA is constructed by a combined fabrication of the self-assembled monolayer and block copolymer lithography approaches. This combination leads to a two-dimensional hexagonal array of the Au dimer structures consisting of a 1.3 nm nanogap. The uniformity and high density of nanogaps of the hPDA result in the physically and optically stabilized dimer array, which allows strong light focusing and a rapid and highly efficient harvesting of photothermal energy in the visible region. Finally, the integrated hPDA with an optofluidic reactor enables 5-fold enhanced Escherichia coli (E. coli) disinfection. We anticipate that the hPDA will be useful in the scalable sustainable energy and environmental process that converts solar energy. [ABSTRACT FROM AUTHOR]

Precise nanostructure geometry that enables the optical biomolecular delivery of nanosensors to the living intracellular environment is highly desirable for precision biological and clinical therapies. However, the optical delivery through membrane barriers utilizing nanosensors remains difficult due to a lack of design guidelines to avoid inherent conflict between optical force and photothermal heat generation in metallic nanosensors during the process. Here, we present a numerical study reporting significantly enhanced optical penetration of nanosensors by engineering nanostructure geometry with minimized photothermal heating generation for penetrating across membrane barriers. We show that by varying the nanosensor geometry, penetration depths can be maximized while heat generated during the penetration process can be minimized. We demonstrate the effect of lateral stress induced by an angularly rotating nanosensor on a membrane barrier by theoretical analysis. Furthermore, we show that by varying the nanosensor geometry, maximized local stress fields at the nanoparticle–membrane interface enhanced the optical penetration process by four-fold. Owing to the high efficiency and stability, we anticipate that precise optical penetration of nanosensors to specific intracellular locations will be beneficial for biological and therapeutic applications. [ABSTRACT FROM AUTHOR]

Background: Characterization of early breast cancer circulating tumor cells (CTCs) may provide valuable information on tumor metastasis. Methods: We used immunomagnetic nanospheres to capture CTCs from the peripheral blood of eight early breast cancer patients and then performed single‐cell RNA sequencing using our proposed bead‐dd‐seq method. Results: CTCs displayed obvious tumor cell characteristics, such as the activation of oxidative stress, proliferation, and promotion of metastasis. CTCs were clustered into two subtypes significantly correlated with the lymph node metastasis status of patients. CTCs in subtype 1 showed a strong metastatic ability because these CTCs have the phenotype of partial epithelial‐mesenchymal transition and enriched transcripts, indicating breast cancer responsiveness and proliferation. Furthermore, DNA damage repair pathways were significantly upregulated in subtype 1. We performed in vitro and in vivo investigations, and found that cellular oxidative stress and further DNA damage existed in CTCs. The activated DNA damage repair pathway in CTCs favors resistance to cisplatin. A checkpoint kinase 1 inhibitor sensitized CTCs to cisplatin in mouse models of breast cancer metastasis. Conclusion: The present study dissects the molecular characteristics of CTCs from early‐stage breast cancer, providing novel insight into the understanding of CTC behavior in breast cancer metastasis. [ABSTRACT FROM AUTHOR]

Simple Summary: The biocultural diversity associated with Gaoligongshan pigs was investigated in the present paper. Six villages in Laowo Township of Lushui City in the Nujiang River watershed, where the Gaoligongshan pigs are primarily raised, were selected to collect information and data related to biocultural diversity. Participatory surveys and semi-structured interviews were conducted to document the semi-wild and free-ranging management pattern of Gaoligongshan pigs. The wild, cultivated, and medicinal plants used in rearing pigs were documented in terms of local knowledge. Most wild forage species are from Polygonaceae and Compositae while Poaceae dominated in cultivated forage plants. The local Bai and Lisu ethnic minorities have accumulated a wealth of biocultural knowledge related to diet, medicine, festivals, and rituals during their long-term rearing activities, and forming a cultural complex about Gaoligongshan pigs. This study demonstrated that the semi-wild and free-ranging management model of the Gaoligongshan pig is consistent with the local natural environment, traditional culture, economic level, and the breed's characteristics. Over 80% proteins consumed by the local people in Nujiang Prefecture of Southwest China, a remote and mountainous area in the Eastern Himalayas, are from pork, or Gaoligongshan pig (a landrace of Sus scrofa domestica Brisson). Previous research on the Gaoligongshan pig has focused on nutritional composition, production performance, and genetic resource characteristics, but neglected the reasons behind the local people's practice. From 2019 to 2022, we have used ethnobiological research methods to comprehensively document the traditional rearing and management patterns and the traditional culture associated with Gaoligongshan pigs. The results show that Gaoligongshan pigs graze in mixed herds with cattle and sheep during the day and prefer to eat 23 wild plant species, in which 17 species have medicinal values. At night, the pigs are artificially fed and rest in the pigsty. The local Bai and Lisu people have developed a creative food culture, rituals, and festivals culture associated with Gaoligongshan pigs. Overall, the biocultural diversity of Gaoligongshan pig contributes to the in situ conservation of genetic diversity of this important hog landrace, and supports rural development in this remote area. [ABSTRACT FROM AUTHOR]

Anticoagulation response to warfarin during the initial stage of therapy varies among individuals. In this study, we aimed to combine pharmacometabolomic and pharmacogenetic data to predict interindividual variation in warfarin response, and, on this basis, suggest an initial daily dose range. The baseline metabolic profiles, genotypes, and clinical information of 160 patients with heart valve disease served as the variables of the function of the last international normalized ratio measured before a patient's discharge (INRday7) to screen for potential biomarkers. The partial least‐squares model showed that two baseline metabolites (uridine and guanosine), one single‐nucleotide variation (VKORC1), and four clinical parameters (weight, creatinine level, amiodarone usage, and initial daily dose) had good predictive power for INRday7 (R2 = 0.753 for the training set, 0.643 for the test set). With these biomarkers, a machine learning algorithm (two‐dimensional linear discriminant analysis‐multinomial logit model) was used to predict the subgroups with extremely warfarin‐sensitive or less warfarin‐sensitive patients with a prediction accuracy of 91% for the training set and 90% for the test set, indicating that individual responses to warfarin could be effectively predicted. Based on this model, we have successfully designed an algorithm,"IniWarD," for predicting an effective dose range in the initial 7‐day warfarin therapy. The results indicate that the daily dose range suggested by the IniWarD system is more appropriate than that of the conventional genotype‐based method, and the risk of bleeding or thrombus due to warfarin could thus be avoided. [ABSTRACT FROM AUTHOR]

Recombination is one of the most important molecular mechanisms of prokaryotic genome evolution, but its exact roles are still in debate. Here we try to infer genome-wide recombination within a species, utilizing a dataset of 149 complete genomes of Escherichia coli from diverse animal hosts and geographic origins, including 45 in-house sequenced with the single-molecular real-time platform. Two major clades identified based on physiological, clinical and ecological characteristics form distinct genetic lineages based on scarcity of interclade gene exchanges. By defining gene-based syntenies for genomic segments within and between the two clades, we build a fine-scale recombination map for this representative global E. coli population. The map suggests extensive within-clade recombination that often breaks physical linkages among individual genes but seldom interrupts the structure of genome organizational frameworks as well as primary metabolic portfolios supported by the framework integrity, possibly due to strong natural selection for both physiological compatibility and ecological fitness. In contrast, the between-clade recombination declines drastically when phylogenetic distance increases to the extent where a 10-fold reduction can be observed, establishing a firm genetic barrier between clades. Our empirical data suggest a critical role for such recombination events in the early stage of speciation where recombination rate is associated with phylogenetic distance in addition to sequence and gene variations. The extensive intraclade recombination binds sister strains into a quasisexual group and optimizes genes or alleles to streamline physiological activities, whereas the sharply declined interclade recombination split the population into clades adaptive to divergent ecological niches. [ABSTRACT FROM AUTHOR]

Abstract Background Traditional Chinese medicine uses various herbs for the treatment of various diseases for thousands of years and it is now time to assess the characteristics and effectiveness of these medicinal plants based on modern genetic and molecular tools. The herb Flos Lonicerae Japonicae (FLJ or Lonicera japonica Thunb.) is used as an anti-inflammatory agent but the chemical quality of FLJ and its medicinal efficacy has not been consistent. Here, we analyzed the transcriptomes and metabolic pathways to evaluate the active medicinal compounds in FLJ and hope that this approach can be used for a variety of medicinal herbs in the future. Results We assess transcriptomic differences between FLJ and L. japonica Thunb. var. chinensis (Watts) (rFLJ), which may explain the variable medicinal effects. We acquired transcriptomic data (over 100 million reads) from the two herbs, using RNA-seq method and the Illumina GAII platform. The transcriptomic profiles contain over 6,000 expressed sequence tags (ESTs) for each of the three flower development stages from FLJ, as well as comparable amount of ESTs from the rFLJ flower bud. To elucidate enzymatic divergence on biosynthetic pathways between the two varieties, we correlated genes and their expression profiles to known metabolic activities involving the relevant active compounds, including phenolic acids, flavonoids, terpenoids, and fatty acids. We also analyzed the diversification of genes that process the active compounds to distinguish orthologs and paralogs together with the pathways concerning biosynthesis of phenolic acid and its connections with other related pathways. Conclusions Our study provides both an initial description of gene expression profiles in flowers of FLJ and its counterfeit rFLJ and the enzyme pool that can be used to evaluate FLJ quality. Detailed molecular-level analyses allow us to decipher the relationship between metabolic pathways involved in processing active medicinal compounds and gene expressions of their processing enzymes. Our evolutionary analysis revealed specific functional divergence of orthologs and paralogs, which lead to variation in gene functions that govern the profile of active compounds.

Human coronaviruses (CoVs) can cause respiratory infection epidemics that sometimes expand into globally relevant pandemics. All human CoVs have sister strains isolated from animal hosts and seem to have an animal origin, yet the process of host jumping is largely unknown. RNA interference (RNAi) is an ancient mechanism in many eukaryotes to defend against viral infections through the hybridization of host endogenous small RNAs (miRNAs) with target sites in invading RNAs. Here, we developed a method to identify potential RNAi-sensitive sites in the viral genome and discovered that human-adapted coronavirus strains had deleted some of their sites targeted by miRNAs in human lungs when compared to their close zoonic relatives. We further confirmed using a phylogenetic analysis that the loss of RNAi-sensitive target sites could be a major driver of the host-jumping process, and adaptive mutations that lead to the loss-of-target might be as simple as point mutation. Up-to-date genomic data of severe acute respiratory syndrome coronavirus 2 and Middle-East respiratory syndromes-CoV strains demonstrate that the stress from host miRNA milieus sustained even after their epidemics in humans. Thus, this study illustrates a new mechanism about coronavirus to explain its host-jumping process and provides a novel avenue for pathogenesis research, epidemiological modeling, and development of drugs and vaccines against coronavirus, taking into consideration these findings. [ABSTRACT FROM AUTHOR]

The CHADS 2 and CHA 2 DS 2 -VASc scores are well-established clinical scales to estimate the risk of stroke in patients with atrial fibrillation (AF). However, the predictive power of the two scales concerning left atrial thrombus (LAT) or spontaneous echo contrast (SEC) has not been well investigated. Therefore, we investigated the predict power of CHADS 2 and CHA 2 DS 2 -VASc scores concerning LAT/SEC; identified clinical, echocardiographic and laboratory predictors of LAT/SEC in addition to the CHADS 2 and CHA 2 DS 2 -VASc scores; and derived a new scale to predict LAT/SEC accurately, it might improve thromboembolic risk stratification in patients with nonvalvular atrial fibrillation. We identified 1102 consecutive AF patients who underwent transesophageal echocardiography (TEE) for the purpose of the exclusion of LAT before catheter ablation, cardioversion or left atrial appendage occlusion. The clinical, echocardiographic and laboratory characteristics of patients were collected from the electronic medical record system. In the study, the prevalence of LAT/SEC was only 4.36%. In the multivariate logistic analysis, hypertension, left atrial enlargement, prior stroke/TIA, left ventricular dysfunction, and renal dysfunction were predictors of LAT/SEC. Receiver operating characteristic curve analysis showed that c-statistics of the CHADS 2 and CHA 2 DS 2 -VASc scores concerning LAT/SEC were 0.673 and 0.643, respectively. We derived a new scale composed of variables from the multivariate logistic analysis that showed a higher c-statistic value (0.761) than the CHADS 2 and CHA 2 DS 2 -VASc scores for the prediction of LAT/SEC. In our cohort, we found two variables not included in the CHA 2 DS 2 -VASc score (renal dysfunction, left atrial enlargement) were independent predictors of LAT/SEC. A new scale combining clinical, echocardiographic and laboratory predictors might improve thromboembolic risk stratification. And there is a great need to carry out a new prospective and multicenter study, with a population more homogenous and including all the determinants for LAT/SEC to establish the independent degree of each variable and the applicability in clinical practice, facilitating the emergence of a new score of thromboembolic risk in patients with nonvalvular atrial fibrillation. • The predictive power of CHA 2 DS 2 -VASc score concerning left atrial thrombus or spontaneous echo contrast is relatively low. • Many echocardiographic and laboratory factors may also predictors of left atrial thrombus or spontaneous echo contrast in AF patients. • A new scale combining clinical, echocardiographic and laboratory predictors might improve thromboembolic risk stratification. [ABSTRACT FROM AUTHOR]

Gallai's conjecture asserts that a connected graph G on n vertices can be decomposed into ⌈ n 2 ⌉ paths. In this paper, we prove that a connected graph with maximum degree 6, in which the vertices of degree 6 form an independent set, can be decomposed into n 2 paths, unless it is K 3 , K 5 and K 5 −. [ABSTRACT FROM AUTHOR]

Background: Obesity has been widely reported to be associated with the disease progression of coronavirus disease 2019 (COVID-19); however, some studies have reported different findings. We conducted a systematic review and meta-analysis to investigate the association between obesity and poor outcomes in patients with COVID-19 pneumonia. Methods: A systematic review and meta-analysis of studies from the PubMed, Embase, and Web of Science databases from 1 November 2019 to 24 May 2020 was performed. Study quality was assessed, and data extraction was conducted. The meta-analysis was carried out using fixed-effects and random-effects models to calculate odds ratios (ORs) of several poor outcomes in obese and non-obese COVID-19 patients. Results: Twenty-two studies (n = 12,591 patients) were included. Pooled analysis demonstrated that body mass index (BMI) was higher in severe/critical COVID-19 patients than in mild COVID-19 patients (MD 2.48 kg/m2, 95% CI [2.00 to 2.96 kg/m2]). Additionally, obesity in COVID-19 patients was associated with poor outcomes (OR = 1.683, 95% CI [1.408–2.011]), which comprised severe COVID-19, ICU care, invasive mechanical ventilation use, and disease progression (OR = 4.17, 95% CI [2.32–7.48]; OR = 1.57, 95% CI [1.18–2.09]; OR = 2.13, 95% CI [1.10–4.14]; OR = 1.41, 95% CI [1.26–1.58], respectively). Obesity as a risk factor was greater in younger patients (OR 3.30 vs. 1.72). However, obesity did not increase the risk of hospital mortality (OR = 0.89, 95% CI [0.32–2.51]). Conclusions: As a result of a potentially critical role of obesity in determining the severity of COVID-19, it is important to collect anthropometric information for COVID-19 patients, especially the younger group. However, obesity may not be associated with hospital mortality, and efforts to understand the impact of obesity on the mortality of COVID-19 patients should be a research priority in the future. [ABSTRACT FROM AUTHOR]

The development of new bioelectronic platforms for direct interactions with oral fluid could open up significant opportunities for healthcare monitoring. A tongue depressor is a widely used medical tool that is inserted into the mouth, where it comes into close contact with saliva. Glucose is a typical salivary biomarker. Herein, we report—for the first time—a tongue depressor-based biosensor for the detection of glucose in both phosphate buffer and real human saliva. Carbon nanotubes (CNTs) are attractive electronic materials, with excellent electrochemical properties. The sensor is constructed by printing CNTs and silver/silver chloride (Ag/AgCl) to form three electrodes in an electrochemical cell: Working, reference, and counter electrodes. The enzyme glucose oxidase (GOD) is immobilized on the working electrode. The glucose detection performance of the sensor is excellent, with a detection range of 7.3 μM to 6 mM. The glucose detection time is about 3 min. The discretion between healthy people's and simulated diabetic patients' salivary samples is clear and easy to tell. We anticipate that the biosensor could open up new opportunities for the monitoring of salivary biomarkers and advance healthcare applications. [ABSTRACT FROM AUTHOR]

Cancer-derived exosomes carry a variety of important biomarkers specific to the formation, invasion and metastasis of tumor tissue. Dynamic monitoring of exosomes originated from cancer cells has clinical significance. Here we proposed a novel method to employ zirconium-metal-organic frameworks (Zr-MOFs) for extracting and identifying exosomes from blood. At first UiO-66 was magnetically modified as the adsorbent to anchor exosomes by forming Zr–O–P bonds. Then UiO-66-NH 2 modified with anti-EpCAM was used to construct the fluorescent probe to recognize the extracted EpCAM-positive exosomes by forming a "MOF-exosome-MOF" structure. The proposed fluorescence detection method was evaluated by quantifying MCF-7 cell-derived exosomes at the concentration as low as 16.72 particles/μl. This method was successfully applied to analyze exosomes in the plasma samples from healthy donors and breast cancer patients, demonstrating that our method might have a great potential in assisting the early diagnosis and in dynamically monitoring the efficacy of cancer treatment. We believe that the method could be extended to the detection of other biomarkers in exosomes derived from cancer cell. • The method can simultaneously complete the extraction and detection of exosomes. • The new method based on the sandwich structure showes high specificity and sensitivity. • The method have a potential in assisting the early diagnosis and dynamically monitoring the efficacy of cancer treatment. [ABSTRACT FROM AUTHOR]

Low nitrogen (NUE) and phosphorus (PUE) use efficiencies in food production in China result in large losses of nitrogen (N) and phosphorus (P) to the environment. The Chinese government formulated policies to increase the NUEs and PUEs. Recent policies aim for zero growth in synthetic fertilizer use after 2020 while ensuring food security. In this study we analyzed how current and improved nutrient management in China can affect future nutrient use efficiencies and nutrient losses from food production. The NUEs and PUEs of food production were quantified using the NUFER (NUtrient flows in Food chains, Environment and Resources use) model for 31 provinces and China in 2013, 2020 and 2050. Results show that national NUE (20%) and PUE (24%) in 2013 are low but vary largely among provinces (12–33% for NUE, 10–53% for PUE). The N and P losses to the air (14 Tg year − 1 of N) and waters (12 Tg year − 1 of N, 2 Tg year − 1 of P) are consequently high in 2013. Three scenarios were analyzed for 2020 and 2050 to explore future trends in NUEs and PUEs, assuming Business As Usual ( BAU ) trends, Zero Fertilizer ( ZF ) growth from 2020 , and Improved Nutrient Management ( INM ). In the BAU scenario, the NUEs and PUEs roughly remain at their low 2013 levels, while nutrient inputs to agriculture are increasing. The losses to the air therefore increase by 37% for N and to waters by 40% for N and 48% for P between 2013 and 2050. In the ZF scenario, the NUEs and PUEs are a few percent higher than in BAU . The associated N and P losses to waters are 8–16% lower than in BAU because of increased recycling of manure to cropland, but still higher than in 2013. Improved nutrient management, as assumed in our INM scenario, may increase NUEs and PUEs to 33% and 59% in 2050. Meanwhile, N and P losses to waters in 2050 are 47% and 83% lower than in 2013, and losses of N to the air 20% lower. We conclude that the policy aimed at zero growth in fertilizer use is a good start, but not very effective in reducing nutrient pollution in China. To substantially reduce N and P losses to the environment it is needed to improve nutrient management by not only reducing fertilization without yield losses, but also by improved manure management and animal production with lower nutrient excretion. [ABSTRACT FROM AUTHOR]