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Genomic studies of lung adenocarcinoma (LUAD) have advanced our understanding of the disease's biology and accelerated targeted therapy. However, the proteomic characteristics of LUAD remain poorly understood. We carried out a comprehensive proteomics analysis of 103 cases of LUAD in Chinese patients. Integrative analysis of proteome, phosphoproteome, transcriptome, and whole-exome sequencing data revealed cancer-associated characteristics, such as tumor-associated protein variants, distinct proteomics features, and clinical outcomes in patients at an early stage or with EGFR and TP53 mutations. Proteome-based stratification of LUAD revealed three subtypes (S-I, S-II, and S-III) related to different clinical and molecular features. Further, we nominated potential drug targets and validated the plasma protein level of HSP 90ß as a potential prognostic biomarker for LUAD in an independent cohort. Our integrative proteomics analysis enables a more comprehensive understanding of the molecular landscape of LUAD and offers an opportunity for more precise diagnosis and treatment.
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Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Proteômica , Adenocarcinoma de Pulmão/genética , Povo Asiático/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Sistemas de Liberação de Medicamentos , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Estadiamento de Neoplasias , Fosfoproteínas/metabolismo , Análise de Componente Principal , Prognóstico , Proteoma/metabolismo , Resultado do Tratamento , Proteína Supressora de Tumor p53/genéticaRESUMO
BACKGROUND: Infants and young children born prematurely are at high risk of severe acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV). In this study, we aimed to assess the global disease burden of and risk factors for RSV-associated ALRI in infants and young children born before 37 weeks of gestation. METHODS: We conducted a systematic review and meta-analysis of aggregated data from studies published between Jan 1, 1995, and Dec 31, 2021, identified from MEDLINE, Embase, and Global Health, and individual participant data shared by the Respiratory Virus Global Epidemiology Network on respiratory infectious diseases. We estimated RSV-associated ALRI incidence in community, hospital admission, in-hospital mortality, and overall mortality among children younger than 2 years born prematurely. We conducted two-stage random-effects meta-regression analyses accounting for chronological age groups, gestational age bands (early preterm, <32 weeks gestational age [wGA], and late preterm, 32 to <37 wGA), and changes over 5-year intervals from 2000 to 2019. Using individual participant data, we assessed perinatal, sociodemographic, and household factors, and underlying medical conditions for RSV-associated ALRI incidence, hospital admission, and three severity outcome groups (longer hospital stay [>4 days], use of supplemental oxygen and mechanical ventilation, or intensive care unit admission) by estimating pooled odds ratios (ORs) through a two-stage meta-analysis (multivariate logistic regression and random-effects meta-analysis). This study is registered with PROSPERO, CRD42021269742. FINDINGS: We included 47 studies from the literature and 17 studies with individual participant-level data contributed by the participating investigators. We estimated that, in 2019, 1 650 000 (95% uncertainty range [UR] 1 350 000-1 990 000) RSV-associated ALRI episodes, 533 000 (385 000-730 000) RSV-associated hospital admissions, 3050 (1080-8620) RSV-associated in-hospital deaths, and 26 760 (11 190-46 240) RSV-attributable deaths occurred in preterm infants worldwide. Among early preterm infants, the RSV-associated ALRI incidence rate and hospitalisation rate were significantly higher (rate ratio [RR] ranging from 1·69 to 3·87 across different age groups and outcomes) than for all infants born at any gestational age. In the second year of life, early preterm infants and young children had a similar incidence rate but still a significantly higher hospitalisation rate (RR 2·26 [95% UR 1·27-3·98]) compared with all infants and young children. Although late preterm infants had RSV-associated ALRI incidence rates similar to that of all infants younger than 1 year, they had higher RSV-associated ALRI hospitalisation rate in the first 6 months (RR 1·93 [1·11-3·26]). Overall, preterm infants accounted for 25% (95% UR 16-37) of RSV-associated ALRI hospitalisations in all infants of any gestational age. RSV-associated ALRI in-hospital case fatality ratio in preterm infants was similar to all infants. The factors identified to be associated with RSV-associated ALRI incidence were mainly perinatal and sociodemographic characteristics, and factors associated with severe outcomes from infection were mainly underlying medical conditions including congenital heart disease, tracheostomy, bronchopulmonary dysplasia, chronic lung disease, or Down syndrome (with ORs ranging from 1·40 to 4·23). INTERPRETATION: Preterm infants face a disproportionately high burden of RSV-associated disease, accounting for 25% of RSV hospitalisation burden. Early preterm infants have a substantial RSV hospitalisation burden persisting into the second year of life. Preventive products for RSV can have a substantial public health impact by preventing RSV-associated ALRI and severe outcomes from infection in preterm infants. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe.
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Recém-Nascido Prematuro , Infecções por Vírus Respiratório Sincicial , Infecções Respiratórias , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Lactente , Fatores de Risco , Recém-Nascido , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Incidência , Hospitalização/estatística & dados numéricos , Saúde Global/estatística & dados numéricos , Pré-Escolar , Vírus Sincicial Respiratório Humano , Mortalidade Hospitalar , Feminino , Doença AgudaRESUMO
Different modes of reproduction evolve rapidly, with important consequences for genome composition. Selfing species often occupy a similar niche as their outcrossing sister species with which they are able to mate and produce viable hybrid progeny, raising the question of how they maintain genomic identity. Here, we investigate this issue by using the nematode Caenorhabditis briggsae, which reproduces as a hermaphrodite, and its outcrossing sister species Caenorhabditis nigoni We hypothesize that selfing species might develop some barriers to prevent gene intrusions through gene regulation. We therefore examined gene regulation in the hybrid F2 embryos resulting from reciprocal backcrosses between F1 hybrid progeny and C. nigoni or C. briggsae F2 hybrid embryos with â¼75% of their genome derived from C. briggsae (termed as bB2) were inviable, whereas those with â¼75% of their genome derived from C. nigoni (termed as nB2) were viable. Misregulation of transposable elements, coding genes, and small regulatory RNAs was more widespread in the bB2 compared with the nB2 hybrids, which is a plausible explanation for the differential phenotypes between the two hybrids. Our results show that regulation of the C. briggsae genome is strongly affected by genetic exchanges with its outcrossing sister species, C. nigoni, whereas regulation of the C. nigoni genome is more robust on genetic exchange with C. briggsae The results provide new insights into how selfing species might maintain their identity despite genetic exchanges with closely related outcrossing species.
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Caenorhabditis , Animais , Caenorhabditis/genética , Genoma , Reprodução/genética , FenótipoRESUMO
MOTIVATION: Automated cell lineage tracing throughout embryogenesis plays a key role in the study of regulatory control of cell fate differentiation, morphogenesis and organogenesis in the development of animals, including nematode Caenorhabditis elegans. However, automated cell lineage tracing suffers from an exponential increase in errors at late embryo because of the dense distribution of cells, relatively low signal-to-noise ratio (SNR) and imbalanced intensity profiles of fluorescence images, which demands a huge amount of human effort to manually correct the errors. The existing image enhancement methods are not sensitive enough to deal with the challenges posed by the crowdedness and low signal-to-noise ratio. An alternative method is urgently needed to assist the existing detection methods in improving their detection and tracing accuracy, thereby reducing the huge burden for manual curation. RESULTS: We developed a new method, termed as DELICATE, that dramatically improves the accuracy of automated cell lineage tracing especially during the stage post 350 cells of C. elegans embryo. DELICATE works by increasing the local SNR and improving the evenness of nuclei fluorescence intensity across cells especially in the late embryos. The method both dramatically reduces the segmentation errors by StarryNite and the time required for manually correcting tracing errors up to 550-cell stage, allowing the generation of accurate cell lineage at large-scale with a user-friendly software/interface. AVAILABILITY AND IMPLEMENTATION: All images and data are available at https://doi.org/10.6084/m9.figshare.26778475.v1. The code and user-friendly software are available at https://github.com/plcx/NucApp-develop. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Type 2 diabetes mellitus is a prevalent metabolic disease, posing a considerable threat to public health. Oligonucleotide drugs have proven to be a promising field of therapy for the diseases. In this study, we reported that a herbal small RNA (sRNA), JGL-sRNA-h7 (B34735529, F1439.L002444.A11), could exhibit potent hypoglycemic effects by targeting glucose-6-phosphatase. Oral administration of sphingosine (d18:1)-JGL-sRNA-h7 bencaosomes ameliorated hyperglycemia and diabetic kidney injury better than metformin in db/db mice. Furthermore, glucose tolerance was also improved in sphingosine (d18:1)-JGL-sRNA-h7 bencaosomes-treated beagle dogs. Our study indicates that JGL-sRNA-h7 could be a promising hypoglycemic oligonucleotide drug.
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Hiperglicemia , Hipoglicemiantes , Animais , Cães , Masculino , Camundongos , Administração Oral , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/veterinária , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Camundongos Endogâmicos C57BL , Oligonucleotídeos/administração & dosagemRESUMO
The purpose of this study is to present a physical layer security scheme for key concealment and distribution based on carrier scrambling. The three-dimensional (3D) Lorenz system is used to generate independent chaotic sequences that encrypt the information with bit, constellation and subcarrier. In order to realize the flexible distribution of the key and ensure its security, the key information is loaded into a specific subcarrier. While key subcarrier and the ciphertext subcarrier are scrambled simultaneously. The encrypted key position information is processed and transmitted in conjunction with the training sequence (TS) to facilitate demodulation by the legitimate receiver. The processed TS can accommodate up to 10 key position information, thereby demonstrating the scheme's exceptional scalability. Experimental results show that the proposed scheme can safely transmit 131.80 Gb/s Orthogonal frequency division multiplexing (OFDM) signals across 2â km 7-core fiber. Meanwhile, the scheme enables simultaneous flexible distribution and concealment of the key, thereby offering a promising solution for physical layer security.
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In this paper, we propose a method for training a key-enhanced chaotic sequence using the convolutional long short term memory neural network (CLSTM-NN) for secure transmission. This method can cope with the potential security risk posed by the degradation of chaotic dynamics when using chaotic model encryption in traditional secure transmissions. The simulation results show that the proposed method improves the key space by 1036 compared to traditional chaotic models, reaching 10241. The method was applied to orthogonal chirp division multiplexing (OCDM). To demonstrate the feasibility of the proposed scheme, we conducted transmission experiments of encrypted 16 quadrature amplitude modulation (QAM) OCDM signals at a speed of 53.25 Gb/s over a 2â km length of 7-core optical fiber and test different encryption schemes. After key enhancements, the overall number of keys in the system can increase from 18 to 105.The results show that there is no significant difference between the bit error rate (BER) performance of the encryption method proposed in this paper and the traditional encryption method. The maximum performance difference between the different systems does not exceed 1 dBm. This fact proves the feasibility of the proposed scheme and provides new ideas for the next generation of secure transmission.
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In this paper, we propose a high spectral efficiency modulation scheme based on joint interaction of orthogonal compressed chirp division multiplexing (OCCDM) and power superimposed code (PSC) under the intensity modulation and direct detection (IM/DD) system. OCCDM is a novel orthogonal chirp division multiplexing technology featuring spectral compression through the implementation of processing similar to a discrete Fourier transform, enhancing the spectral efficiency (SE) through bandwidth savings without loss of orthogonality of each chirp. Meanwhile, PSC technology enables multiple code words being transmitted superimposed on the same chirp. This technique involves allocating varying power levels to different users, thereby distinguishing them, increasing the transmission's net bit rate and substantially boosting the SE. The transmission has been performed experimentally using a 2â km 7-core fiber span. The impact of the above-mentioned technologies on the bit error rate (BER) performance is assessed in the power, frequency, and joint domain. The BER and enhancements in the SE can be balanced when the spectral bandwidth compression factor (α) and power distribution ratio are equal to 0.9 and 4, respectively. The observed outcome leads to the transmission's SE increase to more than double the baseline value, at 2.22 times. Based on the above analysis, we believe this structure is expected to become a potential for developing next-generation PON.
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Diabetic heart disease (DHD) is a serious complication in patients with diabetes. Despite numerous studies on the pathogenic mechanisms and therapeutic targets of DHD, effective means of prevention and treatment are still lacking. The pathogenic mechanisms of DHD include cardiac inflammation, insulin resistance, myocardial fibrosis, and oxidative stress. Macrophages, the primary cells of the human innate immune system, contribute significantly to these pathological processes, playing an important role in human disease and health. Therefore, drugs targeting macrophages hold great promise for the treatment of DHD. In this review, we examine how macrophages contribute to the development of DHD and which drugs could potentially be used to target macrophages in the treatment of DHD.
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Cardiomiopatias Diabéticas , Macrófagos , Estresse Oxidativo , Transdução de Sinais , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Cardiomiopatias Diabéticas/imunologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/etiologia , Animais , Estresse Oxidativo/efeitos dos fármacos , Fibrose , Anti-Inflamatórios/uso terapêutico , Miocárdio/patologia , Miocárdio/metabolismo , Miocárdio/imunologia , Resistência à Insulina , Mediadores da Inflamação/metabolismo , Terapia de Alvo MolecularRESUMO
In this Letter, we propose a method for ultrahigh-order QAM secure transmission and key distribution based on delta-sigma modulation (DSM) and discrete memristive-enhanced chaos (DMEC). The disturbance vectors generated by the DMEC scramble the DSM signals in both frequency and time domains, resulting in highly secure DSM signals. Through the key modulation and power adjustment and then superimposing them on the encrypted signals, the method achieves simultaneous transmission of keys and signals without the need for additional spectral resources. This approach allows for secure communication with continuous key iteration and updates, offering an effective solution for implementing "one-time pad" encryption. In the experimental demonstration, we achieved a secure transmission and key distribution of a 16384QAM signal at a rate of 17.09â Gb/s over 25â km in an intensity-modulated direct detection (IMDD) system, based on DSM.
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BACKGROUND: Smoking remains a major risk factor for the development and progression of chronic obstructive pulmonary disease (COPD). Due to the adolescent smoking associated with worse health state, the age, at which an individual started smoking, might play a key role in shaping the trajectory of COPD development and the severity. METHODS: We conducted an observational study from September 2016 through January 2023 of eligible patients hospitalized with COPD. Patients who started smoking during the alveolar development stage (ADS, smoking initiation ≤ 24 years old) were defined as early smoking patients, and patients who started smoking after ADS (smoking initiation > 24 years old) were defined as late smoking patients. We collected demographic and clinical data characterizing the patients and documented their condition from hospital discharge to follow-up. The primary endpoints were short-term (within one year), 3-year, and long-term (beyond 3 years) all-cause mortality after discharge. RESULTS: Among 697 COPD patients, early smoking patients had a lower smoking cessation rate (P < 0.001) and a higher smoking index (P < 0.001) than late smoking patients. Although adjusted smoking index, early smoking patients still had poorer lung function (P = 0.023), thicker left ventricular diameters (P = 0.003), higher frequency of triple therapy use during stable stage (P = 0.049), and more acute exacerbations in the past year before enrollment (P < 0.05). Survival analysis showed that they had a higher risk of death after discharge within three years (P = 0.004) and beyond three years (P < 0.001). Furthermore, even in early smoking COPD patients who quit smoking after adjusting the smoking index had poorer lung function (P < 0.05) and thicker left ventricular diameters (P = 0.003), and survival analysis also showed that they had a higher long-term mortality rate (P = 0.010) and shorter survival time (P = 0.0128). CONCLUSION: Early smoking COPD patients exhibited multiple adverse clinical outcomes, including heavy cigarette addiction, compromised pulmonary function, augmented left ventricular diameter, and elevated mortality risk. Additional, smoking cessation could not bring enough improvement of health state in early smoking COPD patients as late smoking COPD patients. Consequently, early intervention and specialized cessation approaches for younger smokers are of paramount importance in this context.
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Doença Pulmonar Obstrutiva Crônica , Abandono do Hábito de Fumar , Adolescente , Humanos , Adulto Jovem , Adulto , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fumar/efeitos adversos , Fumar/epidemiologia , Pulmão , PrognósticoRESUMO
Increasing cut-off voltage of lithium cobalt oxide (LCO) (> 4.6 V) is an effective strategy to satisfy the ever-increasing demand for high energy density. However, the irreversible phase transition significantly destroys the structure of high-voltage LCO, especially the surface lattice. Considering that the structural stability of LCO is primarily dominated by the intrinsic merits of electrode-electrolyte interface (EEI), we explored and disclosed the operating mechanism of anion chelating agent tris(pentafluorophenyl) borane (TPFPB) and regulate the CEI layer on LCO electrode. Benefiting from the high HOMO energy level and preferential decomposition of TPFPB-PF6-, a robust LiF-rich CEI layer is constructed and greatly improves the stability of electrode/electrolyte interface. The well-designed electrolyte composed of 1 mol L-1 LiPF6 in EC/EMC with TPFPB additives endows Li/LCO half cells and 4 Ah Gr/LCO pouch cell with enhanced cycling stability under a high voltage condition. This work provides pave a new direction for the development of economical high-voltage LIBs.
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BACKGROUND: Adherence to inhaled medications is key to chronic obstructive pulmonary disease (COPD) control and management. OBJECTIVE: To assess errors and adherence to inhalation therapy in COPD patients, and identify potential factors associated with poor adherence. METHODS: This cross-sectional study was conducted from October 1, 2022, to November 30, 2022, in 24 hospital outpatient departments in different cities of Hunan Province, China. Adherence to inhaled medications was measured using the 10-item Test of Adherence Inventory, and the results were expressed using both descriptive and inferential statistics. RESULTS: A total of 2218 clinically confirmed adult COPD patients completed the questionnaires, and 1423 patients with more than a 3-month history of inhalation therapy were analyzed. This study found that 61.3% of patients made one or more use errors. Not holding the breath after inhalation or holding the breath for less than 3 s had the highest reporting rate (30.7%). A considerable proportion of patients (66.6%) demonstrated suboptimal adherence to inhaled medications. Patients who resided in rural areas (OR 1.45, 95% CI 1.12-1.88), used dual therapy (OR 1.47, 95% CI 1.05-2.05), and exhibited common use errors (OR 3.02, 95% CI 2.39-3.82) were more likely to present suboptimal adherence. Patients with CAT (Chronic Obstructive Pulmonary Disease Assessment Test) score < 10 (OR 0.73, 95% CI 0.56-0.94), a junior high school education and above (OR 0.73, 95% CI 0.57-0.94), and duration of inhaled medication use > 3 years (OR 0.63, 95% CI 0.47-0.83) were associated with better adherence. CONCLUSION: Suboptimal adherence to inhaled medications and many inhalation therapy errors were identified among COPD patients. Common use errors in inhaled medications, CAT score, and education background were predictive of and influenced adherence to inhaled medications. It is necessary to strengthen training in Chinese patients about inhaler use and follow-up intensively with patients throughout treatment, especially for patients with risk factors.
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Adesão à Medicação , Doença Pulmonar Obstrutiva Crônica , Adulto , Humanos , Estudos Transversais , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Administração por Inalação , Fatores de RiscoRESUMO
Enantiomer recognition is usually required in organic synthesis and materials and life sciences. This paper describes an enantiomer recognition method based on ternary dynamic covalent systems constructed via the complexation of chiral amines with a chiral boronate derived from 1,4-phenylenediboric acid and an L-DOPA-modified naphthalenediimide. The ternary systems aggregate into chiral assemblies driven by π-π interactions, and the chirality is transferred from the chiral amines to assemblies with high stereospecificity. Consequently, the enantiomer composition of chiral amines and the absolute configuration of the major enantiomer can be determined according to the sign of the Cotton effect of the ternary system by using circular dichroism (CD) spectroscopy. This method offers the advantage of using the long wavelength CD signals of the boronate at around 520 nm, thereby avoiding interference with those of the carbon skeleton. This ternary system provides a novel approach to the design of enantiomer recognition systems.
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BACKGROUND: Existing studies have presented limited and disparate findings on the nexus between immune cells, plasma metabolites, and metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this study was to investigate the causal relationship between immune cells and MASLD. Additionally, we aimed to identify and quantify the potential mediating role of metabolites. METHODS: A Mendelian randomization (MR) analysis was conducted using two samples of pooled data from genome-wide association studies on MASLD that included 2568 patients and 409,613 control individuals. Additionally, a mediated MR study was employed to quantify the metabolite-mediated immune cell effects on MASLD. RESULTS: In this study, eight immunophenotypes were linked to the risk of MASLD, and thirty-five metabolites/metabolite ratios were linked to the occurrence of MASLD. Furthermore, a total of six combinations of immunophenotypic and metabolic factors demonstrated effects on the occurrence of MASLD, although the mediating effects of metabolites were not significant. CONCLUSION: Our study demonstrated that certain immunophenotypes and metabolite/metabolite ratios have independent causal relationships with MASLD. Furthermore, we identified specific metabolites/metabolite ratios that are associated with an increased risk of MASLD. However, their mediating role in the causal association between immunophenotypes and MASLD was not significant. It is important to consider immune and metabolic disorders among patients with MASLD in clinical practice.
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Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Humanos , Polimorfismo de Nucleotídeo Único , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado Gorduroso/imunologia , Imunofenotipagem , MasculinoRESUMO
Polarization imaging, based on the measurement of polarization parameters containing specific physical information, has found extensive applications across various domains. Among these parameters, polarization angle information plays a crucial role in revealing texture details. However, in practical scenarios, noise during image acquisition can lead to significant degradation of polarization angle information. To address this issue, we introduce a novel, to the best of our knowledge, polarization angle information enhancement method based on polarimetric array imaging. Our proposed method utilizes the principles of polarimetric array imaging to effectively restore texture information embedded within polarization angle images. Through the deployment of a self-designed polarimetric array imaging system, we conducted experiments in diverse scenes to validate the efficacy of our approach. The acquired polarization angle data were subjected to our method for enhancement. The experimental outcomes distinctly illustrate the noise suppression capabilities of our method, showcasing its ability to faithfully reconstruct intricate details obscured by substantial noise interference.
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Soil salinization has been considered as a major environmental threat to plant growth. Different types of salt in saline soil have different effects on germination and seedling growth. Effect of NaCl on germination and seedling establishment in Suaeda liaotungensis have been reported, but its response to alkali stress remains unclear. Our results showed that brown seeds had higher germination rate, however, black seeds had higher germination recovery percentage under alkali stress. Na2CO3 had stronger inhibitory effect on germination and seedling growth than NaHCO3. As the concentration of alkali stress increased, the ROS level of brown seeds gradually ascended, while that of black seeds decreased first and then ascended. MDA content of dimorphic seeds significantly increased under alkali stress. The trend of SOD, POD and CAT activity between dimorphic seeds was similar under the same type of alkali stress. Alkali stress enhanced proline content of dimorphic seeds, and dimorphic seeds in NaHCO3 solution had higher proline content than Na2CO3 solution. Moreover, radicle and shoot tolerance indexes of seedlings in NaHCO3 solution were significantly higher than that of Na2CO3 solution. Under strong alkali stress, seedlings in NaHCO3 solution had significantly lower ROS level and MDA content as well as higher antioxidant enzyme activity than Na2CO3 solution. This study comprehensively compared the morphological and physiological characteristics in germination and seedlings to better reveal the saline-alkali tolerance mechanisms in S. liaotungensis.
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BACKGROUND: Homology-based recombination (HR) is the cornerstone of genetic mapping. However, a lack of sufficient sequence homology or the presence of a genomic rearrangement prevents HR through crossing, which inhibits genetic mapping in relevant genomic regions. This is particularly true in species hybrids whose genomic sequences are highly divergent along with various genome arrangements, making the mapping of genetic loci, such as hybrid incompatibility (HI) loci, through crossing impractical. We previously mapped tens of HI loci between two nematodes, Caenorhabditis briggsae and C. nigoni, through the repeated backcrossing of GFP-linked C. briggsae fragments into C. nigoni. However, the median introgression size was over 7 Mb, indicating apparent HR suppression and preventing the subsequent cloning of the causative gene underlying a given HI phenotype. Therefore, a robust method that permits recombination independent of sequence homology is desperately desired. RESULTS: Here, we report a method of highly efficient targeted recombination (TR) induced by CRISPR/Cas9 with dual guide RNAs (gRNAs), which circumvents the HR suppression in hybrids between the two species. We demonstrated that a single gRNA was able to induce efficient TR between highly homologous sequences only in the F1 hybrids but not in the hybrids that carry a GFP-linked C. briggsae fragment in an otherwise C. nigoni background. We achieved highly efficient TR, regardless of sequence homology or genetic background, when dual gRNAs were used that each specifically targeted one parental chromosome. We further showed that dual gRNAs were able to induce efficient TR within genomic regions that had undergone inversion, in which HR-based recombination was expected to be suppressed, supporting the idea that dual-gRNA-induced TR can be achieved through nonhomology-based end joining between two parental chromosomes. CONCLUSIONS: Recombination suppression can be circumvented through CRISPR/Cas9 with dual gRNAs, regardless of sequence homology or the genetic background of the species hybrid. This method is expected to be applicable to other situations in which recombination is suppressed in interspecies or intrapopulation hybrids.
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Caenorhabditis , Animais , Caenorhabditis/genética , Sistemas CRISPR-Cas , Mapeamento Cromossômico , Genoma , Recombinação GenéticaRESUMO
Introduction: Liver transplantation (LT) is an operation purposed to save the lives of children with acute or chronic liver diseases, hepatic tumors, and some genetic and metabolic diseases. However, patients who underwent LT have a significant risk of intraoperative blood loss and red blood cell (RBC) transfusion, especially in pediatric patients. Methods: In this study, 569 pediatric patients (<18 years old) who underwent LT at a tertiary university hospital between 2013 and 2020 were included. Multiple logistic regression was used to analyze the association between the ratio of intraoperative RBC transfusion to blood loss (IRTBL) and the complications after LT in pediatric patients. IRTBL was divided into quartiles in the adjusted model. Odds ratios, 95% confidence intervals, and p values for trends were calculated. Restricted cubic spline (RCS) regression was used to evaluate the nonlinear association between IRTBL and complications. Results: Compared with the lowest level and the highest level of IRTBL, Q2 and Q3 quartiles of IRTBL showed significantly positive association with early complications. A significantly nonlinear association was observed between the IRTBL and early complications in the RCS model with the multiple adjustments of potential covariates (P overall<0.01, P nonlinear<0.01). However, no significant association was observed between late complications and IRTBL. Conclusion: In this study, we found there was a nonlinear relationship between the ratio of IRTBL and early postoperative complications in pediatric LT patients, which provides a theoretical basis for RBC transfusion in pediatric LT patients.
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BACKGROUND: Carboxymethylpachymaran (CMP) is created by carboxymethylating pachyman (PM), which increases its water solubility and enhances a number of biological activities. Traditional polysaccharides modified by carboxymethylation employ strong chemical techniques. Carboxymethylcellulose (CMC) has been used previously for liquid fermentation to carboxymethyl modify bacterial polysaccharides. This theory can be applied to fungal polysaccharides because Poria cocos has the ability to naturally utilize cellulose. RESULTS: CMC with different degrees of substitution (DS) (0.7, 0.9 and 1.2) were added to P. cocos fermentation medium, and CMPs with different DS (0.38, 0.56 and 0.78, respectively) were prepared by liquid fermentation. The physical and chemical properties and biological activities of the CMPs were determined. Their structures were confirmed by Fourier transform infrared (FTIR) spectroscopy and monosaccharide composition. With the increase of DS, the viscosity and viscosity-average molecular weight of CMPs decreased, whereas polysaccharide content and water solubility increased, although the triple helix structure was not affected. The results of bioactivity assay showed that the higher the DS of CMPs, the higher the 2,2-diphenyl-1-picrylhydrazyl radical scavenging ability, and the stronger the bacterial inhibition ability. CONCLUSION: The present study has developed a method for producing CMPs by P. cocos liquid fermentation. The results of the study confirm that enhancing the DS of CMP could effectively enhance its potential biological activity. The findings provide safe and reliable raw materials for creating CMP-related foods and encourage CMP application in the functional food industry. © 2024 Society of Chemical Industry.