RESUMO
Deep sequencing now provides detailed snapshots of ribosome occupancy on mRNAs. We leverage these data to parameterize a computational model of translation, keeping track of every ribosome, tRNA, and mRNA molecule in a yeast cell. We determine the parameter regimes in which fast initiation or high codon bias in a transgene increases protein yield and infer the initiation rates of endogenous Saccharomyces cerevisiae genes, which vary by several orders of magnitude and correlate with 5' mRNA folding energies. Our model recapitulates the previously reported 5'-to-3' ramp of decreasing ribosome densities, although our analysis shows that this ramp is caused by rapid initiation of short genes rather than slow codons at the start of transcripts. We conclude that protein production in healthy yeast cells is typically limited by the availability of free ribosomes, whereas protein production under periods of stress can sometimes be rescued by reducing initiation or elongation rates.
Assuntos
Modelos Genéticos , Biossíntese de Proteínas , Saccharomyces cerevisiae/genética , Códon/genética , Cadeias de Markov , RNA Mensageiro/metabolismo , RNA de Transferência/metabolismo , Ribossomos/metabolismoRESUMO
The disequilibrium of amyloid ß-peptide (Aß) between the central and peripheral pools has been claimed as an initiating event in Alzheimer's disease (AD). In this study, we employ discoidal high-density lipoproteins (HDL-Disc) mimicking Aß antibody for directional flux of Aß from central to peripheral catabolism, with desirable safety and translation potential. Structurally, HDL-Disc assembly (polyDisc) is prepared with aid of chitosan derivative polymerization. After intranasal administration and response to slightly acidic nasal microenvironment, polyDisc depolymerizes into carrier-free HDL-Disc with chitosan derivatives that adhere to the mucosal layer to reversibly open tight junctions, helping HDL-Disc penetrate the olfactory pathway into brain. Thereafter, HDL-Disc captures Aß into microglia for central clearance or ferries Aß out of the brain for liver-mediated compensatory catabolism. For synergy therapy, intranasal administration of polyDisc can effectively reduce intracerebral Aß burden by 97.3% and vascular Aß burden by 73.5%, ameliorate neurologic damage, and rescue memory deficits in APPswe/PS1dE9 transgenic AD mice with improved safety, especially vascular safety. Collectively, this design provides a proof of concept for developing Aß antibody mimics to mobilize a synergy of central and peripheral Aß clearance for AD treatment.
Assuntos
Doença de Alzheimer , Quitosana , Camundongos , Animais , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Quitosana/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/metabolismo , Camundongos Transgênicos , Modelos Animais de DoençasRESUMO
During early mammalian embryo development, different epigenetic marks undergo reprogramming and play crucial roles in the mediation of gene expression. Currently, several databases provide multi-omics information on early embryos. However, how interconnected epigenetic markers function together to coordinate the expression of the genetic code in a spatiotemporal manner remains difficult to analyze, markedly limiting scientific and clinical research. Here, we present dbEmbryo, an integrated and interactive multi-omics database for human and mouse early embryos. dbEmbryo integrates data on gene expression, DNA methylation, histone modifications, chromatin accessibility, and higher-order chromatin structure profiles for human and mouse early embryos. It incorporates customized analysis tools, such as "multi-omics visualization," "Gene&Peak annotation," "ZGA gene cluster," "cis-regulation," "synergistic regulation," "promoter signal enrichment," and "3D genome." Users can retrieve gene expression and epigenetic profile patterns to analyze synergistic changes across different early embryo developmental stages. We showed the uniqueness of dbEmbryo among extant databases containing data on early embryo development and provided an overview. Using dbEmbryo, we obtained a phase-separated model of transcriptional control during early embryo development. dbEmbryo offers web-based analytical tools and a comprehensive resource for biologists and clinicians to decipher molecular regulatory mechanisms of human and mouse early embryo development.
RESUMO
Ebola (EBOV) and Marburg viruses (MARV) cause severe hemorrhagic fever associated with high mortality rates in humans. A better understanding of filovirus-host interactions that regulate the EBOV and MARV lifecycles can provide biological and mechanistic insight critical for therapeutic development. EBOV glycoprotein (eGP) and MARV glycoprotein (mGP) mediate entry into host cells primarily by actin-dependent macropinocytosis. Here, we identified actin-binding cytoskeletal crosslinking proteins filamin A (FLNa) and B (FLNb) as important regulators of both EBOV and MARV entry. We found that entry of pseudotype psVSV-RFP-eGP, infectious recombinant rVSV-eGP-mCherry, and live authentic EBOV and MARV was inhibited in filamin A knockdown (FLNaKD) cells, but was surprisingly enhanced in filamin B knockdown (FLNbKD) cells. Mechanistically, our findings suggest that differential regulation of macropinocytosis by FLNa and FLNb likely contributes to their specific effects on EBOV and MARV entry. This study is the first to identify the filamin family of proteins as regulators of EBOV and MARV entry. These findings may provide insight into the development of new countermeasures to prevent EBOV and MARV infections.
Assuntos
Ebolavirus , Doença pelo Vírus Ebola , Marburgvirus , Humanos , Filaminas/genética , Ebolavirus/genética , Actinas , Marburgvirus/genética , GlicoproteínasRESUMO
Rational design of structural polarization is vital for modern technologies, as it allows the physical properties of functional materials to be tailored. An effective approach for governing polarization involves the utilization of stereochemical lone-pair electrons (LPEs). However, despite the recognized significance of LPEs in controlling structural polarization, there remains a lack of understanding regarding the quantitative relationship between their expression and the extent of structural polarization. Here, by using pressure to continuously tune the LPE expression, we achieve the precise control and quantification of structural polarization, which brings enhanced second harmonic generation (SHG) of the molecular crystal SbI3·3S8. We introduce the I-Sb-I angle (αÌ ) that describes the degree of LPE expression and establishes a quantitative relationship between αÌ and structural polarization. That is, decreasing αÌ shapes LPE expression from delocalization to localization, which repels the bonding pairs of electrons and thus enhances the structural polarization. In addition, we extend this quantified relationship to a series of molecular crystals and demonstrate its applicability to the design of structural polarization by tailoring LPE expression.
RESUMO
Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, induces deficits in cognition and information processing following chronic abuse. Adolescent ketamine misuse represents a significant global public health issue; however, the neurodevelopmental mechanisms underlying this phenomenon remain largely elusive. This study investigated the long-term effects of sub-chronic ketamine (Ket) administration on the medial prefrontal cortex (mPFC) and associated behaviors. In this study, Ket administration during early adolescence displayed a reduced density of excitatory synapses on parvalbumin (PV) neurons persisting into adulthood. However, the synaptic development of excitatory pyramidal neurons was not affected by ketamine administration. Furthermore, the adult Ket group exhibited hyperexcitability and impaired socialization and working memory compared to the saline (Sal) administration group. These results strongly suggest that sub-chronic ketamine administration during adolescence results in functional deficits that persist into adulthood. Bioinformatic analysis indicated that the gene co-expression module1 (M1) decreased expression after ketamine exposure, which is crucial for synapse development in inhibitory neurons during adolescence. Collectively, these findings demonstrate that sub-chronic ketamine administration irreversibly impairs synaptic development, offering insights into potential new therapeutic strategies.
Assuntos
Neurônios GABAérgicos , Interneurônios , Ketamina , Parvalbuminas , Córtex Pré-Frontal , Sinapses , Animais , Ketamina/farmacologia , Ketamina/administração & dosagem , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Parvalbuminas/metabolismo , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Masculino , Interneurônios/efeitos dos fármacos , Interneurônios/metabolismo , Camundongos , Neurônios GABAérgicos/efeitos dos fármacos , Neurônios GABAérgicos/metabolismo , Camundongos Endogâmicos C57BL , Antagonistas de Aminoácidos Excitatórios/farmacologiaRESUMO
Mixed-cation perovskite solar cells (PSCs) have attracted much attention because of the advantages of suitable bandgap and stability. It is still a challenge to rationally design and modify the perovskite/tin oxide (SnO2) heterogeneous interface for achieving highly efficient and stable PSCs. Herein, a strategy of one-stone-for-three-birds is proposed to achieve multi-functional interface regulation via introducing N-Chlorosuccinimide (NCS) into the solution of SnO2: i) CâO functional group in NCS can induces strong binding affinity to uncoordinated defects (oxygen vacancies, free lead ions, etc) at the buried interface and passivate them; ii) incomplete in situ hydrolysis reactions can occur spontaneously and adjust the pH value of the SnO2 solution to achieve a more matchable energy level; iii) effectively releasing the residual stress of the underlying perovskite. As a result, a champion power conversion efficiency (PCE) of 24.74% is achieved with a device structure of ITO/SnO2/Perovskite/Spiro-OMeTAD/Ag, which is one of the highest values for cesium-formamidinium-methylammonium (CsFAMA) triple cation PSCs. Furthermore, the device without encapsulation can sustain 94.6% of its initial PCE after the storage at room temperature and relative humidity (RH) of 20% for 40 days. The research provides a versatile way to manipulate buried interface for achieving efficient and stable PSCs.
RESUMO
Cellular senescence (CS), a state of permanent growth arrest, is intertwined with tumorigenesis. Due to the absence of specific markers, characterizing senescence levels and senescence-related phenotypes across cancer types remain unexplored. Here, we defined computational metrics of senescence levels as CS scores to delineate CS landscape across 33 cancer types and 29 normal tissues and explored CS-associated phenotypes by integrating multiplatform data from ~20 000 patients and ~212 000 single-cell profiles. CS scores showed cancer type-specific associations with genomic and immune characteristics and significantly predicted immunotherapy responses and patient prognosis in multiple cancers. Single-cell CS quantification revealed intra-tumor heterogeneity and activated immune microenvironment in senescent prostate cancer. Using machine learning algorithms, we identified three CS genes as potential prognostic predictors in prostate cancer and verified them by immunohistochemical assays in 72 patients. Our study provides a comprehensive framework for evaluating senescence levels and clinical relevance, gaining insights into CS roles in cancer- and senescence-related biomarker discovery.
Assuntos
Neoplasias da Próstata , Microambiente Tumoral , Senescência Celular/genética , Genômica , Humanos , Imunoterapia , Masculino , Neoplasias da Próstata/genética , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy stands out as a revolutionary intervention, exhibiting remarkable remission rates in patients with refractory/relapsed (R/R) B-cell malignancies. However, the potential side effects of therapy, particularly cytokine release syndrome (CRS) and infections, pose significant challenges due to their overlapping clinical features. Promptly distinguishing between CRS and infection post CD19 target CAR-T cell infusion (CTI) remains a clinical dilemma. Our study aimed to analyze the incidence of infections and identify key indicators for early infection detection in febrile patients within 30 days post-CTI for B-cell malignancies. METHODS: In this retrospective cohort study, a cohort of 104 consecutive patients with R/R B-cell malignancies who underwent CAR-T therapy was reviewed. Clinical data including age, gender, CRS, ICANS, treatment history, infection incidence, and treatment responses were collected. Serum biomarkers procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were analyzed using chemiluminescent assays. Statistical analyses employed Pearson's Chi-square test, t-test, Mann-Whitney U-test, Kaplan-Meier survival analysis, Cox proportional hazards regression model, Spearman rank correlation, and receiver operating characteristic (ROC) curve analysis to evaluate diagnostic accuracy and develop predictive models through multivariate logistic regression. RESULTS: In this study, 38 patients (36.5%) experienced infections (30 bacterial, 5 fungal, and 3 viral) within the first 30 days of CAR T-cell infusion. In general, bacterial, fungal, and viral infections were detected at a median of 7, 8, and 9 days, respectively, after CAR T-cell infusion. Prior allogeneic hematopoietic cell transplantation (HCT) was an independent risk factor for infection (Hazard Ratio [HR]: 4.432 [1.262-15.565], P = 0.020). Furthermore, CRS was an independent risk factor for both infection ((HR: 2.903 [1.577-5.345], P < 0.001) and severe infection (9.040 [2.256-36.232], P < 0.001). Serum PCT, IL-6, and CRP were valuable in early infection prediction post-CAR-T therapy, particularly PCT with the highest area under the ROC curve (AUC) of 0.897. A diagnostic model incorporating PCT and CRP demonstrated an AUC of 0.903 with sensitivity and specificity above 83%. For severe infections, a model including CRS severity and PCT showed an exceptional AUC of 0.991 with perfect sensitivity and high specificity. Based on the aforementioned analysis, we proposed a workflow for the rapid identification of early infection during CAR-T cell therapy. CONCLUSIONS: CRS and prior allogeneic HCT are independent infection risk factors post-CTI in febrile B-cell malignancy patients. Our identification of novel models using PCT and CRP for predicting infection, and PCT and CRS for predicting severe infection, offers potential to guide therapeutic decisions and enhance the efficacy of CAR-T cell therapy in the future.
Assuntos
Antígenos CD19 , Febre , Imunoterapia Adotiva , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Imunoterapia Adotiva/métodos , Adulto , Antígenos CD19/metabolismo , Infecções/sangue , Idoso , Curva ROC , Adulto Jovem , Estudos RetrospectivosRESUMO
KMT2A-rearranged (KMT2A-r) infant acute lymphoblastic leukemia (ALL) is a devastating malignancy with a dismal outcome, and younger age at diagnosis is associated with increased risk of relapse. To discover age-specific differences and critical drivers that mediate poor outcome in KMT2A-r ALL, we subjected KMT2A-r leukemias and normal hematopoietic cells from patients of different ages to single-cell multiomics analyses. We uncovered the following critical new insights: leukemia cells from patients <6 months have significantly increased lineage plasticity. Steroid response pathways are downregulated in the most immature blasts from younger patients. We identify a hematopoietic stem and progenitor-like (HSPC-like) population in the blood of younger patients that contains leukemic blasts and form an immunosuppressive signaling circuit with cytotoxic lymphocytes. These observations offer a compelling explanation for the ability of leukemias in young patients to evade chemotherapy and immune-mediated control. Our analysis also revealed preexisting lymphomyeloid primed progenitors and myeloid blasts at initial diagnosis of B-ALL. Tracking of leukemic clones in 2 patients whose leukemia underwent a lineage switch documented the evolution of such clones into frank acute myeloid leukemia (AML). These findings provide critical insights into KMT2A-r ALL and have clinical implications for molecularly targeted and immunotherapy approaches. Beyond infant ALL, our study demonstrates the power of single-cell multiomics to detect tumor intrinsic and extrinsic factors affecting rare but critical subpopulations within a malignant population that ultimately determines patient outcome.
Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Antineoplásicos/uso terapêutico , Rearranjo Gênico , Humanos , Imunoterapia , Lactente , Leucemia Mieloide Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMO
BACKGROUND: Adenoid cystic carcinoma is a rare subtype of triple-negative breast carcinoma. These low-grade tumours, which are treated by simple mastectomy and have an excellent prognosis compared to other triple-negative breast carcinomas. Solid-variant adenoid cystic carcinomas have basaloid features and are difficult to distinguish morphologically from other triple-negative breast cancers. Breast adenoid cystic carcinoma exhibits MYB protein overexpression, which can be detected by immunohistochemistry (IHC). AIM: We compared the IHC expression of MYB in solid-variant adenoid cystic carcinoma with that in other triple-negative breast cancers. METHODS: We conducted IHC staining of 210 samples of triple-negative breast cancers, including solid-variant adenoid cystic carcinoma (n = 17), metaplastic breast carcinoma (n = 44), basaloid triple-negative breast cancer (n = 21), and other triple-negative invasive ductal carcinoma (n = 128). We classified nuclear staining of MYB as diffuse/strong (3+), focal moderate (2+), focal weak (1+), or none (0). RESULTS: All 17 solid/basaloid adenoid cystic carcinoma cases exhibited 3+ MYB expression. Of the 21 solid/basaloid triple-negative breast cancers, one (5%) had 2+ expression, seven (33%) 1+ expression, and 13 (62%) 0 expression. Of the 44 metaplastic carcinoma cases, 39 cases (89%) had no (0) staining, and the other five cases had focal weak (1+) or moderate (2+) staining. Among the 128 triple-negative invasive ductal carcinoma cases, 92 cases (72%) had no (0) staining, 36 cases (28%) exhibited focal weak (1+) or moderate (2+) staining. CONCLUSIONS: Our study revealed diffuse/strong MYB staining (3+) only in solid/basaloid adenoid cystic carcinomas. Thus, we recommend routine MYB IHC staining in triple-negative breast carcinoma with solid/basaloid morphology to improve diagnostic accuracy.
Assuntos
Biomarcadores Tumorais , Carcinoma Adenoide Cístico , Imuno-Histoquímica , Proteínas Proto-Oncogênicas c-myb , Neoplasias de Mama Triplo Negativas , Humanos , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/patologia , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/diagnóstico , Feminino , Proteínas Proto-Oncogênicas c-myb/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Idoso , Adulto , Sensibilidade e Especificidade , Idoso de 80 Anos ou maisRESUMO
Three psychrophilic bacteria, designated as strains SQ149T, SQ345T, and S1-1T, were isolated from deep-sea sediment from the South China Sea. All three strains were the most closely related to Thalassotalea atypica RZG4-3-1T based on the 16S rRNA gene sequence analysis (similarity ranged from 96.45 to 96.67â%). Phylogenetic analysis based on the 16S rRNA gene and core-genome sequences showed that three strains formed a cluster within the genus Thalassotalea. The average amino acid identity, average nucleotide identity, and digital DNA-DNA hybridization values among the three strains and closest Thalassotalea species were far below the cut-off value recommended for delineating species, indicating they each represented a novel species. All three strains were Gram-stain-negative, rod-shaped, and contained summed feature 3 (C16â:â1 ω7c and/or C16â:â1 ω6c) as the predominant fatty acid, Q-8 as the major respiratory quinone, and phosphatidylethanolamine and phosphatidylglycerol as predominant polar lipids. Based on the genomic, phylogenetic, and phenotypic characterizations, each strain is considered to represent a novel species within the genus Thalassotalea, for which the names Thalassotalea psychrophila sp. nov. (type strain SQ149T=MCCC 1K04231T=JCM 33807T), Thalassotalea nanhaiensis sp. nov. (type strain SQ345T=MCCC 1K04232T=JCM 33808T), and Thalassotalea fonticola sp. nov. (type strain S1-1T=MCCC 1K06879T=JCM 34824T) are proposed.
Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Sedimentos Geológicos , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Água do Mar , Análise de Sequência de DNA , Sedimentos Geológicos/microbiologia , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Ácidos Graxos/química , China , Água do Mar/microbiologiaRESUMO
In mammals, type I IFNs, which commonly contain one or two disulfide bonds, activate the JAK-STAT signaling pathway through binding to the common cell surface receptor formed by IFN-α/ß receptor (IFNAR)1 and IFNAR2 subunits. Although type I IFNs are also known to be essential for antiviral defense in teleost fish, very little is known about mechanisms underlying the recognition of fish type I IFNs by associated receptors. In this study, we demonstrate that a type I IFN of large yellow croaker Larimichthys crocea (LcIFNi), belonging to a new subgroup of fish type I IFNs, triggers antiviral response via the conserved JAK-STAT pathway through stable binding with a heterodimeric receptor comprising subunits LcCRFB5 and LcCRFB2. LcIFNi binds to LcCRFB5 with a much higher affinity than to LcCRFB2. Furthermore, we determined the crystal structure of LcIFNi at a 1.39 Å resolution. The high-resolution structure is, to our knowledge, the first reported structure of a type I IFN with three disulfide bonds, all of which were found to be indispensable for folding and stability of LcIFNi. Using structural analysis, mutagenesis, and biochemical assays, we identified key LcIFNi residues involved in receptor interaction and proposed a structural model of LcIFNi bound to the LcCRFB2-LcCRFB5 receptor. The results show that LcIFNi-LcCRFB2 exhibits a similar binding pattern to human IFN-ω-IFNAR2, whereas the binding pattern of LcIFNi-LcCRFB5 is quite different from that of IFN-ω-IFNAR1. Altogether, our findings reveal the structural basis for receptor interaction and signaling of a type I IFN with three disulfide bonds and provide new insights into the mechanisms underlying type I IFN recognition in teleosts.
Assuntos
Perciformes , Transdução de Sinais , Animais , Antivirais , Dissulfetos/metabolismo , Peixes/metabolismo , Humanos , Janus Quinases/metabolismo , Mamíferos/metabolismo , Receptor de Interferon alfa e beta/metabolismo , Fatores de Transcrição STAT/metabolismoRESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), often linked with obesity, can also affect individuals with normal weight, a condition known as "lean NAFLD", imposing comparable burdens and adverse effects. However, the impact of diet on lean NAFLD remains underexplored. The objective of this study is to investigate the correlation between the Dietary Inflammatory Index (DII) and NAFLD among Americans, stratified by waist-to-height ratio (WHtR) and body mass index (BMI). METHODS: Five thousand one hundred fifty-two participants from the National Health and Nutrition Examination Survey (NHANES) 2003-2018 were comprised in the final analysis. NAFLD and advanced liver fibrosis were diagnosed by serological markers. Lean and abdominal lean individuals were identified using BMI and WHtR, separately. DII was determined by assigning scores to 28 distinct food parameters based on their inflammatory potential, obtained from the NAHNES website. Differences across DII quartiles were evaluated using the Kruskal-Wallis H Test, Chi-Square Test along with One-Way ANOVA. The correlation between DII and NAFLD was determined by multiple regression models and subgroup analyses. RESULTS: Among the 5152 subjects, 2503 were diagnosed with NAFLD, including 86 cases of lean NAFLD and 8 cases of abdominal lean NAFLD. DII was positively linked with NAFLD (Odds Ratio (OR) = 1.81 [1.48-2.21], P < 0.001) and advanced liver fibrosis (OR = 1.46 [1.02-2.07], P = 0.037). Further analysis revealed that this association was primarily observed in obese or abdominal obese participants (In BMI ≥ 25.00 kg/m^2, OR = 1.56 [1.23-1.98], P < 0.001. In WHtR> 0.50, OR = 1.48 [1.23-1.79], P < 0.001.), rather than their lean counterparts. Subgroup analyses indicated that female individuals, without a diagnosis of hypertension or diabetes appeared to be more sensitive to the rise in DII. CONCLUSIONS: Our data demonstrated a significant positive correlation between DII and NAFLD in the general population. However, the impact of a pro-inflammatory diet was less prominent in lean individuals compared to obese ones.
Assuntos
Índice de Massa Corporal , Inflamação , Hepatopatia Gordurosa não Alcoólica , Inquéritos Nutricionais , Obesidade , Humanos , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Feminino , Masculino , Obesidade/complicações , Pessoa de Meia-Idade , Adulto , Dieta/efeitos adversos , Razão Cintura-Estatura , Magreza/complicações , Fatores de Risco , Cirrose Hepática/patologia , Cirrose Hepática/epidemiologiaRESUMO
Near-field hydrodynamic interactions in active fluids are essential to determine many important emergent behaviors observed, but have not been successfully modeled so far. In this work, we propose an effective model capturing the essence of the near-field hydrodynamic interactions through a tensorial coefficient of resistance, validated numerically by a pedagogic model system consisting of an Escherichia coli bacterium and a passive sphere. In a critical test case that studies the scattering angle of the bacterium-sphere pair dynamics, we prove that the near-field hydrodynamics can make a qualitative difference even for this simple two-body system: Calculations based on the proposed model reveal a region in parameter space where the bacterium is trapped by the passive sphere, a phenomenon that is regularly observed in experiments but cannot be explained by any existing model. In the end, we demonstrate that our model also leads to efficient simulation of active fluids with tens of thousands of bacteria, sufficiently large for investigations of many emergent behaviors.
Assuntos
Escherichia coli/fisiologia , Hidrodinâmica , Modelos Biológicos , Simulação por Computador , SuspensõesRESUMO
Objective: This study aimed to explore the clinical application of aseptic skin repair dressing in facial dermatitis. Patients and Methods: A total of 80 patients with facial dermatitis admitted to Zhejiang Provincial People's Hospital from February 2020 to May 2021 were enrolled. And randomly assigned to the control group and study group, with 40 cases in each group. The control group received nicotinamide and narrow-band red light, while the study group received nicotinamide, narrow-band red light, and sterile skin repair dressing. The clinical efficacy, symptom score, erythema, transepidermal water loss (TEWL), and adverse reactions were compared after treatment. Results: After treatment, the study group exhibited significantly lower symptom scores, erythema amount, and TEWL value compared to the control group (P < .05). The clinical efficacy rate in the study group (97.5%) was significantly higher than that in the control group (82.5%) (P < .05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (2.5% vs. 5%) (P > .05). Conclusion: Aseptic skin repair dressing, employed as an adjunctive therapy for facial dermatitis, demonstrates a noteworthy capacity to effectively mitigate parameters such as patient symptom scores, facial erythema quantity, and TEWL values. Notably, the application of this dressing does not pose an elevated risk of adverse reactions. These merits substantiate the superior therapeutic efficacy of aseptic skin repair dressing in facilitating the treatment of facial dermatitis.
RESUMO
INTRODUCTION: Effective pain management is crucial in cleft lip and palate (CLP) patients undergoing orthognathic surgery for earlier recovery and decreased opioid reliance. Liposomal bupivacaine (Exparel) is a local anesthetic that provides extended postoperative analgesia in adult patients; however, research on its use in adolescents is limited. This study explores the efficacy of liposomal bupivacaine for postoperative pain management in adolescent CLP patients undergoing orthognathic surgery. METHODS: The authors performed a retrospective chart review at their institution between July 2020 and December 2022 to identify patients who underwent LeFort I or mandibular osteotomy. Two cohorts were compared: patients who received liposomal bupivacaine and patients who received standard pain medications alone. Outcome measures included intraoperative pain medications, length of stay, breakthrough opioid use, time to first oral intake, volume of oral intake, and opioids prescribed at discharge. RESULTS: This study included 22 patients who underwent orthognathic surgery. The liposomal bupivacaine group (n=10) demonstrated earlier and greater oral intake during hospitalization compared with controls (n=12). The most significant difference was observed in total breakthrough opioid use, with an average of 8.60 morphine milligram equivalents for liposomal bupivacaine patients compared with 35.1 morphine milligram equivalents for controls (P=0.037). CONCLUSIONS: This study provides the first analysis of liposomal bupivacaine use in adolescent CLP patients undergoing orthognathic surgery, demonstrating a significant reduction in postoperative opioid consumption compared with controls. These results may guide future studies of liposomal bupivacaine within CLP patients, potentially as a component of enhanced recovery after surgery guidelines, as well as in cost-analysis studies.
RESUMO
The confining pressure has a great effect on the internal force of the tunnel. During construction, the confining pressure which has a crucial impact on tunnel construction changes due to the variation of groundwater level and applied load. Therefore, the safety of tunnels must have the magnitude of confining pressure accurately estimated. In this study, a complete tunnel confining pressure time axis was obtained through high-frequency field monitoring, the data are segmented into a training set and a testing set. Using GRU and RNN models, a confining pressure prediction model was established, and the prediction results were analyzed. The results indicate that the GRU model has a fast-training speed and higher accuracy. On the other hand, the training speed of the RNN model is slow, with lower accuracy. The dynamic characteristics of soil pressure during tunnel construction require accurate prediction models to maintain the safety of the tunnel. The comparison between GRU and RNN models not only highlights the advantages of the GRU model but also emphasizes the necessity of balancing speed accuracy in tunnel construction confining pressure prediction modeling. This study is helpful in improving the understanding of soil pressure dynamics and developing effective prediction tools to promote safer and more reliable tunnel construction practices.
RESUMO
The construction of large-diameter shield tunnels underwater involves complex variations in water and earth load outside the tunnel segment, as well as intricate mechanical responses. This study analyzes the variation laws of external loads, axial forces, and bending moments acting on the segment ring during the shield assembly and removal from the shield tail. It accomplishes this through the establishment of an on-site monitoring system based on the Internet of Things (IoT) and proposes a Bayesian-genetic algorithm model to estimate the water and earth pressure. The fluctuation section exhibits a peak load twice as high as that in the stable section. These variations are influenced by Jack thrust, shield shell force, and grouting pressure. The peak load observed in the fluctuation section is twice as high as the load observed in the stable section. During the shield tail removal process, the internal forces undergo significant fluctuations due to changes in both load and boundary conditions, and the peak value of the axial force during the fluctuation section is eight times higher than that during the stable section, while the peak value of the bending moment during the fluctuation section is five times higher than that during the stable section. The earth and water pressure calculated using the inversion analysis method, which relies on the measured internal forces, closely matches the actual measured values. The results demonstrate that the accuracy of the water and earth pressure obtained through inversion analysis is twice as high as that obtained using the full coverage pressure method. These results can serve as a valuable reference for similar projects.
RESUMO
With the advancement of engineering techniques, underground shield tunneling projects have also started incorporating emerging technologies to monitor the forces and displacements during the construction and operation phases of shield tunnels. Monitoring devices installed on the tunnel segment components generate a large amount of data. However, due to various factors, data may be missing. Hence, the completion of the incomplete data is imperative to ensure the utmost safety of the engineering project. In this research, a missing data imputation technique utilizing Random Forest (RF) is introduced. The optimal combination of the number of decision trees, maximum depth, and number of features in the RF is determined by minimizing the Mean Squared Error (MSE). Subsequently, complete soil pressure data are artificially manipulated to create incomplete datasets with missing rates of 20%, 40%, and 60%. A comparative analysis of the imputation results using three methods-median, mean, and RF-reveals that this proposed method has the smallest imputation error. As the missing rate increases, the mean squared error of the Random Forest method and the other two methods also increases, with a maximum difference of about 70%. This indicates that the random forest method is suitable for imputing monitoring data.