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1.
Cell ; 153(7): 1589-601, 2013 Jun 20.
Article in English | MEDLINE | ID: mdl-23791185

ABSTRACT

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.


Subject(s)
Models, Genetic , Protein Biosynthesis , Saccharomyces cerevisiae/genetics , Codon/genetics , Markov Chains , RNA, Messenger/metabolism , RNA, Transfer/metabolism , Ribosomes/metabolism
2.
Proc Natl Acad Sci U S A ; 120(51): e2304213120, 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38085773

ABSTRACT

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.


Subject(s)
Alzheimer Disease , Chitosan , Mice , Animals , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Chitosan/metabolism , Amyloid beta-Protein Precursor/metabolism , Brain/metabolism , Mice, Transgenic , Disease Models, Animal
3.
Genome Res ; 2022 Aug 17.
Article in English | MEDLINE | ID: mdl-35977841

ABSTRACT

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.

4.
PLoS Pathog ; 19(8): e1011595, 2023 08.
Article in English | MEDLINE | ID: mdl-37585478

ABSTRACT

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.


Subject(s)
Ebolavirus , Hemorrhagic Fever, Ebola , Marburgvirus , Humans , Filamins/genetics , Ebolavirus/genetics , Actins , Marburgvirus/genetics , Glycoproteins
5.
Biochem Biophys Res Commun ; 725: 150272, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-38901224

ABSTRACT

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.


Subject(s)
GABAergic Neurons , Interneurons , Ketamine , Parvalbumins , Prefrontal Cortex , Synapses , Animals , Ketamine/pharmacology , Ketamine/administration & dosage , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Parvalbumins/metabolism , Synapses/drug effects , Synapses/metabolism , Male , Interneurons/drug effects , Interneurons/metabolism , Mice , GABAergic Neurons/drug effects , GABAergic Neurons/metabolism , Mice, Inbred C57BL , Excitatory Amino Acid Antagonists/pharmacology
6.
Small ; 20(26): e2308836, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38258401

ABSTRACT

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) C═O 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.

7.
Brief Bioinform ; 23(3)2022 05 13.
Article in English | MEDLINE | ID: mdl-35419596

ABSTRACT

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.


Subject(s)
Prostatic Neoplasms , Tumor Microenvironment , Cellular Senescence/genetics , Genomics , Humans , Immunotherapy , Male , Prostatic Neoplasms/genetics , Tumor Microenvironment/genetics
8.
J Transl Med ; 22(1): 613, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956649

ABSTRACT

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.


Subject(s)
Antigens, CD19 , Fever , Immunotherapy, Adoptive , Humans , Female , Male , Middle Aged , Immunotherapy, Adoptive/methods , Adult , Antigens, CD19/metabolism , Infections/blood , Aged , ROC Curve , Young Adult , Retrospective Studies
9.
Blood ; 139(14): 2198-2211, 2022 04 07.
Article in English | MEDLINE | ID: mdl-34864916

ABSTRACT

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.


Subject(s)
Antineoplastic Agents , Leukemia, Myeloid, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Antineoplastic Agents/therapeutic use , Gene Rearrangement , Humans , Immunotherapy , Infant , Leukemia, Myeloid, Acute/genetics , Myeloid-Lymphoid Leukemia Protein/genetics , Myeloid-Lymphoid Leukemia Protein/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics
10.
Histopathology ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38973399

ABSTRACT

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.

11.
Article in English | MEDLINE | ID: mdl-38805025

ABSTRACT

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 96.67 %). 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 (C16 : 1 ω7c and/or C16 : 1 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.


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Geologic Sediments , Nucleic Acid Hybridization , Phylogeny , RNA, Ribosomal, 16S , Seawater , Sequence Analysis, DNA , Geologic Sediments/microbiology , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Fatty Acids/chemistry , China , Seawater/microbiology
12.
J Immunol ; 209(4): 806-819, 2022 08 15.
Article in English | MEDLINE | ID: mdl-35906001

ABSTRACT

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.


Subject(s)
Perciformes , Signal Transduction , Animals , Antiviral Agents , Disulfides/metabolism , Fishes/metabolism , Humans , Janus Kinases/metabolism , Mammals/metabolism , Receptor, Interferon alpha-beta/metabolism , STAT Transcription Factors/metabolism
13.
Lipids Health Dis ; 23(1): 127, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38685122

ABSTRACT

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.


Subject(s)
Body Mass Index , Inflammation , Non-alcoholic Fatty Liver Disease , Nutrition Surveys , Obesity , Humans , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/complications , Female , Male , Obesity/complications , Middle Aged , Adult , Diet/adverse effects , Waist-Height Ratio , Thinness/complications , Risk Factors , Liver Cirrhosis/pathology , Liver Cirrhosis/epidemiology
14.
Proc Natl Acad Sci U S A ; 118(28)2021 07 13.
Article in English | MEDLINE | ID: mdl-34260387

ABSTRACT

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.


Subject(s)
Escherichia coli/physiology , Hydrodynamics , Models, Biological , Computer Simulation , Suspensions
15.
Article in English | MEDLINE | ID: mdl-38581327

ABSTRACT

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.

16.
J Craniofac Surg ; 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38227634

ABSTRACT

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.

17.
Sensors (Basel) ; 24(5)2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38475093

ABSTRACT

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.

18.
Sensors (Basel) ; 24(3)2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38339583

ABSTRACT

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.

19.
Sensors (Basel) ; 24(4)2024 Feb 18.
Article in English | MEDLINE | ID: mdl-38400469

ABSTRACT

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.

20.
J Environ Manage ; 366: 121875, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39018863

ABSTRACT

Currently, microbial contamination issues have globally brought out a huge health threat to human beings and animals. To be specific, microorganisms including bacteria and viruses display durable ecological toxicity and various diseases to aquatic organisms. In the past decade, the photocatalytic microorganism inactivation technique has attracted more and more concern owing to its green, low-cost, and sustainable process. A variety kinds of photocatalysts have been employed for killing microorganisms in the natural environment. However, two predominant shortcomings including low activity of photocatalysts and diverse impacts of water characteristics are still displayed in the current photocatalytic disinfection system. So far, various strategies to improve the inherent activity of photocatalysts. Other than the modification of photocatalysts, the optimization of environments of water bodies has been also conducted to enhance microorganisms inactivation. In this mini-review, we outlined the recent progress in photocatalytic sterilization of microorganisms. Meanwhile, the relevant methods of photocatalyst modification and the influences of water body characteristics on disinfection ability were thoroughly elaborated. More importantly, the relationships between strategies for constructing advanced photocatalytic microorganism inactivation systems and improved performance were correlated. Finally, the perspectives on the prospects and challenges of photocatalytic disinfection were presented. We sincerely hope that this critical mini-review can inspire some new concepts and ideas in designing advanced photocatalytic disinfection systems.

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