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1.
ACS Appl Mater Interfaces ; 16(28): 36017-36029, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38975983

ABSTRACT

Oral infectious diseases have a significant impact on the health of oral and maxillofacial regions, as well as the overall well-being of individuals. Carvacrol and thymol, two isomers known for their effective antibacterial and anti-inflammatory properties, have gained considerable attention in the treatment of oral infectious diseases. However, their application as topical drugs for oral use is limited due to their poor physical and chemical stability. UiO-66, a metal-organic framework based on zirconium ion (Zr4+), exhibits high drug loading capability. Carvacrol and thymol were efficiently loaded onto UiO-66 with loading rates of 79.60 ± 0.71% and 79.65 ± 0.76%, respectively. The release rates of carvacrol and thymol were 77.82 ± 0.87% and 76.51 ± 0.58%, respectively, after a period of 72 h. Moreover, Car@UiO-66 and Thy@UiO-66 demonstrated excellent antibacterial properties against Candida albicans, Escherichia coli, and Staphylococcus aureus with minimum bactericidal concentrations (MBC) of 0.313 mg/mL, 0.313 mg/mL, and 1.25 mg/mL, respectively. Furthermore, based on the results of the CCK8 cytotoxicity assay, even at concentrations as high as 1.25 mg/mL, Car@UiO-66 and Thy@UiO-66 exhibited excellent biocompatibility with a relative cell survival rate above 50%. These findings suggest that Car@UiO-66 and Thy@UiO-66 possess favorable biocompatibility properties without significant toxicity towards periodontal membrane cells. Additionally, in vivo studies confirmed the efficacy of Car@UiO-66and Thy@UiO-66 in reducing inflammation, promoting bone formation through inhibition of TNF-a and IL6 expression, enhancement of IL10 expression, and acceleration of bone defect healing. Therefore, the unique combination of antibacterial, anti-inflammatory, and osteogenic properties make Car@UiO-66 and Thy@Ui O-66 promising candidates for the treatment of oral infectious diseases and repairing bone defects.


Subject(s)
Anti-Bacterial Agents , Anti-Inflammatory Agents , Candida albicans , Cymenes , Escherichia coli , Metal-Organic Frameworks , Staphylococcus aureus , Thymol , Thymol/chemistry , Thymol/pharmacology , Cymenes/chemistry , Cymenes/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Candida albicans/drug effects , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Mice , Microbial Sensitivity Tests , Rats , Osteogenesis/drug effects , Humans
2.
Fundam Res ; 4(1): 188-198, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38933843

ABSTRACT

Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia, however no effective treatments are available. Here, based on magnetic resonance imaging studies of patients with white matter damage, we found that this damage is associated with disorganized cortical structure. In a mouse model, optogenetic activation of glutamatergic neurons in the somatosensory cortex significantly promoted oligodendrocyte progenitor cell (OPC) proliferation, remyelination in the corpus callosum, and recovery of cognitive ability after cerebral hypoperfusion. The therapeutic effect of such stimulation was restricted to the upper layers of the cortex, but also spanned a wide time window after ischemia. Mechanistically, enhancement of glutamatergic neuron-OPC functional synaptic connections is required to achieve the protection effect of activating cortical glutamatergic neurons. Additionally, skin stroking, an easier method to translate into clinical practice, activated the somatosensory cortex, thereby promoting OPC proliferation, remyelination and cognitive recovery following cerebral hypoperfusion. In summary, we demonstrated that activating glutamatergic neurons in the somatosensory cortex promotes the proliferation of OPCs and remyelination to recover cognitive function after chronic cerebral hypoperfusion. It should be noted that this activation may provide new approaches for treating ischemic vascular dementia via the precise regulation of glutamatergic neuron-OPC circuits.

3.
Appl Microbiol Biotechnol ; 108(1): 383, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38896301

ABSTRACT

Herpes simplex virus type 1 (HSV-1) plays an important role in the field of gene therapy and viral vaccines, especially as an oncolytic virus. However, the mass production of HSV-1 viral vectors remains a challenge in the industry. In this study, a microcarrier-mediated serum-reduced medium culture was used to improve the bioprocess of HSV-1 production and increase HSV-1 yields. The composition of the culture media, which included a basal medium, serum concentration, and glutamine additive, was optimized. The process was successfully conducted in a 1 L bioreactor, and virus production was threefold greater than that of conventional processes with a 10% serum medium. The bead-to-bead transfer process was also developed to further increase scalability. In spinner flasks, the detachment rate increased from 49.4 to 80.6% when combined agitation was performed during digestion; the overall recovery proportion increased from 37.9 to 71.1% after the operational steps were optimized. Specifically, microcarrier loss was reduced during aspiration and transfer, and microcarriers and detached cells were separated with filters. Comparable cell growth was achieved with the baseline process using 2D culture as the inoculum by exchanging the subculture medium. To increase virus production after bead-to-bead transfer, critical parameters, including shear stress during digestion, TrypLE and EDTA concentrations in the subculture, and the CCI, were identified from 47 parameters via correlation analysis and principal component analysis. The optimized bead-to-bead transfer process achieved an average of 90.4% overall recovery and comparable virus production compared to that of the baseline process. This study is the first to report the optimization of HSV-1 production in Vero cells cultured on microcarriers in serum-reduced medium after bead-to-bead transfer. KEY POINTS: • An HSV-1 production process was developed that involves culturing in serum-reduced medium, and this process achieved threefold greater virus production than that of traditional processes. • An indirect bead-to-bead transfer process was developed with over 90% recovery yield in bioreactors. • HSV-1 production after bead-to-bead transfer was optimized and was comparable to that achieved with 2D culture as inoculum.


Subject(s)
Bioreactors , Culture Media , Herpesvirus 1, Human , Virus Cultivation , Herpesvirus 1, Human/growth & development , Bioreactors/virology , Culture Media/chemistry , Chlorocebus aethiops , Virus Cultivation/methods , Vero Cells , Animals
4.
Int J Mol Sci ; 25(12)2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38928469

ABSTRACT

The SPRY domain-containing SOCS box proteins SPSB1, SPSB2, and SPSB4 utilize their SPRY/B30.2 domain to interact with a short region in the N-terminus of inducible nitric oxide synthase (iNOS), and recruit an E3 ubiquitin ligase complex to polyubiquitinate iNOS, resulting in the proteasomal degradation of iNOS. Inhibitors that can disrupt the endogenous SPSB-iNOS interactions could be used to augment cellular NO production, and may have antimicrobial and anticancer activities. We previously reported the rational design of a cyclic peptide inhibitor, cR8, cyclo(RGDINNNV), which bound to SPSB2 with moderate affinity. We, therefore, sought to develop SPSB inhibitors with higher affinity. Here, we show that cyclic peptides cR7, cyclo(RGDINNN), and cR9, cyclo(RGDINNNVE), have ~6.5-fold and ~2-fold, respectively, higher SPSB2-bindng affinities than cR8. We determined high-resolution crystal structures of the SPSB2-cR7 and SPSB2-cR9 complexes, which enabled a good understanding of the structure-activity relationships for these cyclic peptide inhibitors. Moreover, we show that these cyclic peptides displace full-length iNOS from SPSB2, SPSB1, and SPSB4, and that their inhibitory potencies correlate well with their SPSB2-binding affinities. The strongest inhibition was observed for cR7 against all three iNOS-binding SPSB proteins.


Subject(s)
Peptides, Cyclic , Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology , Humans , Suppressor of Cytokine Signaling Proteins/chemistry , Suppressor of Cytokine Signaling Proteins/metabolism , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type II/chemistry , Oligopeptides/chemistry , Oligopeptides/pharmacology , Protein Binding , Structure-Activity Relationship
5.
BMC Med Res Methodol ; 24(1): 125, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831262

ABSTRACT

BACKGROUND: Mediation analysis is a powerful tool to identify factors mediating the causal pathway of exposure to health outcomes. Mediation analysis has been extended to study a large number of potential mediators in high-dimensional data settings. The presence of confounding in observational studies is inevitable. Hence, it's an essential part of high-dimensional mediation analysis (HDMA) to adjust for the potential confounders. Although the propensity score (PS) related method such as propensity score regression adjustment (PSR) and inverse probability weighting (IPW) has been proposed to tackle this problem, the characteristics with extreme propensity score distribution of the PS-based method would result in the biased estimation. METHODS: In this article, we integrated the overlapping weighting (OW) technique into HDMA workflow and proposed a concise and powerful high-dimensional mediation analysis procedure consisting of OW confounding adjustment, sure independence screening (SIS), de-biased Lasso penalization, and joint-significance testing underlying the mixture null distribution. We compared the proposed method with the existing method consisting of PS-based confounding adjustment, SIS, minimax concave penalty (MCP) variable selection, and classical joint-significance testing. RESULTS: Simulation studies demonstrate the proposed procedure has the best performance in mediator selection and estimation. The proposed procedure yielded the highest true positive rate, acceptable false discovery proportion level, and lower mean square error. In the empirical study based on the GSE117859 dataset in the Gene Expression Omnibus database using the proposed method, we found that smoking history may lead to the estimated natural killer (NK) cell level reduction through the mediation effect of some methylation markers, mainly including methylation sites cg13917614 in CNP gene and cg16893868 in LILRA2 gene. CONCLUSIONS: The proposed method has higher power, sufficient false discovery rate control, and precise mediation effect estimation. Meanwhile, it is feasible to be implemented with the presence of confounders. Hence, our method is worth considering in HDMA studies.


Subject(s)
Mediation Analysis , Propensity Score , Humans , Observational Studies as Topic/methods , Confounding Factors, Epidemiologic , Epigenomics/methods , Computer Simulation , Algorithms
6.
Opt Lett ; 49(11): 3238-3241, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824372

ABSTRACT

As the optical communication industry advances, metropolitan area networks (MANs) and radio access networks (RANs) are extensively deployed on a large scale, demanding energy-efficient integrated light sources and simplified digital signal processing (DSP) technologies. The emergence of thin-film lithium niobate (TFLN) has given rise to high-performance, energy-efficient on-chip modulators, making on-chip optical frequency comb (OFC) more appealing. Owing to the phase uniformity and stability of this chip-scale device, it has been possible to eliminate the carrier frequency phase estimation (CPE) in DSP stacks using comb-clone-enabled self-homodyne detection. Here we report the first use, to our knowledge, of a TFLN on-chip electro-optic (EO) frequency comb to realize comb cloning and self-homodyne coherent detection. We transmit three optical pilot tones and eight data channels encoded with 20 Gbaud polarization-multiplexed 16-ary quadrature amplitude modulation (PM-16-QAM) over 10 km and 80 km standard single-mode fibers. The bit error ratios (BERs) of the eight channels reach below 10-3, a result made possible by our on-chip comb. The scalability and mass producibility of on-chip EO combs, combined with the simplified DSP, show potential in our proposed fifth-generation (5G) RAN and MAN transmission scheme.

7.
Alpha Psychiatry ; 25(2): 183-189, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38798803

ABSTRACT

Objective: To explore the association between malnutrition and risk of depression in the elderly. Methods: Relevant studies were searched in PubMed, Web of Science, the Cochrane Library, Scopus, and Embase from the establishment of the database to August 17, 2023. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Stata16.0 software was used for meta-analysis. Results: A total of 8 observational studies were identified with 11 112 participants, of which 2771 elderly patients had depression. The meta-pooled results showed a significant correlation between nutritional status and depression risk (odds ratio (OR) = 2.03, 95% CI = (1.47, 2.81), P < 0.001). Subgroup analysis found that the malnutrition scores of different study types and the diagnostic methods of depression and malnutrition were correlated with the risk of depression. Conclusion: Malnutrition was associated with depression risk in the elderly. Further large-scale multicenter studies should be conducted to test and verify the results.

8.
Pathol Res Pract ; 259: 155369, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38820928

ABSTRACT

Bladder cancer is a common malignancy with a poor prognosis worldwide. Positive cofactor 4 (PC4) is widely reported to promote malignant phenotypes in various tumors. Nonetheless, the biological function and mechanism of PC4 in bladder cancer remain unclear. Here, for the first time, we report that PC4 is elevated in bladder cancer and is associated with patient survival. Moreover, PC4 deficiency obviously inhibited bladder cancer cell proliferation and metastasis by reducing the expression of genes related to cancer stemness (CD44, CD47, KLF4 and c-Myc). Through RNA-seq and experimental verification, we found that activation of the Wnt5a/ß-catenin pathway is involved in the malignant function of PC4. Mechanistically, PC4 directly interacts with Sp1 to promote Wnt5a transcription. Thus, our study furthers our understanding of the role of PC4 in cancer stemness regulation and provides a promising strategy for bladder cancer therapy.


Subject(s)
Gene Expression Regulation, Neoplastic , Kruppel-Like Factor 4 , Neoplastic Stem Cells , Urinary Bladder Neoplasms , Wnt-5a Protein , Animals , Humans , Mice , beta Catenin/metabolism , beta Catenin/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Disease Progression , Kruppel-Like Factor 4/metabolism , Neoplastic Stem Cells/pathology , Neoplastic Stem Cells/metabolism , Sp1 Transcription Factor/metabolism , Sp1 Transcription Factor/genetics , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism , Wnt Signaling Pathway/physiology , Wnt Signaling Pathway/genetics , Wnt-5a Protein/metabolism , Wnt-5a Protein/genetics
9.
ACS Appl Mater Interfaces ; 16(15): 19828-19837, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38567790

ABSTRACT

Passive radiative cooling (PRC) is a zero-energy-consumption technology that reflects sunlight and radiates heat to cold outer space. In this work, a porous poly(vinylidene fluoride)-poly(methyl methacrylate) (PVDF-PMMA) composite film is fabricated by decorating zinc-imidazolate metal-organic framework (MOF) (ZIF-8) particles obtained by phase inversion. Due to the competent scattering via the coral-like hierarchical structures and the vibration excitations of specific functional groups, the prepared film exhibits good solar reflectance (92.6%) and intermediate infrared emittance (99.1%), with an average sub-ambient cooling of 10.4 °C under a solar radiation intensity of 0.6 AM1.5. Additionally, poly(vinylidene fluoride) has a low surface energy, while the ZIF-8 particles and coral-like hierarchical structures enhance the surface roughness, endowing the surface with significant superhydrophobicity characterized by a water contact angle (WCA) of 157.5° and a sliding angle (SA) of 2°. These films exhibit excellent antibacterial properties. When the content of ZIF-8 particles in the film is 300 mg·L-1, the antibacterial rate reaches 100% after 1 h of treatment. Thus, the ZIF-8 porous poly(vinylidene fluoride)-poly(methyl methacrylate) composite (ZPPP) film has potential application prospects in areas with high health and environmental requirements, such as cold chain transportation and public spaces.

10.
Exp Mol Med ; 56(5): 1150-1163, 2024 May.
Article in English | MEDLINE | ID: mdl-38689092

ABSTRACT

Hepatocellular carcinoma (HCC) is associated with a poor prognosis. Our previous study demonstrated that Pleomorphic adenoma gene like-2 (PLAGL2) was a potential therapeutic target in HCC. However, the mechanisms that lead to the upregulation of PLAGL2 in HCC remain unclear. The present study revealed that stress-induced epinephrine increased the expression of PLAGL2, thereby promoting the progression of HCC. Furthermore, PLAGL2 knockdown inhibited epinephrine-induced HCC development. Mechanistically, epinephrine upregulated ubiquitin-specific protease 10 (USP10) to stabilize PLAGL2 via the adrenergic ß-receptor-2-c-Myc (ADRB2-c-Myc) axis. Furthermore, PLAGL2 acted as a transcriptional regulator of USP10, forming a signaling loop. Taken together, these results reveal that stress-induced epinephrine activates the PLAGL2-USP10 signaling loop to enhance HCC progression. Furthermore, PLAGL2 plays a crucial role in psychological stress-mediated promotion of HCC progression.


Subject(s)
Carcinoma, Hepatocellular , DNA-Binding Proteins , Epinephrine , Gene Expression Regulation, Neoplastic , Liver Neoplasms , RNA-Binding Proteins , Signal Transduction , Transcription Factors , Ubiquitin Thiolesterase , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/genetics , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/etiology , Liver Neoplasms/genetics , Epinephrine/metabolism , Epinephrine/pharmacology , Signal Transduction/drug effects , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Animals , Ubiquitin Thiolesterase/metabolism , Ubiquitin Thiolesterase/genetics , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Gene Expression Regulation, Neoplastic/drug effects , Mice , Cell Line, Tumor , Disease Progression , Male , Stress, Physiological , Cell Proliferation
11.
Adv Sci (Weinh) ; 11(23): e2310120, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38647423

ABSTRACT

G-protein-coupled receptors (GPCRs) transmit downstream signals predominantly via G-protein pathways. However, the conformational basis of selective coupling of primary G-protein remains elusive. Histamine receptors H2R and H3R couple with Gs- or Gi-proteins respectively. Here, three cryo-EM structures of H2R-Gs and H3R-Gi complexes are presented at a global resolution of 2.6-2.7 Å. These structures reveal the unique binding pose for endogenous histamine in H3R, wherein the amino group interacts with E2065.46 of H3R instead of the conserved D1143.32 of other aminergic receptors. Furthermore, comparative analysis of the H2R-Gs and H3R-Gi complexes reveals that the structural geometry of TM5/TM6 determines the primary G-protein selectivity in histamine receptors. Machine learning (ML)-based structuromic profiling and functional analysis of class A GPCR-G-protein complexes illustrate that TM5 length, TM5 tilt, and TM6 outward movement are key determinants of the Gs and Gi/o selectivity among the whole Class A family. Collectively, the findings uncover the common structural geometry within class A GPCRs that determines the primary Gs- and Gi/o-coupling selectivity.


Subject(s)
Cryoelectron Microscopy , Receptors, G-Protein-Coupled , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/chemistry , Receptors, G-Protein-Coupled/genetics , Humans , Cryoelectron Microscopy/methods , GTP-Binding Proteins/metabolism , GTP-Binding Proteins/chemistry , GTP-Binding Proteins/genetics , Histamine/metabolism , Histamine/chemistry , Receptors, Histamine H2/metabolism , Receptors, Histamine H2/genetics , Receptors, Histamine H2/chemistry , Receptors, Histamine H3/metabolism , Receptors, Histamine H3/chemistry , Receptors, Histamine H3/genetics , Signal Transduction
12.
Osteoporos Int ; 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38625381

ABSTRACT

Osteoporosis-pseudoglioma syndrome (OPPG) and LRP5 high bone mass (LRP5-HBM) are two rare bone diseases with opposite clinical symptoms caused by loss-of-function and gain-of-function mutations in LRP5. Bisphosphonates are an effective treatment for OPPG patients. LRP5-HBM has a benign course, and age-related bone loss is found in one LRP5-HBM patient. PURPOSE: Low-density lipoprotein receptor-related protein 5 (LRP5) is involved in the canonical Wnt signaling pathway. The gain-of-function mutation leads to high bone mass (LRP5-HBM), while the loss-of-function mutation leads to osteoporosis-pseudoglioma syndrome (OPPG). In this study, the clinical manifestations, disease-causing mutations, treatment, and follow-up were summarized to improve the understanding of these two diseases. METHODS: Two OPPG patients and four LRP5-HBM patients were included in this study. The clinical characteristics, biochemical and radiological examinations, pathogenic mutations, and structural analysis were summarized. Furthermore, several patients were followed up to observe the treatment effect and disease progress. RESULTS: Congenital blindness, persistent bone pain, low bone mineral density (BMD), and multiple brittle fractures were the main clinical manifestations of OPPG. Complex heterozygous mutations were detected in two OPPG patients. The c.1455G > T mutation in exon 7 was first reported. During the follow-up, BMD of two patients was significantly improved after bisphosphonate treatment. On the contrary, typical clinical features of LRP5-HBM included extremely high BMD without fractures, torus palatinus and normal vision. X-ray showed diffuse osteosclerosis. Two heterozygous missense mutations were detected in four patients. In addition, age-related bone loss was found in one LRP5-HBM patient after 12-year of follow-up. CONCLUSION: This study deepened the understanding of the clinical characteristics, treatment, and follow-up of OPPG and LRP5-HBM; expanded the pathogenic gene spectrum of OPPG; and confirmed that bisphosphonates were effective for OPPG. Additionally, it was found that Ala242Thr mutation could not protect LRP5-HBM patients from age-related bone loss. This phenomenon deserves further study.

14.
Arch Toxicol ; 98(7): 1975-1990, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38581585

ABSTRACT

New human life begins in the uterus in a period of both extreme plasticity and sensitivity to environmental disturbances. The fetal stage is also a vital period for central nervous system development, with experiences at this point profoundly and permanently shaping brain structure and function. As such, some brain disorders may originate in utero. Glucocorticoids, a class of essential stress hormones, play indispensable roles in fetal development, but overexposure may have lasting impacts on the brain. In this review, we summarize data from recent clinical and non-clinical studies regarding alterations in fetal brains due to prenatal glucocorticoid overexposure that are associated with nervous system disorders. We discuss relevant changes to brain structure and cellular functions and explore the underlying molecular mechanisms. In addition, we summarize factors that may cause differential outcomes between varying brain regions, and outline clinically feasible intervention strategies that are expected to minimize negative consequences arising from fetal glucocorticoid overexposure. Finally, we highlight the need for experimental evidence aided by new technologies to clearly determine the effects of excessive prenatal glucocorticoid exposure. This review consolidates diverse findings to help researchers better understand the relationship between the prenatal glucocorticoid overexposure and the effects it has on various fetal brain regions, promoting further development of critical intervention strategies.


Subject(s)
Brain Diseases , Brain , Glucocorticoids , Prenatal Exposure Delayed Effects , Humans , Glucocorticoids/adverse effects , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Female , Brain/drug effects , Brain/embryology , Animals , Brain Diseases/chemically induced , Fetal Development/drug effects
15.
Hum Vaccin Immunother ; 20(1): 2344290, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38682698

ABSTRACT

COVID-19 vaccine hesitancy remains problematic among healthcare workers. Social network influences may shape vaccine decision-making, but few studies have examined this in this critical workforce. We assessed the relationship between friends' COVID-19 vaccination attitudes and personal hesitancy among Chinese healthcare personnel. In December 2022-January 2023, a cross-sectional online survey was conducted at a tertiary hospital in China using WeChat. Of the 1832 healthcare personnel who were invited to answer the structured questionnaire, 613 (33.5%) samples had valid data for data analysis. Logistic regression examined the association between friends' hesitancy and participants' own hesitancy, adjusting for confounders. Of 613 healthcare workers included, 266 (43.4%) were hesitant. Those with hesitant friends had 6.34 times higher adjusted odds of hesitating themselves versus those without hesitant friends (95% CI 2.97-13.52). Strong associations persisted across subgroups. Chinese healthcare workers' COVID-19 vaccination hesitancy was highly influenced by perceived friends' attitudes. Fostering pro-vaccine social norms through trusted peer networks could help promote vaccine acceptance in this critical workforce.


Subject(s)
COVID-19 Vaccines , COVID-19 , Friends , Vaccination Hesitancy , Humans , Male , Female , COVID-19 Vaccines/administration & dosage , Vaccination Hesitancy/psychology , Vaccination Hesitancy/statistics & numerical data , Adult , Cross-Sectional Studies , China , COVID-19/prevention & control , COVID-19/psychology , Surveys and Questionnaires , Friends/psychology , Middle Aged , Vaccination/psychology , Vaccination/statistics & numerical data , SARS-CoV-2 , Medical Staff/psychology , Health Personnel/psychology , Attitude of Health Personnel
16.
J Microbiol Methods ; 221: 106928, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38583783

ABSTRACT

The bicistronic expression system that utilizes fluorescent reporters has been demonstrated to be a straightforward method for detecting recombinant protein expression levels, particularly when compared to polyacrylamide gel electrophoresis and immunoblot analysis, which are tedious and labor-intensive. However, existing bicistronic reporter systems are less capable of quantitative measurement due to the lag in reporter expression and its negative impact on target protein. In this work, a plug and play bicistronic construct using mCherry as reporter was applied in the screening of optimal replicon and promoter for Sortase expression in Escherichia coli (E. coli). The bicistronic construct allowed the reporter gene and target open reading frame (ORF) to be co-transcribed under the same promoter, resulting in a highly positive quantitative correlation between the expression titer of Sortase and the fluorescent intensity (R2 > 0.97). With the correlation model, the titer of target protein can be quantified by noninvasively measuring the fluorescent intensity. On top of this, the expression of reporter has no significant effect on the yield of target protein, thus favoring a plug and play design for removing reporter gene to generate a plain plasmid for industrial use.


Subject(s)
Escherichia coli , Genes, Reporter , Luminescent Proteins , Plasmids , Promoter Regions, Genetic , Recombinant Proteins , Escherichia coli/genetics , Escherichia coli/metabolism , Luminescent Proteins/genetics , Plasmids/genetics , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Red Fluorescent Protein , Open Reading Frames , Gene Expression , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Escherichia coli Proteins/genetics , Escherichia coli Proteins/metabolism , Genetic Vectors , Cysteine Endopeptidases/genetics , Cysteine Endopeptidases/metabolism , Gene Expression Regulation, Bacterial , Replicon/genetics
17.
BMC Med Res Methodol ; 24(1): 89, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622516

ABSTRACT

BACKGROUND: Outliers, data points that significantly deviate from the norm, can have a substantial impact on statistical inference and provide valuable insights in data analysis. Multiple methods have been developed for outlier detection, however, almost all available approaches fail to consider the spatial dependence and heterogeneity in spatial data. Spatial data has diverse formats and semantics, requiring specialized outlier detection methodology to handle these unique properties. For now, there is limited research exists on robust spatial outlier detection methods designed specifically under the spatial error model (SEM) structure. METHOD: We propose the Spatial-Θ-Iterative Procedure for Outlier Detection (Spatial-Θ-IPOD), which utilizes a mean-shift vector to identify outliers within the SEM. Our method enables an effective detection of spatial outliers while also providing robust coefficient estimates. To assess the performance of our approach, we conducted extensive simulations and applied it to a real-world empirical study using life expectancy data from multiple countries. RESULTS: Simulation results showed that the masking and JD (Joint Detection) indicators of our Spatial-Θ-IPOD method outperformed several commonly used methods, even in high-dimensional scenarios, demonstrating stable performance. Conversely, the Θ-IPOD method proved to be ineffective in detecting outliers when spatial correlation was present. Moreover, our model successfully provided reliable coefficient estimation alongside outlier detection. The proposed method consistently outperformed other models (both robust and non-robust) in most cases. In the empirical study, our proposed model successfully detected outliers and provided valuable insights in the modeling process. CONCLUSIONS: Our proposed Spatial-Θ-IPOD offers an effective solution for detecting spatial outliers for SEM while providing robust coefficient estimates. Notably, our approach showcases its relative superiority even in the presence of high leverage points. By successfully identifying outliers, our method enhances the overall understanding of the data and provides valuable insights for further analysis.

18.
Genomics ; 116(3): 110831, 2024 05.
Article in English | MEDLINE | ID: mdl-38513875

ABSTRACT

Hepatitis B virus (HBV) infection is a major etiology of hepatocellular carcinoma (HCC). An interesting question is how different are the molecular and phenotypic profiles between HBV-infected (HBV+) and non-HBV-infected (HBV-) HCCs? Based on the publicly available multi-omics data for HCC, including bulk and single-cell data, and the data we collected and sequenced, we performed a comprehensive comparison of molecular and phenotypic features between HBV+ and HBV- HCCs. Our analysis showed that compared to HBV- HCCs, HBV+ HCCs had significantly better clinical outcomes, higher degree of genomic instability, higher enrichment of DNA repair and immune-related pathways, lower enrichment of stromal and oncogenic signaling pathways, and better response to immunotherapy. Furthermore, in vitro experiments confirmed that HBV+ HCCs had higher immunity, PD-L1 expression and activation of DNA damage response pathways. This study may provide insights into the profiles of HBV+ and HBV- HCCs, and guide rational therapeutic interventions for HCC patients.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis B virus , Liver Neoplasms , Carcinoma, Hepatocellular/virology , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/virology , Liver Neoplasms/genetics , Humans , Hepatitis B virus/genetics , Phenotype , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Hepatitis B/virology , Hepatitis B/complications , Hepatitis B/genetics , Genomic Instability , DNA Repair , Multiomics
19.
Acta Cytol ; 68(2): 153-159, 2024.
Article in English | MEDLINE | ID: mdl-38437810

ABSTRACT

INTRODUCTION: The diagnostic value of rapid on-site evaluation (ROSE) in bronchoscopy for lung tumors has been widely researched. However, the diagnostic efficacy of ROSE for pulmonary tuberculosis (TB) has not been extensively assessed yet. This study aimed to examine the value of ROSE in diagnosing pulmonary TB during bronchoscopy, and the relationship between ROSE cytology patterns and acid-fast bacilli (AFB) smears and mycobacterial cultures. METHODS: A retrospective study was conducted at a single respiratory endoscopy center, including 418 patients under clinical or radiological suspicion of having pulmonary TB who underwent bronchoscopy. In addition to the use of ROSE and definitive cytology, material obtained by aspiration/lavage or brushing was sent for AFB smear and mycobacterial culture. If histopathological examination was required, endobronchial biopsy, transbronchial lung biopsy, and transbronchial needle aspiration were performed at the discretion of the clinician. A composite reference standard (CRS) was used as the diagnostic gold standard for this study. The diagnosis obtained by ROSE was compared with the final diagnosis. RESULTS: Of the 418 patients studied, 282 (67.5%) were diagnosed on the basis of bronchoscopic findings, as follows: pulmonary TB, in 238 (84.4%); non-TB, in 44 (15.6%). In 238 pulmonary TB patients, ROSE cytology showed granulomas without necrosis were observed in 107 cases, granulomas and necrosis in 51 cases, caseous necrosis only in 25 cases, and nonspecific inflammation in 55 cases. For the diagnosis of TB according to CRS, ROSE showed the sensitivity, specificity, positive predictive value, and negative predictive value were 76.9%, 68.2%, 92.9%, and 35.3%, respectively. The positivity rate for bacterial detection through acid-fast staining and culture during bronchoscopy was 51.7%. The cytological pattern showed a higher detection rate for bacteria in cases of necrosis. DISCUSSION: The application of ROSE during bronchoscopy is a straightforward procedure that delivers an immediate and precise assessment regarding the adequacy of collected samples, enabling a preliminary diagnosis of pulmonary TB. ROSE has exhibited a higher sensitivity in detecting pulmonary TB compared to microbiological examinations. In addition, the cytological presentation of ROSE tends to show a higher positivity rate for microbiological testing in caseous necrosis. Therefore, samples with these characteristics should be prioritized for microbiological examination after on-site evaluation.


Subject(s)
Bronchoscopy , Tuberculosis, Pulmonary , Humans , Bronchoscopy/methods , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/pathology , Tuberculosis, Pulmonary/microbiology , Retrospective Studies , Female , Male , Middle Aged , Adult , Aged , Predictive Value of Tests , Rapid On-site Evaluation , Mycobacterium tuberculosis/isolation & purification , Young Adult , Lung/pathology , Lung/microbiology , Aged, 80 and over
20.
Opt Lett ; 49(5): 1353-1356, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38427011

ABSTRACT

Broadband amplified spontaneous emission (ASE) light sources are recognized for their cost-effective generation. However, their inherent high-intensity noise and the stringent requirement for time delay matching limits their widespread application in coherent optical telecommunication. Here we propose a broadband ASE source-enabled digital-analog radio-over-fiber (DA-RoF) mobile fronthaul architecture, leveraging semiconductor optical amplifiers (SOAs) and multicore fiber in tandem. Our proposed system uses SOAs to suppress the intensity noise of the ASE carrier and transmits the DA-RoF signal alongside an unmodulated carrier through distinct cores of an 8-core, 1-km fiber. This setup significantly enhances the signal-to-noise ratio (SNR) by 19.4 dB, boosts capacity, and enables self-homodyne detection at the receiver end. We achieve an aggregated bandwidth of 35 GHz (7 cores × 5 GHz), supporting a 2.05-Tb/s CPRI-equivalent data rate with 1024-ary quadrature-amplitude-modulated (1024-QAM) signals. Additionally, we analyze the impact of chromatic dispersion on signal-to-noise ratio for broadband source coherent detection systems. This innovative scheme offers a pragmatic solution for integrating low-cost broadband sources into cost-sensitive fronthaul systems, providing both high capacity and fidelity in massive deployment scenarios.

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