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1.
Emerg Infect Dis ; 30(6): 1173-1181, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38781950

ABSTRACT

Understanding changes in the transmission dynamics of mpox requires comparing recent estimates of key epidemiologic parameters with historical data. We derived historical estimates for the incubation period and serial interval for mpox and contrasted them with pooled estimates from the 2022 outbreak. Our findings show the pooled mean infection-to-onset incubation period was 8.1 days for the 2022 outbreak and 8.2 days historically, indicating the incubation periods remained relatively consistent over time, despite a shift in the major mode of transmission. However, we estimated the onset-to-onset serial interval at 8.7 days using 2022 data, compared with 14.2 days using historical data. Although the reason for this shortening of the serial interval is unclear, it may be because of increased public health interventions or a shift in the mode of transmission. Recognizing such temporal shifts is essential for informed response strategies, and public health measures remain crucial for controlling mpox and similar future outbreaks.


Subject(s)
Disease Outbreaks , Infectious Disease Incubation Period , Mpox (monkeypox) , Humans , Mpox (monkeypox)/epidemiology , Mpox (monkeypox)/history , Mpox (monkeypox)/transmission , Mpox (monkeypox)/virology , History, 21st Century , Global Health
2.
IEEE Trans Cybern ; PP2024 May 17.
Article in English | MEDLINE | ID: mdl-38758614

ABSTRACT

The problem of sampled-data H∞ dynamic output-feedback control for networked control systems with successive packet losses (SPLs) and stochastic sampling is investigated in this article. The aim of using sampled-data control techniques is to alleviate network congestion. SPLs that occur in the sensor-to-controller (S-C) and controller-to-actuator (C-A) channels are modeled using a packet loss model. Additionally, it is assumed that stochastic sampling follows a Bernoulli distribution. A model is established to capture the stochastic characteristics of both the SPL model and stochastic sampling. This model is crucial as it allows us to determine the probability distribution of the sampling interval between successive update instants, which is essential for stability analysis. An exponential mean-square stability condition for the constructed equivalent discrete-time stochastic system, which also guarantees the prescribed H∞ performance, is established by incorporating probability theory. The desired controller is designed using a step-by-step synthesis approach, which may offer lower design conservatism compared to some existing methods. Finally, our designed approach using a networked F-404 engine system model is validated and its merits relative to existing results are discussed. The proposed method is finally validated by employing a networked model of the F-404 engine system. Furthermore, the advantages of our method are presented in comparison to previous results.

3.
Commun Biol ; 7(1): 565, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38745044

ABSTRACT

Circular RNAs (circRNAs) have recently been suggested as potential functional modulators of cellular physiology processes in gastric cancer (GC). In this study, we demonstrated that circFOXP1 was more highly expressed in GC tissues. High circFOXP1 expression was positively associated with tumor size, lymph node metastasis, TNM stage, and poor prognosis in patients with GC. Cox multivariate analysis revealed that higher circFOXP1 expression was an independent risk factor for disease-free survival (DFS) and overall survival (OS) in GC patients. Functional studies showed that increased circFOXP1 expression promoted cell proliferation, cell invasion, and cell cycle progression in GC in vitro. In vivo, the knockdown of circFOXP1 inhibited tumor growth. Mechanistically, we observed ALKBH5-mediated m6A modification of circFOXP1 and circFOXP1 promoted GC progression by regulating SOX4 expression and sponging miR-338-3p in GC cells. Thus, our findings highlight that circFOXP1 could serve as a novel diagnostic and prognostic biomarker and potential therapeutic target for GC.


Subject(s)
AlkB Homolog 5, RNA Demethylase , Disease Progression , Forkhead Transcription Factors , Gene Expression Regulation, Neoplastic , MicroRNAs , RNA, Circular , SOXC Transcription Factors , Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Stomach Neoplasms/metabolism , Stomach Neoplasms/mortality , MicroRNAs/genetics , MicroRNAs/metabolism , SOXC Transcription Factors/genetics , SOXC Transcription Factors/metabolism , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Male , RNA, Circular/genetics , RNA, Circular/metabolism , Female , AlkB Homolog 5, RNA Demethylase/metabolism , AlkB Homolog 5, RNA Demethylase/genetics , Middle Aged , Cell Line, Tumor , Animals , Mice , Cell Proliferation/genetics , Mice, Nude , Prognosis , Mice, Inbred BALB C
4.
Nat Commun ; 15(1): 4275, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769104

ABSTRACT

Modern microprocessor performance is limited by local hot spots induced at high frequency by busy integrated circuit elements such as the clock generator. Locally embedded thermoelectric devices (TEDs) are proposed to perform active cooling whereby thermoelectric effects enhance passive cooling by the Fourier law in removing heat from the hot spot to colder regions. To mitigate transient heating events and improve temperature stability, we propose a novel analytical solution that describes the temperature response of a periodically heated hot spot that is actively cooled by a TED driven electrically at the same frequency. The analytical solution that we present is validated by experimental data from frequency domain thermal reflectance (FDTR) measurements made directly on an actively cooled Si thermoelectric device where the pump laser replicates the transient hot spot. We herein demonstrate a practical method to actively cancel the transient temperature variations on circuit elements with TEDs. This result opens a new path to optimize the design of cooling systems for transient localized hot spots in integrated circuits.

5.
Int Immunopharmacol ; 132: 112024, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38608475

ABSTRACT

Ulcerative colitis (UC) is a recurrent intestinal disease with an increasing incidence worldwide that seriously affects the life of patients. Turtle peptide (TP) is a bioactive peptide extracted from turtles that has anti-inflammatory, antioxidant and anti-aging properties. However, studies investigating the effect of TP on the progression of UC are lacking. The aim of this study was to investigate effects and underlying mechanisms of TP and its derivative peptide GPAGPIGPV (GP-9) in alleviating UC in mice. The results showed that 500 mg/kg TP treatment significantly ameliorated colitis symptoms and oxidative stress in UC mice. TP alleviated intestinal barrier damage in UC mice by promoting mucosal repair and increasing the expression of tight junction proteins (ZO1, occludin and claudin-1). TP also modulated the composition of the gut microbiota by increasing the abundance of the beneficial bacteria Anaerotignum, Prevotellaceae_UCG-001, Alistipes, and Lachno-spiraceae_NK4A136_group and decreasing the abundance of the harmful bacteria Prevotella_9 and Parasutterella. Furthermore, we characterized the peptide composition of TP and found that GP-9 ameliorated the symptoms of dextran sodium sulfate (DSS)-induced colitis in mice by inhibiting the TLR4/NF-κB signaling pathway. In conclusion, TP and its derivative peptides ameliorated DSS-induced ulcerative colitis by inhibiting the expression of inflammatory factors and modulating the composition of the intestinal microbiota; this study provides a theoretical basis for the application of TP and its derivative peptides for their anti-inflammatory activity.


Subject(s)
Anti-Inflammatory Agents , Colitis, Ulcerative , Dextran Sulfate , Gastrointestinal Microbiome , Mice, Inbred C57BL , Peptides , Turtles , Animals , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/pathology , Colitis, Ulcerative/immunology , Gastrointestinal Microbiome/drug effects , Mice , Peptides/therapeutic use , Peptides/pharmacology , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Turtles/microbiology , Turtles/immunology , Male , Toll-Like Receptor 4/metabolism , NF-kappa B/metabolism , Disease Models, Animal , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Colon/pathology , Colon/drug effects , Humans , Oxidative Stress/drug effects , Signal Transduction/drug effects
6.
Ying Yong Sheng Tai Xue Bao ; 35(3): 587-596, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38646745

ABSTRACT

To investigate the longitudinal variation patterns of sapwood, heartwood, bark and stem moisture content along the trunk of artificial Larix olgensis, we constructed mixed effect models of moisture content based on beta regression by combining the effects of sampling plot and sample trees. We used two sampling schemes to calibrate the model, without limiting the relative height (Scheme Ⅰ) and with a limiting height of less than 2 m (Scheme II). The results showed that sapwood and stem moisture content increased gradually along the trunk, heartwood moisture content decreased slightly and then increased along the trunk, and bark moisture content increased along the trunk and then levelled off before increasing. Relative height, height to crown base, stand area at breast height per hectare, age, and stand dominant height were main factors driving moisture content of L. olgensis. Scheme Ⅰ showed the stable prediction accuracy when randomly sampling moisture content measurements from 2-3 discs to calibrate the model, with the mean absolute percentage error (MAPE) of up to 7.2% for stem moisture content (randomly selected 2 discs), and the MAPE of up to 7.4%, 10.5% and 10.5% for sapwood, heartwood and bark moisture content (randomly selected 3 discs), respectively. Scheme Ⅱ was appropriate when sampling moisture content measurements from discs of 1.3 and 2 m height and the MAPE of sapwood, heartwood, bark and stem moisture content reached 7.8%, 11.0%, 10.4% and 7.1%, respectively. The prediction accuracies of all mixed effect beta regression models were better than the base model. The two-level mixed effect beta regression models, considering both plot effect and tree effect, would be suitable for predicting moisture content of each part of L. olgensis well.


Subject(s)
Larix , Plant Stems , Water , Larix/growth & development , Larix/chemistry , Plant Stems/chemistry , Plant Stems/growth & development , Water/analysis , Water/chemistry , Regression Analysis , Wood/chemistry , Models, Theoretical , Forecasting
7.
Opt Express ; 32(7): 12405-12418, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38571063

ABSTRACT

An innovative ultra-sensitive, dual-functional sensor employing a D-shaped microchannel photonic crystal fiber (PCF) for refractive index (RI) and temperature measurements is proposed and comprehensively investigated. Its high-sensitivity is achieved through the incorporation of gold (Au) and magnesium fluoride (MgF2) as plasmonic materials in the micro-rectangular channel. This configuration significantly enhances the interaction between the surface plasmon polaritons (SPPs) field and y-polarized evanescent field on external surfaces. Additionally, the integration of a temperature-sensitive fluid within the sensor allows for precise detection of temperature changes. Our simulations demonstrate a broad detection spectrum, covering RI values from 1.27 to 1.43 and temperatures ranging from 45°C to 100°C. The sensor achieves peak sensitivities of 31800nm/RIU for RI and 49 nm/°C for temperature. Besides, the sensor only has a cladding consisting of three air holes to enhance coupling and reduce the difficulty of preparation. Importantly, the sensor's performance remains robust against minor structural alterations in the PCF, indicating high fault tolerance. Given its high sensitivity, extensive detection range, and strong fabrication stability, this PCF-SPR sensor offers significant potential for applications in biochemical sensing and environmental monitoring.

8.
J Adv Nurs ; 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38586889

ABSTRACT

AIM: To examine the main effects and interaction effects of outcome expectations (e.g., anticipated satisfactory salary and benefits), nurse identity (a sense of membership in the nursing profession), and information-access efficiency of the electronic medical record system (how the system enables nurses to quickly retrieve the needed information) on nurses' retention. DESIGN: This study uses a cross-sectional survey and adopts proportionate random sampling to recruit a representative sample of nurses of a medical centre in Taiwan. METHODS: This study successfully obtained completed questionnaires from 430 nurses during December 2021 to January 2022. Data are analysed by using hierarchical regressions. RESULTS: Positive outcome expectations and identification as a member in the nursing profession are associated with retention. Information-access efficiency strengthens the link between outcome expectations and retention, while nurse identity weakens this link. CONCLUSION: Outcome expectations can help retain nurses, particularly those who perceive high levels of information-access efficiency and possess weak nurse identity. That is, outcome expectations have a complementary role with nurse identity in retaining nurses. IMPLICATIONS FOR THE PROFESSION: Nurse managers should devise means to build positive outcome expectations for nurses. In addition, either strengthening nurses' identification with the nursing profession or improving the information-access efficiency of the electronic medical system may also help retain nurses. IMPACT: This study examined how to transform outcome expectation to nurse retention, offering nurse managers to devise new means to retain nurses. REPORTING METHOD: STROBE statement was chosen as EQUATOR checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

9.
Ann Hematol ; 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38472362

ABSTRACT

Multiple myeloma (MM) stands as the second most prevalent hematological malignancy, constituting approximately 10% of all hematological malignancies. Current guidelines recommend upfront autologous stem cell transplantation (ASCT) for transplant-eligible MM patients. This study seeks to delineate factors influencing post-ASCT outcomes in MM patients. Our cohort comprised 150 MM patients from Taipei Veterans General Hospital, with progression-free survival (PFS) as the primary endpoint and overall survival (OS) as the secondary endpoint. A Cox proportional hazards model was employed to discern potential predictive factors for survival. ASCT age ≥ 65 (hazard ratio [HR] 1.94, 95% confidence interval [CI] 1.08-3.47) and the presence of extramedullary disease (HR 2.53, 95% CI 1.53-4.19) negatively impacted PFS. Conversely, treatment response ≥ VGPR before ASCT (HR 0.52, 95% CI 0.31-0.87) and total CD34+ cells collected ≥ 4 × 106 cells/kg on the first stem cell harvesting (HR 0.52, 95% CI 0.32-0.87) were positively associated with PFS. For OS, patients with ISS stage III (HR 2.06, 95% CI 1.05-4.04), the presence of extramedullary disease (HR 3.92, 95% CI 2.03-7.58), light chain ratio ≥ 100 before ASCT (HR 7.08, 95% CI 1.45-34.59), post-ASCT cytomegalovirus infection (HR 9.43, 95% CI 3.09-28.84), and a lower conditioning melphalan dose (< 140 mg/m2; HR 2.75, 95% CI 1.23-6.17) experienced shorter OS. In contrast, post-ASCT day + 15 absolute monocyte counts (D15 AMC) > 500/µl (HR 0.36, 95% CI 0.17-0.79) and post-ASCT day + 15 platelet counts (D15 PLT) > 80,000/µl (HR 0.48, 95% CI 0.24-0.94) were correlated with improved OS. Significantly, early PLT and AMC recovery on day + 15 predicting longer OS represents a novel finding not previously reported. Other factors also align with previous studies. Our study provides real-world insights for post-ASCT outcome prediction beyond clinical trials.

10.
Angew Chem Int Ed Engl ; 63(17): e202400424, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38433094

ABSTRACT

Halide superionic conductors (SICs) are drawing significant research attention for their potential applications in all-solid-state batteries. A key challenge in developing such SICs is to explore and design halide structural frameworks that enable rapid ion movement. In this work, we show that the close-packed anion frameworks shared by traditional halide ionic conductors face intrinsic limitations in fast ion conduction, regardless of structural regulation. Beyond the close-packed anion frameworks, we identify that the non-close-packed anion frameworks have great potential to achieve superionic conductivity. Notably, we unravel that the non-close-packed UCl3-type framework exhibit superionic conductivity for a diverse range of carrier ions, including Li+, Na+, K+, and Ag+, which are validated through both ab initio molecular dynamics simulations and experimental measurements. We elucidate that the remarkable ionic conductivity observed in the UCl3-type framework structure stems from its significantly more distorted site and larger diffusion channel than its close-packed counterparts. By employing the non-close-packed anion framework as the key feature for high-throughput computational screening, we also identify LiGaCl3 as a promising candidate for halide SICs. These discoveries provide crucial insights for the exploration and design of novel halide SICs.

11.
Sci Adv ; 10(13): eadm9859, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38536921

ABSTRACT

Loss-of-function mutations in KEAP1 frequently occur in lung cancer and are associated with poor prognosis and resistance to standard of care treatment, highlighting the need for the development of targeted therapies. We previously showed that KEAP1 mutant tumors consume glutamine to support the metabolic rewiring associated with NRF2-dependent antioxidant production. Here, using preclinical patient-derived xenograft models and antigenic orthotopic lung cancer models, we show that the glutamine antagonist prodrug DRP-104 impairs the growth of KEAP1 mutant tumors. We find that DRP-104 suppresses KEAP1 mutant tumors by inhibiting glutamine-dependent nucleotide synthesis and promoting antitumor T cell responses. Using multimodal single-cell sequencing and ex vivo functional assays, we demonstrate that DRP-104 reverses T cell exhaustion, decreases Tregs, and enhances the function of CD4 and CD8 T cells, culminating in an improved response to anti-PD1 therapy. Our preclinical findings provide compelling evidence that DRP-104, currently in clinical trials, offers a promising therapeutic approach for treating patients with KEAP1 mutant lung cancer.


Subject(s)
Lung Neoplasms , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Glutamine/metabolism , Kelch-Like ECH-Associated Protein 1/genetics , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Enzyme Inhibitors/therapeutic use , Mutation
12.
Ying Yong Sheng Tai Xue Bao ; 35(2): 307-320, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38523087

ABSTRACT

The complex stand structure and high species diversity of natural forests pose great challenges for analyzing stand growth and formulating reasonable plans for forest management. The height-diameter relationship is of great significance for predicting stand growth and formulating forest management measures. Based on survey data of 48 broad-leaved mixed forest plots in Maoershan, we classified 23 tree species into four groups based on species structure, growth characteristics and bionomics. We established a generalized model including stand, tree competition, species mixing and species diversity variables by reparameterization method, and a two-level mixed effect model of plot and tree species group. We tested the prediction ability of the model by leave-one-out cross-validation method. The results showed that the Ratkowsky (1990) model was the optimal basic model. The introduction of dominant height, basal area of trees larger than the object tree, basal area proportion of each species, and Shannon index could better explain the height-diameter relationship of broad-leaved mixed forest in Maoershan. The introduction of the mixed effect model of plot and tree species group could significantly improve the prediction accuracy of the model, with a Ra2 of 0.83. Under the same gradient of environmental factors, intolerant tree species exhibited higher tree heights than shade-tolerant tree species. In this study, we used the constructed tree height-diameter model to analyze the effects of species mixing and tree functional traits on tree height, which provided a theoretical basis for accurately predicting height of different tree species and analyzing the growth relationships in broadleaved mixed forests.


Subject(s)
Pinus , China , Ecology
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(1): 184-189, 2024 Feb.
Article in Chinese | MEDLINE | ID: mdl-38387919

ABSTRACT

OBJECTIVE: To investigate the predictive value of platelet doubling (platelet count doubling) after one course of hypomethylating agents (HMA) on the treatment response and efficacy of myelodysplastic syndrome (MDS). METHODS: Clinical and pathological data of 75 patients who received HMA in our hospital from January 2017 to March 2022 were collected and analyzed. All patients were divided into two groups according to whether their platelet count doubled after one course of treatment, including platelet doubling group and non-doubling group, and statistical analysis was performed to compare the treatment response and efficacy between the two groups. In addition, platelet count changes were compared between azacitidine and decitabine therapy. RESULTS: Compared with the non-doubling platelet count group, the ORR of the doubling platelet group was significantly better after 3 courses of treatment (P =0.002), and there was a statistically significant difference in the number of HI between the two groups (P =0.005). In addition, the median survival time (MST) was 26 months in the platelet doubling group and 11 months in the non-doubling group (P =0.001). The overall survival (OS) and 1- and 2-year survival rates of the platelet doubling group were also significantly better than those of the non-doubing group. Multivariate COX analysis showed that platelet count doubling was an independent predictor of OS in MDS patients after 1 course of treatment (P =0.013). There was no significant difference in the response rate of platelet count doubling between MDS patients treated with azacitidine and decitabine (33.3% vs 23.8%, P >0.05). CONCLUSION: Platelet count doubling after one course of treatment can be used as a predictor of response rate and survival of demethylated drug therapy in MDS patients. In addition, there was no significant difference in the response rate of platelets in MDS patients treated with azacitidine or dicetabine.


Subject(s)
Antimetabolites, Antineoplastic , Myelodysplastic Syndromes , Humans , Decitabine/therapeutic use , Platelet Count , Treatment Outcome , Antimetabolites, Antineoplastic/therapeutic use , Retrospective Studies , Myelodysplastic Syndromes/drug therapy , Azacitidine/therapeutic use
14.
Sci Data ; 11(1): 218, 2024 Feb 17.
Article in English | MEDLINE | ID: mdl-38368451

ABSTRACT

As an important forestry pest, Coronaproctus castanopsis (Monophlebidae) has caused serious damage to the globally valuable Gutianshan ecosystem, China. In this study, we assembled the first chromosome-level genome of the female specimen of C. castanopsis by merging BGI reads, HiFi long reads and Hi-C data. The assembled genome size is 700.81 Mb, with a scaffold N50 size of 273.84 Mb and a contig N50 size of 12.37 Mb. Hi-C scaffolding assigned 98.32% (689.03 Mb) of C. Castanopsis genome to three chromosomes. The BUSCO analysis (n = 1,367) showed a completeness of 91.2%, comprising 89.2% of single-copy BUSCOs and 2.0% of multicopy BUSCOs. The mapping ratio of BGI, second-generation RNA, third-generation RNA and HiFi reads are 97.84%, 96.15%, 97.96%, and 99.33%, respectively. We also identified 64.97% (455.3 Mb) repetitive elements, 1,373 non-coding RNAs and 10,542 protein-coding genes. This study assembled a high-quality genome of C. castanopsis, which accumulated valuable molecular data for scale insects.


Subject(s)
Forestry , Genome, Insect , Hemiptera , Female , Chromosomes , Ecosystem , Phylogeny , RNA , Hemiptera/genetics
15.
Chin J Integr Med ; 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38386252

ABSTRACT

OBJECTIVE: To investigate the potential role of Tongxinluo (TXL) in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury (MIRI) in mice. METHODS: A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 min. According to a random number table, 66 mice were randomly divided into 6 groups (n=11 per group): the sham group, the model group, the LY-294002 group, the TXL group, the TXL+LY-294002 group and the benazepril (BNPL) group. The day after modeling, TXL and BNPL were administered by gavage. Intraperitoneal injection of LY-294002 was performed twice a week for 4 consecutive weeks. Echocardiography was used to measure cardiac function in mice. Masson staining was used to evaluate the degree of myocardial fibrosis in mice. Qualitative and quantitative analysis of endothelial mesenchymal transition (EndMT) after MIRI was performed by immunohistochemistry, immunofluorescence staining and flow cytometry, respectively. The protein expressions of platelet endothelial cell adhesion molecule-1 (CD31), α-smoth muscle actin (α-SMA), phosphatidylinositol-3-kinase (PI3K) and phospho protein kinase B (p-AKT) were assessed using Western blot. RESULTS: TXL improved cardiac function in MIRI mice, reduced the degree of myocardial fibrosis, increased the expression of CD31 and inhibited the expression of α-SMA, thus inhibited the occurrence of EndMT (P<0.05 or P<0.01). TXL significantly increased the protein expressions of PI3K and p-AKT (P<0.05 or P<0.01). There was no significant difference between TXL and BNPL group (P>0.05). In addition, the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention, eliminated the protective effect of TXL, further supporting the protective effect of TXL. CONCLUSION: TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.

16.
Res Sq ; 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38410458

ABSTRACT

Virus specific PD-1+ TCF-1+ TOX+ stem-like CD8+ T cells are essential for maintaining T cell responses during chronic infection and are also critical for PD-1 directed immunotherapy. In this study we have used the mouse model of chronic LCMV infection to examine when these virus specific stem-like CD8+ T cells are generated during the course of chronic infection and what is the role of antigen in maintaining the stem-like program. We found that these stem-like CD8+ T cells are generated early (day 5) during chronic infection and that antigen is essential for maintaining their stem-like program. This early generation of stem-like CD8+ T cells suggested that the fate commitment to this cell population was agnostic to the eventual outcome of infection and the immune system prepares a priori for a potential chronic infection. Indeed, we found that an identical virus specific stem-cell like CD8+ T cell population was also generated during acute LCMV infection but these cells were lost once the virus was cleared. To determine the fate of these early PD-1+TCF-1+TOX+ stem-like CD8+ T cells that are generated during both acute and chronic LCMV infection we set up two reciprocal adoptive transfer experiments. In the first experiment we transferred day 5 stem-like CD8+ T cells from chronically infected into acutely infected mice and examined their differentiation after viral clearance. We found that these early stem-like CD8+ T cells downregulated canonical markers of the chronic stem-like CD8+ T cells and expressed markers (CD127 and CD62L) associated with central memory CD8+ T cells. In the second experiment, we transferred day 5 stem-like cells from acutely infected mice into chronically infected mice and found that these CD8+ T cells could function like resource cells after transfer into a chronic environment by generating effector CD8+ T cells in both lymphoid and non-lymphoid tissues while also maintaining the number of stem-like CD8+ T cells. These findings provide insight into the generation and maintenance of virus specific stem-like CD8+ T cells that play a critical role in chronic viral infection. In particular, our study highlights the early generation of stem-like CD8+ T cells and their ability to adapt to either an acute or chronic infection. These findings are of broad significance since these novel stem-like CD8+ T cells play an important role in not only viral infections but also in cancer and autoimmunity.

17.
PLOS Glob Public Health ; 4(2): e0002961, 2024.
Article in English | MEDLINE | ID: mdl-38416781

ABSTRACT

COVID-19 vaccination rates for children globally are relatively low. This study aimed to investigate parental vaccine hesitancy and parents' acceptance of a COVID-19 for their children for their children in the United States, China, Taiwan, India, Indonesia, and Malaysia.We analyzed data from an opt-in, internet-based cross-sectional study (n = 23,940). Parents were asked about their acceptance of a COVID-19 vaccine for their children, and if they would accept the vaccine with different risk and effectiveness profiles for themselves. Poisson regression was used to generate prevalence ratios (PR) of the relationship between vaccine acceptance for a child and vaccine profile, by country and waves and overall. Between August 2020 and June 2021, COVID-19 vaccine acceptance for children decreased in the United States (89% to 72%) and Taiwan (79% to 71%), increased in India (91% to 96%) and Malaysia (81% to 91%), and was stable in Indonesia (86%) and China (at 87%-90%). Vaccine risk and effectiveness profiles did not consistently affect parent's acceptance of a COVID-19 vaccine for their children. Instead, being not hesitant was a large driver of vaccine acceptance (PR: 1.24, 95% CI: 1.14, 1.36). Adolescent COVID-19 vaccination have already been established in many high and middle-income countries, but our study suggests that there is a movement of vaccine hesitancy which could impede the success of future pediatric and adolescent COVID-19 vaccination programs.

18.
Immunity ; 57(2): 271-286.e13, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38301652

ABSTRACT

The immune system encodes information about the severity of a pathogenic threat in the quantity and type of memory cells it forms. This encoding emerges from lymphocyte decisions to maintain or lose self-renewal and memory potential during a challenge. By tracking CD8+ T cells at the single-cell and clonal lineage level using time-resolved transcriptomics, quantitative live imaging, and an acute infection model, we find that T cells will maintain or lose memory potential early after antigen recognition. However, following pathogen clearance, T cells may regain memory potential if initially lost. Mechanistically, this flexibility is implemented by a stochastic cis-epigenetic switch that tunably and reversibly silences the memory regulator, TCF1, in response to stimulation. Mathematical modeling shows how this flexibility allows memory T cell numbers to scale robustly with pathogen virulence and immune response magnitudes. We propose that flexibility and stochasticity in cellular decisions ensure optimal immune responses against diverse threats.


Subject(s)
CD8-Positive T-Lymphocytes , Memory T Cells , Epigenesis, Genetic , Clone Cells , Immunologic Memory , Cell Differentiation
19.
Pain Physician ; 27(2): E255-E262, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38324791

ABSTRACT

BACKGROUND: Chronic low back pain (CLBP) is a significant health challenge with a high prevalence rate. Sleep disorders, which are prevalent among adults, have been linked with CLBP. However, the intricate relationship between sleep and pain adds complexity to our understanding of CLBP. OBJECTIVES: To investigate the association between CLBP and sleep disorders, with a focus on the potential role of sleep disorders as a risk factor for CLBP. STUDY DESIGN: Cross-sectional study based on publicly available data from the National Health and Nutrition Examination Survey (NHANES) for one cycle (2009-2010). SETTING: The NHANES employs a complex, multistage probability sampling design to select a nationally representative sample. METHODS: In this study, we included patients aged 20 to 69 years from the NHANES 2009-2010 cycle. After eliminating cases with missing data, a total of 863 patients remained. Baseline characteristics were analyzed by stratifying patients based on their CLBP status to assess initial inter-group disparities. Due to age imbalances between groups, we employed a 1:1 propensity score matching (PSM) method, reducing the sample to 508 patients. The association between CLBP and trouble sleeping was investigated following this calibration using a multivariate logistic regression analysis. RESULTS: Upon categorizing the baseline characteristics of 863 patients based on CLBP, we identified that those within the CLBP group tended to be older and had a greater prevalence of health conditions, including cancer, hypertension, and cardiovascular disease (CVD). Notably, the prevalence of sleep disorders was higher in the CLBP group than in the non-CLBP group (P < 0.001). After implementing an age-based PSM for the 2 groups, 508 patients were selected from the initial 863 patients. After adjusting for various confounders using multivariate logistic regression, our analysis revealed a strong association between sleep disorders and an increased risk of CLBP. LIMITATIONS: This is a cross-sectional study, and therefore causality cannot be established. CONCLUSIONS: This study underscores the significant association between sleep disorders and an elevated risk of CLBP, highlighting the need for comprehensive management strategies that consider the role of sleep disorders in CLBP.


Subject(s)
Chronic Pain , Low Back Pain , Sleep Wake Disorders , Humans , Adult , Nutrition Surveys , Low Back Pain/diagnosis , Cross-Sectional Studies , Sleep , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/complications , Chronic Pain/epidemiology
20.
Rev Sci Instrum ; 95(2)2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38345452

ABSTRACT

Numerous scientific satellites require micronewton thrusters for compensating environmental disturbances. The mass flow control proportional valve plays a crucial role in precisely regulating the thrust. To meet the high resolution and wide range requirements of the thrusters, this paper introduces a novel proportional valve with two sets of independently controllable piezoelectric stack. One set of the piezo-stack is used to compensate the stroke loss of the valve core, mainly caused by the deformation of the valve seat. The valve sealing mechanism is carefully analyzed to reduce the stroke loss. Another set of the stack works as the primary actuator, enabling the high mass flow control resolution. Two sets of independently controlled piezoelectric stacks not only expand the range and improve the range ratio but also provide redundancy and enhance reliability. This means that the actuator can still operate at lower ranges even if one piezo-stack is damaged. The piezo-actuators are assembled using U-shaped connectors, creating a compact and space-efficient overall design. Experimental tests have been conducted to verify the performance of the valve, which demonstrated a mass flow range of 0-675 µg/s with a resolution better than 0.1 µg/s and a flow noise below 0.1 µg/s/Hz1/2 at 0.1 mHz-1 Hz.

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