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Proceedings of the National Academy of... Jul 2024Organisms often swim through density-stratified fluids. Here, we investigate the dynamics of active particles swimming in fluid density gradients and report theoretical...
Organisms often swim through density-stratified fluids. Here, we investigate the dynamics of active particles swimming in fluid density gradients and report theoretical evidence of taxis as a result of these gradients (densitaxis). Specifically, we calculate the effect of density stratification on the dynamics of a force- and torque-free spherical squirmer and show that density gradients induce reorientation that tends to align swimming either parallel or normal to the gradient depending on the swimming gait. In particular, swimmers that propel by generating thrust in the front (pullers) rotate to swim parallel to gradients and hence display (positive or negative) densitaxis, while swimmers that propel by generating thrust in the back (pushers) rotate to swim normal to the gradients. This work could be useful to understand the motion of marine organisms in ocean or be leveraged to sort or organize a suspension of active particles by modulating density gradients.
PubMed: 38935563
DOI: 10.1073/pnas.2405466121 -
JMIR Public Health and Surveillance Jun 2024Information on the public's preferences for current public health and social measures (PHSMs) and people's mental health under PHSMs is insufficient.
BACKGROUND
Information on the public's preferences for current public health and social measures (PHSMs) and people's mental health under PHSMs is insufficient.
OBJECTIVE
This study aimed to quantify the public's preferences for varied PHSMs and measure the level of pandemic fatigue in the COVID-19 normalization stage in China.
METHODS
A nationwide cross-sectional study with a discrete choice experiment and psychometric scales was conducted to assess public preferences for and attitudes toward PHSMs, using the quota sampling method. The COVID-19 Pandemic Fatigue Scale (CPFS) was used to screen fatigue levels among respondents. The multinomial logit model, latent class model, and Mann-Whitney test were used for statistical analysis. We also conducted subgroup analysis based on sex, age, monthly income, mental health status, and pandemic fatigue status.
RESULTS
A total of 689 respondents across China completed the survey. The discrete choice experiment revealed that respondents attached the greatest importance to the risk of COVID-19 infection within 3 months (45.53%), followed by loss of income within 3 months (30.69%). Vulnerable populations (low-income populations and elderly people) were more sensitive to the risk of infection, while younger respondents were more sensitive to income loss and preferred nonsuspension of social places and transportation. Migrants and those with pandemic fatigue had less acceptance of the mandatory booster vaccination and suspension of transportation. Additionally, a higher pandemic fatigue level was observed in female respondents, younger respondents, migrants, and relatively lower-income respondents (CPFS correlation with age: r=-0.274, P<.001; correlation with monthly income: r=-0.25, P<.001). Mandatory booster COVID-19 vaccination was also not preferred by respondents with a higher level of pandemic fatigue, while universal COVID-19 booster vaccination was preferred by respondents with a lower level of pandemic fatigue.
CONCLUSIONS
Pandemic fatigue is widely prevalent in respondents across China, and respondents desired the resumption of normal social life while being confronted with the fear of COVID-19 infection in the normalization stage of COVID-19 in China. During future pandemics, the mental burden and adherence of residents should be considered for the proper implementation of PHSMs.
Topics: Humans; COVID-19; China; Male; Female; Adult; Cross-Sectional Studies; Middle Aged; Public Health; Young Adult; Fatigue; Pandemics; Adolescent; Aged; Choice Behavior; Surveys and Questionnaires
PubMed: 38935420
DOI: 10.2196/45840 -
Health & Justice Jun 2024People incarcerated in jails are highly impacted by the opioid epidemic, and overdose education and naloxone distribution (OEND) is an effective strategy to reduce...
BACKGROUND
People incarcerated in jails are highly impacted by the opioid epidemic, and overdose education and naloxone distribution (OEND) is an effective strategy to reduce opioid overdose deaths. This study examines barriers and facilitators of fast-track OEND implementation within the jails in the Wave 1 Kentucky counties of the HEALing Communities Study during the COVID-19 pandemic.
METHODS
Meeting minutes with jail stakeholders were qualitatively coded using the Practical, Robust Implementation and Sustainability Model (PRISM) as the coding framework. The analysis highlighted the top barriers and facilitators to fast-track OEND implementation within the PRISM framework.
RESULTS
Space and staffing shortages related to the COVID-19 pandemic, disruptions in interorganizational programming from pandemic-related service suspensions, and a lack of technological solutions (e.g., reliable Internet access) for socially distanced delivery were the top barriers to fast-track OEND implementation. In addition, there were limitations on non-jail staff access to jails during COVID-19. Top facilitators included jail leadership support, the option to prioritize high-risk groups, and the incorporation of OEND processes into existing communications and management software. While the COVID-19 pandemic strained jail infrastructure, jail and partner agency collaboration led to creative implementation strategies for the successful integration of OEND into jail operations. Urban jails were more likely than rural jails to be early adopters of OEND during the public health emergency.
CONCLUSIONS
Understanding the barriers to and facilitators of OEND within jails will improve implementation efforts seeking to curb opioid overdose deaths. Jail leadership support and interorganizational efforts were key facilitators to implementation; therefore, it is recommended to increase buy-in with multiple agencies to promote success. Challenges brought on by COVID-19 have resulted in a need for innovative solutions for implementation.
CLINICAL TRIAL INFORMATION
ClinicalTrials.gov, NCT04111939, Submitted 30 September 2019, https://clinicaltrials.gov/study/NCT04111939?titles=HEALing%20Communities%20Study&rank=1 .
PubMed: 38935213
DOI: 10.1186/s40352-024-00283-8 -
Journal of the American Heart... Jul 2024Current protocols generate highly pure human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in vitro that recapitulate characteristics of mature...
BACKGROUND
Current protocols generate highly pure human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in vitro that recapitulate characteristics of mature in vivo cardiomyocytes. Yet, a risk of arrhythmias exists when hiPSC-CMs are injected into large animal models. Thus, understanding hiPSC-CM maturational mechanisms is crucial for clinical translation. Forkhead box (FOX) transcription factors regulate postnatal cardiomyocyte maturation through a balance between FOXO and FOXM1. We also previously demonstrated that p53 activation enhances hiPSC-CM maturation. Here, we investigate whether p53 activation modulates the FOXO/FOXM1 balance to promote hiPSC-CM maturation in 3-dimensional suspension culture.
METHODS AND RESULTS
Three-dimensional cultures of hiPSC-CMs were treated with Nutlin-3a (p53 activator, 10 μM), LOM612 (FOXO relocator, 5 μM), AS1842856 (FOXO inhibitor, 1 μM), or RCM-1 (FOXM1 inhibitor, 1 μM), starting 2 days after onset of beating, with dimethyl sulfoxide (0.2% vehicle) as control. P53 activation promoted hiPSC-CM metabolic and electrophysiological maturation alongside FOXO upregulation and FOXM1 downregulation, in n=3 to 6 per group for all assays. FOXO inhibition significantly decreased expression of cardiac-specific markers such as TNNT2. In contrast, FOXO activation or FOXM1 inhibition promoted maturational characteristics such as increased contractility, oxygen consumption, and voltage peak maximum upstroke velocity, in n=3 to 6 per group for all assays. Further, by single-cell RNA sequencing of n=2 LOM612-treated cells compared with dimethyl sulfoxide, LOM612-mediated FOXO activation promoted expression of cardiac maturational pathways.
CONCLUSIONS
We show that p53 activation promotes FOXO and suppresses FOXM1 during 3-dimensional hiPSC-CM maturation. These results expand our understanding of hiPSC-CM maturational mechanisms in a clinically-relevant 3-dimensional culture system.
Topics: Myocytes, Cardiac; Forkhead Box Protein M1; Tumor Suppressor Protein p53; Humans; Induced Pluripotent Stem Cells; Cell Differentiation; Cell Culture Techniques, Three Dimensional; Cells, Cultured; Signal Transduction; Forkhead Box Protein O1
PubMed: 38934864
DOI: 10.1161/JAHA.123.033155 -
MSystems Jun 2024The application of fecal metaproteomics to large-scale studies of the gut microbiota requires high-throughput analysis and standardized experimental protocols. Although...
The application of fecal metaproteomics to large-scale studies of the gut microbiota requires high-throughput analysis and standardized experimental protocols. Although high-throughput protein cleanup and digestion methods are increasingly used in shotgun proteomics, no studies have yet critically compared such protocols using human fecal samples. In this study, human fecal protein extracts were processed using several different protocols based on three main approaches: filter-aided sample preparation (FASP), solid-phase-enhanced sample preparation (SP3), and suspension trapping (S-Trap). These protocols were applied in both low-throughput (i.e., microtube-based) and high-throughput (i.e., microplate-based) formats, and the final peptide mixtures were analyzed by liquid chromatography coupled to high-resolution tandem mass spectrometry. The FASP-based methods and the combination of SP3 with in-StageTips (iST) yielded the best results in terms of the number of peptides identified through a database search against gut microbiome and human sequences. The efficiency of protein digestion, the ability to preserve hydrophobic peptides and high molecular weight proteins, and the reproducibility of the methods were also evaluated for the different protocols. Other relevant variables, including interindividual variability of stool, duration of protocols, and total costs, were considered and discussed. In conclusion, the data presented here can significantly contribute to the optimization and standardization of sample preparation protocols in human fecal metaproteomics. Furthermore, the promising results obtained with the high-throughput methods are expected to encourage the development of automated workflows and their application to large-scale gut microbiome studies.IMPORTANCEFecal metaproteomics is an experimental approach that allows the investigation of gut microbial functions, which are involved in many different physiological and pathological processes. Standardization and automation of sample preparation protocols in fecal metaproteomics are essential for its application in large-scale studies. Here, we comparatively evaluated different methods, available also in a high-throughput format, enabling two key steps of the metaproteomics analytical workflow (namely, protein cleanup and digestion). The results of our study provide critical information that may be useful for the optimization of metaproteomics experimental pipelines and their implementation in laboratory automation systems.
PubMed: 38934547
DOI: 10.1128/msystems.00661-24 -
Journal of Clinical Apheresis Jun 2024Membranous nephropathy is the most common cause of nephrotic syndrome (NS) in non-diabetic adults; in 80% of patients it is idiopathic (PMN). PMN has an autoimmune...
Membranous nephropathy is the most common cause of nephrotic syndrome (NS) in non-diabetic adults; in 80% of patients it is idiopathic (PMN). PMN has an autoimmune pathogenesis, 70%-85% of patients have increased titer of antibodies to the podocyte membrane antigen PLA2R. The etiological, prognostic and predictive role of the Ab anti-PLA2R is demonstrated. Standard therapy consists in anti-CD20 monoclonal antibody rituximab (RTX) combined with steroids or immunosuppressants according to the risk of progressive loss of kidney function. The immunosuppressive therapies are potentially associated to severe adverse events that lead to protocol suspension. Given their pivotal pathogenetic role, serum clearance of anti-PLA2R with plasmapheresis could have a beneficial impact on NS, particularly in patients not requiring or tolerating standard therapies. In this series, we present three cases of PMN anti-PLA2R related treated with a RTX plus plasmapheresis approach and demonstrate its overall effective role on anti-PLA2R titer and clinical outcomes.
Topics: Humans; Plasmapheresis; Glomerulonephritis, Membranous; Receptors, Phospholipase A2; Rituximab; Male; Middle Aged; Female; Adult; Autoantibodies; Immunosuppressive Agents
PubMed: 38934513
DOI: 10.1002/jca.22134 -
Heliyon Jun 2024The relation between aphids and Sclerotinia stem rot (SSR) in oilseed rape is rarely examined because they are often studied alone. We have observed a significant...
The relation between aphids and Sclerotinia stem rot (SSR) in oilseed rape is rarely examined because they are often studied alone. We have observed a significant correlation between the number of aphids and the occurrence of SSR in our field studies. Electropenetrography (EPG) was used to evaluate the effects of (Linnaeus) on two oilseed rape cultivars while acquiring, vectoring and inoculating of Lib. (de Bary) ascospores. The results demonstrated that aphid feeding followed by the application of an ascospore suspension significantly increased incidence. Aphids were capable of adhering to ascospores and carrying them to healthy plants, thereby causing diseases. The results of the EPG analysis indicated that aphid feeding behaviour was significantly altered in all leaf tissue levels following infection with . Aphids initiated their first puncture significantly sooner than the control group, began probing mesophyll cells earlier, significantly increased the frequency of both short probes and intracellular punctures and had a significantly shorter pathway duration. On infected aphid-susceptible cultivars, aphids secreted more saliva but had reduced ingestion compared with aphids feeding on non-infected oilseed rape. In addition, ascospores can affect aphid feeding behaviour by adhering to aphids. Aphids carrying ascospores punctured cells earlier, with a significant increase in the frequency and duration of short probes and cell punctures, shortened pathway durations, increased salivation and reduced ingestion compared with aphids not carrying ascospores. On aphid-susceptible cultivars, aphids carrying ascospores delayed puncture onset, but on resistant cultivars, puncture onset was shortened. There is a correlation between aphids and . The impact of on aphid feeding behaviour is directional, favouring the spread of the fungus. This promotion does not appear to be altered by the aphid resistance of the cultivar.
PubMed: 38933983
DOI: 10.1016/j.heliyon.2024.e32429 -
Fundamental Research May 2024The environmental stability of infectious viruses in the laboratory setting is crucial to the transmission potential of human respiratory viruses. Different experimental... (Review)
Review
The environmental stability of infectious viruses in the laboratory setting is crucial to the transmission potential of human respiratory viruses. Different experimental techniques or conditions used in studies over the past decades have led to diverse understandings and predictions for the stability of viral infectivity in the atmospheric environment. In this paper, we review the current knowledge on the effect of simulated atmospheric conditions on the infectivity of respiratory viruses, mainly focusing on influenza viruses and coronaviruses, including severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus. First, we summarize the impact of the experimental conditions on viral stability; these involve the methods of viral aerosol generation, storage during aging and collection, the virus types and strains, the suspension matrixes, the initial inoculum volumes and concentrations, and the drying process. Second, we summarize and discuss the detection methods of viral infectivity and their disadvantages. Finally, we integrate the results from the reviewed studies to obtain an overall understanding of the effects of atmospheric environmental conditions on the decay of infectious viruses, especially aerosolized viruses. Overall, this review highlights the knowledge gaps in predicting the ability of viruses to maintain infectivity during airborne transmission.
PubMed: 38933192
DOI: 10.1016/j.fmre.2023.12.017 -
Journal of Medicinal Chemistry Jun 2024Respiratory syncytial virus (RSV) is a major cause of hospitalization in infants, the elderly, and immune-compromised patients. While a half-life extended monoclonal...
Respiratory syncytial virus (RSV) is a major cause of hospitalization in infants, the elderly, and immune-compromised patients. While a half-life extended monoclonal antibody and 2 vaccines have recently been approved for infants and the elderly, respectively, options to prevent disease in immune-compromised patients are still needed. Here, we describe spiro-azetidine oxindoles as small molecule RSV entry inhibitors displaying favorable potency, developability attributes, and long-acting PK when injected as an aqueous suspension, suggesting their potential to prevent complications following RSV infection over a period of 3 to 6 months with 1 or 2 long-acting intramuscular (IM) or subcutaneous (SC) injections in these immune-compromised patients.
PubMed: 38932487
DOI: 10.1021/acs.jmedchem.4c00514 -
Plant Disease Jun 2024Artemisia argyi is a perennial herb native to East Asia. It is an important traditional Chinese medicinal plant known for its strong flavor and medicinal effects. It is...
Artemisia argyi is a perennial herb native to East Asia. It is an important traditional Chinese medicinal plant known for its strong flavor and medicinal effects. It is rich in active ingredients and has a wide range of biological activities, including anti-inflammatory, antioxidant, and immune regulation properties. From May to July in 2023, a serious leaf rot outbreak occurred on A. argyi in several farms (approximately 200 acres) in Tanghe county (32°46'44" N, 112°43'13" E), Henan Province, China. The incidence rate reached 65% (n=200). Pale yellow spots (1-2 cm in diameter) first appeared on the leaves, then expanded to form irregular yellowish-brown lesions, eventually causing the entire leaves to wither. Diseased leaves (30) were collected and cut into 5 x 5 mm2 pieces in the areas between infected and healthy tissues. The excised plant tissues were sterilized in 75% ethanol and 1% sodium hypochlorite solution for 30 seconds and one minute, respectively. The tissues were then rinsed with sterile water and placed on potato dextrose agar (PDA) followed by incubating at 25 °C for 3 days. The isolated strains belonged to the genera Fusarium and Alternaria. After pathogenicity verification, 25 purified Fusarium strains were obtained. Three representative strains (AC-Q, AC-X, AC-Y) from different regions were used for further studies. Each strain formed abundant aerial mycelium that was initially white and later developed into purple pigments. Aerial conidiophores were sparsely branched, terminating with verticillate phialides. Macroconidia were slender, straight, and measured 21.8 to 47.5 × 3.1 to 4.4 μm, with two to four septa. Microconidia were clavate and measured 8.31 to 11.6 × 2.1 to 3.5 μm. Morphological characteristics were consistent with the species description of Fusarium verticillioides (Sacc.) Nirenberg 1976 (Leslie and Summerell, 2006). The rDNA internal transcribed spacer (ITS), β-tubulin gene (tub2), translation elongation factor 1-alpha gene (tef1), calmodulin (cmdA), RNA polymerase II largest subunit (rpb1) and RNA polymerase II second largest subunit (rpb2) were amplified for molecular identification (O'Donnell et al., 2022). The sequences were deposited in GenBank with accession Nos. OR960548, OR960552, OR960555 (ITS), OR972413, OR972414, OR972415 (tub2), OR797685, OR797686, OR797687 (tef1), OR972410, OR972411, OR972412 (cmdA), PP035106, PP035107, PP035108 (rpb1), and PP035109, PP035110, PP035111 (rpb2). BLASTn analysis of AC-Q sequences exhibited 99 to 100% similarity with F. verticillioides sequences (strains CBS 576.78) MT010888 of cmdA, MT0109566 of rpb1, and MT010972 of rpb2. A phylogenetic tree was constructed with concatenated sequences (tub2, tef1, cmdA, rpb1, rpb2), alongside the sequences of the type strains using the neighbor-joining method. The three strains formed a clade with the type strain CBS 576.78 of F. verticillioides, and were separated from other Fusarium spp. These morphological and molecular identifications indicated that the pathogen was F. verticillioides. Pathogenicity was tested on 10 healthy 2-month-old potted seedlings by spraying them with a conidial suspension (106 conidia ml-1), and 5 seedlings were sprayed with sterilized water as a control. The plants were placed in a climate incubator at 28°C and a relative humidity of approximately 90%. Ten days after seedling inoculation, typical lesions were observed on the treated plants, except in the control group. The reisolated strains were identified as F. verticillioides by morphological and molecular characterization, fulfilling Koch's postulates. F. verticillioides is known to cause Fusarium ear rot on maize, as well as diseases on other plants in China such as Brassica rapa (Akram et al., 2020) and Schizonepeta tenuifolia (Li et al., 2024). This is the first report of F. verticillioides causing leaf rot on A. argyi worldwide. Identification of the pathogen is crucial for implementing management approaches to reduce yield losses.
PubMed: 38932449
DOI: 10.1094/PDIS-03-24-0667-PDN