The Expression Profile of mRNA and tRNA Genes in Splenocytes and Neutrophils after In Vivo Delivery of Antitumor Short Hairpin RNA of Indoleamine 2,3- Dioxygenase.

RNA-based therapeutics are considered as novel treatments for human diseases. Our previous study demonstrated that treatment with short-hairpin RNA against Ido1 (IDO shRNA) suppresses tumor growth, detects Th1-bias immune responses, and elevates expression of tryptophan transfer RNA (tRNATrp) in total splenocytes. In addition, depletion of Ly6g+ neutrophils attenuates the effect of IDO shRNA. The aim of this study was to investigate the regulatory network and the expression profile of tRNAs and other non-coding RNAs in IDO shRNA-treated spleens. The total splenocytes and magnetic bead-enriched splenic neutrophils were collected from the lung tumor bearing mice, which were treated with IDO shRNA or scramble IDO shRNA, and the collected cells were subsequently subjected to RNA sequencing. The gene ontology analysis revealed the different enrichment pathways in total splenocytes and splenic neutrophils. Furthermore, the expression of tRNA genes was identified and validated. Six isoacceptors of tRNA, with different expression patterns between total splenocytes and splenic neutrophils, were observed. In summary, our findings not only revealed novel biological processes in IDO shRNA-treated total splenocytes and splenic neutrophils, but the identified tRNAs and other non-coding RNAs may contribute to developing a novel biomarker gene set for evaluating the clinical efficiency of RNA-based cancer immunotherapies.

How to effectively obtain informed consent in trauma patients: a systematic review.

BACKGROUND: Obtaining adequate informed consent from trauma patients is challenging and time-consuming. Healthcare providers must communicate complicated medical information to enable patients to make informed decisions. This study aimed to explore the challenges of obtaining valid consent and methods of improving the quality of the informed consent process for surgical procedures in trauma patients. METHODS: We conducted a systematic review of relevant English-language full-text original articles retrieved from PubMed (1961-August 2018) that had experimental or observational study design and involved adult trauma patients. Studies involving informed consent in clinical or research trials were excluded. Titles and abstracts of searched articles were reviewed and relevant data were extracted with a structured form. Results were synthesized with a narrative approach. RESULTS: A total of 2044 articles were identified in the initial search. Only eight studies were included in the review for narrative synthesis. Six studies involved orthopedic surgeries, one involved nasal bone surgeries, and one involved trauma-related limb debridement. Only one study was conducted in an emergency department. Information recall was poor for trauma patients. Risk recall and comprehension were greater when written or video information was provided than when information was provided only verbally. Patient satisfaction was also greater when both written and verbal information were provided than when verbal information alone was provided; patients who received video information were more satisfied than patients who received written or verbal information. CONCLUSIONS: Many articles have been published on the subject of informed consent, but very few of these have focused on trauma patients. More empirical evidence is needed to support the success of informed consent for trauma patients in the emergency department, especially within the necessarily very limited time frame. To improve the informed consent process for trauma patients, developing a structured and standardized informed consent process may be necessary and achievable; its effectiveness would require evaluation. Adequately educating and training healthcare providers to deliver structured, comprehensive information to trauma patients is crucial. Institutions should give top priority to ensuring patient-centered health care and improved quality of care for trauma patients.

Spontaneous pneumocephalus and subdural hemorrhage after sneezing.

Spontaneous pneumocephalus is defined as the presence of air in the absence of intracranial factors. The management of spontaneous pneumocephalus can be conservative or surgical, and surgical intervention could be urgently required if clinical deterioration is rapid. Here, we report a case of pneumocephalus and subdural hemorrhage after sneezing. A 24-year-old male reported to our emergency department with a chief complaint of headache and dizziness. The patient gave a history of onset of headache and dizziness after 2 episodes of heavy sneezing. There was neither a history of recent traumatic episode or previous surgery, nor any signs and symptoms of recent fever or upper respiratory tract infections. Physical examination showed no specific findings. Computed tomography was performed, which showed subdural hemorrhage and PNC in the left occipital lobe, left hemomastoid, and maxillary hemosinus. A neurosurgeon was consulted, who suggested admission in the intensive care unit. An otolaryngologist was then consulted for the left ear otorrhea and hearing impairment. Otoscopic examination showed hemotympanum of the left ear, for which pain control and conservative treatment was suggested. The patient was transferred to general ward 4 days later, since the following brain computed tomography showed resolution of the hemorrhage, and discharged 6 days later because of the improved signs and symptoms. Pneumocephalus and intracranial hemorrhage can occur without a history of trauma or surgery. Special attention is required if headache, dizziness, or other neurologic signs and symptoms occur immediately after sneezing. Intracranial hemorrhage and penumocephalus should be considered in the differential diagnosis.

Chest wall hematoma after central venous hemodialysis catheter insertion.

There were few case reports discuss about iatrogenic chest wall hematoma. Although it is rare life threatening, it still can result in significant morbidity. A 68-year-old woman with histories of end-stage renal disease under regular hemodialysis and congestive heart failure was sent to our emergency department because of progression of ecchymosis over the anterior chest wall a few hours after hemodialysis. The right subclavian hemodialysis catheter was inserted for hemodialysis on the same day. She did not have a history of bleeding disorders and was not taking any antiplatelet or anticoagulant agents. Additionally, she had no recent trauma episodes. Physical examination revealed a large ecchymosis over the anterior right chest wall with swelling and tenderness. Blood examination showed no specific finding. Contrast-enhanced computed tomography of the chest revealed a hyperdense lesion with extravasation over the right chest wall, suggesting the presence of a hematoma with active bleeding. Local compression was applied. However, hematoma expansion was still noted. Therefore, we consulted a thoracic surgeon concerning surgical intervention. During the operation, active bleeding of the intramuscular arterial branch of the right pectoralis major was encountered. After surgical repair, no more bleeding was noted. It is important to confirm the possible cause of chest wall hematoma. Treating the underlying disease and discontinuing anticoagulation and antiplatelet agents should be considered. For iatrogenic chest wall hematoma, bleeding control should be the priority. Contrast-enhanced computed tomography could be arranged if there are no contraindications.

Oxidized Low-Density Lipoprotein-Deteriorated Psoriasis Is Associated with the Upregulation of Lox-1 Receptor and Il-23 Expression In Vivo and In Vitro.

Psoriasis is a chronic inflammatory skin disease. Even though scientists predict that abnormalities in lipid metabolism play an important role in the pathogenesis of psoriasis, the actual underlying mechanisms are still unclear. Therefore, understanding the possible relationship between mechanisms of the occurrence of psoriasis and dyslipidemia is an important issue that may lead to the development of effective therapies. Under this principle, we investigated the influences of hyperlipidemia in imiquimod (IMQ)-induced psoriasis-like B6.129S2-Apoetm1Unc/J mice and oxidized low-density lipoprotein (oxLDL) in tumor necrosis factor (TNF)-α-stimulated Hacat cells. In our study, we showed that a high-cholesterol diet aggravated psoriasis-like phenomena in IMQ-treated B6.129S2-Apoetm1Unc/J mice. In vitro analysis showed that oxLDL increased keratinocyte migration and lectin-type oxLDL receptor 1 (LOX-1) expression. Evidence suggested that interleukin (IL)-23 was a main cytokine in the pathogenesis of psoriasis. High-cholesterol diet aggravated IL-23 expression in IMQ-treated B6.129S2-Apoetm1Unc/J mice, and oxLDL induced IL-23 expression mediated by LOX-1 in TNF-α-stimulated Hacat cells. Therefore, it will be interesting to investigate the factors for the oxLDL induction of LOX-1 in psoriasis. LOX-1 receptor expression may be another novel treatment option for psoriasis and might represent the most promising strategy.

Serum neutrophil gelatinase-associated lipocalin and resistin are associated with dengue infection in adults.

BACKGROUND: Dengue is a major health problem in tropical areas, including Taiwan. Dengue virus infection affects various types of cells and results in elevation of serum inflammatory molecules. Because these molecules may be associated with dengue virus infection, the aim of this study was to identify novel molecules in febrile patients with dengue infection. In addition, we determined whether these molecules were correlated with the count of leukocytes and platelets. METHODS: Febrile adults (Age >18 years old) who presented to the emergency department and were confirmed dengue virus infection were enrolled in this study. Serum from dengue patients and healthy controls was collected and serum level of sepsis-associated inflammatory molecules was measured by Luminex assay. RESULTS: Elevated level of macrophage migration inhibitory factor, soluble vascular cell adhesion molecule-1, sFasL, resistin and interferon-γ were detected in patients' serum. Higher levels of neutrophil gelatinase-associated lipocalin (NGAL) and resistin were detected in dengue patients with normal leukocyte count and all dengue patients, respectively. Furthermore, the serum level of NGAL, but not resistin, was correlated with cell count in dengue patients. CONCLUSION: Our results revealed that resistin and NGAL are novel dengue-associated molecules. These results may help elucidate the regulatory mechanisms of anti-dengue immune responses.

Serum Galectin-9 and Galectin-3-Binding Protein in Acute Dengue Virus Infection.

Dengue fever is a serious threat for public health and induces various inflammatory cytokines and mediators, including galectins and glycoproteins. Diverse immune responses and immunological pathways are induced in different phases of dengue fever progression. However, the status of serum galectins and glycoproteins is not fully determined. The aim of this study was to investigate the serum concentration and potential interaction of soluble galectin-1, galectin-3, galectin-9, galectin-3 binding protein (galectin-3BP), glycoprotein 130 (gp130), and E-, L-, and P-selectin in patients with dengue fever in acute febrile phase. In this study, 317 febrile patients (187 dengue patients, 150 non-dengue patients that included 48 patients with bacterial infection and 102 patients with other febrile illness) who presented to the emergency department and 20 healthy controls were enrolled. Our results showed the levels of galectin-9 and galectin-3BP were significantly higher in dengue patients than those in healthy controls. Lower serum levels of galectin-1, galectin-3, and E-, L-, and P-selectin in dengue patients were detected compared to bacteria-infected patients, but not to healthy controls. In addition, strong correlation between galectin-9 and galectin-3BP was observed in dengue patients. In summary, our study suggested galectin-9 and galectin-3BP might be critical inflammatory mediators in acute dengue virus infection.

From-core and from-end direct C-H arylations: a step-saving new synthetic route to thieno[3,4-c]pyrrole-4,6-dione (TPD)-incorporated D--π-A-π-D functional oligoaryls.

In contrast to the traditional multistep synthesis, herein an efficient and fewer-steps new synthetic strategy is demonstrated for the facile preparation of organic-electronically important D-π-A-π-D-type oligoaryls through sequential direct CH arylations. This methodology has shown that the synthesis of thieno[3,4-c]pyrrole-4,6-dione (TPD)- or furano[3,4-c]pyrrole-4,6-dione (FPD)-centred target molecules could be accessed step-economically either from the core structure (acceptor) or from the end structure (donor), which supplied a more flexible and succinct new synthetic alternative to the preparation of the π-functional small-molecule semiconducting materials. In addition, optical and electrochemical properties of the synthesized oligoaryls were examined.

Optimization protein productivity of human interleukin-2 through codon usage, gene copy number and intracellular tRNA concentration in CHO cells.

Transfer RNA (tRNA) abundance is one of the critical factors for the enhancement of protein productivity in prokaryotic and eukaryotic hosts. Gene copy number of tRNA and tRNA codon usage bias are generally used to match tRNA abundance of protein-expressing hosts and to optimize the codons of recombinant proteins. Because sufficient concentration of intracellular tRNA and optimized codons of recombinant proteins enhanced translation efficiency, we hypothesized that sufficient supplement of host's tRNA improved protein productivity in mammalian cells. First, the small tRNA sequencing results of CHO-K1 cells showed moderate positive correlation with gene copy number and codon usage bias. Modification of human interleukin-2 (IL-2) through codons with high gene copy number and high codon usage bias (IL-2 HH, modified on Leu, Thr, Glu) significantly increased protein productivity in CHO-K1 cells. In contrast, modification through codons with relatively high gene copy number and low codon usage bias (IL-2 HL, modified on Ala, Thr, Val), or relatively low gene copy number and low codon usage bias (IL-2 LH, modified on Ala, Thr, Val) did not increase IL-2 productivity significantly. Furthermore, supplement of the alanine tRNA or threonine tRNA increased IL-2 productivity of IL-2 HL. In summary, we revealed a potential strategy to enhance productivity of recombinant proteins, which may be applied in production of protein drug or design of DNA vaccine.

Transcriptomic analysis of lipoteichoic acid­treated undifferentiated and neutrophil­like differentiated HL­60 cells.

Toll-like receptor 2 (TLR2) is an important sensor for innate immune cells, including neutrophils, for the recognition of pathogen infection. Lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria, is a TLR2 ligand. LTA-induced TLR2 signaling pathways are well established in neutrophils. However, experimental studies regarding transcriptional regulation and the molecular mechanisms in primary human neutrophils are limited due to their short lifespan. The promyelocytic leukemia cell line, HL-60, can differentiate into a neutrophil-like phenotype following treatment with dimethyl sulfoxide. The aim of the present study was to investigate whether differentiated HL-60 (dHL-60) cells induced a similar gene expression profile upon LTA treatment as that previously determined for primary human neutrophils. After 4 or 24 h of Staphylococcus aureus LTA treatment, undifferentiated HL-60 (uHL-60) and dHL-60 cells were collected for RNA sequencing. The results demonstrated that hundreds of identical differentially expressed genes (DEGs) were observed in 1 and 10 µg/ml LTA-treated dHL-60 cells following 4 and 24 h of incubation, while almost no DEGs between LTA-treated HL-60 and dHL-60 cells were observed. Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses (KEGG), it was noted that the pathways of shared DEGs between the 1 and 10 µg/ml LTA-treated dHL-60 cells at both time points were significantly enriched in immune and inflammatory response-related pathways, such as cellular response to tumor necrosis factor, interleukin-1, interferon γ, neutrophil chemotaxis, the NF-κB signaling pathway and the Toll-like receptor signaling pathway. In addition, when comparing the effect of 1 and 10 µg/ml LTA treatment on dHL60 cells, it was found that all enriched GO and KEGG pathways were associated with the TLR signaling pathways of neutrophils. The results of the present study provided important information for the implementation of mRNA profiling in LTA-treated dHL-60 cells and may indicate the feasibility of using dHL-60 cells as a research model for TLR2 signaling in human neutrophils.

Insight into the diurnal variations and potential sources of ambient PM2.5-bound polycyclic aromatic hydrocarbons during spring in Northern Taiwan.

In recent decades, polycyclic aromatic hydrocarbons (PAHs), the primary organic pollutants associated with particulate matter (PM), have attracted significant attention due to their carcinogenic and mutagenic potential. However, past studies have lacked exploration into the diurnal variation characteristics of PAHs, primarily due to limited analytical technical capabilities. This study utilized a thermal-desorption device coupled with gas chromatography/mass spectrometry (TD-GC/MS) to identify the levels of PAHs in PM2.5 during short periods (3-hr) and aimed to investigate the diurnal variations, possible sources, and potential health risks associated with PM2.5-bound PAHs in northern Taiwan. The mean concentration of total PAHs in PM2.5 was 1.22 ± 0.69 ng m-3 during the sampling period, with high molecular weight PAHs dominating. Source apportionment by the positive matrix factorization (PMF) model indicated that industrial emissions and traffic emissions (57.7 %) were the predominant sources of PAHs, with petroleum volatilization and coal/biomass combustion (42.3 %) making a lesser contribution. Diurnal variations of industrial and traffic emissions showed higher concentrations during traffic rush hours, while petroleum volatilization and coal/biomass combustion displayed higher concentrations at noon. Results from the potential source contribution function (PSCF) and the concentration weighted trajectory (CWT) model suggested that industrial emissions and traffic emissions mostly originated from local sources and were concentrated in the vicinity of the sampling site and the coastal area of western Taiwan. Source-attributed excess cancer risk (ECR) showed that industrial and traffic emissions had the highest cancer risks during morning traffic peak hours (1.69 ×10-5), while petroleum volatilization and coal/biomass combustion reached the maximum at noon (4.75 ×10-6). As a result, efforts to reduce PAH emissions from industrial and vehicle exhaust sources, especially during morning traffic hours, can help mitigate their adverse impact on human health.

Exploring the characteristics and source-attributed health risks associated with polycyclic aromatic hydrocarbons and metal elements in atmospheric PM2.5 during warm and cold periods in the northern metropolitan area of Taiwan.

Polycyclic aromatic hydrocarbons (PAHs) and metal elements are commonly considered hazardous air pollutants due to their toxic, mutagenic, and carcinogenic properties. However, few studies have simultaneously examined their potential sources and health effects. This study aimed to quantify the PAHs and metal elements in atmospheric PM2.5, investigating their characteristics and potential sources to assess associated health risks in the northern metropolitan area of Taiwan. The measurements indicated that the mean concentrations of total PAHs and metal elements in PM2.5 were 0.97 ± 0.52 ng m-3 and 590 ± 200 ng m-3, respectively. Utilizing the positive matrix factorization profiles, the PAH pollution was classified into two sources: industrial emissions, traffic emissions, and coal combustion (69%) were the predominant sources of PAHs, with petroleum volatilization and biomass burning (31%) making a lesser contribution. Similarly, we traced metal elements to three potential sources: natural sources (48%), a combined source of industrial emissions, coal combustion, and traffic exhaust (32%), and a blend of non-exhaust emissions from traffic and waste incineration sources (20%). Results from the potential source contribution function model suggested that the emissions of PAHs and metals could be influenced by the eastern regions of China, although local sources, including waste incinerators, traffic, shipping, and harbor activities, were identified as the primary contributors. Source-attributed excess cancer risk revealed that industry, traffic, and coal combustion had the highest cancer risk posed by PAHs in the cold period (1.0 × 10-5), while the greatest cancer risk among metal elements was linked to non-exhaust emissions from traffic and waste incineration emissions (2.0 × 10-5). This research underscores the importance of considering source contributions to health risk and emission reduction when addressing PM2.5 pollution. These findings have direct implications for policymakers, providing them with valuable insights to develop strategies that protect public health from the detrimental effects of PAH and metal element exposure.

Prothymosin α accelerates dengue virus-induced thrombocytopenia.

Thrombocytopenia is the hallmark finding in dengue virus (DENV) infection. Prothymosin α (ProT) has both intracellular and extracellular functions involved in cell cycle progression, cell differentiation, gene regulation, oxidative stress response, and immunomodulation. In this study, we found that ProT levels were elevated in dengue patient sera as well as DENV-infected megakaryoblasts and their culture supernatants. ProT transgenic mice had reduced platelet counts with prolonged bleeding times. Upon treatment with DENV plus anti-CD41 antibody, they exhibited severe skin hemorrhage. Furthermore, overexpression of ProT suppressed megakaryocyte differentiation. Infection with DENV inhibited miR-126 expression, upregulated DNA (cytosine-5)-methyltransferase 1 (DNMT1), downregulated GATA-1, and increased ProT expression. Upregulation of ProT led to Nrf2 activation and reduced reactive oxygen species production, thereby suppressing megakaryopoiesis. We report the pathophysiological role of ProT in DENV infection and propose an involvement of the miR-126-DNMT1-GATA-1-ProT-Nrf2 signaling axis in DENV-induced thrombocytopenia.

Site-specific thrombus formation: advancements in photothrombosis-on-a-chip technology.

Thrombosis, characterized by blood clot formation within vessels, poses a significant medical challenge. Despite extensive research, the development of effective thrombosis therapies is hindered by substantial costs, lengthy development times, and high failure rates in medication commercialization. Conventional pre-clinical models often oversimplify cardiovascular disease, leading to a disparity between experimental results and human physiological responses. In response, we have engineered a photothrombosis-on-a-chip system. This microfluidic model integrates human endothelium, human whole blood, and blood flow dynamics and employs the photothrombotic method. It enables precise, site-specific thrombus induction through controlled laser irradiation, effectively mimicking both normal and thrombotic physiological conditions on a single chip. Additionally, the system allows for the fine-tuning of thrombus occlusion levels via laser parameter adjustments, offering a flexible thrombus model with varying degrees of obstruction. Additionally, the formation and progression of thrombosis noted on the chip closely resemble the thrombotic conditions observed in mice in previous studies. In the experiments, we perfused recalcified whole blood with Rose Bengal into an endothelialized microchannel and initiated photothrombosis using green laser irradiation. Various imaging methods verified the model's ability to precisely control thrombus formation and occlusion levels. The effectiveness of clinical drugs, including heparin and rt-PA, was assessed, confirming the chip's potential in drug screening applications. In summary, the photothrombosis-on-a-chip system significantly advances human thrombosis modeling. Its precise control over thrombus formation, flexibility in the thrombus severity levels, and capability to simulate dual physiological states on a single platform make it an invaluable tool for targeted drug testing, furthering the development of organ-on-a-chip drug screening techniques.

Quantum Dot-Vitrimer Composites: An Approach for Reprocessable, Self-Healable, and Sustainable Luminescent Materials.

Quantum dots (QDs) are of great concern in many fields. However, they suffer from high toxicity and may lead to environmental pollution. We report the development of a QD-vitrimer composite with reprocessable, self-healable, and sustainable properties. Our QD-vitrimer composite reveals fine transparency and highly uniform QDs distribution without significant aggregation. The photoluminescence quantum yield (PLQY) is basically about four times higher than the commercial QD films. The QD-vitrimer composites can be recycled at least three times without any significant loss in structure and luminescence efficiency. A prototype light-emitting diode device is fabricated to demonstrate the promising potential of QD-vitrimer composites in real application. This research sheds light on developing environmentally friendly luminescent materials and opens up an avenue for designing advanced nanomaterials-vitrimer composites.

Spatial distributions of PM10-bound metal elements in the central part of western Taiwan and their potential emission sources and the carcinogenic health risks.

This study aimed to investigate the spatial distribution of metal elements in PM10 and their potential sources and associated health risks over a period of two years in eight locations in the central part of western Taiwan. The study revealed that the mass concentration of PM10 and the total mass concentration of 20 metal elements in PM10 were 39.0 µg m-3 and 4.74 µg m-3, respectively, with total metal elements accounting for approximately 13.0% of PM10. Of the total metal elements, 95.6% were crustal elements (Al, Ca, Fe, K, Mg, and Na), with trace elements (As, Ba, Cd, Cr, Co, Cu, Ga, Mn, Ni, Pb, Sb, Se, V, and Zn) contributing only 4.4%. Spatially, the inland areas exhibited higher PM10 concentrations due to lee-side topography and low wind speeds. In contrast, the coastal regions exhibited higher total metal concentrations because of the dominance of crustal elements from sea salt and crustal soil. Four primary sources of metal elements in PM10 were identified as sea salt (58%), re-suspended dust (32%), vehicle emissions and waste incineration (8%), and industrial emissions and power plants (2%). The positive matrix factorization (PMF) analysis results indicated that natural sources like sea salt and road dust contributed up to 90% of the total metal elements in PM10, while only 10% was attributed to human activities. The excess cancer risks (ECRs) associated with As, Co, and Cr(VI) were greater than 1 × 10-6, and the total ECR was 6.42 × 10-5. Although only 10% of total metal elements in PM10 came from human activities, they contributed to 82% of the total ECR.

Comparative single-cell profiling reveals distinct cardiac resident macrophages essential for zebrafish heart regeneration.

Zebrafish exhibit a robust ability to regenerate their hearts following injury, and the immune system plays a key role in this process. We previously showed that delaying macrophage recruitment by clodronate liposome (-1d_CL, macrophage-delayed model) impairs neutrophil resolution and heart regeneration, even when the infiltrating macrophage number was restored within the first week post injury (Lai et al., 2017). It is thus intriguing to learn the regenerative macrophage property by comparing these late macrophages vs. control macrophages during cardiac repair. Here, we further investigate the mechanistic insights of heart regeneration by comparing the non-regenerative macrophage-delayed model with regenerative controls. Temporal RNAseq analyses revealed that -1d_CL treatment led to disrupted inflammatory resolution, reactive oxygen species homeostasis, and energy metabolism during cardiac repair. Comparative single-cell RNAseq profiling of inflammatory cells from regenerative vs. non-regenerative hearts further identified heterogeneous macrophages and neutrophils, showing alternative activation and cellular crosstalk leading to neutrophil retention and chronic inflammation. Among macrophages, two residential subpopulations (hbaa+ Mac and timp4.3+ Mac 3) were enriched only in regenerative hearts and barely recovered after +1d_CL treatment. To deplete the resident macrophage without delaying the circulating macrophage recruitment, we established the resident macrophage-deficient model by administrating CL earlier at 8 d (-8d_CL) before cryoinjury. Strikingly, resident macrophage-deficient zebrafish still exhibited defects in revascularization, cardiomyocyte survival, debris clearance, and extracellular matrix remodeling/scar resolution without functional compensation from the circulating/monocyte-derived macrophages. Our results characterized the diverse function and interaction between inflammatory cells and identified unique resident macrophages prerequisite for zebrafish heart regeneration.

A Biomimicking and Multiarm Self-Indicating Nanoassembly for Site-Specific Photothermal-Potentiated Thrombolysis Assessed in Microfluidic and In Vivo Models.

Thrombolytic and antithrombotic therapies are limited by short circulation time and the risk of off-target hemorrhage. Integrating a thrombus-homing strategy with photothermal therapy are proposed to address these limitations. Using glycol chitosan, polypyrrole, iron oxide and heparin, biomimicking GCPIH nanoparticles are developed for targeted thrombus delivery and thrombolysis. The nanoassembly achieves precise delivery of polypyrrole, exhibiting biocompatibility, selective accumulation at multiple thrombus sites, and enhanced thrombolysis through photothermal activation. To simulate targeted thrombolysis, a microfluidic model predicting thrombolysis dynamics in realistic pathological scenarios is designed. Human blood assessments validate the precise homing of GCPIH nanoparticles to activated thrombus microenvironments. Efficient near-infrared phototherapeutic effects are demonstrated at thrombus lesions under physiological flow conditions ex vivo. The combined investigations provide compelling evidence supporting the potential of GCPIH nanoparticles for effective thrombus therapy. The microfluidic model also offers a platform for advanced thrombolytic nanomedicine development.

Factors influencing neutralizing antibody titers elicited by coronavirus disease 2019 vaccines.

The World Health Organization has highlighted the importance of an international standard (IS) for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) neutralizing antibody titer detection to calibrate diagnostic techniques. We applied an IS to calibrate neutralizing antibody titers (NTs) (international units/mL) in response to coronavirus disease 2019 (COVID-19) vaccination. Moreover, the association between different factors and neutralizing antibodies was analyzed. A total of 1667 serum samples were collected from participants receiving different COVID-19 vaccines. Antibody titers were determined by a microneutralization assay using live viruses in a biosafety level 3 (BSL-3) laboratory and a commercial serological MeDiPro kit. The titer determined using the MeDiPro kit was highly correlated with the NT determined using live viruses and calibrated using IS. Fever and antipyretic analgesic treatment were related to neutralizing antibody responses in ChAdOx1-S and BNT162b2 vaccinations. Individuals with diabetes showed a low NT elicited by MVC-COV1901. Individuals with hypertension receiving the BNT162b2 vaccine had lower NTs than those without hypertension. Our study provided the international unit (IU) values of NTs in vaccinated individuals for the development of vaccines and implementation of non-inferiority trials. Correlation of the influencing factors with NTs can provide an indicator for selecting COVID-19 vaccines based on personal attributes.

Overview of Neutralization Assays and International Standard for Detecting SARS-CoV-2 Neutralizing Antibody.

We aimed to review the existing literature on the different types of neutralization assays and international standards for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We comprehensively summarized the serological assays for detecting neutralizing antibodies against SARS-CoV-2 and demonstrated the importance of an international standard for calibrating the measurement of neutralizing antibodies. Following the coronavirus disease outbreak in December 2019, there was an urgent demand to detect neutralizing antibodies in patients or vaccinated people to monitor disease outcomes and determine vaccine efficacy. Therefore, many approaches were developed to detect neutralizing antibodies against SARS-CoV-2, such as microneutralization assay, SARS-CoV-2 pseudotype virus assay, enzyme-linked immunosorbent assay (ELISA), and rapid lateral flow assay. Given the many types of serological assays for quantifying the neutralizing antibody titer, the comparison of different assay results is a challenge. In 2020, the World Health Organization proposed the first international standard as a common unit to define neutralizing antibody titer and antibody responses against SARS-CoV-2. These standards are useful for comparing the results of different assays and laboratories.