Porcine reproductive and respiratory syndrome virus infection triggers HMGB1 release to promote inflammatory cytokine production

AbstractThe high mobility group box 1 (HMGB1) protein is an endogenous damage-associated molecular pattern (DAMP) molecule involved in the pathogenesis of various infectious agents. Based on meta-analysis of all publicly available microarray datasets, HMGB1 has recently been proposed as the most significant immune modulator during the porcine response to porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, the function of HMGB1 in PRRSV pathogenesis is unclear. In this study, we found that PRRSV infection triggers the translocation of HMGB1 from the nucleus to the extracellular milieu in MARC-145 cells and porcine alveolar macrophages. Although HMGB1 has no effect on PRRSV replication, HMGB1 promotes PRRSV-induced NF-κB activation and subsequent expression of inflammatory cytokines through receptors RAGE, TLR2 and TLR4. Our findings show that HMGB1 release, triggered by PRRSV infection, enhances the efficiency of virus-induced inflammatory responses, thereby providing new insights into the pathogenesis of PRRSV infection

Knowledge and attitudes of healthcare workers in Chinese intensive care units regarding 2009 H1N1 influenza pandemic

<p>Abstract</p> <p>Background</p> <p>To describe the knowledge and attitudes of critical care clinicians during the 2009 H1N1 influenza pandemic.</p> <p>Methods</p> <p>A survey conducted in 21 intensive care units in 17 provinces in China.</p> <p>Results</p> <p>Out of 733 questionnaires distributed, 695 were completed. Three hundred and fifty-six respondents (51.2%) reported their experience of caring for H1N1 patients. Despite the fact that 88.5% of all respondents ultimately finished an H1N1 training program, only 41.9% admitted that they had the knowledge of 2009 H1N1 influenza. A total of 572 respondents (82.3%) expressed willingness to care for H1N1 patients. Independent variables associated with increasing likelihood to care for patients in the logistic regression analysis were physicians or nurses rather than other professionals (odds ratio 4.056 and 3.235, p = 0.002 and 0.007, respectively), knowledge training prior to patient care (odds ratio 1.531, p = 0.044), and the confidence to know how to protect themselves and their patients (odds ratio 2.109, p = 0.001).</p> <p>Conclusion</p> <p>Critical care clinicians reported poor knowledge of H1N1 influenza, even though most finished a relevant knowledge training program. Implementation of appropriate education program might improve compliance to infection control measures, and willingness to work in a pandemic.</p

Unraveling the immunological landscape in acute pancreatitis progression to sepsis: insights from a Mendelian randomization study on immune cell traits

BackgroundAcute pancreatitis (AP) is a severe digestive system disorder with a significant risk of progressing to sepsis, a major cause of mortality. Unraveling the immunological pathways in AP is essential for developing effective treatments, particularly understanding the role of specific immune cell traits in this progression.MethodsEmploying a bidirectional two-sample Mendelian Randomization (MR) approach, this study first examined the causal relationship between AP and 731 immune cell traits to identify those significantly associated with AP. Subsequently, we explored the causal associations between 731 immune cell traits and sepsis. The analysis utilized extensive genome-wide association studies (GWAS) summary datasets, with a focus on identifying common immune cell traits with statistically significant causal associations between AP and sepsis.ResultsOur investigation identified 44 immune cell traits unidirectionally associated with AP and 36 traits unidirectionally associated with sepsis. Among these, CD127 on CD28+ CD45RA- CD8+ T cells emerged as a common mediator, accounting for 5.296% of the increased risk of sepsis in AP patients. This finding highlights the significant role of specific memory CD8+ T cells in the pathophysiology of AP and its progression to sepsis.ConclusionThis study elucidates the critical role of specific immune cell traits, particularly CD127hi memory CD8+ T cells, in the progression of AP to sepsis. Our findings provide a foundation for future research into targeted immune-modulatory therapies, potentially improving patient outcomes in AP-related sepsis and offering new insights into the complex immunological dynamics of this condition

Chip-scale solar thermal electrical power generation

There is an urgent need for alternative compact technologies that can derive and store energy from the sun, especially the large amount of solar heat that is not effectively used for power generation. Here, we report a combination of solution- and neat-film-based molecular solar thermal (MOST) systems, where solar energy can be stored as chemical energy and released as heat, with microfabricated thermoelectric generators to produce electricity when solar radiation is not available. The photophysical properties of two MOST couples are characterized both in liquid with a catalytical cycling setup and in a phase-interconvertible neat film. Their suitable photophysical properties let us combine them individually with a microelectromechanical ultrathin thermoelectric chip to use the stored solar energy for electrical power generation. The generator can produce, as a proof of concept, a power output of up to 0.1 nW (power output per unit volume up to 1.3 W m−3). Our results demonstrate that such a molecular thermal power generation system has a high potential to store and transfer solar power into electricity and is thus potentially independent of geographical restrictions.This work was supported by the K. & A. Wallenberg Foundation, the Swedish Foundation for Strategic Research, the Swedish Research Council Formas, the Swedish Energy Agency, the European Research Council (ERC) under grant agreement CoG, PHOTHERM - 101002131, the Catalan Institute of Advanced Studies (ICREA), and the European Union's Horizon 2020 Framework Programme under grant agreement no. 951801. The MEMS-TEG chip manufacture and experimentation were supported by the National Natural Science Foundation of China (grant 51776126). The authors would like to thank the Center for Advanced Electronic Materials and Devices (AEMD) and Instrumental Analysis Center of Shanghai Jiao Tong University (SJTU) and the startup fund of Shanghai Jiao Tong University. We thank Dr. Sarah Lerch and Prof. Ben Greatrex for reading and commenting on the manuscript. We acknowledge Neuroncollective.com and Daniel Spacek for the graphical abstract.With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).Peer reviewe

On-Line Analysis of Oil-Dissolved Gas in Power Transformers Using Fourier Transform Infrared Spectrometry

To address the problem of on-line dissolved gas analysis (DGA) of a power transformer, a Fourier transform infrared (FT-IR) spectrometer was used to develop an analysis instrument. Carbon monoxide (CO), carbon dioxide (CO2), methane (CH4), ethane (C2H6), ethylene (C2H4) and acetylene (C2H2) were the analytes for the FT-IR spectrometer while propane (C3H8), propylene (C3H6), propyne (C3H4), n-butane (n-C4H10) and iso-butane (iso-C4H10) were the interferents, which might exist in the dissolved gas but are not currently used as analytes for detecting an internal fault. The instrument parameters and analysis approach are first introduced. Specifically, an absorption spectra reading approach by switching two cone-type gas cells into separate light-paths was presented for reducing the effects of gas in the gaps between gas cells and spectrometers, scanning the background spectrum without clearing the sample cell, and increasing the dynamics. Then, the instrument was tested with a standard gas mixture that was extracted from insulation oil in a power transformer. The testing results show that the detection limit of every analyte component is lower than 0.1 &#956;L/L, and the detection limits of all analytes meet the detection requirements of oil-dissolved gas analysis, which means that the FT-IR spectrometer may be an ideal instrument due to its benefits, such as being maintenance-free and having a high stability

Involvement of tryptophan hydroxylase 2 gene polymorphisms in susceptibility to tic disorder in Chinese Han population

<p>Abstract</p> <p>Background</p> <p>Tryptophan hydroxylase-2 (TPH2) is a potential candidate gene for screening tic disorder (TD).</p> <p>Methods</p> <p>A case–control study was performed to examine the association between the TPH2 gene and TD. The Sequenom® Mass ARRAY iPLEX GOLD System was used to genotype two single nucleotide polymorphisms (SNPs) of the TPH2 gene in 149 TD children and in 125 normal controls.</p> <p>Results</p> <p>For rs4565946, individuals with the TT genotype showed a significantly higher risk of TD than those with TC plus CC genotypes [odds ratio (OR) =3.077, 95% confidence interval (CI): 1.273–7.437; <it>P</it> = 0.009], as did male TD children with the TT genotype (OR = 3.228, 95% CI: 1.153–9.040; <it>P</it> = 0.020). The G allele of rs4570625 was significantly more frequent in TD children with higher levels of tic symptoms (Yale Global Tic Severity Scale, YGTSS) than those in controls among the male children (OR = 1.684, 95%: 1.097–2.583; <it>P</it> = 0.017]. TD children with severe tic symptoms had significantly higher frequencies of rs4546946 TT genotype than did normal controls in boys (OR = 3.292, 95% CI: 1.139–9.513; <it>P</it> = 0.022). We also found that genotype distributions of both SNPs were different between the Asian and European populations.</p> <p>Conclusions</p> <p>Our results indicated that the TT genotype of rs4565946 is a potential genetic risk factor for TD, and the allele G of rs4570625 might be associated with the severity of tic symptoms in boys. These polymorphisms might be susceptibility loci for TD in the Chinese Han population. Because of the confounding of co-existing attention deficit hyperactivity disorder (ADHD),these findings need to be confirmed by studies in much larger samples.</p

Polymyxin B-induced skin hyperpigmentation: a rare case report and literature review

Abstract Background Polymyxin B (PMB), which is regarded as the ultimate antibacterial treatment against some intractable gram-negative bacteria with its outstanding anti-bacterial activities, inflicts several adverse effects on patients. However, skin hyperpigmentaion (SH) induced by PMB is very rare. Here, we report a case of polymyxin B-induced skin hyperpigmentation (PMB-iSH) in a 21-year-old female. To the best of our knowledge, this is the first case of PMB-iSH in China. Case presentation A 21-year-old female patient with sepsis received the administration of PMB by intravenous injection for the treatment of multi-drug resistant Klebsiella pneumoniae (MDR-KP) infection. She later suffered from a rare adverse drug reaction (ADR), namely PMB-iSH, after 5-day PMB administration during her treatment. There were multiple red rashes spread on the whole body skin at first. With the rashes fading away, SH with dark round spots appeared, associated with no pain or pruritus. The skin of the head and neck was darkened evidently, and dark brown spots were spread on the skin of trunk and limbs. About a month after her admission, urged by the relatives, the patient was transferred back to the local hospital for further treatment in the end, and her skin color didn’t recover to the previous state at that time. Conclusion Both our case and the literature review highlight that PMB can give rise to SH indeed. Clinicians and pharmacists should attach great importance to this rare pigmentary disorder and further investigation is warranted

PKM2/STAT1-mediated PD-L1 upregulation on neutrophils during sepsis promotes neutrophil organ accumulation by serving an anti-apoptotic role

Abstract Background Delayed neutrophil apoptosis during sepsis may impact neutrophil organ accumulation and tissue immune homeostasis. Elucidating the mechanisms underlying neutrophil apoptosis may help identify potential therapeutic targets. Glycolysis is critical to neutrophil activities during sepsis. However, the precise mechanisms through which glycolysis regulates neutrophil physiology remain under-explored, especially those involving the non-metabolic functions of glycolytic enzymes. In the present study, the impact of programmed death ligand-1 (PD-L1) on neutrophil apoptosis was explored. The regulatory effect of the glycolytic enzyme, pyruvate kinase M2 (PKM2), whose role in septic neutrophils remains unaddressed, on neutrophil PD-L1 expression was also explored. Methods Peripheral blood neutrophils were isolated from patients with sepsis and healthy controls. PD-L1 and PKM2 levels were determined by flow cytometry and Western blotting, respectively. Dimethyl sulfoxide (DMSO)-differentiated HL-60 cells were stimulated with lipopolysaccharide (LPS) as an in vitro simulation of septic neutrophils. Cell apoptosis was assessed by annexin V/propidium iodide (annexin V/PI) staining, as well as determination of protein levels of cleaved caspase-3 and myeloid cell leukemia-1 (Mcl-1) by Western blotting. An in vivo model of sepsis was constructed by intraperitoneal injection of LPS (5 mg/kg) for 16 h. Pulmonary and hepatic neutrophil infiltration was assessed by flow cytometry or immunohistochemistry. Results PD-L1 level was elevated on neutrophils under septic conditions. Administration of neutralizing antibodies against PD-L1 partially reversed the inhibitory effect of LPS on neutrophil apoptosis. Neutrophil infiltration into the lung and liver was also reduced in PD-L1−/− mice 16 h after sepsis induction. PKM2 was upregulated in septic neutrophils and promoted neutrophil PD-L1 expression both in vitro and in vivo. In addition, PKM2 nuclear translocation was increased after LPS stimulation, which promoted PD-L1 expression by directly interacting with and activating signal transducer and activator of transcription 1 (STAT1). Inhibition of PKM2 activity or STAT1 activation also led to increased neutrophil apoptosis. Conclusion In this study, a PKM2/STAT1-mediated upregulation of PD-L1 on neutrophils and the anti-apoptotic effect of upregulated PD-L1 on neutrophils during sepsis were identified, which may result in increased pulmonary and hepatic neutrophil accumulation. These findings suggest that PKM2 and PD-L1 could serve as potential therapeutic targets

The impact of fluid resuscitation via colon on patients with severe acute pancreatitis

Abstract Severe acute pancreatitis (SAP) is a life-threatening disease. Fluid Resuscitation Via Colon (FRVC) may be a complementary therapy for early controlled fluid resuscitation. But its clinical application has not been reported. This study aims to explore the impact of FRVC on SAP. All SAP patients with the first onset within 72 h admitted to the hospital were included from January 2014 to December 2018 through electronic databases of Ruijin hospital and were divided into FRVC group (n = 103) and non-FRVC group (n = 78). The clinical differences before and after the therapy between the two groups were analyzed. Of the 181 patients included in the analysis, the FRVC group received more fluid volume and reached the endpoint of blood volume expansion ahead of the non-FRVC group. After the early fluid resuscitation, the inflammation indicators in the FRVC group were lower. The rate of mechanical ventilation and the incidence of hypernatremia also decreased significantly. Using pure water for FRVC was more helpful to reduce hypernatremia. However, Kaplan–Meier 90-day survival between the two groups showed no difference. These results suggest that the combination of FRVC might benefit SAP patients in the early stage of fluid resuscitation, but there is no difference between the prognosis of SAP patients and that of conventional fluid resuscitation. Further prospective study is needed to evaluate the effect of FRVC on SAP patients

Clinical and molecular genetic characterization of familial MECP2 duplication syndrome in a Chinese family

Abstract Background Chromosomal duplication at the Xq28 region including the MECP2 gene, share consistent clinical phenotypes and a distinct facial phenotype known as MECP2 duplication syndrome. The typical clinical features include infantile hypotonia , mild dysmorphic features, a broad range of neurodevelopmental disorders, recurrent infections, and progressive spasticity. Methods This Chinese MECP2 duplication syndrome family includes six patients (five males and one female), and four asymptomatic female carriers. Two kinds of chips including 4x180K CNV + SNP chip and custom 8x60K CNV chip were used to detect MECP2 duplication, and then fluorescent in situ hybridization (FISH) analysis was performed to identify the exact copy number of MECP2. X-chromosome inactivation (XCI) analysis on AR gene was detected for all female family members, and the m icrosatellite analysis on MECP2 was used to validate the recombination event on MECP2 region. Results The affected male subjects presented with a broad range of neurodevelopmental symptoms (severe intellectual disability, developmental delay, seizure, language deficit, and autism spectrum disorder) as well as facial dysmorphism and other symptoms which were consistent with that of Western patients previous reported. Seizure is reported in Chinese patients for the first time. In addition, we validated three recombination events for the MECP2-duplication allele during maternal transmission due to X homologous recombination. Conclusions We provided the largest known Chinese pedigree with MECP2 duplication syndrome. The detailed clinical description and molecular genetic characterization in all affected family members further delineate the typical phenotype of this genomic disorder in Chinese population