Cystatin F attenuates neuroinflammation and demyelination following murine coronavirus infection of the central nervous system.

BACKGROUND: Cystatin F is a secreted lysosomal cysteine protease inhibitor that has been implicated in affecting the severity of demyelination and enhancing remyelination in pre-clinical models of immune-mediated demyelination. How cystatin F impacts neurologic disease severity following viral infection of the central nervous system (CNS) has not been well characterized and was the focus of this study. We used cystatin F null-mutant mice (Cst7-/-) with a well-established model of murine coronavirus-induced neurologic disease to evaluate the contributions of cystatin F in host defense, demyelination and remyelination. METHODS: Wildtype controls and Cst7-/- mice were intracranially (i.c.) infected with a sublethal dose of the neurotropic JHM strain of mouse hepatitis virus (JHMV), with disease progression and survival monitored daily. Viral plaque assays and qPCR were used to assess viral levels in CNS. Immune cell infiltration into the CNS and immune cell activation were determined by flow cytometry and 10X genomics chromium 3' single cell RNA sequencing (scRNA-seq). Spinal cord demyelination was determined by luxol fast blue (LFB) and Hematoxylin/Eosin (H&E) staining and axonal damage assessed by immunohistochemical staining for SMI-32. Remyelination was evaluated by electron microscopy (EM) and calculation of g-ratios. RESULTS: JHMV-infected Cst7-/- mice were able to control viral replication within the CNS, indicating that cystatin F is not essential for an effective Th1 anti-viral immune response. Infiltration of T cells into the spinal cords of JHMV-infected Cst7-/- mice was increased compared to infected controls, and this correlated with increased axonal damage and demyelination associated with impaired remyelination. Single-cell RNA-seq of CD45 + cells enriched from spinal cords of infected Cst7-/- and control mice revealed enhanced expression of transcripts encoding T cell chemoattractants, Cxcl9 and Cxcl10, combined with elevated expression of interferon-g (Ifng) and perforin (Prf1) transcripts in CD8 + T cells from Cst7-/- mice compared to controls. CONCLUSIONS: Cystatin F is not required for immune-mediated control of JHMV replication within the CNS. However, JHMV-infected Cst7-/- mice exhibited more severe clinical disease associated with increased demyelination and impaired remyelination. The increase in disease severity was associated with elevated expression of T cell chemoattractant chemokines, concurrent with increased neuroinflammation. These findings support the idea that cystatin F influences expression of proinflammatory gene expression impacting neuroinflammation, T cell activation and/or glia cell responses ultimately impacting neuroinflammation and neurologic disease.

Corrigendum: Quercetin suppresses ovariectomy-induced osteoporosis in rat mandibles by regulating autophagy and the NLRP3 pathway.

[This corrects the article DOI: 10.1177/15353702231211977.].

Advancements in Research on Duck Tembusu Virus Infections.

Duck Tembusu Virus (DTMUV) is a pathogen of the Flaviviridae family that causes infections in poultry, leading to significant economic losses in the duck farming industry in recent years. Ducks infected with this virus exhibit clinical symptoms such as decreased egg production and neurological disorders, along with serious consequences such as ovarian hemorrhage, organ enlargement, and necrosis. Variations in morbidity and mortality rates exist across different age groups of ducks. It is worth noting that DTMUV is not limited to ducks alone; it can also spread to other poultry such as chickens and geese, and antibodies related to DTMUV have even been found in duck farm workers, suggesting a potential risk of zoonotic transmission. This article provides a detailed overview of DTMUV research, delving into its genomic characteristics, vaccines, and the interplay with host immune responses. These in-depth research findings contribute to a more comprehensive understanding of the virus's transmission mechanism and pathogenic process, offering crucial scientific support for epidemic prevention and control.

Carbon pools in forest systems and new estimation based on an investigation of carbon sequestration.

Forests, the ancient wooden giants, are both symbols of natural beauty and reservoirs of carbon stocks. The current climate crisis has created an urgent need for an in-depth study of forest ecosystems and carbon stocks. Based on forest inventory data from field surveys and four bioclimatic zones [Zone 1 (Z1, humid forest), Zone 2 (Z2, semi-humid forest), Zone 3 (Z3, semi-humid to semi-arid forest-grassland), and Zone 4 (Z4, semi-arid typical grassland)], two methods [Method 1 (M1) and Method 2 (M2)] were used to estimate carbon stocks in forest ecosystems in Shaanxi Province, China, and explored the spatial patterns of carbon pools and potential influences. The total forest ecosystem carbon pool amounted to 520.80 Tg C, of which 53.60% was stored aboveground, 17.16% belowground, and 29.24% in soil (depth of 0-10 cm). Spatially, there were marked north-south gradients in both biomass (Z2 > Z3 > Z1 > Z4) and soil organic carbon densities (Z1 > Z2 > Z3 > Z4). The differences between aboveground and belowground biomass carbon density across broadleaf, needle-leaf, and broadleaf and needle-leaf mixed forest were not pronounced, while soil organic carbon density had the order of broadleaf (18.38 Mg C/ha) > needle-leaf (11.29 Mg C/ha) > broadleaf and needle-leaf mixed forest (10.33 Mg C/ha). Under an ideal scenario that excludes external factors, mainly forest growth, the sequestration potential of forest biomass by 2032 was estimated by M1 as 85.43 Tg, and by M2 to be substantially higher at 176.21 Tg. As of 2062, M1 estimated 155.97 Tg of sequestration potential for forest biomass. The spatial patterns of forest biomass and soil carbon density were closely related to climatic factors, and these relationships allowed the spatial division into two distinct climatic regions. Moreover, biomass carbon density was significantly correlated with the normalized difference vegetation index, soil silt, and elevation. This study provides key information for promoting the strategic shift from light-green to deep-green forest systems in Shannxi Province and updates the estimation methods of forest ecosystems' carbon pools based on field surveys.

Miniaturized inkjet-printed flexible ion-selective sensing electrodes with the addition of graphene in PVC layer for fast response real-time monitoring applications.

In this letter, we propose a miniaturization scheme of inkjet printed ionic sensing electrodes by adding graphene into the ion-selective PVC film not only to reduce the impedance of the ionic liquid layer of the electrode but also to increase the electrode capacitance for the reduction of the response time. Based on the scheme, we present a fully inkjet-printed electrochemical ion-selective sensor comprising a working electrode and reference electrode, which are inkjet-printed Ag NPs/PEDOT:PSS-graphene/PVC-graphene and Ag/AgCl(s)/ionic liquid PVC-graphene layer structures, respectively. The printed ion-selective working electrode has been miniaturized to a size of 22,400 µm2 equivalent to a square shape of ∼150 × 150 µm2 comparable to the size of a human cell. By adding graphene to the ion selective PVC film, more than 90 % charge transfer resistance reduction can be achieved and the shunt capacitance is increased by 3.4-fold in shunt capacitance compared to the film without graphene, thereby more than 33 % reduction of the response time required to reach equilibrium. Meanwhile, these miniaturized potassium sensors using the working electrodes with/without adding graphene have been integrated with in-lab signal-processing and wireless-transmission module to yield similar results to the one measured by commercial electrochemical workstation showing a great potential for real-time monitoring in portable clinical trials. Specifically, the proposed sensor utilizing graphene-enhanced electrodes demonstrates a linearity uncertainty of 2.9 mV, which is approximately half of the uncertainty observed in the sensors lacking graphene integration.

Three-photon excited fluorescence microscopy enables imaging of blood flow, neural structure and inflammatory response deep into mouse spinal cord in vivo.

Nonlinear optical microscopy enables non-invasive imaging in scattering samples with cellular resolution. The spinal cord connects the brain with the periphery and governs fundamental behaviors such as locomotion and somatosensation. Because of dense myelination on the dorsal surface, imaging to the spinal grey matter is challenging, even with two-photon microscopy. Here we show that three-photon excited fluorescence (3PEF) microscopy enables multicolor imaging at depths of up to ~550 µm into the mouse spinal cord, in vivo. We quantified blood flow across vessel types along the spinal vascular network. We then followed the response of neurites and microglia after occlusion of a surface venule, where we observed depth-dependent structural changes in neurites and interactions of perivascular microglia with vessel branches upstream from the clot. This work establishes that 3PEF imaging enables studies of functional dynamics and cell type interactions in the top 550 µm of the murine spinal cord, in vivo.

Effects of mitral valve disease etiology on the outcomes of mechanical and biological valve replacement: retrospective cohort study.

INTRODUCTION: The choice of an artificial mitral valve (MV) is a crucial clinical decision that affects the long-term survival and quality of life of patients. However, current guidelines recommend selecting MV based on patient age and life expectancy at the time of mitral valve replacement (MVR), without considering the etiology of MV disease. This study aimed to investigate whether MV disease etiology should be considered when choosing a valve for MVR and to evaluate the impact of MV disease etiology on long-term patient survival. METHODS: Using data (2002-2018) from Taiwan's National Health Insurance Research Database, the authors conducted a nationwide retrospective cohort study to compare the biological and mechanical valves in terms of all-cause mortality as the primary outcome. The inverse probability of the treatment weighting method was used to reduce the effects of the confounding factors. The following etiologies were assessed: infective endocarditis, rheumatic heart disease, ischemic mitral regurgitation, and degenerative mitral regurgitation. RESULTS: In patients aged below 70 years, it was observed that mechanical valves demonstrated an association with benefits compared to biological valves in the context of survival. In patients with infective endocarditis aged below 72 years, mechanical valves were associated with survival benefits, but not in those with stroke during hospitalization. These valves were also found to be linked with survival advantages for patients with rheumatic heart disease aged below 60 years and for those with degenerative mitral regurgitation aged below 72 years. However, no age-dependent effects of valve type on all-cause mortality were observed in patients with ischemic mitral regurgitation. CONCLUSION: The etiology of MV disease appears to be important in the selection of a suitable MV and determination of a cutoff age for mechanical and biological MVR.

Expeditious Synthesis of Gwanakoside A and the Chloronaphthol Glycoside Congeners.

The synthesis of gwanakoside A, a chlorinated naphthol bis-glycoside, and its analogues was achieved through stepwise chlorination and donor-equivalent controlled regioselective phenol glycosylation with glycosyl N-phenyltrifluoroacetimidates as donors. Gwanakoside A displayed considerable inhibitory effects against various cancer cells and Staphylococcus aureus strains.

Early Surgery for Infective Endocarditis Complicated With Neurologic Injury.

OBJECTIVES: To estimate the association between early surgery and the risk of mortality in patients with left-sided infective endocarditis in the context of stroke. DESIGN: Retrospective cohort study. SETTING: This study was a multiinstitution study based on the Chang Gung Research Database, which contains electronic medical records from 7 hospitals in northern and southern Taiwan; these include 2 medical centers, 2 regional hospitals, and 3 district hospitals. PARTICIPANTS: Patients with active left-sided infective endocarditis who underwent valve surgery between September 2002 and December 2018. INTERVENTIONS: The authors divided patients into 2 groups, with versus without preoperative neurologic complications, had undergone early (within 7 d) or later surgery, and with brain ischemia or hemorrhage. MEASUREMENTS AND MAIN RESULTS: Three hundred ninety-two patients with a median time from diagnosis to surgery of 6 days were included. No significant differences in postoperative stroke, in-hospital mortality, or follow-up outcomes were observed between the patients with and without neurologic complications. Among the patients with preoperative neurologic complications, patients who underwent early surgery had a lower 30-day postoperative mortality rate (13.1% v 25.8%; hazard ratio, 0.21; 95% CI 0.07-0.67). In the subgroup analysis of the comparison between brain ischemia and hemorrhage groups, there was no significant between-group difference in the in-hospital outcomes or outcomes after discharge. CONCLUSIONS: Early cardiac surgery may be associated with more favorable clinical outcomes in patients with preoperative neurologic complications. Thus, preoperative neurologic complications should not delay surgical interventions.

Rubisco Accumulation Factor1-like (RAFL) interacts with RAF1 to mediate Rubisco assembly in Arabidopsis.

Rubisco catalysis a rate-limiting step in photosynthesis. It is a complex of eight large (RbcL) and eight small (RbcS) subunits. The biogenesis of Rubisco requires assembly chaperones. One of the key Rubisco assembly chaperones, Rubisco accumulation factor1 (RAF1), assembled as a dimer, acts downstream of chaperonin-assisted RbcL folding by stabilizing RbcL antiparallel dimers for assembly into RbcL8 complexes. In maize, lacking RAF1 causes Rubisco deficient and seedling lethal. A RAF1 homologue, RAF1-like (RAFL), has been detected in Arabidopsis. We found RAFL shares 61.98 % sequence similarity with RAF1. They have similar conserved domains, predicted 3D structures and gene expression pattern. Phylogenetic tree analysis showed that RAFL and RAF1 only present in analyzed dicots, while only one copy of RAF presented in monocots, mosses and green algae. Combined analysis by three different protein-protein interaction methods showed that RAFL interacts with RAF1 both in vivo and in vitro. Taken together, we conclude that RAFL and RAF1 are close paralogous genes, and they can form heterodimer and/or homodimers to mediate Rubisco assembly in Arabidopsis.

Exposure to particulate matter may affect semen quality via trace metals: Evidence from a retrospective cohort study on fertile males.

Particulate matter (PM) exposure may be associated with male semen quality. Besides, PM exposure induces up and down levels of trace metals in tissues or organs. The levels of trace metals in semen are critical for adverse male semen quality. This study aims to evaluate the concentrations of seminal-level trace metals in fertile men and assess its associations with PM exposure and to explore the mediation role of trace metals in seminal plasma plays in the relationship between PM exposure and semen quality. Total 1225 fertile men who participated in a cohort study from 2014 to 2016 were finally recruited. Multivariate linear regression was applied to explore associations between each two of PM exposure, trace metals and semen parameters. 1-year PM2.5 and PM10 exposure levels were positively associated with arsenic (As), mercury (Hg), lanthanum (La), praseodymium (Pr), neodymium (Nd) but negatively associated with vanadium (V), magnesium (Mg), strontium (Sr), barium (Ba) in semen. It was also found that most of the elements were associated with total sperm number, followed by sperm concentration. Redundancy analysis (RDA) also determined several strong positive correlations or negative correlations between 1-year PM exposure and trace metals. Mediation analysis found that trace metals had a potentially compensatory or synergetic indirect effect on the total effect of the association between 1-year PM exposure and semen quality. The retrospective cohort study provides long-term PM exposure that may cause abnormal semen quality by affecting seminal plasma element levels.

The role of autophagy in SIM mediated anti-inflammatory osteoclastogenesis through NLRP3 signaling pathway.

BACKGROUND: Inflammatory bone resorption is a prominent risk factor for implantation failure. Simvastatin (SIM) has anti-inflammatory effects independent of cholesterol lowering and reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts. However, the specific mechanism of inflammatory bone loss alleviation by SIM remains to be elucidated. We hypothesized that SIM relieves inflammatory bone loss by modulating autophagy and suppressing the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) signaling pathway. METHODS AND RESULTS: RAW264.7 cells were stimulated by lipopolysaccharide (LPS) after being pretreated with various concentrations of SIM. Osteoclast (OC) differentiation, formation and activity were evaluated by tartrate-resistant acid phosphatase staining, F-actin ring staining and bone resorption pit assays, respectively. We observed autophagosomes by transmission electron microscopy. Then NLRP3 inhibitor MCC950 was used to further explore the corresponding molecular mechanism underlying anti-inflammatory bone resorption, the expression of autophagy-related proteins and NLRP3 signaling pathway factors in pre-OCs were evaluated by western blot analysis, and the expression of OC-specific molecules was analyzed using reverse transcription-quantitative polymerase chain reaction. The results showed that SIM decreased the expression of tumor necrosis factor-α, whereas increased Interleukin-10. In addition, SIM inhibited LPS-induced OC differentiation, formation, bone resorption activity, the level of autophagosomes, and OC-specific markers. Furthermore, SIM significantly suppressed autophagy by downregulating LC3II, Beclin1, ATG7, and NLRP3-related proteins expression while upregulating P62 under inflammatory conditions. CONCLUSIONS: SIM may reduce autophagy secretion to attenuate LPS-induced osteoclastogenesis and the NLRP3 signaling pathway participates in this process, thus providing theoretical basis for the application of this drug in peri-implantitis.

Sex Differences in Epidemiological Distribution and Outcomes of Surgical Mitral Valve Disease.

BACKGROUND: Mitral valve (MV) disease is the most common form of valvular heart disease. Findings that indicate women have a higher risk for unfavorable outcomes than men remain controversial. This study aimed to determine the sex-based differences in epidemiological distributions and outcomes of surgery for MV disease.Methods and Results: Overall, 18,572 patients (45.3% women) who underwent MV surgery between 2001 and 2018 were included. Outcomes included in-hospital death and all-cause mortality during follow up. Subgroup analysis was conducted across different etiologies, including infective endocarditis (IE), degenerative, ischemic, and rheumatic mitral pathology. The overall MV repair rate was lower in women than in men (20.5% vs. 30.6%). After matching, 6,362 pairs (woman : man=1 : 1) of patients were analyzed. Women had a slightly higher risk for in-hospital death than men (10.8% vs. 9.8%; odds ratio [OR]: 1.11, 95% confidence interval [CI]: 0.99-1.24; P=0.075). Women tended to have a higher incidence of de novo dialysis (9.8% vs. 8.6%; P=0.022) and longer intensive care unit stay (8 days vs. 7.1 days; P<0.001). Women with IE had poorer in-hospital outcomes than men; however, there were no sex differences in terms of all-cause mortality. CONCLUSIONS: Sex-based differences of MV intervention still persist. Although long-term outcomes were comparable between sexes, women, especially those with IE, had worse perioperative outcomes than men.

Outcomes of Endovascular Treatment for Infective Aortic Aneurysms　- A Multicenter Retrospective Study.

BACKGROUND: In Taiwan, infective native aortic aneurysms (INAAs) are relatively common, so the aim of present study was to demonstrate the comparative outcomes of endovascular repair for thoracic and abdominal INAAs.Methods and Results: Patients with naïve thoracic or abdominal INAAs managed with endovascular repair between 2001 and 2018 were included in this multicenter retrospective cohort. The confounding factors were adjusted with propensity score (PS). Of the 39 thoracic and 43 abdominal INAA cases, 41 (50%) presented with aneurysmal rupture, most of which were at the infrarenal abdominal (n=35, 42.7%) or descending thoracic aorta (n=25, 30.5%). Salmonella spp. was the most frequently isolated pathogen. The overall in-hospital mortality rate was 18.3%. The risks of in-hospital death and death due to rupture were significantly lower with thoracic INAAs (12.8% vs. 23.3%; PS-adjusted odds ratio (OR) 0.24, 95% confidence interval (CI) 0.06-0.96; 0.1% vs. 9.3%; PS-adjusted OR 0.11, 95% CI 0.01-0.90). During a mean follow-up of 2.5 years, the risk of all-cause death was significantly higher with thoracic INAAs (35.3% vs. 15.2%; PS-adjusted HR 6.90, 95% CI 1.69-28.19). Chronic kidney disease (CKD) was associated with death. CONCLUSIONS: Compared with thoracic INAAs, endovascular repair of abdominal INAAs was associated with a significantly higher in-hospital mortality rate. However, long-term outcomes were worse for thoracic INAAs, with CKD and infections being the most important predictor and cause of death, respectively.

Association of Valve Size and Hemodynamic Performance With Clinical Outcomes in Aortic Valve Replacement　- A Long-Term Follow-up in an Asian Population.

BACKGROUND: Studies of the influence of smaller body type on the severity of prosthesis-patient mismatch (PPM) after small-sized surgical aortic valve replacement (SAVR) are few, but the issue is particularly relevant for Asian patients.Methods and Results: 695 patients who underwent SAVR with bioprosthetic valves had their hemodynamic valve performance analyzed at 3 months, 1 year, 3 years, and 5 years after operation, and clinical outcomes were assessed. The patients were stratified into 3 valve size groups: 19/21, 23, and 25/27 mm. A smaller valve was associated with higher mean pressure gradients at the 4 time points after operation (P trend <0.05). However, the 3 valve size groups demonstrated no significant differences in the risk of clinical events. At none of the time points did patients with projected PPM show increased mean pressure gradients (P>0.05), whereas patients with measured PPM did (P<0.05). Compared with patients with projected PPM, those with measured PPM demonstrated higher rates of infective endocarditis readmission (adjusted hazard ratio [aHR] 3.31, 95% confidence interval [CI] 1.06-10.39) and a higher risk of composite outcomes (aHR 1.45, 95% CI 0.95-2.22, P=0.087). CONCLUSIONS: Relative to those receiving larger valves, patients receiving small bioprosthetic valves had poorer hemodynamic performance but did not demonstrate differences in clinical events in long-term follow-up.

Alterations in sperm DNA methylation may as a mediator of paternal air pollution exposure and offspring birth outcomes: Insight from a birth cohort study.

Paternal exposure to environmental risk factors influences the offspring health. This study aimed to evaluate the association between paternal air pollution exposure mediated by sperm DNA methylation and adverse birth outcomes in offspring. We recruited 1607 fertile men and their partners from 2014 to 2016 and collected semen samples to detect sperm DNA methylation. Multivariate linear regression and weighted quantile sum regression models were used to assess the associations between paternal air pollution exposure and offspring birth outcomes. A critical exposure window was identified. Reduced representation bisulfite sequencing was used to detect sperm DNA methylation. The results demonstrated that high paternal exposure to PM2.5 (ß = -211.31, 95% CI: (-386.37, -36.24)), PM10 (ß = -178.20, 95% CI: (-277.13, -79.27)), and NO2 (ß = -84.22, 95% CI: (-165.86, -2.57)) was negatively associated with offspring's birthweight, especially in boys. Additionally, an early exposure window of 15-69 days before fertilization was recognized to be the key exposure window, which increased the risk of low birth weight and small for gestational age. Furthermore, paternal co-exposure to six air pollutants contributed to lower birthweight (ß = -51.91, 95% CI: (-92.72, -11.10)) and shorter gestational age (ß = -1.72, 95% CI: (-3.26, -0.17)) and PM2.5 was the most weighted pollutant. Paternal air pollution exposure resulted in 10,328 differentially methylated regions and the IGF2R gene was the key gene involved in the epigenetic process. These differentially methylated genes were predominantly associated with protein binding, transcriptional regulation, and DNA templating. These findings indicate that spermatogenesis is a susceptible window during which paternal exposure to air pollution affects sperm DNA methylation and the birth outcomes of offspring.

Duck Tembusu virus infection activates the MKK3/6-p38 MAPK signaling pathway to promote virus replication.

Duck Tembusu virus (DTMUV) infection poses a serious threat to ducks, chickens, and geese, causing a range of detrimental effects, including reduced egg production, growth retardation, and even death. These consequences lead to substantial economic losses for the Chinese poultry industry. Although it is established that various viral infections can trigger activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway, the precise role and mechanisms underlying p38 MAPK activation in DTMUV infection remain poorly understood. To address this knowledge gap, we conducted a study to investigate whether the replication of DTMUV necessitates the activation of p38 MAPK. We found that DTMUV infection stimulates activation of the MKK3/6-p38 MAPK pathway, and the activation of p38 MAPK increases with viral titer. Subsequently, the use of the small molecule inhibitor SB203580 significantly reduced DTMUV replication by inhibiting p38 MAPK activity. Furthermore, downregulation of p38 MAPK protein expression by siRNA also inhibited DTMUV replication, whereas transient transfection of p38 MAPK protein promoted DTMUV replication. Interestingly, we found that the DTMUV capsid protein activates p38 MAPK, and there is interaction between DTMUV capsid and p38 MAPK. Finally, we found that DTMUV infection induces elevated mRNA expression of IFN-α, IFN-ß, IFN-γ, IL-1ß, IL-6, and IL-12, which is associated with p38 MAPK activity. These results indicated that virus hijacking of p38 activation is a crucial event for DTMUV replication, and that pharmacological blockade of p38 activation represents a potential anti-DTMUV strategy.

Mechanical Versus Bioprosthetic Aortic Valve Replacement in Patients Undergoing Bentall Procedure.

BACKGROUND: The widely used Bentall procedure is the criterion standard treatment for aortic root pathology. Studies comparing the long-term outcomes of bioprosthetic and mechanical valves in patients undergoing the Bentall procedure are limited. METHODS AND RESULTS: Patients who underwent the Bentall procedure with a bioprosthetic or mechanical valve between 2001 and 2018 were identified from Taiwan's National Health Insurance Research Database. The primary outcome of interest was all-cause mortality. Inverse probability of treatment weighting was performed to compare the 2 prosthetic types. In total, 1052 patients who underwent the Bentall procedure were identified. Among these patients, 351 (33.4%) and 701 (66.6%) chose bioprosthetic and mechanical valves, respectively. After inverse probability of treatment weighting, no significant differences in the in-hospital mortality (odds ratio, 0.96 [95% CI, 0.77-1.19]; P=0.716) and all-cause mortality (34.1% vs. 38.1%; hazard ratio, 0.90 [95% CI, 0.78-1.04]; P=0.154) were observed between the groups. The benefits of relative mortality associated with mechanical valves were apparent in younger patients and persisted until ≈50 years of age. CONCLUSIONS: No differences in survival benefits were observed between the valves in patients who underwent the Bentall procedure. Additionally, bioprosthetic valves may be a reasonable choice for patients aged >50 years when receiving the Bentall procedure in this valve-in-valve era.

Microglia influence immune responses and restrict neurologic disease in response to central nervous system infection by a neurotropic murine coronavirus.

Intracranial (i.c.) inoculation of susceptible mice with a glial-tropic strain of mouse hepatitis virus (JHMV), a murine coronavirus, results in an acute encephalomyelitis followed by viral persistence in white matter tracts accompanied by chronic neuroinflammation and demyelination. Microglia serve numerous functions including maintenance of the healthy central nervous system (CNS) and are among the first responders to injury or infection. More recently, studies have demonstrated that microglia aid in tailoring innate and adaptive immune responses following infection by neurotropic viruses including flaviviruses, herpesviruses, and picornaviruses. These findings have emphasized an important role for microglia in host defense against these viral pathogens. In addition, microglia are also critical in optimizing immune-mediated control of JHMV replication within the CNS while restricting the severity of demyelination and enhancing remyelination. This review will highlight our current understanding of the molecular and cellular mechanisms by which microglia aid in host defense, limit neurologic disease, and promote repair following CNS infection by a neurotropic murine coronavirus.

Transcriptomic analysis reveals upregulated host metabolisms and downregulated immune responses or cell death induced by acute African swine fever virus infection.

The African swine fever virus is a virulent and communicable viral disease that can be transmitted by infected swine, contaminated pork products, or soft tick vectors. Nonstructural proteins encoded by ASFV regulate viral replication, transcription, and evasion. However, the mechanisms underlying the host response to ASFV infection remain incompletely understood. In order to enhance comprehension of the biology and molecular mechanisms at distinct time intervals (6, 12, 24 h) post infection, transcriptome analyses were executed to discern differentially expressed genes (DEGs) between ASFV and mock-infected PAMs. The transcriptomic analysis unveiled a total of 1,677, 2,122, and 2,945 upregulated DEGs and 933, 1,148, and 1,422 downregulated DEGs in ASFV- and mock-infected groups at 6, 12, and 24 h.p.i.. The results of the transcriptomic analysis demonstrated that the infection of ASFV significantly stimulated host metabolism pathways while concurrently inhibiting the expression of various immune responses and cell death pathways. Our study offers crucial mechanistic insights into the comprehension of ASFV viral pathogenesis and the multifaceted host immune responses. The genes that were dysregulated may serve as potential candidates for further exploration of anti-ASFV strategies.