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.

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.

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.

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.

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.

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.

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.

Microglia Do Not Restrict SARS-CoV-2 Replication following Infection of the Central Nervous System of K18-Human ACE2 Transgenic Mice.

Unlike SARS-CoV-1 and MERS-CoV, infection with SARS-CoV-2, the viral pathogen responsible for COVID-19, is often associated with neurologic symptoms that range from mild to severe, yet increasing evidence argues the virus does not exhibit extensive neuroinvasive properties. We demonstrate SARS-CoV-2 can infect and replicate in human iPSC-derived neurons and that infection shows limited antiviral and inflammatory responses but increased activation of EIF2 signaling following infection as determined by RNA sequencing. Intranasal infection of K18 human ACE2 transgenic mice (K18-hACE2) with SARS-CoV-2 resulted in lung pathology associated with viral replication and immune cell infiltration. In addition, ∼50% of infected mice exhibited CNS infection characterized by wide-spread viral replication in neurons accompanied by increased expression of chemokine (Cxcl9, Cxcl10, Ccl2, Ccl5 and Ccl19) and cytokine (Ifn-λ and Tnf-α) transcripts associated with microgliosis and a neuroinflammatory response consisting primarily of monocytes/macrophages. Microglia depletion via administration of colony-stimulating factor 1 receptor inhibitor, PLX5622, in SARS-CoV-2 infected mice did not affect survival or viral replication but did result in dampened expression of proinflammatory cytokine/chemokine transcripts and a reduction in monocyte/macrophage infiltration. These results argue that microglia are dispensable in terms of controlling SARS-CoV-2 replication in in the K18-hACE2 model but do contribute to an inflammatory response through expression of pro-inflammatory genes. Collectively, these findings contribute to previous work demonstrating the ability of SARS-CoV-2 to infect neurons as well as emphasizing the potential use of the K18-hACE2 model to study immunological and neuropathological aspects related to SARS-CoV-2-induced neurologic disease. IMPORTANCE Understanding the immunological mechanisms contributing to both host defense and disease following viral infection of the CNS is of critical importance given the increasing number of viruses that are capable of infecting and replicating within the nervous system. With this in mind, the present study was undertaken to evaluate the role of microglia in aiding in host defense following experimental infection of the central nervous system (CNS) of K18-hACE2 with SARS-CoV-2, the causative agent of COVID-19. Neurologic symptoms that range in severity are common in COVID-19 patients and understanding immune responses that contribute to restricting neurologic disease can provide important insight into better understanding consequences associated with SARS-CoV-2 infection of the CNS.

Fluoroquinolones and Risk of Aortic Aneurysm or Dissection in Patients With Congenital Aortic Disease and Marfan Syndrome.

BACKGROUND: Fluoroquinolone use can be associated with an increased risk of aortic aneurysm (AA) or aortic dissection (AD). The US Food and Drug Administration recently warned against fluoroquinolone use for high-risk patients, such as those with Marfan syndrome. However, the association between fluoroquinolone use and AA/AD risk was unknown in these high-risk patients and therefore it was studied in this work.Methods and Results: Data were collected from a national database between 2000 and 2017 for 550 patients with AA/AD and any congenital aortic disease (mean age 41.5 years; 415 with Marfan syndrome). A case cross-over study was conducted to compare the risk of aortic events (AA/AD) associated with fluoroquinolone and amoxicillin use between the hazard period (from -60 days to -1 day) and a randomly selected reference period (-180 to -121 days; -240 to -181 days; and -300 to -241 days). Compared to the reference period without fluoroquinolone use, fluoroquinolone use during the hazard period was not associated with a greater risk of AA/AD (1.09% vs. 1.09%; odds ratio [OR] 1.000; 95% confidence interval [CI] 0.32-3.10), AA (OR 0.67; 95% CI 0.11-3.99), or AD (OR 1.33; 95% CI 0.30-5.96) in patients with congenital aortic disease or Marfan syndrome. This lack of association was maintained in subgroup analysis, including Marfan syndrome or not, age (≤50 vs. >50 years) and sex. CONCLUSIONS: Fluoroquinolone use was not associated with an increased risk of AA/AD in patients with congenital aortic disease, including Marfan syndrome. More evidence is required for a fluoroquinolone pharmacovigilance plan in these patients.

Effect of Hospital Volume on Outcome of Extracorporeal Membrane Oxygenation Support　- Nationwide Population-Based Cohort Study in Taiwan.

BACKGROUND: In modern critical care, extracorporeal membrane oxygenation (ECMO) is crucial in the management of severe respiratory and cardiac failure. Nationwide studies of the relationship between hospital volume and outcomes of ECMO use are unavailable.Methods and Results: Using Taiwan's National Health Insurance Research Database, we identified 11,734 adult patients who received ECMO support in 101 hospitals between January 1, 2001, and December 31, 2017. Outcomes included in-hospital mortality, 1-year mortality, and ECMO-related complications. Cox proportional hazards model, locally estimated scatterplot smoothing, and restricted cubic spline regression were used to analyze the volume-outcome relationship. The overall in-hospital mortality rate was 65.5%, and the 1-year mortality rate was 70.6% in this database. The 101 hospitals were divided into 4 groups based on annual volume. The in-hospital and 1-year mortality rates were significantly lower in the high-volume group (annual volume >40) than in the low-volume group (annual volume <10). CONCLUSIONS: For critical care, high-volume hospitals have superior short-term and mid-term outcomes. To make the medical system equitable and reasonable, establishing a rapid and efficient nationwide referral system should be considered.

Surgical volume and outcomes of surgical ablation for atrial fibrillation: a nationwide population-based cohort study.

BACKGROUND: Atrial fibrillation is the most common cardiac arrythmia and causes many complications. Sinus rhythm restoration could reduce late mortality of atrial fibrillation patients. The Maze procedure is the gold standard for surgical ablation of atrial fibrillation. Higher surgical volume has been documented with favorable outcomes of various cardiac procedures such as mitral valve surgery and aortic valve replacement. We aimed to determine the volume-outcome relationship (i.e., association between surgical volume and outcomes) for the concomitant Maze procedure during major cardiac surgeries. METHODS: This nationwide population-based cohort study retrieved data from the Taiwan National Health Insurance Research Database. Adult patients undergoing concomitant Maze procedures during 2010-2017 were identified; consequently, 2666 patients were classified into four subgroups based on hospital cumulative surgery volumes. In-hospital outcomes and late outcomes during follow-up were analyzed. Logistic regression and Cox proportional hazards model were used to analyze the volume-outcome relationship. RESULTS: Patients undergoing Maze procedures at lower-volume hospitals tended to be frailer and had higher comorbidity scores. Patients in the highest-volume hospitals had a lower risk of in-hospital mortality than those in the lowest-volume hospitals [adjusted odds ratio, 0.30; 95% confidence interval (CI), 0.15-0.61; P < 0.001]. Patients in the highest-volume hospitals had lower rates of late mortality than those in the lowest-volume hospitals, including all-cause mortality [adjusted hazard ratio (aHR) 0.53; 95% CI 0.40-0.68; P < 0.001] and all-cause mortality after discharge (aHR 0.60; 95% CI 0.44-0.80; P < 0.001). CONCLUSIONS: A positive hospital volume-outcome relationship for concomitant Maze procedures was demonstrated for in-hospital and late follow-up mortality. The consequence may be attributed to physician skill/experience, experienced multidisciplinary teams, and comprehensive care processes. We suggest referring patients with frailty or those requiring complicated cardiac surgeries to high-volume hospitals to improve clinical outcomes. TRIAL REGISTRATION: the institutional review board of Chang Gung Memorial Hospital approved all data usage and the study protocol (registration number: 202100151B0C502).

Research progress on the biosynthesis and delivery of iron-sulfur clusters in the plastid.

Iron-sulfur (Fe-S) clusters are ancient protein cofactors ubiquitously exist in organisms. They are involved in many important life processes. Plastids are semi-autonomous organelles with a double membrane and it is believed to originate from a cyanobacterial endosymbiont. By learning form the research in cyanobacteria, a Fe-S cluster biosynthesis and delivery pathway has been proposed and partly demonstrated in plastids, including iron uptake, sulfur mobilization, Fe-S cluster assembly and delivery. Fe-S clusters are essential for the downstream Fe-S proteins to perform their normal biological functions. Because of the importance of Fe-S proteins in plastid, researchers have made a lot of research progress on this pathway in recent years. This review summarizes the detail research progress made in recent years. In addition, the scientific problems remained in this pathway are also discussed.

The influence of meteorological factors and total malignant tumor health risk in Wuhu city in the context of climate change.

With the increasing severity of the malignant tumors situation worldwide, the impacts of climate on them are receiving increasing attention. In this study, for the first time, all-malignant tumors were used as the dependent variable and absolute humidity (AH) was innovatively introduced into the independent variable to investigate the relationship between all-malignant tumors and meteorological factors. A total of 42,188 cases of malignant tumor deaths and meteorological factors in Wuhu City were collected over a 7-year (2014-2020) period. The analysis method combines distributed lagged nonlinear modeling (DLNM) as well as generalized additive modeling (GAM), with prior pre-analysis using structural equation modeling (SEM). The results showed that AH, temperature mean (T mean) and diurnal temperature range (DTR) all increased the malignant tumors mortality risk. Exposure to low and exceedingly low AH increases the malignant tumors mortality risk with maximum RR values of 1.008 (95% CI: 1.001, 1.015, lag 3) and 1.016 (95% CI: 1.001, 1.032, lag 1), respectively. In addition, low and exceedingly low T mean exposures also increased the risk of malignant tumors mortality, the maximum RR was 1.020 (95% CI: 1.006, 1.034) for low T mean and 1.035 (95% CI: 1.014, 1.058) for exceedingly low T mean. As for DTR, all four levels (exceedingly low, low, high, exceedingly high, from low to high) of exposure increased the risk of death from malignant tumors, from exceedingly low to exceedingly high maximum RR values of 1.018 (95% CI: 1.004, 1.032), 1.011 (95% CI: 1.005, 1.017), 1.006 (95% CI: 1.001, 1.012) and 1.019 (95% CI: 1.007, 1.031), respectively. The results of the stratified analysis suggested that female appear to be more sensitive to humidity, while male require additional attention to reduce exposure to high level of DTR.

Deterministic Loading of Microwaves onto an Artificial Atom Using a Time-Reversed Waveform.

Loading quantum information deterministically onto a quantum node is an important step toward a quantum network. Here, we demonstrate that coherent-state microwave photons with an optimal temporal waveform can be efficiently loaded onto a single superconducting artificial atom in a semi-infinite one-dimensional (1D) transmission-line waveguide. Using a weak coherent state (the number of photons (N) contained in the pulse ≪1) with an exponentially rising waveform, whose time constant matches the decoherence time of the artificial atom, we demonstrate a loading efficiency of 94.2% ± 0.7% from 1D semifree space to the artificial atom. The high loading efficiency is due to time-reversal symmetry: the overlap between the incoming wave and the time-reversed emitted wave is up to 97.1% ± 0.4%. Our results open up promising applications in realizing quantum networks based on waveguide quantum electrodynamics.

Estimating divergent forest carbon stocks and sinks via a knife set approach.

Forest carbon stocks and sinks (CSSs) have been widely estimated using climate classification tables and linear regression (LR) models with common independent variables (IVs) such as the average diameter at breast height (DBH) of stems and root shoot ratio. However, this approach is relatively ineffective when the explanatory power of IVs is lower than that of unobservable variables. Various environmental and anthropogenic factors affect target variables that cause the correlation between them to be chaotic. Here, we designed a knife set (KS) approach combining LR models and the wandering through random forests (WTF) algorithm and applied it in a specific case of Phyllostachys edulis (Carrière) J. Houz. (P. edulis) forests, which have an irregular relationship between their belowground carbon (BGC) stocks and average DBH. We then validated the KS approach performed by cluster computing to estimate the aboveground carbon (AGC) and BGC stocks and the total net primary production (TNPP). The estimated CSSs were compared to the benchmark of the methodology that applied Tier 1 in the Intergovernmental Panel on Climate Change (IPCC) Guidelines for National Greenhouse Gas Inventories via 10-fold cross validation, and the KS approach significantly increased precision and accuracy of estimations. Our approach provides general insights to accurately estimate forest CSSs relying on evidence-based field data, even if some target variables are divergent in specific forest types. We also pointed out the reason why current fancy models containing machine learning (ML) or deep learning algorithms are not effective in predicting the target variables of certain chaotic systems is perhaps that the total explanatory power of observable variables is less than that of the total unobservable variables. Quantifying unobservable variables into observable variables is a linchpin of future works related to chaotic system estimation.

MAC2 is a long-lasting marker of peripheral cell infiltrates into the mouse CNS after bone marrow transplantation and coronavirus infection.

Microglia are the primary resident myeloid cells of the brain responsible for maintaining homeostasis and protecting the central nervous system (CNS) from damage and infection. Monocytes and monocyte-derived macrophages arising from the periphery have also been implicated in CNS pathologies, however, distinguishing between different myeloid cell populations in the CNS has been difficult. Here, we set out to develop a reliable histological marker that can assess distinct myeloid cell heterogeneity and functional contributions, particularly in the context of disease and/or neuroinflammation. scRNAseq from brains of mice infected with the neurotropic JHM strain of the mouse hepatitis virus (JHMV), a mouse coronavirus, revealed that Lgals3 is highly upregulated in monocyte and macrophage populations, but not in microglia. Subsequent immunostaining for galectin-3 (encoded by Lgals3), also referred to as MAC2, highlighted the high expression levels of MAC2 protein in infiltrating myeloid cells in JHMV-infected and bone marrow (BM) chimeric mice, in stark contrast to microglia, which expressed little to no staining in these models. Expression of MAC2 was found even 6-10 months following BM-derived cell infiltration into the CNS. We also demonstrate that MAC2 is not a specific label for plaque-associated microglia in the 5xFAD mouse model, but only appears in a distinct subset of these cells in the presence of JHMV infection or during aging. Our data suggest that MAC2 can serve as a reliable and long-lasting histological marker for monocyte/macrophages in the brain, identifying an accessible approach to distinguishing resident microglia from infiltrating cells in the CNS under certain conditions.

The Kv1.3 ion channel acts as a host factor restricting viral entry.

Virus entry into cells is the initial stage of infection and involves multiple steps, and interfering viral entry represents potential antiviral approaches. Ion channels are pore-forming membrane proteins controlling cellular ion homeostasis and regulating many physiological processes, but their roles during viral infection have rarely been explored. Here, the functional Kv1.3 ion channel was found to be expressed in human hepatic cells and tissues. The Kv1.3 was then revealed to restrict HCV entry via inhibiting endosome acidification-mediated viral membrane fusion. The Kv1.3 was also demonstrated to inhibit DENV and ZIKV with an endosome acidification-dependent entry, but have no effect on SeV with a neutral pH penetration. A Kv1.3 antagonist PAP-1 treatment accelerated animal death in ZIKV-infected Ifnar1-/- mice. Moreover, Kv1.3-deletion was found to promote weight loss and reduce survival rate in ZIKV-infected Kv1.3-/- mice. Altogether, the Kv1.3 ion channel behaves as a host factor restricting viral entry. These findings broaden understanding about ion channel biology.

Association between ambient particulate matter exposure and semen quality in fertile men.

BACKGROUND: Several studies have suggested adverse effects of particulate matter (PM) exposure on male reproductive health; few have investigated the association between PM exposure and semen quality in a large population of fertile men. METHODS: We evaluated 14 parameters of semen quality in 1554 fertile men in Nanjing from 2014 to 2016. Individual exposure to particular matter ≤10 µm in diameter (PM10) and ≤ 2.5 µm in diameter (PM2.5) during key periods of sperm development (0-90, 0-9, 10-14, 15-69, and 70-90 days before semen collection) were estimated by inverse distance weighting interpolation. Associations between PM exposure and semen quality were estimated using multivariable linear regression. RESULTS: Higher 90-days average PM2.5 was in association with decreased sperm motility (2.21% for total motility, 1.93% for progressive motility per 10 µg/m3 increase, P <  0.001) and four quantitative aspects of sperm motion (curvilinear velocity (VCL), straight line velocity (VSL), average path velocity (VAP), and amplitude of lateral head displacement (ALH), P <  0.01). The association between PM2.5 exposure and semen quality were generally stronger for the earlier exposure window (70-90 days prior to ejaculation) than for recent exposure (0-9, 10-14, or 15-69 days). In the subgroup of men who had normal sperm parameters (n = 1019), similar results were obtained. Ninety-days PM10 exposure was associated only with decreased VCL and VAP and was not related to sperm concentration. CONCLUSIONS: Exposure to PM2.5 adversely affects semen quality, specifically lower sperm motility, in fertile men.

De novo structural determination of oligosaccharide isomers in glycosphingolipids using logically derived sequence tandem mass spectrometry.

Despite the importance of carbohydrates in biological systems, structural determination of carbohydrates remains difficult because of the large number of isomers. In this study, a new mass spectrometry method, namely logically derived sequence tandem mass spectrometry (LODES/MSn), was developed to characterize oligosaccharide structures. In this approach, sequential collision-induced dissociation (CID) of oligosaccharides is performed in an ion trap mass spectrometer to identify the linkage position, anomeric configuration, and stereoisomers of each monosaccharide in the oligosaccharides. The CID sequences are derived from carbohydrate dissociation mechanisms. LODES/MSn does not require oligosaccharide standards or the prior knowledge of the rules and principles of biosynthetic pathways; thus LODES/MSn is particularly useful for the investigation of undiscovered oligosaccharides. We demonstrated that the structure of core oligosaccharides in glycosphingolipids can be identified from more than 500 000 isomers using LODES/MSn. The same method can be applied for determining the structures of other oligosaccharides, such as N-, and O-glycans, and free oligosaccharides in milk.