Spatially resolved land and grid model of carbon neutrality in China.

China has committed to achieve net carbon neutrality by 2060 to combat global climate change, which will require unprecedented deployment of negative emissions technologies, renewable energies (RE), and complementary infrastructure. At terawatt-scale deployment, land use limitations interact with operational and economic features of power systems. To address this, we developed a spatially resolved resource assessment and power systems planning optimization that models a full year of power system operations, sub-provincial RE siting criteria, and transmission connections. Our modeling results show that wind and solar must be expanded to 2,000 to 3,900 GW each, with one plausible pathway leading to 300 GW/yr combined annual additions in 2046 to 2060, a three-fold increase from today. Over 80% of solar and 55% of wind is constructed within 100 km of major load centers when accounting for current policies regarding land use. Large-scale low-carbon systems must balance key trade-offs in land use, RE resource quality, grid integration, and costs. Under more restrictive RE siting policies, at least 740 GW of distributed solar would become economically feasible in regions with high demand, where utility-scale deployment is limited by competition with agricultural land. Effective planning and policy formulation are necessary to achieve China's climate goals.

Uncovering ghost introgression through genomic analysis of a distinct eastern Asian hickory species.

Ghost introgression, or the transfer of genetic material from extinct or unsampled lineages to sampled species, has attracted much attention. However, conclusive evidence for ghost introgression, especially in plant species, remains scarce. Here, we newly assembled chromosome-level genomes for both Carya sinensis and Carya cathayensis, and additionally re-sequenced the whole genomes of 43 C. sinensis individuals as well as 11 individuals representing 11 diploid hickory species. These genomic datasets were used to investigate the reticulation and bifurcation patterns within the genus Carya (Juglandaceae), with a particular focus on the beaked hickory C. sinensis. By combining the D-statistic and BPP methods, we obtained compelling evidence that supports the occurrence of ghost introgression in C. sinensis from an extinct ancestral hickory lineage. This conclusion was reinforced through the phylogenetic network analysis and a genome scan method VolcanoFinder, the latter of which can detect signatures of adaptive introgression from unknown donors. Our results not only dispel certain misconceptions about the phylogenetic history of C. sinensis but also further refine our understanding of Carya's biogeography via divergence estimates. Moreover, the successful integration of the D-statistic and BPP methods demonstrates their efficacy in facilitating a more precise identification of introgression types.

YWHAZ variation causes intellectual disability and global developmental delay with brain malformation.

YWHAZ encodes an adapter protein 14-3-3ζ, which is involved in many signaling pathways that control cellular proliferation, migration and differentiation. It has not been definitely correlated to any phenotype in OMIM. To investigate the role of YWHAZ gene in intellectual disability and global developmental delay, we conducted whole-exon sequencing in all of the available members from a large three-generation family and we discovered that a novel variant of the YWHAZ gene was associated with intellectual disability and global developmental delay. This variant is a missense mutation of YWHAZ, p.Lys49Asn/c.147A > T, which was found in all affected members but not found in other unaffected members. We also conducted computational modeling and knockdown/knockin with Drosophila to confirm the role of the YWHAZ variant in intellectual disability. Computational modeling showed that the binding energy was increased in the mutated protein combining with the ligand indicating that the c147A > T variation was a loss-of-function variant. Cognitive defects and mushroom body morphological abnormalities were observed in YWHAZ c.147A > T knockin flies. The YWHAZ knockdown flies also manifested serious cognitive defects with hyperactivity behaviors, which is consistent with the clinical features. Our clinical and experimental results consistently suggested that YWHAZ was a novel intellectual disability pathogenic gene.

Transcription factor DIVARICATA1 positively modulates seed germination in response to salinity stress.

Seed germination is a critical checkpoint for plant growth under unfavorable environmental conditions. In Arabidopsis (Arabidopsis thaliana), the abscisic acid (ABA) and gibberellic acid (GA) signaling pathways play important roles in modulating seed germination. However, the molecular links between salinity stress and ABA/GA signaling are not well understood. Herein, we showed that the expression of DIVARICATA1 (DIV1), which encodes a MYB-like transcription factor, was induced by GA and repressed by ABA, salinity, and osmotic stress in germinating seeds. DIV1 positively regulated seed germination in response to salinity stress by directly regulating the expression of DELAY OF GERMINATION 1-LIKE 3 (DOGL3) and GA-STIMULATED ARABIDOPSIS 4 (GASA4) and indirectly regulating the expression of several germination-associated genes. Moreover, NUCLEAR FACTOR-YC9 (NF-YC9) directly repressed the expression of DIV1 in germinating seeds in response to salinity stress. These results help reveal the function of the NF-YC9-DIV1 module and provide insights into the regulation of ABA and GA signaling in response to salinity stress during seed germination in Arabidopsis.

Detection of Ghost Introgression Requires Exploiting Topological and Branch Length Information.

In recent years, the study of hybridization and introgression has made significant progress, with ghost introgression-the transfer of genetic material from extinct or unsampled lineages to extant species-emerging as a key area for research. Accurately identifying ghost introgression, however, presents a challenge. To address this issue, we focused on simple cases involving 3 species with a known phylogenetic tree. Using mathematical analyses and simulations, we evaluated the performance of popular phylogenetic methods, including HyDe and PhyloNet/MPL, and the full-likelihood method, Bayesian Phylogenetics and Phylogeography (BPP), in detecting ghost introgression. Our findings suggest that heuristic approaches relying on site-pattern counts or gene-tree topologies struggle to differentiate ghost introgression from introgression between sampled non-sister species, frequently leading to incorrect identification of donor and recipient species. The full-likelihood method BPP uses multilocus sequence alignments directly-hence taking into account both gene-tree topologies and branch lengths, by contrast, is capable of detecting ghost introgression in phylogenomic datasets. We analyzed a real-world phylogenomic dataset of 14 species of Jaltomata (Solanaceae) to showcase the potential of full-likelihood methods for accurate inference of introgression.

Genomic Insights into Adaptation to Karst Limestone and Incipient Speciation in East Asian Platycarya spp. (Juglandaceae).

When challenged by similar environmental conditions, phylogenetically distant taxa often independently evolve similar traits (convergent evolution). Meanwhile, adaptation to extreme habitats might lead to divergence between taxa that are otherwise closely related. These processes have long existed in the conceptual sphere, yet molecular evidence, especially for woody perennials, is scarce. The karst endemic Platycarya longipes, and its only congeneric species, P. strobilacea, which is widely distributed in the mountains in East Asia, provide an ideal model for examining the molecular basis of both convergent evolution and speciation. Using chromosome-level genome assemblies of both species, and whole genome resequencing data from 207 individuals spanning their entire distribution range, we demonstrate that P. longipes and P. strobilacea form two species-specific clades, which diverged around 2.09 million years ago. We find an excess of genomic regions exhibiting extreme interspecific differentiation, potentially due to long-term selection in P. longipes, likely contributing to the incipient speciation of the genus Platycarya. Interestingly, our results unveil underlying karst adaptation in both copies of the calcium influx channel gene TPC1 in P. longipes. TPC1 has previously been identified as a selective target in certain karst-endemic herbs, indicating a convergent adaptation to high calcium stress among karst-endemic species. Our study reveals the genic convergence of TPC1 among karst endemics, and the driving forces underneath the incipient speciation of the two Platycarya lineages.

Genomic Insights into Adaptation to Karst Limestone and Incipient Speciation in East Asian Platycarya spp. (Juglandaceae).

When challenged by similar environmental conditions, phylogenetically distant taxa often independently evolve similar traits (convergent evolution). Meanwhile, adaptation to extreme habitats might lead to divergence between taxa that are otherwise closely related. These processes have long existed in the conceptual sphere, yet molecular evidence, especially for woody perennials, is scarce. The karst endemic Platycarya longipes and its only congeneric species, Platycarya strobilacea, which is widely distributed in the mountains in East Asia, provide an ideal model for examining the molecular basis of both convergent evolution and speciation. Using chromosome-level genome assemblies of both species, and whole-genome resequencing data from 207 individuals spanning their entire distribution range, we demonstrate that P. longipes and P. strobilacea form two species-specific clades, which diverged around 2.09 million years ago. We find an excess of genomic regions exhibiting extreme interspecific differentiation, potentially due to long-term selection in P. longipes, likely contributing to the incipient speciation of the genus Platycarya. Interestingly, our results unveil underlying karst adaptation in both copies of the calcium influx channel gene TPC1 in P. longipes. TPC1 has previously been identified as a selective target in certain karst-endemic herbs, indicating a convergent adaptation to high calcium stress among karst-endemic species. Our study reveals the genic convergence of TPC1 among karst endemics and the driving forces underneath the incipient speciation of the two Platycarya lineages.

Age-specific Dose Catalog for Diagnostic Fluoroscopy and Fluoroscopically Guided Interventional Procedures from a Pediatric Hospital.

Background Fluoroscopy is an imaging modality associated with a wide range of dose levels, characterized using a variety of dose metrics, including effective dose. However, for clinical procedures, effective dose is a seldom-used and unregulated metric in the United States, and thus, it is not extensively studied in radiology despite potentially large clinical implications for patients, especially children and infants. Purpose To formulate and report a dose catalog across all diagnostic and interventional radiology (IR) fluoroscopy examination or procedure types at a specialized tertiary care pediatric hospital. Materials and Methods In this retrospective study, dose metrics taken from radiation dose structured reports of fluoroscopy between October 2014 and March 2023 were analyzed. The reports included fluoroscopy across 18 diagnostic examination types and 24 IR procedure types. The National Cancer Institute dosimetry system for Radiography and Fluoroscopy Monte Carlo software was used to estimate age-specific effective dose from dose-area product (DAP). The DAP-to-effective dose conversion factors were estimated per IR procedure type and diagnostic fluoroscopy examination type based on age. Results A total of 11 536 individual diagnostic fluoroscopy examinations (18 types) and 8017 individual IR procedures (24 types) were analyzed. Median effective dose values per diagnostic fluoroscopy examination type ranged from 0.0010 to 0.44 mSv (mean, 0.0808 mSv ± 0.0998 [SD]). Calculated DAP-to-effective dose conversion factors ranged from 0.04 to 2.48 mSv/Gy · cm2 (mean, 0.758 mSv/Gy · cm2 ± 0.614) across all diagnostic fluoroscopy examination types. Median effective dose values per IR procedure type ranged from 0.0007 to 3.90 mSv (mean, 0.6757 mSv ± 0.8989). Calculated DAP-to-effective dose conversion factors ranged from 0.001 to 0.87 mSv/Gy · cm2 (mean, 0.210 mSv/Gy · cm2 ± 0.235) across all IR procedure types. Conclusion A pediatric fluoroscopy dose catalog was created, including age-specific effective dose, using a repeatable robust method based on accurate clinical data. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Borrego and Balter in this issue.

Response of the root anatomical structure of Carex moorcroftii to habitat drought in the Western Sichuan Plateau of China.

MAIN CONCLUSION: The anatomical structures of Carex moorcroftii roots showing stronger plasticity during drought had a lower coefficient of variation in cell size in the same habitats, while those showing weaker plasticity had a higher coefficient of variation. The complementary relationship between these factors comprises the adaptation mechanism of the C. moorcroftii root to drought. To explore the effects of habitat drought on root anatomy of hygrophytic plants, this study focused on roots of C. moorcroftii. Five sample plots were set up along a soil moisture gradient in the Western Sichuan Plateau to collect experimental materials. Paraffin sectioning was used to obtain root anatomy, and one-way ANOVA, correlation analysis, linear regression analysis, and RDA ranking were applied to analyze the relationship between root anatomy and soil water content. The results showed that the root transverse section area, thickness of epidermal cells, exodermis and Casparian strips, and area of aerenchyma were significantly and positively correlated with soil moisture content (P < 0.01). The diameter of the vascular cylinder and the number and total area of vessels were significantly and negatively correlated with the soil moisture content (P < 0.01). The plasticity of the anatomical structures was strong for the diameter and area of the vascular cylinder and thickness of the Casparian strip and epidermis, while it was weak for vessel diameter and area. In addition, there was an asymmetrical relationship between the functional adaptation of root anatomical structure in different soil moisture and the variation degree of root anatomical structure in the same soil moisture. Therefore, the roots of C. moorcroftii can shorten the water transport distance from the epidermis to the vascular cylinder, increase the area of the vascular cylinder and the number of vessels, and establish a complementary relationship between the functional adaptation of root anatomical structure in different habitats and the variation degree of root anatomical structure in the same habitat to adapt to habitat drought. This study provides a scientific basis for understanding the response of plateau wetland plants to habitat changes and their ecological adaptation strategies. More scientific experimental methods should be adopted to further study the mutual coordination mechanisms of different anatomical structures during root adaptation to habitat drought for hygrophytic plants.

Gut microbiota-derived acetate attenuates lung injury induced by influenza infection via protecting airway tight junctions.

BACKGROUND: Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host's response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown. METHODS: A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA). RESULTS: IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1ß). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner. CONCLUSION: Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.

Blood urea nitrogen to albumin ratio is a novel predictor of fatal outcome for patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is associated with a high death rate and lacks a targeted therapy plan. The ratio of blood urea nitrogen to albumin, known as BAR, is a valuable method for assessing the outlook of various infectious diseases. The objective of this research was to evaluate the effectiveness of BAR in forecasting the outcome of individuals with SFTS. Four hundred and thirty-seven patients with SFTS from two clinical centers were included in this study according to inclusion and exclusion criteria. Clinical characteristics and test parameters of SFTS patients were analyzed between survival and fatal groups. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression suggested that BAR might serve as a standalone prognostic indicator for patients with SFTS in the initial phase (hazard ratio = 18.669, 95% confidence interval [CI]: 8.558-40.725, p < 0.001). And BAR had a better predictive effectiveness in clinical outcomes in patients with SFTS with an AUC of 0.832 (95% CI: 0.788-0.876, p < 0.001), a cutoff value of 0.19, a sensitivity of 0.812, and a specificity of 0.726 compared to C-reactive protein, procalcitonin, and platelet to lymphocyte ratio via receiver operating characteristic curve. KM (Kaplan Meier) curves demonstrated that high level of BAR was associated with poor survival condition in patients with SFTS. Furthermore, the high level of BAR was associated with long hospital stays and test paraments of kidney, liver, and coagulation function in survival patients. So, BAR could be used as a promising early warning biomarker of adverse outcomes in patients with SFTS.

On-chip integrated metasystem for spin-dependent multi-channel color holography.

On-chip integrated metasurface driven by in-plane guided waves is of great interests in various light-field manipulation applications such as colorful augmented reality and holographic display. However, it remains a challenge to design colorful multichannel holography by a single on-chip metasurface. Here we present metasurfaces integrated on top of a guided-wave photonic slab that achieves multi-channel colorful holographic light display. An end-to-end scheme is used to inverse design the metasurface for projecting off-chip preset multiple patterns. Particular examples are presented for customized patterns that were encoded into the metasurface with a single-cell meta-atom, working simultaneously at RGB color channels and for several different diffractive distances, with polarization dependence. Holographic images are generated at 18 independent channels with such a single-cell metasurface. The proposed design scheme is easy to implement, and the resulting device is viable for fabrication, promising plenty of applications in nanophotonics.

Melatonin improves influenza virus infection-induced acute exacerbation of COPD by suppressing macrophage M1 polarization and apoptosis.

BACKGROUND: Influenza A viruses (IAV) are extremely common respiratory viruses for the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), in which IAV infection may further evoke abnormal macrophage polarization, amplify cytokine storms. Melatonin exerts potential effects of anti-inflammation and anti-IAV infection, while its effects on IAV infection-induced AECOPD are poorly understood. METHODS: COPD mice models were established through cigarette smoke exposure for consecutive 24 weeks, evaluated by the detection of lung function. AECOPD mice models were established through the intratracheal atomization of influenza A/H3N2 stocks in COPD mice, and were injected intraperitoneally with melatonin (Mel). Then, The polarization of alveolar macrophages (AMs) was assayed by flow cytometry of bronchoalveolar lavage (BAL) cells. In vitro, the effects of melatonin on macrophage polarization were analyzed in IAV-infected Cigarette smoking extract (CSE)-stimulated Raw264.7 macrophages. Moreover, the roles of the melatonin receptors (MTs) in regulating macrophage polarization and apoptosis were determined using MTs antagonist luzindole. RESULTS: The present results demonstrated that IAV/H3N2 infection deteriorated lung function (reduced FEV20,50/FVC), exacerbated lung damages in COPD mice with higher dual polarization of AMs. Melatonin therapy improved airflow limitation and lung damages of AECOPD mice by decreasing IAV nucleoprotein (IAV-NP) protein levels and the M1 polarization of pulmonary macrophages. Furthermore, in CSE-stimulated Raw264.7 cells, IAV infection further promoted the dual polarization of macrophages accompanied with decreased MT1 expression. Melatonin decreased STAT1 phosphorylation, the levels of M1 markers and IAV-NP via MTs reflected by the addition of luzindole. Recombinant IL-1ß attenuated the inhibitory effects of melatonin on IAV infection and STAT1-driven M1 polarization, while its converting enzyme inhibitor VX765 potentiated the inhibitory effects of melatonin on them. Moreover, melatonin inhibited IAV infection-induced apoptosis by suppressing IL-1ß/STAT1 signaling via MTs. CONCLUSIONS: These findings suggested that melatonin inhibited IAV infection, improved lung function and lung damages of AECOPD via suppressing IL-1ß/STAT1-driven macrophage M1 polarization and apoptosis in a MTs-dependent manner. Melatonin may be considered as a potential therapeutic agent for influenza virus infection-induced AECOPD.

Inferring Physical Properties of Symmetric States from the Fewest Copies.

Learning physical properties of high-dimensional states is crucial for developing quantum technologies but usually consumes an exceedingly large number of samples which are difficult to afford in practice. In this Letter, we use the methodology of quantum metrology to tackle this difficulty, proposing a strategy built upon entangled measurements for dramatically reducing sample complexity. The strategy, whose characteristic feature is symmetrization of observables, is powered by the exploration of symmetric structures of states which are ubiquitous in physics. It is provably optimal under some natural assumption, efficiently implementable in a variety of contexts, and capable of being incorporated into existing methods as a basic building block. We apply the strategy to different scenarios motivated by experiments, demonstrating exponential reductions in sample complexity.

Impact of Ghost Introgression on Coalescent-Based Species Tree Inference and Estimation of Divergence Time.

The species studied in any evolutionary investigation generally constitute a small proportion of all the species currently existing or that have gone extinct. It is therefore likely that introgression, which is widespread across the tree of life, involves "ghosts," that is, unsampled, unknown, or extinct lineages. However, the impact of ghost introgression on estimations of species trees has rarely been studied and is poorly understood. Here, we use mathematical analysis and simulations to examine the robustness of species tree methods based on the multispecies coalescent model to introgression from a ghost or extant lineage. We found that many results originally obtained for introgression between extant species can easily be extended to ghost introgression, such as the strongly interactive effects of incomplete lineage sorting (ILS) and introgression on the occurrence of anomalous gene trees. The relative performance of the summary species tree method (ASTRAL) and the full-likelihood method (*BEAST) varies under different introgression scenarios, with the former being more robust to gene flow between nonsister species, whereas the latter performing better under certain conditions of ghost introgression. When an outgroup ghost (defined as a lineage that diverged before the most basal species under investigation) acts as the donor of the introgressed genes, the time of root divergence among the investigated species generally was overestimated, whereas ingroup introgression, as commonly perceived, can only lead to underestimation. In many cases of ingroup introgression that may or may not involve ghost lineages, the stronger the ILS, the higher the accuracy achieved in estimating the time of root divergence, although the topology of the species tree is more prone to be biased by the effect of introgression. [Anomalous gene trees; divergence time; ghost introgression; multispecies coalescent; simulation; species tree.].

CoNi-N/P-Doped Carbon Nanotubes as Catalysts for Efficient Oxygen Reduction Reaction.

Transition metals (TMs) supported by heteroatom-doped carbon materials are considered to be the potential alternatives to the Pt/C catalyst owing to their low cost, outstanding electrocatalytic efficiency, and excellent electrochemical durability. In this paper, N/P-doped carbon nanotube (CNT) (N/P-CNT)-supported monometallic (Co, Ni) and bimetallic (CoNi) catalysts were synthesized by one-step pyrolysis using diammonium hydrogen phosphate, 2-methylimidazole and organometallic salts as precursors, and the CNT as the catalyst carrier; the effects of transition TM types and pyrolysis temperature (Tp) on the microstructure and electrochemical properties were explored. The analysis exhibited that the CoNi bimetallic catalyst was superior to both Co and Ni monometallic catalysts, and the catalysts pyrolyzed at 900 °C exhibited a better graphitization degree. The optimal CoNi-N/P-CNT-900 displayed remarkable oxygen reduction reaction electrocatalytic performance with a half-wave potential (E1/2) of 0.86 V and excellent methanol tolerance and stability. Moreover, the Zn-air battery coated with CoNi-N/P-CNT-900 demonstrated a larger open circuit voltage of 1.577 V, a larger peak power density of 212.89 mW cm-2 at 357.8 mA cm-2, as well as a higher specific capacity of 799 mA h gZn-1, superior to that of the Pt/C catalyst (1.492 V, 96.04 mW cm-2 at 216.8 mA cm-2, 735 mA h gZn-1), showing outstanding practical value. This study is expected to promote the commercialization of the electrocatalysts.

Surf4 (Surfeit Locus Protein 4) Deficiency Reduces Intestinal Lipid Absorption and Secretion and Decreases Metabolism in Mice.

BACKGROUND: Postprandial dyslipidemia is a causative risk factor for cardiovascular disease. The majority of absorbed dietary lipids are packaged into chylomicron and then delivered to circulation. Previous studies showed that Surf4 (surfeit locus protein 4) mediates very low-density lipoprotein secretion from hepatocytes. Silencing hepatic Surf4 markedly reduces the development of atherosclerosis in different mouse models of atherosclerosis without causing hepatic steatosis. However, the role of Surf4 in chylomicron secretion is unknown. METHODS: We developed inducible intestinal-specific Surf4 knockdown mice (Surf4IKO) using Vil1Cre-ERT2 and Surf4flox mice. Metabolic cages were used to monitor mouse metabolism. Enzymatic kits were employed to measure serum and tissue lipid levels. The expression of target genes was detected by qRT-PCR and Western Blot. Transmission electron microscopy and radiolabeled oleic acid were used to assess the structure of enterocytes and intestinal lipid absorption and secretion, respectively. Proteomics was performed to determine changes in protein expression in serum and jejunum. RESULTS: Surf4IKO mice, especially male Surf4IKO mice, displayed significant body weight loss, increased mortality, and reduced metabolism. Surf4IKO mice exhibited lipid accumulation in enterocytes and impaired fat absorption and secretion. Lipid droplets and small lipid vacuoles were accumulated in the cytosol and the endoplasmic reticulum lumen of the enterocytes of Surf4IKO mice, respectively. Surf4 colocalized with apoB and co-immunoprecipitated with apoB48 in differentiated Caco-2 cells. Intestinal Surf4 deficiency also significantly reduced serum triglyceride, cholesterol, and free fatty acid levels in mice. Proteomics data revealed that diverse pathways were altered in Surf4IKO mice. In addition, Surf4IKO mice had mild liver damage, decreased liver size and weight, and reduced hepatic triglyceride levels. CONCLUSIONS: Our findings demonstrate that intestinal Surf4 plays an essential role in lipid absorption and chylomicron secretion and suggest that the therapeutic use of Surf4 inhibition requires highly cell/tissue-specific targeting.

Development and validation of a nonverbal consensus-based semantic memory paradigm in patients with epilepsy.

OBJECTIVE: Brain areas implicated in semantic memory can be damaged in patients with epilepsy (PWE). However, it is challenging to delineate semantic processing deficits from acoustic, linguistic, and other verbal aspects in current neuropsychological assessments. We developed a new Visual-based Semantic Association Task (ViSAT) to evaluate nonverbal semantic processing in PWE. METHOD: The ViSAT was adapted from similar predecessors (Pyramids & Palm Trees test, PPT; Camels & Cactus Test, CCT) comprised of 100 unique trials using real-life color pictures that avoid demographic, cultural, and other potential confounds. We obtained performance data from 23 PWE participants and 24 control participants (Control), along with crowdsourced normative data from 54 Amazon Mechanical Turk (Mturk) workers. RESULTS: ViSAT reached a consensus >90% in 91.3% of trials compared to 83.6% in PPT and 82.9% in CCT. A deep learning model demonstrated that visual features of the stimulus images (color, shape; i.e., non-semantic) did not influence top answer choices (p = 0.577). The PWE group had lower accuracy than the Control group (p = 0.019). PWE had longer response times than the Control group in general and this was augmented for the semantic processing (trial answer) stage (both p < 0.001). CONCLUSIONS: This study demonstrated performance impairments in PWE that may reflect dysfunction of nonverbal semantic memory circuits, such as seizure onset zones overlapping with key semantic regions (e.g., anterior temporal lobe). The ViSAT paradigm avoids confounds, is repeatable/longitudinal, captures behavioral data, and is open-source, thus we propose it as a strong alternative for clinical and research assessment of nonverbal semantic memory.

Melatonin Rescues Influenza A Virus-Induced Cellular Energy Exhaustion via OMA1-OPA1-S in Acute Exacerbation of COPD.

Although rapid progression and a poor prognosis in influenza A virus (IAV) infection-induced acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are frequently associated with metabolic energy disorders, the underlying mechanisms and rescue strategies remain unknown. We herein demonstrated that the level of resting energy expenditure increased significantly in IAV-induced AECOPD patients and that cellular energy exhaustion emerged earlier and more significantly in IAV-infected primary COPD bronchial epithelial (pDHBE) cells. The differentially expressed genes were enriched in the oxidative phosphorylation (OXPHOS) pathway; additionally, we consistently uncovered much earlier ATP exhaustion, more severe mitochondrial structural destruction and dysfunction, and OXPHOS impairment in IAV-inoculated pDHBE cells, and these changes were rescued by melatonin. The level of OMA1-dependent cleavage of OPA1 in the mitochondrial inner membrane and the shift in energy metabolism from OXPHOS to glycolysis were significantly increased in IAV-infected pDHBE cells; however, these changes were rescued by OMA1-siRNA or melatonin further treatment. Collectively, our data revealed that melatonin rescued IAV-induced cellular energy exhaustion via OMA1-OPA1-S to improve the clinical prognosis in COPD. This treatment may serve as a potential therapeutic agent for patients in which AECOPD is induced by IAV.

Construction of Coordination Spaces with Narrow Pore Windows in Co-Based Metal-Organic Frameworks toward CO2/N2 Separation.

Carbon emission reduction is an important measure to mitigate the greenhouse effect, which has become a hotspot in global climate change research. To contribute to this, here, we fabricated two Co-based metal-organic frameworks (Co-MOFs), namely, {[Co3(NTB)2(bib)]·(DMA)2·(H2O)4}n (DZU-211) and {[Co3(NTB)2(bmip)]·(DMA)2}n (DZU-212) (H3NTB = 4,4',4″-nitrilotribenzoic acid, bib = 1,4-bis(imidazol-1-yl)-butane, bmip = 1,3-bis(2-methyl-1H-imidazol-1-yl)propane) to realize efficient CO2/N2 separation by dividing coordination spaces into suitable pores with narrow windows. DZU-211 reveals a 3D open porous framework, while DZU-212 exhibits a 3D double-fold interpenetrated structure. The two MOFs both possess large coordination spaces and small open pore sizes, via the bib ligand insertion and framework interpenetration, respectively. Comparatively, DZU-211 reveals superior selective CO2 uptake properties due to its more suitable pore characteristics. Gas sorption experiments show that DZU-211 has a CO2 uptake of 52.6 cm3 g-1 with a high simulated CO2/N2 selectivity of 101.7 (298 K, 1 atm) and a moderate initial adsorption heat of 38.1 kJ mol-1. Moreover, dynamic breakthrough experiments confirm the potential application of DZU-211 as a CO2 separation material from postcombustion flue gases.