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Objective: To investigate the effects of Urtica macrorrhiza Hand.-Mazz. rhamnnogalacturonans (UMRG), and Urtica macrorrhiza Hand.-Mazz. arabinogalactan (UMAG) on the immunological function by regulating phagocytic and polarization of macrophages. Methods: The effects of UMRG and UMAG on the viability of macrophage were studied by the cell counting kit-8 (CCK-8). The effects of UMRG and UMAG on the phagocytosis of macrophage were investigated by neutral red assay, flow cytometry and laser confocal microscopy. The effects of UMRG and UMAG on macrophage polarization were studied by flow cytometry. The effects of UMRG and UMAG on the secretion of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were detected by Griess assay and enzyme-linked immunosorbent assay (ELISA). Results: UMRG and UMAG exhibited no significant cytotoxicity to macrophages in the concentration range of 10~320 µg/mL. Both UMRG and UMAG significantly enhanced the macrophage phagocytosis of neutral red and model antigens (P

Abstract Symbiotic nitrogen fixation (SNF) in legume-rhizobia serves as a sustainable source of nitrogen (N) in agriculture. However, the addition of inorganic N fertilizers significantly inhibits SNF, and the underlying mechanisms remain not-well understood. Here, we report that inorganic N disrupts iron (Fe) homeostasis in soybean nodules, leading to a decrease in SNF efficiency. This disruption is attributed to the inhibition of the Fe transporter genes Natural Resistance-Associated Macrophage Protein 2a and 2b (GmNRAMP2a&2b) by inorganic N. GmNRAMP2a&2b are predominantly localized at the tonoplast of uninfected nodule tissues, affecting Fe transfer to infected cells and consequently, modulating SNF efficiency. In addition, we identified a pair of N-signal regulators, nitrogen-regulated GARP-type transcription factors 1a and 1b (GmNIGT1a&1b), that negatively regulate the expression of GmNRAMP2a&2b, which establishes a link between N signaling and Fe homeostasis in nodules. Our findings reveal a plausible mechanism by which soybean adjusts SNF efficiency through Fe allocation in response to fluctuating inorganic N conditions, offering valuable insights for optimizing N and Fe management in legume-based agricultural systems.

Laser additive manufacturing with mixed powders of aluminum alloy and silicon carbide (SiC) or boron carbide (B4C) is investigated in this experiment. With various mixing ratios of SiC/Al to form metal matrix composites (MMC), their mechanical and physical properties are empirically investigated. Parameters such as laser power, scan speed, scan pattern, and hatching space are optimized to obtain the highest density for each mixing ratio of SiC/Al. The mechanical and thermal properties are systematically investigated and compared with and without heat treatment. It shows that 2 wt% of SiC obtained the highest strength and Young’s modulus. Graded composite additive manufacturing (AM) of MMC is also fabricated and characterized. Various types of MMC devices, such as heat sink using graded SiC MMC and grid type three-dimensional (3D) neutron collimators using boron carbide (B4C), were also fabricated to demonstrate their feasibility for applications.

Leukapheresis is a treatment used to reduce leukocytes to decrease the number of white blood cells in circulation and prevent the risks of hyperviscosity and cerebrovascular and pulmonary leukostasis. We present a case of pro-B-cell acute lymphoblastic leukemia (ALL) with hyperleukocytosis in a 6-month-old infant, characterized by a positive KMT2A/AFF1 fusion gene with a leukocyte count of 1,755 × 109/L. After two consecutive sessions of leukapheresis, the white blood cell count decreased to 55 × 109/L. The infant recovered after the high-dose methotrexate chemotherapy. These results demonstrate that leukapheresis is a feasible treatment option for acute hyperleukocytic leukemia in infants with ALL.

This study aimed to evaluate the seroprevalence of Bordetella pertussis and persistence of antibodies following vaccination. We recruited 6060 healthy subjects from five provinces of China during 2017–2018. Serum IgG antibodies against pertussis toxin (anti-PT IgG) and filamentous hemagglutinin (anti-FHA IgG), and serum IgA antibodies against pertussis toxin (anti-PT IgA) were measured by ELISA. Geometric mean concentration (GMC), seropositivity rate, and recent infection rate were calculated. Among 0–6 years-olds, the anti-PT IgG, anti-PT IgA, and anti-FHA IgG GMCs were 6.4 IU/ml (95% CI 6.1–6.8), 2.8 IU/ml (95% CI 2.7–2.8), and 13.3 IU/ml (95% CI 12.4–14.2), respectively. The anti-PT IgG GMC increased in accordance with the primary vaccination series (4–6 months) and the toddler booster (18–24 months), but declined thereafter through to age 5 years [4.7 IU/ml (95% CI 4.2–5.4)]. The seropositivity rate of pertussis in >6 year-olds was 9.0% (95% CI 8.1–9.9) and the recent infection rate was 3.3% (95% CI, 2.7–3.8). Recent infection rate began to increase from 6 years of age, with peaks at 9, 20, 40, and ≥60 years of age. The anti-PT IgG GMCs of children aged 0–6 years who were vaccinated with DTaP, DTaP-IPV//PRP～T, and DTaP-Hib were 5.9 IU/ml (95% CI 5.6–6.3), 20.7 IU/ml (95% CI 15.6–27.8), and 11.7 IU/ml (95% CI 7.5–18.1) (p

We examined the impact of varying ageing times (0, 6, 12, and 15 months) on the alterations in the concentration of key volatile compounds in Cheddar cheese as it ripened. With PCA of E-nose and PLS-DA of gas GC–MS and GC-IMS, the cheddar cheese samples could be identified from one another. As the cheese samples ripened longer, their overall acid, ester, and aldehyde concentrations increased. The important flavor biomarkers of ripened Cheddar cheese were 1-hexanol, 1-octen-3-ol, 2,6-dimethylpyrazine, octanal, decanal, 1-pentanol, butanoic acid ethyl ester, (E)-2-octenal, nonanoic acid, hexanal, dimethyltrisulfide, (E)-2-undecenal, and 1-heptanol, according to chemometric methods. The cheese samples that were ripened for 0 and 6 months showed a considerable contribution of the milky flavor. There was a strong negative association between the milky flavor and acetic acid. The aged Cheddar cheese exhibited distinct nutty, sour, and fruity flavors after 12 and 15 months. The fruity flavor was highly positively correlated with hexanal, octanal, and 2-heptanone, butanoic acid, ethyl ester, and acetic acid. The sour and nutty flavors were also strongly positively correlated with acids, while the sour and nutty flavors were positively influenced by ethyl hexanoate and benzaldehyde. This study provides data on the composition and variations in the flavor profile of ripening cheddar cheese.

PurposeIt is crucial to identify biomarkers that influence the aging process and associated health risks, given the growing severity of the global population aging issue. The objectives of our research were to evaluate cardiac metabolic index (CMI) as a novel biomarker for identifying individuals at increased risk of accelerated biological aging and to assess its use in guiding preventive strategies for aging-related health risks.MethodsThe National Health and Nutrition Examination Survey (NHANES) provided cross-sectional data on participants with complete information on CMI, phenotypic age (PA), and other variables. Analyses of variance and weighted χ2 tests were conducted to assess differences between groups. The relationship between CMI and biological aging was investigated using a weighted multivariate logistic regression model, restricted cubic spline (RCS) regression analysis, subgroup analysis, and interaction testing.ResultsA positive correlation between CMI and biological aging was observed in 6,272 participants. RCS regression analysis confirmed the non-linear relationship, identifying significant inflection point at 1.10. In the crude or adjusted models, the OR (95% CI), for the highest group versus the reference were 3.608 (3.108, 4.188), 3.397 (2.920, 3.952), and 1.550 (1.299, 1.850), respectively, when categorizing CMI into different groups. Subgroup analyses and interaction tests indicate that the association between CMI and biological aging remained consistent across different subgroups. Gender, race, education level, marital status, poverty income ratio (PIR), drinking status and diabetes had an interaction with CMI in relation to biological aging.ConclusionAn elevated CMI is linked to increased risk for biological aging. This relationship may inform more effective prevention and treatment strategies for biological aging in the future. CMI be integrated into routine health screenings or aging assessments by healthcare professionals.

Abstract Chemotherapy‐based combination regimens are recommended as first‐line treatment for colorectal cancer. However, multidrug resistance (MDR) and limited drug infiltration in tumor microenvironment remain critical challenges. Herein, a pH/redox dual activated supramolecular DAS@CD‐OxPt (IV) nanoparticles (NPs) via host‐guest molecular recognition to achieve relay drugs delivery of active oxaliplatin (OxPt (IV)) and Src inhibitor dasatinib (DAS) between tumor cells is developed. DAS@CD‐OxPt (IV) NPs exhibit prolonged circulation in the blood and intra‐tumoral retention. Triggered by the endo/lysosome (pH 5.0), flexible DAS@CD‐OxPt (IV) NPs exhibited proton‐driven in situ assembly to form nanofiber in tumor cells. Dual chemotherapeutic agents released from DAS@CD‐OxPt (IV) NPs synergistically cause irreversible DNA damage by blocking p53‐mediated DNA repair. Supramolecular nanofibers can further serve as the “ammunition depot” to continuously release drugs from dying cells and transport them into neighboring tumor cells, leading to domino‐like cell death and enhanced immunogenicity. Furthermore, DAS@CD‐OxPt (IV) NPs combined with immune checkpoint blockade (ICB) therapy strikingly suppress CT26 tumor growth and pulmonary metastasis.

Mitotic anaphase onset is a key cellular process tightly regulated by multiple kinases. The involvement of mitogen-activated protein kinases (MAPKs) in this process has been established in Xenopus egg extracts. However, the detailed regulatory cascade remains elusive, and it is also unknown whether the MAPK-dependent mitotic regulation is evolutionarily conserved in the single-cell eukaryotic organisms such as fission yeast (Schizosaccharomyces pombe). Here, we show that two MAPKs in S. pombe indeed act in concert to restrain anaphase-promoting complex/cyclosome (APC/C) activity upon activation of the spindle assembly checkpoint (SAC). One MAPK, Pmk1, binds to and phosphorylates Slp1Cdc20, the co-activator of APC/C. Phosphorylation of Slp1Cdc20 by Pmk1, but not by Cdk1, promotes its subsequent ubiquitylation and degradation. Intriguingly, Pmk1-mediated phosphorylation event is also required to sustain SAC under environmental stress. Thus, our study establishes a new underlying molecular mechanism of negative regulation of APC/C by MAPK upon stress stimuli, and provides a previously unappreciated framework for regulation of anaphase entry in eukaryotic cells.

BackgroundThe gut microbiota is known to have a significant impact on the development of food allergy, and several recent studies have suggested that both oral microbiota, which first come into contact with allergenic foods, may have a profound influence on the development of food allergy.MethodsIn this study, we have established an ovalbumin-sensitive mice model by utilizing ovalbumin as a sensitizing agent. Subsequently, we performed a comprehensive analysis of the gut and oral microbiota in ovalbumin-sensitive mice and the control mice using full-length 16S rRNA sequencing analysis.ResultsInterestingly, both the gut and oral microbiota of ovalbumin-sensitized mice exhibited significant dysbiosis. The relative abundance of s__Lactobacillus_intestinalis in the gut microbiota of ovalbumin-sensitive mice exhibited a significant decrease, whereas the abundance of s__Agrobacterium_radiobacter and s__Acinetobacter_sp__CIP_56_2 displayed a significant increase. Furthermore, the relative abundance of s__unclassified_g__Staphylococcus, s__Streptococcus_hyointestinalis, and s__unclassified_g__Dechloromonas in the oral microbiota of ovalbumin-sensitive mice revealed a significant decrease. In contrast, the abundance of 63 other species, including s__Proteiniclasticum_ruminis, s__Guggenheimella_bovis, and s__Romboutsia_timonensis, demonstrated a significant increase. The random forest classifier achieved the best accuracy in predicting the outcome of food allergy using three gut and three oral biomarkers, with accuracies of 94.12 and 100%, respectively. Based on the predictions of the PICRUSt2 analysis, the only consistent finding observed across multiple samples from both the groups of mice was a significant up-regulation of the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway in the ovalbumin-sensitized mice.ConclusionOur study demonstrates that ovalbumin-sensitized mice experience substantial alterations in both gut and oral microbial composition and structure, and specific strains identified in this study may serve as potential biomarkers for food allergy screening. Moreover, our findings highlight that the oral environment, under the same experimental conditions, exhibited greater precision in detecting a larger number of species. Additionally, it is worth noting that the NOD-like receptor signaling pathway plays a vital role in the pathogenesis of OVA (ovalbumin)-induced allergy. These findings will generate novel concepts and strategies in the realm of food allergy prevention and treatment.

BackgroundConcomitant administration of COVID-19, influenza, and pneumococcal vaccines could reduce the burden on healthcare systems. However, the immunogenicity and safety of various combinations of a third booster dose of SARS-CoV-2 inactivated vaccine (CoronaVac), inactivated quadrivalent influenza vaccine (IIV4), and 23-valent pneumococcal polysaccharide vaccine (PPV23), particularly in different age groups, is still unknown.MethodsA phase 4, randomized, open-label, controlled trial was conducted in Beijing, China. 636 healthy adults were divided into two age groups (18-59 and ≥60 years) and randomized equally into three groups: CoronaVac and IIV4 followed by PPV23; CoronaVac and PPV23 followed by IIV4; or CoronaVac followed by IIV4 and PPV23, with a 28-day interval between vaccinations. Immunogenicity was evaluated by measuring antibody titers, and safety was monitored. ClinicalTrials.gov Identifier: NCT05298800.ResultsCo-administration of a third dose of CoronaVac, IIV4, and PPV23 in any combination was safe. Among adults aged 18-59, co-administration with PPV23 maintained non-inferiority of antibody levels for CoronaVac and IIV4, despite a slight reduction in antibody responses. This reduction was not observed in participants ≥60 years. Furthermore, co-administration of IIV4 and PPV23 affected seroconversion rates for both vaccines.ConclusionsCo-administration of the third dose of SARS-CoV-2 inactivated vaccine with the influenza vaccine, followed by PPV23, may be optimal for adults aged 18-59. In adults ≥60, all vaccine combinations were immunogenic, suggesting a flexible vaccination approach. Since antibody measurements were taken 28 days post-vaccination, ongoing surveillance is essential to assess the longevity of the immune responses.

Objectives: To evaluate the neutralizing antibody (NAb) levels against the SARS-CoV-2 Omicron variants BF.7, BQ.1, BQ.1.1, XBB.1, and XBB.1.5 after vaccination and natural infection. Methods: The NAbs against the different viral strains of 490 individuals with SARS-CoV-2 and 187 without SARS-CoV-2 in the Beijing COVID-19 outbreak during December 2022 to January 2023 were analyzed. Results: In uninfected individuals, limited levels of NAbs were produced against the prototype and variant strains after two doses vaccine but significantly increased after three or four doses of the vaccine. The infected individuals had high NAbs levels against the BF.7, BQ.1, and BQ.1.1 variants and moderate NAbs levels against the XBB.1 and XBB.1.5 variants. The highest NAbs levels were observed after two inoculation doses. The third and fourth doses vaccine did not result in a significant increase the NAbs levels. After the last dose of vaccination, the NAbs levels peaked at 12 months for the prototype and BF.7 and between 6 to 12 months for the BQ.1, BQ.1.1, XBB.1, and XBB.1.5 variants. Conclusions: The immune response decreases as the virus mutates. If booster vaccination is considered necessary, it is suggested for at least 6 months after infection.

Severe capacity degradation at high operating voltages and poor interphase stability at elevated temperature have thus far precluded the practical application of LiNi0.5Mn1.5O4 (LNMO) as a cathode material for lithium-ion batteries. Addressing these challenges through a combination of experimental and theoretical methods in this work, we demonstrate how a fluorinated carbonate electrolyte enables both high-voltage and high temperature operation by mitigating the traditional interfacial reactions observed in electrolytes with conventional carbonate solvents. Computational studies confirm the exceptional oxidation stability of fluorinated carbonate electrolyte which reduces deprotonation at high voltage. The mitigated deprotonation will then minimize the formation of HF acid which corrodes the LNMO surface and leads to phase transformation and poor interphases. With fluorinated carbonate electrolyte at elevated temperature, it was found on LNMO’s subsurface a reduced amount of Mn3O4 phase which can block Li+ transfer and result in drastic cell failure. Leveraging this approach, LNMO/graphite full cells with a high loading of 3.0 mAh/cm2 achieve excellent cycling stability, retaining ∼84 % of their initial capacity at room temperature (25 °C) after 200 cycles and ∼68 % after 100 cycles at 55 °C. This advanced electrolyte also shows promise for improving calendar life, retaining >30 % more capacity than the carbonate baseline after high temperature storage. These results indicate that electrolytes based on fluorinated carbonates are a promising strategy for overcoming the remaining challenges toward practical commercial application of LNMO.

Abstract Background The thirteen-valent pneumococcal conjugate vaccine (PCV13) is not included in the national immunization program and is administered voluntarily with informed consent in China. In preparation for assessing the impact of pilot introduction in Hainan Province, we conducted a carriage study among children under 5 years of age from four locations in Hainan Province, China. Methods From March to June 2022, nasopharyngeal (NP) swabs, collected from healthy children aged younger than 59 months who lived in the 4 different locations (Haikou, Wanning, Baisha and Qiongzhong) in Hainan Province, were tested for pneumococcus using conventional culture. Pneumococcal isolates were serotyped using the Quellung reaction. Risk factors associated with pneumococcal colonization were assessed using univariate analysis and multivariable logistic regression adjusting for age, daycare attendance and other factors. Results Pneumococcus was isolated in 710 (30.4%) of the 2333 children enrolled. Of 737 pneumococci, 29 serotypes were identified; 60.9% were PCV13 serotypes; the most common vaccine serotypes were 6B (20.4%), 19F (13.0%), 6A (11.9%) and 23F (6.1%); and the most common nonvaccine serotypes were 23A (12.9%), 34 (6.1%) and nontypeable (NT) pneumococci (5.6%). Children vaccinated with PCV13 had lower carriage (17.7% vs 32.5%; P = 0.0001) and fewer PCV13 serotypes (41.9% vs 62.7%; P = 0.0017) compared to unimmunized children. After adjustment, NP carriage was higher among children attending daycare (aOR = 2.3, 95% CI: 1.7–3.2), living in rural areas (aOR = 1.4, 95% CI: 1.1–1.8), living with siblings (aOR = 1.3, 95% CI: 1.0–1.6) and whose mothers had completed senior high/technical secondary school (aOR = 1.5, 95% CI: 1.1–2.0). In contrast, completion of 3–4 doses of PCV13 were associated with a lower carriage rate (aOR = 0.6, 95% CI: 0.4–0.9). Conclusions We established the baseline of pneumococcal carriage, serotype distribution and PCV13 immunization rates among healthy children under 5 years of age in Hainan Province, prior to the introduction of PCV13 into the national immunization program. The high proportion of PCV13 serotypes suggests that PCV13 introduction will likely have a substantial impact on pneumococcal carriage in Hainan Province. Graphical Abstract

With advancements in additive manufacturing (AM) techniques, high-quality triply periodic minimal surface (TPMS) structures can now be produced. TPMS walled heat exchangers (HX) hold significant potential for industrial applications and are receiving increasing attention. This paper explores the impact of various TPMS design variables on flow and thermal performance to optimize TPMS heat exchangers for compactness, high efficiency, and low pressure drop. The design variables examined include the type of TPMS lattice, unit cell size, wall thickness, aspect ratio, TPMS orientation, and equivalent thickness. The study reveals that the flow and heat transfer performance of TPMS structures are significantly affected by these design variables. For the Gyroid, Diamond, and SplitP lattices, performance is nearly identical when the surface-to-volume ratio is kept constant. The average velocity of the fluid in the TPMS HX should be 0.3 m/s. The corresponding Re is between 300~800. Thin wall thickness, small equivalent thickness, and flat lattice configurations can significantly reduce pressure drop while maintaining the overall heat transfer coefficient. Additionally, the angle between the flow direction and TPMS orientation can increase pressure drop. Three aluminum heat exchangers were successfully printed using an AM machine, and testing results are comparable with theoretical prediction.

Unfermented jujube pulp (UFJP), fermented jujube pulp (FJP) in high and low doses were fed to constipated ICR mice. Defecation function, serum gastrointestinal regulatory peptide, fecal short-chain fatty acids (SCFAs) and gut microbial composition were assessed. Results showed that high-dose FJP could protect intestinal mucosa tissue, shorten the first black feces defecating time by 17 % and increase the number and wet weights of black feces by 72 % and 71 %, respectively, within 6 h. High-dose FJP significantly down-regulated the somatostatin level and up-regulated gastrin level in constipated mice, compared with low-dose FJP and UFJP. High-dose FJP intervention regulated the microbiota profile, which afterwards restored microbiota, like Bacteroidetes, Bifidobacterium and Lactobacillus, to a less unhealthy state. This study provides convincing in vivo evidence that high-dose FJP supplementation through daily diet could be a promising approach to effectively alleviate constipation and modulate gut health.

The Chenghai Fault in the Chuan–Dian block terminates at the northwestern segment of the Red River Fault, and is a significant seismogenic structure. The kinematic evolution of this fault should be closely related to the regional tectonic deformation. However, it is difficult to obtain information on structural deformation of the Chenghai Fault due to the large amount of precipitation and well-developed vegetation. The Chenghai normal faulting may drive drainage reorganization in this region, which provides a new perspective for reconstructing and evaluating the tectonic history. High-resolution digital elevation models (DEM) obtained by remote sensing greatly facilitate the study of drainage evolution and active tectonics. We use two methods (χ-plot and Gilbert metrics) to measure the drainage divide stability based on the ALOS DEM (12.5 m resolution) and further reproduce the drainage evolution process in response to the asymmetric uplift by numerical modeling. The results show that the Chenghai–Jinsha drainage divide, hosted by the footwall block of the Chenghai Fault, is migrating westward (away from the Chenghai Fault) and will continue moving ~2.2–3.5 km to reach a steady state. Its migration is controlled by the Chenghai normal faulting. The Chenghai–Jinsha drainage divide formed close to the Chenghai Fault’s surface trace and continues to migrate westward in response to the asymmetric uplift. It only took a few million years for the Chenghai–Jinsha drainage divide to migrate to its current location based on the numerical modeling. The restoration of the drainage reorganization implies that the Chenghai Fault initiated in the Pliocene, which probably results from kinematic reversal along the Red River Fault.

Nonanal, (E)-2-nonenal, (E,E)-2,4-nonadienal, and (E,Z)-2,6-nonadienal were used to study the effect of number and position of the unsaturated bond in aliphatic aldehydes on meat flavorings. Cysteine-Amadori and thiazolidine derivatives were synthesized, identified by UPLC-TOF/MS and NMR, and quantitatively by UPLC-MS/MS. The polyunsaturated aldehydes exhibited higher inhibition than monounsaturated aldehydes, and monounsaturated aldehydes exhibited higher inhibition than saturated aldehydes, mainly manifested by the inhibition of the cysteine-Amadori formation and acceleration of the thiazolidine derivatives formation. The effect of unsaturated bonds position in aliphatic aldehydes on the initial Maillard reaction stage was similar. The cysteine played an important role in catalyzing the reaction of aliphatic aldehydes. A total of 109 volatile compounds derived by heating prepared thiazolidine derivatives degradation were detected by GC-MS. Formation pathways of volatile compounds were proposed by retro-aldol, oxidation, etc. Particularly, a route to form thiazole by the decarboxylation reaction of thiazolidine derivatives which derivatives from formaldehyde reacting with cysteine was proposed.

We characterize the suitability of two additive manufactured materials for use in shielding thermal neutrons for neutron scattering instrumentation. We compare two different boron based additive manufactured masks to a traditionally manufactured boron nitride mask in a real-use case scenario. The first additive manufactured mask is a composite of aluminum and boron carbide. The second additive manufactured mask is a composite of boron carbide and cyanoacrylate. We report the thermal conductivity of the aluminum boron carbide mask in comparison to other relevant materials. The aluminum boron carbide material may find use in shielding applications where thermal conductivity, a low total neutron scattering cross section, and low toxicity are criteria.

The spindle unit is the core component of a machine, and its stiffness is a key performance characteristic. The stiffness consistency is a key index to measure the stiffness of spindle units; however, there is a lack of unified evaluation methods for the spindle unit stiffness consistency. This paper proposes a comprehensive method for the evaluation of the spindle unit stiffness consistency based on fluctuations and comprehensive weights. First, the consistency of the spindle unit stiffness evaluation indices is expressed based on the fluctuations. Secondly, the subjective and objective weights of the spindle unit stiffness evaluation indices are given based on the AHP and CRITIC weight assignment methods. To obtain the comprehensive weights of the evaluation indices, the subjective and objective weights are synthesized based on the linear weighting method. Then, the consistency level of the spindle unit stiffness is obtained by the weighted summation of the comprehensive weights and fluctuations of the evaluation indices. Finally, the stiffness consistency of a group of spindle units is evaluated based on this method, and the evaluation result shows a 10.63% fluctuation, which indicates that its stiffness consistency level is class B, in line with the factory production requirements.

Triply periodic minimal surface (TPMS) heat exchangers (HXs) have been investigated in this paper along with additive manufacturing (AM). Heat transfer coefficients, pressure drops, and thermal capacity were systematically evaluated as functions of wall thickness, lattice cell density, and materials. It turns out that when thermal conductivity is above 100 W/m·K, gyroid HXs are less sensitive to variations in thickness and thermal conductivity. Additive manufacturing of 20 kW aluminum heat exchangers was successful and testing results are comparable with theoretical prediction. To the best of our knowledge, this is the first demonstration of a working prototype of TPMS HXs.

Abstract Purpose The diagnosis of pulmonary hamartoma (PH) based on computed tomography (CT) is a challenge, especially in patients with atypical imaging characteristics. This study was aimed at summarizing the imaging characteristic of 18F-Fluoro-d-glucose positron emission tomography-computed tomography (18F-FDG PET-CT) in PH and exploring the application value of PET-CT in the diagnosis of PH. Data and methods Patients diagnosed with PH who had undergone PET-CT from literature pertaining were retrospectively analyzed, which were cases of publications from the Cochrane Library, PubMed, Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI) and Wanfang databases, from 2008 to June 2022. The other 20 cases of the collection were patients from our hospital from 2008 to June 2022. Patients’ symptoms, imaging characteristics of chest CT, PET-CT characteristics, the reason for PET-CT and the complications were analyzed. Results In this retrospective study, a total of 216 patients were diagnosed with PH and had been examined by PET-CT. 20 of the cases were patients of our hospital from January 2008 to June 2022. The other cases were collected from the literature. The mean diameter of most PH lesions is 1.7 ± 1.0 cm. The mean maximum standardized uptake value (SUVmax) of the PH lesions was 1.2 ± 1.1. Most of their SUVmax were lower than internationally recognized cut-off value (SUVmax = 2.5). PET-CT was superior to CT in the diagnosis of PH but there was a correlation of between CT diagnosis and PET-CT diagnosis for the PH lesions. In order to draw the Receiver operating characteristic (ROC), we selected 29 patients with a clear SUVmax value of their PH lesion, and 29 lung cancer patients with clear SUVmax value in our hospital were collected as a control group. ROC curve analysis showed that the area under curve (AUC) of SUVmax was 0.899, and the optimal diagnostic threshold was SUVmax > 2.65. PET-CT could distinguish PH from malignant lesions with a sensitivity of 89.66% by applying a SUVmax of 2.65 as a cut-off in this study. Conclusion PET-CT might be a useful tool to diagnose PH, which shows a better diagnostic sensitivity than CT. But PET-CT can not be used as a single diagnostic approach, which should be combined with other methods and the patients’ history to make the most correct diagnosis.

To obtain high-quality walnut meal protein, the process conditions for extraction of walnut meal protein by alkaline solubilization and acid precipitation method and purification of walnut meal protein by glycolytic enzyme were optimized by single-factor experiments and response surface method, respectively, and the functional properties such as solubility, water absorption, and emulsification were analyzed. The optimal extraction process conditions were: pH12, temperature 55 ℃, time 90 min, and material-liquid ratio 1:40 g/mL. Under these conditions, the extraction rate of walnut meal protein could reach 81.89%±1.64%, and its settling point was pH4.5. The optimal purification process conditions were: pH4.5, material-to-liquid ratio 1:40 g/mL, enzymatic digestion time 129 min, enzymatic digestion temperature 53°C, and enzyme addition 0.4%. The purity of walnut meal protein purified under these conditions could reach 94.48%±1.83%. The results of functional properties of walnut protein showed that its solubility was 24.82%, water absorption 3.06 g/g, oil absorption 3.15 g/g, emulsification 16.10 m2/g, emulsification stability 38.87 min, foaming 30.53% and foaming stability 75.44% under the same pH conditions, and the purified walnut protein had better functional properties.

Epidemic cerebrospinal meningitis is a respiratory infectious disease caused by Neisseria meningitidis, most commonly manifesting as meningitis and septicaemia. Due to the lack of effective prevention measures, serogroup B Neisseria meningitidis (MenB) has become one of dominant epidemic bacterial groups. In recent years, the emergence of reverse vaccinology has greatly promoted the research on serogroup B meningococcal vaccine, and researches on the vaccine have also made a breakthrough. In order to develop a more effective meningococcal vaccine, this article reviews the research progress on new protein antigen vaccine, outer membrane vesicle vaccine and recombinant protein vaccine in the field of MenB vaccine.

Abstract As the indispensable second cellular messenger, calcium signaling is involved in the regulation of almost all physiological processes by activating specific target proteins. The importance of calcium ions (Ca2+) makes its “Janus nature” strictly regulated by its concentration. Abnormal regulation of calcium signals may cause some diseases; however, artificial regulation of calcium homeostasis in local lesions may also play a therapeutic role. “Calcium overload,” for example, is characterized by excessive enrichment of intracellular Ca2+, which irreversibly switches calcium signaling from “positive regulation” to “reverse destruction,” leading to cell death. However, this undesirable death could be defined as “calcicoptosis” to offer a novel approach for cancer treatment. Indeed, Ca2+ is involved in various cancer diagnostic and therapeutic events, including calcium overload-induced calcium homeostasis disorder, calcium channels dysregulation, mitochondrial dysfunction, calcium-associated immunoregulation, cell/vascular/tumor calcification, and calcification-mediated CT imaging. In parallel, the development of multifunctional calcium-based nanomaterials (e.g., calcium phosphate, calcium carbonate, calcium peroxide, and hydroxyapatite) is becoming abundantly available. This review will highlight the latest insights of the calcium-based nanomaterials, explain their application, and provide novel perspective. Identifying and characterizing new patterns of calcium-dependent signaling and exploiting the disease element linkage offer additional translational opportunities for cancer theranostics.

Improving phosphorus (P) acquisition efficiency is important for sustainable agriculture. Here, the authors report a natural variation in an upstream open reading frame of a SEC12-like gene GmPHF1 is crucial for protein abundance and spatial distribution of GmPHF1, which contribute to P acquisition diversity in soybean.

ABSTRACT Trichosporon asahii is an emerging opportunistic pathogen that causes potentially fatal disseminated trichosporonosis. The global prevalence of coronavirus disease 2019 (COVID-19) poses an increasing fungal infection burden caused by T. asahii. Allicin is the main biologically active component with broad-spectrum antimicrobial activity in garlic. In this study, we performed an in-depth analysis of the antifungal characteristics of allicin against T. asahii based on physiological, cytological, and transcriptomic assessments. In vitro, allicin inhibited the growth of T. asahii planktonic cells and biofilm cells significantly. In vivo, allicin improved the mean survival time of mice with systemic trichosporonosis and reduced tissue fungal burden. Electron microscopy observations clearly demonstrated damage to T. asahii cell morphology and ultrastructure caused by allicin. Furthermore, allicin increased intracellular reactive oxygen species (ROS) accumulation, leading to oxidative stress damage in T. asahii cells. Transcriptome analysis showed that allicin treatment disturbed the biosynthesis of cell membrane and cell wall, glucose catabolism, and oxidative stress. The overexpression of multiple antioxidant enzymes and transporters may also place an additional burden on cells, causing them to collapse. Our findings shed new light on the potential of allicin as an alternative treatment strategy for trichosporonosis. IMPORTANCE Systemic infection caused by T. asahii has recently been recognized as an important cause of mortality in hospitalized COVID-19 patients. Invasive trichosporonosis remains a significant challenge for clinicians, due to the limited therapeutic options. The present work suggests that allicin holds great potential as a therapeutic candidate for T. asahii infection. Allicin demonstrated potent in vitro antifungal activity and potential in vivo protective effects. In addition, transcriptome sequencing provided valuable insights into the antifungal effects of allicin.

Abstract Background The alcohol consumption pattern, alcoholic liver disease (ALD) prevalence and related risk factors among alcohol drinkers in Beijing haven’t been fully elucidated. Hence, a cross-sectional study was conducted to investigate potential link among these factors. Methods A two-stage stratified cluster sampling was carried out in Beijing. All participants were 25 years of age or older, possessed with medical insurance, and lived in Beijing for over 6 months. As part for this investigation, participants were asked to answer a questionnaire and undergo physical examination. The questionnaire included demographic information, alcohol intake, and medical history. The physical examination included physical and Fibrotouch tests. Moreover, 10 ml blood sample was collected from each subject to examine liver functions, perform routine blood, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV). Results Overall, 74,988 residents participated in our study. The proportion of current drinkers among all participants was 46.10%. The differences in gender, region, age group, education, annual household income, and occupation among lifetime abstainers, former drinkers, non-weekly and weekly drinkers were significantly different (P

Objectives: To determine the status of immune responses after primary and booster immunization for SARS-CoV-2 variants and evaluate the differences in disease resistance based upon titers of neutralizing antibodies (NAbs) against the variants. Methods: Participants aged 18–59 years received 2 doses of inactivated COVID-19 vaccine, 14 days apart, and a booster dose after 12 months. Blood samples were collected before vaccination (baseline), 1 and 6 months after primary immunization, and at multiple instances within 21 days of the booster dose. NAbs against the spike protein of Wuhan-Hu-1 and 3 variants were measured using pseudovirus neutralization assays. Results: Of 400 enrolled participants, 387 completed visits scheduled within 6 months of the second dose and 346 participants received the booster dose in the follow-up research. After 1 month of primary immunization, geometric mean titers (GMTs) of NAbs peaked for Wuhan-Hu-1, whereas GMTs of other variants were

Purpose: To investigate the baseline levels of serotype-specific IgG antibodies to Streptococcus pneumoniae (S. pneumoniae) and assess their impact on the assessment of vaccine immunogenicity. Methods: We used a subset of serum samples from a randomized controlled trial. The blood of 584 healthy participants was collected on day 0 before and day 28 after the 23-valent pneumococcal polysaccharide vaccine (PPSV23) vaccination. Serotype-specific IgG against PPSV23-covered serotypes were measured by the World Health Organization (WHO) reference enzyme-linked immunosorbent assay (ELISA). Vaccine immunogenicity was compared using conversion rates (proportion of participants with IgG levels following immunization that are 2-fold greater than the baseline) and geometric mean fold rises (GMFRs) between the two groups, which were grouped according to pre-vaccination (baseline) IgG antibody levels. Results: Our data showed that over half of individuals have baseline IgG levels for 15 out of 23 serotypes above 1.3 µg/mL, and geometric mean concentrations (GMCs) were generally higher in the elderly group and the female group; significant differences were found in 15 serotypes for vaccine immunogenicity based on the seroconversion rate or GMFRs between individuals with baseline IgG ≥ 1.3 µg/mL and individuals with baseline IgG < 1.3 µg/mL. The seroconversion rate decreased with the increase of baseline IgG levels according to a linear regression model. Conclusions: The assessment of vaccine immunogenicity could be impacted by the fact that many adults had high baseline antibody levels. This study is registered in the Chinese Clinical Trial Registry, number NCT05298800.

Minimally invasive interventional embolization has tremendous advantages over conventional surgery in the treatment of vascular diseases and malignant tumors. Particularly, liquid embolic agents have garnered much attention owing to their properties of deep vascular penetration and full occlusion of vasculature independent of thrombus formation, which relies on the patient's coagulation system. Despite their drawbacks, traditional liquid embolic agents, such as lipiodol, N-butyl-2-cyanoacrylate, and Onyx, have benefited numerous patients. The original liquid embolic agents have been modified and optimized, and novel liquid embolic agents have also been developed using different strategies and mechanisms. This minireview provides a brief overview of liquid embolic agents, including approved and potential ones. Challenges, prospects, and rational design guidelines are also discussed. This review may spark interest in liquid embolic agents and open new avenues for the smart design of improved embolic agents in the development of personalized and precision medicine.

Abstract Background The incidence of hepatitis A virus (HAV) infection is low in Beijing, China, but the risk of outbreaks still exists. It is difficult to identify possible sources of infection among sporadic cases based on a routine surveillance system. Therefore, a more effective surveillance system needs to be established. Methods The epidemiological data of hepatitis A were obtained from a routine surveillance system. Patients with HAV confirmed at the local hospitals were asked to complete a questionnaire that included additional case information and possible sources of infection. Serum and fecal specimens were also collected for testing HAV RNA by polymerase chain reaction. In addition, the 321-nucleotide segment of the VP1/2A junction region was sequenced to determine the HAV genotype. Results In 2019, 110 HAV cases were reported in Beijing, with an incidence rate of 0.51/100,000. 61(55.5%) of these patients were male. The greatest proportion of these patients were aged from 30 to 60 years. The rate was lower in suburban and rural areas compared to urban areas. Contaminated food consumption, particularly seafood consumption, was the primary potential source of infection. Among the 16 specimens of confirmed HAV cases that could be sequenced, 93.8% were HAV IA, and 6.3% were HAV IB. In addition, the samples collected from all HAV sequences in this investigation showed 89.4–100% nucleotide homology. Two groups (each with three sporadic cases) showed 100% nucleotide homology. The three sporadic cases in one group had the same possible source of infection: contaminated salad with raw vegetables and seafood. In the other group, the three sporadic cases did not have an epidemiological connection. Conclusions In a low HAV prevalent area, such as in Beijing, incorporating molecular epidemiology into the routine surveillance system could help inform possible clusters of outbreaks and provide support for earlier control of HAV transmission. Nevertheless, increased sampling from detected cases and improved specimen quality are needed to implement such a system.

Walnut protein isolate (WPI) is a nutritious protein with poor solubility, which severely limits its application. In this study, composite nanoparticles were prepared from WPI and soy protein isolate (SPI) using the pH-cycle technology. The WPI solubility increased from 12.64 to 88.53% with a WPI: SPI ratio increased from 1: 0.01 to 1: 1. Morphological and structural analyses illustrated that interaction forces with hydrogen bonding as the main effect jointly drive the binding of WPI to SPI and that protein co-folding occurs during the neutralization process, resulting in a hydrophilic rigid structure. In addition, the interfacial characterization showed that the composite nanoparticle with a large surface charge enhanced the affinity with water molecules, prevented protein aggregation, and protected the new hydrophilic structure from damage. All these parameters helped to maintain the stability of the composite nanoparticles in a neutral environment. Amino acid analysis, emulsification capacity, foaming, and stability analysis showed that the prepared WPI-based nanoparticles exhibited good nutritional and functional properties. Overall, this study could provide a technical reference for the value-added use of WPI and an alternative strategy for delivering natural food ingredients.

Abstract Background The utilization of noninvasive positive pressure ventilation (NPPV) is becoming more and more common, especially in patients with acute or chronic respiratory failure. The purpose of our study is to analyze the factors that influence the efficacy of NPPV in the treatment of respiratory failure caused by a variety of etiology. Methods From May 2011 to April 2020, patients treated with NPPV during hospitalization in the First Affiliated Hospital of Soochow University were enrolled. According to the clinical outcome of NPPV treatment and whether converted to invasive mechanical ventilation, patients were divided into the success group and the failure group. The clinical data and the characteristics of NPPV application were compared between the two groups. Results A total of 3312 patients were enrolled, including 2025 patients in the success group and 1287 patients in the failure group. Univariate analysis suggested that there were no statistical differences in patients' age, gender, use of analgesia and/or sedation, complicated with barotrauma, inspiratory positive airway pressure and expiratory positive airway pressure between the success and failure groups (P > 0.05). However, there were statistically significant differences in serum albumin levels, Ca2+ concentration, blood glucose levels, duration of NPPV treatment and length of hospital stay between the success and failure groups (P

To evaluate the immunogenicity of inactivated COVID-19 vaccines administered at different intervals. Subjects who had received two doses of inactivated COVID-19 vaccines at an interval of 21 days or 1–7 months were selected to collect 5 ml of venous blood after the second dose for the detection of specific IgG antibody against SARS-CoV-2 using the chemiluminescent immunoassay. Blood samples were collected from 348 and 174 individuals vaccinated at an interval of 21 days or 1–7 months, respectively. Seropositive rate 2 weeks after two doses of vaccination at 21-days and 1–7 months interval was 95.7% and 97.1%, respectively, with no statistically significant difference. The post-vaccination antibody level was 23.7 with 21-days interval, higher than 14.2 with 1–7 months interval. Among the individuals vaccinated with two doses more than 1-month apart, seropositive rate was 98.5%, 90.0%, 91.7%, and 100% with 1- month (1–2 months, 2 months was not included, the same below), 2- month, 3- month, and 4–7 months of interval, respectively, and no statistically significant difference was observed. Appropriate extension of the vaccination interval between two doses of inactivated COVID-19 vaccine does not affect the production of specific IgG antibodies. The inactivated COVID-19 vaccine should be administered in accordance with the recommended vaccination schedule, and the vaccination interval can be extended appropriately under special circumstances.

A molecular sensory science approach was used to explore the effects of ultrasonic treatment on aroma compounds of watermelon juice. Watermelon juice was submitted to ultrasonic power at 325 W for 20 min. Ultrasonic treatment reduced odor related to cucumber and green descriptors, whilst significantly improved odors related to sweet, floral, and fruity descriptors, thus contributing to the overall flavor of watermelon juice. Compared with untreated watermelon juice, the amount and concentration of volatile compounds in ultrasonicated watermelon juice increased by 82.50% and 111.84%, respectively. Notably, 22 alkene compounds were newly formed in ultrasonicated watermelon juice, which contributed to sweet and fruity aroma of watermelon juice. The findings of the present study suggest that ultrasonic treatment may be a potential method to improve the overall flavor of watermelon juice.

Rice productivity has considerably improved due to the effective employment of heterosis, but the genetic basis of heterosis for grain shape and weight remains uncertain. For studying the genetic dissection of heterosis for grain shape/weight and their relationship with grain yield in rice, quantitative trait locus (QTL) mapping was performed on 1,061 recombinant inbred lines (RILs), which was developed by crossing xian/indica rice Quan9311B (Q9311B) and Wu-shan-si-miao (WSSM). Whereas, BC1F1 (a backcross F1) was developed by crossing RILs with Quan9311A (Q9311A) combined with phenotyping in Hefei (HF) and Nanning (NN) environments. Overall, 114 (main-effect, mQTL) and 359 (epistatic QTL, eQTL) were identified in all populations (RIL, BC1F1, and mid-parent heterosis, HMPs) for 1000-grain weight (TGW), grain yield per plant (GYP) and grain shape traits including grain length (GL), grain width (GW), and grain length to width ratio (GLWR). Differential QTL detection revealed that all additive loci in RILs population do not show heterotic effects, and few of them affect the performance of BC1F1. However, 25 mQTL not only contributed to BC1F1’s performance but also contributed to heterosis. A total of seven QTL regions was identified, which simultaneously affected multiple grain traits (grain yield, weight, shape) in the same environment, including five regions with opposite directions and two regions with same directions of favorable allele effects, indicating that partial genetic overlaps are existed between different grain traits. This study suggested different approaches for obtaining good grain quality with high yield by pyramiding or introgressing favorable alleles (FA) with the same direction of gene effect at the QTL regions affecting grain shape/weight and grain yield distributing on different chromosomes, or introgressing or pyramiding FA in the parents instead of fixing additive effects in hybrid as well as pyramiding the polymorphic overdominant/dominant loci between the parents and eliminating underdominant loci from the parents. These outcomes offer valuable information and strategy to develop hybrid rice with suitable grain type and weight.

Polymer systems can be designed into different structures and morphologies according to their physical and chemical performance requirements, and are considered as one of the most promising controlled delivery systems that can effectively improve the cancer therapeutic index. However, the majority of the polymer delivery systems are designed to be simple spherical nanostructures. To explore morphology/size-oriented delivery performance optimization, here, we synthesized three novel cylindrical polymer brushes (CPBs) by atom transfer radical polymerization (ATRP), which were cellulose-g-(CPT-b-OEGMA) (CCO) with different lengths (~86, ~40, and ~21 nm). The CPBs are composed of bio-degradable cellulose as the carrier, poly(ethylene glycol) methyl ether methacrylate (OEGMA) as hydrophily block, and glutathione (GSH)-responsive hydrophobic camptothecin (CPT) monomer as loaded anticancer drug. By controlling the chain length of the initiator, three kinds of polymeric prodrugs with different lengths (CCO-1, CCO-2, and CCO-3) could be self-organized into unimolecular micelles in water. We carried out comparative studies of three polymers, whose results verified that the shorter CPBs exhibited higher drug release efficiency, more cellular uptake, and enhanced tumor permeability, accompanied by shortened blood circulation time and lower tumor accumulation. As evidenced by in vivo experiments, the shorter CPBs exhibited higher anti-tumor efficiency, revealing that the size advantage has a higher priority than the anisotropic structure advantage. This provided vital information as to design an anisotropic polymer-based drug delivery system for cancer therapy.

Objective: To investigate the mechanisms of wall shear stress (WSS) responsible for the effects of high-intensity interval exercise (HIIE) on vascular endothelial function in young obese males.Methods: A within-subject study design was used. We examined the response of the reactive hyperemia index (RHI) to acute HIIE in young obese males (n = 20, age = 20.38 ± 1.40 years, body mass index [BMI] = 31.22 ± 3.57, body fat percentage [BF (%)] = 31.76 ± 3.57). WSS was manipulated using 100, 80, or 60 mmHg cuff inflation during the HIIE to determine the proper inflation capable of maintaining WSS near baseline levels. One-way repeated measures analysis of variance and LSD post hoc tests were performed to compare changes in WSS and vascular endothelial function at baseline HIIE and following HIIE using different cuff inflations.Results: There were no significant differences in RHI and WSS between the three cuff inflation values (p > 0.05). WSS was significantly higher in obese male individuals after HIIE and HIIE with 100 mmHg cuff inflation (p = 0.018, p = 0.005) than that at baseline, with no significant differences observed comparing HIIE and HIIE with 100 mmHg inflation (p = 0.23). The RHI after HIIE was significantly higher (p = 0.012) than that at baseline, while no significant differences were detected after HIIE at 100 mmHg (p = 0.91). The RHI was significantly lower after HIIE with 100 mmHg than that after HIIE (p = 0.007). WSS (p = 0.004) and RHI (p = 0.017) were significantly higher after HIIE than that at baseline, while no significant differences were observed after HIIE with either 80 or 60 mmHg cuff inflation (baseline vs. HIIE + 80 mmHg: WSS: p = 0.33, RHI: p = 0.38; baseline vs. HIIE + 60 mmHg: WSS: p = 0.58, RHI: p = 0.45). WSS was similar to HIIE, after HIIE with either 80 or 60 mmHg inflation (p = 0.36, p = 0.40). However, RHI was significantly higher for HIIE than for HIIE with both 80 and 60 mmHg inflation (p = 0.011, p = 0.006).Conclusion: HIIE could significantly improve WSS and vascular endothelial function. HIIE intervention with 60 or 80 mmHg inflation might enhance WSS near the baseline level. HIIE-induced acute changes in WSS may provide the primary physiological stimulus for vascular endothelial adaptation to HIIE in young obese males.

Nian zhuan has its aroma as one of the perceived principal characteristics. The current study was aimed mainly to investigate the potential to include the aroma of nian zhuan as a new target criterion into the green wheat product chain. By improving the conditions for the traditional processing of nian zhuan, the optimal processing conditions were determined as green wheat (GW) 14 d, steaming the green wheat with the skin (SGWS) 26 min and cooked green wheat peeled (CGWP) 280 min, to evaluate the feasibility of using electronic nose (E-nose) and gas chromatography mass spectrometry (GC-MS) to discriminate nian zhuan in different stages. E-nose was used to recognize nian zhuan odors in different processing stages, and GC-MS to identify the individual volatile compounds. A total of 139 volatile compounds were detected by GC-MS, of which 71 key were screened by t-test (P < 0.01). The W1W, W1S, W2W and W2S sensors of E-nose gave higher responses to all samples, and effectively discriminated the samples. The most volatile compounds were produced in the millstone milling (MSM) stage of nian zhuan, and millstone could promote the release of volatile compounds from cooked green wheat by milling.

ObjectiveTo study the tissue-infiltrating immune cells of the emphysema phenotype of chronic obstructive pulmonary disease (COPD) and find the molecular mechanism related to the development of emphysema to offer potential targets for more precise treatment of patients with COPD.MethodsCombined analyses of COPD emphysema phenotype lung tissue-related datasets, GSE47460 and GSE1122, were performed. CIBERSORT was used to assess the distribution of tissue-infiltrating immune cells. Weighted gene co-expression network analysis (WGCNA) was used to select immune key genes closely related to clinical features. Rt-qPCR experiments were used for the validation of key genes. Emphysema risk prediction models were constructed by logistic regression analysis and a nomogram was developed.ResultsIn this study, three immune cells significantly associated with clinical features of emphysema (FEV1 post-bronchodilator % predicted, GOLD Stage, and DLCO) were found. The proportion of neutrophils (p=0.025) infiltrating in the emphysema phenotype was significantly increased compared with the non-emphysema phenotype, while the proportions of M2 macrophages (p=0.004) and resting mast cells (p=0.01) were significantly decreased. Five immune-related differentially expressed genes (DEGs) were found. WGCNA and clinical lung tissue validation of patients with emphysema phenotype were performed to further screen immune-related genes closely related to clinical features. A key gene (SERPINA3) was selected and included in the emphysema risk prediction model. Compared with the traditional clinical prediction model (AUC=0.923), the combined prediction model, including SERPINA3 and resting mast cells (AUC=0.941), had better discrimination power and higher net benefit.ConclusionThis study comprehensively analyzed the tissue-infiltrating immune cells significantly associated with emphysema phenotype, including M2 macrophages, neutrophils, and resting mast cells, and identified SERPINA3 as a key immune-related gene.

The activated spindle assembly checkpoint (SAC) potently inhibits the anaphase-promoting complex/cyclosome (APC/C) to ensure accurate chromosome segregation at anaphase. Early studies have recognized that the SAC should be silenced within minutes to enable rapid APC/C activation and synchronous segregation of chromosomes once all kinetochores are properly attached, but the underlying silencers are still being elucidated. Here, we report that the timely silencing of SAC in fission yeast requires dnt1+, which causes severe thiabendazole (TBZ) sensitivity and increased rate of lagging chromosomes when deleted. The absence of Dnt1 results in prolonged inhibitory binding of mitotic checkpoint complex (MCC) to APC/C and attenuated protein levels of Slp1Cdc20, consequently slows the degradation of cyclin B and securin, and eventually delays anaphase entry in cells released from SAC activation. Interestingly, Dnt1 physically associates with APC/C upon SAC activation. We propose that this association may fend off excessive and prolonged MCC binding to APC/C and help to maintain Slp1Cdc20 stability. This may allow a subset of APC/C to retain activity, which ensures rapid anaphase onset and mitotic exit once SAC is inactivated. Therefore, our study uncovered a new player in dictating the timing and efficacy of APC/C activation, which is actively required for maintaining cell viability upon recovery from the inhibition of APC/C by spindle checkpoint.