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Complex biological mechanisms and unidentified therapeutic targets for amyotrophic lateral sclerosis (ALS) significantly hinder the development of effective treatments. Given these challenges, reliable disease models that accurately replicate ALS phenotypes with relevant biological underpinnings are essential for advancing precision medicine in ALS. Patient-derived induced pluripotent stem cell (iPSC) organoids have emerged as an innovative tool for disease modeling and drug evaluation. Growing evidence highlights the advantages of organoids in replicating ALS phenotypes and supporting drug development. However, challenges remain in utilizing organoids for ALS drug testing and other neurodegenerative diseases. In this review we summarize the current progress in ALS model development, encompassing both in vitro and in vivo non-human models, as well as iPSC-derived human models. Furthermore, within the context of ALS drug screening, we discuss critical considerations for applying organoids to evaluate disease-associated phenotypes and to accurately reflect disease-related symptoms.

Internal solitary waves (ISWs) are extensively present in the Andaman Sea. Their generation and propagation can cause damage to offshore engineering structures and pose a threat to the safe navigation of submarines. Consequently, the ability to accurately predict ISWs is of considerable significance. This study addresses this challenge by analyzing the primary factors influencing ISWs propagation in the Andaman Sea, revealing that both water depth and stratification significantly affect propagation velocity. A CNN-LSTM hybrid neural network model, based on multiple features and the self-attention mechanism, has been constructed by incorporating the characteristics of ISWs (ISW-Attention-CNN-LSTM Net, IACL Net), aiming to predict the propagation of ISWs in the Andaman Sea. The dataset for this model was derived from Sentinel-1A ascending and descending orbit images of the Andaman Sea, spanning the years 2018–2023. From these, 864 images displaying clear ISWs characteristics were selected, resulting in the extraction of 5383 ISWs sample points along with their associated oceanic environmental parameters. The model utilizes the leading wavefront of the ISW wave packet as input to generate predictions of ISWs, which are subsequently compared with satellite observation data. The model's prediction results indicate that after one semidiurnal tidal cycle, the RMSE between the predicted dominant ISW wave crest and satellite observations is 3.891 km. Running the model over two semidiurnal tidal cycles produced similar results. Compared with other machine learning models, the prediction performance shows improvements across various metrics, demonstrating the model's robustness in predicting ISW.

Abstract The peacock blenny Salaria pavo is notorious for its extreme male sexual polymorphism, with large males defending nests and younger reproductive males mimicking the appearance and behavior of females to parasitically fertilize eggs. The lack of a reference genome has, to date, limited the understanding of the genetic basis of the species phenotypic plasticity. Here, we present the first reference genome assembly of the peacock blenny using PacBio HiFi long-reads and Hi-C sequencing data. The final assembly of the S. pavo genome spanned 735.90 Mbp, with a contig N50 of 3.69 Mbp and a scaffold N50 of 31.87 Mbp. A total of 98.77% of the assembly was anchored to 24 chromosomes. In total, 24,008 protein-coding genes were annotated, and 99.0% of BUSCO genes were fully represented. Comparative analyses with closely related species showed that 86.2% of these genes were assigned to orthogroups. This high-quality genome of S. pavo will be a valuable resource for future research on this species’ reproductive plasticity and evolutionary history.

Abstract Background The association between the geriatric nutritional risk index (GNRI) and osteosarcopenia in older adults with type 2 diabetes mellitus (T2DM) is not clear. Methods A total of 573 individuals with T2DM were included in this cross-sectional study. Osteosarcopenia was defined as the presence of both osteoporosis and sarcopenia. Appendicular skeletal muscle mass and bone mineral density (BMD) was measured by dual energy X-ray absorptiometry to diagnose sarcopenia and osteoporosis. Multivariate analyses were used to assess the association between Geriatric Nutritional Risk Index (GNRI) and osteosarcopenia. Results The patients were divided into four groups: robust (n = 367), osteoporosis alone (n = 154), sarcopenia alone (n = 29), and osteosarcopenia (n = 23). The GNRI was the lowest in osteosarcopenia group and was positively correlated with skeletal muscle index (SMI) (r = 0.122, p = 0.004), grip strength (r = 0.154, p

Abstract The immune system undergoes progressive functional remodeling from neonatal stages to old age. Therefore, understanding how aging shapes immune cell function is vital for precise treatment of patients at different life stages. Here, we constructed the first transcriptomic atlas of immune cells encompassing human lifespan, ranging from newborns to supercentenarians, and comprehensively examined gene expression signatures involving cell signaling, metabolism, differentiation, and functions in all cell types to investigate immune aging changes. By comparing immune cell composition among different age groups, HLA highly expressing NK cells and CD83 positive B cells were identified with high percentages exclusively in the teenager (Tg) group, whereas unknown_T cells were exclusively enriched in the supercentenarian (Sc) group. Notably, we found that the biological age (BA) of pediatric COVID-19 patients with multisystem inflammatory syndrome accelerated aging according to their chronological age (CA). Besides, we proved that inflammatory shift- myeloid abundance and signature correlate with the progression of complications in Kawasaki disease (KD). The shift- myeloid signature was also found to be associated with KD treatment resistance, and effective therapies improve treatment outcomes by reducing this signaling. Finally, based on those age-related immune cell compositions, we developed a novel BA prediction model PHARE ( https://xiazlab.org/phare/ ), which can apply to both scRNA-seq and bulk RNA-seq data. Using this model, we found patients with coronary artery disease (CAD) also exhibit accelerated aging compared to healthy individuals. Overall, our study revealed changes in immune cell proportions and function associated with aging, both in health and disease, and provided a novel tool for successfully capturing features that accelerate or delay aging.

ABSTRACTFollowing the national dynamic zero-COVID strategy adjustment, the utilization of broad-spectrum nasal neutralizing antibodies may offer an alternative approach to controlling the outbreak of Omicron variants between late 2022 and early 2023 in China. This study involved an investigator-initiated trial (IIT) to assess the pharmacokinetic, safety and efficacy of the F61 nasal spray. A total of 2,008 participants were randomly assigned to receive F61 nasal spray (24 mg/0.8 mL/dose) or normal saline (0.8 mL/dose) and 1336 completed the follow-up in the IIT. Minimal absorption of F61 antibody into the bloodstream was detected in individuals receiving F61 nasal spray for seven consecutive days. No treatment-emergent adverse reactions of grade 3 severity or higher were reported. In the one-dose cohort, the 7-day cumulative SARS-CoV-2 infection rate was 79.0% in the F61 group and 82.6% in the placebo group, whereas, in the multiple-dose (once daily for 7 consecutive days) cohort, the rates were 6.55% in the F61 group and 23.83% in the placebo group. The laboratory-confirmed efficacy of F61 was 3.78% (−3.74%–10.75%) in the one-dose cohort and 72.19% (57.33%–81.87%) in the multiple-dose cohort. In the real-world study, 60,225 volunteers in four different regions were administered the F61 nasal spray based on the subject's wishes, over 90% efficacy rate was observed against different Omicron variants. The F61 nasal spray, with its favourable safety profile, could be a promising prophylactic monoclonal antibody against SARS-CoV-2 VOCs.

Background Laparoscopic techniques are being widely applied for peritoneal dialysis (PD) catheter (PDC) placement. The suture passer is a novel fixation tool that aims to reduce catheter migration. We compared the clinical value of the suture passer combined with two-hole laparoscopic PDC placement to open surgical placement by evaluating preoperative and postoperative conditions, as well as the onset of complications in both groups.Methods A retrospective study was conducted including 169 patients who underwent PDC placement surgery from January 2021 to May 2023. Based on the method employed, patients were divided into two groups: the suture passer combined with a two-hole laparoscopy group (SLG) and the open surgical group (SG). Comprehensive patient information, including general data, preoperative and postoperative indicators, peritoneal function after surgery, and the incidence rate of complications, were collected and analyzed.Results The SLG showed a statistically significant decrease in operative time, intraoperative blood loss, and 6-month postoperative drift rate compared to the SG (p

Background The potential impact of elevated intra-abdominal pressure (IAP) on residual renal function (RRF) has not been determined. The objective of this study was to investigate the relationship between IAP and the rate of RRF decline in newly initiated peritoneal dialysis (PD) patients, and to identify the optimal IAP threshold value for delaying the deterioration of RRF.Methods A cohort of 62 newly initiated PD patients who completed both 6- and 12-month follow-up evaluations was obtained using the Durand method. A logistic regression model was used to identify variables associated with a rapid decline in RRF. Receiver operating characteristic (ROC) curves were generated to determine the optimal threshold value. Another retrospective cohort analysis was performed to validate the identified critical value.Results For each 1 cmH2O increase in IAP, the risk of a rapid decline in the RRF increased by a factor of 1.679. Subsequent analysis revealed that patients in the high IAP group had more significant decreases in residual renal estimated glomerular filtration rate (eGFR) (Z = −3.694, p

Heat-moisture treatment (HMT) could improve the structure and physicochemical characteristics of rice starch, the structural changes of amylose and amylopectin needed to be further investigated. Hence, the starch, amylose and amylopectin were modified by HMT with different moisture contents (MC). As MC increased, starch granules became irregular, amylose appeared molten while amylopectin was less damaged. The crystal structure of starch was disrupted by HMT. The increase in the double helix structure of amylose exhibited more drastic tendency towards molecular rearrangement than amylopectin did. In addition, the reduced proportion of amylopectin A chain could affect the rearrangement of amylose. The solubility and pasting temperature improved, but the enthalpy decreased. Moderate MC (20 %, 25 %) could enhance the viscosity and dynamic viscoelasticity. HMT promoted the conversion of RDS to RS, which was significantly increased by 85.26 % at HMT-40 %. These findings contributed to a better understanding of the mechanisms by which HMT affected starch.

Abstract Dysmobility Syndrome (DMS), is a combination, that is analogous to the approach taken with metabolic syndrome, The diagnosis of DMS is complex. So this study aimed to explore the relationship between 25-(OH) Vit D with Dysmobility Syndrome (DMS)in type 2 diabetes mellitus(T2DM) patients. This is a cross-sectional study, including 330 patients (67.0 ± 8.8 years old) with T2DM who were admitted to the Qinhuangdao First Hospital from October 2020 to February 2022. Selected independent variables include grip strength, six-meter gait speed, level of 25-(OH) vitamin D, and bone mineral density (BMD) measured by Dual-energy X-ray (DXA). DMS includes six conditions: osteoporosis, low muscle mass, low muscle strength, slow gait speed, occurrences of falls in the past year ≥ 1, and obesity, having three or more of these conditions were diagnosed with DMS. Patients were classified based on DMS. The detection rate of DMS in patients with T2DM was 25.5%. The proportion of vitamin deficiency is 67.9% in patients with T2DM. The 25-(OH) Vit D deficiency was defined based on the 25th percentile into two groups;

Abstract CD8+ T cell immune responses are regulated by multi-layer networks, while the post-translational regulation remains largely unknown. Transmembrane ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane proteins. Here, by targeting the sheddase A Disintegrin and Metalloprotease (ADAM)17, we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8+ T cells. Transcriptomic and proteomic analysis revealed the involvement of post-translational regulation in CD8+ T cells. T cell-specific deletion of ADAM17 led to a dramatic increase in effector CD8+ T cell differentiation and enhanced cytolytic effects to eliminate pathogens and tumors. Mechanistically, ADAM17 regulated CD8+ T cells through cleavage of membrane CD122. ADAM17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8+ T cells. Intriguingly, inhibition of ADAM17 in CD8+ T cells improved the efficacy of chimeric antigen receptor (CAR) T cells in solid tumors. Our findings reveal a critical post-translational regulation in CD8+ T cells, providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity.

Largemouth bass (LMB, Microterus salmoides) is an important commercial freshwater fish, and body color is a key economic trait for quality improvement. Gene editing has not been established in LMB due to the unavailability of one-cell fertilized eggs. In this study, three types of pigment cells, melanophores, iridophores and xanthophores were identified in LMB and melanophores were found first appeared in the iris of eyes in larvae 1.5 days after hatching. The fertilized eggs were obtained through hormonal induction (5 μg/kg LHRH-A3, 600 IU/kg hCG and 2 mg/kg DOM) and artificial insemination, and the tyrb (tyrosinase b) or csf1ra (colony-stimulating factor 1 receptor a) gRNA and Cas9 mRNA were microinjected into the fertilized eggs at the one-cell stage for targeted gene editing. The target site was designed on the first exon of tyrb and the second exon of csf1ra, respectively. The efficiency of mutation was gRNA and Cas9 mRNA concentration dependent, and 400 ng/μl gRNA and 800 ng/μl Cas9 mRNA were recommended as the appropriate injection dose for genome editing in LMB. Enzyme-digestion and sanger-sequencing demonstrated that the CRISPR/Cas9 system is available for the gene editing of LMB. The tyrb mutation resulted in reduced melanin and even albinism in eye and body of larvae, while the csf1ra mutation led to reddish body color, reduced xanthophores and melanophores in juvenile and adult fish with high mutation rate. Our results indicated that the CRISPR/Cas9 gene-editing system was successfully established in LMB. The mutation of body color related genes provided great convenience for the observation of mutant phonotypes and produced improved strains of LMB. It is the first successful application of gene-editing technology in LMB, which has taken a key step in studying the gene function and molecular mechanism and provided a novel method for improving the economic traits of LMB aquaculture.

Infantile Epileptic Spasm Syndrome (IESS) is a group of infantile spasm syndromes of various etiologies that typically present in early infancy, predispose to refractory epilepsy, and leave intellectual disability. Ketogenic diet therapy (KDT) is a non-pharmacologic treatment modality for medically refractory IESS. Recent scientific evidence supported the efficacy, safety, and tolerability of KDT for the treatment of IESS. KDT not only reduces the frequency of seizures in infants with IESS, but also improve their cognition and long-term prognosis. Recently, it has also received increasing attention as a potential treatment for neurological disorders. This reviewed the recent research progress of KDTs for the treatment of IESS, and discussed the different types and the mechanisms of KDTs, the expansion of KDT applications, the influencing factors, and future research issues.

Summary: The sea cucumber Apostichopus japonicus, a key species in Chinese aquaculture, plays a significant evolutionary role within the Echinodermata phylum. However, the sex determination mechanism in this species remains poorly understood. Here, we conducted extensive sex surveys and sampling of eight wild populations, investigating the sex-related SNPs and insertion or deletions (indels) through bulk segregation analysis (BSA) and genome-wide association study (GWAS) analysis. Our findings suggest that A. japonicus employs a polygenic sex determination (PSD) system, with solute carrier family 8 (SLC8A) being the candidate gene for sex determination, encoding sodium-calcium exchanger (NCX1). The analysis of normalized sequencing depth reveals variations across chromosomes 6, 13, 14, 16, and 18, supporting the PSD system. We also identified 541.656 kb of male-specific sequences and screened five markers (C77185, C98086, C64977, C125, and C876) for molecular sex identification. Overall, this study provides new insights into A. japonicus sex determination, highlighting a complex multi-gene mechanism rather than a simple XX/XY system.

ObjectiveTo explore the effectiveness and safety of the ketogenic diet (KD) in children with drug resistant epilepsy (DRE) caused by structural etiology.MethodsThe children were categorized into acquired brain injury group and malformations of cortical development (MCD) group based on the etiology. Follow-up assessments were performed at 1, 3, and 6 months after KD treatment to observe seizure reduction, behavioral and cognitive improvements, adverse reactions events, and reasons for discontinuation withdrawal. Statistical analysis was conducted on the results.ResultsWe found the seizure-free rates at 1, 3, and 6 months were 4.8% (2/42), 19% (8/42), and 21.4% (9/42), respectively. The seizure control effective rates were 42.9% (18/42), 52.4% (22/42), and 54.8% (23/42) at the corresponding time points. Compared to the acquired brain injury group, the MCD group showed a higher seizure control effective rate. Further analysis within the MCD group revealed the highest efficacy in focal cortical dysplasia (FCD). At the 3-month follow-up, cognitive and behavioral improvements were observed in 69% (29/42) of children. The main reasons for discontinuation were lack of efficacy and poor compliance.SignificanceFinally, we get that KD is a safe and effective treatment for drug resistant epilepsy caused by structural etiology, with the added benefit of improving behavioral and cognitive abilities in children. The efficacy is higher in children with MCD, particularly in cases of FCD. Early intervention with KD is recommended for this population.

Mimicking the structure of natural bone collagen fibers/hydroxyapatite (HA) to synthesize large size of HA for accelerated bone repair remains a challenge. Herein, silicon nitride nanowires (SN)-graphene (GE) was designed by the chemical vapor deposition, forming SN-GE (SG) similar to collagen fibers. Then, the large size HA was assembled onto SG by pulsed electrochemical deposition, the SG/HA (SGH) mimics the collagen fibers/HA structure of bone. The introduction of SG induces HA to large size grow in the form of coral-like. HA can be grown on a large size inextricably with the existence of GE modified layers. On the one hand, the upright GE sheets effectively increases the surface roughness which enhances the nucleation site of HA. On the other hand, the CO provides chemical bonding and induces HA nucleation. Compared with SN/HA(SH), the porosity of SGH decreased by 71%. The average diameter of the SGH is (9.76 ± 0.25) μm. Compared with SH, the diameter of SGH is 22 times larger than the diameter of SH. Indicating that SG induces large size growth of HA. Our work can provide a general strategy for the efficient preparation of biological scaffolds with large size HA that can be used in bone tissue engineering.

To simplify the composite propellant formulation and address the current issue of the single-functionality present in existing additives, the multi-cyano, amine-based polybutadiene (AEHTPB-CN) was prepared based on AEHTPB by adopting appropriate synthesis strategies. By replacing 10% of HTPB binder in the propellant formulation, it can effectively enhance the interfacial bond strength between the propellant binder matrix and solid fillers (AP (ammonium perchlorate) and RDX (cyclotrimethylene-trinitramine)), the mechanical properties of the HTPB/AP/RDX/Al propellant were superior to blank control propellant with an improvement of 35.4% in tensile strength, 62.0% enhancement in elongation at break, and reduce the propellant burn rate by 10.7% with any energy loss. The function mechanism of AEHTPB-CN was systematically elucidated through experiments and computer simulation techniques. The results show that the tertiary amine group in AEHTPB-CN can react with AP to form ammonium ionic bonds, and the hydroxyl and cyano groups can form hydrogen bonding interactions with AP, which enables AEHTPB-CN to be firmly adsorbed on the AP surface through chemical and physical interactions. For RDX, the interfacial bonding effect of AEHTPB-CN is attributed to their ability to form C–H⋅⋅⋅N≡C weak hydrogen bonding interaction between the cyano group and RDX methylene group.

In view of the natural endowment of mercury in fossil fuels and mineral resources, as well as the mercury emission controlling and regulating in the energy and resource utilization processes, the research and development on the mercury continuous emissions monitoring system (Hg-CEMS) with proprietary intellectual property rights is the most important requirement in science and technology in China. As a critical component of the Hg-CEMS system, the flue gas pretreatment system is a core technology that limits the development and application of the Hg-CEMS technology in China. This paper presents a comprehensive review of the research progress in the four key modules of the Hg-CEMS flue gas pretreatment technology, including the dilution sampling, Hg0/Hg2+ separation, Hg2+ reduction and Hg2+ calibration gas generation. Firstly, the dilution sampling techniques are highlighted in their characteristics and principles. The working principles, structures, and design considerations of the critical parameters for both critical hole and thermal dilution injectors are summarized. Emphasis is focused on the connection of numerical simulation with the optimal design methodology for the thermal dilution injector and critical hole. Secondly, regarding the Hg0/Hg2+ separation technology, various partitioning methodologies encompassing the wet absorption separation, physical adsorption separation and chemical adsorption separation are discussed. Particular attention is given to the separation and adsorption efficiency of the advanced dry chemical adsorption techniques involving the novel selective adsorbents of KCl and CaO with their updated theoretical and experimental outcomes under practical operating conditions. Thirdly, in aspect of the Hg2+ reduction technology, a comparative analysis of wet chemical reduction, low-temperature reduction and high-temperature reduction techniques is expatiated. Particular focus is on the active components of solid-state reducing agents, the impact of temperature on the reduction of divalent mercury, and the detrimental influences of flue gas components on the re-oxidation of the reduced elemental mercury in the low-temperature reduction techniques. An in-depth investigation of the impact of filler materials, acidic gas components and acid removal techniques on the reduction of divalent mercury in the high-temperature reduction techniques is highlighted. Finally, facing the technical problems, a solid generation method of the Hg2+ calibration gas is invented and its industrial utilization feasibility is verified in chemistry and experiments. In conjunction with the current status of research and application of the Hg-CEMS technology, the research technical routs, the solutions to some problems and development prospect for the above-mentioned four key modules are put forward.

(1) Background: The implication of type 2 (T2) inflammatory response in COVID-19 remains controversial. This study aimed to evaluate the association of eosinophils, neutrophils expressing eosinophilic surface markers and T2 cytokines with the severity and outcome of COVID-19. (2) Methods: Patients who were admitted to hospital due to COVID-19 from 18 December 2022 to 31 January 2023 were enrolled. Peripheral blood WBC and differentials, T2 cellular markers (subsets of eosinophils and neutrophils expressing eosinophilic surface markers) and cytokines at admission were measured and compared between subjects with different disease severities and outcomes. (3) Results: Ten mild-to-moderate and 22 severe-to-very severe cases were enrolled for analysis. Of these patients, seven died of severe-to-very severe disease. The severe-to-very severe patients showed a higher number of neutrophils, but lower numbers of eosinophils, lymphocytes cells and neutrophils expressing eosinophilic surface markers. Similarly, deceased cases were also characterized by increased neutrophils, but decreased eosinophils and neutrophils expressing eosinophilic surface markers. The levels of T2 cytokines failed to demonstrate a significant correlation with the severity or outcome of COVID-19. (4) Conclusions: Eosinophils and neutrophils expressing eosinophilic surface markers were associated with milder disease and better outcomes of COVID-19, suggesting that a T2 inflammatory response may confer a potential protective effect against the disease.

Limosilactobacillus reuteri is a species of lactobacillus present in the gastrointestinal tract of animals and may contribute to the balance of intestinal flora. This study aimed to investigate the effects and correlations of L. reuteri on both intestinal flora and muscle fiber characteristics of Sunit sheep, with the objective of enhancing meat quality. Twelve 8-month-old Sunit sheep were randomly divided into two groups: control (fed without L. reuteri) and L. reuteri group. The results showed that L. reuteri had a significant positive impact on meat quality, particularly improving the tenderness of sheep meat compared with the control group, with values of 69.8 and 76.8 N, respectively (P < 0.05). L. reuteri group showed significantly more type I muscle fibers (23% vs. 13%) and higher succinate dehydrogenase activity than the control group, while lactate dehydrogenase activity was significantly lower (P < 0.05). The L. reuteri group showed significantly higher expression of genes encoding colonic epithelial nutrient transport (GPR43) and immune barrier function (Zonulin) than the control group. At the genus level, Alistipes and Methanobacterium were significantly different between L. reuteri and control groups (P < 0.05), with L. reuteri group showing an increase of 2.9 times and a decrease of 8.0 times compared to the control group, respectively. At the species level, Succiniclasticum ruminis and Bacteroides sp. 43_108 were significantly (P < 0.05) lower and higher, respectively in L. reuteri group than those in the control group. Butyric acid exhibited the highest concentration in L. reuteri group, reaching 7.52 mmol/L. In conclusion, supplementation with L. reuteri may affect muscle fiber characteristics, enhance intestinal health, and facilitate carbohydrate digestion of Sunit sheep. This study offers novel insights into the use of feed additives for improving meat quality.

PurposeApproximately one-third of hepatocellular carcinoma (HCC) cases are characterized by alpha-fetoprotein (AFP) negativity (AFP-NHCC. Among these patients, around 60% exhibit des-gamma-carboxyprothrombin (DCP) positivity, and DCP-positive patients have a poorer prognosis. As a curative treatment, recurrence after liver resection poses significant challenges to the prognosis of HCC patients. Therefore, it is necessary to determine the relevant risk factors of these patients and provide timely treatment options.MethodsThis study included 540 patients who underwent resection at Beijing You’an Hospital. 292 patients from 2014 to 2018 constituted the training cohort, while 248 patients from 2018 to 2020 constituted the validation cohort. All patients underwent routine follow-ups until December 2023. Variables were identified through Cox regression, and a nomogram was developed. The nomogram was evaluated using time-dependent receiver operating characteristic curves (ROC), calibration curves, Decision curve analysis (DCA), and Kaplan-Meier (KM) curve analysisResultsWe found that age, tumor number, tumor size, γ-glutamyl transpeptidase (γ-GT), and prothrombin time (PT) are independent risk factors for HCC recurrence, and a nomogram was developed and validated based on this result to predict recurrence-free survival (RFS) at 1, 2, and 3 years. The performance of the nomogram was further confirmed by the ROC curve, calibration curve, and DCA, all of which showed favorable results. The KM curve analysis clearly distinguishes between two groups of people with different risks in terms of prognosis in both the training and validation sets.ConclusionIn summary, we established and validated a novel nomogram by multivariate Cox regression analysis to predict recurrence in DCP-positive patients with AFP-NHCC after resection. The nomogram, including age, tumor number, tumor size, γ-GT, and PT, demonstrates better predictive ability for AFP-NHCC patients with DCP positive.

Introduction:Bougainvillea glabra “Elizabeth Angus“ is a thorny woody vine or shrub. However, the hard thorns are considered a deficiency in its ornamental value.Methods: To find the genes and pathways related to the hardening process of the thorns on the stems of B. glabra, the eukaryotic unreferenced transcriptome sequencing analysis was conducted to explore the 3 stages of the thorn-hardening process. Total RNA was extracted from thorns and stems, and transcriptome libraries were constructed and sequenced using unreferenced Illumina sequencing.Results: Gene function annotation was performed using various databases, resulting in 8937 co-annotated genes. The density distribution of Fragments Per Kilobase of transcript per Million mapped reads (FPKM) depicted the overall gene expression patterns. The study found that stage 2 as the period of highest gene expression activity during the thorns hardening process in B. glabra. Differential expression analysis revealed that during thorn-hardening, 1045 genes up-regulated and 391 genes down-regulated significantly in thorns at stage 2 compared to stage 1 (early stage of thorns formation). Meanwhile, 938 genes up-regulated and 784 genes down-regulated significantly in stems. At stage 3, as thorns became harder, 63 genes exhibited notable expression increase and 98 genes’ expression decreased obviously within thorns, and 46 genes up-regulated and 29 genes down-regulated in stems, compared to stage 2. Phenylpropanoid biosynthesis was the key step in the hardening process of the thorns of B. glabra. The formation and hardening of thorns on the stem of B. glabra was a process in which lignin gradually accumulated in the thorns, and several genes were involved in this process. They include PAL (EC:4.3.1.24), CYP73A (EC:1.14.14.91), 4CL (EC:6.2.1.12), CCR (EC:1.2.1.44), CAD (EC:1.1.1.195) and POX (EC:1.11.1.7).Discussion: This transcriptome analysis offers insights into the molecular mechanisms underlying thorns development in this plant species.

Abstract Leaf senescence, the last stage of leaf development, is essential for crop yield by promoting nutrition relocation from senescence leaves to new leaves and seeds. NAC (NAM/ATAF1/ATAF2/CUC2) proteins, one of the plant-specific transcription factors, widely distribute in plants and play important roles in plant growth and development. Here, we identified a new NAC member OsNAC103 and found that it plays critical roles in leaf senescence and plant architecture in rice. OsNAC103 mRNA levels were dramatically induced by leaf senescence as well as different phytohormones such as ABA, MeJA and ACC and abiotic stresses including dark, drought and high salinity. OsNAC103 acts as a transcription factor with nuclear localization signals at the N terminal and a transcriptional activation signal at the C terminal. Overexpression of OsNAC103 promoted leaf senescence while osnac103 mutants delayed leaf senescence under natural condition and dark-induced condition, meanwhile, senescence-associated genes (SAGs) were up-regulated in OsNAC103 overexpression (OsNAC103-OE) lines, indicating that OsNAC103 positively regulates leaf senescence in rice. Moreover, OsNAC103-OE lines exhibited loose plant architecture with larger tiller angles while tiller angles of osnac103 mutants decreased during the vegetative and reproductive growth stages due to the response of shoot gravitropism, suggesting that OsNAC103 can regulate the plant architecture in rice. Taken together, our results reveal that OsNAC103 plays crucial roles in the regulation of leaf senescence and plant architecture in rice.

Introduction: Both innate and adaptive immune system undergo evolution from low to high vertebrates. Due to the limitation of conventional approaches in identifying broader spectrum of immune cells and molecules from various vertebrates, it remains unclear how immune molecules evolve among vertebrates. Objectives: Here, we utilized carry out comparative transcriptome analysis in various immune cells across seven vertebrate species. Methods: Single-cell RNA sequencing (scRNA-seq). Results: We uncovered both conserved and species-specific profiling of gene expression in innate and adaptive immunity. Macrophages exhibited highly-diversified genes and developed sophisticated molecular signaling networks along with evolution, indicating effective and versatile functions in higher species. In contrast, B cells conservatively evolved with less differentially-expressed genes in analyzed species. Interestingly, T cells represented a dominant immune cell populations in all species and unique T cell populations were identified in zebrafish and pig. We also revealed compensatory TCR cascade components utilized by different species. Inter-species comparison of core gene programs demonstrated mouse species has the highest similarity in immune transcriptomes to human. Conclusions: Therefore, our comparative study reveals gene transcription characteristics across multiple vertebrate species during the evolution of immune system, providing insights for species-specific immunity as well as the translation of animal studies to human physiology and disease.

Abstract Ferroptosis is an iron-dependent cell death mechanism involving the accumulation of lipid peroxides. As a critical regulator, glutathione peroxidase 4 (GPX4) has been demonstrated to be downregulated in epilepsy. However, the mechanism of ferroptosis in epilepsy remains unclear. In this study, bioinformatics analysis, analysis of epilepsy patient blood samples and cell and mouse experiments revealed strong associations among epilepsy, ferroptosis, microRNA-211-5p and purinergic receptor P2X 7 (P2RX7). P2RX7 is a nonselective ligand-gated homotrimeric cation channel, and its activation mainly increases neuronal activity during epileptic seizures. In our study, the upregulation of P2RX7 in epilepsy was attributed to the downregulation of microRNA (miR)-211-5p. Furthermore, P2RX7 has been found to regulate GPX4/HO-1 by alleviating lipid peroxidation induced by suppression of the MAPK/ERK signaling pathway in murine models. The dynamic decrease in miR-211-5p expression induces hypersynchronization and both nonconvulsive and convulsive seizures, and forebrain miR-211-5p suppression exacerbates long-lasting pentylenetetrazole-induced seizures. Additionally, in this study, induction of miR-211-5p expression or genetic-silencing of P2RX7 significantly reduced the seizure score and duration in murine models through the abovementioned pathways. These results suggest that the miR-211-5p/P2RX7 axis is a novel target for suppressing both ferroptosis and epilepsy.

Internal solitary waves (ISWs) resonate with meter-scale surface waves, which causes crests to overturn and waves to break strongly, generating many whitecaps. We analyze the polarized SAR characteristics of ISWs based on nonpolarized scattering theory and polarization decomposition theory. The surface breaking waves induced by ISWs generate short-scale waves carrying Bragg waves on the one hand, which enhances the polarized Bragg scattering (PD) contribution at the decimeter or centimeter scale and generate additional nonpolarized scattering (NP) contribution through specular scattering on the other hand. The copolarized scattering intensity in ISW regions is always higher than that in unperturbed sea surface under both L and C bands, with higher PD and NP contributions. The average PD is 1.3 (1.7) times higher than that of the unperturbed sea surface, and the average NP is approximately 82% (165%) higher than that of the sea surface. The PD and NP values associated with the convergent zones are always larger than those associated with the divergent zones, indicating that breaking waves mainly occur in convergence. The results of $\bm{HA}\alpha$ decomposition show that the scattering mechanism of ISWs is surface scattering with reduced scattering entropy and mean scattering angle. We construct compact polarization based on fully polarized SAR, and extract polarization parameters that indicate increased degree of polarization at ISWs, which supports our inference of enhanced specular scattering.

This investigation studies the properties and composition of extracellular polymeric substances (EPS) of the four tolerant bacterial strains [NH (Cellulosimicrobium cellulans), TH, YH, and HE (Pseudomonas aeruginosa)] under perfluorobutanesulfonic acid (PFBS) stress. The strains were acquired from athickened sludge in a fluorine chemical park. Each strain’s EPS were isolated by heating and centrifugation, and their growth, metabolic activity, and EPS alteration research pre- and post-stress were assessed and compared. The strain type was identified by morphological observation and 16S rDNA gene sequence analysis. Under PFBS (100 μg·L−1) stress, the four tolerant strains NH, TH, YH, and HE showed 38.10%, 29.26%, 35.92%, and 30.48% removal of PFBS on day 4, respectively, and the strain’s EPS had a substantial impact on main component protein (PR) and polysaccharide (PS) contents. The NH microorganism’s ability to metabolize organic matter was markedly stronger; it had a higher quantity, and its impact on main EPS content was greater than the other three tolerant strains. The three-dimensional excitation–emission matrix results showed marked alterations in tryptophan and aromatic protein peaks in the tolerant strain’s EPS. Furthermore, the FTIR analysis showed that the intensity of the functional groups in the proteins (-OH, C=O, -NH, and -CN) and the polysaccharides (-OH, C-O-C, and C-O) changed significantly. This investigation indicated that the proteins and polysaccharides of the tolerant strain’s EPS could provide more binding sites for PFBS adsorption, where the NH strain had the best biosorption capacity. This research provides a theoretical basis for elucidating efficient biosorbents.

Abstract Background Our study aimed to investigate whether serum total IgE and blood eosinophils were associated with radiological features of bronchiectasis in a Chinese cohort. Methods We retrospectively enrolled bronchiectasis patients who visited Peking University Third Hospital from Jan 1st, 2012 to Oct 7th, 2021. The clinical, laboratory and chest CT characteristics were analyzed in association with serum total IgE level and blood eosinophil count. Results A total of 125 bronchiectasis patients were enrolled, with 50.4% (63/125) female, and a mean age of 62.4 ± 14.1 years. The median serum total IgE level and blood eosinophil count were 47.7 (19.8, 123.0) KU/L and 140 (90, 230) cells/µl, respectively. In patients with a higher than normal (normal range, 0–60 KU/L) total IgE (43.2%, n = 54), more lobes were involved [4 (3, 5) vs. 3 (2, 4), p = 0.008], and mucus plugs were more common (25.9% vs. 9.9%, p =0.017) on HRCT, as compared to those with a normal level of total IgE. The higher IgE group was more likely to have bilateral involvement (p = 0.059), and had numerically higher Smith and Bhalla scores, but the differences were not statistically significant. In patients with an eosinophil count ≥ 150 cells/µl (49.6%, n = 62), the number of lobes involved was greater [4 (3, 5) vs. 3 (2, 4), p = 0.015], and the Smith and Bhalla scores were higher [9 (5, 12) vs. 6 (3, 9), p = 0.009, 7 (5, 11) vs. 5 (3, 9), p = 0.036]. The Smith score was correlated positively with the eosinophil count (r = 0.207, p = 0.020). Fractional exhaled nitric oxide (FeNO) was correlated with total IgE (r = 0.404, p = 0.001) and eosinophil count (r = 0.310, p = 0.014). Conclusions Our study demonstrated that serum total IgE and the blood eosinophil count were associated with the radiological extent and severity of bronchiectasis, necessitating further investigation on the role of T2 inflammation in structural abnormalities of this heterogeneous disease.

Abstract Sea cucumber is a morphologically diverse and ecologically important clade of echinoderms. The sea cucumber Apostichopus japonicus is the most economically valuable species of sea cucumber. The initial assembly of the A. japonicus genome was released in 2017. However, this genome assembly is fragmented and lacks relative position information of genes on chromosomes. In this study, we produced a high-quality chromosome-level genome of A. japonicus using Pacbio HiFi long-reads and Hi-C sequencing data. The assembled A. japonicus genome spanned 671.60 Mb with a contig N50 size of 17.20 Mb and scaffold N50 size of 29.65 Mb. A total of 99.9% of the assembly was anchored to 23 chromosomes. In total, 19,828 genes were annotated, and 97.2% of BUSCO genes were fully represented. This high-quality genome of A. japonicus will not only aid in the development of sustainable aquaculture practices, but also lay a foundation for a deeper understanding of their genetic makeup, evolutionary history, and ecological adaptation.

Abstract Background With the widespread use of low-dose computed tomography for lung cancer screening, the detection rate of pulmonary lesions manifesting as ground-glass opacities (GGOs) has been increasing dramatically. The volume doubling time (VDT) has been introduced in clinical practice to monitor the potential growth rate of GGOs during long-term follow-up periods. Case presentation A 72-year-old never-smoker female diagnosed with mixed GGO manifested abruptly accelerated growth with sudden decreased VDT from 400 to 36 days. A thoracoscopic left lower lobectomy with mediastinal lymph node dissection was performed, and the diagnosis was stage IB large-cell neuroendocrine carcinoma (LCNEC). Next-generation sequencing of the tumor highlights an EML4-ALK gene fusion. Conclusions The LCNEC may present as GGO with longer VDT in the early stage. VDT should calculate by the whole size either on the entire tumor diameter or on consolidation diameter. It is recommended that meticulous long-term follow-up with dynamic VDT monitoring may help select high-risk GGOs performing timely semi-elective surgical resection in clinical practice.

Abstract T cells are crucial for immune functions to maintain health and prevent disease. T cell development occurs in a stepwise process in the thymus and mainly generates CD4+ and CD8+ T cell subsets. Upon antigen stimulation, naïve T cells differentiate into CD4+ helper and CD8+ cytotoxic effector and memory cells, mediating direct killing, diverse immune regulatory function, and long-term protection. In response to acute and chronic infections and tumors, T cells adopt distinct differentiation trajectories and develop into a range of heterogeneous populations with various phenotype, differentiation potential, and functionality under precise and elaborate regulations of transcriptional and epigenetic programs. Abnormal T-cell immunity can initiate and promote the pathogenesis of autoimmune diseases. In this review, we summarize the current understanding of T cell development, CD4+ and CD8+ T cell classification, and differentiation in physiological settings. We further elaborate the heterogeneity, differentiation, functionality, and regulation network of CD4+ and CD8+ T cells in infectious disease, chronic infection and tumor, and autoimmune disease, highlighting the exhausted CD8+ T cell differentiation trajectory, CD4+ T cell helper function, T cell contributions to immunotherapy and autoimmune pathogenesis. We also discuss the development and function of γδ T cells in tissue surveillance, infection, and tumor immunity. Finally, we summarized current T-cell-based immunotherapies in both cancer and autoimmune diseases, with an emphasis on their clinical applications. A better understanding of T cell immunity provides insight into developing novel prophylactic and therapeutic strategies in human diseases.

Abstract Digestive autoimmune conditions are a growing challenge to global health. Risk factors associated with autoimmune digestive diseases are complex, including genetic variation, immunological dysfunction, and various environmental factors. To improve our understanding of the mechanisms behind digestive autoimmune conditions, including factors causing gastrointestinal manifestations and pathogenesis, BMC Immunology has launched a new Collection “The digestive system and autoimmunity”.

Sea cucumber (Apostichopus japonicus) is one of the cultured species with the highest production value to a single species in China’s marine agricultural industry with high nutritional and medicinal value. Body color influences numerous biological functions in sea cucumbers, and it has become a key trait in selective breeding. It is found that a cultivation environment with strong light intensity leads to a lighter body color of A. japonicus compared to dark conditions. However, little research has been conducted on the molecular mechanisms regulating body color in different breeding environments. In this study, we used Illumina sequencing to examine gene expression patterns in green and purple A. japonicus exposed to different culture conditions. Overall, the genes in the body wall of purple individuals were more affected by the environment. We also identified pathways that were potentially influenced by the breeding environment, such as “Drug metabolism - cytochrome P450”, “Porphyrin and chlorophyll metabolism”, “Phosphatidylinositol signaling system”, “TGF-beta signaling”, and “mTOR signaling”. The aim of this study was to determine the light conditions and breeding environment that are more favorable to the requirements of body color in A. japonicus and apply them to the selection of high-quality breeds. The results obtained will support the breeding of A. japonicus with specific traits and the production of seedlings to promote the development of this maricultural industry.

BackgroundThe impact of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on patients with bronchiectasis in terms of symptoms, self-management and medical resource utilization was unknown.ObjectiveTo describe the impact of infection by SARS-CoV-2 on fluctuation of symptoms, self-management and medical resource utilization of patients with bronchiectasis during the pandemic of COVID-19.MethodsThis was a single-center cross-sectional questionnaire study performed in Peking University Third Hospital. An online questionnaire investigation addressing the impact of SARS-CoV-2 infection on respiratory symptoms, self-management and medical resource utilization was conducted among patients with bronchiectasis during the COVID-19 surge in December 2022 in Beijing, China.ResultsFive hundred patients with bronchiectasis, with 285 (57%) females, and a mean (±SD) age of 57.9 ± 15.1 years, completed the telephone questionnaire. The reported prevalence of COVID-19 was 81.2% (406/500). Of the 406 COVID-19 patients, 89.2% experienced fever lasting mostly for no more than 3 days, 70.6 and 61.8% reported exacerbated cough and sputum production respectively, and 17.7% reported worsened dyspnea. Notable 37.4% of the patients with COVID-19 experienced symptoms consistent with the definition of an acute exacerbation of bronchiectasis. However, 76.6% (311/406) of the infected patients did not seek medical care but managed at home. Of the patients who visited hospitals, 26.3% (25/95) needed hospitalization and 2.1% (2/95) needed ICU admission. Multi-factors logistic regression analysis showed that younger age (p = 0.012) and not using a bronchodilator agent(p = 0.022) were independently associated with SARS-CoV-2 infection, while a history of exacerbation of bronchiectasis in the past year (p = 0.006) and daily use of expectorants (p = 0.002) were associated with emergency visit and/or hospitalization for patients with bronchiectasis after SARS-CoV-2 infection.ConclusionDuring the COVID-19 surge, the infection rate of SARS-CoV-2 in patients with bronchiectasis was high, and most of the patients experienced new-onset or exacerbated respiratory symptoms, but only a minority needed medical visits. Our survey results further underscore the importance of patients’ disease awareness and self-management skills during a pandemic like COVID-19.

Walnut oil oxidizes and becomes rancid during storage, that could be significantly affecting flavor and quality. This study aimed to monitor the volatile compounds present in walnut oil during storage, identify the characteristic markers of walnut oil at different oxidation levels, and establish a correlation network analysis based on the relationship between the olfactory analyzer and the characteristic markers to understand their correlation. The results indicated that the oxidation level of walnut oil had a positive correlation with the response of the olfactory analyzer. 219 volatile compounds were identified in walnut oil, with 89 identified as key volatile compounds (VIP >1). Among these, compounds such as (E, E)-2,4-decadienal (6.10%–23.04%)，(E, E)-2,4-heptadienal (2.23%–13.61%)，(E)-2-octenal (0.95%–11.71%)， hexanoic acid (1.63%–4.30%)，1-octen-3-ol (2.53%–19.01%)，(Z)-2-heptenal (5.95%–25.01%)，2,3-dihydro-furan (1.08%–3.20%)，2-pentyl-furan (0.13%–0.54%), pyrazine (0.33%–1.32%), hexanal (24.52%–1.33%)，3-hethylbutylacetate (12.44%–1.29%)， 2-methyl butyl acetate (7.74%–1.56%) and ethenyl hexanoate (4.39%–0.41%) were found to be characteristic volatile compounds in the oxidation process of walnut oil. Furthermore, the correlation network analysis revealed a strong correlation between the olfactory analyzer sensors and the characteristic volatile compounds. The findings of this study can provide valuable data for the development of rapid determination of the oxidation level of walnut oil.

This research explored the influences of ultrasonic and thermal treatments on the structure, functional properties, and beany flavor of soy protein isolate (SPI). In comparison with traditional thermal treatment, ultrasonic treatment effectively induced protein structural unfolding and exposure of hydrophobic groups, which reduced relative content of α-helix, increased relative content of β-turn, β-sheet and random coil, and improved the solubility, emulsifying and foaming properties of SPI. Both treatments significantly decreased the species and contents of flavor compounds, such as hexanal, (E)-2-nonenal, (Z)-2-heptenal and (E)-2-hexenal in SPI. The relative content of hexanal in the major beany flavor compound decreased from 11.69% to 6.13% and 5.99% at 350 W ultrasonic power and 150 s thermal treatment procedure, respectively. After ultrasonic treatment, structural changes in SPI were significantly correlated with functional properties but showed a weak correlation with flavor. Conversely, the opposite trend was observed for thermal treatment. Thus, using ultrasonic treatment to induce and stabilise the denatured state of proteins is feasible to improve the functional properties and beany flavor of SPI.

In order to study the bactericidal mechanism of slightly acidic electrolyzed water (SAEW) against Salmonella enteritidis, the effects of SAEW on cell membrane permeability, cell membrane integrity, reactive oxygen species (ROS), and intracellular ATP of Salmonella enteritidis were studied. The results showed that 2.04 lg (CFU/g) of Salmonella enteritidis on the surface of eggshells was inactivated after the SAEW treatment at the available chlorine concentration of 10 mg/L for 1 min. Moreover, relative to the control group, the conductivity of bacterial suspension of Salmonella enteritidis was increased from 13.78±0.13 ms/cm to 16.32±0.10 ms/cm (P

This article investigates one of the earliest attempts to systematically construct a building tradition and incorporate it into modern Chinese architectural design. These efforts were put forth by Liang Sicheng (1901–1972), one of the most distinguished Chinese architects and architectural historians, in the 1920s and 1930s in China, informed by the strong collective intention to honour the Chinese past. This article provides a historical and critical reflection on this collective intention that is still shared nowadays by architects and architectural theorists.This article examines in depth the evolution of the different ways Liang used the building past and constructed the Chinese architectural traditions in different crucial stages of his architectural career in the 1920s and 1930s. It uses architectural drawing as both the research subject and the research method. Three of Liang’s representative drawings from these crucial professional stages are juxtaposed and investigated to reveal this evolution using the iconography and iconology method.

Abstract Background Anesthesia and surgery can induce perioperative neurocognitive disorders (PND). Mitochondrial dysfunction has been proposed to be one of the earliest triggering events in surgery-induced neuronal damage. Dexmedetomidine has been demonstrated to attenuate the impairment of cognition in aged rats induced by surgery in our previous study. Methods Male Sprague-Dawley rats underwent hepatic apex resection under anesthesia with propofol to clinically mimic human abdominal surgery. The rats were divided into three groups: Control group, Model group and Dexmedetomidine (Dex) group. Cognitive function was evaluated with the Morris water maze (MWM), Open Field Test (OFT)and Novel object recognition task (NOR). Ultrastructural change in neuronal mitochondria was measured by transmission electron microscopy. Mitochondrial function was measured by mitochondrial membrane potential and activities of mitochondrial complexes. Neuronal morphology was observed with H&E staining and the activation of glial cells was observed by immunohistochemistry in the hippocampus. Protein levels were measured by Western blot (WB) and immunofluorescence at 3 and 7 days after surgery. Results Surgery-induced cognitive decline lasts three days, but not seven days after surgery in the model group. Transmission electron microscope showed the mitochondrial structure damage in the model group, similar changes were not induced in the Dex group. Dexmedetomidine may reverse the decrease in mitochondrial membrane potential and mitochondrial complex activity. Compared with the Control group, the expression of cytochrome c was significantly increased in model group by Western blot and immunofluorescence on days 3, but not day 7. Rats from the Model group expressed significantly greater levels of Iba-1 and GFAP compared with the Control group and the Dex group. Conclusion Dexmedetomidine appears to reverse surgery-induced behavior, mitigate the higher density of Iba-1 and GFAP, reduce the damage of mitochondrial structure and function by alleviating oxidative stress and protect mitochondrial respiratory chain, thus increasing cytochrome c oxidase (COX) expression and downregulate the expression of cytochrome c protein in the hippocampus of rats.

Carbon burial potential in marine sediments plays an important role in global warming. However, they are easily disturbed by human activities in coastal areas. In this study, marine sediment samples were collected from the coastal area of Bohai Bay, and the effects of exogenous inputs on the carbon content and forms were evaluated. Results showed that the carbon content in sediments ranged from 12.45 g/kg to 19.14 g/kg, with an average of 16.23 g/kg ± 2.78 g/kg, and the average organic carbon (C-Org) content is 12.68 ± 1.14 g/kg, which accounts for about 75% of the total carbon storage in sediment. The content of inorganic carbon (CaCO3) did not change significantly, but the content of C-Org in the estuary area was significantly higher than that in other areas. The proportions of active components in C-Org such as light organic carbon (LOC) and neutral organic carbon (NOC) were relatively low, accounting for approximately 9.49% and 18.15% of the total organic carbon, respectively. The spatial distribution characteristics of LOC and NOC were similar to that of C-Org in the study area. This indicates that human activities have increased the content of C-Org and its active components in marine sediments. Although C-Org and its active components are of relatively low abundance, both are easily affected by human activities which increase pollutants associated with the active components of organic carbon in coastal sediments. Therefore, further consideration should be given to reducing the pollutants carried by exogenous inputs, so that cleaner carbon can be buried in the sediments of Bohai Bay.

Regulatory T cells (Tregs) are instrumental in maintaining immune tolerance and preventing destructive autoimmunity, but how heterogeneous Treg populations are established remains largely unknown. Here, we show that Zfp335 deletion in Tregs failed to differentiate into effector Tregs (eTregs) and lose Treg-suppressive function and that KO mice exhibited early-onset lethal autoimmune inflammation with unrestricted activation of conventional T cells. Single-cell RNA-Seq analyses revealed that Zfp335-deficient Tregs lacked a eTreg population and showed dramatic accumulation of a dysfunctional Treg subset. Mechanistically, Zfp335-deficient Tregs displayed reduced oxidative phosphorylation and dysfunctional mitochondrial activity. Further studies revealed that Zfp335 controlled eTreg differentiation by regulating fatty acid oxidation (FAO) through direct targeting of the FAO enzyme Hadha. Importantly, we demonstrate a positive correlation between ZNF335 and HADHA expression in human eTregs. Our findings reveal that Zfp335 controls FAO-driven eTreg differentiation to establish immune tolerance.

In order to further realize the resource reuse of walnut meal after oil extraction, walnut meal was used as raw material to prepare polypeptide, and its angiotensin-converting enzyme (ACE) inhibitory activity was investigated. The ACE inhibitory peptides were prepared from walnut meal protein by alkaline solution and acid precipitation. The hydrolysis degree and ACE inhibition rate were used as indexes to optimize the preparation process by single-factor experiment and response surface method. The components with the highest ACE activity were screened by ultrafiltration, and their antioxidant activities were evaluated in vitro. The effect of gastrointestinal digestion on the stability of walnut peptide was analyzed by measuring molecular weight and ACE inhibition rate. The results showed that the optimal extraction conditions were pH 9.10, hydrolysis temperature 54.50 °C, and hydrolysis time 136 min. The ACE inhibition rate of walnut meal hydrolysate (WMH) prepared under these conditions was 63.93% ± 0.43%. Under the above conditions, the fraction less than 3 kDa showed the highest ACE inhibitory activity among the ACE inhibitory peptides separated by ultrafiltration. The IC50 value of scavenging ·OH free radical was 1.156 mg/mL, the IC50 value of scavenging DPPH free radical was 0.25 mg/mL, and the IC50 value of scavenging O2− was 3.026 mg/mL, showing a strong total reducing ability. After simulated gastrointestinal digestion in vitro, the ACE inhibitory rate of walnut peptide decreased significantly, but it still maintained over 90% ACE inhibitory activity. This study provides a reference for the application of low-molecular-weight walnut peptide as a potential antioxidant and ACE inhibitor.

Abstract Background Nocardia is a facultative intracellular pathogen that infects the lungs and brains of immunocompromised patients with consequences that can be fatal. The incidence of such infections is rising, immunocompetent individuals are also being infected, and there is a need to learn more about this neglected bacterial pathogen and the interaction with its human host. Results We have applied dual RNA-seq to assess the global transcriptome changes that occur simultaneously in Nocardia farcinica (N. farcinica) and infected human epithelial alveolar host cells, and have tested a series of mutants in this in vitro system to identify candidate determinants of virulence. Using a mouse model, we revealed the profiles of inflammation-related factors in the lung after intranasal infection and confirmed that nbtB and nbtS are key virulence genes for Nocardia infection in vivo. Regarding the host response to infection, we found that the expression of many histones was dysregulated during the infection of lung cells, indicating that epigenetic modification might play a crucial role in the host during Nocardia infection. In our mouse model, Nocardia infection led to neurological symptoms and we found that 15 of 22 Nocardia clinical strains tested could cause obvious PD-like symptoms. Further experiments indicated that Nocardia infection could activate microglia and drive M1 microglial polarization, promote iNOS and CXCL-10 production, and cause neuroinflammation in the substantia nigra, all of which may be involved in causing PD-like symptoms. Importantly, the deletion of nbtS in N. farcinica completely attenuated the neurological symptoms. Conclusions Our data contribute to an in-depth understanding of the characteristics of both the host and Nocardia during infection and provide valuable clues for future studies of this neglected human pathogen, especially those addressing the underlying causes of infection-related neurological symptoms.

Abstract Background Irisin is a novel myokine both in mice and humans, and it can also be secreted by adipose tissue and the liver in a small amounts. There are few studies on irisin and bone metabolism. The aim of this study was to assess the relationship between serum irisin levels and bone metabolism and analyze its related factors in Han young male with pre-diabetic individuals. Methods This cross-sectional study included 41 pre-diabetes and 45 normal glucose tolerance (NGT). Anthropometric measurements, including height, weight, waist circumference (WC), and bone mineral content (BMC), were performed. All patients underwent an oral glucose tolerance test (OGTT) after 8 h of fasting, and the levels of glucose, insulin, lipids, serum irisin and bone turnover markers were measured. Results The levels of serum irisin (4.4 ± 1.4 vs. 6.3 ± 1.5 µg/mL), P1NP and OC were significantly lower and CTX was significantly higher in the pre-diabetes group (P 0.05). Serum irisin levels negatively correlated with BMI (r =-0.325), FPG (r =-0.329), TG (r =-0.339) (P

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs), especially the latest Omicron, have exhibited severe antibody evasion. Broadly neutralizing antibodies with high potency against Omicron are urgently needed for understanding the working mechanisms and developing therapeutic agents. In this study, we characterized the previously reported F61, which was isolated from convalescent patients infected with prototype SARS-CoV-2, as a broadly neutralizing antibody against all VOCs including Omicron BA.1, BA.1.1, BA.2, BA.3 and BA.4 sublineages by utilizing antigen binding and cell infection assays. We also identified and characterized another broadly neutralizing antibody D2 with epitope distinct from that of F61. More importantly, we showed that a combination of F61 with D2 exhibited synergy in neutralization and protecting mice from SARS-CoV-2 Delta and Omicron BA.1 variants. Cryo-Electron Microscopy (Cryo-EM) structures of the spike-F61 and spike-D2 binary complexes revealed the distinct epitopes of F61 and D2 at atomic level and the structural basis for neutralization. Cryo-EM structure of the Omicron-spike-F61-D2 ternary complex provides further structural insights into the synergy between F61 and D2. These results collectively indicated F61 and F61-D2 cocktail as promising therapeutic antibodies for combating SARS-CoV-2 variants including diverse Omicron sublineages.

Local traditions have been the critical considerations in the current project of iterating architectural modernities outside of the West. Situated in these emerging debates, this article investigates an underrepresented artistic architectural modernity created by Liu Jipiao in the late-1920s China and re-evaluates the relationships among the past, tradition, and modernity. It recovers the method Liu used and how he used it to address the “past,” invent “tradition,” and create an “artistic modernity.” Moreover, it adopts the concept of collective identity to interrogate the way in which Liu harnessed the contemporary Chinese architectural zeitgeist to promote both his chosen method and the artistic modernity. Two related desires – the desire for designing tradition and the desire to define what it is to be both “Chinese” and an “architect” – had interwoven together, creating the artistic architectural modernity. This article thus explores the possibilities of China’s multiple architectural modernities, investigating more diverse positions for the past and tradition than previous research has revealed. Meanwhile, the article’s use of the concept of collective identity unveils more perspectives on Chinese architects’ longstanding desire for tradition in building Chinese modernity and avoids simplifying the motivation for this desire into a political stance on national identity.

Both Orthohantaviruses (HV) and Whenzhou Mammarenaviruses (WENV) are rodents borne viruses, allowing them to spread simultaneously in the same area and infect humans. To explore the potential threat of HV and WENV to public health safety, an environmental and laboratory investigation was conducted in 2020–2021, in Jiangxi province, China. A total of 461 small mammals of 7 species and paired sera from 43 suspected HFRS cases were collected from Jiangxi Province, China. Viral genomic RNA and specific antibodies against HV and WENV were detected to evaluate the epidemic situation of the two viruses. Hantaan virus (HTNV), seoul virus (SEOV) and WENV RNA were detected in the lungs of the captured mammals, which resulted 4.1% and 7.4% of HV and WENV RNA positive respectively. Co-infections of WENV and SEOV were detected from Rattus norvegicus, Mus musculus and Rattus flavipectus with an overall co-infection rate of 0.65%. The detection rates of antibodies in the blood against HV and WENV were 11.9% (55/461), and 13.2% (61/461) respectively. The prevalence of viral infection and viral genetic characters varied among the selected areas. In the paired sera of 43 suspected HFRS cases, 38 were with HV infection, 11 were with WENV IgG, and 7 with a 4-fold or more of WENV IgG titer elevation. These results revealed the fact of the co-circulating and coinfection of HV and WENV in the same area at the same time, which might impact on public health safety.

Timely and effective pest detection is essential for agricultural production, facing challenges such as complex backgrounds and a vast number of parameters. Seeking solutions has become a pressing matter. This paper, based on the YOLOv5 algorithm, developed the PestLite model. The model surpasses previous spatial pooling methods with our uniquely designed Multi-Level Spatial Pyramid Pooling (MTSPPF). Using a lightweight unit, it integrates convolution, normalization, and activation operations. It excels in capturing multi-scale features, ensuring rich extraction of key information at various scales. Notably, MTSPPF not only enhances detection accuracy but also reduces the parameter size, making it ideal for lightweight pest detection models. Additionally, we introduced the Involution and Efficient Channel Attention (ECA) attention mechanisms to enhance contextual understanding. We also replaced traditional upsampling with Content-Aware ReAssembly of FEatures (CARAFE), which enable the model to achieve higher mean average precision in detection. Testing on a pest dataset showed improved accuracy while reducing parameter size. The mAP50 increased from 87.9% to 90.7%, and the parameter count decreased from 7.03 M to 6.09 M. We further validated the PestLite model using the IP102 dataset, and on the other hand, we conducted comparisons with mainstream models. Furthermore, we visualized the detection targets. The results indicate that the PestLite model provides an effective solution for real-time target detection in agricultural pests.

In recent years, there have been significant advancements in the research of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV). However, several limitations and challenges still exist. For instance, researchers face constraints regarding experimental conditions and the feasibility of sample acquisition for studying SFTSV. To enhance the quality and comprehensiveness of SFTSV research, we opted to employ PMA-induced THP-1 cells as a model for SFTSV infection. Multiple time points of SFTSV infection were designed to capture the dynamic nature of the virus–host interaction. Through a comprehensive analysis utilizing various bioinformatics approaches, including diverse clustering methods, MUfzz analysis, and LASSO/Cox machine learning, we performed dynamic analysis and identified key genes associated with SFTSV infection at the host cell transcriptomic level. Notably, successful clustering was achieved for samples infected at different time points, leading to the identification of two important genes, PHGDH and NLRP12. And these findings may provide valuable insights into the pathogenesis of SFTSV and contribute to our understanding of host–virus interactions.