Search

Abstract Thyroid cancer treatments often impact patients’ quality of life (QOL). The transoral endoscopic thyroidectomy vestibular approach (TOETVA) gets lot attention as a scarless alternative, but its influence on postoperative QOL remains unclear. This study compares TOETVA and open surgery outcomes regarding postoperative QOL, scar satisfaction, and mental health in thyroid cancer patients to inform surgical decision-making. We retrospectively analyzed 221 thyroid cancer patients treated between January 2017 and September 2024: 136 underwent open surgery, and 85 had TOETVA. QOL was assessed using the EORTC QLQ-C30 and THYCA-QOL questionnaires. Scar appearance was evaluated with the Patient and Observer Scar Assessment Scale (POSAS), and mental health with the Hospital Anxiety and Depression Scale (HADS). EORTC QLQ-C30 scores showed no significant difference in overall QOL between TOETVA and open surgery (global health status: 81.31 vs. 83.43, P = 0.420). The open surgery group had higher summary THYCA-QOL scores (15.33 vs. 12.41, P = 0.033). While univariate analysis linked TOETVA to fewer thyroid cancer-specific symptoms (P = 0.033), multivariate analysis did not (P = 0.198). TOETVA patients had better scar satisfaction (P

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder in which mitochondrial dysfunction and neuroinflammation play crucial roles in its progression. Our previous studies found that cornuside from Cornus officinalis Sieb.Et Zucc is an anti-AD candidate, however, its underlying mechanism remains unknown. In the present study, AD mice were established by intracerebroventricular injection of Aβ1−42 and treated with cornuside (3, 10, 30 mg/kg) for 2 weeks. Cornuside significantly ameliorated behavioral deficits, protected synaptic plasticity and relieved neuronal damage in Aβ1−42 induced mice. Importantly, cornuside decreased NLRP3 inflammasome activation, characterized by decreased levels of NLRP3, ASC, Caspase-1, GSDMD, and IL-1β. Furthermore, cornuside promoted mitophagy accompanied by decreasing SQSTM1/p62 and promoting LC3B-I transforming into LC3B-II, via Pink1/Parkin signaling instead of FUNDC1 or BNIP3 pathways. In order to investigate the relationship between NLRP3 inflammasome and mitophagy in the neuroprotective mechanism of cornuside, we established an in-vitro model in BV2 cells exposed to LPS and Aβ1−42. And cornuside inhibited NLRP3 inflammasome activation and subsequent cytokine release, also protected neurons from damaging factors in microenvironment of conditional culture. Cornuside improved mitochondrial function by promoting oxidative phosphorylation and glycolysis, decreasing the production of ROS and mitochondrial membrane potential depolarization. Besides, mitophagy was also facilitated with increased colocalization of MitoTracker with LC3B and Parkin, and Pink1/Parkin, FUNDC1 and BNIP3 pathways were all involved in the mechanism of cornuside. By blocking the formation of autophagosomes by 3-MA, the protective effects on mitochondria, the inhibition on NLRP3 inflammasome as well as neuronal protection in conditional culture were eliminated. There is reason to believe that the promotion of mitophagy plays a key role in the NLRP3 inhibition of cornuside. In conclusion, cornuside re-establishes the mitophagy flux which eliminates damaged mitochondria and recovers mitochondrial function, both of them are in favor of inhibiting NLRP3 inflammasome activation, then alleviating neuronal and synaptic damage, and finally improving cognitive function.

Abstract To investigate the pleiotropic mechanisms linking brain structure and function to alcohol drinking and tobacco smoking, we integrated genome-wide data generated by the GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN; up to 805,431 participants) with information related to 3935 brain imaging-derived phenotypes (IDPs) available from UK Biobank (N = 33,224). We observed global genetic correlation of smoking behaviors with white matter hyperintensities, the morphology of the superior longitudinal fasciculus, and the mean thickness of pole-occipital. With respect to the latter brain IDP, we identified a local genetic correlation with age at which the individual began smoking regularly (hg38 chr2:35,895,678–36,640,246: rho = 1, p = 1.01 × 10−5). This region has been previously associated with smoking initiation, educational attainment, chronotype, and cortical thickness. Our genetically informed causal inference analysis using both latent causal variable approach and Mendelian randomization linked the activity of prefrontal and premotor cortex and that of superior and inferior precentral sulci, and cingulate sulci to the number of alcoholic drinks per week (genetic causality proportion, gcp = 0.38, p = 8.9 × 10−4, rho = −0.18 ± 0.07; inverse variance weighting, IVW beta = −0.04, 95%CI = −0.07–−0.01). This relationship could be related to the role of these brain regions in the modulation of reward-seeking motivation and the processing of social cues. Overall, our brain-wide investigation highlighted that different pleiotropic mechanisms likely contribute to the relationship of brain structure and function with alcohol drinking and tobacco smoking, suggesting decision-making activities and chemosensory processing as modulators of propensity towards alcohol and tobacco consumption.

Abstract Background Screening of malignant hematological diseases is of great importance for their diagnosis and subsequent treatment. This study constructed an optimal screening model for malignant hematological diseases based on routine blood cell parameters. Methods The venous blood samples of 1751 patients collected from 10 tertiary hospitals in China were divided into a training set (1223 cases) and a validation set (528 cases). In addition to the clinical diagnostic information of the samples in the training set, 26 blood cell parameters including morphological parameters were selected using manual screening and filtering to construct eight machine learning models. These models were used to identify hematological malignancies among the validation set. Results Comparison of the discrimination, calibration and clinical detection performance of the eight machine learning models revealed that the artificial neural network (ANN) model performed the optimal in identifying malignant haematological diseases in the validation set (528 cases), with an area under the receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity of 0.906, 0.857, 0.832 and 0.884, respectively. Conclusion The ANN model constructed can be used for screening of malignant hematological diseases, especially in primary hospitals that lack comprehensive diagnosis, and this ANN model will help patients to get diagnosis and treatment of malignant hematological diseases as early as possible.

Polysaccharides and polyphenols are important active substances in many foods and their raw materials. The interaction of polysaccharide and polyphenol may affect their physicochemical properties and functional activity respective, which also alter the nutritional and sensory qualities of food. This paper describes the means of characterizing food-derived polysaccharide and polyphenol interactions, including Fourier transform infrared (FT-IR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy, and interaction mechanisms such as enzyme-catalyzed reactions and free radical-induced reactions was also summarized. In addition, this paper focuses on the effects of concentration, pH, temperature and ionic strength on the interaction between polysaccharides and polyphenols, and further generalizes the alteration of physicochemical properties such as solubility and crystallinity, as well as bioactivities such as antioxidant and antimicrobial activities of polysaccharides and polyphenols under the interaction. Numerous research indicated that the formation of polysaccharide-polyphenol complexes had excellent biological activity and stability, promising good application prospects in food industry, healthcare, and other fields.

Abstract Background Persistent infection with high-risk human papillomavirus (HPV) is a significant risk factor for cervical cancer. HPV typing and cytology are conducted in women of appropriate age to assess the risk of cervical lesions and to guide the need for further diagnostic procedures such as colposcopy, cervical biopsy, or treatment. This article explores methods to predict the risks of high-grade precancerous cervical lesions based on high-risk HPV typing. Methods We conducted a retrospective analysis of HPV typing data from 158,565 women, including 19,707 who underwent ThinPrep cytologic testing (TCT), 7,539 who had colposcopy examinations, and 4,762 who had biopsies. We evaluated the sensitivity, specificity, and risk parameters of high-grade lesions associated with high-risk HPV types. Results (1) The overall prevalence of HPV infection was 17.89%, with the most prevalent types being HPV52 (4.44%), HPV58 (2.10%), HPV53 (1.96%), HPV81 (1.85%), HPV42 (1.75%), and HPV16 (1.44%). (2) The sensitivity and specificity of detecting high-grade lesions in TCT, colposcopy, and biopsy, based on high-risk HPV typing, demonstrated a strong linear correlation with the infection rate of each type. (3) HPV16 was confirmed to have a higher risk of CIN2 + in biopsies using a self-defined risk parameter. (4) The top five HPV types with the highest PPVs and pathogenicity risks in biopsies were HPV45, HPV16, HPV58, HPV33, and HPV18. Conclusion In Changsha, China, HPV52, HPV58, and HPV53 were the most prevalent and contributed significantly to high-grade lesions. After adjusting for infection rates, a self-defined risk parameter was proposed as a measure of the intrinsic risks of high-grade lesions associated with high-risk HPV types. Focused monitoring of prevalent high-risk HPV types such as HPV45, HPV16, HPV58, HPV33, and HPV18, which show the highest pathogenicity risks, is recommended in our region.

Abstract Glioblastoma multiforme (GBM) is characterized by pronounced immune escape and resistance to chemotherapy-induced apoptosis. Preliminary investigations revealed a marked overexpression of gasdermin E (GSDME) in GBM. Notably, cisplatin (CDDP) demonstrated a capacity of inducing pyroptosis by activating caspase-3 to cleave GSDME, coupled with the release of proinflammatory factors, indicating the potential as a viable approach of inducing anti-tumor immune activation. For the effective delivery of CDDP, the CDDP-polyphenol nanocomplexes were prepared, and catalase and copper ions were incorporated to fortify structural integrity, enhance glutathione (GSH) responsiveness, and ameliorate tumor hypoxia. Additionally, BV2 microglial cells were engineered to overexpress programmed death-1 (PD-1), and the membrane is employed for nanocomplex coating, effectively blocking the CDDP-induced upregulation of programmed death ligand 1 (PD-L1). Furthermore, the angiopep-2 peptide was modified to efficiently cross the blood brain barrier and specifically target GBM cells. In vitro analyses confirmed potent cytotoxicity and characteristic induction of pyroptosis. In vivo assays corroborated the enhancement of tumor targeting, culminating in an obvious suppression of tumor proliferation. A notable activation of immune cells was observed within tumors and lymph nodes, indicative of a synergistic effect of chemotherapy and immunotherapy, underscoring its potential as a safe and efficacious therapeutic strategy against GBM.

Abstract Background A. muciniphila (AKK) has attracted extensive research interest as a potential next-generation probiotics, but its role in intestinal pathology is remains unclear. Herein, this study was conducted to investigate the effects of A. muciniphila DSM 22,959 on growth performance, intestinal barrier function, microecology and inflammatory response of weaned piglets stimulated by dextran sulfate sodium salt (DSS). Method Twenty-four Duroc × Landrace × Yorkshire (DLY) weaned piglets used for a 2 × 2 factorial arrangement of treatments were divided into four groups with six piglets in each group. From 1 to 15 d, the CA and DA groups were orally fed with 1.0 × 1011 colony-forming units A. muciniphila per day, while the CON and DCON groups were received gastric infusion of anaerobic sterile saline per day. The pigs were orally challenged (DCON, DA) or not (CON, CA) with DSS from day 9 to the end of the experiment and slaughtered on day 16. Results Presence of A. muciniphila in DSS-challenged weaned pigs resulted in numerically increased diarrhea rate, blood neutrophilic granulocyte, serum C-reactive protein and immunoglobulin M levels, and numerically reduced final weight, average daily feed intake and average daily gain. The decrease in intestinal villus height, villous height: crypt depth ratio and digestibility was accompanied by lower expression of ZO1, ZO2, Claudin1, DMT1, CAT1, SGLT1 and PBD114 genes, as well as decreased enzyme activities of intestinal alkaline phosphatase, lactase, sucrase and maltase of piglets in DA group compared to piglets in DCON group. The abundance of Bifdobacterium, Lactobacillus, A. muciniphila, Ruminococcus gnavus was numerically higher in digesta of pigs in DA group than those in DCON group. The inflammatory responses of piglets were dramatically changed by the simultaneous presence of A. muciniphila and DSS: expression level of IL17A, IL17F, IL23, RORγt, Stat3 was elevated in DA pigs compared to the other pig groups. Conclusions Our result showed that the oral A. muciniphila aggravates DSS-induced health damage of weaned piglet, which may attribute to the deteriorating intestinal morphology, dysbiosis of microbiota and inflammatory response disorders.

Abstract Breast cancer became the most prevalent malignancy among women, and HER2 expression status is critical for treatment decisions. With the emergence of ADC drugs, HER2 low-expressing patients who previously did not respond well to traditional anti-HER2 therapies may now benefit. In this study, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were applied to assess HER2 expression in 349 patients with HER2-non-positive breast cancer. Our analysis revealed that HER2-low tumors exhibited fewer grade III tumors (39.74% and 55.65%, respectively, P = 0.005) and higher positivity for estrogen receptor (ER, 88.89% vs. 61.74%, P

Abstract This research demonstrates that DCC-2036 (Rebastinib), a potent third-generation tyrosine kinase inhibitor (TKI), effectively suppresses tumor growth in colorectal cancer (CRC) models with functional immune systems. The findings underscore the capacity of DCC-2036 to enhance both the activation and cytotoxic functionality of CD8+ T cells, which are crucial for facilitating anti-tumor immune responses. Through comprehensive multi-omics investigations, significant shifts in both gene and protein expression profiles were detected, notably a marked decrease in DKK1 levels. This reduction in DKK1 was linked to diminished CD8+ T cell effectiveness, correlating with decreased FGR expression. Moreover, our findings identify FGR as a pivotal modulator that influences DKK1 expression via the PI3K-AKT-SP1 signaling cascade. Correlative analysis of clinical specimens supports the experimental data, showing that increased levels of FGR and DKK1 in CRC tissues are associated with inferior clinical outcomes and reduced efficacy of immunotherapeutic interventions. Consequently, targeting the FGR-AKT-SP1-DKK1 pathway with DCC-2036 could potentiate immunotherapy by enhancing CD8+ T cell functionality and their tumor infiltration. This strategy may contribute significantly to the refinement of therapeutic approaches for CRC, potentially improving patient prognoses.

Abstract Informatization plays a leading role in promoting the deep integration of technology and industry and stimulating the vitality of new business creation. Based on city-level data from 2003 to 2022, this study investigates the effect of informatization on urban entrepreneurial activity and the mechanisms using the establishment of “pilot zones for informatization and industrialization integration” as a policy shock and employing a time-varying difference-in-differences (DID) method. The findings show that informatization significantly enhances urban entrepreneurial activity. Moreover, this effect is stronger in the smart manufacturing and service industries, as well as in cities with superior economic levels and higher administrative rankings. The mechanism test reveals that informatization mainly stimulates urban entrepreneurial activity by enhancing technical talents and technological foundations, expanding market demand, and improving the investment environment. This study not only enriches research on the correlation between informatization and entrepreneurship but also provides important theoretical basis and policy implications for fully leveraging the advantages of informatization construction and promoting urban entrepreneurship development.

Abstract CD73, an ectoenzyme responsible for adenosine production, is often elevated in immuno-suppressive tumor environments. Inhibition of CD73 activity holds great promise as a therapeutic strategy for CD73-expressing cancers. In this study, we have developed a therapeutic anti-human CD73 antibody cocktail, HB0045. HB0045 is a 1:1 mixture of two humanized monoclonal IgG1 antibodies (mAbs), HB0038 and HB0039. The cocktail not only harnesses the advantages of its parental mAbs in enzyme inhibition but also shows a significantly greater capability of promoting T cell proliferation in vitro. Structural analyses show that HB0045 effectively locks the CD73 dimer in a “partially open” non-active conformation through a double lock mechanism. In various animal models of syngeneic and xenograft tumors, HB0045 inhibits tumor growth more potently than the single mAbs. Collectively, our findings provide functional and structural insights into the mechanism of a CD73-targeting antibody cocktail.

Background: As traditional autopsy rates decline, the importance of forensic imaging, particularly postmortem computed tomography (PMCT), grows for non-invasive cause of death determination and evidence collection in legal investigations, with unique considerations required for frozen corpses due to the lack of systematic imaging characteristic studies. Aims and Objectives: This study aims to fill the gap in current knowledge by systematically analyzing the PMCT imaging characteristics of frozen corpses. Materials and Methods: This study utilized postmortem computed tomography (PMCT) and postmortem computed tomography angiography (PMCTA) to examine tissue changes during the freezing and thawing process in a total of 61 corpses. Results: The results demonstrated that imaging changes in the brain were most pronounced during freezing and thawing, with a clear correlation to the duration of freezing/thawing and the position of the corpses. Typical ice crystal artifacts were observed in body fluids after freezing, while thawing led to a marked increase and redistribution of internal gas. Serial angiographic studies revealed “pseudo-brain hemorrhage” in the brainstem and cerebellum in several cases due to incomplete thawing and transport. Conclusion: This study provides a comprehensive analysis of the CT imaging characteristics of frozen corpses, elucidating the imaging features during the freezing and thawing processes.

Abstract In the present work, we propose to explore the productions of the bottom and bottom-strange mesons in the high-energy pion and kaon-induced reactions on a proton target. The cross sections are evaluated with an effective Lagrangian constructed by the heavy-quark limit and chiral symmetry. Our estimations show that at $$P_\pi =80$$ P π = 80 GeV, the cross sections for B(5279), $$B^*(5325)$$ B ∗ ( 5325 ) , $$B_0^*(5722)$$ B 0 ∗ ( 5722 ) , $$B_1^\prime (5716)$$ B 1 ′ ( 5716 ) , $$B_1(5721)$$ B 1 ( 5721 ) and $$B_2^*(5747)$$ B 2 ∗ ( 5747 ) production processes are estimated to be 3.19–86.26, 1.86–51.29, 0.88–24.33, 0.86–23.69, 162.35–4477.66, and 57.16–1604.43 nb, respectively, where uncertainties arise from the model parameter. In addition, the cross sections for the corresponding bottom-strange mesons production processes are very similar. From the heavy quark effective theory point of view, the ratios between the cross sections for bottom mesons and bottom-strange mesons should be similar and the present estimations are consistent with the expectation of heavy quark limit. In particular, the cross-section ratios related to the states in the same doublets are of order one. The cross sections related to the states in the T doublets are about two orders larger than those related to the states in the S doublets.

Abstract Objective Apolipoprotein O (APOO) has been identified through bioinformatic prediction analysis as being highly expressed in various tumors, including breast cancer (BRCA). However, further investigations are required to understand and confirm APOO’s biological role in BRCA. Methods Bioinformatic analyses were employed to identify genes’ expression statuses and their relationship with the prognoses of patients. The genes’ functions were determined in cell line by gain or loss of function assays. Mechanistic studies were carried out by western blot. Results Our study reveals a correlation between increased APOO expression and poorer clinical outcomes in BRCA patients. The diagnostic value of APOO was demonstrated by Receiver Operating Characteristic (ROC) curve analysis, showing a notable area under the curve (AUC) of 0.937. Additionally, we observed that APOO knockdown impedes cell proliferation and migration. Gene Set Enrichment Analysis (GSEA) suggests that APOO expression is associated with the regulation of apoptosis and autophagy signaling pathways. Experimentally, modifying APOO expression in vitro influenced apoptosis and autophagy in BRCA cells. In conclusion, our findings indicate a significant link between APOO expression and BRCA progression, mediated through APOO’s impact on cellular apoptosis and autophagy. Conclusions Our data show that APOO controls BRCA process through apoptosis and autophagy signal pathway, which might provide multiple promising choices for the treatment of BRCA.

Introduction: The interplay between influential factors and the incidence of subthreshold depression (SD) in young adults remains poorly understood. Objectives: This study sought to understand the dietary habits, gut microbiota composition, etc. among individuals with SD in young adults and to investigate their association with SD occurrence. Methods: Employing a cross-sectional approach, 178 individuals with SD, aged 18–32 years, were matched with 114 healthy counterparts. SD status was evaluated using the Zung Self-rating Depression Scale (SDS), Zung Self-rating Anxiety Scale (SAS), Beck Depression Inventory 2nd version (BDI-II), the 17-item Hamilton Rating Scales of Depression (HAMD-17), and Pittsburgh Sleep Quality Index (PSQI). Metagenomic sequencing was utilized to identify fecal microbial profiles. Dietary patterns were discerned via factor analysis of a 25-item food frequency questionnaire (FFQ). Logistic regression analysis and mediation analysis were performed to explore the potential links between gut microbiota, dietary patterns, and incident SD. Results: Data on dietary habits were available for 292 participants (mean [SD] age, 22.1 [2.9] years; 216 [73.9 %] female). Logistic regression analysis revealed that dietary patterns Ⅰ (odds ratio [OR], 0.34; 95 % CI, 0.15–0.75) and IV (OR, 0.39; 95 % CI, 0.17–0.86 and OR, 0.39; 95 % CI, 0.18–0.84) were associated with reduced risk of SD. Distinct microbial profiles were observed in young adults with SD, marked by increased microbial diversity and taxonomic alterations. Moreover, mediation analysis suggested Veillonella atypica as a potential mediator linking SDS or BDI-II scores with a healthy dietary pattern rich in bean products, coarse grains, nuts, fruits, mushrooms, and potatoes (β = 0.25, 95 % CI: 0.02–0.78 and β = 0.18, 95 % CI: 0.01–0.54). Conclusions: Our findings highlight the complex interplay between dietary patterns, gut microbiota, and the risk of developing SD in young adults, underscoring the potential for dietary interventions and microbiome modulation in mental health promotion.

Abstract The controllable fabrication of patterned p-type and n-type channels with precise doping control presents a significant challenge, impeding the realization of complementary metal-oxide-semiconductor (CMOS) logic using a single van der Waals material. However, such an achievement could offer substantial benefits by enabling continued transistor scaling and unprecedented interlayer interconnect technologies. In this study, we devise a precise method for two-dimensional (2D) semiconductor substitutional doping, which allows for the production of wafer-scale 2H-MoTe2 thin films with specific p-type or n-type doping. Notably, we extend this approach to the synthesis of spatially selective doped 2H-MoTe2 thin films via a one-step growth method, facilitating the monolithic integration of p-type and n-type semiconductor channels. Leveraging this advancement, we successfully fabricate a chip-sized 2D CMOS inverter array that demonstrates excellent device performance and yield. Collectively, these findings represent a significant stride towards the practical incorporation of 2D semiconductors in very large-scale integration technology.

Abstract Background Oxidative stress significantly impacts growth performance and liver function in piglets. Ferulic acid (FA) works as an antioxidant, however, the role and mechanism of FA in the regulation of diquat-induced oxidative stress in piglets are less known. This study was designed to investigate the effects of FA on growth performance and antioxidant capacity in piglets with diquat challenge. Methods Thirty-two healthy DLY (Duroc × Landrace × Yorkshire) piglets (13.24 ± 0.19 kg) were randomly divided into one of two diets including 0 or 4 g/kg FA for 14 d. On d 15, all pigs were intraperitoneally injected diquat or sterile saline. Results Dietary supplementation with ferulic acid (FA) significantly improved the average daily gain (ADG) and decreased feed-gain ratio (F/G) of piglets. Here, dietary FA supplementation reduced serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities in diquat challenged piglets. Furthermore, diquat infusion increased reactive oxygen radicals (ROS) level in liver, decreased the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC) and increased malondialdehyde (MDA) content in the liver and serum. Supplementation with FA significantly increased T-AOC and T-SOD activities and decreased MDA and ROS levels. FA down-regulated gene and protein expression of Keap1, and up-regulated protein expression of Nrf2 and HO-1 in the liver of piglets with diquat challenge. Importantly, diquat challenge increased the ratio of late apoptosis, increased serum levels of IL-1β, IL-18 and lactate dehydrogenase (LDH), and up-regulated pyroptosis-related genes in the liver. FA supplementation reduced the ratio of late apoptosis and down-regulated mRNA expression of Caspase-1. Accordingly, FA addition reduced concentration of IL-1β, IL-18, and LDH under diquat challenge. Conclusions Diquat-induced oxidative stress reduced growth performance and impaired liver function in piglets. Dietary FA supplementation enhanced the antioxidant capacity and reduced the degree of hepatocyte pyroptosis, thereby alleviating the oxidative damage in the liver and mitigating the impact of diquat on growth performance of piglets.

Abstract Vestibular hair cells are mechanoreceptors critical for detecting head position and motion. In mammals, hair cell loss causes vestibular dysfunction as spontaneous regeneration is nearly absent. Constitutive expression of exogenous ATOH1, a hair cell transcription factor, increases hair cell regeneration, however, these cells fail to fully mature. Here, we profiled mouse utricles at 14 time points, and defined transcriptomes of developing and mature vestibular hair cells. To mimic native hair cells which downregulate endogenous ATOH1 as they mature, we engineered viral vectors carrying the supporting cell promoters GFAP and RLBP1. In utricles damaged ex vivo, both CMV-ATOH1 and GFAP-ATOH1 increased regeneration more effectively than RLBP1-ATOH1, while GFAP-ATOH1 and RLBP1-ATOH1 induced hair cells with more mature transcriptomes. In utricles damaged in vivo, GFAP-ATOH1 induced regeneration of hair cells expressing genes indicative of maturing type II hair cells, and more hair cells with bundles and synapses than untreated organs. Together our results demonstrate the efficacy of spatiotemporal control of ATOH1 overexpression in inner ear hair cell regeneration.

Abstract Sir2-HerA is a widely distributed antiphage system composed of a RecA-like ATPase (HerA) and an effector with potential NADase activity (Sir2). Sir2-HerA is believed to provide defense against phage infection in Sir2-dependent NAD+ depletion to arrest the growth of infected cells. However, the detailed mechanism underlying its antiphage activity remains largely unknown. Here, we report functional investigations of Sir2-HerA from Staphylococcus aureus (SaSir2-HerA), unveiling that the NADase function of SaSir2 can be allosterically activated by the binding of SaHerA, which then assembles into a supramolecular complex with NADase activity. By combining the cryo-EM structure of SaSir2-HerA in complex with the NAD+ cleavage product, it is surprisingly observed that Sir2 protomers that interact with HerA are in the activated state, which is due to the opening of the α15-helix covering the active site, allowing NAD+ to access the catalytic pocket for hydrolysis. In brief, our study provides a comprehensive view of an allosteric activation mechanism for Sir2 NADase activity in the Sir2-HerA immune system.

The lack of a direct map between control fields and desired control objectives poses a significant challenge in applying quantum control theory to quantum technologies. Here, we propose an analytical framework to precisely control a limited set of quantum states and construct desired coherent superpositions using a well-designed laser pulse sequence with optimal amplitudes, phases, and delays. This theoretical framework that corresponds to a multilevel pulse-area theorem establishes a straightforward mapping between the control parameters of the pulse sequence and the amplitudes and phases of rotational states within a specific subspace. As an example, we utilize this approach to generate 15 distinct and desired rotational superpositions of ultracold polar molecules, leading to 15 desired field-free molecular orientations. By optimizing the superposition of the lowest 16 rotational states, we demonstrate that this approach can achieve a maximum orientation value of |〈cosθ〉|_{max} above 0.99, which is very close to the global optimal value of 1 that could be achieved in an infinite-dimensional state space. This work marks a significant advancement in achieving precise control over multilevel subsystems within molecules. It holds potential applications in molecular alignment and orientation, as well as in various interdisciplinary fields related to the precise quantum control of ultracold polar molecules, opening up considerable opportunities in molecular-based quantum techniques.

In this study, we investigate the production of potential ΣcΣ¯c molecular states in nucleon-antinucleon collisions using a quasipotential Bethe-Salpeter equation approach. Both isoscalar and isovector bound states with quantum numbers JPC=0−+ and 1−− are generated from the ΣcΣ¯c interaction, which is modeled through the exchange of light mesons. The cross-section for the scattering process pp¯→pp¯ is calculated with annihilation effects taken into account, and the results are consistent with experimental data. However, no significant structures related to the ΣcΣ¯c state are observed in this process. Using the parameters determined from this analysis, we also investigate the reaction pp¯→ΛcΛ¯c, predicting a cross-section on the order of 10 pb with a dip near the ΣcΣ¯c threshold. We present the poles of four molecular states, noting that the state 0(1−−) exhibits a width much larger than those of the other three states, albeit still very small. For the isoscalar bound state with quantum numbers I(JPC)=0(1−−), a clear dip is observed near the ΣcΣ¯c threshold in the ΛcΛ¯c channel, with a cross-section on the order of 1 pb. Although a dip is also identified in the ΛcΛ¯c channel for the bound state with quantum numbers I(JPC)=0(0−+), it exhibits a very narrow width and a smaller cross-section, suggesting that highly precise experiments would be necessary to detect it. No significant structures are observed in the NN¯ final state for any of the four studied states. Based on these findings, we propose searching for the ΣcΣ¯c molecular state with I(JPC)=0(1−−) in the process NN¯→ΛcΛ¯c, which is accessible at P¯ANDA.

BackgroundSeptic shock (SS) is a syndrome with high mortality. Early forewarning and diagnosis of SS, which are critical in reducing mortality, are still challenging in clinical management. ObjectiveWe propose a simple and fast risk-stratified forewarning model for SS to help physicians recognize patients in time. Moreover, further insights can be gained from the application of the model to improve our understanding of SS. MethodsA total of 5125 patients with sepsis from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database were divided into training, validation, and test sets. In addition, 2180 patients with sepsis from the eICU Collaborative Research Database (eICU) were used as an external validation set. We developed a simplified risk-stratified early forewarning model for SS based on the weight of evidence and logistic regression, which was compared with multi-feature complex models, and clinical characteristics among risk groups were evaluated. ResultsUsing only vital signs and rapid arterial blood gas test features according to feature importance, we constructed the Septic Shock Risk Predictor (SORP), with an area under the curve (AUC) of 0.9458 in the test set, which is only slightly lower than that of the optimal multi-feature complex model (0.9651). A median forewarning time of 13 hours was calculated for SS patients. 4 distinct risk groups (high, medium, low, and ultralow) were identified by the SORP 6 hours before onset, and the incidence rates of SS in the 4 risk groups in the postonset interval were 88.6% (433/489), 34.5% (262/760), 2.5% (67/2707), and 0.3% (4/1301), respectively. The severity increased significantly with increasing risk in both clinical features and survival. Clustering analysis demonstrated a high similarity of pathophysiological characteristics between the high-risk patients without SS diagnosis (NS_HR) and the SS patients, while a significantly worse overall survival was shown in NS_HR patients. On further exploring the characteristics of the treatment and comorbidities of the NS_HR group, these patients demonstrated a significantly higher incidence of mean blood pressure

By using the hourly visibility, temperature, pressure, humidity, wind, and atmospheric particulate concentration data in Chongqing from 2015 to 2023, the characteristics of low visibility (visibility

IntroductionHepatocellular carcinoma (HCC) is the most prevalent liver cancer and a leading cause of cancer-related deaths worldwide. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) plays a critical role in RNA metabolism, including alternative splicing, which is linked to cancer progression. Our study investigated the role of hnRNPA1 in HCC and its potential as a therapeutic target.MethodsWe analyzed hnRNPA1 expression in HCC tissues compared to non-tumor tissues using RNA-seq and immunohistochemistry. hnRNPA1 was knocked down in Hep G2 cells to assess its impact on cell proliferation, migration, and apoptosis using scratch assays, flow cytometry, qPCR, and Western blot. We also explored the interaction between hnRNPA1 and ZNF207, as well as its splicing effects and downstream signaling pathways by RIP assay, bioinformatics, qPCR and Western blot.ResultshnRNPA1 was significantly upregulated in HCC tissues compared to normal tissues, correlating with poor patient survival. hnRNPA1 knockdown reduced Hep G2 cell proliferation and migration while increasing apoptosis. We identified that hnRNPA1 bound to ZNF207 and regulated its exon 9 skipping, influencing ZNF207 splicing and the PI3K/Akt/mTOR pathway, key regulators of cell growth and survival.ConclusionOur findings demonstrate that hnRNPA1 promotes HCC progression by regulating ZNF207 splicing and the PI3K/Akt/mTOR pathway. hnRNPA1-ZNF207 interaction represents a potential therapeutic target for HCC, providing insights into the molecular mechanisms underlying HCC progression.

Abstract High-order diffraction (HOD) from optical microstructures is undesirable in many applications because of the accompanying ghosting patterns and loss of efficiency. In contrast to suppressing HOD with subwavelength structures that challenge the fabrication of large-scale devices, managing HOD is less developed due to the lack of an efficient method for independently manipulating HOD. Here, we report independent manipulation of HODs, which are unexploited for subdiffraction-limit focusing in diffractive lenses, through an analytical formula that correlates the diffraction order and the width of each zone. The large spatial frequencies offered by the HODs enable our lenses to reduce the lateral focal size down to 0.44 λ even without any subwavelength feature (indispensable in most high-NA diffractive lenses), facilitating large-scale manufacture. Experimentally, we demonstrate high-order lens-based confocal imaging with a center-to-center dry resolution of 190 nm, the highest among visible-light confocal microscopies, and laser-ablation lithography with achieved direct-writing resolution of 400 nm (0.385 λ).

Abstract Background The netrin-1/CD146 pathway regulates colorectal cancer (CRC) liver metastasis, angiogenesis, and vascular development. However, few investigations have yet examined the biological function of netrin-1/CD146 complex in CRC. In this work, we investigated the relationship between the netrin-1/CD146 axis and S100 proteins in sentinel lymph node, and revealed a possible new clue for vascular metastasis of CRC. Methods The expression levels of netrin-1 and CD146 proteins in CRC, as well as S100A8 and S100A9 proteins in the sentinel lymph nodes were determined by immunohistochemistry. Using GEPIA and UALCAN, we analyzed netrin-1 and CD146 gene expression in CRC, their association with CRC stage, and their expression levels and prognosis in CRC patients. Results The expression level of netrin-1 in N1a+1b (CRC lymphatic metastasis groups, exculded N1c) was positively increased with N0 (p = 0.012). The level of netrin-1 protein was positively correlated with CD146 protein (p 0.05). Conclusions The netrin-1/CD146 and netrin-1/S100A9 axis in CRC tissues might related with early stage of lymph node metastasis, thus providing potential novel channels for blocking lymphatic metastasis and guiding biomarker discovery in CRC patients.

Abstract Background Addressing the shortage of high-quality protein resources, this study was conducted to investigate the effects of replacing soybean meal (SBM) with different levels of enzymolysis-fermentation compound protein feed (EFCP) in the diets of growing-finishing pigs, focusing on growth performance, nutrients digestibility, carcass traits, and meat quality. Methods Sixty DLY (Duroc × Landrace × Yorkshire) pigs with an initial body weight of 42.76 ± 2.05 kg were assigned to 5 dietary treatments in a 2 × 2 + 1 factorial design. These dietary treatments included a corn-soybean meal diet (CON), untreated compound protein feed (UCP) substitution 50% (U50) and 100% SBM (U100) diets, and EFCP substitution 50% (EF50) and 100% SBM (EF100) diets. Each treatment had 6 pens (replicates) with 2 pigs per pen, and the experiment lasted 58 d, divided into phase I (1–28 d) and phase II (29–58 d). Following phase I, only the CON, U50, and EF50 groups were continued for phase II, each with 5 replicate pens. On d 59, a total of 15 pigs (1 pig/pen, 5 pens/treatment) were euthanized. Results During phase I, the EF50 group had a higher average daily gain (ADG) in pigs (P

The aim of this study was to investigate the reasons for the differences in lipid accumulation between lean and obese pigs. The bile acids with varying levels within two types of pigs were found and then in vitro experiments were conducted to identify whether these bile acids can directly affect lipid accumulation. Fourteen pigs, including seven lean and seven obese pigs with body weights of approximately 80 kg, were fed the same diet at an amount approximately equivalent to 3% of their respective body weights daily for 42 d. In vitro, 3T3-L1 preadipocytes were cultured in medium with high glucose levels and were differentiated into mature adipocytes using differentiation medium. Then, bile acids were added to mature adipocytes for 4 d. The results showed that there was a difference in body lipids levels and gut microbiota composition between obese and lean pigs (P

Two new species Laccaria pseudoalba and L. subroseoalbescens are described and illustrated, based on morphological characteristics and molecular phylogenetic analysis. Two new records, Laccaria umbilicata and L. yunnanensis from Thailand, are also reported. Laccaria subroseoalbescens is characterized by small basidiomata, stipe equal with an enlarged base, and nearly subclavate, pale pink to light orange. Laccaria pseudoalba is characterized by pale orange to orange white pileus, has umbo when young on the pileus, and fistulose stipe of the pale to pastel red color. Phylogenetic analysis based on sequence data from rDNA internal transcribed spacer ITS1-5.8S-ITS2 rDNA (ITS), nuc 28S rDNA (28S), RNA polymerase II subunit 2 (rpb2), and translation elongation factor 1-α (tef1-α) are provided as further evidence. Molecular analysis confirms the phylogenetic positions of the two new species and two new records. The differences in characteristics of these two new species and closely related species are discussed herein.

Abstract Background Appropriate iron supplementation is essential for neonatal growth and development. However, there are few reports on the effects of iron overload on neonatal growth and immune homeostasis. Thus, the aim of this study was to investigate the effects of iron nutrition on neonatal growth and intestinal immunity by administering different levels of iron to neonatal pigs. Results We found that iron deficiency and iron overload resulted in slow growth in neonatal pigs. Iron deficiency and iron overload led to down-regulation of jejunum intestinal barrier and antioxidant marker genes, and promoted CD8+ T cell differentiation in jejunum and mesenteric lymph nodes (MLN) of pigs, disrupting intestinal health. Moreover, iron levels altered serum iron and tissue iron status leading to disturbances in redox state, affecting host innate and adaptive immunity. Conclusions These findings emphasized the effect of iron nutrition on host health and elucidated the importance of iron in regulating redox state and immunity development. This study provided valuable insights into the regulation of redox state and immune function by iron metabolism in early life, thus contributing to the development of targeted interventions and nutritional strategies to optimize iron nutrition in neonates.

Abstract Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants has long been suggested but its molecular basis remains poorly understood. Here, we identify a class of SARS-CoV-2 neutralizing public antibodies defined by their shared usage of VL6-57 light chains. Although heavy chains of diverse genotypes are utilized, convergent HCDR3 rearrangements have been observed among these public antibodies to cooperate with germline VL6-57 LCDRs to target a convergent epitope defined by RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this class of VL6-57 antibodies is present in SARS-CoV-2-naive individuals and is clonally expanded in most COVID-19 patients. We confirm that Omicron-specific substitutions at S371, S373 and S375 mediate escape of antibodies of the VL6-57 class. These findings support that this class of public antibodies constitutes a potential immune pressure promoting the introduction of S371L/F-S373P-S375F in Omicron variants. The results provide further molecular evidence to support that antigenic evolution of SARS-CoV-2 is driven by antibody mediated population immunity.

Abstract Non-genetic mechanisms have recently emerged as important drivers of anticancer drug resistance. Among these, the drug tolerant persister (DTP) cell phenotype is attracting more and more attention and giving a predominant non-genetic role in cancer therapy resistance. The DTP phenotype is characterized by a quiescent or slow-cell-cycle reversible state of the cancer cell subpopulation and inert specialization to stimuli, which tolerates anticancer drug exposure to some extent through the interaction of multiple underlying mechanisms and recovering growth and proliferation after drug withdrawal, ultimately leading to treatment resistance and cancer recurrence. Therefore, targeting DTP cells is anticipated to provide new treatment opportunities for cancer patients, although our current knowledge of these DTP cells in treatment resistance remains limited. In this review, we provide a comprehensive overview of the formation characteristics and underlying drug tolerant mechanisms of DTP cells, investigate the potential drugs for DTP (including preclinical drugs, novel use for old drugs, and natural products) based on different medicine models, and discuss the necessity and feasibility of anti-DTP therapy, related application forms, and future issues that will need to be addressed to advance this emerging field towards clinical applications. Nonetheless, understanding the novel functions of DTP cells may enable us to develop new more effective anticancer therapy and improve clinical outcomes for cancer patients.

Abstract This study investigates the nature of the $$X_0(2900)$$ X 0 ( 2900 ) and $$\chi _{c0}(3930)$$ χ c 0 ( 3930 ) based on experimental results of the process $$B^+$$ B + $$\rightarrow $$ → $$D^+ D^- K^+$$ D + D - K + . We focus on the S-wave $$D^{*-}K^{*+}$$ D ∗ - K ∗ + and $$D_s^+D_s^-$$ D s + D s - molecular states, which can be related to the $$X_0(2900)$$ X 0 ( 2900 ) and $$\chi _{c0}(3930)$$ χ c 0 ( 3930 ) , respectively. Using effective Lagrangians, we construct the potential kernel of the $$D^{*-}K^{*+}$$ D ∗ - K ∗ + – $$D^{-}K^{+}$$ D - K + and $$D_s^+D_s^-$$ D s + D s - – $$D^+D^-$$ D + D - interactions with a one-boson-exchange model, and determine the scattering amplitudes and their poles through a quasipotential Bethe–Salpeter equation approach. By incorporating the potential kernel into the three-body decay process $$B^+$$ B + $$\rightarrow $$ → $$D^+ D^- K^+$$ D + D - K + , we evaluate the $$D^-K^+$$ D - K + and $$D^+D^-$$ D + D - invariant mass spectra, as well as the Dalitz plot, using Monte Carlo simulation. A satisfactory fit to the $$D^-K^+$$ D - K + and $$D^+D^-$$ D + D - invariant mass spectra is achieved after introducing additional Breit–Wigner resonances, $$X_1(2900)$$ X 1 ( 2900 ) , $$\psi (3770)$$ ψ ( 3770 ) , and $$\chi _{c2}(3930)$$ χ c 2 ( 3930 ) . Prominent signals of the $$X_0(2900)$$ X 0 ( 2900 ) and $$\chi _{c0}(3930)$$ χ c 0 ( 3930 ) states appear as peaks in the $$D^-K^+$$ D - K + and $$D^+D^-$$ D + D - invariant mass spectra near 2900 and 3930 MeV, respectively. Clear event concentration from the $$X_0(2900)$$ X 0 ( 2900 ) and $$\chi _0(3930)$$ χ 0 ( 3930 ) is evident as strips in the Dalitz plot. The results suggest that both $$X_0(2900)$$ X 0 ( 2900 ) and $$\chi _{c0}(3930)$$ χ c 0 ( 3930 ) can be interpreted as molecular states, with the inclusion of $$X_1(2900)$$ X 1 ( 2900 ) and $$\chi _2(3930)$$ χ 2 ( 3930 ) necessary to describe structures in the $$D^-K^+$$ D - K + and $$D^+D^-$$ D + D - invariant mass spectra, respectively.

Key Clinical Message This study reports a Chinese male patient with a novel MeCP2 p.Lys254*variant. Upon birth, the patient presented with typical symptoms, such as abnormal electroencephalogram, immature sleep rhythm, hypotonia, feeding difficulties, pulmonary fluid accumulation, horizontal fissures in the lungs, hypoventilation, and heart defects. Abstract MeCP2 is a gene located on the X chromosome and the main pathogenic gene responsible for Rett syndrome, which mainly occurs in females. Herein, we identified a male patient with a novel MeCP2 p.Lys254* variant through whole‐exome sequencing, although both parents are wild type. Upon birth, the patient presented with typical symptoms, such as abnormal electroencephalogram, immature sleep rhythm, hypotonia, feeding difficulties, pulmonary fluid accumulation, horizontal fissures in the lungs, hypoventilation, and other symptoms. Period of breathing support, but also found that the boy had a heart defect and horizontal fissure in the lungs. Our discovery of a new spontaneous MeCP2 nonsense mutation enriches the understanding of Rett syndrome and provides a reference for its early diagnosis and treatment.

Green development is key to promoting regional sustainable development. We construct an evaluation index system for green development levels based on the “sansheng” dimensions—production, living, and ecology. We rely on the “sansheng” (production, living, and ecology) dimensions, combined with the analytic hierarchy process (AHP) and the entropy weight method to analyze indicator weights, to construct an evaluation index system for green development levels. This system enables the identification of the evolution patterns of green development and the analysis of driving factors in the Chengdu-Chongqing economic zone from the “sansheng” perspective. The results indicate that: (1) The green development level in the Chengdu-Chongqing Economic Zone has been continuously rising, with the average index increasing from 0.197 to 0.254. Yuzhong District and Chengdu City have shown particularly high green development levels; in 2020, the green development level index for Yuzhong District reached 0.568, while Chengdu City’s index reached 0.522. (2) The spatial clustering of green development levels in the Chengdu-Chongqing economic zone exhibited a trend of first strengthening and then weakening, with the highest clustering degree observed in 2015. (3) National strategies have significantly promoted the improvement of regional green development levels. The average green development index during the pre-establishment, initial development, and rapid development stages of the Chengdu-Chongqing Economic Zone increased from 0.205 to 0.229, and then to 0.254. (4) The Theil index results show an increase in the disparity of green development levels among different regions within the Chengdu-Chongqing Economic Zone.The results of the optimal scaling regression model show that the driving factors with a significant impact on the level of green development include the Number of physicians per million people, Public library book collections Per 100 people, Per capita regional GDP, and Number of secondary schools Per million people, each contributing over 15% to the impact. These findings provide valuable data support for formulating regional economic development strategies and are conducive to advancing sustainable development.

Gastric mixed adenoneuroendocrine carcinoma (MANEC) is a rare and highly aggressive malignancy characterized by both exocrine and neuroendocrine components. Treatment options for metastatic cases are limited, with typical therapeutic approaches involving a combination of chemotherapy and immunotherapy. A 68-year-old male with metastatic gastric MANEC was treated with targeted therapy, immunotherapy, and chemotherapy, including S-1, apatinib, cadonilimab, and paclitaxel. After six cycles, the liver metastases resolved completely, and the primary tumor achieved partial remission, leading to conversion surgery. The patient underwent a radical D2 gastrectomy with R0 resection, including proximal gastrectomy, splenectomy, omentectomy, and esophagogastric anastomosis, along with radiofrequency ablation of liver metastases. Postoperative pathology confirmed the disappearance of liver metastases but revealed residual adenocarcinoma in the primary gastric lesion and neuroendocrine components in the perigastric lymph nodes. The patient was discharged seven days post-surgery. Five months postoperatively, new liver metastases were detected, exhibiting neuroendocrine differentiation. The patient was subsequently treated with a maintenance regimen of S-1 and pembrolizumab. This case highlights the significant heterogeneity of gastric MANEC and the challenges in managing such cases. While conversion surgery can be effective in certain contexts, the high likelihood of postoperative recurrence and metastasis, particularly in neuroendocrine components, necessitates cautious consideration. Further research is needed to evaluate the long-term benefits of conversion surgery in metastatic gastric MANEC and to develop tailored therapeutic strategies.

Alzheimer’s disease (AD) is a neurodegenerative disorder that severely impacts cognitive function, posing significant physical and psychological burdens on patients and substantial economic challenges to families and society, particularly in aging populations where its prevalence is rising. Current diagnostic and therapeutic strategies, including pharmacological treatments and non-pharmacological interventions, exhibit considerable limitations in early diagnosis, etiological treatment, and disease management. This study aims to investigate the application of artificial intelligence (AI) in the early diagnosis and progression monitoring of AD through a bibliometric analysis of relevant literature. A systematic search in the Web of Science Core Collection identified 530 publications related to AI and AD, consisting of 361 original research articles and 169 review articles, with a notable increase in annual publication rates, particularly between 2019 and 2024. The United States and China emerged as leading contributors, emphasizing the importance of international collaboration. Institutional analysis revealed that Harvard University and Indiana University System are at the forefront, highlighting the role of academic institutions in fostering interdisciplinary research. Furthermore, the Journal of Alzheimer’s Disease was identified as the most influential publication outlet. Key highly cited papers provided essential theoretical foundations for ongoing research. This study underscores the growing relevance of AI in AD research and suggests promising avenues for future investigations, particularly in enhancing diagnostic accuracy and therapeutic strategies through advanced data analytics and machine learning techniques.

Re-emerging human adenovirus type 55 (HAdV55) has become a significant threat to public health due to its widespread circulation and the association with severe pneumonia, but an effective anti-HAdV55 agent remains unavailable. Herein, we report the generation of macaque-derived, human-like monoclonal antibodies (mAbs) protecting against HAdV55 infection with high potency. Using fluorophore-labelled HAdV55 virions as probes, we isolated specific memory B cells from rhesus macaques (Macaca mulatta) that were immunized twice with an experimental vaccine based on E1-, E3-deleted, replication-incompetent HAdV55. We cloned a total of 19 neutralizing mAbs, nine of which showed half-maximal inhibitory concentrations below 1.0 ng/ml. These mAbs recognized the hyper-variable-region (HVR) 1, 2, or 7 of viral hexon protein, or the fibre knob. In transgenic mice expressing human desmoglein-2, the major cellular receptor for HAdV55, a single intraperitoneal injection with hexon-targeting mAbs efficiently prevented HAdV55 infection, and mAb 29C12 showed protection at a dose as low as 0.004 mg/kg. Fibre-targeting mAb 28E8, however, showed protection only at a dose up to 12.5 mg/kg. In tree shrews that are permissive for HAdV55 infection and disease, mAb 29C12 effectively prevented HAdV55-caused pneumonia. Further analysis revealed that fibre-targeting mAbs blocked the attachment of HAdV55 to host cells, whereas hexon-targeting mAbs, regardless of their targeting HVRs, mainly functioned at post-attachment stage via inhibiting viral endosomal escape. Our results indicate that hexon-targeting mAbs have great anti-HAdV55 activities and warrant pre-clinical and clinical evaluation.

This study presents a mathematical modeling and numerical investigation of oscillatory flow induced microdroplet breakup in low melting point alloy (LMPA)-in-water two-phase flow system in a microchannel. The effects of perturbation flow Weber number, and oscillating frequencies on the droplet breakup dynamics have been elucidated. Lowering the wall temperature will accelerate the solidification process of LMPA droplets, giving rise to the rapid formation of ultra-small particles with size down to 1 micron in less than 3 ms. The versatile approach combines oscillatory flow dominated droplet breakup process and phase change process, leading to the formation of LMPA microparticles with monodispersed size distribution and well-tailored properties by using a straight microchannel, which obviates the need for sophisticated design and complex fabrication process of microdevices. This work will provide a strategy to manipulating LMPA droplet size and structure for the massive production of ultra-small LMPA microparticles via a facile control over the flow conditions in the two-phase flow in a microfluidic system. It will open up for a diversity of applications of LMPA microparticles in various fields such as energy storage and thermal management.

Optical micromotors are powerful tools for trapping and rotating microparticles in various fields of bio-photonics. Conventionally, optical micromotors are built using bulk optics, such as microscope objectives and SLMs. However, optical fibers provide an attractive alternative, offering a flexible photon platform for optical micromotor applications. In this paper, we present an optical micromotor designed for 3D manipulation and rotation based on a single fiber optical vortex tweezer. A tightly focused vortex beam is excited by preparing a spiral zone plate with an ultrahigh numerical aperture of up to 0.9 at the end facet of a functionalized fiber. The focused vortex beam can optically manipulate and rotate a red blood cell in 3D space far from the fiber end facet. The trapping stiffness in parallel and perpendicular orientations to the fiber axis are measured by stably trapping a standard 3-µm silica bead. The rotational performance is analyzed by rotating a trimer composed of silica beads on a glass slide, demonstrating that the rotational frequency increases with rising optical power and the rotational direction is opposite to the topological charge of the spiral zone plate. The proposed fiber micromotor with its flexible manipulation of microparticle rotation circumvents the need for the precise relative position control of multiple fiber combinations and the use of specialized fibers. The innovations hold promising potential for applications in microfluidic pumping, biopsy, micromanipulation, and other fields.

BackgroundAlzheimer’s disease (AD) is a neurodegenerative disorder marked by cognitive decline and memory loss. Recent research underscores the crucial role of astrocytes in AD. This study reviews research trends and contributions on astrocytes in AD from 2000 to 2024, shedding light on the evolving research landscape.MethodsWe conducted a bibliometric analysis using data from the Web of Science Core Collection, covering publications from January 1, 2000, to July 6, 2024, on “Alzheimer’s disease” and “astrocytes.” We identified 5,252 relevant English articles and reviews. For data visualization and analysis, we used VOSviewer, CiteSpace, and the R package “bibliometrix,” examining collaboration networks, co-citation networks, keyword co-occurrence, and thematic evolution.ResultsBetween 2000 and 2024, 5,252 publications were identified, including 4,125 original research articles and 1,127 review articles. Publications increased significantly after 2016. The United States had the most contributions (1,468), followed by China (836). Major institutions were the University of California system (517) and Harvard University (402). The Journal of Alzheimer’s Disease published the most articles (215). Verkhratsky A was the top author with 51 papers and 1,585 co-citations.ConclusionOur extensive bibliometric analysis indicates a significant increase in research on astrocytes in AD over the past 20 years. This study emphasizes the growing acknowledgment of astrocytes’ crucial role in AD pathogenesis and points to future research on their mechanisms and therapeutic potential.

Genistin is an isoflavone of soybean, with estrogenic activity. This experiment was conducted to investigate its effect on reproductive performance, antioxidant capacity, and immunity in gestating sows. Seventy-two sows (Landrace × Yorkshire) were selected and randomly divided into two treatment groups (n = 36) based on their backfat thickness, parity and fed with basal diet or supplementation of 150 mg/ kg genistin to the basal diet based on DMI for the entire gestation period. Results showed that dietary genistin supplementation significantly increased the average number of live born per litter (p < 0.05), and tended to increase the number of healthy piglets per litter (p = 0.058), but decreased the average weight of live born per litter (p < 0.05). Dietary genistin supplementation significantly decreased the number of mummified and stillbirths per litter (p < 0.05). Moreover, the average daily feed intake (ADFI) and total feed intake of the gestating sows were also increased in the genistin-supplemented group (p < 0.05). Genistin significantly increased the serum concentrations of catalase (CAT), immunoglobulin A (IgA), IgG, and IgM at 35 days of gestation (p < 0.05). The serum concentrations of interleukin-10 (IL-10) and interferon-γ (IFN-γ) were also increased upon genistin supplementation (p < 0.05). However, genistin supplementation tended to decrease the serum concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and leptin at 85 days of gestation (p = 0.081 and p = 0.096, respectively). Interestingly, genistin supplementation decreased the transcript abundance of interferon-γ (IFN-γ) and placental imprinting gene H19, but significantly increased the transcript abundance of insulin-like growth factor I (IGF-I) and amino acid transporters such as the sodium-coupled neutral amino acid transporter 2 (SNTA2) and SNAT4 in the placenta (p < 0.05). These results suggested that dietary genistin supplementation during gestation can improve the reproductive performance of sows, which was probably associated with improving of antioxidant capacity and immunity, as well as changes of transcript abundance of critical functional genes in the placenta.

Grape seed proanthocyanidin (GSP) is a kind of plant polyphenols with a wide variety of biological activities. In this study, we explored the effect of dietary GSP supplementation on growth performance, nutrient digestibility, and intestinal microbiota in growing pigs. A total of 180 growing pigs (30.37 ± 0.31 kg) were randomly assigned to five treatment groups, each consisting of six replicate pens with six pigs per pen. The pigs received either a basal diet (control) or a basal diet supplemented with GSP at 15, 30, 60, or 120 mg/kg. The trial lasted for 33 days, and blood and fecal samples were collected for biochemical measurements. GSP supplementation at a dose from 30 to 120 mg/kg decreased the ratio of feed intake to gain (F:G) (p

Background: Observational studies provide evidence of correlations between cancer and the immune system. Previous research has established associations between immune traits and the propensity for developing certain cancers. However, a systematic exploration of these connections remains largely uncharted. Therefore, further investigation is needed to examine the causal association between cancer and immune cell traits using Mendelian randomization (MR) approach. Methods: We identified genetic instruments for breast cancer (BC), lung cancer (LC), endometrial cancer (EC), ovarian cancer (OC), prostate cancer (PC), and their subtype cancers to investigate their potential causal impact on immune traits. Data on cancer and immune cell traits were obtained from the IEU Open GWAS project. To assess whether these five cancer types and subtype cancers have a causal association with immune cell traits, we conducted two-sample MR analyses. Additionally, we conducted bidirectional MR analyses to examine the direction of causal relationships and adjusted for potentially related pleiotropy through multivariable MR analysis. Results: We have identified several causal relationships between different types of cancer and immune traits. We found that breast cancer may influence 49 immune cell traits, endometrial cancer may influence 38, lung cancer may influence 25, ovarian cancer may influence 19, and prostate cancer may influence 28. Among these, breast cancer and lung cancer were associated with four common immune traits: CD25 on IgD− CD38dim, CD25 on sw mem, CD24 on IgD− CD38−, and CD25 on IgD− CD38−. Lung cancer and prostate cancer shared four immune traits: CD25 on IgD+ CD24+, CD25 on IgD+ CD38−, CD66b on CD66b++ myeloid cell, DN (CD4−CD8−) AC. Endometrial cancer and ovarian cancer shared two immune traits: TD DN (CD4−CD8−) %DN, EM DN (CD4−CD8−) %DN. Breast cancer and endometrial cancer shared one immune trait: CD20 on IgD− CD38dim. Endometrial cancer and prostate cancer shared one immune trait: CCR2 on myeloid DC. Lastly, breast cancer, lung cancer, and prostate cancer shared one immune trait: CD25 on CD24+ CD27+. Additionally, we identified specific immune traits that may serve as protective or risk factors for cancers. We found 14 immune traits may influence breast cancer, 9 immune traits may influence endometrial cancer, 22 immune traits may influence lung cancer, 9 immune traits may influence ovarian cancer, and 14 immune traits may influence prostate cancer. Among these, breast cancer and prostate cancer shared three immune traits: HLA DR++ monocyte %monocyte, HLA DR on plasmacytoid DC, and HLA DR on DC. Lung cancer and ovarian cancer shared one immune trait: CD62L− monocyte %monocyte. Prostate cancer and endometrial cancer shared one immune trait: HLA DR on CD33dim HLA DR + CD11b+. Lastly, ovarian cancer and prostate cancer shared one immune trait: CD3 on resting Treg. Conclusions: Our MR study suggests a potential relationship between immune traits and cancers, particularly highlighting 14 immune traits that are simultaneously influenced by two or three of five cancer types, while also indicating that 6 immune traits may simultaneously contribute to the development of two of the cancers. This elucidation enables us to reveal a significant involvement of immune traits in cancer progression, providing critical insights into how immune traits affect cancer susceptibility.

Maternal dietary supplementation with chitosan oligosaccharide (COS) has been considered as a potential intervention to mitigate the occurrence of intrauterine growth restriction (IUGR) and improve postnatal growth. The present study investigated the effect of COS as a dietary supplement for sows during late gestation and lactation on their productivity, placental function, and the intestinal health of IUGR piglets. From day (d) 85 of late gestation to d 21 of lactation, 30 sows were randomly divided into either a control group (basal diet) or a COS group (basal diet + 100 mg kg−1 COS). At d 21 of lactation, eight normal and eight IUGR littermates from eight litters belong to control sows, as well as eight IUGR littermates from COS sows, were selected for further analysis. The results showed a significant reduction in the number of stillbirths and mummies in COS groups (p

Medicine food homology is a special existence that combines the therapeutic effects of medicine and the nutritional value of food, making it possible for people to obtain health through daily diet. In this review, not only the concept, origin, and development of medicine food homology were introduced, but also the basic information of 102 medicine food homology substances authoritatively released by the Chinese Ministry of Health were summarized in detail and classified according to different methods. Moreover, the major pharmacological activities and underlying mechanisms of these 102 substances were concluded, and several creative ideas were proposed for the future development of new medicine food homology substances in the future. Collectively, this review provided a scientific basis and theoretical reference for the further exploration and utilization of new medicine food homology substances. Overall, the study of medicine food homology possesses a broad development prospect and great application value.

Infectious gastroenteritis is the major cause for diarrhea in piglets. The protection of spray-dried plasma (SDP) on viral gastroenteritis during the progression of rotavirus (RV) infection remain unclear. In this study, 64 weanling piglets were randomly assigned to control diets (n = 40) and SDP diets (n = 24) for 14 days, and then pigs were challenged with RV on day 15. Pigs were sacrificed on day 14 (normal condition), day 18 (manifestation stage), and day 21 (convalescent stage) of the trial. Prior to RV infection, SDP increased ADG, M1 macrophages and CD4+ T cells in different organs without increasing proinflammatory cytokines, indicating a more robust immunity with less inflammation. During the manifestation of infection, SDP enhanced mucosal immunity by increasing M1 macrophages, M1/M2 ratio and cytokines in mucosa and increasing intraepithelial CD8+ T cells for RV clearance. During the convalescence, SDP promoted M2 macrophage polarization and reduced pro-inflammatory cytokines to facilitate intestinal repair and prevent prolonged inflammation. Collectively, SDP enhanced mucosal immunity to promote viral clearance and maintained immune homeostasis to prevent long-lasting inflammation as a therapeutically approach for infectious gastroenteritis.