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The increasing incidence and mortality rates of cerebrovascular disease impose a heavy burden on both patients and society. Retinal imaging techniques, such as fundus photography, optical coherence tomography, and optical coherence tomography angiography, can be used for rapid, non-invasive evaluation of cerebral microcirculation and brain function since the retina and the central nervous system share similar embryonic origin characteristics and physiological features. This article aimed to review retinal imaging biomarkers related to cerebrovascular diseases and their applications in cerebrovascular diseases (stroke, cerebral small vessel disease [CSVD], and vascular cognitive impairment [VCI]), thus providing reference for early diagnosis and prevention of cerebrovascular diseases.

Gastrointestinal cancers account for approximately one-third of the total global cancer incidence and mortality with a poor prognosis. It is one of the leading causes of cancer-related deaths worldwide. Most of these diseases lack effective treatment, occurring as a result of inappropriate models to develop safe and potent therapies. As a novel preclinical model, tumor patient-derived organoids (PDOs), can be established from patients’ tumor tissue and cultured in the laboratory in 3D architectures. This 3D model can not only highly simulate and preserve key biological characteristics of the source tumor tissue in vitro but also reproduce the in vivo tumor microenvironment through co-culture. Our review provided an overview of the different in vitro models in current tumor research, the derivation of cells in PDO models, and the application of PDO model technology in gastrointestinal cancers, particularly the applications in combination with CRISPR/Cas9 gene editing technology, tumor microenvironment simulation, drug screening, drug development, and personalized medicine. It also elucidates the ethical status quo of organoid research and the current challenges encountered in clinical research, and offers a forward-looking assessment of the potential paths for clinical organoid research advancement.

Various pathological mechanisms represent distinct therapeutic targets for cognitive disorders, but a balance between clearance and production is essential for maintaining the stability of the brain’s internal environment. Thus, the glymphatic system may represent a common pathway by which to address cognitive disorders. Using the established model of the glymphatic system as our foundation, this review disentangles and analyzes the components of its clearance mechanism, including the initial inflow of cerebrospinal fluid, the mixing of cerebrospinal fluid with interstitial fluid, and the outflow of the mixed fluid and the clearance. Each section summarizes evidence from experimental animal models and human studies, highlighting the normal physiological properties of key structures alongside their pathological manifestations in cognitive disorders. The same pathologic manifestations of different cognitive disorders appearing in the glymphatic system and the same upstream influences are main points of interest of this review. We conclude this article by discussing new findings and outlining the limitations identified in current research progress.

Indirubins are natural occurring alkaloids extracted from indigo dye-containing plants. Indirubins could inhibit various kinases, and might be used to treat chronic myelocytic leukemia, cancer and neurodegenerative disorders. 7-bromoindirubin-3-oxime (7Bio), an indirubin derivative derived from indirubin-3-oxime, possesses inhibitory effects against cyclin-dependent kinase-5 (CDK5) and glycogen synthase kinase-3β (GSK3β), two pharmacological targets of Alzheimer's disease (AD). In this study, we have discovered that 2.3–23.3 μg/kg 7Bio effectively prevented β-amyloid (Aβ) oligomer-induced impairments of spatial cognition and recognition without affecting bodyweight and motor functions in mice. Moreover, 7Bio potently inhibited Aβ oligomer-induced expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Furthermore, 7Bio significantly prevented the decreased expression of synapsin-1 and PSD-95, biomarkers of pre-synaptic and post-synaptic proteins in Aβ oligomer-treated mice. The mean optical density (OD) with hyper-phosphorylated tau (pTau), glial fibrillary acidic protein (GFAP) and CD45 positive staining in the hippocampus of 7Bio-treated mice were significantly decreased compared to those of Aβ oligomer-treated mice. In addition, Western blotting analysis showed that 7Bio attenuated Aβ oligomer-decreased expression of pSer9-GSK3β. Those results suggested that 7Bio could potently inhibit Aβ oligomer-induced neuroinflammation, synaptic impairments, tau hyper-phosphorylation, and activation of astrocytes and microglia, which may contribute to the neuroprotective effects of 7Bio. Based on these findings, we expected that 7Bio might be developed as a novel anti-AD lead compound.

β-Amyloid (Aβ) is regarded as an important pathogenic target for Alzheimer’s disease (AD), the most prevalent neurodegenerative disease. Aβ can assemble into oligomers and fibrils, and produce neurotoxicity. Therefore, Aβ aggregation inhibitors may have anti-AD therapeutic efficacies. It was found, here, that the marine-derived alkaloid, fascaplysin, inhibits Aβ fibrillization in vitro. Moreover, the new analogue, 9-methylfascaplysin, was designed and synthesized from 5-methyltryptamine. Interestingly, 9-methylfascaplysin is a more potent inhibitor of Aβ fibril formation than fascaplysin. Incubation of 9-methylfascaplysin with Aβ directly reduced Aβ oligomer formation. Molecular dynamics simulations revealed that 9-methylfascaplysin might interact with negatively charged residues of Aβ42 with polar binding energy. Hydrogen bonds and π⁻π interactions between the key amino acid residues of Aβ42 and 9-methylfascaplysin were also suggested. Most importantly, compared with the typical Aβ oligomer, Aβ modified by nanomolar 9-methylfascaplysin produced less neuronal toxicity in SH-SY5Y cells. 9-Methylfascaplysin appears to be one of the most potent marine-derived compounds that produces anti-Aβ neuroprotective effects. Given previous reports that fascaplysin inhibits acetylcholinesterase and induces P-glycoprotein, the current study results suggest that fascaplysin derivatives can be developed as novel anti-AD drugs that possibly act via inhibition of Aβ aggregation along with other target mechanisms.

The oligomer of β-amyloid (Aβ) is considered the main neurotoxin in Alzheimer’s disease (AD). Therefore, the inhibition of the formation of Aβ oligomer could be a target for AD therapy. In this study, with the help of the dot blotting assay and transmission electronic microscopy, it was have discovered that 5-hydroxycyclopenicillone, a cyclopentenone recently isolated from a sponge-associated fungus, effectively reduced the formation of Aβ oligomer from Aβ peptide in vitro. Molecular dynamics simulations suggested hydrophobic interactions between 5-hydroxycyclopenicillone and Aβ peptide, which might prevent the conformational transition and oligomerization of Aβ peptide. Moreover, Aβ oligomer pre-incubated with 5-hydroxycyclopenicillone was less toxic when added to neuronal SH-SY5Y cells compared to the normal Aβ oligomer. Although 5-hydroxycyclopenicillone is not bioavailable in the brain in its current form, further modification or encapsulation of this chemical might improve the penetration of 5-hydroxycyclopenicillone into the brain. Based on the current findings and the anti-oxidative stress properties of 5-hydroxycyclopenicillone, it is suggested that 5-hydroxycyclopenicillone may have potential therapeutic efficacy in treating AD.

Abstract In patients with gastric cancer (GC), metastatic progression through the lymphatic, haematogenous, peritoneal, and ovarian routes is the ultimate cause of death. We developed a nomogram to estimate cancer-specific survival (CSS) in patients with T1 gastric cancer based on log odds of positive lymph nodes (LODDS). A total of 2,221 patients from the Surveillance, Epidemiology, and End Results (SEER) database were split into training and internal validation cohorts, while an external validation cohort included 165 patients from our hospital. Multivariate Cox regression analysis revealed that age, sex, tumour size, LODDS score, and M stage were independent prognostic factors for CSS. The LODDS outperformed the N stage and positive lymph node (PLN) count in terms of predictive ability and is recognised as an independent prognostic factor for nomogram construction. In the training and internal and external validation sets, the 1-year AUCs of the columniogram were 0.732, 0.672, and 0.719, respectively. The 3-year AUCs were 0.705, 0.692, and 0.638, respectively. The 5-year AUCs were 0.726, 0.698, and 0.713, respectively, indicating good predictive power. The calibration curve revealed that the predicted survival rate was consistent with the actual survival rate in the three groups. The ROC and DCA demonstrated that the nomogram has more potential in predicting prognosis than the existing AJCC staging system. We constructed and validated a novel nomogram leveraging LODDS, which effectively estimates the CSS at 1, 3, and 5 years for individuals with gastric cancer.

Abstract Aims Acute‐on‐chronic liver failure (ACLF) is defined as acute liver injury superimposed on chronic liver disease, resulting in a significantly increased short‐term mortality rate. Serum lipids are associated with the severity of liver disease and contribute to the prognostic assessment for cirrhosis and liver failure. However, the presentation of serum lipids varies in different studies, making it difficult to draw definitive conclusions. This study aimed to investigate the predictive value of serum lipids for short‐term prognosis in patients with ACLF. Methods This retrospective analysis was conducted using the clinical data of patients hospitalized for ACLF between January 2018 and December 2021. The collected data were subjected to Least Absolute Shrinkage and Selection Operator and logistic regression analyses to identify the independent predictors of 28‐day and 90‐day mortality. Separate regression models were developed for each identified serum lipid. These models were combined with the Model for End‐Stage Liver Disease (MELD), MELD combined with serum sodium concentration (MELD‐Na), Chronic Liver Failure Consortium Acute‐on‐chronic Liver Failure (CLIF‐C ACLF), and Chinese Group on the Study of Severe Hepatitis B‐ACLF (COSSH‐ACLF) scores to construct new models. The performance of these models was evaluated using the area under the receiver operating characteristic curve (AUC), Nagelkerke R2, Brier score, net reclassification index (NRI), and integrated discrimination improvement (IDI) to assess the prognostic ability of serum lipids. Results This study included 266 patients with ACLF, of whom 25.9% (69/266) died within 28 days and 38.5% (102/265, with 1 lost to follow‐up) died within 90 days. The independent predictors of 28‐day mortality were age, the presence of overt hepatic encephalopathy at admission, high‐density lipoprotein cholesterol (HDL‐C) levels, and international normalized ratio (INR). The independent predictors of 90‐day mortality were age, albumin levels, serum creatinine levels, and INR. The comparative analysis revealed that the AUC of all other models exceeded that of HDL‐C (p 0.050). Conclusions Serum HDL‐C is an independent predictor of 28‐day mortality in patients with ACLF. Although it has inferior predictive ability when considered alone, HDL‐C enhances the predictive capacity of MELD, MELD‐Na, and COSSH‐ACLF when incorporated into these models.

IntroductionAfrican swine fever (ASF) is a highly contagious hemorrhagic fever disease in pigs caused by African swine fever virus (ASFV). It is very difficult to control and prevent ASF outbreaks due to the absence of safe and effective vaccines.MethodsIn order to develop a safe and effective ASF vaccine for the control and prevention of ASF, two ASFV recombinant vesicular stomatitis virus (VSV) live vector vaccine prototypes, containing the gene of p72, and a chimera of p30 and p54, were developed based on the replication-competent VSV, and named VSV-p72 and VSV-p35. The immune potency of VSV-p72 or VSV-p35 alone and in combination was evaluated in BALB/c mice via intramuscular and intranasal vaccination.ResultsThe results indicated that whether administered alone or in combination, the two vaccine prototypes showed acceptable safety in mice and, more importantly, induced high-level specific antibodies against p72, p30, and p54 of ASFV and a strong cellular immune response 28 days after vaccination. The sera from mice vaccinated with the vaccine prototypes significantly inhibited ASFV from infecting porcine alveolar macrophages (PAMs) in vitro. Most notably, the immunized sera from a mixture of VSV-p35 and VSV-p72 inhibited ASFV from infecting PAMs, with an inhibition rate of up to 78.58%.ConclusionOverall, our findings suggest that ASFV recombinant VSV live vector vaccine prototypes may become a promising candidate vaccine for the control and prevention of ASF.

This study proposes a recognition model for different drying methods of grain using hyperspectral imaging technology (HSI) and multivariate analysis. Fresh harvested grain samples were dried using three different methods: rotating ventilation drying, mechanical drying, and natural drying. Hyperspectral images of the samples were collected within the 388–1065 nm band range. The spectral features of the samples were extracted using principal component analysis (PCA), while the texture features were extracted using second-order probability statistical filtering. Partial least squares regression (PLSR) drying models with different characteristics were established. At the same time, a BPNN (Back-propagation neural network, BPNN) based on spectral texture fusion features was established to compare the recognition effects of different models. Texture analysis indicated that the mean-image had the clearest contour, and the texture characteristics of mechanical drying were smaller than those of rotating ventilation drying and natural drying. The BPNN model established using spectral-texture feature variables showed the best performance in distinguishing grain in different drying modes, with a prediction model obtained based on the correlation coefficients of special variables. The spectral and texture feature values were fused for pseudo-color visualization expression, and the three drying methods of grain showed different colors. This study provides a reference for non-destructive and rapid detection of grain with different drying methods.

Abstract Background African swine fever (ASF) is a highly fatal disease in domestic pigs caused by ASF virus (ASFV), for which there is currently no commercial vaccine available. The genome of ASFV encodes more than 150 proteins, some of which have been included in subunit vaccines but only induce limited protection against ASFV challenge. Methods To enhance immune responses induced by ASFV proteins, we expressed and purified three fusion proteins with each consisting of bacterial lipoprotein OprI, 2 different ASFV proteins/epitopes and a universal CD4+ T cell epitope, namely OprI-p30-modified p54-TT, OprI-p72 epitopes-truncated pE248R-TT, and OprI-truncated CD2v-truncated pEP153R-TT. The immunostimulatory activity of these recombinant proteins was first assessed on dendritic cells. Then, humoral and cellular immunity induced by these three OprI-fused proteins cocktail formulated with ISA206 adjuvant (O-Ags-T formulation) were assessed in pigs. Results The OprI-fused proteins activated dendritic cells with elevated secretion of proinflammatory cytokines. Furthermore, the O-Ags-T formulation elicited a high level of antigen-specific IgG responses and interferon-γ-secreting CD4+ and CD8+ T cells after stimulation in vitro. Importantly, the sera and peripheral blood mononuclear cells from pigs vaccinated with the O-Ags-T formulation respectively reduced ASFV infection in vitro by 82.8% and 92.6%. Conclusions Our results suggest that the OprI-fused proteins cocktail formulated with ISA206 adjuvant induces robust ASFV-specific humoral and cellular immune responses in pigs. Our study provides valuable information for the further development of subunit vaccines against ASF.

Vegetable oils, which are considered potential lubricants, are composed of different types and proportions of fatty acids. Because of their diverse types and varying compositions, they exhibit different lubrication performances. The genetic function approximation algorithm was used to model the quantitative structure–property relationship between fatty acid structure and the wear scar diameter and friction coefficients measured by four-ball friction and wear tests. Based on the models with adjusted R2 greater than 0.9 and fatty acid compositions of vegetable oils, the wear scar diameter and friction coefficients of Xanthoceras sorbifolia bunge oil and Soybean oil as validation oil samples were predicted. The difference between the predicted and experimental values was small, indicating that the models could accurately predict the lubrication performances of vegetable oils. The lubrication performances of 14 kinds of vegetable oils were predicted by GFA-QSPR models, and the primary factors influencing their lubrication properties were studied by cluster analysis. The results show that the content of C18:1 has a positive effect on the lubrication performances of vegetable oils, while the content of C18:3 has a negative effect, and the length of the carbon chain of fatty acids significantly affects their lubrication properties.

Abstract Background African swine fever (ASF) is a highly fatal swine disease, which threatens the global pig industry. There is no commercially available vaccine against ASF and effective subunit vaccines would represent a real breakthrough. Methods In this study, we expressed and purified two recombinant fusion proteins, OPM (OprI-p30-modified p54) and OPMT (OprI-p30-modified p54-T cell epitope), which combine the bacterial lipoprotein OprI with ASF virus proteins p30 and p54. Purified recombinant p30 and modified p54 expressed alone or fused served as controls. The activation of dendritic cells (DCs) by these proteins was first assessed. Then, humoral and cellular immunity induced by the proteins were evaluated in mice. Results Both OPM and OPMT activated DCs with elevated expression of relevant surface molecules and proinflammatory cytokines. Furthermore, OPMT elicited the highest levels of antigen-specific IgG responses, cytokines including interleukin-2, interferon-γ, and tumor necrosis factor-α, and proliferation of lymphocytes. Importantly, the sera from mice vaccinated with OPM or OPMT neutralized more than 86% of ASF virus in vitro. Conclusions Our results suggest that OPMT has good immunostimulatory activities and immunogenicity in mice, and might be an appropriate candidate to elicit immune responses in swine. Our study provides valuable information on further development of a subunit vaccine against ASF.

African swine fever virus (ASFV) causes a highly lethal hemorrhagic viral disease (ASF) of pigs that results in serious losses in China and elsewhere. The development of a vaccine and diagnosis technology for ASFV is essential to prevent and control the spread of ASF. The p72 protein of ASFV is highly immunogenic and reactive, and is a dominant antigen in ASF vaccine and diagnostic research. In this study, 17 p72 monoclonal antibodies (mAbs) were generated. Epitope mapping by a series of overlapping peptides expressed in Escherichia coli showed that these mAbs recognized a total of seven (1–7) linear B cell epitopes. These mAbs did not show significant neutralizing activity. Epitopes 1 (249HKPHQSKPIL258), 2 (69PVGFEYENKV77), 5 (195VNGNSLDEYSS205), and 7 (223GYKHLVGQEV233) are novel. Sequence alignment analysis revealed that the identified epitopes were highly conserved among 27 ASFV strains from nine genotypes. Preliminary screening using known positive and negative sera indicated the diagnostic potential of mAb-2B8D7. The results provide new insights into the antigenic regions of ASFV p72 and will inform the diagnosis of ASFV.

African swine fever virus (ASFV) is a highly infectious and lethal double-stranded DNA virus that is responsible for African swine fever (ASF). ASFV was first reported in Kenya in 1921. Subsequently, ASFV has spread to countries in Western Europe, Latin America, and Eastern Europe, as well as to China in 2018. ASFV epidemics have caused serious pig industry losses around the world. Since the 1960s, much effort has been devoted to the development of an effective ASF vaccine, including the production of inactivated vaccines, attenuated live vaccines, and subunit vaccines. Progress has been made, but unfortunately, no ASF vaccine has prevented epidemic spread of the virus in pig farms. The complex ASFV structure, comprising a variety of structural and non-structural proteins, has made the development of ASF vaccines difficult. Therefore, it is necessary to fully explore the structure and function of ASFV proteins in order to develop an effective ASF vaccine. In this review, we summarize what is known about the structure and function of ASFV proteins, including the most recently published findings.

Two quantitative structure–property relationship (QSPR) models of hindered phenolic antioxidants in lubricating oils were established to help guide the molecular structure design of antioxidants. Firstly, stepwise regression (SWR) was used to filter out essential molecular descriptors without autocorrelation, including electronic, topological, spatial, and structural descriptors, and multiple linear regression (MLR) was used to construct QSPR models based on the screened variables. The two models are statistically sound, with R2 values of 0.942 and 0.941, respectively. The models’ reliability was verified by the frontier molecular orbital energy gaps of the antioxidants. A hindered phenolic additive was designed based on the models. Its antioxidant property is calculated to be 20.9% and 11.0% higher than that of typical commercial antioxidants methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate and 2,2′-methylenebis(6-tert-butyl-4-methylphenol), respectively. The structure–property relationship of hindered phenolic antioxidants in lubricating oil obtained by computer-assisted analysis can not only predict the antioxidant properties of existing hindered phenolic additives but also provide theoretical basis and data support for the design or modification of lubricating oil additives with higher antioxidant properties.

Abstract Background Foot-and-mouth disease (FMD) is a devastating animal disease. Anti-non-structural protein (NSP) antibody detection is very important for confirming suspected cases, evaluating the prevalence of infection, certifying animals for trade and controlling the disease. Methods In this study, a competitive chemiluminescence immunoassay (3B-cCLIA) was developed for the rapid detection of antibodies against NSPs in different species of livestock animals using the monoclonal antibody (mAb) 9E2 as a competitive antibody that recognizes NSP 3B. Results The cut-off value (50%), diagnostic sensitivity (Dsn) (97.20%, 95.71%, and 96.15%) and diagnostic specificity (Dsp) (99.51%, 99.43%, and 98.36) of the assay were estimated by testing a panel of known-background sera from swine, cattle and sheep, respectively. The accuracy rate of the 3B-cCLIA was further validated and subsequently compared with that of two commercial diagnostic kits. The early diagnostic results showed that antibodies recognizing NSPs developed later (approximately 1–2 days) than antibodies recognizing structural proteins. Furthermore, anti-NSP antibody presence in animals vaccinated multiple times (false positives), especially cattle and sheep, was confirmed, and the false-positive rate increased with the number of vaccinations. Conclusions These results indicate that the 3B-cCLIA is suitable for the rapid detection of antibodies against FMDV NSP 3B in a wide range of species.