Important role of Bacillus subtilis as a probiotic and vaccine carrier in animal health maintenance.

Bacillus subtilis is a widespread Gram-positive facultative aerobic bacterium that is recognized as generally safe. It has shown significant application value and great development potential in the animal farming industry. As a probiotic, it is frequently used as a feed growth supplement to effectively replace antibiotics due to its favourable effects on regulating the intestinal flora, improving intestinal immunity, inhibiting harmful microorganisms, and secreting bioactive substances. Consequently, the gut health and disease resistance of farmed animals can be improved. Both vegetative and spore forms of B. subtilis have also been utilized as vaccine carriers for delivering the antigens of infectious pathogens for over a decade. Notably, its spore form is regarded as one of the most prospective for displaying heterologous antigens with high activity and stability. Previously published reviews have predominantly focused on the development and applications of B. subtilis spore surface display techniques. However, this review aims to summarize recent studies highlighting the important role of B. subtilis as a probiotic and vaccine carrier in maintaining animal health. Specifically, we focus on the beneficial effects and underlying mechanisms of B. subtilis in enhancing disease resistance among farmed animals as well as its potential application as mucosal vaccine carriers. It is anticipated that B. subtilis will assume an even more prominent role in promoting animal health with in-depth research on its characteristics and genetic manipulation tools.

Genome-Wide Association Analysis and Genetic Parameters for Egg Production Traits in Peking Ducks.

Egg production traits are crucial in the poultry industry, including age at first egg (AFE), egg number (EN) at different stages, and laying rate (LR). Ducks exhibit higher egg production capacity than other poultry species, but the genetic mechanisms are still poorly understood. In this study, we collected egg-laying data of 618 Peking ducks from 22 to 66 weeks of age and genotyped them by whole-genome resequencing. Genetic parameters were calculated based on SNPs, and a genome-wide association study (GWAS) was performed for these traits. The SNP-based heritability of egg production traits ranged from 0.09 to 0.54. The GWAS identified nine significant SNP loci associated with AFE and egg number from 22 to 66 weeks. These loci showed that the corresponding alleles were positively correlated with a decrease in the traits. Moreover, three potential candidate genes (ENSAPLG00020011445, ENSAPLG00020012564, TMEM260) were identified. Functional enrichment analyses suggest that specific immune responses may have a critical impact on egg production capacity by influencing ovarian function and oocyte maturation processes. In conclusion, this study deepens the understanding of egg-laying genetics in Peking duck and provides a sound theoretical basis for future genetic improvement and genomic selection strategies in poultry.

Metabolism and distribution of two major constituents of 'Xing-Nao-Jing Injection'-germacrone and curdione in rats.

Germacrone and curdione are germacrane-type sesquiterpenoids that are widely distributed and have extensive pharmacological activities; they are the main constituents of 'Xing-Nao-Jing Injection' (XNJ). Studies on the metabolic features of germacrane-type sesquiterpenoids are limited. In this study, the metabolites of germacrone and curdione were characterized by UHPLC-Q-Exactive Oribitrap mass spectrometry after they were orally administered to rats. In total, 60 and 76 metabolites were found and preliminarily identified in rats administered germacrone and curdione, respectively, among which at least 123 potential new compounds were included. New metabolic reactions of germacrane-type sesquiterpenoids were identified, which included oxidation (+4 O and +5 O), ethylation, methyl-sulfinylation, vitamin C conjugation, and cysteine conjugation reactions. Among the 136 metabolites (including 113 oxidation metabolites, two glucuronidation, two methylation, nine methyl-sulfinylation, three ethylation, six cysteine conjugation, and one Vitamin C conjugation metabolites), 32 metabolites were detected in nine organs, and the stomach, intestine, liver, kidneys, and small intestine were the main organs for the distribution of these metabolites. All 136 metabolites were detected in urine and 64 of them were found in feces. The results of this study not only contribute to research on in vivo processes related to germacrane-type sesquiterpenoids but also provide a strong foundation for a better understanding of in vivo processes and the effective forms of germacrone, curdione, and XNJ.

Intermolecular α-Functionalization of Benzylamides with N-Nucleophiles via Oxidative Umpolung: Synthesis of Tetrasubstituted 3,3'-Oxindoles.

A hypervalent iodine-mediated intermolecular α-umpolung reaction between α-aryl- or alkyl-substituted amides and benzotriazoles or purine derivatives as N-centered nucleophiles has been established. The reaction involves sequential intra/intermolecular oxidative C-N couplings in a controlled manner, affording tetrasubstituted 3,3'-oxindoles in moderate to good yields. This approach efficiently addresses the challenges in constructing tetrasubstituted carbon centers via α-umpolung functionalizations of carbonyl compounds and serves as a new strategy for synthesizing biologically important 3,3'-disubstituted oxindoles.

18F-FDG PET/CT Radiomics-Based Multimodality Fusion Model for Preoperative Individualized Noninvasive Prediction of Peritoneal Metastasis in Advanced Gastric Cancer.

PURPOSE: This study was designed to develop and validate a machine learning-based, multimodality fusion (MMF) model using 18F-fluorodeoxyglucose (FDG) PET/CT radiomics and kernelled support tensor machine (KSTM), integrated with clinical factors and nuclear medicine experts' diagnoses to individually predict peritoneal metastasis (PM) in advanced gastric cancer (AGC). METHODS: A total of 167 patients receiving preoperative PET/CT and subsequent surgery were included between November 2006 and September 2020 and were divided into a training and testing cohort. The PM status was confirmed via laparoscopic exploration and postoperative pathology. The PET/CT signatures were constructed by classic radiomic, handcrafted-feature-based model and KSTM self-learning-based model. The clinical nomogram was constructed by independent risk factors for PM. Lastly, the PET/CT signatures, clinical nomogram, and experts' diagnoses were fused using evidential reasoning to establish the MMF model. RESULTS: The MMF model showed excellent performance in both cohorts (area under the curve [AUC] 94.16% and 90.84% in training and testing), and demonstrated better prediction accuracy than clinical nomogram or experts' diagnoses (net reclassification improvement p < 0.05). The MMF model also had satisfactory generalization ability, even in mucinous adenocarcinoma and signet ring cell carcinoma which have poor uptake of 18F-FDG (AUC 97.98% and 89.71% in training and testing). CONCLUSIONS: The 18F-FDG PET/CT radiomics-based MMF model may have significant clinical implications in predicting PM in AGC, revealing that it is necessary to combine the information from different modalities for comprehensive prediction of PM.

Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma.

Circular RNAs (circRNAs) are ideal biomarkers of oral squamous cell carcinoma (OSCC) because of their highly stable closed-loop structure, and they can act as microRNA (miRNA) sponges to regulate OSCC progression. By analyzing clinical samples, we identified circCPNE1, a dysregulated circRNA in OSCC, and its expression level was negatively correlated with the clinical stage of OSCC patients. Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1, which was then identified as a miR-330-3p sponge. MiR-330-3p was recognized as a tumor promoter in multiple studies, consistent with our finding that it could promote the proliferation, migration, and invasion of OSCC cells. These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression. Therefore, we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p (a miRNA inhibitory analog) via electrostatic interactions to form PP@miR nanoparticles (NPs). Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination (2/5), which confirmed the critical role of miR-330-3p in OSCC development. These findings provide a new perspective for the development of OSCC treatments.

AppleQSM: Geometry-Based 3D Characterization of Apple Tree Architecture in Orchards.

The architecture of apple trees plays a pivotal role in shaping their growth and fruit-bearing potential, forming the foundation for precision apple management. Traditionally, 2D imaging technologies were employed to delineate the architectural traits of apple trees, but their accuracy was hampered by occlusion and perspective ambiguities. This study aimed to surmount these constraints by devising a 3D geometry-based processing pipeline for apple tree structure segmentation and architectural trait characterization, utilizing point clouds collected by a terrestrial laser scanner (TLS). The pipeline consisted of four modules: (a) data preprocessing module, (b) tree instance segmentation module, (c) tree structure segmentation module, and (d) architectural trait extraction module. The developed pipeline was used to analyze 84 trees of two representative apple cultivars, characterizing architectural traits such as tree height, trunk diameter, branch count, branch diameter, and branch angle. Experimental results indicated that the established pipeline attained an R2 of 0.92 and 0.83, and a mean absolute error (MAE) of 6.1 cm and 4.71 mm for tree height and trunk diameter at the tree level, respectively. Additionally, at the branch level, it achieved an R2 of 0.77 and 0.69, and a MAE of 6.86 mm and 7.48° for branch diameter and angle, respectively. The accurate measurement of these architectural traits can enable precision management in high-density apple orchards and bolster phenotyping endeavors in breeding programs. Moreover, bottlenecks of 3D tree characterization in general were comprehensively analyzed to reveal future development.

Multi-omics reveals the molecular mechanism of the combined toxic effects of PFOA and 4-HBP exposure in MCF-7 cells and the key player: mTORC1.

With the discovery of evidence that many endocrine-disrupting chemicals (EDCs) in the environment influence human health, their toxic effects and mechanisms have become a hot topic of research. However, investigations into their endocrine-disrupting toxicity under combined binary exposure, especially the molecular mechanism of combined effects, have rarely been documented. In this study, two typical EDCs, perfluorooctanoic acid (PFOA) and 4-hydroxybenzophenone (4-HBP), were selected to examine their combined effects and molecular mechanism on MCF-7 cell proliferation at environmentally relevant exposure concentrations. We have successfully established a model to evaluate the binary combined toxic effects of endocrine disruptors, presenting combined effects in a simple and direct way. Results indicated that the combined effect changed from additive to synergistic from 1.25 × 10-8 M to 4 × 10-7 M. Metabolomics analyses suggested that exposure to PFOA and 4-HBP caused significant alterations in purine metabolism, arginine, and proline metabolism and had superimposed influences on metabolism. Enhanced combined effects were observed in glycine, serine, and threonine metabolic pathways compared to exposure to PFOS and 4-HBP alone. Additionally, the differentially expressed genes (DEGs) are primarily involved in Biological Processes, especially protein targeting the endoplasmic reticulum, and significantly impact the oxidative phosphorylation and thermogenesis-related KEGG pathway. By integrating metabolome and transcriptome analyses, PFOA and 4-HBP regulate purine metabolism, the TCA cycle, and endoplasmic reticulum protein synthesis in MCF-7 cells via mTORC1, which provides genetic material, protein, and energy for cell proliferation. Furthermore, molecular docking confirmed the ability of PFOA and 4-HBP to stably bind the estrogen receptor, indicating that they have different binding pockets. Collectively, these findings will offer new insights into understanding the mechanisms by which EDCs produce combined toxicity.

Refractory degradable dissolved organic matter (R-DOM) driving nitrogen removal by the electric field coupled iron­carbon biofilter (E-ICBF): Performance and microbial mechanisms.

Researches on the advanced nitrogen (N) removal of municipal tailwater always overlooked the value of refractory degradable dissolved organic matter (R-DOM). In this study, a novel electric field coupled iron­carbon biofilter (E-ICBF) was utilized to explore the performance and microbial changes with polyethylene glycol (PEG) as the representative R-DOM. Results demonstrated that the removal efficiencies of E-ICBF for nitrate nitrogen (NO3--N), ammonia nitrogen (NH4+-N), and total nitrogen (TN) improved by 28.76 %, 12.96 %, and 28.45 %, compared to quartz sand biofilter (SBF). Moreover, removal efficiencies of NO3--N and TN in E-ICBF with R-DOM went up by 12.11 % and 14.02 % compared to methanol. Additionally, both PEG and the electric field reduced the microbial richness and diversity. However, PEG promoted the increase of denitrifying bacteria abundance including unclassified_f_Comamonadaceae, Thauera, and unclassified_f_Gallionellaceae. The electric field improved the abundances of genes related to N removal (hao, nasC, nasA, nifH, nifD, nifK) and PEG further enhanced the effect. The abundances of key enzymes [EC:1.7.5.1], [EC:1.7.2.1], [EC:1.7.2.4], and [EC:1.7.2.5] decreased due to the addition of PEG and the electric field mitigated the negative influence. Additionally, the electric field changed relationships between microorganisms and pollutant removal, and improved interspecific relationships between denitrifying bacterial genera and other genera in E-ICBF.

Mild-Temperature Supercritical Water Confined in Hydrophobic Metal-Organic Frameworks.

Fluids under extreme confinement show characteristics significantly different from those of their bulk counterpart. This work focuses on water confined within the complex cavities of highly hydrophobic metal-organic frameworks (MOFs) at high pressures. A combination of high-pressure intrusion-extrusion experiments with molecular dynamic simulations and synchrotron data reveals that supercritical transition for MOF-confined water takes place at a much lower temperature than in bulk water, ∼250 K below the reference values. This large shifting of the critical temperature (Tc) is attributed to the very large density of confined water vapor in the peculiar geometry and chemistry of the cavities of Cu2tebpz (tebpz = 3,3',5,5'-tetraethyl-4,4'-bipyrazolate) hydrophobic MOF. This is the first time the shift of Tc is investigated for water confined within highly hydrophobic nanoporous materials, which explains why such a large reduction of the critical temperature was never reported before, neither experimentally nor computationally.

Oxidation of chromium(â ¢): A potential risk of using chemical oxidation processes for the remediation of 2-chlorophenol contaminated soils.

Chemical oxidation processes are widely used for the remediation of organically contaminated soils, but their potential impact on variable-valence and toxic metals such as chromium (Cr) is often overlooked. In this study, we investigated the risk of Cr(Ⅲ) oxidation in soils during the remediation of 2-chlorophenol (2-CP) contaminated soils using four different processes: Potassium permanganate (KMnO4), Modified Fenton (Fe2+/H2O2), Alkali-activated persulfate (S2O82-/OH-), and Fe2+-activated persulfate (S2O82-/Fe2+). Our results indicated that the KMnO4, Fe2+/H2O2, and S2O82-/Fe2+ processes progressively oxidized Cr(III) to Cr(Ⅵ) during the 2-CP degradation. The KMnO4 process likely involved direct electron transfer, while the Fe2+/H2O2 and S2O82-/Fe2+ processes primarily relied on HO• and/or SO4•- for the Cr(III) oxidation. Notably, after 4 h of 2-CP degradation, the Cr(VI) content in the KMnO4 process surpassed China's 3.0 mg kg-1 risk screening threshold for Class I construction sites, and further exceeded the 5.7 mg kg-1 limit for Class II construction sites after 8 h. Conversely, the S2O82-/OH- process exhibited negligible oxidation of Cr(III), maintaining a low oxidation ratio of 0.13%, as highly alkaline conditions induced Cr(III) precipitation, reducing its exposure to free radicals. Cr(III) oxidation ratio was directly proportional to oxidant dosage, whereas the Fe2+/H2O2 process showed a different trend, influenced by the concentration of reductants. This study provides insights into the selection and optimization of chemical oxidation processes for soil remediation, emphasizing the imperative for thorough risk evaluation of Cr(III) oxidation before their application.

Chloride Corrosion Process of Concrete with Different Water-Binder Ratios under Variable Temperature Drying-Wetting Cycles.

In this paper, four water-binder ratios (w/b) of 0.29, 0.33, 0.39, and 0.46 were designed. A variable test temperature was implemented in the drying-wetting cycle test according to the temperature fluctuations in the actual service environment, and the constant temperature test was established as the control group. The mechanical properties and chloride corrosion resistance of concrete with different w/b ratios under variable temperature drying-wetting cycles, as well as the microstructure changes, phase composition, and damage mechanism inside the concrete, were investigated. The results showed that the mechanical properties of concrete increased first and then decreased with drying-wetting cycles increasing, whereas the chloride corrosion resistance continued to decline. A higher w/b exacerbated the deterioration of the concrete performance. A higher w/b increased the porosity, chloride diffusion depth, and chloride content, thus reducing the resistance of chloride corrosion. Compared with w/b = 0.29, the compressive strength, splitting tensile strength, mass, and relative dynamic elasticity modulus of w/b = 0.46 exposed to 60 drying-wetting cycles decreased by 54.50%, 52.44%, 0.96%, and 6.50%, respectively, while the porosity, peak chloride content, and erosion depth increased by 45.12%, 70.45%, and 45.00%. Compared with the drying-wetting cycle with a constant temperature, the cumulative damage caused by the drying-wetting cycle with a variable temperature was greater, resulting in more severe deterioration of concrete performance. The increase in the test temperature significantly accelerated the diffusion rate, penetration depth, and chemical binding capacity of chloride ions. After 60 drying-wetting cycles, the peak chlorine content and erosion depth of w/b = 0.46 under variable temperature cycles were 15.38% and 10.32% higher than those under a constant temperature, while the compressive strength, splitting tensile strength, mass, and relative dynamic elastic modulus were reduced by 7.76%, 14.81%, 0.33%, and 2.40%, respectively. Microscopic analysis confirmed that higher w/b and variable temperature cycles accelerated the decay of mechanical properties and the decline of chloride corrosion resistance. According to the numerical fitting analysis, the w/b should be 0.29~0.39 under the condition that the mechanical properties and chloride corrosion resistance of concrete are met.

Exosome is a Fancy Mobile Sower of Ferroptosis.

Exosomes, nano-sized small extracellular vesicles, have been shown to serve as mediators between intercellular communications by transferring bioactive molecules, such as non-coding RNA, proteins, and lipids from secretory to recipient cells, modulating a variety of physiological and pathophysiological processes. Recent studies have gradually demonstrated that altered exosome charges may represent a key mechanism driving the pathological process of ferroptosis. This review summarizes the potential mechanisms and signal pathways relevant to ferroptosis and then discusses the roles of exosome in ferroptosis. As well as transporting iron, exosomes may also indirectly convey factors related to ferroptosis. Furthermore, ferroptosis may be transmitted to adjacent cells through exosomes, resulting in cascading effects. It is expected that further research on exosomes will be conducted to explore their potential in ferroptosis and will lead to the creation of new therapeutic avenues for clinical diseases.

Novel CDK19-Targeted Radiotracers: A Potential Design Strategy to Improve the Pharmacokinetics and Tumor Uptake.

Cyclin-dependent kinase 19 (CDK19) is overexpressed in prostate cancer, making it an attractive target for both imaging and therapy. Since little is known about the optimized approach for radioligands of nuclear proteins, linker optimization strategies were used to improve pharmacokinetics and tumor absorption, including the adjustment of the length, flexibility/rigidity, and hydrophilicity/lipophilicity of linkers. Molecular docking was conducted for virtual screening and followed by IC50 determination. Both BALB/c mice and P-16 xenografts were used for tissue distribution and PET/CT imaging. The ligand 68Ga-10c demonstrated high absorption in tumor 5 min after injection and sustains long-term imaging within 3 h. Furthermore, 68Ga-10c exhibited slow clearance within the tumor and was predominantly metabolized in both the liver and kidneys, showing the potential to alleviate metabolic pressure and enhance tissue safety. Therefore, the linker optimization strategy is well suited for CDK19 and provides a reference for the radioactive ligands of other nuclear targets.

POLQ inhibition attenuates the stemness and ferroptosis resistance in gastric cancer cells via downregulation of dihydroorotate dehydrogenase.

Gastric cancer (GC) contains subpopulations of cancer stem cells (CSCs), which are described as the main contributors in tumor initiation and metastasis. It is necessary to clarify the molecular mechanism underlying CSCs phenotype and develop novel biomarkers and therapeutic targets for gastric cancer. Here, we show that POLQ positively regulates stem cell-like characteristics of gastric cancer cells, knockdown of POLQ suppressed the stemness of GC cells in vitro and in vivo. Further mechanistic studies revealed that POLQ knockdown could downregulate the expression of dihydroorotate dehydrogenase (DHODH). DHODH overexpression rescued the reduced stemness resulted by POLQ knockdown. Furthermore, we found that POLQ expression correlated with resistance to ferroptosis, and POLQ inhibition renders gastric cancer cells more vulnerable to ferroptosis. Further investigation revealed that POLQ regulated DHODH expression via the transcription factors E2F4, thereby regulating ferroptosis resistance and stemness of gastric cancer cells. Given the importance of POLQ in stemness and ferroptosis resistance of GC, we further evaluated the therapeutic potential of POLQ inhibitor novobiocin, the results show that novobiocin attenuates the stemness of GC cells and increased ferroptosis sensitivity. Moreover, the combination of POLQ inhibitor and ferroptosis inducer synergistically suppressed MGC-803 xenograft tumor growth and diminished metastasis. Our results identify a POLQ-mediated stemness and ferroptosis defense mechanism and provide a new therapeutic strategy for gastric cancer.

Exopolysaccharides and Surface-Layer Proteins Expressed by Biofilm-State Lactiplantibacillus plantarum Y42 Play Crucial Role in Preventing Intestinal Barrier and Immunity Dysfunction of Balb/C Mice Infected by Listeria monocytogenes ATCC 19115.

Our previous study showed that Lactiplantibacillus plantarum Y42 in the biofilm state can produce more exopolysaccharides and surface-layer proteins and showed a stronger promoting effect on intestinal barrier function than that in the planktonic state. In this study, oral administration of the live/pasteurized planktonic or biofilm L. plantarum Y42 and its metabolites (exopolysaccharides and surface-layer proteins) increased the expression of Occludin, Claudin-1, ZO-1, and MUC2 in the gut of the Balb/C mice after exposure to Listeria monocytogenes ATCC 19115 and inhibited the activation of the NLRP3 inflammasome pathway, which in turn reduced the levels of inflammatory cytokines IL-1ß and IL-18 in the serum of the mice. Furthermore, oral administration of the live/pasteurized planktonic or biofilm L. plantarum Y42 and its metabolites increased the abundance of beneficial bacteria (e.g., Lachnospiraceae_NK4A136_group and Prevotellaceae_UCG-001) while reducing the abundance of harmful bacteria (e.g., norank_f__Muribaculaceae) in the gut of the mice, in line with the increase of short-chain fatty acids and indole derivatives in the feces of the mice. Notably, biofilm L. plantarum Y42 exerted a better preventing effect on the intestinal barrier dysfunction of the Balb/C mice due to the fact that biofilm L. plantarumY42 expressed more exopolysaccharides and surface-layer proteins than the planktonic state. These results provide data support for the use of exopolysaccharides and surface-layer proteins extracted from biofilm-state L. plantarum Y42 as functional food ingredients in preventing intestinal barrier dysfunction.

Chromosomal 3q amplicon encodes essential regulators of secretory vesicles that drive secretory addiction in cancer.

Cancer cells exhibit heightened secretory states that drive tumor progression. Here, we identify a chromosome 3q amplicon that serves as a platform for secretory regulation in cancer. The 3q amplicon encodes multiple Golgi-resident proteins, including the scaffold Golgi integral membrane protein 4 (GOLIM4) and the ion channel ATPase Secretory Pathway Ca2+ Transporting 1 (ATP2C1). We show that GOLIM4 recruits ATP2C1 and Golgi phosphoprotein 3 (GOLPH3) to coordinate calcium-dependent cargo loading and Golgi membrane bending and vesicle scission. GOLIM4 depletion disrupts the protein complex, resulting in a secretory blockade that inhibits the progression of 3q-amplified malignancies. In addition to its role as a scaffold, GOLIM4 maintains intracellular manganese (Mn) homeostasis by binding excess Mn in the Golgi lumen, which initiates the routing of Mn-bound GOLIM4 to lysosomes for degradation. We show that Mn treatment inhibits the progression of multiple types of 3q-amplified malignancies by degrading GOLIM4, resulting in a secretory blockade that interrupts pro-survival autocrine loops and attenuates pro-metastatic processes in the tumor microenvironment. Potentially underlying the selective activity of Mn against 3q-amplified malignancies, ATP2C1 co-amplification increases Mn influx into the Golgi lumen, resulting in a more rapid degradation of GOLIM4. These findings show that functional cooperativity between co-amplified genes underlies heightened secretion and a targetable secretory addiction in 3q-amplified malignancies.

Establishment and verification of a nomogram that predicts the risk for coronary slow flow.

Background: Coronary slow flow (CSF) has gained significance as a chronic coronary artery disease, but few studies have integrated both biological and anatomical factors for CSF assessment. This study aimed to develop and validate a simple-to-use nomogram for predicting CSF risk by combining biological and anatomical factors. Methods: In this retrospective case-control study, 1042 patients (614 CSF cases and 428 controls) were randomly assigned to the development and validation cohorts at a 7:3 ratio. Potential predictive factors were identified using least absolute shrinkage and selection operator regression and subsequently utilized in multivariate logistic regression to construct the nomogram. Validation of the nomogram was assessed by discrimination and calibration. Results: N-terminal pro brain natriuretic peptide, high density lipoprotein cholesterol, hemoglobin, left anterior descending artery diameter, left circumflex artery diameter, and right coronary artery diameter were independent predictors of CSF. The model displayed high discrimination in the development and validation cohorts (C-index 0.771, 95% CI: 0.737-0.805 and 0.805, 95% CI: 0.757-0.853, respectively). The calibration curves for both cohorts showed close alignment between predicted and actual risk estimates, demonstrating improved model calibration. Decision curve analysis suggested high clinical utility for the predictive nomogram. Conclusion: The constructed nomogram accurately and individually predicts the risk of CSF for patients with suspected CSF and may be considered for use in clinical care.

Oral Administration of Fermented Milk from Co-Starter Containing Lactobacillus plantarum Y44 Shows an Ameliorating Effect on Hypertension in Spontaneously Hypertensive Rats.

Fermented dairy foods such as yogurt exhibit some beneficial effects on consumers, including relieving the symptoms of hypertension. This study aims to obtain fermented dairy products from a co-starter that have a great flavor and the auxiliary function of reducing blood pressure after longtime consumption. Commercial starter cultures composed of Lactobacillus delbrueckii subsp. bulgaricus CICC 6047 and Streptococcus thermophilus CICC 6038 were combined with Lactobacillus plantarum strains Y44, Y12, and Y16, respectively, as a combined starter culture to ferment the mixed milk of skim milk and soybean milk. The fermented milk produced using the combined starter culture mixed with L. plantarum Y44 showed an angiotensin-converting-enzyme (ACE) inhibitory activity (53.56 ± 0.69%). Some peptides that regulate blood pressure were released in the fermented milk, such as AMKPWIQPK, GPVRGPFPII, LNVPGEIVE, NIPPLTQTPV, and YQEPVL. In spontaneously hypertensive rat (SHR) oral-administration experiments compared with the gavage unfermented milk group, the gavage feeding of SHRs with the fermented milk produced using the combined starter culture mixed with L. plantarum Y44 significantly reduced the blood pressure of the SHRs after long-term intragastric administration, shown with the systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreasing by 23.67 ± 2.49 mmHg and 15.22 ± 2.62 mmHg, respectively. Moreover, the abundance of short-chain fatty acids (SCFA), bacterial diversity in the gut microbiota, and SCFA levels including acetic acid, propionic acid, and butyric acid in the feces of the SHRs were increased via oral administration of the fermented milk produced using the combined starter culture containing L. plantarum Y44. Furthermore, the ACE-angiotensin II (Ang II)-angiotensin type 1 (AT 1) axis was downregulated, the angiotensin-converting-enzyme 2 (ACE 2)-angiotensin(1-7) (Ang1-7)-Mas receptor axis of the SHRs was upregulated, and then the RAS signal was rebalanced. The fermented milk obtained from the combined starter culture shows the potential to be a functional food with antihypertension properties.

A novel intelligent model for visualized inference of medical diagnosis: A case of TCM.

How to present an intelligent model based on known diagnostic knowledge to assist medical diagnosis and display the reasoning process is an interesting issue worth exploring. This study developed a novel intelligent model for visualized inference of medical diagnosis with a case of Traditional Chinese Medicine (TCM). Four classes of TCM's diagnosis composed of Yin deficiency, Liver Yin deficiency, Kidney Yin deficiency, and Liver-Kidney Yin deficiency were selected as research examples. According to the knowledge of diagnostic points in "Diagnostics of TCM", a total of 2000 samples for training and testing were randomly generated for the four classes of TCM's diagnosis. In addition, a total of 60 clinical samples were collected from hospital clinical cases. Training samples were sent to the pre-training language model of Chinese Bert for training to generate intelligent diagnostic module. Simultaneously, a mathematical algorithm was developed to generate inferential digraphs. In order to evaluate the performance of the model, the values of accuracy, F1 score, Mse, Loss and other indicators were calculated for model training and testing. And the confusion matrices and ROC curves were plotted to estimate the predictive ability of the model. The novel model was also compared with RF and XGBOOST. And some instances of inferential digraphs with the model were displayed and analyzed. It may be a new attempt to solve the problem of interpretable and inferential intelligent models in the field of artificial intelligence on medical diagnosis of TCM.