Comparison of magnetic susceptibility probes relevantly used in soil contamination applications.

Magnetic susceptibility (MS) technology can achieve the efficient rough measurement, mapping, and pollution assessment of soil heavy metal concentrations in topsoil due to atmospheric dust contamination. However, previous studies of commonly used MS field probes (MS2D, MS2F, and MS2K) have not dealt with the range of magnetic signal detection and the attenuation characteristics of the signal with respect to distance. In this study, the vertical and horizontal measurement ranges of the MS2D, MS2F, and MS2K probes were explored through laboratory and field experiments, and the intensity of their magnetic signals was further compared and analyzed in the field. The results showed that the magnetic signal intensity of the three probes decreased exponentially with distance. The penetration depths of the MS2D, MS2F, and MS2K probes were 8.5, 2.4, and 3.0 cm, respectively, and the horizontal detection boundary lengths of their magnetic signals were 32, 8, and 6.8 cm, respectively. In the field surface soil MS detection, the magnetic measurement signals of the MS2F and MS2K probes showed a weak linear correlation with the MS2D probe (R2 of 0.43 and 0.50, respectively), while the MS2F and MS2K probes had a significantly better correlation (R2 = 0.68) with each other. In general, the MS2D probe and MS2K probe correlation had a slope close to unity, meaning MS2K probes had good mutual substitution. Furthermore, results of this study improve the effectiveness of the MS evaluation of heavy metal pollution in urban topsoil.

Dynamic Mitigation Mechanisms of Rime Icing with Propagating Surface Acoustic Waves.

Ice accretion on economically valuable and strategically important surfaces poses significant challenges. Current anti-/de-icing techniques often have critical issues regarding their efficiency, convenience, long-term stability, or sustainability. As an emerging ice mitigation strategy, the thin-film surface acoustic wave (SAW) has great potentials due to its high energy efficiency and effective integration on structural surfaces. However, anti-/de-icing processes activated by SAWs involve complex interfacial evolution and phase changes, and it is crucial to understand the nature of dynamic solid-liquid-vapor phase changes and ice nucleation, growth, and melting events under SAW agitation. In this study, we systematically investigated the accretion and removal of porous rime ice from structural surfaces activated by SAWs. We found that icing and de-icing processes are strongly linked with the dynamical interfacial phase and structure changes of rime ice under SAW activation and the acousto-thermally induced localized heating that facilitate the melting of ice crystals. Subsequently, interactions of SAWs with the formed thin water layer at the ice/structure interface result in significant streaming effects that lead to further damage and melting of ice, liquid pumping, jetting, or nebulization.

Droplet-Based Microfluidic Tool to Quantify Viscosity of Concentrating Protein Solutions.

PURPOSE: Measurement of the viscosity of concentrated protein solutions is vital for the manufacture and delivery of protein therapeutics. Conventional methods for viscosity measurements require large solution volumes, creating a severe limitation during the early stage of protein development. The goal of this work is to develop a robust technique that requires minimal sample. METHODS: In this work, a droplet-based microfluidic device is developed to quantify the viscosity of protein solutions while concentrating in micrometer-scale droplets. The technique requires only microliters of sample. The corresponding viscosity is characterized by multiple particle tracking microrheology (MPT). RESULTS: We show that the viscosities quantified in the microfluidic device are consistent with macroscopic results measured by a conventional rheometer for poly(ethylene) glycol (PEG) solutions. The technique was further applied to quantify viscosities of well-studied lysozyme and bovine serum albumin (BSA) solutions. Comparison to both macroscopic measurements and models (Krieger-Dougherty model) demonstrate the validity of the approach. CONCLUSION: The droplet-based microfluidic device provides accurate quantitative values of viscosity over a range of concentrations for protein solutions with small sample volumes (~ µL) and high compositional resolution. This device will be extended to study the effect of different excipients and other additives on the viscosity of protein solutions.

A Co-Delivery System of Curcumin and p53 for Enhancing the Sensitivity of Drug-Resistant Ovarian Cancer Cells to Cisplatin.

In order to enhance the sensitivity of drug-resistant ovarian cancer cells to cisplatin (DDP), a co-delivery system was designed for simultaneous delivery of curcumin (CUR) and p53 DNA. Firstly, the bifunctional peptide K14 composed of tumor targeting peptide (tLyP-1) and nuclear localization signal (NLS) was synthesized. A nonviral carrier (PEI-K14) was synthesized by cross-linking low molecular weight polyethyleneimine (PEI) with K14. Then, CUR was coupled to PEI-K14 by matrix metalloproteinase 9 (MMP9)-cleavable peptide to prepare CUR-PEI-K14. A co-delivery system, named CUR-PEI-K14/p53, was obtained by CUR-PEI-K14 and p53 self-assembly. Furthermore, the physicochemical properties and gene transfection efficiency were evaluated. Finally, ovarian cancer cisplatin-resistant (SKOV3-DDP) cells were selected to evaluate the effect of CUR-PEI-K14/p53 on enhancing the sensitivity of drug-resistant cells to DDP. The CUR-PEI-K14/DNA complexes appeared uniformly dispersed and spherical. The particle size was around 20-150 nm and the zeta potential was around 18-37 mV. It had good stability, high transfection efficiency, and low cytotoxicity. CUR-PEI-K14/p53 could significantly increase the sensitivity of SKOV3-DDP cells to DDP, and this effect was better as combined with DDP. The sensitizing effect might be related to the upregulation of p53 messenger RNA (mRNA), the downregulation of P-glycoprotein (P-gp) mRNA, and the upregulation of BCL2-Associated X (bax) mRNA. CUR-PEI-K14/p53 can be used as an effective strategy to enhance the sensitivity of drug-resistant ovarian cancer cells to DDP.

Validation of the targeted metabolomic pathway in the hippocampus and comparative analysis with the prefrontal cortex of social defeat model mice.

The proportion of major depressive disorder (MDD) patients around the world has increased remarkably. Although many studies of MDD have been conducted based on classic hypotheses, like alteration of the hypothalamic-pituitary-adrenal axis or monoamine neurotransmitters, the mechanisms underlying MDD remain unclear. Aiming to further investigate the mechanisms of MDD, liquid chromatography-tandem mass spectrometry was employed to measure target metabolites in the hippocampus (HIPPO) of chronic social defeat stress model mice. Compared with control mice, stress-susceptible mice showed a reduction of 5-hydroxyindoleacetic acid and kynurenic acid in the tryptophan pathway, and an increased level of dopamine in the catecholamine pathway, while stress-resilient mice displayed a reduction of 5-hydroxytryptamine in the tryptophan pathway. The altered levels of key molecules related to the tryptophan or dopamine metabolic pathways were validated by real-time quantitative polymerase chain reaction or western blotting. Comparative analysis with previous targeted metabolomics results in the prefrontal cortex (PFC) of chronic social defeat stress mice revealed that the altered metabolites manifested in specific brain areas, and only the dopamine metabolic pathway was perturbed in both the HIPPO and PFC after stress. Additionally, correlation analysis validated that levels of kynurenic acid in the HIPPO, along with glutamic acid, L-3, 4-dihydroxyphenylalanine, and vanillylmandelic acid in the PFC, were correlated with depression-like behaviors. This study provides a unique perspective on the potential molecular mechanisms of stress susceptibility and stress resilience.

Clostridium butyricum miyairi 588 has preventive effects on chronic social defeat stress-induced depressive-like behaviour and modulates microglial activation in mice.

Recent studies have suggested the neuroprotective effects of Clostridium butyricum on mood disorders. However, the potential role of Clostridium butyricum in modulating the gut-brain-axis remains unknown. Here, we applied the commercial Clostridium butyricum Miyairi 588 (CBM588) strain to assess psychological behavioural alterations in mice exposed to chronic social defeat stress (CSDS). We found that preventive treatment with CBM588 for 28 days ameliorated depressive-like behaviours in CSDS mice. We showed that CSDS led to increases in cytokines (IL-1ß, IL-6, and TNF-α), intestinal dysfunction and hippocampal microglial activation, while CBM588 partially relieved these alterations. By applying 16S sequencing, we found that Firmicutes was more abundant in the faeces of CBM588/CSDS mice than in the faeces of placebo/CSDS mice, and depression-like behaviours in the mice were correlated with certain strains (including Clostridium leptum, Blautia coccoides, Family_XIII_UCG-001, Candidatus Arthromitus sp-SFB-mouse-Japan and Streptococcus hyointestinalis) at the species level. Our results illustrated the preventive effect of CBM588 against stress, suggesting the beneficial role of CBM588 in regulating neuroinflammation via the gut-brain-axis. This study provides novel strategies for clinical and scientific investigations of depressive disorders.

The polymorphic CAG repeat in exon 1 of androgen receptor is associated with level of HDL cholesterol and hypertension in Chinese middle-aged and elderly men.

OBJECTIVE: The length of the CAG repeats in exon 1 of the androgen receptor (AR) gene has been shown to be inversely correlated with AR transcriptional activity. This study aimed to investigate the correlations between the length of CAG repeat in AR and serum lipids and hypertension in Chinese men. DESIGN AND PATIENTS: The relationship between length of the CAG repeat in exon 1 of AR with prevalence of hypertension and the levels of serum lipids among Chinese men (aged ≥40 years). MEASUREMENTS: The physical condition of the subjects was examined and recorded. The concentrations of blood lipids and sex hormones were measured, and the CAG repeat lengths of the AR gene were determined. RESULTS: The length of the AR CAG repeats was associated with HDL cholesterol (HDL-C) concentration, and the stepwise multiple regression model showed that this association was independent of body mass index (BMI), triglycerides (TG) and total cholesterol (TC), although these factors influence HDL-C concentration. Furthermore, men with <22 vs men with ≥22 CAG repeats showed higher blood pressure and higher prevalence of hypertension. Shorter CAG repeat numbers were associated with the increased risk of hypertension in a multivariate logistic regression analysis (odds ratio = 0·715; 95% confidence interval, 0·517-0·989; P = 0·043). No significant correlation of AR CAG repeat polymorphism with sex hormone levels, TG, LDL cholesterol (LDL-C) or TC was found. CONCLUSIONS: This study provides evidence that men carrying shorter (<22) AR CAG repeats have lower HDL-C level and increased risk of hypertension. The androgenic activity may differ due to the polymorphic length of CAG repeats of the AR gene.

Targeted Metabolomic Pathway Analysis and Validation Revealed Glutamatergic Disorder in the Prefrontal Cortex among the Chronic Social Defeat Stress Mice Model of Depression.

Major depressive disorder (MDD) is a severe psychiatric disease that has critically affected life quality for millions of people. Chronic stress is gradually recognized as a primary pathogenesis risk factor of MDD. Despite the remarkable progress in mechanism research, the pathogenesis mechanism of MDD is still not well understood. Therefore, we conducted a liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection of 25 major metabolites of tryptophanic, GABAergic, and catecholaminergic pathways in the prefontal cortex (PFC) of mice in chronic social defeat stress (CSDS). The depressed mice exhibit significant reduction of glutamate in the GABAergic pathway and an increase of L-DOPA and vanillylmandelic acid in catecholaminergic pathways. The data of real-time-quantitative polymerase chain reaction (RT-qPCR) and Western blotting analysis revealed an altered level of glutamatergic circuitry. The metabolomic and molecular data reveal that the glutamatergic disorder in mice shed lights to reveal a mechanism on depression-like and stress resilient phenotype.

Differential co-expression and regulation analyses reveal different mechanisms underlying major depressive disorder and subsyndromal symptomatic depression.

BACKGROUND: Recent depression research has revealed a growing awareness of how to best classify depression into depressive subtypes. Appropriately subtyping depression can lead to identification of subtypes that are more responsive to current pharmacological treatment and aid in separating out depressed patients in which current antidepressants are not particularly effective. Differential co-expression analysis (DCEA) and differential regulation analysis (DRA) were applied to compare the transcriptomic profiles of peripheral blood lymphocytes from patients with two depressive subtypes: major depressive disorder (MDD) and subsyndromal symptomatic depression (SSD). RESULTS: Six differentially regulated genes (DRGs) (FOSL1, SRF, JUN, TFAP4, SOX9, and HLF) and 16 transcription factor-to-target differentially co-expressed gene links or pairs (TF2target DCLs) appear to be the key differential factors in MDD; in contrast, one DRG (PATZ1) and eight TF2target DCLs appear to be the key differential factors in SSD. There was no overlap between the MDD target genes and SSD target genes. Venlafaxine (Efexor™, Effexor™) appears to have a significant effect on the gene expression profile of MDD patients but no significant effect on the gene expression profile of SSD patients. CONCLUSION: DCEA and DRA revealed no apparent similarities between the differential regulatory processes underlying MDD and SSD. This bioinformatic analysis may provide novel insights that can support future antidepressant R&D efforts.

Divergent Urinary Metabolic Phenotypes between Major Depressive Disorder and Bipolar Disorder Identified by a Combined GC-MS and NMR Spectroscopic Metabonomic Approach.

Bipolar disorder (BD) is a complex debilitating mental disorder that is often misdiagnosed as major depressive disorder (MDD). Therefore, a large percentage of BD subjects are incorrectly treated with antidepressants in clinical practice. To address this challenge, objective laboratory-based tests are needed to discriminate BD from MDD patients. Here, a combined gas chromatography-mass spectrometry (GC-MS)-based and nuclear magnetic resonance (NMR) spectroscopic-based metabonomic approach was performed to profile urine samples from 76 MDD and 43 BD subjects (training set) to identify the differential metabolites. Samples from 126 healthy controls were included as metabolic controls. A candidate biomarker panel was identified by further analyzing these differential metabolites. A testing set of, 50 MDD and 28 BD subjects was then used to independently validate the diagnostic efficacy of the identified panel using an area under the receiver operating characteristic curve (AUC). A total of 20 differential metabolites responsible for the discrimination between MDD and BD subjects were identified. A panel consisting of six candidate urinary metabolite biomarkers (propionate, formate, (R*,S*)2,3-dihydroxybutanoic acid, 2,4-dihydroxypyrimidine, phenylalanine, and ß-alanine) was identified. This panel could distinguish BD from MDD subjects with an AUC of 0.913 and 0.896 in the training and testing sets, respectively. These results reveal divergent urinary metabolic phenotypes between MDD and BD. The identified urinary biomarkers can aid in the future development of an objective laboratory-based diagnostic test for distinguishing BD from MDD patients.

Is pindolol augmentation effective in depressed patients resistant to selective serotonin reuptake inhibitors? A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis was conducted to assess the use of pindolol augmentation in depressed patients resistant to selective serotonin reuptake inhibitor (SSRI) therapy. METHODS: A comprehensive search of PubMed, Cochrane, Embase, Web of Science, and PsychINFO databases from 1970 through December 2013 was conducted. Only randomized controlled trials (RCTs) studied on unipolar SSRI-resistant depressed adults were included. The primary outcome was mean change scores of depressive symptom on the depression rating scales, assessed with standardized mean differences. RESULTS: Five RCTs consisting of 154 patients met all inclusion and exclusion criteria. The overall pooled effect size in the primary and secondary efficacy analysis showed no significant effects of pindolol plus SSRI therapy (standardized mean difference = -0.43, p = 0.24; OR = 1.92, p = 0.39, respectively). In terms of acceptability, there was no statistical difference in either tolerability or safety between the two groups (OR = 0.46, p = 0.40; OR = 0.90, p = 0.94, respectively). These estimates remained robust through several sensitivity and subgroup analyses, except 7.5 mg-qd pindolol augmentation did show a significant benefit over 2.5-mg tid pindolol augmentation. CONCLUSIONS: Pindolol augmentation may not be suitable for treatment-resistant depression patients with SSRI-resistant depression. However, once-daily high-dose pindolol (7.5 mg qd) appears to show a promising benefit in these patients.

Identification and validation of urinary metabolite biomarkers for major depressive disorder.

Major depressive disorder (MDD) is a widespread and debilitating mental disorder. However, there are no biomarkers available to aid in the diagnosis of this disorder. In this study, a nuclear magnetic resonance spectroscopy-based metabonomic approach was employed to profile urine samples from 82 first-episode drug-naïve depressed subjects and 82 healthy controls (the training set) in order to identify urinary metabolite biomarkers for MDD. Then, 44 unselected depressed subjects and 52 healthy controls (the test set) were used to independently validate the diagnostic generalizability of these biomarkers. A panel of five urinary metabolite biomarkers-malonate, formate, N-methylnicotinamide, m-hydroxyphenylacetate, and alanine-was identified. This panel was capable of distinguishing depressed subjects from healthy controls with an area under the receiver operating characteristic curve (AUC) of 0.81 in the training set. Moreover, this panel could classify blinded samples from the test set with an AUC of 0.89. These findings demonstrate that this urinary metabolite biomarker panel can aid in the future development of a urine-based diagnostic test for MDD.

Phase change surfaces with porous metallic structures for long-term anti/de-icing application.

HYPOTHESIS: Ice mitigation has received increasing attention due to the severe safety and economic threats of icing hazards to modern industries. Slippery icephobic surface is a potential ice mitigation approach due to its ultra-low ice adhesion strength, great humidity resistance, and effective delay of ice nucleation. However, this approach currently has limited practical applications because of serious liquid depletion in the icing/de-icing process. EXPERIMENTS: A new strategy of phase change materials (PCM)-impregnation porous metallic structures (PIPMSs) was proposed to develop phase changeable icephobic surfaces in this study, and aimed to solve the rapid depletion via the phase changeable interfacial interactions. FINDINGS: Evaluation of surface icephobicity and interfacial analysis proved that the phase changeable surfaces (PIPMSs) worked as an effective and durable icephobic platform by significantly delaying ice nucleation, providing long-term humid tolerance, low ice adhesion strength of as-prepared samples (less than 5 kPa), and signally improved maintaining capacity of impregnated PCMs (less than 10 % depletion) after 50 icing/de-icing cycles. To explore the interfacial responses, phase change models consisting of the unfrozen quasi-liquid layer and solid lubricant layer at the ice/PIPMSs interfaces were established, and the involved icephobic mechanisms of PIPMSs were studied based on the analysis of interfacial interactions.

Anisotropic Icephobic Mechanisms of Textured Surface: Barrier or Accelerator?

Icing has been seen as an economic and safety hazard due to its threats to aviation, power generation, offshore platforms, etc., where passive icephobic surfaces with a surface texturing design have the potential to address this problem. However, the intrinsic icephobic principles associated with the surface textures, energy, elasticity, and hybrid effects are still unclear. To explore the anisotropic wettability, ice nucleation, and ice detaching behaviors, a series of textured poly(dimethylsiloxane) (PDMS)-based coatings with various texture orientations were proposed through a simple stamping method with surface functionalization. The anisotropic hydrophobic/icephobic phenomena and mechanisms were discovered from wettability evaluation, experimentally studied by icing/deicing experiments, and finally verified by microscopic numerical simulations. One-way analysis of variance (one-way ANOVA analysis) was used to analyze the effect of surface textures on hydrophobic/icephobic properties, which assisted in understanding anisotropic phenomena. Typical anisotropic ice nucleation and growth on the textured coatings were clarified using in situ environmental scanning electron microscope (ESEM) characterization. The ice/coating interfacial stress responses were studied by numerical stimulation at the microscopic level, further verifying the localized, amplified, and propagated stress at the ice/coating interface. The theoretical anisotropic responses, barrier effect, and accelerating effect were verified to interpret the anisotropic wettability and icephobicity, depending on the specific surface conditions. This study revealed the basics of the anisotropic icephobic mechanisms of textured icephobic surfaces, further facilitating the R&D of passive icephobic surfaces.

A tough and bioadhesive injectable hydrogel formed with maleimidyl alginate and pristine gelatin.

Injectable hydrogels have wide applications in clinical practice. However, the development of tough and bioadhesive ones based on biopolymers, along with biofriendly and robust crosslinking strategies, still represents a great challenge. Herein, we report an injectable hydrogel composed of maleimidyl alginate and pristine gelatin, for which the precursor solutions could self-crosslink via mild Michael-type addition without any catalyst or external energy upon mixing. This hydrogel is tough and bioadhesive, which can maintain intactness as well as adherence to the defect of porcine skin under fierce bending and twisting, warm water bath, and boiling water shower. Besides, it is biocompatible, bioactive and biodegradable, which could support the growth and remodeling of cells by affording an extracellular matrix-like environment. As a proof of application, we demonstrate that this hydrogel could significantly accelerate diabetic skin wound healing, thereby holding great potential in healthcare.

Patchy profile sign in RAPID software: a specific marker for intracranial atherosclerotic stenosis in acute ischemic stroke.

Purpose: Identifying the etiology of acute ischemic stroke (AIS) before endovascular treatment (EVT) is important but challenging. In CT perfusion imaging processed by perfusion software, we observed a phenomenon called patchy profile sign (PPS), that is, the hypoperfusion morphology in RAPID software is a discontinuous sheet pattern. This phenomenon is predominantly observed in patients diagnosed with intracranial atherosclerotic stenosis (ICAS). The study intends to assess whether the PPS can be used to differentiate ICAS from intracranial embolism. Method: Patients with AIS due to M1 segment occlusion of the MCA who underwent mechanical thrombectomy were retrospectively enrolled. The receiver operating characteristic (ROC) curve analysis was performed to assess the value of PPS in predicting ICAS. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the PPS for prediction of ICAS were calculated. Results: A total of 51 patients were included in the study. The PPS was observed in 10 of 19 (52.6%) patients with ICAS, and in 2 of 32 (6.3%) patients with intracranial embolism (p < 0.001). Interobserver agreement for identifying PPS was excellent (κ = 0.944). The sensitivity, specificity, PPV, NPV, and accuracy of the PPS for predicting ICAS were 52.6, 93.8, 83.3, 76.9, and 78.4%, respectively. Conclusion: The PPS on RAPID software is an imaging marker with high specificity for ICAS. Larger sample sizes are imperative to validate the findings.

Synergistic Effects of Multiple Excipients on Controlling Viscosity of Concentrated Protein Dispersions.

Viscosity control is essential for the manufacturing and delivery of concentrated therapeutic proteins. Limited availability of the precious protein-based drugs hinders the characterization and screening of the formulation conditions with new types or different combinations of excipients. In this work, a droplet-based microfluidic device with incorporated multiple particle tracking microrheology (MPT) is developed to quantify the effects of two excipients, arginine hydrochloride (ArgHCl) and caffeine, on the viscosity of concentrated bovine gamma globulin (BGG) dispersions at two different values of pH. The effectiveness of both ArgHCl and caffeine show dependence on the BGG concentration and solution pH. The data set with high compositional resolution provides useful information to guide formulation with multiple viscosity-reducing excipients and quantification appropriate to start elucidating the connection to protein-protein interaction mechanisms. Overall, this work has demonstrated that the developed microfluidic approach has the potential to effectively assess the impact of multiple excipients on the viscosity and provide data for computational methods to predict viscosity for high concentration protein formulations.

Effect of heating history on the emission of volatile organic compounds from asphalt materials.

Asphalt binders release hazardous fumes during high-temperature heating that severely endanger human health and pollute the environment. In this study, a volatile organic compound (VOC) generation and detection device comprising a portable VOC detector was developed, and two heating modes (intermittent and continuous heating) were established to explore the influence of heating history on the VOC emission behavior of five asphalt samples. The changes in the VOC species and content, as determined by the heating history, were analyzed via gas chromatography-mass spectrometry (GC-MS). Finally, the key factors affecting the emission of VOCs from asphalt are discussed based on the four components of asphalt materials. The results indicated that the emission of VOCs from asphalt materials under intermittent heating conditions decreased significantly with increasing heating history (significantly fewer VOCs, including 13 common components such as alkanes, benzenes, and hydrocarbon derivatives, were emitted under this condition than under continuous heating conditions at the same temperature point). Compared with continuous heating, intermittent heating is more conducive for studying asphalt VOCs. Under intermittent heating, different asphalt materials exhibited similar VOC emission curves; the VOCs were mainly emitted during the first two heating stages (200 and 180 °C, respectively). Thus, it can be deduced that asphalt VOC emissions were induced by the synchronized actions of the four components of asphalt materials. Therefore, different components can contribute to the emission of several VOCs of the same composition. The heavy and light components mainly facilitate the emission of common components with carbon atomic numbers <18 and > 18, respectively.

Artificial intelligence-accelerated high-throughput screening of antibiotic combinations on a microfluidic combinatorial droplet system.

Microfluidic platforms have been employed as an effective tool for drug screening and exhibit the advantages of lower reagent consumption, higher throughput and a higher degree of automation. Despite the great advancement, it remains challenging to screen complex antibiotic combinations in a simple, high-throughput and systematic manner. Meanwhile, the large amounts of datasets generated during the screening process generally outpace the abilities of the conventional manual or semi-automatic data analysis. To address these issues, we propose an artificial intelligence-accelerated high-throughput combinatorial drug evaluation system (AI-HTCDES), which not only allows high-throughput production of antibiotic combinations with varying concentrations, but can also automatically analyze the dynamic growth of bacteria under the action of different antibiotic combinations. Based on this system, several antibiotic combinations displaying an additive effect are discovered, and the dosage regimens of each component in the combinations are determined. This strategy not only provides useful guidance in the clinical use of antibiotic combination therapy and personalized medicine, but also offers a promising tool for the combinatorial screenings of other medicines.

The Effect of Oat Hay, Alfalfa Hay, and Their Combined Diets on the Morphology and Function of the Pancreas in Preweaning Yak Calves.

In this study, we used a combination of animal nutrition and nontargeted metabolomics to investigate the effects of feeding different sources forages rations on the morphology and function of the pancreas in preweaning yak calves, providing theoretical guidance and important references for the healthy and high-quality rearing of yak calves. At 45 days old, 21 yak calf males were divided into OP, AP, and AOP groups, with seven animals in each group, which were fed with oat hay, alfalfa hay, and mixed oat and alfalfa hay, respectively. Five calves from each group were selected randomly to slaughter after a pretest period of 21 days and the official period of 120 days, when the average daily feed intake reached 1 kg. During the test, the growth and pancreas weight of yak calves were recorded, and the morphology and function of the pancreas tissues were determined using tissue sectioning methods, enzyme-linked immunosorbent assay (ELISA) tests, and nontargeted metabolomics strategies. The results showed that the body weight and pancreatic organ index of yak calves in the AOP group were significantly higher than those of the AP and OP groups. Compared to the AP and OP groups, the AOP group had considerably lower ratios of the area of the pancreatic endocrine component and overall percentage of that section of the organ, and the AOP group increased pancreatic amylase activity and a higher concentration of growth inhibitor. The AP group had significantly higher levels of the differential metabolites L-ascorbic acid, spermidine, spermine, and dopaquinone in the glutathione, ß-alanine, and tyrosine metabolic pathways than the OP group. The AOP group had significantly lower levels of the differential metabolites spermine and phenylacetylglycine in the glutathione and phenylalanine metabolic pathways than the AP group. In summary, compared to feeding oat or alfalfa hay alone, combined feeding oat hay and alfalfa hay is more beneficial to promote the morphological and functional development of the pancreas in preweaning yak calves, so as to enhance the digestion and absorption of nutrients in the diet and maintain the positive regulation of blood glucose levels. This provides an important basis for the optimized forage supply of healthy and high-quality rearing in preweaning yak calves.