Migratory herbivorous waterfowl track multiple resource waves during spring migration.

East Asian herbivorous waterfowl intensively use farmland in spring, next to their natural habitat. Accordingly, they might have expanded their migration strategy from merely tracking the green wave of newly emerging vegetation to also incorporating the availability of post-harvest agricultural seeds (here dubbed the seed wave). However, if and how waterfowl use multiple food resources to time their seasonal migration is still unknown. We test this migration strategy using 167 spring migration tracks of five East Asian herbivorous waterfowl species and mixed-effect resource selection function models. We found that all study species arrived at their core stopover sites in the Northeast China Plain after agricultural seeds became available, extended their stay after spring vegetation emerged and arrived at their breeding sites around the emergence of vegetation. At the core stopover sites, all study species used snowmelt as a cue to track seed availability, although smaller-bodied species tended to arrive later. At the breeding sites, swans tracked the onset of vegetation emergence and geese tracked the mid- or end phases of snowmelt. Our findings suggest that waterfowl track multiple resource waves to fine-tune their migration, highlighting new opportunities for conservation.

Development and application of a qPCR-based method coupled with spore trapping to monitor airborne pathogens of wheat causing stripe rust, powdery mildew, and Fusarium head blight.

Common wheat (Triticum aestivum L.) production in China is challenged by stripe (yellow) rust, powdery mildew, and Fusarium head blight (FHB). Airborne inoculum of these pathogens is the causative driver of disease epidemics. Thus, monitoring of airborne inoculum on such fungal diseases is expected to provide some reliable estimations of disease development, especially by targeting multiple diseases simultaneously. This paper reports the development of a new practical qPCR-based method coupled with spore trapping to quantify simultaneously airborne inoculum of Puccinia striiformis f. sp. tritici, Blumeria graminis f. sp. tritici, and Fusarium graminearum & Fusarium asiaticum and discusses its potential use in disease-risk warnings. The technique can detect DNA of Pst, Bgt, and Fg at quantities as low as 0.2 pg (i.e. representing 0.65 urediniospores, 1.18 conidia, and 10 macroconidia, respectively), and neither Triticum aestivum DNA nor DNA of other common wheat pathogens were amplified. A linear relationship was produced between the number of spores on tape determined by qPCR and conventional microscopy, with a small variation (R2 value 0.97 to 0.99 depending on pathogen species). The daily concentrations of spores of the three pathogens were monitored using a Burkard 7-day recording spore trap, and the airborne spores were collected from a field near Langfang City, Hebei Province, China. The patterns of spore concentration dynamics in the air determined by triplex qPCR were close to those counted by conventional microscopy in a duplicated sub-sample. The developed assay can be an alternative to conventional microscopy to process large samples. This will improve monitoring power by providing timely risk warning information to growers regarding the timing of fungicide applications.

Structural basis of Frizzled 4 in recognition of Dishevelled 2 unveils mechanism of WNT signaling activation.

WNT signaling is fundamental in development and homeostasis, but how the Frizzled receptors (FZDs) propagate signaling remains enigmatic. Here, we present the cryo-EM structure of FZD4 engaged with the DEP domain of Dishevelled 2 (DVL2), a key WNT transducer. We uncover a distinct binding mode where the DEP finger-loop inserts into the FZD4 cavity to form a hydrophobic interface. FZD4 intracellular loop 2 (ICL2) additionally anchors the complex through polar contacts. Mutagenesis validates the structural observations. The DEP interface is highly conserved in FZDs, indicating a universal mechanism by which FZDs engage with DVLs. We further reveal that DEP mimics G-protein/ß-arrestin/GRK to recognize an active conformation of receptor, expanding current GPCR engagement models. Finally, we identify a distinct FZD4 dimerization interface. Our findings delineate the molecular determinants governing FZD/DVL assembly and propagation of WNT signaling, providing long-sought answers underlying WNT signal transduction.

The hemostatic molecular mechanism of Sanguisorbae Radix's pharmacological active components based on HSA: Spectroscopic investigations, molecular docking and dynamics simulation.

The interactions between human serum albumin (HSA) and the hemostatic components of the Chinese medicine Sanguisorbae Radix (SR), specifically phenolic acid compounds such as caffeic acid (CA), ferulic acid (FA) and their 1:1 mixture (1:1) were studied to investigate the molecular mechanism underlying the hemostatic effect of SR. Network pharmacology combined with the experimental and computational data revealed that HSA is one of the hemostatic targets to SR phenolic acids. SDS-PAGE and multi-spectroscopy demonstrated that the phenolic acids bind to the Sudlow site I on HSA, altering its structure and influencing its migration velocity. There is an observed synergistic effect upon the mixture of CA and FA. Quantum chemistry, molecular docking, and molecular dynamics simulations indicate that the binding of phenolic acids to HSA is stable, and variations in binding efficiency are associated with the hydrophobicity of the substituent at the C3 position of the side chain, and also, the key amino acids and functional groups for hemostasis of SR were identified, along with the active sites that contribute to the synergistic enhancement by phenolic acids.

Bioaccessibility and bioavailability assessment of cadmium in rice: In vitro simulators with/without gut microbiota and validation through in vivo mouse and human data.

Assessing the bioaccessibility and bioavailability of cadmium (Cd) is crucial for effective evaluation of the exposure risk associated with intake of Cd-contaminated rice. However, limited studies have investigated the influence of gut microbiota on these two significant factors. In this study, we utilized in vitro gastrointestinal simulators, specifically the RIVM-M (with human gut microbial communities) and the RIVM model (without gut microbial communities), to determine the bioaccessibility of Cd in rice. Additionally, we employed the Caco-2 cell model to assess bioavailability. Our findings provide compelling evidence that gut microbiota significantly reduces Cd bioaccessibility and bioavailability (p<0.05). Notably, strong in vivo-in vitro correlations (IVIVC) were observed between the in vitro bioaccessibilities and bioavailabilities, as compared to the results obtained from an in vivo mouse bioassay (R2 = 0.63-0.65 and 0.45-0.70, respectively). Minerals such as copper (Cu) and iron (Fe) in the food matrix were found to be negatively correlated with Cd bioaccessibility in rice. Furthermore, the results obtained from the toxicokinetic (TK) model revealed that the predicted urinary Cd levels in the Chinese population, based on dietary Cd intake adjusted by in vitro bioaccessibility from the RIVM-M model, were consistent with the actual measured levels (p > 0.05). These results indicated that the RIVM-M model represents a potent approach for measuring Cd bioaccessibility and underscore the crucial role of gut microbiota in the digestion and absorption process of Cd. The implementation of these in vitro methods holds promise for reducing uncertainties in dietary exposure assessment.

Advancing polarity-transcendent design: Development of a photoelectrochemical sensor with extended detection range.

In photoelectrochemical (PEC) sensors, traditional detection modes such as "signal-on", "signal-off", and "polarity-switchable" limit target signals to a single polarity range, necessitating novel design strategies to enhance the operational scope. To overcome this limitation, we propose, for the first time, a "polarity-transcendent" design concept that enables a continuous response across the polarity spectrum, significantly broadening the sensor's concentration detection range. This concept is exemplified in our new "background-enhanced signal-off polarity-switchable" (BESOPS) mode, where the model analyte let-7a activates a cascade shearing reaction of a DNAzyme walker in conjunction with CRISPR/Cas12a, quantitatively peeling off Cu2O-H2 strands at the Cu2O/TiO2 electrode interface to expose the TiO2 surface. This exposure generates an anodic photocurrent at the expense of the cathodic photocurrent from Cu2O/TiO2, facilitating a seamless transition of the target signal from cathodic to anodic. Through systematic experiments and comparative analyses, the BESOPS sensor demonstrates highly sensitive and precise quantification of let-7a, with a detection limit of 2.5 aM and a broad operating range of 10 aM to 10 nM. Its performance exceeds most reported sensor platforms, highlighting the significant potential of our polarity-transcendent design in expanding the operational range of PEC sensors. This innovative approach paves the way for developing next-generation PEC sensors with enhanced applicability and heightened sensitivity in various critical fields.

Engineering heterostructured Mo2C/MoS2 catalyst with hydrophilicity/aerophobicity via carbothermal shock for efficient alkaline hydrogen evolution.

The exploration of high-performance hydrogen evolution reaction (HER) catalysts is conducive to the development of clean hydrogen energy, yet still remains a challenge. Herein, we rapidly synthesize the Mo2C/MoS2 heterostructure on carbon paper (Mo2C/MoS2-CP) via carbothermal shock in only two seconds. The construction of the Mo2C/MoS2 heterostructure regulates the electronic structure of the Mo site and facilitates charge transfer during the HER process. Moreover, the catalyst exhibits enhanced hydrophilicity and aerophobicity, facilitating optimal electrolyte-catalyst interaction and efficient hydrogen bubble detachment for accelerated mass transfer. Consequently, Mo2C/MoS2-CP exhibits superior intrinsic alkaline HER activity, and excellent stability for 100 h. This finding provides a novel insight into the development of outstanding HER catalysts.

Dual-Locked Probe with Activatable Sonoafterglow Luminescence for Precise Imaging of MET-Induced Liver Injury.

Metformin (MET) is currently the first-line treatment for type 2 diabetes mellitus (T2DM). However, overdose and long-term use of MET may induce a serious liver injury. What's worse, diagnosis of MET-induced liver injury remains challenging in clinic. Although several probes have been reported for imaging MET-induced liver injury utilizing upregulated hepatic H2S as a biomarker, they are still at risk of nonspecific activation in complex physiological environments and rely on light excitation with limited imaging depth. Herein, we rationally designed and developed a dual-locked probe, DPA-H2S, for precise imaging of MET-induced liver injury by H2S-activated sonoafterglow luminescence. DPA-H2S is a small molecule consisting of a sonosensitizer protoporphyrin IX (PpIX) and an afterglow substrate that is dual-locked with a H2S-responsive 2,4-dinitrobenzene group and a 1O2-responsive electron-rich double bond. When employing DPA-H2S for imaging of MET-induced liver injury in vivo, since the PpIX moiety can produce 1O2 in situ at the liver site under focused ultrasound (US) irradiation, the two locks of DPA-H2S can be specifically activated by the highly upregulated H2S at the liver injury sites and the in situ generated 1O2, respectively. Thus, the sonoafterglow signal of DPA-H2S is significantly turned on, enabling precise imaging of the MET-induced liver injury. In vitro results showed that, through H2S-activated sonoafterglow luminescence, DPA-H2S was capable of imaging H2S with good sensitivity and high selectivity and realized deep tissue imaging (∼20 mm, signal-to-background ratio (SBR) = 3.4). Furthermore, we successfully applied DPA-H2S for precise in vivo imaging of MET-induced liver injury. We anticipate that our dual-locked probe, DPA-H2S, may serve as a promising tool in assisting the diagnosis of MET-induced liver injury in clinics and informing the clinical utilization of MET in the near future.

Identification of wheat stripe rust inoculum sources and dispersal routes responsible for initial rust establishment in southern Henan of China.

Wheat stripe rust (yellow rust), caused by Puccinia striiformis f. sp. tritici (Pst), is an important airborne disease worldwide. Pst inoculum strength in southern Henan in winter or early spring is important for spring epidemic in the main autumn-sown wheat-growing regions of China. However, there is limited knowledge about the source and time of initial infection on winter wheat in southern Henan. The first occurrence of wheat stripe rust in southern Henan was recorded annually from 2011-2022, from which we used the backward trajectory approach to infer the likely source of Pst inoculum responsible for the initial disease occurrence. The results suggested that the Pst inoculum responsible for initial rust established in the winter in southern Henan originated from the Gansu Pst oversummering area in China, whereas it originated from the adjacent winter Pst sporulation regions in southern Shaanxi and northwestern Hubei if Pst symptoms were first observed in early spring in southern Henan. Another possible Pst source is southern Hubei where Pst can also sporulate in the winter. Thus, early Pst development in winter in the main wheat production in China (Henan) is likely to be caused by Pst inoculum spread from the oversummering inocula or Pst epidemics in autumn seedlings in Gansu.

Obesity and 1-year all-cause survival of adult intensive care patients with heart failure: data from the MIMIC-IV.

BACKGROUND: Heart failure is a disease that threatens global public safety. In recent years, the obesity paradox has been studied in cardiovascular disease and other fields. With the progress of aging, metabolic changes and regulation of fat function, it also provides many bridges for the dialogue between disease and molecular metabolism. The purpose of this study is to investigate the effect of obesity on the outcome of adult intensive care patients with heart failure combined with age factors. METHOD: Data were derived from the fourth-generation Medical Information Marketplace for Intensive Care (MIMIC-IV version2.1) using structured query language on the Navicat (12.0.11) platform. People were divided into two groups based on the body mass index (BMI), one group with BMI ≥ 30 kg/m² and another group with BMI < 30 kg/m². Afterwards, the patients were divided into two subgroups based on their ages. One group included patients aged<60, and the other included patients aged ≥ 60. The extracted information includes demographic characteristics, laboratory findings, comorbidities, scores. Main results included in-hospital mortality, ICU mortality, and 1-year mortality. Secondary outcomes included hospital interval and ICU interval, use of renal replacement therapy, and rates of noninvasive and invasive ventilation support. RESULT: In this cohort study, 3390 people were in the BMI<30 group, 2301 people were in the BMI ≥ 30 group, 960 people were in the age<60 group, and 4731 people were in the age ≥ 60 group, including 3557 patients after propensity score matching in high age group. Among patients aged ≥ 60, BMI ≥ 30 group vs. BMI<30 group showed significantly lower in-hospital mortality (13% vs. 16%) and one-year mortality (41% vs. 55%), respectively. Neither primary nor secondary outcomes were significantly described in the competition among patients aged under 60. Restricted cubic spline reveals a J-shaped nonlinear association between BMI and clinical endpoints within the entire cohort. Kaplan-Meier curves revealed a survival advantage in BMI ≥ 30 group (p < 0.001). Following age stratification, a beneficial effect of BMI categories on one-year mortality risk was observed in heart failure patients aged ≥ 60 (Univariable HR, 0.71, 95% CI, 0.65-0.78, p < 0.001; Multivariable HR, 0.74, 95% CI, 0.67-0.81, p < 0.001), but not in those under 60 years old. OUTCOME: In ICU patients with heart failure, obesity offers a survival benefit to those aged ≥ 60. No obesity paradox was observed in patients younger than 60 years old. The obesity paradox applies to patients aged ≥ 60 with heart failure.

The molecular and network mechanisms of antilipidemic potential effects of Ganfule capsules in nonalcoholic fatty liver disease.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder characterized by hepatic steatosis, inflammation and fibrosis. Ganfule (GFL), a traditional Chinese medicine, has demonstrated therapeutic potential in the treatment of NAFLD but the mechanisms involved are not fully understood.To evaluate the biochemical mechanisms of GFL in treating NAFLD by examining its effects on biological networks, key therapeutic targets, histopathological changes and clinical implications. Methods: Chemical component screening, key target prediction, biological functional enrichment analysis, lipid profile localization analysis and complex network analysis were performed on GFL using multi-database mining, network analysis and molecular docking. An NAFLD rat model was then established and treated with different doses of GFL. Histopathological evaluation and western blotting were used to verify the expression levels of key target proteins in GFL-treated NAFLD rats. Results: Network analysis analysis identified 12 core targets, 12 core active ingredients and 7 core Chinese medicinal herbs in GFL potentially involved in the treatment of NAFLD. Biological functional enrichment analysis revealed the involvement of lipid metabolism, apoptosis and intracellular signaling pathways. Molecular docking confirmed a strong affinity between GFL's core compounds and certain target proteins. Histopathological examination of an NAFLD rat model showed reduced hepatocellular steatosis after GFL treatment. Western blotting revealed significant downregulation of PPARA and PPARD protein expression and upregulation of PIK3CG and PRKACA protein expression in NAFLD rats treated with lower doses of GFL. Conclusions: Our results suggest that GFL modulates key proteins involved in lipid metabolism and apoptosis pathways. GFL improved the histopathological features of NAFLD rats by regulating lipid metabolism as well as reducing hepatocyte apoptosis and hepatocellular steatosis. These findings offer insights into the biochemical mechanism of action of GFL and support its use in the treatment for NAFLD.

A Dual-Focus Workflow for Simultaneously Engineering High Activity and Thermal Stability in Methyl Parathion Hydrolase.

Industrial fermentation applications typically require enzymes that exhibit high stability and activity at high temperatures. However, efforts to simultaneously improve these properties are usually limited by a trade-off between stability and activity. This report describes a computational strategy to enhance both activity and thermal stability of the mesophilic organophosphate-degrading enzyme, methyl parathion hydrolase (MPH). To predict hotspot mutation sites, we assembled a library of features associated with the target properties for each residue and then prioritized candidate sites by hierarchical clustering. Subsequent in silico screening with multiple algorithms to simulate selective pressures yielded a subset of 23 candidate mutations. Iterative parallel screening of mutations that improved thermal stability and activity yielded, MPHase-m5b, which exhibited 13.3 °C higher Tm and 4.2 times higher catalytic activity than wild-type (WT) MPH over a wide temperature range. Systematic analysis of crystal structures, molecular dynamics (MD) simulations, and Quantum Mechanics/Molecular Mechanics (QM/MM) calculations revealed a wider entrance to the active site that increased substrate access with an extensive network of interactions outside the active site that reinforced αß/ßα sandwich architecture to improve thermal stability. This study thus provides an advanced, rational design framework to improve efficiency in engineering highly active, thermostable biocatalysts for industrial applications.

The Role of TGFBR3 in the Development of Lung Cancer.

The Transforming Growth Factor-ß (TGF-ß) mediates embryonic development, maintains cellular homeostasis, regulates immune function, and is involved in a wide range of other biological processes. TGF-ß superfamily signaling pathways play an important role in cancer development and can promote or inhibit tumorigenesis. Type III TGF-ß receptor (TGFBR3) is a co-receptor in the TGF-ß signaling pathway, which often occurs with reduced or complete loss of expression in many cancer patients and can act as a tumor suppressor gene. The reduction or deletion of TGFBR3 is more pronounced compared to other elements in the TGF-ß signaling pathway. In recent years, lung cancer is one of the major malignant tumors that endanger human health, and its prognosis is poor. Recent studies have reported that TGFBR3 expression decreases to varying degrees in different types of lung cancer, both at the tissue level and at the cellular level. The invasion, metastasis, angiogenesis, and apoptosis of lung cancer cells are closely related to the expression of TGFBR3, which strengthens the inhibitory function of TGFBR3 in the evolution of lung cancer. This article reviews the mechanism of TGFBR3 in lung cancer and the influencing factors associated with TGFBR3. Clarifying the physiological function of TGFBR3 and its molecular mechanism in lung cancer is conducive to the diagnosis and treatment of lung cancer.

Current insights and assumptions on α-synuclein in Lewy body disease.

Lewy body disorders are heterogeneous neurological conditions defined by intracellular inclusions composed of misshapen α-synuclein protein aggregates. Although α-synuclein aggregates are only one component of inclusions and not strictly coupled to neurodegeneration, evidence suggests they seed the propagation of Lewy pathology within and across cells. Genetic mutations, genomic multiplications, and sequence polymorphisms of the gene encoding α-synuclein are also causally linked to Lewy body disease. In nonfamilial cases of Lewy body disease, the disease trigger remains unidentified but may range from industrial/agricultural toxicants and natural sources of poisons to microbial pathogens. Perhaps due to these peripheral exposures, Lewy inclusions appear at early disease stages in brain regions connected with cranial nerves I and X, which interface with inhaled and ingested environmental elements in the nasal or gastrointestinal cavities. Irrespective of its identity, a stealthy disease trigger most likely shifts soluble α-synuclein (directly or indirectly) into insoluble, cross-ß-sheet aggregates. Indeed, ß-sheet-rich self-replicating α-synuclein multimers reside in patient plasma, cerebrospinal fluid, and other tissues, and can be subjected to α-synuclein seed amplification assays. Thus, clinicians should be able to capitalize on α-synuclein seed amplification assays to stratify patients into potential responders versus non-responders in future clinical trials of α-synuclein targeted therapies. Here, we briefly review the current understanding of α-synuclein in Lewy body disease and speculate on pathophysiological processes underlying the potential transmission of α-synucleinopathy across the neuraxis.

Racial and social-economic inequalities in systemic chemotherapy use among adult glioblastoma patients following surgery and radiotherapy.

Not all patients with glioblastoma multiforme (GBM) eligible for systemic chemotherapy after upfront surgery and radiotherapy finally receive it. The information on patients with GBM was retrieved from the surveillance, epidemiology, and end results database. Patients who underwent upfront surgery or biopsy and external beam radiotherapy between 2010 and 2019 were eligible for systemic chemotherapy. The available patient and tumor characteristics were assessed using multivariable logistic regression and chi-squared test. Out of the 16,682 patients eligible, 92.1% underwent systemic chemotherapy. The characteristics linked to the lowest systemic chemotherapy utilization included tumors of the brain stem/cerebellum (P = 0.01), former years of diagnosis (P = 0.001), ≥ 80 years of age (P < 0.001), Hispanic, Non-Hispanic Asian, Pacific Islander, or Black race (P < 0.001), non-partnered status (P < 0.001), and low median household income (P = 0.006). Primary tumor site, year of diagnosis, age, race, partnered status, and median household income correlated with the omission of systemic chemotherapy in GBM in adult patients.

Improving the lesion appearance on FLAIR images synthetized from quantitative MRI: a fast, hybrid approach.

OBJECTIVE: The image quality of synthetized FLAIR (fluid attenuated inversion recovery) images is generally inferior to its conventional counterpart, especially regarding the lesion contrast mismatch. This work aimed to improve the lesion appearance through a hybrid methodology. MATERIALS AND METHODS: We combined a full brain 5-min MR-STAT acquisition followed by FLAIR synthetization step with an ultra-under sampled conventional FLAIR sequence and performed the retrospective and prospective analysis of the proposed method on the patient datasets and a healthy volunteer. RESULTS: All performance metrics of the proposed hybrid FLAIR images on patient datasets were significantly higher than those of the physics-based FLAIR images (p < 0.005), and comparable to those of conventional FLAIR images. The small difference between prospective and retrospective analysis on a healthy volunteer demonstrated the validity of the retrospective analysis of the hybrid method as presented for the patient datasets. DISCUSSION: The proposed hybrid FLAIR achieved an improved lesion appearance in the clinical cases with neurological diseases compared to the physics-based FLAIR images, Future prospective work on patient data will address the validation of the method from a diagnostic perspective by radiological inspection of the new images over a larger patient cohort.

Insight into the mechanism of adsorption and release of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in sewage by modeling regional suspended particles for evaluation of the influence on monitoring of cannabis illicit abuse.

The adsorption of 11-nor-9-carboxy-∆9-tetrahydrocannabinol (THC-COOH) by the suspended particles in sewage makes it fail to accurately monitor cannabis abuse. In this work, the model sewage sample was prepared through equivalent mixing the sewage from 10 different sewage treatment plants in Guangdong province of China and used as a comprehensive representative for investigating the adsorption and release behavior of THC-COOH on the suspended particles under different temperature and pH. The solid-liquid distribution of THC-COOH in sewage depended strongly on the adsorption and release properties which were susceptible to the temperature and pH, specially adjusting pH to 11.0 could release more than 90 % of THC-COOH from the suspended particles. By means of the kinetics models, pseudo-second-order kinetic and Weber-Morris models revealed the mechanism of adsorption and release of THC-COOH in sewage that was a relatively reversible and controllable process with multiple interactions, and then it was further confirmed by the validation experiment in a variety of actual sewage samples. According to the suggested pH, the modification of the existing detection protocol prior to high performance liquid chromatography-tandem triple quadrupole mass spectrometry (HPLC-TQ-MS/MS), was successfully applied to determination of THC-COOH in the stimulated positive samples, and the recoveries and RSDs were respectively 95.48-99.79 % and 4.0-5.6 %. The finding could greatly help improving the accuracy of not only the detection of THC-COOH in sewage but also the estimation data of the consumption level of cannabis in the related regions.

Machine Learning for Additive Manufacturing of Functionally Graded Materials.

Additive Manufacturing (AM) is a transformative manufacturing technology enabling direct fabrication of complex parts layer-by-layer from 3D modeling data. Among AM applications, the fabrication of Functionally Graded Materials (FGMs) has significant importance due to the potential to enhance component performance across several industries. FGMs are manufactured with a gradient composition transition between dissimilar materials, enabling the design of new materials with location-dependent mechanical and physical properties. This study presents a comprehensive review of published literature pertaining to the implementation of Machine Learning (ML) techniques in AM, with an emphasis on ML-based methods for optimizing FGMs fabrication processes. Through an extensive survey of the literature, this review article explores the role of ML in addressing the inherent challenges in FGMs fabrication and encompasses parameter optimization, defect detection, and real-time monitoring. The article also provides a discussion of future research directions and challenges in employing ML-based methods in the AM fabrication of FGMs.

Vaccarin suppresses diabetic nephropathy through inhibiting the EGFR/ERK1/2 signaling pathway.

Diabetic nephropathy (DN) is recognized as one of the primary causes of chronic kidney disease and end-stage renal disease. Vaccarin (VAC) confers favorable effects on cardiovascular and metabolic diseases, including type 2 diabetes mellitus (T2DM). Nonetheless, the potential role and mechanism of VAC in the etiology of DN have yet to be completely elucidated. In this study, a classical mouse model of T2DM is experimentally induced via a high-fat diet (HFD)/streptozocin (STZ) regimen. Renal histological changes are assessed via H&E staining. Masson staining and immunohistochemistry (IHC) are employed to assess renal fibrosis. RT-PCR is utilized to quantify the mRNA levels of renal fibrosis, oxidative stress and inflammation markers. The levels of malondialdehyde (MDA) and reactive oxygen species (ROS), as well as the content of glutathione peroxidase (GSH-Px), are measured. The protein expressions of collagen I, TGF-ß1, α-SMA, E-cadherin, Nrf2, catalase, SOD3, SOD2, SOD1, p-ERK, p-EGFR (Y845), p-EGFR (Y1173), p-NFκB P65, t-ERK, t-EGFR and t-NFκB P65 are detected by western blot analysis. Our results reveal that VAC has a beneficial effect on DN mice by improving renal function and mitigating histological damage. This is achieved through its inhibition of renal fibrosis, inflammatory cytokine overproduction, and ROS generation. Moreover, VAC treatment effectively suppresses the process of epithelial-mesenchymal transition (EMT), a crucial characteristic of renal fibrosis, in high glucose (HG)-induced HK-2 cells. Network pharmacology analysis and molecular docking identify epidermal growth factor receptor (EGFR) as a potential target for VAC. Amino acid site mutations reveal that Lys-879, Ile-918, and Ala-920 of EGFR may mediate the direct binding of VAC to EGFR. In support of these findings, VAC reduces the phosphorylation levels of both EGFR and its downstream mediator, extracellular signal-regulated kinase 1/2 (ERK1/2), in diabetic kidneys and HG-treated HK-2 cells. Notably, blocking either EGFR or ERK1/2 yields renal benefits similar to those observed with VAC treatment. Therefore, this study reveals that VAC attenuates renal damage via inactivation of the EGFR/ERK1/2 signaling axis in T2DM patients.

Pickering emulsion of pepper essential oil stabilized by Octenyl succinic acid starch: Characterization, in vitro release and anticancer activity.

Under high humidity and high temperature conditions, the quality of pepper essential oil easily deteriorates, and the oxidation of oil restricts its application, especially for the insolubility in water. This study investigated pepper essential oil encapsulated in Pickering emulsion with octenyl succinic acid starch, which was effectively able to reduce 100 times of the release rate. The smooth surface and complete particles of the emulsion were observed and no new chemical bonds were formed. The minimum particle sizes were 2.05 µm and 1.89 µm, when the Pickering emulsion was set to different storage conditions at pH 5 and 0.1 M NaCl, respectively. During gastrointestinal digestion, the release of essential oils was effectively delayed in the Pickering emulsion and the digestibility of the emulsion was 16.93% in 120 min. Compared with untreated cells, Pickering emulsion can effectively inhibit the proliferation of MCF-7 (52.71%). All these results indicate that OSA starch stabilized pepper essential oil can effectively increase solubility, improve stability, and expand the application range. Therefore, it can provide a theoretical basis for applications of pepper essential oil, especially for the functional drug application.