A Comparative Study on the Composition and Structure of Human Milk Phospholipids and its Natural Resources: Based on a Similarity Evaluation Model.

Human milk phospholipids (HMPLs) play an indispensable role in the neurodevelopment and growth of infants. In this study, a total of 37 phospholipid fatty acid (PLFA) species and 139 phospholipid molecular species were detected from human milk and other natural phospholipid sources (including 5 animal-derived species and 2 plant species). Moreover, a similarity evaluation model for HMPLs was established, including phospholipid classes, PLFAs, and phospholipid molecular species, to evaluate their natural substitutes. The closest scores for HMPL substitute in these three dimensions was 0.89, 0.72, and 0.77, which belonged to mare milk, goat milk, and camel milk, respectively. The highest comprehensive similarity score was obtained by camel milk at 0.75, while the lowest score was observed in soybean phospholipid (0.22). Therefore, these results not only monitored the stereochemical structure of HMPLs and their substitutes, but also further provided new insights for the development of infant formulae.

Bimetallic PtAu-Decorated SnO2 Nanospheres Exhibiting Enhanced Gas Sensitivity for Ppb-Level Acetone Detection.

Acetone is a biomarker found in the expired air of patients suffering from diabetes. Therefore, early and accurate detection of its concentration in the breath of such patients is extremely important. We prepared Tin(IV) oxide (SnO2) nanospheres via hydrothermal treatment and then decorated them with bimetallic PtAu nanoparticles (NPs) employing the approach of in situ reduction. The topology, elemental composition, as well as crystal structure of the prepared materials were studied via field emission scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and X-ray diffraction. The findings revealed that bimetallic PtAu-decorated SnO2 nanospheres (PtAu/SnO2) were effectively synthesized as well as PtAu NPs evenly deposited onto the surface of the SnO2 nanospheres. Pure SnO2 nanospheres and PtAu/SnO2 sensors were prepared, and their acetone gas sensitivity was explored. The findings demonstrated that in comparison to pristine SnO2 nanosphere sensors, the sensors based on PtAu/SnO2 displayed superior sensitivity to acetone of 0.166-100 ppm at 300 °C, providing a low theoretical limit of detection equal to 158 ppm. Moreover, the PtAu/SnO2 sensors showed excellent gas response (Ra/Rg = 492.3 to 100 ppm), along with fast response and recovery (14 s/13 s to 10 ppm), good linearity of correlation, excellent repeatability, long-term stability, and satisfactory selectivity at 300 °C. This improved gas sensitivity was because of the electron sensitization of the Pt NPs, the chemical sensitization of the Au NPs, as well as the synergistic effects of bimetallic PtAu. The PtAu/SnO2 sensors have considerable potential for the early diagnosis and screening of diabetes.

Deep learning for risk stratification of thymoma pathological subtypes based on preoperative CT images.

OBJECTIVES: This study aims to develop an innovative, deep model for thymoma risk stratification using preoperative CT images. Current algorithms predominantly focus on radiomic features or 2D deep features and require manual tumor segmentation by radiologists, limiting their practical applicability. METHODS: The deep model was trained and tested on a dataset comprising CT images from 147 patients (82 female; mean age, 54 years ± 10) who underwent surgical resection and received subsequent pathological confirmation. The eligible participants were divided into a training cohort (117 patients) and a testing cohort (30 patients) based on the CT scan time. The model consists of two stages: 3D tumor segmentation and risk stratification. The radiomic model and deep model (2D) were constructed for comparative analysis. Model performance was evaluated through dice coefficient, area under the curve (AUC), and accuracy. RESULTS: In both the training and testing cohorts, the deep model demonstrated better performance in differentiating thymoma risk, boasting AUCs of 0.998 and 0.893 respectively. This was compared to the radiomic model (AUCs of 0.773 and 0.769) and deep model (2D) (AUCs of 0.981 and 0.760). Notably, the deep model was capable of simultaneously identifying lesions, segmenting the region of interest (ROI), and differentiating the risk of thymoma on arterial phase CT images. Its diagnostic prowess outperformed that of the baseline model. CONCLUSIONS: The deep model has the potential to serve as an innovative decision-making tool, assisting on clinical prognosis evaluation and the discernment of suitable treatments for different thymoma pathological subtypes. KEY POINTS: • This study incorporated both tumor segmentation and risk stratification. • The deep model, using clinical and 3D deep features, effectively predicted thymoma risk. • The deep model improved AUCs by 16.1pt and 17.5pt compared to radiomic model and deep model (2D) respectively.

Positive regulation of the Eucommia rubber biosynthesis-related gene EuFPS1 by EuWRKY30 in Eucommia ulmoides.

Eucommia rubber is a secondary metabolite from Eucommia ulmoides that has attracted much attention because of its unique properties and enormous potential for application. However, the transcriptional mechanism regulating its biosynthesis has not yet been determined. Farnesyl pyrophosphate synthase is a key enzyme in the Eucommia rubber biosynthesis. In this study, the promoter of EuFPS1 was used as bait, EuWRKY30 was screened from the cDNA library of EuFPS1 via a yeast one-hybrid system. EuWRKY30 belongs to the WRKY IIa subfamily and contains a WRKY domain and a C2H2 zinc finger motif, and the expressed protein is located in the nucleus. EuWRKY30 and EuFPS1 exhibited similar tissue expression patterns, and yeast one-hybrid and dual-luciferase experiments confirmed that EuWRKY30 directly binds to the W-box element in the EuFPS1 promoter and activates its expression. Moreover, the overexpression of EuWRKY30 significantly upregulated the expression level of EuFPS1, further increasing the density of the rubber particles and Eucommia rubber content. The results of this study indicated that EuWRKY30 positively regulates EuFPS1, which plays a critical role in the synthesis of Eucommia rubber, provided a basis for further analysis of the underlying transcriptional regulatory mechanisms.

Suppressing ACQ of molecular photosensitizers by distorting the conjugated-plane for enhanced tumor photodynamic therapy.

Non-AIE-type molecular photosensitizers (PSs) suffer from the aggregation-caused-quenching (ACQ) effect in an aqueous medium due to the strong hydrophobic and π-π interactions of their conjugated planes, which significantly hinders the enhancement of tumor photodynamic therapy (PDT). So far, some ionic PSs have been reported with good water-solubility, though the ACQ effect can still be induced in a biological environment rich in ions, leading to unsatisfactory in vivo delivery and fluorescence imaging performance. Hence, designing molecular PSs with outstanding anti-ACQ properties in water is highly desirable, but it remains a tough challenge for non-AIE-type fluorophores. Herein, we demonstrated a strategy for the design of porphyrin-type molecular PSs with remarkable solubility and anti-ACQ properties in an aqueous medium, which was assisted by quantum chemical simulations. It was found that cationic branched side chains can induce serious plane distortion in diphenyl porphyrin (DPP), which was not observed for tetraphenyl porphyrin (TPP) with the same side chains. Moreover, the hydrophilicity of the chain spacer is also crucial to the plane distortion for attaining the desired anti-ACQ properties. Compared to ACQ porphyrin, anti-ACQ porphyrin displayed type-I ROS generation in hypoxia and much higher tumor accumulation efficacy by blood circulation, leading to highly efficient in vivo PDT for hypoxic tumors. This study demonstrates the power of sidechain chemistry in tuning the configuration and aggregation behaviors of porphyrins in water, offering a new path to boost the performance of PSs to fulfill the increasing clinical demands on cancer theranostics.

Recent Advances of Graphene Quantum Dots in Chemiresistive Gas Sensors.

Graphene quantum dots (GQDs), as 0D graphene nanomaterials, have aroused increasing interest in chemiresistive gas sensors owing to their remarkable physicochemical properties and tunable electronic structures. Research on GQDs has been booming over the past decades, and a number of excellent review articles have been provided on various other sensing principles of GQDs, such as fluorescence-based ion-sensing, bio-sensing, bio-imaging, and electrochemical, photoelectrochemical, and electrochemiluminescence sensing, and therapeutic, energy and catalysis applications. However, so far, there is no single review article on the application of GQDs in the field of chemiresistive gas sensing. This is our primary inspiration for writing this review, with a focus on the chemiresistive gas sensors reported using GQD-based composites. In this review, the various synthesized strategies of GQDs and its composites, gas sensing enhancement mechanisms, and the resulting sensing characteristics are presented. Finally, the current challenges and future prospects of GQDs in the abovementioned application filed have been discussed for the more rational design of advanced GQDs-based gas-sensing materials and innovative gas sensors with novel functionalities.

Spatiotemporal miRNA and transcriptomic network dynamically regulate the developmental and senescence processes of poplar leaves.

Poplar is an important afforestation and urban greening species. Poplar leaf development occurs in stages, from young to mature and then from mature to senescent; these are accompanied by various phenotypic and physiological changes. However, the associated transcriptional regulatory network is relatively unexplored. We first used principal component analysis to classify poplar leaves at different leaf positions into two stages: developmental maturity (the stage of maximum photosynthetic capacity); and the stage when photosynthetic capacity started to decline and gradually changed to senescence. The two stages were then further subdivided into five intervals by gene expression clustering analysis: young leaves, the period of cell genesis and functional differentiation (L1); young leaves, the period of development and initial formation of photosynthetic capacity (L3-L7); the period of maximum photosynthetic capacity of functional leaves (L9-L13); the period of decreasing photosynthetic capacity of functional leaves (L15-L27); and the period of senescent leaves (L29). Using a weighted co-expression gene network analysis of regulatory genes, high-resolution spatiotemporal transcriptional regulatory networks were constructed to reveal the core regulators that regulate leaf development. Spatiotemporal transcriptome data of poplar leaves revealed dynamic changes in genes and miRNAs during leaf development and identified several core regulators of leaf development, such as GRF5 and MYB5. This in-depth analysis of transcriptional regulation during leaf development provides a theoretical basis for exploring the biological basis of the transcriptional regulation of leaf development and the molecular design of breeding for delaying leaf senescence.

Design and Development of a Hair-like Sensor with Bridge-Type Flexible Amplification Mechanisms.

Compared with lever-type amplification mechanisms, bridge-type flexible amplification mechanisms have advantages in terms of amplification ratio and structural compactness. Therefore, they can effectively replace the lever-type amplification mechanism in the existing hair-like sensors and realize the development of miniature hair-like sensors with high sensitivity. With that in mind, a highly sensitive hair-like sensor based on a bridge-type amplification mechanism with distributed flexibility is presented to measure the airflow rate. First, the structural composition and operating principle of the hair-like sensor are described. Then, detailed design and analysis of the hair-like sensor are carried out, focusing on the design of the hair post structure, amplification mechanism, and resonator. Furthermore, the designed hair-like sensor is processed and prepared, and some experimental studies are conducted. The experimental results demonstrate that the developed hair-like sensor can measure the airflow rate with high sensitivity up to 8.56 Hz/(m/s)2. This provides a new concept for the structural design of hair-like sensors and expands the application of bridge-type flexible amplification mechanisms in the field of micro/nano sensors.

Fabrication and Characterization of Novel Food-Grade Bigels Based on Interfacial and Bulk Stabilization.

Novel food-grade bigels were fabricated using zein nanoparticles for interfacial stabilization and non-surfactant gelators (beeswax and tapioca) for bulk stabilization. The present study demonstrated the importance of interfacial stability for biphasic gels and sheds light on the roles of the gelation mechanism and the oil/water ratio of a bigel on its microstructure, physical properties, and digestion behaviors. The results indicated that it is not an easy task to realize homogenization and subsequent gelation in beeswax-tapioca biphasic systems, as no amphiphilic components existed. However, applying the binding of zein nanoparticles at the oil-water interface allowed us to produce a homogeneous and stable bigel (oil fraction reach 40%), which exhibited enhanced structural and functional properties. Oleogel structures play a crucial role in determining the deformation response of bigel systems. As the oil content increased, the mechanical strength and elastic properties of bigels were enhanced. In the meantime, clear bigel-type transitions were observed. In addition, the fabricated bigels were shown to be beneficial for delayed digestion, and the lowest degree of lipolysis could be found in bigel with 50% oleogel.

Application of Zebrafish as a Model for Anti-Cancer Activity Evaluation and Toxicity Testing of Natural Products.

Developing natural product-based anti-cancer drugs/agents is a promising way to overcome the serious side effects and toxicity of traditional chemotherapeutics for cancer treatment. However, rapid assessment of the in vivo anti-cancer activities of natural products is a challenge. Alternatively, zebrafish are useful model organisms and perform well in addressing this challenging issue. Nowadays, a growing number of studies have utilized zebrafish models to evaluate the in vivo activities of natural compounds. Herein, we reviewed the application of zebrafish models for evaluating the anti-cancer activity and toxicity of natural products over the past years, summarized its process and benefits, and provided future outlooks for the development of natural product-based anti-cancer drugs.

GPR18 and GPR55-related Ligands Serving as Antagonists or Agonists: Current Situation, Challenges and Perspectives.

GPCR superfamily, the largest known family of membrane receptors, consists of six classes from A to F. GPR18 and GPR55, δ-branch of A class, had been reported to have no confirmed endogenous ligand and were named as "orphan receptors". Previous studies suggest that both GPR18 and GPR55 are possibly related to the migration and proliferation of cancer cells, macrophages and other inflammation-associated immune cells. Thus, they may be potential targets for inflammation, cancer and analgesia therapy. In this paper, we aimed to summarize the chemical structures and bioactivities of the agonists and antagonists of GPR18 and GPR55; moreover, we have briefly discussed the challenges and future perspectives in this field. This review will be beneficial for further design and synthesis of efficient agonists and antagonists towards GPR18 and GPR55- related disease treatment.

Synthesis and biological evaluation of novel demethylzeylasteral derivatives as potential anticancer agents.

Demethylzeylasteral (DEM), a class of terpenoids isolated from natural plants, frequently exhibits moderate or limited inhibitory effect on tumor growth across multiple cancer types. Thus, here we attempted to elevate the anti-tumor efficacy of DEM by altering active groups in its chemical structure. Initially, we synthesized a series of novel DEM derivatives 1-21 through performing a series of modifications of its phenolic hydroxyl groups at C-2/3, C-4 and C-29 positions. The anti-proliferative activities of these new compounds were subsequently assessed using three human cancer cell line models (A549, HCT116 and HeLa) and CCK-8 assay. Our data showed that compared to original DEM compound, derivative 7 exhibited remarkable inhibition effect on A549 (16.73 ± 1.07 µM), HCT116 (16.26 ± 1.94 µM) and HeLa (17.07 ± 1.09 µM), almost reaching to the same level of DOX. Moreover, the structure-activity relationships (SARs) of the synthesized DEM derivatives were discussed in detail. We found that treatment with derivative 7 only led to moderate cell cycle arrest at S-phase in a concentration-dependent manner. Meanwhile, derivative 7 treatment markedly induced apoptosis in tumor cells. Consistent with this observation, our subsequent docking analysis showed that derivative 7 is capable of activating caspase-3 through interaction with the His 121 and Gly 122 residues of the enzyme. Overall, we have developed a new series of DEM derivatives with elevated anti-tumor efficacy relative to its parent form. The results suggested that derivative 7 has great potential to be employed as an anticancer agent candidate for natural product-based cancer chemotherapy.

Isosteviol derivatives as protein tyrosine Phosphatase-1B inhibitors: Synthesis, biological evaluation and molecular docking.

Protein tyrosine phosphatase (PTP1B) antagonizes insulin signaling and acts as a potential therapeutic target for insulin resistance associated with obesity and type II diabetes. In this work, a series of isosteviol derivatives 1-28 was synthesized and the inhibitory activity on PTP1B was evaluated by double antibody sandwich ELISA (DAS-ELISA) in vitro. Most isosteviol derivatives showed moderate PTP1B inhibitory activities. Among them, derivatives 10, 13, 24, 27 showed remarkable bioactivities with IC50 values ranging from 0.24 to 0.40 µM. Particularly, derivative 24 exhibited the best inhibitory activity against PTP1B (IC50 = 0.24 µM) in vitro; moreover, it showed 7-fold selectivity to PTP1B over T-cell protein tyrosine phosphatase (TCPTP) and 14-fold selectivity to PTP1B over cell division cycle 25 homolog B (CDC25B). Molecular docking studies demonstrated the hydrogen bond interaction between 24 and LYS-116 residue in PTP1B might be essential for the inhibitory activity. The results suggested that derivative 24 has great potential to be employed as drug candidate for the treatment of obesity and type II diabetes.

Formula milk brands marketing on Chinese social media Weibo - a content analysis.

Background: Parents' feeding practices in the first 2 years of life have profound effects on children's survival, health and development throughout their lives. Decisions on how to feed infants and young children should be based on the best information and evidence, not influenced by commercial interests. China is the largest and fastest-growing market for formula milk products. Social media has emerged as a distinctive marketing avenue that can reach consumers directly. Weibo is one of the most popular Chinese social media platforms. This study examined four of the most popular milk formula brands' official Weibo accounts: Biotime, Mead Johnson, YiLi-Prokido, and Friso. Question: What messages posted and what marketing practices and tactics are used by formula milk brands on Weibo. Methods: We manually downloaded all posts in the four accounts between 1 January and 31 December 2018. Based on previous studies, we developed a marketing practices coding framework and selected ten mutually exclusive categories for coding and analysing the posts. Findings: Among 2667 original posts analysed, 65% were from three dominant categories: user engagement (939/2667, 35.2%), parenting advice (516/2667, 19.3%), and celebrity endorsement (327/2667, 12.3%). Other categories included making pseudo-health or nutrition claims and portraying breastfeeding as a painful or problematic experience. Conclusion: Widespread marketing practices and tactics were found in the four examined Weibo accounts of formula milk brands. Monitoring and regulation of formula milk marketing on social media are urgently needed. Social media platforms should also be held accountable for protecting a supportive breastfeeding environment.

Boosting Type-I and Type-II ROS Production of Water-Soluble Porphyrin for Efficient Hypoxic Tumor Therapy.

As the most successful clinically approved photosensitizers, porphyrins have been extensively employed in the photodynamic therapy (PDT) of cancers. However, their poor water solubility, aggregation-induced self-quenching on ROS generation, and a low tolerance for a hypoxic condition usually result in unsatisfied therapeutic outcomes. Therefore, great efforts have been dedicated to improving the PDT efficacy of porphyrin-type photosensitizers in treating hypoxic tumors, including combination with additional active components or therapies, which can significantly complicate the therapeutic process. Herein, we report a novel water-soluble porphyrin with O-linked cationic side chains, which exhibits good water solubility, high photostability, and significantly enhanced ROS generation efficacy in both type-I and type-II photodynamic pathways. We have also found that the end charges of side chains can dramatically affect the ROS generation of the porphyrin. The cationic porphyrin exhibited high in vitro PDT efficacy with low IC50 values both in normoxia and hypoxia. Hence, during in vivo PDT study, the cationic porphyrin displayed highly effective tumor ablation capability. This study demonstrates the power of side-chain chemistry in tuning the photodynamic property of porphyrin, which offers a new effective strategy to enhance the anticancer performance of photosensitizers for fulfilling the increasing demands for cancer therapy in clinics.

An Overview of Thrombin Inhibitors in the Perspective of Structureactivity Relationships.

Thrombosis is one of the most important pathogenic factors related to cardiovascular diseases. Presently, thrombin inhibitors have gradually gained prominence in clinical practice due to their unique potential, such as dabigatran. Nevertheless, the risk of bleeding is not completely eliminated, and the threats of gastrointestinal bleeding are even increased in some cases. Therefore, developing new oral thrombin inhibitors with low side effects is urgent. In this paper, we summarized recent advances in the newly synthesized and isolated thrombin inhibitors from 2000 to 2019 and their structure-activity relationships (SARs) along with structure-dependent pharmacokinetic parameters, guiding the next generation of oral thrombin inhibitors.

One-Pot Synthesis of Pt High Index Facets Catalysts for Electrocatalytic Oxidation of Ethanol.

Direct ethanol fuel cell (DEFC) has attracted wide attention due to its wide range of fuel sources, cleanliness, and high efficiency. However, the problems of low catalytic efficiency and poor catalyst stability still exist in DEFC catalysts, which restrict its rapid development. With chloroplatinic acid (H2PtCl6·6H2O) as the precursor, Polyvinylpyrrolidone (PVP) plays the role of surfactant, stabilizer, and reducing agent in the experiment. Glycine is the surface control agent and co-reducing agent. Pt high-index facets nanocatalyst was prepared with the one-pot hydrothermal method by adjusting the amount of PVP and glycine. X-Ray Diffraction (XRD), transmission electron microscope (TEM), and scanning electron microscope (SEM) were used to characterize the micro-structure of the nanocatalyst, and the influence of PVP and glycine on the synthesis of high-index facets catalyst was studied. The electrocatalytic performance of the catalyst was tested with an electrochemical workstation, and it was found that the performance of the prepared catalyst was better than that of the commercial catalyst. When the mass ratio of PVP and Pt was 50:1 and the molar ratio of glycine and Pt was 24:1, Pt nanocatalysts with {310}, {520} and {830} high exponential facets were prepared. The electrochemical test results showed that the peak current density of ethanol oxidation was 2.194 m2/g, and the steady-state current density was 0.241 mA/cm2, which was 5.7 times higher than that of commercial catalyst. The results of this paper show that due to the defects such as steps and kinks on the surface of the high-index facets, the active sites are increased, thus showing excellent electrocatalytic performance. This study provides a theoretical basis for the development and commercial application of high index facets nanocatalysts.

Therapeutic potential of demethylzeylasteral, a triterpenoid of the genus Tripterygium wilfordii.

Pentacyclic triterpenoids are important natural products widely presenting in nature with rich bioactivities. Tripterygium wilfordii Hook. f., a precious Chinese medicinal material, is used to cure rheumatoid arthritis, nephrotic syndrome, systemic lupus erythematosus. Triterpenoids are one of the important active components of Tripterygium wilfordii Hook. f. Demethylzeylasteral extracted from Tripterygium wilfordii Hook. f. had numerous pharmacological effects, including anticancer, anti-inflammatory, immune suppression, anti-fertility, antivirus, antimicrobial. In this paper, we summarized comprehensively pharmacological activities of demethylzeylasteral for potential application as a therapeutic agent.

Facile Hydrothermal Synthesis of SnO2 Nanoflowers for Low-Concentration Formaldehyde Detection.

In this work, SnO2 nanoflowers were prepared by a simple one-step hydrothermal process. The morphology and structure of SnO2 nanoflowers were characterized by SEM, TEM, Raman spectroscopy, and XRD, which demonstrated the good crystallinity of the SnO2 tetrahedron structure of the as-synthesized materials. In addition, the sensing properties of SnO2 nanoflowers were studied in detail. It was found that the SnO2 nanoflower-based gas sensor exhibits excellent gas response (9.2 to 120 ppm), fast response and recovery (2/15 s to 6 ppm), good linearity of correlation between response (S) vs. concentration (C) (lgS = 0.505 lgC - 0.147, R2 = 0.9863), superb repeatability, and selectivity at 300 °C. The outstanding performance can also be attributed to the high specific surface area ratio and size of SnO2 nanoflowers close to the thickness of the electron depletion layer that can provide abundant active sites, promote the rate of interaction, and make it easier for gas molecules to diffuse into the interior of the material. Therefore, SnO2 nanoflowers can be an ideal sensing material for real-time monitoring of low-concentration HCHO.

Daphnetin, a Coumarin in Genus Stellera Chamaejasme Linn: Chemistry, Bioactivity and Therapeutic Potential.

Coumarins is a huge family of phenolic compounds containing a common structure of 2H-1-benzopyran-2-one. Nowadays, more than 1,300 natural-based coumarins have been identified in a variety of plants, bacteria and fungi, many of them exhibited promising biomedical performance. Daphnetin (7,8-dihydroxycoumarin), a typical coumarin, showed a couple of bioactivities such as anti-cancer, antibacterial, anti-inflammatory and anti-arthritis. In the treatment of diseases, it has been verified that daphnetin has outstanding therapeutic effects on diabetes, arthritis, transplant rejection, cancer and even on central nervous system diseases. In China, it is being used for clinical applications, about 93 patent publications were associated with daphnetin. Due to its wide therapeutic potentials in clinical applications, numerous research on the action mechanisms and synthetic methods of daphnetin have been performed to support the future developments. Herein, we summarized the chemical synthetic methodologies, bioactivities, therapeutic potentials and structure-activity relationships of daphnetin and its derivatives. Moreover, the state-of-the-arts in current daphnetin study and future perspective in this field were discussed. Hopefully, this review would be beneficial for the discovery of new coumarin-based biomedicine in the near future.