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.

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.

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.

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.

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.

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.

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.

Progress in Isoindolone Alkaloid Derivatives from Marine Microorganism: Pharmacology, Preparation, and Mechanism.

Compound 1 (SMTP-7, also FGFC1), an isoindolone alkaloid from marine fungi Starchbotrys longispora FG216 and fungi Stachybotrys microspora IFO 30018, possessed diverse bioactivities such as thrombolysis, anti-inflammatory and anti-oxidative properties, and so on. It may be widely used for the treatment of various diseases, including cerebral infarction, stroke, ischemia/reperfusion damage, acute kidney injury, etc. Especially in cerebral infarction, compound 1 could reduce hemorrhagic transformation along with thrombolytic therapy, as the traditional therapies are accompanied with bleeding risks. In the latest studies, compound 1 selectively inhibited the growth of NSCLC cells with EGFR mutation, thus demonstrating its excellent anti-cancer activity. Herein, we summarized pharmacological activities, preparation of staplabin congeners-especially compound 1-and the mechanism of compound 1, with potential therapeutic applications.

Ultralow detection limit and ultrafast response/recovery of the H2 gas sensor based on Pd-doped rGO/ZnO-SnO2 from hydrothermal synthesis.

Hydrogen (H2) sensors are of great significance in hydrogen energy development and hydrogen safety monitoring. However, achieving fast and effective detection of low concentrations of hydrogen is a key problem to be solved in hydrogen sensing. In this work, we combined the excellent gas sensing properties of tin(IV) oxide (SnO2) and zinc oxide (ZnO) with the outstanding electrical properties of reduced graphene oxide (rGO) and prepared palladium (Pd)-doped rGO/ZnO-SnO2 nanocomposites by a hydrothermal method. The crystal structure, structural morphology, and elemental composition of the material were characterized by FE-SEM, TEM, XRD, XPS, Raman spectroscopy, and N2 adsorption-desorption. The results showed that the Pd-doped ZnO-SnO2 composites were successfully synthesized and uniformly coated on the surface of the rGO. The hydrogen gas sensing performance of the sensor prepared in this work was investigated, and the results showed that, compared with the pure Pd-doped ZnO-SnO2 sensor, the Pd-doped rGO/ZnO-SnO2 sensor modified with 3 wt% rGO had better hydrogen (H2)-sensing response of 9.4-100 ppm H2 at 380 °C. In addition, this sensor had extremely low time parameters (the response time and recovery time for 100 ppm H2 at 380 °C were 4 s and 8 s, respectively) and an extremely low detection limit (50 ppb). Moreover, the sensor exhibited outstanding repeatability and restoration. According to the analysis of the sensing mechanism of this nanocomposite, the enhanced sensing performance of the Pd-doped rGO/ZnO-SnO2 sensor is mainly due to the heterostructure of rGO, ZnO, and SnO2, the excellent electrical and physical properties of rGO and the synergy between rGO and Pd.

A Review on Structure-Activity Relationships of Glycyrrhetinic Acid Derivatives with Diverse Bioactivities.

Pentacyclic triterpenoids, consisting of six isoprene units, are a kind of natural active substance. At present, numerous pentacyclic triterpenes have been identified and classified into four subgroups of oleanane, ursane, lupane, and xylene on the basis of the carbon skeleton. Among them, oleanane is the most popular due to its rich backbone and diverse bioactivities. 18ß-Glycyrrhetinic acid (GA), an oleanane-type pentacyclic triterpene isolated from licorice roots, possesses diverse bioactivities, including antitumor, anti-inflammatory, antiviral, antimicrobial, enzyme inhibitor, hepatoprotective, and so on. It has received more attention in medicinal chemistry due to the advantages of easy access and rich bioactivity. Thus, numerous novel lead compounds have been synthesized using GA as a scaffold. Herein, we summarize the structure-activity relationship and synthetic methodologies of GA derivatives from 2010 to 2020, as well as the most active GA derivatives. Finally, we anticipate that this review can benefit future research on structural modifications of GA to enhance bioactivity and provide an example for developing pentacyclic triterpene-based novel drugs.

Novel Bioactive Polyketides Isolated from Marine Actinomycetes: An Update Review from 2013 to 2019.

Marine organism-associated actinobacteria represent a valuable resource for marine drugs due to their abundant secondary metabolites. The special environments in the ocean, for instance, high salt, high pressure, low temperature and oligotrophy, not only adapt to survival of actinomycetes but also enhance molecular diversity of actinomycete secondary metabolites production, thus making marine actinomycetes important sources of marine-based bioactive compounds, especially polyketides. Herein, we summarized the structures and pharmacological activities of polyketides from actinobacteria associated with marine organisms from 2013 to 2019; moreover, the main source species of actinomycetes were discussed as well. We expected that this review would be helpful for future in-depth research and development of marine-based bioactive polyketides.

Epigenetic Input Dictates the Threshold of Targeting of the Integrin-Dependent Pathway in Non-small Cell Lung Cancer.

We investigated the therapeutic potential of targeting integrin/FAK-dependent signaling, an adhesion receptor-mediated pathway that has been increasingly linked to non-small cell lung cancer (NSCLC) malignancy. Our analysis of the TCGA cohort showed that a subset of pro-tumorigenic integrins, including α1ß1, α2ß1, α3ß1, α5ß1, and α6ß4, were frequently amplified or upregulated at the genomic or mRNA level in KRAS or EGFR mutation/overexpression-enriched adenocarcinomas. These alterations appeared complementary, correlated with poor patient survival (p < 0.0072), and were collaborative with KRAS mutation-coupled αv integrins (p < 0.00159). Since integrin/FAK-dependent signaling is tightly coupled with normal human physiology, we sought to use a synthetic lethal-type targeting comprising of VS-6063, a chemical inhibitor of integrin-mediated FAK activity, and A549 cells, which carry a KRAS mutation and EGFR overexpression. Our screening analysis revealed that JQ1 and IBET-762, inhibitors of epigenetic reader BRD4, and LBH589, a pan inhibitor of histone deacetylases (HDACs), exhibited synergy with VS-6063 in mitigating tumor cell viability. This epigenetic link was corroborated by strong effects of additional inhibitors and RNAi-mediated knockdown of FAK and BRD4 or its downstream effector, c-Myc. Low doses of JQ1 (≤0.5 µM) markedly escalated efficacy of VS-6063 across a panel of 10 NSCLC cell lines. This catalyst-like effect is in line with the oncogenic landscape in the TCGA cohort since c-Myc falls downstream of the KRAS and EGFR oncogenes. Mechanistically, co-inhibiting the integrin-FAK and BRD4/c-Myc axes synergistically induced apoptotic cell death and DNA damage response, and impaired stemness-associated tumorsphere formation. These effects were accompanied by a marked inhibition of Akt- and p130Cas/Src-dependent signaling, but not Erk1/2 activity. Meanwhile, JQ1 alone or in combination with VS-6063 attenuated cell-cell adhesion and extracellular matrix (ECM)-dependent cell spreading, which is reminiscent of phenotype induced by malfunctional E-cadherin or integrins. Paradoxically, this phenotypic impact coincided with downregulation of epithelial-mesenchymal transition (EMT)-inducting transcription factor ZEB1 or Snail. Finally, we showed that the effect of the VS-6063/JQ1 combination was nearly equivalent to that of VS-6063 plus Carboplatin or Osimertinib. Overall, our study indicates that the integrin/FAK and BRD4/c-Myc axes cooperatively drive NSCLC virulence, and a co-targeting may provide a line of therapy capable of overcoming EGFR/KRAS-driven malignancy.

Recent Advances on Marine Alkaloids from Sponges.

Alkaloids from marine secondary metabolites have received extensive attention from pharmacists in recent years. Miscellaneous alkaloids derived from marine sponges possessed various pharmacological activities including cytotoxicity, antimicrobial, antioxidant, and so on. Herein, we summarized 149 marine alkaloids from sponges based on their structures and bioactivities reported from 2015 to 2020 and analyzed the production environment of marine sponges with rich alkaloids. Moreover, we discussed biosynthesis routes of pyrrole and guanidine alkaloids from marine sponges Agelas and Monanchora. This article will be beneficial for future research on drugs from marine natural products.

Red-Emissive Carbon Quantum Dots for Nuclear Drug Delivery in Cancer Stem Cells.

Large doses of anticancer drugs entering cancer cell nuclei are found to be effective at killing cancer cells and increasing chemotherapeutic effectiveness. Here we report red-emissive carbon quantum dots, which can enter into the nuclei of not only cancer cells but also cancer stem cells. After doxorubicin was loaded at the concentration of 30 µg/mL on the surfaces of carbon quantum dots, the average cell viability of HeLa cells was decreased to only 21%, while it was decreased to 50% for free doxorubicin. The doxorubicin-loaded carbon quantum dots also exhibited a good therapeutic effect by eliminating cancer stem cells. This work provides a potential strategy for developing carbon quantum-dot-based anticancer drug carriers for effective eradication of cancers.

Structure-activity relationship and synthetic methodologies of α-santonin derivatives with diverse bioactivities: A mini-review.

α-Santonin, a sesquiterpene lactone isolated from Artemisia Santonica, possesses diverse bioactivities including antioxidant, anti-inflammation, immunosuppressive, anti-roundworm, anti-malaria, etc. However, its bioactivities are not satisfactory and need to be further optimized. Thus, many α-santonin derivatives were synthesized on the basis of rings A, B and C for the discovery of new analogues with prominent bioactivities. Herein, we reviewed and discussed the related synthetic methodologies, diverse bioactivities and structure-activity relationships (SAR) of α-santonin derivatives.