The fast advances of theranostic nanomedicine enable the rational design and construction of diverse functional nanoplatforms for versatile biomedical applications, among which gas-generating nanoplatforms (GGNs) have emerged very recently as unique theranostic nanoplatforms for broad gas therapies. Here, the recent developments of the rational design and chemical construction of versatile GGNs for efficient gas therapies by either exogenous physical triggers or endogenous disease-environment responsiveness are reviewed. These gases involve some therapeutic gases that can directly change disease status, such as oxygen (O2 ), nitric oxide (NO), carbon monoxide (CO), hydrogen (H2 ), hydrogen sulfide (H2 S) and sulfur dioxide (SO2 ), and other gases such as carbon dioxide (CO2 ), dl-menthol (DLM), and gaseous perfluorocarbon (PFC) for supplementary assistance of the theranostic process. Abundant nanocarriers have been adopted for gas delivery into lesions, including poly(d,l-lactic-co-glycolic acid), micelles, silica/mesoporous silica, organosilica, MnO2 , graphene, Bi2 Se3 , upconversion nanoparticles, CaCO3 , etc. Especially, these GGNs have been successfully developed for versatile biomedical applications, including diagnostic imaging and therapeutic use. The biosafety issue, challenges faced, and future developments on the rational construction of GGNs are also discussed for further promotion of their clinical translation to benefit patients.

Gas-Generating Nanoplatforms: Material Chemistry, Multifunctionality, and Gas Therapy.

Slope stability prediction for circular mode failure using gradient boosting machine approach based on an updated database of case histories

As a traditional medical intervention in Asia and a complementary and alternative medicine in western countries, traditional Chinese medicine (TCM) has attracted global attention in the life science field. TCM provides extensive natural resources for medicinal compounds, and these resources are generally regarded as effective and safe for use in drug discovery. However, owing to the complexity of compounds and their related multiple targets of TCM, it remains difficult to dissect the mechanisms of action of herbal medicines at a holistic level. To solve the issue, in the review, we proposed a novel approach of systems pharmacology to identify the bioactive compounds, predict their related targets, and illustrate the molecular mechanisms of action of TCM. With a predominant focus on the mechanisms of actions of TCM, we also highlighted the application of the systems pharmacology approach for the prediction of drug combination and dynamic analysis, the synergistic effects of TCMs, formula dissection, and theory analysis. In summary, the systems pharmacology method contributes to understand the complex interactions among biological systems, drugs, and complex diseases from a network perspective. Consequently, systems pharmacology provides a novel approach to promote drug discovery in a precise manner and a systems level, thus facilitating the modernization of TCM.

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Systems Pharmacology for Investigation of the Mechanisms of Action of Traditional Chinese Medicine in Drug Discovery.

Drug discovery aims at finding new compounds with specific chemical properties for the treatment of diseases. In the last years, the approach used in this search presents an important component in computer science with the skyrocketing of machine learning techniques due to its democratization. With the objectives set by the Precision Medicine initiative and the new challenges generated, it is necessary to establish robust, standard and reproducible computational methodologies to achieve the objectives set. Currently, predictive models based on Machine Learning have gained great importance in the step prior to preclinical studies. This stage manages to drastically reduce costs and research times in the discovery of new drugs. This review article focuses on how these new methodologies are being used in recent years of research. Analyzing the state of the art in this field will give us an idea of where cheminformatics will be developed in the short term, the limitations it presents and the positive results it has achieved. This review will focus mainly on the methods used to model the molecular data, as well as the biological problems addressed and the Machine Learning algorithms used for drug discovery in recent years.

A review on machine learning approaches and trends in drug discovery.

Earthquakes have always attracted civil and geotechnical engineers’ attention, especially when it comes to the liquefaction potential of soil. This paper investigates the feasibility of cla...

Feasibility of Stochastic Gradient Boosting Approach for Evaluating Seismic Liquefaction Potential Based on SPT and CPT Case Histories

Design, synthesis, nitric oxide release and antibacterial evaluation of novel nitrated ocotillol-type derivatives.

Estimation of elimination half-lives of organic chemicals in humans using gradient boosting machine.

A series of novel ocotillol-type furoxan derivatives was synthesized by coupling various furoxans to 3-OH of 6-deoxy ocotillol, and their in vitro nitric oxide (NO) releasing capability was studied. The discharge of NO was examined after 30 min at two different concentrations, the results showed that all of the compounds tested could release NO in a dose-dependent manner. All of the synthesized compounds released similar amounts of NO at 100 μM, whereas at 500 μM these compounds showed more difference, in which compound II1, II3, II4, III2 displayed higher potency in releasing NO at this concentration. Analysis of the in vitro data showed that the derivatives bearing the same furoxan group on different ocotillol cores possessed various NO releasing capacity, suggesting that the structure of carrier of NO releasing groups may affect the NO release. Indeed, except compound II2, 24(S)-6-deoxy ocotillol derivatives from compound 6 with different furoxan substitutions at 3-OH and III2 displayed enhanced NO releasing capacity, compared to other compounds derived from compounds 5 and 9. The results illustrated that the functional group and the stereochemistry on the ocotillol structure may affect the NO release of furoxans.

Design, synthesis and in vitro NO-releasing activities of ocotillol-type furoxans.

Design and synthesis of 28-hydroxy protopanaxadiol as a novel probe template.

Background Colorectal cancer (CRC) is one of the most prevalent malignances worldwide. However, CRC with situs inversus totalis (SCRC) is extremely rare, and molecular characterization of this disease has never been investigated. Methods Tumor tissue samples from 8 patients with SCRC and 33 CRC patients without situs inversus totalis (NSCRC) were subjected to multigene next-generation sequencing. Results The most frequently mutated genes in SCRC were APC, TP53, CHEK2, MDC1, GNAQ, KRAS, and SMAD4. A high frequency of SCRC tumors had mutations in DNA damage repair genes. Single amino acid substitutions in the DNA damage repair genes caused by continuous double base substitution was identified in the majority of this population. Furthermore, mutational profiles showed notable differences between the SCRC and NSCRC groups. In particular, CHEK2, MDC1, GNAQ, SMAD4, BRCA1, HLA-B, LATS2, and NLRC5 mutations were more frequently observed in SCRC patients. The mutation loci distributions of KRAS in the SCRC cohort differed from that of the NSCRC cohort. Additionally, differences in the targeted genomic profiles and base substitution patterns were observed between the two groups. Conclusions These findings comprehensively revealed a molecular characterization of SCRC, which will contribute to the development of personalized therapy and improved clinical management of SCRC patients.

Xiaochen Zhang

Papers

Design, synthesis, nitric oxide release and antibacterial evaluation of novel nitrated ocotillol-type derivatives.

Estimation of elimination half-lives of organic chemicals in humans using gradient boosting machine.

Design, synthesis and in vitro NO-releasing activities of ocotillol-type furoxans.

Design and synthesis of 28-hydroxy protopanaxadiol as a novel probe template.

Comprehensive Molecular Profiling of Colorectal Cancer With Situs Inversus Totalis by Next-Generation Sequencing