Programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade has been approved as the standard-of-care for the treatment of non-small cell lung cancer (NSCLC). Yet, the population of ...patients who benefit from the treatment remains modest, some of whom would get relapsed and progressed eventually. Combination therapy has emerged as an effective way to broaden beneficiaries from PD-1/PD-L1 immunotherapy and overcome or delay the resistance. In this review, we discuss the PD-1/PD-L1 blockade in combination with conventional chemotherapy, targeted therapy or immunotherapy. Meanwhile, we illustrate their underlying mechanisms in regulating the process of the cancer-immunity cycle, providing the rationale for the PD-1/PD-L1 blockade-based combination therapy. The challenges of combination regimens are also addressed.
Isobavachalcone (IBC), a naturally occurring chalcone, is mainly isolated from the seeds of Psoralea corylifolia Linn. IBC demonstrates multiple pharmacological activities, including anti-cancer, ...anti-microbial, anti-inflammatory, antioxidative, neuroprotective, and among others. Several potential targets of IBC, such as AKT, dihydroorotate dehydrogenase (DHODH), have been identified. The pharmacokinetic profiles of IBC have been reported as well. In this review, the pharmacological activities, the underlying mechanisms, the potential targets, and the pharmacokinetic profiles of IBC were summarized. IBC might be a promising lead compound for drug discovery.
A summary of the pharmacological activities and the underlying mechanisms of IBC. Display omitted
Self‐organized stimuli‐responsive smart materials with adjustable attributes are highly desirable for a plethora of device applications. Simple cubic lattice is quite uncommon in soft condensed ...matter due to its lower packing factor. Achieving a stable simple cubic soft lattice and endowing such a lattice with dynamic reconstruction capability solely by a facile light irradiation are of paramount significance for both fundamental studies and engineering explorations. Herein, an elegant stable self‐organized simple cubic soft lattice, i.e., blue phase II, in a chiral liquid crystal (LC) system is disclosed, which is stable down to room temperature and exhibits both reversible lattice deformation and transformation to a helical superstructure, i.e., cholesteric LC, by light stimulation. Such an amazing trait is attained by doping a judiciously designed achiral photoresponsive molecular switch functionalized polyhedral oligomeric silsesquioxane nanocage into a chiral LC host. An unprecedented reversible collapse and reconstruction of such a high symmetric simple cubic blue phase II driven by light has been achieved. Furthermore, a well‐defined conglomerate micropattern composed of simple cubic soft lattice and helical superstructure, which is challenging to fabricate in organic and inorganic crystalline materials, is produced using photomasking technology. Moreover, the promising photonic application based on such a micropattern is demonstrated.
A reversible and dynamic transformation between a stable simple cubic lattice and a helical superstructure is achieved via light irradiation in a photoresponsive blue phase liquid crystal enabled by a molecular‐switch‐functionalized nanocage. Leveraging this capability, unprecedented light‐driven recording, erasing, and rewriting of well‐defined biphasic micropatterns are demonstrated and photonic applications of such micropatterns are explored.
In this study, we report the emergence of two-dimensional (2D) branching fractal structures (BFS) in the nanoconfinement between the active and the support layer of a thin-film-composite polyamide ...(TFC-PA) nanofiltration membrane. These BFS are crystal dendrites of NaCl formed when salts are either added to the piperazine solution during the interfacial polymerization process or introduced to the nascently formed TFC-PA membrane before drying. The NaCl dosing concentration and the curing temperature have an impact on the size of the BFS but not on the fractal dimension (∼1.76). The BFS can be removed from the TFC-PA membranes by simply dissolving the crystal dendrites in deionized water, and the resulting TFC-PA membranes have substantially higher water fluxes (three- to fourfold) without compromised solute rejection. The flux enhancement is believed to be attributable to the distributed reduction in physical binding between the PA active layer and the support layer, caused by the exertion of crystallization pressure when the BFS formed. This reduced physical binding leads to an increase in the effective area for water transport, which, in turn, results in higher water flux. The BFS-templating method, which includes the interesting characteristics of 2D crystal dendrites, represents a facile, low-cost, and highly practical method of enhancing the performance of the TFC-PA nanofiltration membrane without having to alter the existing infrastructure of membrane fabrication.
Flowering plants (angiosperms) are dominant components of global terrestrial ecosystems, but phylogenetic relationships at the familial level and above remain only partially resolved, greatly ...impeding our full understanding of their evolution and early diversification. The plastome, typically mapped as a circular genome, has been the most important molecular data source for plant phylogeny reconstruction for decades.
Here, we assembled by far the largest plastid dataset of angiosperms, composed of 80 genes from 4792 plastomes of 4660 species in 2024 genera representing all currently recognized families. Our phylogenetic tree (PPA II) is essentially congruent with those of previous plastid phylogenomic analyses but generally provides greater clade support. In the PPA II tree, 75% of nodes at or above the ordinal level and 78% at or above the familial level were resolved with high bootstrap support (BP ≥ 90). We obtained strong support for many interordinal and interfamilial relationships that were poorly resolved previously within the core eudicots, such as Dilleniales, Saxifragales, and Vitales being resolved as successive sisters to the remaining rosids, and Santalales, Berberidopsidales, and Caryophyllales as successive sisters to the asterids. However, the placement of magnoliids, although resolved as sister to all other Mesangiospermae, is not well supported and disagrees with topologies inferred from nuclear data. Relationships among the five major clades of Mesangiospermae remain intractable despite increased sampling, probably due to an ancient rapid radiation.
We provide the most comprehensive dataset of plastomes to date and a well-resolved phylogenetic tree, which together provide a strong foundation for future evolutionary studies of flowering plants.
Epithelial‐mesenchymal transition (EMT) plays important roles in the metastasis of solid tumors. In this study, the effect of toosendanin (TSN), a natural insecticide extracted from Melia toosendan ...Sieb et Zucc, on transforming growth factor‐β1 (TGF‐β1)‐induced EMT was investigated. EMT was induced by TGF‐β1 in A549 and H1975 lung cancer cells. The morphological alterations were observed with a microscopy. The protein expression and localization of EMT biomarkers were determined by Western blotting and immunofluorescence. The migration, invasion, and adhesion were determined by wound‐healing, transwell, and adhesion assays. TGF‐β1 treatment induced spindle‐shaped alterations of cells, upregulation of N‐cadherin, Vimentin, p‐ERK1/2, and downregulation of E‐cadherin. The abilities of migration, invasion, and adhesion were also enhanced. These effects were significantly reversed by TSN at very low concentration (<10 nM). Furthermore, silence Snail significantly reversed TGF‐β1‐induced EMT biomarkers. In addition, TGF‐β1‐induced phosphorylation of ERK1/2 without affecting p38 mitogen‐activated protein kinases and Jun N‐terminal kinase. PD98059 and U0126, inhibitors of ERK1/2, showed similar inhibitory effect to that of TSN. In summary, TSN significantly inhibited TGF‐β1‐induced EMT and migration, invasion, and adhesion through ERK/Snail pathway in lung cancer cells. This study provides novel anticancer effects and molecular mechanisms for TSN.
Triptolide (TPL), a key biologically active component of the Chinese medicinal herb Tripterygium wilfordii Hook. f., has potent anti-inflammation and anti-cancer activities. Its anti-proliferative ...and pro-apoptotic effects have been reported to be related to the inhibition of Nuclear Factor κB (NF-κB) and Nuclear Factor of Activated T-cells (NFAT) mediated transcription and suppression of HSP70 expression. The direct targets and precise mechanisms that are responsible for the gene expression inhibition, however, remain unknown. Here, we report that TPL inhibits global gene transcription by inducing proteasome-dependent degradation of the largest subunit of RNA polymerase II (Rpb1) in cancer cells. In the presence of proteosome inhibitor MG132, TPL treatment causes hyperphosphorylation of Rpb1 by activation of upstream protein kinases such as Positive Transcription Elongation Factor b (P-TEFb) in a time and dose dependent manner. Also, we observe that short time incubation of TPL with cancer cells induces DNA damage. In conclusion, we propose a new mechanism of how TPL works in killing cancer. TPL inhibits global transcription in cancer cells by induction of phosphorylation and subsequent proteasome-dependent degradation of Rpb1 resulting in global gene transcription, which may explain the high potency of TPL in killing cancer.
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Salvia miltiorrhiza Bunge (Danshen), a famous traditional Chinese herb, has been used clinically for the treatment of various diseases for centuries. Document data showed that ...tanshinones, a class of lipophilic abietane diterpenes rich in this herb, possess multiple biological effects in vitro and in vivo models. Among which, 15,16-dihydrotanshinone I (DHT) has received much attention in recent years. In this systematical review, we carefully selected, analyzed, and summarized high-quality publications related to pharmacological effects and the underlying mechanisms of DHT. DHT has anti-cancer, cardiovascular protective, anti-inflammation, anti-Alzheimer's disease, and other effects. Furthermore, several molecules such as hypoxia-inducible factor (HIF-1α), human antigen R (HuR), acetylcholinesterase (AchE), etc. have been identified as the potential targets for DHT. The diverse pharmacological activities of DHT provide scientific evidence for the local and traditional uses of Salvia miltiorrhiza Bunge. We concluded that DHT might serve as a lead compound for drug discovery in related diseases while further in-depth investigations are still needed.
Rhizoma Alismatis (RA), the dried rhizome of Alisma orientale (Sam.) Juzep, is a common traditional herbal medicine named Ze Xie in Chinese. RA is an important herbal component of a number of ...well‐known Chinese medicinal preparations. It has been used to treat various ailments, such as dysuria, edema, nephropathy, hyperlipidemia, and diabetes. A wide range of chemical compounds, mainly triterpenoids, sesquiterpenoids, and diterpenoids, have been isolated from RA; among which the protostane‐type triterpenoids, termed alisols, have attracted the most attention owing to their unique chemical structures and various biological activities. The extract and active compounds of RA possess a wide spectrum of pharmacological effects (e.g., diuretic, antimetabolic disorder, hepatoprotective, immunomodulatory, antiosteoporotic, anti‐inflammatory, antitumor, antibacterial, and antiviral activities). Previous toxicological evaluations indicated that the RA extracts are relatively safe and have no serious side effects within certain dose ranges. This paper reviews the up‐to‐date information on the ethnomedicinal application, phytochemistry, pharmacology, and toxicology of RA. This information will be useful for a better understanding of the therapeutic potential of RA.
Saponins are glycosides with triterpenoid or spirostane aglycones that demonstrate various pharmacological effects against mammalian diseases. To promote the research and development of anticancer ...agents from saponins, this review focuses on the anticancer properties of several typical naturally derived triterpenoid saponins (ginsenosides and saikosaponins) and steroid saponins (dioscin, polyphyllin, and timosaponin) isolated from Chinese medicines. These saponins exhibit in vitro and in vivo anticancer effects, such as anti-proliferation, anti-metastasis, anti-angiogenesis, anti-multidrug resistance, and autophagy regulation actions. In addition, related signaling pathways and target proteins involved in the anticancer effects of saponins are also summarized in this work.
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