Synthetic Routes and Clinical Application of Representative Small-Molecule EGFR Inhibitors for Cancer Therapy.

The epidermal growth factor receptor (EGFR) plays a pivotal role in cancer therapeutics, with small-molecule EGFR inhibitors emerging as significant agents in combating this disease. This review explores the synthesis and clinical utilization of EGFR inhibitors, starting with the indispensable role of EGFR in oncogenesis and emphasizing the intricate molecular aspects of the EGFR-signaling pathway. It subsequently provides information on the structural characteristics of representative small-molecule EGFR inhibitors in the clinic.

Synthesis and clinical application of new drugs approved by FDA in 2023.

In 2023, the U.S. Food and Drug Administration (FDA) granted approval to a total of 55 new drugs, comprising 29 new chemical entities (NCEs) and 25 new biological entities (NBEs).

Harmonizing the craft of crafting clinically endorsed small-molecule BCR-ABL tyrosine kinase inhibitors for the treatment of hematological malignancies.

The advancement and practical use of small-molecule tyrosine kinase inhibitors (TKIs) that specifically target the BCR-ABL fusion protein have introduced a revolutionary era of precision medicine for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). This review offers a comprehensive exploration of the synthesis, mechanisms of action, and clinical implementation of clinically validated TKIs in the context of BCR-ABL, emphasizing the remarkable strides made in achieving therapeutic precision. We delve into the intricate design and synthesis of these small molecules, highlighting the synthetic strategies and modifications that have led to increased selectivity, enhanced binding affinities, and reduced off-target effects.

The BRD4 Inhibitor dBET57 Exerts Anticancer Effects by Targeting Superenhancer-Related Genes in Neuroblastoma.

Neuroblastoma (NB) is the most common solid tumor of the neural crest cell origin in children and has a poor prognosis in high-risk patients. The oncogene MYCN was found to be amplified at extremely high levels in approximately 20% of neuroblastoma cases. In recent years, research on the targeted hydrolysis of BRD4 to indirectly inhibit the transcription of the MYCN created by proteolysis targeting chimaera (PROTAC) technology has become very popular.

BRD4 inhibitor GNE987 exerts anti-cancer effects by targeting super-enhancers in neuroblastoma.

Background: Neuroblastoma (NB) is a common extracranial malignancy with high mortality in children. Recently, super-enhancers (SEs) have been reported to play a critical role in the tumorigenesis and development of NB via regulating a wide range of oncogenes Thus, the synthesis and identification of chemical inhibitors specifically targeting SEs are of great urgency for the clinical therapy of NB. This study aimed to characterize the activity of the SEs inhibitor GNE987, which targets BRD4, in NB.

Barrier performance and biodegradability of antibacterial poly(butylene adipate-co-terephthalate) nanocomposites reinforced with a new MWCNT-ZnO nanomaterial.

A new nanomaterial or nano-filler in the form of multiwalled carbon nanotube-zinc oxide (MWCNT-ZnO) was synthesized for the purpose of modifying poly(butylene adipate-co-terephthalate) (PBAT) and its derivative (modified PBAT or MPBAT) through a melt-blending method (MPBAT was obtained by introducing maleic anhydride groups into PBAT). The effect of the new nano-filler on the properties of resultant nanocomposites was determined from the characterization of mechanical properties, morphology, crystallinity, thermal stability, barrier properties, hydrophilicity, conductivity, antibacterial property, and biodegradability. The results showed that MPBAT nanocomposites had stronger mechanical properties, better barrier properties, and higher electrical conductivity than PBAT nanocomposites.

MiR-1197-3p regulates testosterone secretion in goat Leydig cells via targeting PPARGC1A.

As a fundamental regulator of mitochondrial function, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) acts as a powerful coactivator of many transcriptional factors that relate to steroidogenesis, while the regulatory mechanism remains unclear. In the present study, testosterone secretion of goat Leydig cells (LCs) mediated by miR-1197-3p via PPARGC1A was investigated. We found PPARGC1A protein was diversely localized in testis, and the expression of PPARGC1A in testis of 9-month-old goat was significantly higher than that in 3-month-old goat.

Large-scale gene expression reveals different adaptations of Hyalopterus persikonus to winter and summer host plants.

Host alternation, an obligatory seasonal shifting between host plants of distant genetic relationship, has had significant consequences for the diversification and success of the superfamily of aphids. However, the underlying molecular mechanism remains unclear. In this study, the molecular mechanism of host alternation was explored through a large-scale gene expression analysis of the mealy aphid Hyalopterus persikonus on winter and summer host plants.

Identification, expression pattern, and feature analysis of cuticular protein genes in the pine moth Dendrolimus punctatus (Lepidoptera: Lasiocampidae).

Cuticular proteins (CPs) are vital components of the insects' cuticle that support movement and protect insect from adverse environmental conditions. The CPs exist in a large number and diversiform structures, thus, the accurate annotation is the first step to interpreting their roles in insect growth. The rapid development of sequencing technology has simplified the access to the information on protein sequences, especially for non-model species.

Transcriptome Characterization of Dendrolimus punctatus and Expression Profiles at Different Developmental Stages.

The pine moth Dendrolimus punctatus (Walker) is a common insect pest that confers serious damage to conifer forests in south of China. Extensive physiology and ecology studies on D. punctatus have been carried out, but the lack of genetic information has limited our understanding of the molecular mechanisms behind its development and resistance.

[Schistosomiasis control effect of measures of replacing cattle with machine for cultivation and forbidding depasturage of livestock on marshlands in marshland and lake regions].

Objective: To evaluate the schistosomiasis control effect of the measures of replacing cattle with machine for cultivation and forbidding depasturage of livestock on marshlands in marshland and lake regions.

Methods: The retrospective review and field survey were implemented in the Jiangling and Gongan counties of Hubei Province where were implemented with the measure of replacing cattle with machine for cultivation, and Yuanjiang and Huarong counties of Hunan Province where were implemented with the measure of forbidding the depasturage of livestock on marshlands. The schistosome infection status of human, cattle, and Oncomelania hupensis snails, and schistosome-infested field excreta were surveyed from 2007 to 2013.