Discovery of A-910, a Highly Potent and Orally Bioavailable Dual MerTK/Axl-Selective Tyrosine Kinase Inhibitor.

TAM receptor tyrosine kinases have emerged as promising therapeutic targets for cancer treatment due to their roles in both tumor intrinsic survival mechanisms and suppression of antitumor immunity within the tumor microenvironment. Inhibiting MerTK and Axl selectively is believed to hinder cancer cell survival, reverse the protumor myeloid phenotype, and suppress efferocytosis, thereby eliciting an antitumor immune response. In this study, we present the discovery of , a highly potent and selective dual MerTK/Axl inhibitor, achieved through a structure-based medicinal chemistry campaign.

An aquaporin and an aquaglyceroporin have roles in low temperature adaptation of mosquitoes (Anopheles sinensis).

Mosquitoes (Anopheles sinensis), widely geographically distributed in Asia including China, are the primary vector of the malaria parasite Plasmodium vivax and other parasitic diseases such as Malayan filariasis. An. sinensis can survive through low winter temperatures.

Mineralization Reduces the Toxicity and Improves Stability and Protective Immune Response Induced by .

Vaccination is an ideal strategy for the control and prevention of toxoplasmosis. However, the thermostability and effectiveness of vaccines limit their application. Here, calcium mineralization was used to fabricate tachyzoites as immunogenic core-shell particles with improved immune response and thermostability.

Brown adipocyte mineralocorticoid receptor deficiency impairs metabolic regulation in diet-induced obese mice.

Activation of brown adipose tissue (BAT) contributes to energy dissipation and metabolic health. Although mineralocorticoid receptor (MR) antagonists have been demonstrated to improve metabolism under obesity, the underlying mechanisms remain incompletely understood. We aimed to evaluate the role of BAT MR in metabolic regulation.

Effects of plant residues on C:N:P of soil, microbial biomass, and extracellular enzyme in an alpine mea-dow on the Qinghai-Tibetan Plateau, China.

Plant residues can affect C:N:P of soil, microbial biomass, and extracellular enzyme, but the effects are still unclear. We conducted a field experiment in an alpine meadow on the eastern part of the Qinghai-Tibetan Plateau to explore the effects of removing aboveground plant or roots and adding plant residues on the C:N:P of soil, microbial biomass, and extracellular enzyme. The results showed that removing aboveground plant biomass significantly decreased soil C:N (the change was -23.

[Microbiota structure and diversity in at different developmental stages].

Objective: To investigate the diversity and composition of microflora in laboratory-reared at different developmental stages and larval habitat waters.

Methods: The larval habitat waters and different developmental stages of laboratory-reared were collected, and the V3 and V4 regions of the bacterial gene were sequenced using Illumina Miseq next-generation sequencing. The abundance and diversity of the microflora were examined using alpha diversity index in at different developmental stages, and the difference in the microflora compositions was compared in at different developmental stages using principal component analysis (PCA).

A Novel Insight into Paraptosis-Related Classification and Signature in Lower-Grade Gliomas.

Lower-grade gliomas (LGG) are the most common intracranial malignancies that readily evolve to high-grade gliomas and increase drug resistance. Paraptosis is defined as a nonapoptotic form of programmed cell death, which is gradually focused on patients with gliomas to develop treatment options. However, the specific role of paraptosis in LGG and its correlation is still vague.

A Pooled Analysis of the PCR for the Detection of Candida Auris.

Background: Candida auris is an opportunistic pathogen with multiple drug resistance. Therefore, researchers conducted a meta-analysis to review PCR's ability to diagnose Candida auris to promote the development of accurate Candida auris diagnosis.

Methods: Researchers systematically retrieved relevant articles from PubMed, Cochrane Library, Embase, and Web of Science.

[Time to initial diagnosis of imported malaria and its influencing factors in Jiangsu Province].

Objective: To investigate the health-seeking behaviors of imported malaria cases after returning to China, and to investigate the factors affecting the time to initial diagnosis, so as to provide the scientific evidence for early identification of imported malaria cases and prevention of severe cases development and secondary transmission.

Methods: The individual demographic features, and the disease onset and the time to initial diagnosis of imported malaria cases in Jiangsu Province in 2019 were captured from the National Notifiable Disease Report System and the Information Management System for Parasitic Disease Control in China. The characteristics of health-seeking behaviors and epidemiological features of imported malaria cases were descriptively analyzed, and the factors affecting the time to initial diagnosis of imported malaria cases after returning to China were identified using multivariate logistic regression analysis.

[Harder maintained than achieved: Challenges of maintaining malaria-free in China].

On June 2021, China was certified malaria-free by WHO. However, the global number and death of malaria cases have recently increased, and the malaria vectors will continue to inhabit in China, resulting in a high difficulty in consolidation of malaria elimination achievements. Hereby, we analyze the current challenges and propose the future priority of the national malaria control program in China, in order to provide insights into prevention of re-establishment of imported malaria in the country.

The biofunctionalization of titanium nanotube with chitosan/genipin heparin hydrogel and the controlled release of IL-4 for anti-coagulation and anti-thrombus through accelerating endothelialization.

The valve replacement is the main treatment of heart valve disease. However, thrombus formation following valve replacement has always been a major clinical drawback. Accelerating the endothelialization of cardiac valve prosthesis is the main approach to reduce thrombus.

Identification of differentially expressed genes and signaling pathways with Candida infection by bioinformatics analysis.

Background: Opportunistic Candida species causes severe infections when the human immune system is weakened, leading to high mortality.

Methods: In our study, bioinformatics analysis was used to study the high-throughput sequencing data of samples infected with four kinds of Candida species. And the hub genes were obtained by statistical analysis.

The complete mitochondrial genome of major malaria vector (Diptera: Culicidae) in China.

(Xu and Feng 1975) is the major vector of malaria in Eastern and Southern China. The species is considered a synonym of (Baisas & Hu, 1936), although they differ in several key biological characteristics. Here, we report the complete mitochondrial genome of for the first time.

[Epidemiological characteristics of imported malaria in Jiangsu Province from 2012 to 2020].

Objective: To analyze the epidemiological characteristics of imported cases with infections in Jiangsu Province from 2012 to 2020, so as to provide insights into the development of the imported malaria control strategy in the province.

Methods: All data pertaining to cases with definitive diagnosis of malaria in Jiangsu Province from 2012 to 2020 were captured from the National Notifiable Disease Report System and the Information Management System for Parasitic Disease Control in China, including the date of going abroad and returning to China, time of malaria infections overseas, date of malaria onset, initial diagnosis and definitive diagnosis. All data pertaining to epidemic status were descriptively analyzed.

Effect of BCG Vaccination against SARS-CoV-2 Infection.

Based on previous studies, we found that Bacillus Calmette-Guérin (BCG) vaccination may play a role in preventing SARS-CoV-2 infection. Therefore, we conducted a meta-analysis to investigate this protective effect. We searched the Embase, PubMed, Web of Science, Cochrane Library, BioRxiv, and MedRxiv databases for studies that evaluated the relationship between BCG vaccination and SARS-CoV-2 infection or COVID-19 disease.

[Surveillance of mosquitoes in Jiangsu Province from 2018 to 2019].

Objective: To investigate the distribution and density of mosquito populations and the resistance of to insecticides in Jiangsu Province in 2018 and 2019.

Methods: During the period from June to October in 2018 and 2019, six counties (districts, cities) were sampled in southern, northern and central Jiangsu Province as surveillance sites. The density of mosquitoes was measured overnight using the light trapping technique.

Organocatalytic Direct Asymmetric Indolization from Anilines by Enantioselective [3 + 2] Annulation.

We report the efficient syntheses of chiral tetrahydroindole pyrazolinones by the asymmetric [3 + 2] cascade cyclizations (indolizations) of simple aniline derivatives with pyrazolinone ketimines as 2C synthons. The chiral phosphoric-acid-catalyzed system uses a concerted π-π interaction/dual H-bond control strategy to catalytically direct the asymmetric aniline, which undergoes a highly chemo-, regio-, and enantioselective [3 + 2] cascade annulation, furnishing a series of optically active tetra-hydroindole pyrazolinones with two contiguous chiral aza-quaternary carbon centers in excellent yields with excellent enantioselectivities. This method features a relatively broad substrate scope for amines and 2-naphthylamines and highlights the emerging value of direct chiral indolizations from simple amine sources in organic synthesis.

[Epidemic situation of malaria in Jiangsu Province in 2019].

Objective: To analyze the epidemic situation of malaria in Jiangsu Province in 2019, so as to provide the scientific basis for the development of the strategy for the prevention of re-introduction of imported malaria.

Methods: The malaria case report information, epidemiological case investigation information, epidemic foci investigation and management report in Jiangsu Province in 2019 were collected, and all epidemiological data were descriptively analyzed.

Results: A total of 244 malaria cases were reported in Jiangsu Province in 2019, and all cases were laboratory-confirmed overseas imported cases, including 4 cases with vivax malaria, 206 cases with falciparum malaria, 12 cases with malariae malaria and 22 cases with ovale malaria.

[Study on emergency metabolic changes of larvae following exposure to deltamethrin].

Objective: To analyze the changes of small molecular metabolites in the larvae of a deltamethrin-sensitive strain of following exposure to deltamethrin, so as to provide the scientific basis for investigating the metabolic pathway and screening metabolic markers of deltamethrin in .

Methods: The 50% and 75% lethal concentrations (LC and LC) of deltamethrin against the larvae of a deltamethrin-sensitive strain of were calculated in laboratory. The type and content of larvae metabolites were detected using high performance liquid chromatography and mass spectrometry (LC-MS/MS) following exposure to deltamethrin at LC and LC for 30 min and 24 h, and the changes of metabolites were analyzed.

Impact of genetic variation in CYP2C19, CYP2D6, and CYP3A4 on oxycodone and its metabolites in a large database of clinical urine drug tests.

Urine drug testing (UDT) is a tool for monitoring drug use, including oxycodone. While variation in cytochrome P450 (CYP) genes is known to alter oxycodone metabolism, its impact on UDT results of oxycodone and its metabolites has not been well-studied. Here, multivariate analysis was performed on retrospective UDT results of 90,379 specimens collected from 14,684 genotyped patients prescribed oxycodone.

Genetic Diversity Analysis of Surface-Related Antigen (SRA) in Imported From Africa to China.

surface-related antigen (SRA) is located on the surfaces of gametocyte and merozoite and has the structural and functional characteristics of potential targets for multistage vaccine development. However, little information is available regarding the genetic polymorphism of . To determine the extent of genetic variation about by characterizing the sequence, 74 samples were collected from migrant workers who returned to China from 12 countries of Africa between 2015 and 2019.

Genome-wide CRISPR/Cas9 screening identifies CARHSP1 responsible for radiation resistance in glioblastoma.

Glioblastomas (GBM) is the most common primary malignant brain tumor, and radiotherapy plays a critical role in its therapeutic management. Unfortunately, the development of radioresistance is universal. Here, we identified calcium-regulated heat-stable protein 1 (CARHSP1) as a critical driver for radioresistance utilizing genome-wide CRISPR activation screening.

Balancing Properties with Carboxylates: A Lead Optimization Campaign for Selective and Orally Active CDK9 Inhibitors.

Cyclin-dependent kinase 9 (CDK9) is a serine/threonine kinase involved in the regulation of transcription elongation. An inhibition of CDK9 downregulates a number of short-lived proteins responsible for tumor maintenance and survival, including the antiapoptotic BCL-2 family member MCL-1. As pan-CDK inhibitors under development have faced dosing and toxicity challenges in the clinical setting, we generated selective CDK9 inhibitors that could be amenable to an oral administration.