Scalable total synthesis of saxitoxin and related natural products.

Saxitoxin (STX, 1), a potent neurotoxin from shellfish, first isolated in 1957, offers immense pharmaceutical potential due to its interaction with voltage-gated sodium channels, that are ubiquitously present in all excitable cells of the central and periphperal nervous system. Hundreds of synthetic studies towards this end have been disclosed thus far, yet, a fully modular and scalable approach to the family remains elusive. Thus, here we show how a tactical combination of radical retrosynthesis, biocatalysis, and C-H functionalization logic can be combined to solve this problem resulting in a scalable approach to the STX family in less than 10 steps including the first total synthesis of neosaxitoxin (neoSTX, 4), a hydroxylated naturally occurring STX analog previously under clinical investigation.

Large-scale protein interactome reveals lineage-specific genes driving plant-parasitic nematode adaptive innovations.

Mounting evidence suggests that lineage-specific genes drive phenotype diversity. Plant-parasitic nematodes (PPNs), among the most destructive plant pathogens, have evolved innovated traits required for plant parasitism, yet the genetic basis remains unclear. Here, we identify PPN lineage-specific genes (PPNLSGs) and analyze the large-scale protein interactome of their encoded proteins (PPNLSPs).

Shaping local identity through public health: the role of social integration among new-generation rural migrants in urban China.

Background: The health of migrant populations has become a critical public health concern amid China's rapid urbanization, especially within the framework of the "Healthy China" initiative aimed at reducing health disparities. While existing research has extensively examined the challenges rural migrants face regarding employment, housing, and access to services, the specific role of public health services in shaping local identity remains underexplored. This study investigates how public health influences local identity among new-generation rural migrants and examines the mediating role of social integration in this relationship, addressing a significant gap in the migration and public health literature.

Transformer-based prototype network for Chinese nested named entity recognition.

Nested named entity recognition (NNER), a subtask of named entity recognition (NER), aims to recognize more types of entities and complex nested relationships, presenting challenges for real-world applications. Traditional methods, such as sequence labeling, struggle with the task because of the hierarchical nature of these relationships. Although NNER methods have been extensively studied in various languages, research on Chinese NNER (CNNER) remains limited, despite the complexity added by ambiguous word boundaries and flexible word usage in Chinese.

Coordinated inheritance of extrachromosomal DNAs in cancer cells.

The chromosomal theory of inheritance dictates that genes on the same chromosome segregate together while genes on different chromosomes assort independently. Extrachromosomal DNAs (ecDNAs) are common in cancer and drive oncogene amplification, dysregulated gene expression and intratumoural heterogeneity through random segregation during cell division. Distinct ecDNA sequences, termed ecDNA species, can co-exist to facilitate intermolecular cooperation in cancer cells.

An allosteric cyclin E-CDK2 site mapped by paralog hopping with covalent probes.

More than half of the ~20,000 protein-encoding human genes have paralogs. Chemical proteomics has uncovered many electrophile-sensitive cysteines that are exclusive to subsets of paralogous proteins. Here we explore whether such covalent compound-cysteine interactions can be used to discover ligandable pockets in paralogs lacking the cysteine.

Defect by design: Harnessing the "petal effect" for advanced hydrophobic surface applications.

Hypothesis: In the interfacial wetting boundary, the superhydrophobic surface is often damaged, and the anisotropic wettability of its surface has attracted many researchers' attention. The "petal effect" surface has typical anisotropic wettability. We predict that under the dual conditions of structural defects and high impact velocity, the "petal effect" becomes more adhesive on the surface.

Identification of a Homozygous Mutation of CCDC40 in a Chinese Infertile Man with MMAF and PCD-like Phenotypes.

Asthenozoospermia is the most common factor of male infertility, mainly caused by multiple morphological abnormalities of the sperm flagella (MMAF) and primary ciliary dyskinesia (PCD). Previous studies have shown that genetic factors may contribute to MMAF and PCD. The study aimed to identify novel potentially pathogenic gene mutations in a Chinese infertile man with MMAF and PCD-like phenotypes.

Synthesis and characterization of Cu-labeled Geldanamycin derivative for imaging HSP90 expression in breast cancer.

Heat shock protein 90 (HSP90) plays a crucial role in cancer cell growth and metastasis by stabilizing overexpressed signaling proteins. Inhibiting HSP90 has emerged as a promising anti-cancer strategy. In this study, we aimed to develop and characterize a HSP90-targeted molecular imaging probe, [Cu]Cu-DOTA-BDA-GM, based on a specific HSP90 inhibitor, geldanamycin (GM), for PET imaging of cancers.

Silencing Ditylenchus destructor cathepsin L-like cysteine protease has negative pleiotropic effect on nematode ontogenesis.

Ditylenchus destructor is a migratory plant-parasitic nematode that severely harms many agriculturally important crops. The control of this pest is difficult, thus efficient strategies for its management in agricultural production are urgently required. Cathepsin L-like cysteine protease (CPL) is one important protease that has been shown to participate in various physiological and pathological processes.

Proteomic Ligandability Maps of Spirocycle Acrylamide Stereoprobes Identify Covalent ERCC3 Degraders.

Covalent chemistry coupled with activity-based protein profiling (ABPP) offers a versatile way to discover ligands for proteins in native biological systems. Here, we describe a set of stereo- and regiochemically defined spirocycle acrylamides and the analysis of these electrophilic "stereoprobes" in human cancer cells by cysteine-directed ABPP. Despite showing attenuated reactivity compared to structurally related azetidine acrylamide stereoprobes, the spirocycle acrylamides preferentially liganded specific cysteines on diverse protein classes.

Immunological regulation by Toll-1 and Spätzle-4 in larval density-dependent prophylaxis of the oriental armyworm, Mythimna separata.

High population density has been shown to alter insect prophylactic immunity. Toll-Spätzle pathway performs a key function in insect innate immune response. To determine the role of Toll and Spätzle, two main components of Toll-Spätzle pathway, in the density-dependent prophylaxis of Mythimna separata.

Expanding the ligandable proteome by paralog hopping with covalent probes.

More than half of the ~20,000 protein-encoding human genes have at least one paralog. Chemical proteomics has uncovered many electrophile-sensitive cysteines that are exclusive to a subset of paralogous proteins. Here, we explore whether such covalent compound-cysteine interactions can be used to discover ligandable pockets in paralogs that lack the cysteine.

Characterization, Bioactivity, and Biodistribution of 35 kDa Hyaluronan Fragment.

It has been reported that hyaluronic acid (HA) with a 35 kDa molecular weight (HA35) acts biologically to protect tissue from injury, but its biological properties are not yet fully characterized. This study aimed to evaluate the cellular effects and biodistribution of HA35 compared to HA with a 1600 kDa molecular weight (HA1600). We assessed the effects of HA35 and HA1600 on cell migration, NO and ROS generation, and gene expression in cultured macrophages, microglia, and lymphocytes.

An eNAMPT-neutralizing mAb reduces post-infarct myocardial fibrosis and left ventricular dysfunction.

Myocardial infarction (MI) triggers adverse ventricular remodeling (VR), cardiac fibrosis, and subsequent heart failure. Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is postulated to play a significant role in VR processing via activation of the TLR4 inflammatory pathway. We hypothesized that an eNAMPT specific monoclonal antibody (mAb) could target and neutralize overexpressed eNAMPT post-MI and attenuate chronic cardiac inflammation and fibrosis.

High-throughput detection of mycophenolic acid in human plasma based on sensitive and rapid fluorescence nitrogen-doped carbon dots sensing platform.

In this experiment, a water-soluble, nitrogen-doped yellow-green fluorescent N-doped carbon dots (N-CDs) were synthesized by one-step hydrothermal method using β-cyclodextrin as carbon source and L-phenylalanine as nitrogen source. The fluorescence quantum yield of the obtained N-CDs was as high as 9.96%, and the N-CDs exhibited photostability at different pH, ionic strength and temperature.

Use of radiolabeled hyaluronic acid for preclinical assessment of inflammatory injury and acute respiratory distress syndrome.

Unlabelled: Acute respiratory distress syndrome (ARDS) is accompanied by a dramatic increase in lung hyaluronic acid (HA), leading to a dose-dependent reduction of pulmonary oxygenation. This pattern is associated with severe infections, such as COVID-19, and other important lung injury etiologies. HA actively participates in molecular pathways involved in the cytokine storm of COVID-19-induced ARDS.

A Sterically Tuned Directing Auxiliary Promotes Catalytic 1,2-Carbofluorination of Alkenyl Carbonyl Compounds.

The site-selective palladium-catalyzed three-component coupling of unactivated alkenyl carbonyl compounds, aryl- or alkenylboronic acids, and N-fluorobenzenesulfonimide is described herein. Tuning of the steric environment on the bidentate directing auxiliary enhances regioselectivity and facilitates challenging C(sp )-F reductive elimination from a Pd intermediate to afford 1,2-carbofluorination products in moderate to good yields.

Impact of fireworks burning on air quality during the Spring Festival in 2021-2022 in Linyi, a central city in the North China Plain.

The management of fireworks has been strengthened during the Spring Festival in 2022 compared with that in 2021 in Linyi, a central city in the North China Plain. Online measurements of the chemical components of PM were conducted during the Spring Festival in 2021-2022 to assess the influence of fireworks burning (FB) on air quality. Remarkable achievements have been made in improving air quality during FB period (FBP) in 2021-2022 attributing to the stringent regional emission reduction measures, fireworks control, and favorable meteorological conditions with the concentrations of PM, water-soluble ions, and carbonaceous aerosols decreasing by 73.

Ginkgolide A Participates in LPS-Induced PMVEC Injury by Regulating miR-224 and Inhibiting p21 in a Targeted Manner.

Most studies have focused on the protective effects of ginkgolide A against ischemia/reperfusion-induced cardiomyopathy and injury of the brain, liver, and other organs, but there are few reports about the protection of lung tissues. This study was designed to clarify the protection of ginkgolide A against lipopolysaccharide (LPS)-induced pulmonary microvascular endothelial cell (PMVEC) injury. PMVECs were extracted and fell into control, LPS, and ginkgolide A groups.

Ozone pollution in the plate and logistics capital of China: Insight into the formation, source apportionment, and regional transport.

As the logistics and plate capital of China, the sources and regional transport of O in Linyi are different from those in other cities because of the significant differences in industrial structure and geographical location. Twenty-five ozone pollution episodes (OPEs, 52 days) were identified in 2021, with a daily maximum 8-h moving average O concentration (O) of 184.5 ± 22.

Novel compound heterozygous variants of DNAH17 in a Chinese infertile man with multiple morphological abnormalities of sperm flagella.

Multiple morphological abnormalities of the sperm flagellum (MMAF) have been reported to be an important cause of male infertility and reflect a heterogeneous genetic disorder. Previous studies have identified dozens of candidate pathogenic genes for MMAF, but the aetiology in approximately 50% of cases remains unexplained. The present study aimed to identify novel potentially pathogenic gene variants of MMAF.

Coupling of Thiols and Aryl Halides Mediated by Dicyclohexano-18- crown-6 and Potassium Carbonate.

Aims: A simple, transition-metal-free C-S coupling protocol for the synthesis of aryl thioethers is reported.

Background: Sulfur-containing moieties are ubiquitous in pharmaceutical drugs and materials and therefore methods for their construction are of great importance. One approach entails the catalytic coupling of an aryl halohydrocarbon with a thiol, but the transition metal catalysts usually used are prone to poisoning by participating sulfur species and efficient catalysis is usually only achieved after complex ligand optimization.

Discovery of the non-cosmopolitan lineages in Candidatus Thermoprofundales.

The recently proposed order Candidatus Thermoprofundales, currently containing only one family-level lineage Marine Benthic Group-D (MBG-D), is distributed in global subsurface ecosystems and ecologically important, but its diversity, evolution and metabolism remain largely unknown. Here we described two novel family-level specialized lineages in Ca. Thermoprofundales, JdFR-43 and HyVt, which are restricted to specific biotopes (primarily in marine hydrothermal vents and occasionally in oil reservoirs and hot springs) in contrast to the cosmopolitan lineage MBG-D.