Pediatric hypereosinophilic syndrome associated with liver damage, portal vein, splenic vein and superior mesenteric vein thromboses: a case report.

Background: The hypereosinophilic syndrome (HES) is a group of rare blood disorders characterized by persistent eosinophilia and damage to multiple organs. HES can be either primary, secondary or idiopathic. Secondary HES are commonly caused by parasitic infections, allergic reactions or cancer.

[Clinical features of children with coronavirus disease 2019 caused by Delta variant infection in different age groups].

Objectives: To study the clinical features of children with coronavirus disease 2019 (COVID-19) caused by Delta variant infection in different ages groups.

Methods: A total of 45 children with COVID-19 caused by Delta variant infection who were hospitalized in the designated hospital in Henan Province, China, from November 17 to December 17, 2021, were included. They were divided into three groups: <6 years group (=16), 6-13 years group (=16), and >13 years group (=13).

Fam96b recruits brain-type creatine kinase to fuel mitotic spindle formation.

Mitosis is a complicated and ordered process with high energy demands and metabolite fluxes. Cytosolic creatine kinase (CK), an enzyme involved in ATP homeostasis, has been shown to be essential to chromosome movement during mitotic anaphase in sea urchin. However, it remains elusive for the molecular mechanism underlying the recruitment of cytosolic CK by the mitotic apparatus.

[Clinical features of children with coronavirus disease 2019 Delta variant infection after vaccination with inactivated SARS-CoV-2 vaccine].

Objectives: To study the clinical features of children with coronavirus disease 2019 (COVID-19) Delta variant infection vaccinated or not vaccinated with inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine.

Methods: A total of 11 children with COVID-19 Delta variant infection who were vaccinated with inactivated SARS-CoV-2 vaccine and were hospitalized in the designated hospital in Henan Province, China, from November 3 to December 17, 2021 were enrolled as the vaccinated group. Thirty-one children with COVID-19 Delta variant infection who were not vaccinated and were hospitalized during the same period were enrolled as the unvaccinated group.

A High-Quality Haplotype-Resolved Genome of Common Bermudagrass ( L.) Provides Insights Into Polyploid Genome Stability and Prostrate Growth.

Common bermudagrass ( L.) is an important perennial warm-season turfgrass species with great economic value. However, the reference genome is still deficient in , which severely impedes basic studies and breeding studies.

CCT2 is an aggrephagy receptor for clearance of solid protein aggregates.

Protein aggregation is a hallmark of multiple human pathologies. Autophagy selectively degrades protein aggregates via aggrephagy. How selectivity is achieved has been elusive.

Modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells.

Congenital cataracts are the leading cause of childhood blindness. To date, surgical removal of cataracts is the only established treatment, but surgery is associated with multiple complications, which often lead to visual impairment. Therefore, mechanistic studies and drug-candidate screening have been intrigued by the aims of developing novel therapeutic strategies.

Human Ccr4 and Caf1 Deadenylases Regulate Proliferation and Tumorigenicity of Human Gastric Cancer Cells via Modulating Cell Cycle Progression.

Cancer cells generally have reprogrammed gene expression profiles to meet the requirements of survival, continuous division, and metastasis. An interesting question is whether the cancer cells will be affected by interfering their global RNA metabolism. In this research, we found that human Ccr4a/b (hCcr4a/b) and Caf1a/b (hCaf1a/b) deadenylases, the catalytic components of the Ccr4-Not complex, were dysregulated in several types of cancers including stomach adenocarcinoma.

A novel F30S mutation in γS-crystallin causes autosomal dominant congenital nuclear cataract by increasing susceptibility to stresses.

Despite of increasingly accumulated genetic variations of autosomal dominant congenital cataracts (ADCC), the causative genes of many ADCC patients remains unknown. In this research, we identified a novel F30S mutation in γS-crystallin from a three-generation Chinese family with ADCC. The patients possessing the F30S mutation exhibited nuclear cataract phenotype.

Diverse functions of deadenylases in DNA damage response and genomic integrity.

DNA damage response (DDR) is a coordinated network of diverse cellular processes including the detection, signaling, and repair of DNA lesions, the adjustment of metabolic network and cell fate determination. To deal with the unavoidable DNA damage caused by either endogenous or exogenous stresses, the cells need to reshape the gene expression profile to allow efficient transcription and translation of DDR-responsive messenger RNAs (mRNAs) and to repress the nonessential mRNAs. A predominant method to adjust RNA fate is achieved by modulating the 3'-end oligo(A) or poly(A) length via the opposing actions of polyadenylation and deadenylation.

Translation Efficiency and Degradation of ER-Associated mRNAs Modulated by ER-Anchored poly(A)-Specific Ribonuclease (PARN).

Translation is spatiotemporally regulated and endoplasmic reticulum (ER)-associated mRNAs are generally in efficient translation. It is unclear whether the ER-associated mRNAs are deadenylated or degraded on the ER surface in situ or in the cytosol. Here, we showed that ER possessed active deadenylases, particularly the poly(A)-specific ribonuclease (PARN), in common cell lines and mouse tissues.

Lanosterol modulates proteostasis via dissolving cytosolic sequestosomes/aggresome-like induced structures.

Sequestration of misfolded proteins into distinct cellular compartments plays a pivotal role in proteostasis and proteopathies. Cytoplasmic ubiquitinated proteins are sequestered by p62/SQSTM1 to deposit in sequestosomes or aggresome-like induced structures (ALIS). Most aggresome or ALIS regulators identified thus far are recruiters, while little is known about the disaggregases or dissolvers.

Semiholoenzyme optimizes activity and stability of a hyperthermostable iron-superoxide dismutase.

Metal ion coordination is an essential step for the maturation of metalloenzymes. Generally, the metal coordination sites are thought to be fully occupied to achieve the maximum activity and stability. In this research, we compared the structural features, activity and stability of the apo-, semiholo- and holo-forms of a hyperthermostable tetrameric Fe-superoxide dismutase (SOD).

The Intrinsically Disordered C-Terminal Domain Triggers Nucleolar Localization and Function Switch of PARN in Response to DNA Damage.

Poly(A)-specific ribonuclease (PARN), a multifunctional multi-domain deadenylase, is crucial to the regulation of mRNA turnover and the maturation of various non-coding RNAs. Despite extensive studies of the well-folding domains responsible for PARN catalysis, the structure and function of the C-terminal domain (CTD) remains elusive. PARN is a cytoplasm-nucleus shuttle protein with concentrated nucleolar distribution.

Dissimilarity in the Contributions of the N-Terminal Domain Hydrophobic Core to the Structural Stability of Lens β/γ-Crystallins.

Vertebrate lens β/γ-crystallins share a conserved tertiary structure consisting of four Greek-key motifs divided into two globular domains. Numerous inherited mutations in β/γ-crystallins have been linked to cataractogenesis. In this research, the folding mechanism underlying cataracts caused by the I21N mutation in βB2 was investigated by comparing the effect of mutagenesis on the structural features and stability of four β/γ-crystallins, βB1, βB2, γC, and γD.

Contributions of the C-terminal domain to poly(A)-specific ribonuclease (PARN) stability and self-association.

Poly(A)-specific ribonuclease (PARN) catalyzes the degradation of mRNA poly(A) tail to regulate translation efficiency and mRNA decay in higher eukaryotic cells. The full-length PARN is a multi-domain protein containing the catalytic nuclease domain, the R3H domain, the RRM domain and the C-terminal intrinsically unstructured domain (CTD). The roles of the three well-structured RNA-binding domains have been extensively studied, while little is known about CTD.

Lanosterol and 25-hydroxycholesterol dissociate crystallin aggregates isolated from cataractous human lens via different mechanisms.

Cataract, a crystallin aggregation disease, is the leading cause of human blindness worldwide. Surgery is the only established treatment of cataracts and no anti-cataract drugs are available thus far. Recently lanosterol and 25-hydroxycholesterol have been reported to redissolve crystallin aggregates and partially restore lens transparency in animals.

Introduction of an extra tryptophan fluorophore by cataract-associating mutations destabilizes βB2-crystallin and promotes aggregation.

β/γ-Crystallins are predominant structural proteins in vertebrate lens with unique properties of extremely high solubility, long-term stability and resistance to UV damage. Four conserved Trp residues in β/γ-crystallins account for UV absorbance and thereafter fluorescence quenching to avoid photodamage. Herein we found that βB2-crystallin Trp fluorescence was greatly enhanced by the introduction of an extra unquenched Trp fluorophore by cataract-associated mutations S31W and R145W.

Synthesis, Evaluation, and Structure-Activity Relationship Study of Lanosterol Derivatives To Reverse Mutant-Crystallin-Induced Protein Aggregation.

We describe here the development of potent synthetic analogues of the naturally occurring triterpenoid lanosterol to reverse protein aggregation in cataracts. Lanosterol showed superiority to other scaffolds in terms of efficacy and generality in previous studies. Various modified lanosterol derivatives were synthesized via modification of the side chain, ring A, ring B, and ring C.

The cataract-causing mutation G75V promotes γS-crystallin aggregation by modifying and destabilizing the native structure.

Congenital cataract is one of the leading causes of childhood blindness worldwide. About half of heredity cataracts are caused by mutations in various crystallins. However, the underlying mechanisms have not been elucidated for most of crystallin mutations.

Increasing susceptibility to oxidative stress by cataract-causing crystallin mutations.

Cataract, a crystallin protein aggregation disease, is the leading cause of human blindness worldwide. Congenital cataract may be induced by many factors and genetic disorders accounts for about half of the cases. Inherited mutations can promote cataract formation by affecting crystallin structure, solubility, stability, protein interactions and aggregatory propensity.

Effects of cataract-causing mutations W59C and W151C on βB2-crystallin structure, stability and folding.

β/γ-Crystallins, the predominant structural proteins in vertebrate lens with lifelong stability to maintain lens transparency, share a high similarity in their primary sequences and tertiary structures. Four conserved Trp residues have been shown to be important to γ-crystallin structure, stability and protection against UV irradiation, whereas their roles in β-crystallins remain elusive. Herein we found that two congenital cataract-causing mutations, W59C and W151C, dramatically decreased βB2-crystallin solubility and stability against thermal and guanidine hydrochloride-induced denaturation.

Cataract-causing mutation S228P promotes βB1-crystallin aggregation and degradation by separating two interacting loops in C-terminal domain.

β/γ-Crystallins are predominant structural proteins in the cytoplasm of lens fiber cells and share a similar fold composing of four Greek-key motifs divided into two domains. Numerous cataract-causing mutations have been identified in various β/γ-crystallins, but the mechanisms underlying cataract caused by most mutations remains uncharacterized. The S228P mutation in βB1-crystallin has been linked to autosomal dominant congenital nuclear cataract.

Congenital microcornea-cataract syndrome-causing mutation X253R increases βB1-crystallin hydrophobicity to promote aggregate formation.

The high solubility and lifelong stability of crystallins are crucial to the maintenance of lens transparency and optical properties. Numerous crystallin mutations have been linked to congenital cataract, which is one of the leading causes of newborn blindness. Besides cataract, several crystallin mutations have also been linked to syndromes such as congenital microcornea-cataract syndrome (CMCC).