LncRNAs chaperoning dynamic protein condensates in cancer cells.

In this issue of Molecular Cell, Sun et al. reveal that the long non-coding RNA (lncRNA) DNAJC3-AS1 plays a dual role in maintaining the rRNA processing function of fibrillarin (FBL) in cancer cells. It promotes FBL condensation while preventing abnormal aggregation, offering new therapeutic insights for cancer treatment by targeting lncRNAs involved in the regulation of FBL condensation.

Hapalindole Q suppresses autophagosome-lysosome fusion by promoting YAP1 degradation via chaperon-mediated autophagy.

Autophagy is a conserved catabolic process crucial for maintaining cellular homeostasis and has emerged as a promising therapeutic target for many diseases. Mechanistically novel small-molecule autophagy regulators are highly desirable from a pharmacological point of view. Here, we report the macroautophagy-inhibitory effect of hapalindole Q, a member of the structurally intriguing but biologically understudied hapalindole family of indole terpenoids.

Homologous Peptide Foldamer Promotes FUS Aggregation and Triggers Cancer Cell Death.

Fused in sarcoma (FUS), a multifunctional deoxyribonucleic acid (DNA)/ribonucleic acid (RNA)-binding protein, has been implicated in various cancer types, including sarcoma and leukemia. Despite its association with these diseases, there has been limited exploration of FUS as a cancer therapy target, primarily because its dynamic nature makes it difficult to target specifically. In this study, we explored a kind of β-sheet peptide foldamer, named β-TAT, to influence FUS aggregation by targeting its RNA recognition motifs (RRM).

Improved ECG-gated cardiac cine imaging with variable initial value based tiny golden-angle radial trajectory.

Background: Breath-held electrocardiogram-gated cardiac cine imaging (ECG-CINE), as the gold standard for assessing cardiac function in magnetic resonance imaging (MRI), is prone to motion artifacts. Conventional golden-angle (CGA) sampling has emerged as a promising technique for mitigating motion effects in real-time cardiac cine imaging. However, in ECG-CINE, the irregular re-binning of radial k-space profiles based on CGA can exacerbate k-space non-uniformity, resulting in severe streaking artifacts.

Treatment expectations of patients and clinicians: a cross-sectional study.

Importance: Understanding treatment expectations of patients and their clinicians is of great importance in improving personalized medical services and enhancing patient safety systems.

Objective: To investigate treatment expectations of patients and their clinicians and compare differences between both, by using a pair of validated structured assessment tools covering three key aspects/dimensions of clinical interests.

Design Setting And Participants: This single-center cross-sectional study was conducted at Peking Union Medical College Hospital in China.

Hsp90α forms condensate engaging client proteins with RG motif repeats.

Hsp90α, a pivotal canonical chaperone, is renowned for its broad interaction with numerous protein clients to maintain protein homeostasis, chromatin remodeling, and cell growth. Recent studies indicate its role in modifying various components of membraneless organelles (MLOs) such as stress granules and processing bodies, suggesting its participation in the regulation of protein condensates. In this study, we found that Hsp90α possesses an inherent ability to form dynamic condensates .

Diagnostic value of contrast-enhanced ultrasound and shear-wave elastography for small breast nodules.

Background: The study aims to evaluate the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) and shear-wave elastography (SWE) in detecting small malignant breast nodules in an effort to inform further refinements of the Breast Imaging Reporting and Data System (BI-RADS) classification system.

Methods: This study retrospectively analyzed patients with breast nodules who underwent conventional ultrasound, CEUS, and SWE at Gongli Hospital from November 2015 to December 2019. The inclusion criteria were nodules ≤ 2 cm in diameter with pathological outcomes determined by biopsy, no prior treatments, and solid or predominantly solid nodules.

VAMP2 chaperones α-synuclein in synaptic vesicle co-condensates.

α-Synuclein (α-Syn) aggregation is closely associated with Parkinson's disease neuropathology. Physiologically, α-Syn promotes synaptic vesicle (SV) clustering and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly. However, the underlying structural and molecular mechanisms are uncertain and it is not known whether this function affects the pathological aggregation of α-Syn.

Phase-separated ParB enforces diverse DNA compaction modes and stabilizes the parS-centered partition complex.

The tripartite ParABS system mediates chromosome segregation in the majority of bacterial species. Typically, DNA-bound ParB proteins around the parS sites condense the chromosomal DNA into a higher-order multimeric nucleoprotein complex for the ParA-driven partition. Despite extensive studies, the molecular mechanism underlying the dynamic assembly of the partition complex remains unclear.

Machine learning predictor PSPire screens for phase-separating proteins lacking intrinsically disordered regions.

The burgeoning comprehension of protein phase separation (PS) has ushered in a wealth of bioinformatics tools for the prediction of phase-separating proteins (PSPs). These tools often skew towards PSPs with a high content of intrinsically disordered regions (IDRs), thus frequently undervaluing potential PSPs without IDRs. Nonetheless, PS is not only steered by IDRs but also by the structured modular domains and interactions that aren't necessarily reflected in amino acid sequences.

Phosphorylation-Regulated Dynamic Phase Separation of HIP-55 Protects Against Heart Failure.

Background: Heart failure (HF), which is the terminal stage of many cardiovascular diseases, is associated with low survival rates and a severe financial burden. The mechanisms, especially the molecular mechanism combined with new theories, underlying the pathogenesis of HF remain elusive. We demonstrate that phosphorylation-regulated dynamic liquid-liquid phase separation of HIP-55 (hematopoietic progenitor kinase 1-interacting protein of 55 kDa) protects against HF.

Development and psychometric validation of the hospitalized patients' expectations for treatment scale-clinician version.

Objective: Patient safety management systems in general hospitals require a comprehensive tool for assessing the expectations of inpatients across different wards. This study aimed to develop and psychometrically validate a new scale, the hospitalized patients' expectations for treatment scale-clinician version (HOPE-C), to meet this requirement.

Methods: We interviewed 35 experts and 10 inpatients while developing the HOPE-C scale.

Bioactive compounds and biological functions of medicinal plant-derived extracellular vesicles.

Extracellular vesicles (EVs) are tiny lipid bilayer-enclosed membrane particles released from a variety of cell types into the surrounding environment. These EVs have massive participated in cell-to-cell communication and interspecies communication. In recent years, plant-derived extracellular vesicles (PDEVs) and "exosome-like" EVs populations found in distinct plants have attracted widespread attention.

Lack of causal association between epilepsy and dementia: A Mendelian randomization analysis.

Objective: Epidemiological studies have reported an association between epilepsy and dementia. However, the causal relationship between epilepsy and the risk of dementia is not clear. We aimed to inspect the causal effect of epilepsy on memory loss and dementia.

The validity and IRT psychometric analysis of Chinese version of Difficult Doctor-Patient Relationship Questionnaire (DDPRQ-10).

Objective: The doctor-patient relationship (DPR) plays a crucial role in the Chinese healthcare system, functioning to improve medical quality and reduce medical costs. This study examined the psychometric properties of the Chinese version of the Difficult Doctor-Patient Relationship Questionnaire (DDPRQ-10) among general hospital inpatients in China.

Methods: The research recruited 38 resident doctors responsible for 120 participants, and factor analyses were used to assess the construct validity of the scale.

CuP nanocrystals filled halloysite nanotubes for chemodynamic therapy of breast cancer.

Copper-based Fenton-like agents have the ability to convert weakly oxidizing HO into highly oxidizing hydroxyl radicals (·OH) at tumor sites during chemodynamic therapy (CDT). In this study, the interfacial attraction properties between the negatively charged OCP in sodium phosphathynolate (NaOCP) and the positively charged environment inside the lumen of halloysite nanotubes (HNTs) were utilized to synthesize CuP nanoparticles in situ within the HNTs. The study investigated the chemical composition, morphology, and structure of Cu P@HNTs.

Superhard bulk high-entropy carbides with enhanced toughness via metastable in-situ particles.

Despite the extremely high hardness of recently proposed high-entropy carbides (HECs), the low fracture toughness limits their applications in harsh mechanical environment. Here, we introduce a metastability engineering strategy to achieve superhard HECs with enhanced toughness via in-situ metastable particles. This is realized by developing a (WTaNbZrTi)C HEC showing a solid solution matrix with uniformly dispersed in-situ tetragonal and monoclinic ZrO particles.

Development and psychometric validation of the hospitalized patients' expectations for treatment scalepatient version.

Objectives: A general expectation measurement of inpatients across wards is needed in the patient safety management systems of general hospitals. This study developed and psychometrically validated a new scale fulfilling the requirements above: the Hospitalized Patients' Expectations for Treatment Scale-Patient version (HOPE-P).

Methods: A total of 35 experts and ten inpatients were interviewed during the formulation of the HOPE-P scale, which was initially designed with three dimensions: doctor-patient communication expectations, treatment outcome expectations, and disease management expectancy.

The causal relationship between circulating biomarkersand the risk of bipolar disorder: A two-sample Mendelian randomization study.

Objective: To identify susceptible biomarkers for the development of bipolar disorder (BD), we conducted a Mendelian Randomization (MR) design to screen circulating proteins for the potential risk of bipolar disorder systematically.

Methods: We performed a two-sample Mendelian randomization (MR) analysis to estimate the causality of 4782 human circulating proteins on the risk of bipolar disorder. 376 circulating biomarkers were selected in MR estimation (4406 circulating proteins with less than 3 SNPs were excluded) with 5368 European descents.

β-Microglobulin coaggregates with Aβ and contributes to amyloid pathology and cognitive deficits in Alzheimer's disease model mice.

Extensive studies indicate that β-amyloid (Aβ) aggregation is pivotal for Alzheimer's disease (AD) progression; however, cumulative evidence suggests that Aβ itself is not sufficient to trigger AD-associated degeneration, and whether other additional pathological factors drive AD pathogenesis remains unclear. Here, we characterize pathogenic aggregates composed of β-microglobulin (βM) and Aβ that trigger neurodegeneration in AD. βM, a component of major histocompatibility complex class I (MHC class I), is upregulated in the brains of individuals with AD and constitutes the amyloid plaque core.

Emotional distress and burnout at a fever clinic in China: Comparison between different periods of COVID-19.

Background: Frontline healthcare workers (FHWs) experienced psychological stress and heavy workload during COVID-19 pandemic. This study examined the psychological symptoms and occupational burnout of FHWs in a fever clinic during different periods of the pandemic.

Methods: A cross-sectional survey of FHWs in the fever clinic of a tertiary hospital was carried out during both the outbreak period and regular period of COVID-19.

The Chinese version of patient-doctor-relationship questionnaire (PDRQ-9): Factor structure, validation, and IRT psychometric analysis.

Objective: The patient-doctor relationship has been considered as a crucial concept in primary healthcare, while the medical reform launched by the Chinese government in 2009 has brought significant changes to the healthcare system, which made it urgent to introduce reliable measurement instruments for assessing today's doctor-patient relationship in China. This study examined the psychometric properties of the Chinese version of the Patient-Doctor-Relationship Questionnaire-9 item (PDRQ-9) scale among general hospital inpatients in China.

Materials And Methods: A total of 203 participants responded to the survey, of which 39 completed retest after 7 days.

HPV 16 E6 promotes growth and metastasis of esophageal squamous cell carcinoma cells in vitro.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies worldwide. Increasing evidence suggests that human papillomavirus (HPV) infection may be associated with the etiology of ESCC. However, the precise role of HPV in ESCC remains unclear.

A redox switch regulates the assembly and anti-CRISPR activity of AcrIIC1.

Anti-CRISPRs (Acrs) are natural inhibitors of bacteria's CRISPR-Cas systems, and have been developed as a safeguard to reduce the off-target effects of CRISPR gene-editing technology. Acrs can directly bind to CRISPR-Cas complexes and inhibit their activities. However, whether this process is under regulation in diverse eukaryotic cellular environments is poorly understood.

Heat-shock chaperone HSPB1 regulates cytoplasmic TDP-43 phase separation and liquid-to-gel transition.

While acetylated, RNA-binding-deficient TDP-43 reversibly phase separates within nuclei into complex droplets (anisosomes) comprised of TDP-43-containing liquid outer shells and liquid centres of HSP70-family chaperones, cytoplasmic aggregates of TDP-43 are hallmarks of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Here we show that transient oxidative stress, proteasome inhibition or inhibition of the ATP-dependent chaperone activity of HSP70 provokes reversible cytoplasmic TDP-43 de-mixing and transition from liquid to gel/solid, independently of RNA binding or stress granules. Isotope labelling mass spectrometry was used to identify that phase-separated cytoplasmic TDP-43 is bound by the small heat-shock protein HSPB1.