Prodigiosin inhibits proliferation and induces apoptosis through influencing amino acid metabolism in multiple myeloma.

The recurrence of drug-resistant and expensive treatment drugs are major causes of the low survival rate of multiple myeloma (MM) patients. Exploring a safe, effective, low-cost and novel drug treatment for MM is a promising strategy to relieve the burden of MM patients. In this study, we found that prodigiosin could inhibit MM cell proliferation and induce MM cell apoptosis, however, it had a lesser cytotoxic effect on normal B cells within the IC range of MM cells.

Nemo-like kinase disrupts nuclear import and drives TDP43 mislocalization in ALS.

Cytoplasmic TDP43 mislocalization and aggregation are pathological hallmarks of amyotrophic lateral sclerosis (ALS). However, the initial cellular insults that lead to TDP43 mislocalization remain unclear. In this study, we demonstrate that Nemo-like kinase (NLK)-a proline-directed serine/threonine kinase-promotes the mislocalization of TDP43 and other RNA-binding proteins by disrupting nuclear import.

Biphenylene-Based Crystalline Foam Carbon Allotropes.

Developing new allotropes with excellent properties and high synthesizability is an intriguing and challenging topic for carbon materials. Based on the experimental biphenylene monolayers, varied three-dimensional crystalline foam carbon allotropes with parallel channels in the structure are theoretically designed. These calculated foam carbon structures are mostly semimetals or semiconductors.

Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): a randomized, blinded, crossover trial.

Background: Guidelines recognized dual combination in initial antihypertensive therapy. Studies found that low-dose quadruple combination were superior to monotherapy. However, whether low-dose quadruple therapy is better than dual combination is unknown.

TDP43 autoregulation gives rise to dominant negative isoforms that are tightly controlled by transcriptional and post-translational mechanisms.

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation.

Increasing plant diversity enhances soil organic carbon storage in typical wetlands of northern China.

Soil organic carbon plays an important role in climate change mitigation, and can be strongly affected by plant diversity. Although a positive effect of plant diversity on soil organic carbon storage has been confirmed in grasslands and forests, it remains unclear whether this effect exists in wetlands. In this study, we investigated plant diversity, soil properties and soil organic carbon across five typical wetlands of northern China, to test the effect of plant diversity on soil organic carbon and clarified the regulators.

Molecular Visualization of Neuronal TDP43 Pathology .

Nuclear exclusion and cytoplasmic accumulation of the RNA-binding protein TDP43 are characteristic of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite this, the origin and ultrastructure of cytosolic TDP43 deposits remain unknown. Accumulating evidence suggests that abnormal RNA homeostasis can drive pathological TDP43 mislocalization, enhancing RNA misprocessing due to loss of nuclear TDP43 and engendering a cycle that ends in cell death.

Stress granule formation helps to mitigate neurodegeneration.

Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known.

TDP43 autoregulation gives rise to shortened isoforms that are tightly controlled by both transcriptional and post-translational mechanisms.

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, highly prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation.

Heat stress at the bicellular stage inhibits sperm cell development and transport into pollen tubes.

For successful double fertilization in flowering plants (angiosperms), pollen tubes deliver 2 nonmotile sperm cells toward female gametes (egg and central cell, respectively). Heatwaves, especially during the reproduction period, threaten male gametophyte (pollen) development, resulting in severe yield losses. Using maize (Zea mays) as a crop and grass model system, we found strong seed set reduction when moderate heat stress was applied for 2 d during the uni- and bicellular stages of pollen development.

Counter-regulation of RNA stability by UPF1 and TDP43.

RNA quality control is crucial for proper regulation of gene expression. Disruption of nonsense mediated mRNA decay (NMD), the primary RNA decay pathway responsible for the degradation of transcripts containing premature termination codons (PTCs), can disrupt development and lead to multiple diseases in humans and other animals. Similarly, therapies targeting NMD may have applications in hematological, neoplastic and neurological disorders.

Initial treatment with a single capsule containing half-dose quadruple therapy versus standard-dose dual therapy in hypertensive patients (QUADUAL): statistical analysis plan for a randomized, blinded, crossover trial.

Background: Combined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial antihypertensive therapy. Recent studies have also pointed out that the quadruple combination of very low-dose antihypertensive drugs is superior to single drugs.

The RALF signaling pathway regulates cell wall integrity during pollen tube growth in maize.

Autocrine signaling pathways regulated by RAPID ALKALINIZATION FACTORs (RALFs) control cell wall integrity during pollen tube germination and growth in Arabidopsis (Arabidopsis thaliana). To investigate the role of pollen-specific RALFs in another plant species, we combined gene expression data with phylogenetic and biochemical studies to identify candidate orthologs in maize (Zea mays). We show that Clade IB ZmRALF2/3 mutations, but not Clade III ZmRALF1/5 mutations, cause cell wall instability in the sub-apical region of the growing pollen tube.

Stress granule formation helps to mitigate neurodegeneration.

Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known.

Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): Study protocol for a randomized, blinded, crossover trial.

Background: Combined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial antihypertensive therapy. Recent studies have also pointed out that the quadruple combination of very low-dose antihypertensive drugs is superior to single drugs.

A moderated mediation analysis of depression and age on the relationship between resilience and frailty among HIV-positive adults.

Background: Given the continuing challenges frailty poses among people living with human immunodeficiency virus (HIV) (PLHIV), accumulating evidence suggests that frailty is linked to psychological factors. However, the mutual influences of resilience, depression, and frailty have not yet been clarified. This study aimed to identify the potential mechanistic pathway through which psychological factors mitigate frailty.

Environmental noise exposure and health outcomes: an umbrella review of systematic reviews and meta-analysis.

Background: Environmental noise is becoming increasingly recognized as an urgent public health problem, but the quality of current studies needs to be assessed. To evaluate the significance, validity and potential biases of the associations between environmental noise exposure and health outcomes.

Methods: We conducted an umbrella review of the evidence across meta-analyses of environmental noise exposure and any health outcomes.

Neuronal activity regulates Matrin 3 abundance and function in a calcium-dependent manner through calpain-mediated cleavage and calmodulin binding.

RNA-binding protein (RBP) dysfunction is a fundamental hallmark of amyotrophic lateral sclerosis (ALS) and related neuromuscular disorders. Abnormal neuronal excitability is also a conserved feature in ALS patients and disease models, yet little is known about how activity-dependent processes regulate RBP levels and functions. Mutations in the gene encoding the RBP Matrin 3 (MATR3) cause familial disease, and MATR3 pathology has also been observed in sporadic ALS, suggesting a key role for MATR3 in disease pathogenesis.

RNA methylation influences TDP43 binding and disease pathogenesis in models of amyotrophic lateral sclerosis and frontotemporal dementia.

RNA methylation at adenosine N6 (m6A) is one of the most common RNA modifications, impacting RNA stability, transport, and translation. Previous studies uncovered RNA destabilization in amyotrophic lateral sclerosis (ALS) models in association with accumulation of the RNA-binding protein TDP43. Here, we show that TDP43 recognizes m6A RNA and that RNA methylation is critical for both TDP43 binding and autoregulation.

Ubiquilin-2 regulates pathological alpha-synuclein.

The key protein implicated in Parkinson's disease and other synucleinopathies is α-synuclein, and a post-translationally modified form of the protein, phosphorylated at serine 129 (pS129), is a principal component in Lewy bodies, a pathological hallmark of PD. While altered proteostasis has been implicated in the etiology of Parkinson's disease, we still have a limited understanding of how α-synuclein is regulated in the nervous system. The protein quality control protein Ubiquilin-2 (UBQLN2) is known to accumulate in synucleinopathies, but whether it directly regulates α-synuclein is unknown.

Nuclear import receptors are recruited by FG-nucleoporins to rescue hallmarks of TDP-43 proteinopathy.

Background: Cytoplasmic mislocalization and aggregation of TAR DNA-binding protein-43 (TDP-43) is a hallmark of the amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) disease spectrum, causing both nuclear loss-of-function and cytoplasmic toxic gain-of-function phenotypes. While TDP-43 proteinopathy has been associated with defects in nucleocytoplasmic transport, this process is still poorly understood. Here we study the role of karyopherin-β1 (KPNB1) and other nuclear import receptors in regulating TDP-43 pathology.

The Association between Gut Microbiome and Pregnancy-Induced Hypertension: A Nested Case-Control Study.

(1) Background: Pregnancy-induced hypertension (PIH) is associated with obvious microbiota dysbiosis in the third trimester of pregnancy. However, the mechanisms behind these changes remain unknown. Therefore, this study aimed to explore the relationship between the gut microbiome in early pregnancy and PIH occurrence.

Mediating effects of resilience on frailty and depression among older Chinese people living with HIV/AIDS: a cross-sectional study in Hunan.

Background: Little is known about the ambiguous and complex relationship between frailty, resilience and depression in older adults living with HIV (OALHIV). Thus, the current study aimed to further clarify the relationship, as well as to investigate whether resilience plays a mediating role and to quantify the mediating effect.

Methods: A cross-sectional study was conducted on patients who were aged ≥50 y with HIV/AIDS at the First Hospital of Changsha City from June to August 2019.

The efficacy of Da Chaihu decoction combined with metformin tablets for type 2 diabetes mellitus: A systematic review and meta-analysis.

Objective: To assess the efficacy of Da Chaihu decoction combined with metformin tablets on patients with type 2 diabetes compared with metformin alone.

Methods: This systematic review and meta-analysis is written based on 2020 PRISMA Extension for Chinese Herbal Medicines 2020 (PRISMA-CHM 2020) reporting guidelines. We reviewed all the relevant studies from a search of the following databases from inception to February 2022 without any language restriction: Excerpta Medica Database (EMBASE), Google Scholar, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Information, Wanfang Data, and the Chinese Biomedical Literature Database(CBM).

The lagged effect and attributable risk of apparent temperature on hand, foot, and mouth disease in Changsha, China: a distributed lag non-linear model.

Hand, foot, and mouth disease (HFMD) is the leading Category C infectious disease affecting millions of children in China every year. In the context of global climate change, the understanding and quantification of the impact of weather factors on human health are particularly critical to the development and implementation of climate change adaptation and mitigation strategies. The aim of this study was to quantify the attributable burden of a combined bioclimatic indicator (apparent temperature) on HFMD and to identify temperature-specific sensitive populations.