Mood assessments of family caregivers of patients with severe brain injury in China.

OBJECTIVES: Long-term care of severe brain injury patients places a significant mental burden on family caregivers, yet few studies have reported the situation in China. We aimed to describe the mood states of family caregivers of patients with severe brain injury and examine the influencing factors that affect caregivers' moods. METHODS: Cross-sectional survey was used to assess the mood profiles of Chinese family caregivers between February 2019 and February 2020. Demographic data of caregivers and patients, the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder scale (GAD-7) were used to assess the level of depressive and anxiety symptoms. The quality of life score was also assessed by a visual analog scale, and the Coma Recovery Scale-Revised was used to assess the patient's consciousness. RESULT: One hundred and one patients with severe brain injury (57 unresponsive wakefulness syndrome, UWS) between the age of 14 and 70 and their main family caregivers were enrolled in the study. Most caregivers displayed depressive (n = 62) and anxiety symptoms (n = 65), with 17 and 20 of these family caregivers reporting (moderately) severe depressive symptom and severe anxiety symptom, respectively. The caregiver's depressive symptom level significantly decreased as the patient's injury lasted longer (r = - 0.208, P = 0.037). Moreover, the age of the patient negatively related to the levels of depressive (r = - 0.310, P = 0.002) and anxiety symptoms (r = - 0.289, P = 0.003) in caregivers. There was a significant positive correlation between anxiety and depressive symptoms scores in family caregivers (r = 0.838, P < 0.001). The higher the level of anxiety (r = - 0.273, P = 0.006) and depressive symptoms (r = - 0.265, P = 0.007), the worse the quality of life. CONCLUSION: Many family caregivers of patients with severe brain injury experience various levels of anxiety and depressive symptoms in China. Tailor-made psychological help seems imperative. Researchers and doctors can provide information about patient's conditions to assist family members in discussing rehabilitation options for patients in different states of consciousness will help to ease anxiety of family caregivers.

Perception of diagnosis by family caregivers in severe brain injury patients in China.

OBJECTIVES: Surrogate decision-making by family caregivers for patients with severe brain injury is influenced by the availability and understanding of relevant information and expectations for future rehabilitation. We aimed to compare the consistency of family caregivers' perceptions with clinical diagnoses and to inform their expectation of prognosis in the future. METHODS: The Coma Recovery Scale-Revised was used to assess the diagnosis of inpatients with severe brain injury between February 2019 and February 2020. A main family caregiver was included per patient. The family caregiver's perception of the patient's consciousness and expectations of future recovery were collected through questionnaires and compared consistently with the clinical diagnosis. RESULTS: The final sample included 101 main family caregivers of patients (57 UWS, unresponsive wakefulness syndrome, 37 MCS, minimally conscious state, 7 EMCS, emergence from MCS) with severe brain injury. Only 57 family caregivers correctly assessed the level of consciousness as indicated by the CRS-R, showing weak consistency (Kappa = 0.217, P = 0.002). Family caregivers' demographic characteristics and CRS-R diagnosis influenced the consistency between perception and clinical diagnosis. Family caregivers who provided hands-on care to patients showed higher levels of consistent perception (AOR = 12.24, 95% CI = 2.06-73.00, P = 0.006). Compared to UWS, the family caregivers of MCS patients were more likely to have a correct perception (OR = 7.68, 95% CI = 1.34-44.06). Family caregivers had positive expectations for patients' recovery in terms of both communication and returning to normal life. CONCLUSION: Nearly half of family caregivers have inadequate understanding of their relative's level of consciousness, and most of them report overly optimistic expectations that do not align with clinical diagnosis. Providing more medical information to family caregivers to support their surrogate decision-making process is essential.

MBL2 polymorphism may be a protective factor of autoimmune thyroid disease susceptibility.

Genetic susceptibility is an essential pathogenetic mechanism in autoimmune thyroid disease (AITD). MBL2 gene polymorphisms have been shown to play a vital role in the pathogenesis of multiple autoimmune disorders, but its contribution to AITD is unclear. The aim of this study was to assess the linkage between MBL2 gene polymorphisms and AITD susceptibility in a Chinese Han population. One thousand seven hundred sixty seven subjects consisting of 965 AITD patients and 802 controls from a Chinese Han population were enrolled in the case-control study. Four common single-nucleotide polymorphisms (SNPs) in the MBL2 gene were tested using high-throughput sequencing technology for sequence-based SNP genotyping. The allele and genotype distribution results showed that the minor alleles of rs198266, rs10824793, and rs4935046 were significantly lower in Hashimoto's thyroiditis (HT) patients than in healthy controls. In further genetic model analysis, the dominant models of rs1982266, rs10824793, and rs4935046 for MBL2 in the AITD group exhibited a lower risk of morbidity. Finally, we discovered that haplotype AAGC was associated with Graves' disease (GD), while AGC was associated with HT. Our study provides strong evidence for a genetic correlation between MBL2 and AITD, and the polymorphism of the MBL2 gene may be a protective factor for AITD, especially for HT. These findings can advance our understanding of the etiology of AITD, as well as provide guidance for prevention and intervention toward AITD.

Imbalanced Text Sentiment Classification Based on Multi-Channel BLTCN-BLSTM Self-Attention.

With the continuous expansion of the field of natural language processing, researchers have found that there is a phenomenon of imbalanced data distribution in some practical problems, and the excellent performance of most methods is based on the assumption that the samples in the dataset are data balanced. Therefore, the imbalanced data classification problem has gradually become a problem that needs to be studied. Aiming at the sentiment information mining of an imbalanced short text review dataset, this paper proposed a fusion multi-channel BLTCN-BLSTM self-attention sentiment classification method. By building a multi-channel BLTCN-BLSTM self-attention network model, the sample after word embedding processing is used as the input of the multi-channel, and after fully extracting features, the self-attention mechanism is fused to strengthen the sentiment to further fully extract text features. At the same time, focus loss rebalancing and classifier enhancement are combined to realize text sentiment predictions. The experimental results show that the optimal F1 value is up to 0.893 on the Chnsenticorp-HPL-10,000 corpus. The comparison and ablation of experimental results, including accuracy, recall, and F1-measure, show that the proposed model can fully integrate the weight of emotional feature words. It effectively improves the sentiment classification performance of imbalanced short-text review data.

Hydroxychloroquine use reduces mortality risk in systemic lupus erythematosus: A systematic review and meta-analysis of cohort studies.

OBJECTIVE: Hydroxychloroquine (HCQ) is widely used in patients with systemic lupus erythematosus (SLE), but its effects on the mortality have not reached a definite conclusion. In this systematic review and meta-analysis, we aimed to assess whether HCQ use could reduce the risk of mortality in SLE patients. METHODS: PubMed, Embase, Web of Science, and Cochrane database were searched from inception to April 17, 2022 without language restrictions to explore the relationship between HCQ use and SLE mortality. The relative risk (HR) was pooled using the STATA software. RESULTS: A total of 21 studies with a pooled patient population of 26,037 were included in the study, including 14 studies on the association between HCQ alone and mortality risk and seven studies on the association between HCQ/chloroquine (CQ) and mortality risk. The pooled findings suggested that HCQ significantly reduced the overall mortality risk of SLE (pooled HR 0.46, 95% CI 0.38-0.57, p < 0.001). In subgroup analysis of SLE complications, HCQ use also decreased the risk of death in SLE patients with renal (HR=0.43, 95% CI 0.26-0.70, p = 0.001) and cardiopulmonary involvement (HR=0.37, 95% CI= 0.25-0.54, p < 0.001). In addition, HCQ use was also protective against the risk of mortality in SLE patients in different regions, such as Asia (HR=0.46, 95% CI=0.33-0.64, p < 0.001), Europe (HR= 0.40, 95% CI = 0.22-0.71, p = 0.002), and America (HR=0.52, 95% CI= 0.42-0.64, p < 0.001). CONCLUSION: Our data suggested that HCQ use was associated with a reduced risk of mortality in patients with SLE.

PLEK2 promotes the proliferation and migration of non-small cell lung cancer cells in a BRD4-dependent manner.

BACKGROUND: It has been reported that Pleckstrin 2 (PLEK2) acts as an oncogene in non-small cell lung cancer (NSCLC). Bromodomain containing protein 4 (BRD4), an important transcriptional regulator of tumorigenesis, has been shown to play a key role in NSCLC. However, whether BRD4 regulates the transcription of PLEK2 and further promotes the proliferation and migration of NSCLC remains unknown. METHODS AND RESULTS: In this study, we performed western blotting, real-time quantitative polymerase chain reaction, immunofluorescence, cell scratch wound assay and chromatin immunoprecipitation. According to these results, we found that PLEK2 plays a tumor­promoting role in NSCLC via the PI3K/AKT signaling pathway. Moreover, BRD4 expression is significantly upregulated in NSCLC cell lines and suppression of BRD4 expression by siBRD4 and JQ-1 inhibits NSCLC cell lines proliferation and migration. Prominently, we first confirmed that BRD4 binds to the promoter region of the PLEK2 gene, which explains the mechanism by which BRD4 regulates the transcription of PLEK2 gene from the perspective of epigenetics. CONCLUSIONS: The present study suggested that PLEK2 promotes the proliferation and migration of NSCLC in a BRD4-dependent manner and provided key insights into the potential avenues for preventing and treating NSCLC.

A Rationally Designed Building Block of the Putative Magnetoreceptor MagR.

The ability of animals to perceive guidance cues from Earth's magnetic field for orientation and navigation has been supported by a wealth of behavioral experiments, yet the nature of this sensory modality remains fascinatingly unresolved and wide open for discovery. MagR has been proposed as a putative magnetoreceptor based on its intrinsic magnetism and its complexation with a previously suggested key protein in magnetosensing, cryptochrome, to form a rod-like polymer structure. Here, we report a rationally designed single-chain tetramer of MagR (SctMagR), serving as the building block of the hierarchical assembly of MagR polymer. The magnetic trapping experiment and direct magnetic measurement of SctMagR demonstrated the possibility of magnetization of nonmagnetic cells via overexpressing a single protein, which has great potential in various applications. SctMagR, as reported in this study, serves as a prototype of designed magnetic biomaterials inspired by animal magnetoreception. The features of SctMagR provide insights into the unresolved origin of the intrinsic magnetic moment, which is of considerable interest in both biology and physics. © 2022 Bioelectromagnetics Society.

Identification and genotoxicity evaluation of potential impurities in rabeprazole sodium using in silico and in vitro analyses.

Rabeprazole sodium is a widely used drug for gastrointestinal disorders. Several analytical methods for identifying rabeprazole sodium and its impurities have been reported. However, the genotoxicity of rabeprazole sodium and its impurities is still unclear. Thus, it is necessary to develop analytical methods that can identify the structures of its impurities and evaluate their genotoxicity. Here, we used high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry for identifying the impurities in rabeprazole sodium enteric-coated tablets. Impurities in the samples were matched with synthesized impurities based on the exact mass and secondary mass spectrometry characteristics and then subjected to in silico analysis using the Derek and Sarah software, as well as in vitro genotoxicity evaluations. Our method successfully identified the impurities as 2-[[4-(3-methoxy propane)-3-methyl-N-oxido-2-pyridyl] methyl sulfonyl]-1H-benzimidazole (impurity I), 2-[[4-(3-methoxy propane)-3-methyl-2-pyridyl]methyl sulfonyl]-benzimidazole (impurity II), 2-[[4-(3-methoxy propane)-3-methyl-2-pyridyl] methionyl]-1H-benzimidazole (impurity III), and 2-mercapto benzimidazole (impurity IV). In silico analysis predicted that impurity III demonstrated a structural alert; thus, this impurity was evaluated for in vitro genotoxicity using the Ames test and chromosomal aberration assay. Impurity III at concentrations of 7.5-30 µg/mL had an aberration rate of over 5% with or without S-9 mix. Furthermore, impurity III at concentrations of 40-1000 µg/plate significantly increased the number of mutagenic colonies with or without S-9 mix. These results indicated that impurity III should be regulated to the limit of 0.01%.

The traditional herbal formulation, Jianpiyifei II, reduces pulmonary inflammation induced by influenza A virus and cigarette smoke in mice.

Chronic obstructive pulmonary disease (COPD) is a worldwide chronic inflammatory lung disease, and influenza A virus (IAV) infection is a common cause of acute exacerbations of COPD (AECOPD). Therefore, targeting viral infections represents a promising strategy to prevent the occurrence and development of inflammatory flare ups in AECOPD. Jianpiyifei II (JPYFII) is a traditional herbal medicine used in China to treat patients with COPD, and its clinical indications are not well understood. However, investigation of the anti-inflammatory effects and underlying mechanism using an animal model of smoking have been reported in a previous study by our group. In addition, some included herbs, such as Radix astragali and Radix aupleuri, were reported to exhibit antiviral effects. Therefore, the aim of the present study was to investigate whether JPYFII formulation relieved acute inflammation by clearing the IAV in a mouse model that was exposed to cigarette smoke experimentally. JPYFII formulation treatment during smoke exposure and IAV infection significantly reduced the number of cells observed in bronchoalveolar lavage fluid (BALF), expression of proinflammatory cytokines, chemokines, superoxide production, and viral load in IAV-infected and smoke-exposed mice. However, JPYFII formulation treatment during smoke exposure alone did not reduce the number of cells in BALF or the expression of Il-6, Tnf-a, and Il-1ß. The results demonstrated that JPYFII formulation exerted an antiviral effect and reduced the exacerbation of lung inflammation in cigarette smoke (CS)-exposed mice infected with IAV. Our results suggested that JPYFII formulation could potentially be used to treat patients with AECOPD associated with IAV infection.

Weipixiao attenuate early angiogenesis in rats with gastric precancerous lesions.

BACKGROUND: Angiogenesis is a pathobiological hallmark of gastric cancer. However, rare studies focus on angiogenesis in gastric precancerous lesions (GPL). Weipixiao (WPX), a Chinese herbal preparation, is proved clinically effective in treating GPL. Here, we evaluated WPX's anti-angiogenic potential for GPL, and also investigated the possibility of its anti-angiogenic mechanisms. METHODS: HPLC analysis was applied to screen the major chemical components of WPX. After modeling N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced GPL in male Sprague-Dawley rats, different doses of WPX were administrated orally for 10 weeks. Next, we performed histopathological examination using routine H&E staining and HID-AB-PAS staining. In parallel, we assessed angiogenesis revealed by microvessel density (MVD) using CD34 immunostaining, and subsequently observe microvessel ultrastructure in gastric mucosa under Transmission Electron Microscope. Finally, we detect expression of angiogenesis-associated markers VEGF and HIF-1α using immunohistochemistry. Moreover, mRNA expressions of ERK1, ERK2, Cylin D1 as well as HIF-1α in gastric mucosa were determined by quantitative real-time reverse transcription- polymerase chain reaction. RESULTS: We observed the appearance of active angiogenesis in GPL rats, and demonstrated that WPX could reduce microvascular abnormalities and attenuate early angiogenesis in most of GPL specimens with a concomitant regression of most intestinal metaplasia (IM) and a portion of gastric epithelial dysplasia (GED). In parallel, WPX could suppress HIF-1α mRNA expression (P < 0.01) as well as protein expression (although without statistical significance), and could markedly inhibit VEGF protein expression in GPL rats. Mechanistically, WPX intervention, especially at low dose, caused a significant decrease in the ERK1 and Cylin D1 mRNA levels. However, WPX might probably have no regulatory effect on ERK2 amplification. CONCLUSIONS: WPX could attenuate early angiogenesis and temper microvascular abnormalities in GPL rats. This might be partly achieved by inhibiting on the angiogenesis-associated markers HIF-1α and VEGF, and on the ERK1/Cylin D1 aberrant activation.

Astragaloside IV reverses MNNG-induced precancerous lesions of gastric carcinoma in rats: Regulation on glycolysis through miRNA-34a/LDHA pathway.

This study was designed to investigate the precancerous lesions of gastric carcinoma (PLGC)-reversing mechanisms of astragaloside IV (ASIV) in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced PLGC rats. All rats were sacrificed after 10-week treatment. Gastric tissue was analyzed by using histopathology and electron microscope. To be fully evidenced, LDHA, p53, TIGAR, MCT1, MCT4, HIF-1α, CD147, and miRNA-34a were detected by Western blotting and Real-time Quantitative polymerase chain reaction (RT-qPCR). As histopathology and electron microscope showed, it can be clearly observed that the area of dysplasia was reduced in ASIV groups, indicating that MNNG-induced PLGC was markedly reversed by ASIV. Moreover, compared with model group, a significant decrease in gene expressions of LDHA, MCT1, MCT4, HIF-1α, CD147, and TIGAR was observed whereas miRNA-34a level was increased in ASIV groups. A significant up-regulation induced by MNNG in protein levels of LDHA, MCT1, MCT4, HIF-1α, and CD147 was attenuated in rats treated with ASIV. In contrast, the decreased expression of TIGAR was restored by ASIV. Interestingly, up-regulation of p53 expression induced by MNNG was further increased in ASIV groups. In brief, these results implied that abnormal glycolysis was relieved by ASIV via regulation of the expressions of LDHA, p53, TIGAR, MCT1, MCT4, HIF-1α, CD147, and miRNA-34a.

Lineage tracing of Sox2-expressing progenitor cells in the mouse inner ear reveals a broad contribution to non-sensory tissues and insights into the origin of the organ of Corti.

The transcription factor Sox2 is both necessary and sufficient for the generation of sensory regions of the inner ear. It regulates expression of the Notch ligand Jag1 in prosensory progenitors, which signal to neighboring cells to up-regulate Sox2 and sustain prosensory identity. However, the expression pattern of Sox2 in the early inner ear is very broad, suggesting that Sox2-expressing progenitors form a wide variety of cell types in addition to generating the sensory regions of the ear. We used Sox2-CreER mice to follow the fates of Sox2-expressing cells at different stages in ear development. We find that Sox2-expressing cells in the early otocyst give rise to large numbers of non-sensory structures throughout the inner ear, and that Sox2 only becomes a truly prosensory marker at embryonic day (E)11.5. Our fate map reveals the organ of Corti derives from a central domain on the medial side of the otocyst and shows that a significant amount of the organ of Corti derives from a Sox2-negative population in this region.

Characterization of the transcriptome of nascent hair cells and identification of direct targets of the Atoh1 transcription factor.

Hair cells are sensory receptors for the auditory and vestibular system in vertebrates. The transcription factor Atoh1 is both necessary and sufficient for the differentiation of hair cells, and is strongly upregulated during hair-cell regeneration in nonmammalian vertebrates. To identify genes involved in hair cell development and function, we performed RNA-seq profiling of purified Atoh1-expressing hair cells from the neonatal mouse cochlea. We identified >600 enriched transcripts in cochlear hair cells, of which 90% have not been previously shown to be expressed in hair cells. We identified 233 of these hair cell genes as candidates to be directly regulated by Atoh1 based on the presence of Atoh1 binding sites in their regulatory regions and by analyzing Atoh1 ChIP-seq datasets from the cerebellum and small intestine. We confirmed 10 of these genes as being direct Atoh1 targets in the cochlea by ChIP-PCR. The identification of candidate Atoh1 target genes is a first step in identifying gene regulatory networks for hair-cell development and may inform future studies on the potential role of Atoh1 in mammalian hair cell regeneration.

Gene-gene and gene-sex epistatic interactions of DNMT1, DNMT3A and DNMT3B in autoimmune thyroid disease.

The aim of this study was to investigate the associations of DNA methyltransferases (DNMTs) polymorphisms with susceptibility to autoimmune thyroid diseases (AITDs) and to test gene-gene/gene-sex epistasis interactions. Eight single-nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A and DNMT3B were selected and genotyped by multiplex polymerase chain reaction combined with ligase detection reaction method (PCR-LDR). A total of 685 Graves' disease (GD) patients, 353 Hashimoto's thyroiditis (HT) patients and 909 healthy controls were included in the final analysis. Epistasis was tested by additive model, multiplicative model and general multifactor dimensionality reduction (general MDR). Rs2424913 (DNMT3B) and rs2228611 (DNMT1) were associated with susceptibility to AITD and GD in the dominant and overdominant model, respectively (rs2424913: P=0.009 for AITD, P=0.0041 for GD; rs2228611: P=0.035 for AITD, P=0.043 for GD). Multiplicative and multiple high dimensional gene-gene or gene-sex interactions were also observed in this study. We have found evidence for a potential role of rs2424913 (DNMT3B) and rs2228611 (DNMT1) in AITD susceptibility and identified novel gene-gene/gene-sex interactions in AITD. Our study may highlight sex and genes of DNMTs family as contributors to the pathogenesis of AITD.

Genome-wide DNA methylation analysis in Graves' disease.

As an autoimmune disease, Graves' disease (GD) is associated with many genetic and environmental risk factors. Although the exact mechanism remains unclear, epigenetic determinants, such as DNA methylation, are thought to contribute to the pathogenesis of GD. Here, we for the first time reported the DNA methylation pattern in GD through a high-throughput analysis. In order to investigate genome-wide DNA methylation profile of GD, methyl-DNA immunoprecipitation (MeDIP) and Nimblegen human DNA methylation 3 × 720 K promoter plus CpG island microarrays were used to identify differentially methylated regions (DMRs) from blood samples in GD patients. Quantitative methylation-specific PCR (qMSP) was used to validate the methylation state of candidate genes. Transcription level of each gene was estimated by quantitative real-time PCR (qRT-PCR). A total of 132 hypermethylated and 133 hypomethylated regions were identified in GD. The methylation of ICAM1 in GD patients and normal controls was significantly different (p<0.05). In the female group, significantly decreased methylation was observed in GD patients compared with normal controls (p<0.05). The transcription of ICAM1 at the mRNA level was significantly higher in GD patients compared with normal controls (p<0.05). Besides, the transcription of DNMT1 and MECP2 at the mRNA level was significantly decreased in GD patients compared with normal controls (p<0.05). Our findings revealed that the DNA methylation pattern in GD was distinct from that of controls. These results provided new molecular insights into the pathogenesis of GD.

Aberrant expression of miRNA and mRNAs in lesioned tissues of Graves' disease.

BACKGROUND AND AIMS: Abnormal microRNA (miRNA) expression is found in many diseases including autoimmune diseases. However, little is known about the role of miRNA regulation in Graves' disease (GD). Here, we simultaneously detected different expressions of miRNA and mRNAs in thyroid tissues via a high-throughput transcriptomics approach, known as microarray, in order to reveal the relationship between aberrant expression of miRNAs and mRNAs spectrum and GD. METHODS: Totally 7 specimens of thyroid tissue from 4 GD patients and 3 controls were obtained by surgery for microarray analysis. Then, 30 thyroid specimens (18 GD and 12 controls) were also collected for further validation by quantitative real-time PCR ( qRT-PCR ). RESULTS: Statistical analysis showed that the expressions of 5 specific miRNA were increased significantly while those of other 18 miRNA were decreased in thyroid tissue of GD patients (FC ≥ 1.3 or ≤ 0.77 and p<0.05). In addition, the transcription of 1271 mRNAs was up-regulated, while the expression of 777 mRNAs transcripts was down-regulated (FC ≥ 2.0 or ≤ 0.5 and p<0.05). Furthermore, integrated analysis of differentially expressed miRNA and their target mRNAs demonstrated that 2 miRNA (miR-22 and miR-183) were increased while their potential target mRNAs were decreased. 3 miRNA (miR-101, miR-197 and miR-660) were decreased while their potential target mRNAs were increased. The above findings from microarray screening were confirmed by qRT-PCR in more samples. The results were consistent with those observed in the microarray assays. CONCLUSION: Our study highlights the possibility that miRNA-target gene network may be involved in the pathogenesis of GD and could provide new insights into understanding the pathophysiological mechanisms of GD.

Conditional deletion of Atoh1 reveals distinct critical periods for survival and function of hair cells in the organ of Corti.

Atonal homolog1 (Atoh1) encodes a basic helix-loop-helix protein that is the first transcription factor to be expressed in differentiating hair cells. Previous work suggests that expression of Atoh1 in prosensory precursors is necessary for the differentiation and survival of hair cells, but it is not clear whether Atoh1 is required exclusively for these processes, or whether it regulates other functions later during hair cell maturation. We used EGFP-tagged Atoh1 knock-in mice to demonstrate for the first time that Atoh1 protein is expressed in hair cell precursors several days before the appearance of differentiated markers, but not in the broad pattern expected of a proneural gene. We conditionally deleted Atoh1 at different points in hair cell development and observe a rapid onset of hair cell defects, suggesting that the Atoh1 protein is unstable in differentiating hair cells and is necessary through an extended phase of their differentiation. Conditional deletion of Atoh1 reveals multiple functions in hair cell survival, maturation of stereociliary bundles, and auditory function. We show the presence of distinct critical periods for Atoh1 in each of these functions, suggesting that Atoh1 may be directly regulating many aspects of hair cell function. Finally, we show that the supporting cell death that accompanies loss of Atoh1 in hair cells is likely caused by the abortive trans-differentiation of supporting cells into hair cells. Together our data suggest that Atoh1 regulates multiple aspects of hair cell development and function.

Comparative transcriptomic analysis revealed important processes underlying the static magnetic field effects on Arabidopsis.

Static magnetic field (SMF) plays important roles in various biological processes of many organisms including plants, though the molecular mechanism remains largely unclear. Here in this study, we evaluated different magnetic setups to test their effects on growth and development on Arabidopsis (Arabidopsis thaliana), and discovered that plant growth was significantly enhanced by inhomogeneous SMF generated by a regular triangular prism magnet perpendicular to the direction of gravity. Comparative transcriptomic analysis revealed that auxin synthesis and signal transduction genes were upregulated by SMF exposure. SMF also facilitated plants to maintain the iron homeostasis. The expression of iron metabolism-related genes was downregulated by SMF, however, the iron content in plant tissues remains relatively unchanged. Furthermore, SMF exposure also helped the plants to reduce ROS level and synergistically maintain the oxidant balance by enhanced activity of antioxidant enzymes and accumulation of nicotinamide. Taken together, our data suggested that SMF is involved in regulating the growth and development of Arabidopsis thaliana through maintaining iron homeostasis and balancing oxidative stress, which could be beneficial for plant survival and growth. The work presented here would extend our understanding of the mechanism and the regulatory network of how magnetic field affects the plant growth, which would provide insights into the development of novel plant synthetic biology technologies to engineer stress-resistant and high-yielding crops.

A new generation of structural biologists in China.

We have asked young scientists who spoke at our recent Cell Symposium "Structural biology from the nanoscale to cellular mesoscale" in Huangshan, China to tell us more about themselves and their exciting research in this collection of Voices.

On the evolutionary trail of MagRs.

Magnetic sense, or termed magnetoreception, has evolved in a broad range of taxa within the animal kingdom to facilitate orientation and navigation. MagRs, highly conserved A-type iron-sulfur proteins, are widely distributed across all phyla and play essential roles in both magnetoreception and iron-sulfur cluster biogenesis. However, the evolutionary origins and functional diversification of MagRs from their prokaryotic ancestor remain unclear. In this study, MagR sequences from 131 species, ranging from bacteria to humans, were selected for analysis, with 23 representative sequences covering species from prokaryotes to Mollusca, Arthropoda, Osteichthyes, Reptilia, Aves, and mammals chosen for protein expression and purification. Biochemical studies revealed a gradual increase in total iron content in MagRs during evolution. Three types of MagRs were identified, each with distinct iron and/or iron-sulfur cluster binding capacity and protein stability, indicating continuous expansion of the functional roles of MagRs during speciation and evolution. This evolutionary biochemical study provides valuable insights into how evolution shapes the physical and chemical properties of biological molecules such as MagRs and how these properties influence the evolutionary trajectories of MagRs.