Targeting c-Myc transactivation by LMNA inhibits tRNA processing essential for malate-aspartate shuttle and tumour progression.

BACKGROUND: A series of studies have demonstrated the emerging involvement of transfer RNA (tRNA) processing during the progression of tumours. Nevertheless, the roles and regulating mechanisms of tRNA processing genes in neuroblastoma (NB), the prevalent malignant tumour outside the brain in children, are yet unknown. METHODS: Analysis of multi-omics results was conducted to identify crucial regulators of downstream tRNA processing genes. Co-immunoprecipitation and mass spectrometry methods were utilised to measure interaction between proteins. The impact of transcriptional regulators on expression of downstream genes was measured by dual-luciferase reporter, chromatin immunoprecipitation, western blotting and real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) methods. Studies have been conducted to reveal impact and mechanisms of transcriptional regulators on biological processes of NB. Survival differences were analysed using the log-rank test. RESULTS: c-Myc was identified as a transcription factor driving tRNA processing gene expression and subsequent malate-aspartate shuttle (MAS) in NB cells. Mechanistically, c-Myc directly promoted the expression of glutamyl-prolyl-tRNA synthetase (EPRS) and leucyl-tRNA synthetase (LARS), resulting in translational up-regulation of glutamic-oxaloacetic transaminase 1 (GOT1) as well as malate dehydrogenase 1 (MDH1) via inhibiting general control nonrepressed 2 or activating mechanistic target of rapamycin signalling. Meanwhile, lamin A (LMNA) inhibited c-Myc transactivation via physical interaction, leading to suppression of MAS, aerobic glycolysis, tumourigenesis and aggressiveness. Pre-clinically, lobeline was discovered as a LMNA-binding compound to facilitate its interaction with c-Myc, which inhibited aminoacyl-tRNA synthetase expression, MAS and tumour progression of NB, as well as growth of organoid derived from c-Myc knock-in mice. Low levels of LMNA or elevated expression of c-Myc, EPRS, LARS, GOT1 or MDH1 were linked to a worse outcome and a shorter survival time of clinical NB patients. CONCLUSIONS: These results suggest that targeting c-Myc transactivation by LMNA inhibits tRNA processing essential for MAS and tumour progression.

Autophagy-related protein 5 (ATG5) interacts with bone marrow stromal cell antigen 2 (BST2) to stimulate HBV replication through antagonizing the antiviral activity of BST2.

Hepatitis B virus (HBV) infection is a major global health burden with 820 000 deaths per year. In our previous study, we found that the knockdown of autophagy-related protein 5 (ATG5) significantly upregulated the interferon-stimulated genes (ISGs) expression to exert the anti-HCV effect. However, the regulation of ATG5 on HBV replication and its underlying mechanism remains unclear. In this study, we screened the altered expression of type I interferon (IFN-I) pathway genes using RT² Profiler™ PCR array following ATG5 knock-down and we found the bone marrow stromal cell antigen 2 (BST2) expression was significantly increased. We then verified the upregulation of BST2 by ATG5 knockdown using RT-qPCR and found that the knockdown of ATG5 activated the Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway. ATG5 knockdown or BST2 overexpression decreased Hepatitis B core Antigen (HBcAg) protein, HBV DNA levels in cells and supernatants of HepAD38 and HBV-infected NTCP-HepG2. Knockdown of BST2 abrogated the anti-HBV effect of ATG5 knockdown. Furthermore, we found that ATG5 interacted with BST2, and further formed a ternary complex together with HBV-X (HBx). In conclusion, our finding indicates that ATG5 promotes HBV replication through decreasing BST2 expression and interacting with it directly to antagonize its antiviral function.

The Numerical Simulations and Experimental Study of an 8-Inch SiC Single Crystal with Reduced BPD Density.

The basal plane dislocation (BPD) density is one of the most important defects affecting the application of SiC wafers. In this study, numerical simulations and corresponding experiments were conducted to investigate the influence of cooling processes, seed-bonding methods, and graphite crucible materials on the BPD density in an 8-inch N-type 4H-SiC single crystal grown by the physical vapor transport (PVT) method. The results showed that the BPD density could be effectively reduced by increasing the cooling rate, optimizing the seed-bonding method, and adopting a graphite crucible with a similar coefficient of thermal expansion as the SiC single crystal. The BPD density in the experiments showed that a high cooling rate reduced the BPD density from 4689 cm-2 to 2925 cm-2; optimization of the seed-bonding method decreased the BPD density to 1560 cm-2. The BPD density was further reduced to 704 cm-2 through the adoption of a graphite crucible with a smaller thermal expansion coefficient.

Cascaded signal amplification strategy for ultra-specific, ultra-sensitive, and visual detection of Shigella flexneri.

Pathogen infections including Shigella flexneri have posed a significant threat to human health for numerous years. Although culturing and qPCR were the gold standards for pathogen detection, time-consuming and instrument-dependent restrict their application in rapid diagnosis and economically less-developed regions. Thus, it is urgently needed to develop rapid, simple, sensitive, accurate, and low-cost detection methods for pathogen detection. In this study, an immunomagnetic beads-recombinase polymerase amplification-CRISPR/Cas12a (IMB-RPA-CRISPR/Cas12a) method was built based on a cascaded signal amplification strategy for ultra-specific, ultra-sensitive, and visual detection of S. flexneri in the laboratory. Firstly, S. flexneri was specifically captured and enriched by IMB (Shigella antibody-coated magnetic beads), and the genomic DNA was released and used as the template in the RPA reaction. Then, the RPA products were mixed with the pre-loaded CRISPR/Cas12a for fluorescence visualization. The results were observed by naked eyes under LED blue light, with a sensitivity of 5 CFU/mL in a time of 70 min. With no specialized equipment or complicated technical requirements, the IMB-RPA-CRISPR/Cas12a diagnostic method can be used for visual, rapid, and simple detection of S. flexneri and can be easily adapted to monitoring other pathogens.

Precise Capture and Dynamic Release of Circulating Liver Cancer Cells with Dual-Histidine-Based Cell Imprinted Hydrogels.

Circulating tumor cells (CTCs) detection presents significant advantages in diagnosing liver cancer due to its noninvasiveness, real-time monitoring, and dynamic tracking. However, the clinical application of CTCs-based diagnosis is largely limited by the challenges of capturing low-abundance CTCs within a complex blood environment while ensuring them alive. Here, an ultrastrong ligand, l-histidine-l-histidine (HH), specifically targeting sialylated glycans on the surface of CTCs, is designed. Furthermore, HH is integrated into a cell-imprinted polymer, constructing a hydrogel with precise CTCs imprinting, high elasticity, satisfactory blood compatibility, and robust anti-interference capacities. These features endow the hydrogel with excellent capture efficiency (>95%) for CTCs in peripheral blood, as well as the ability to release CTCs controllably and alive. Clinical tests substantiate the accurate differentiation between liver cancer, cirrhosis, and healthy groups using this method. The remarkable diagnostic accuracy (94%), lossless release of CTCs, material reversibility, and cost-effectiveness ($6.68 per sample) make the HH-based hydrogel a potentially revolutionary technology for liver cancer diagnosis and single-cell analysis.

Metagenomic analysis of individual mosquito viromes reveals the geographical patterns and drivers of viral diversity.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.

Total Infectome Characterization of Respiratory Infections during the 2022-23 COVID-19 Outbreak in China Revealed Extensive Coinfections with Links to SARS-CoV-2 Status, Age, and Disease Severity.

Between 7 December 2022 and 28 February 2023, China experienced a new wave of COVID-19 that swept across the entire country and resulted in an increasing amount of respiratory infections and hospitalizations. The purpose of this study is to reveal the intensity and composition of coinfecting microbial agents. In total, 196 inpatients were recruited from The Third People's Hospital of Shenzhen, and 169 respiratory and 73 blood samples were collected for metagenomic next-generation sequencing. The total "Infectome" was characterized and compared across different groups defined by the SARS-CoV-2 detection status, age groups, and severity of disease. Our results revealed a total of 22 species of pathogenic microbes (4 viruses, 13 bacteria, and 5 fungi), and more were discovered in the respiratory tract than in blood. The diversity of the total infectome was highly distinguished between respiratory and blood samples, and it was generally higher in patients that were SARS-CoV-2-positive, older in age, and with more severe disease. At the individual pathogen level, HSV-1 seemed to be the major contributor to these differences observed in the overall comparisons. Collectively, this study reveals the highly complex respiratory infectome and high-intensity coinfection in patients admitted to the hospital during the period of the 2023 COVID-19 pandemic in China.

A Fast-Charge Graphite Anode with a Li-Ion-Conductive, Electron/Solvent-Repelling Interface.

Graphite has been serving as the key anode material of rechargeable Li-ion batteries, yet is difficultly charged within a quarter hour while maintaining stable electrochemistry. In addition to a defective edge structure that prevents fast Li-ion entry, the high-rate performance of graphite could be hampered by co-intercalation and parasitic reduction of solvent molecules at anode/electrolyte interface. Conventional surface modification by pitch-derived carbon barely isolates the solvent and electrons, and usually lead to inadequate rate capability to meet practical fast-charge requirements. Here we show that, by applying a MoOx-MoNx layer onto graphite surface, the interface allows fast Li-ion diffusion yet blocks solvent access and electron leakage. By regulating interfacial mass and charge transfer, the modified graphite anode delivers a reversible capacity of 340.3 mAh g-1 after 4000 cycles at 6 C, showing promises in building 10-min-rechargeable batteries with a long operation life.

Combining dredging with modified zeolite thin-layer capping to control nitrogen release from eutrophic lake sediment.

Dredging is widely used to control internal sediment nitrogen (N) pollution during eutrophic lake restoration. However, the effectiveness of dredging cannot be maintained for long periods during seasonal temperature variations. This study used modified zeolite (MZ) as a thin-layer capping material to enhance dredging efficiency during a year-long field sediment core incubation period. Our results showed that dredging alone more effectively reduced pore water N, N flux, and sediment N content than MZ capping but showed more dramatic changes during the warm seasons. The N flux in dredged sediment in summer was 1.8 and 2.5 times that in spring and autumn, respectively, indicating a drastic N regeneration process in the short term. In contrast, the combination method reduced the extra 10% pore water N, 22% N flux, and 8% sediment organic N content compared with dredging alone and maintained high stability during seasonal changes. The results indicated that the addition of MZ to the surface of dredged sediment not only enhanced the control effect of dredging by its adsorption capacity but may also smooth the N regeneration process via successive accumulation (in the channel of the material) and activation of bacteria for months, which was evidenced by the variation in microbial diversity in the MZ treatment. As a result, the combination of dredging with modified zeolite simultaneously enhanced the efficiency and stability of the single dredging method in controlling sediment N content and its release, exhibiting great prospects for long-term application in eutrophic lakes with severe pollution from internal N loading.

Automating the Human Connectome Project's Temporal ICA Pipeline.

Functional magnetic resonance imaging (fMRI) data are dominated by noise and artifacts, with only a small fraction of the variance relating to neural activity. Temporal independent component analysis (tICA) is a recently developed method that enables selective denoising of fMRI artifacts related to physiology such as respiration. However, an automated and easy to use pipeline for tICA has not previously been available; instead, two manual steps have been necessary: 1) setting the group spatial ICA dimensionality after MELODIC's Incremental Group-PCA (MIGP) and 2) labeling tICA components as artifacts versus signals. Moreover, guidance has been lacking as to how many subjects and timepoints are needed to adequately re-estimate the temporal ICA decomposition and what alternatives are available for smaller groups or even individual subjects. Here, we introduce a nine-step fully automated tICA pipeline which removes global artifacts from fMRI dense timeseries after sICA+FIX cleaning and MSMAll alignment driven by functionally relevant areal features. Additionally, we have developed an automated "reclean" Pipeline for improved spatial ICA (sICA) artifact removal. Two major automated components of the pipeline are 1) an automatic group spatial ICA (sICA) dimensionality selection for MIGP data enabled by fitting multiple Wishart distributions; 2) a hierarchical classifier to distinguish group tICA signal components from artifactual components, equipped with a combination of handcrafted features from domain expert knowledge and latent features obtained via self-supervised learning on spatial maps. We demonstrate that the dimensionality estimated for the MIGP data from HCP Young Adult 3T and 7T datasets is comparable to previous manual tICA estimates, and that the group sICA decomposition is highly reproducible. We also show that the tICA classifier achieved over 0.98 Precision-Recall Area Under Curve (PR-AUC) and that the correctly classified components account for over 95% of the tICA-represented variance on multiple held-out evaluation datasets including the HCP-Young Adult, HCP-Aging and HCP-Development datasets under various settings. Our automated tICA pipeline is now available as part of the HCP pipelines, providing a powerful and user-friendly tool for the neuroimaging community.

Hsa_circ_0007321 regulates Zika virus replication through miR-492/NFKBID/NF-κB signaling pathway.

IMPORTANCE: Over the past decade, increasing evidence has shown that circular RNAs (circRNAs) play important regulatory roles in viral infection and host antiviral responses. However, reports on the role of circRNAs in Zika virus (ZIKV) infection are limited. In this study, we identified 45 differentially expressed circRNAs in ZIKV-infected A549 cells by RNA sequencing. We clarified that a downregulated circRNA, hsa_circ_0007321, regulates ZIKV replication through targeting of miR-492 and the downstream gene NFKBID. NFKBID is a negative regulator of nuclear factor-κB (NF-κB), and we found that inhibition of the NF-κB pathway promotes ZIKV replication. Therefore, this finding that hsa_circ_0007321 exerts its regulatory role on ZIKV replication through the miR-492/NFKBID/NF-κB signaling pathway has implications for the development of strategies to suppress ZIKV and possibly other viral infections.

Sodium salicylate ameliorates exercise-induced muscle damage in mice by inhibiting NF-kB signaling.

BACKGROUND: Eccentric muscle contraction can cause muscle damage, which reduces the efficiency of exercise. Previous evidence suggested that Sodium salicylate (SS) could improve the repair of aged muscle. This study intends to investigate whether SS can impact skeletal muscle damage caused by eccentric exercise. METHODS: Eccentric treadmill exercise was performed to induce muscle damage in mice. Plasma levels of muscle damage markers were estimated. RT-qPCR was employed for detecting mRNA levels of proinflammatory mediators in murine gastrocnemius muscle. Immunofluorescence staining of laminin/DAPI was utilized for quantifying centrally nucleated myofibers in the gastrocnemius muscle. Western blotting was implemented to examine protein levels of mitsugumin 53 (MG53), matrix metalloproteinase (MMP)-2/9, and NF-κB signaling-related markers. RESULTS: SS administration reduced muscle damage marker production in the plasma and decreased the levels of proinflammatory mediators, MG53 and MMP-2/9 in mice after exercise. SS alleviated the severity of muscle damage in the gastrocnemius of mice after eccentric exercise. SS blocked NF-κB signaling pathway in the gastrocnemius muscle. CONCLUSION: SS administration ameliorates skeletal muscle damage caused by eccentric exercise in the mouse model.

circ-hnRNPU inhibits NONO-mediated c-Myc transactivation and mRNA stabilization essential for glycosylation and cancer progression.

BACKGROUND: Recent evidence reveals the emerging functions of circular RNA (circRNA) and protein glycosylation in cancer progression. However, the roles of circRNA in regulating glycosyltransferase expression in gastric cancer remain to be determined. METHODS: Circular RNAs (circRNAs) were validated by Sanger sequencing. Co-immunoprecipitation, mass spectrometry, and RNA sequencing assays were applied to explore protein interaction and target genes. Gene expression regulation was observed by chromatin immunoprecipitation, RNA immunoprecipitation, dual-luciferase reporter, real-time quantitative RT-PCR, and western blot assays. Gain- and loss-of-function studies were performed to observe the impacts of circRNA and its partners on the glycosylation, growth, invasion, and metastasis of gastric cancer cells. RESULTS: Circ-hnRNPU, an exonic circRNA derived from heterogenous nuclear ribonuclear protein U (hnRNPU), was identified to exert tumor suppressive roles in protein glycosylation and progression of gastric cancer. Mechanistically, circ-hnRNPU physically interacted with non-POU domain containing octamer binding (NONO) protein to induce its cytoplasmic retention, resulting in down-regulation of glycosyltransferases (GALNT2, GALNT6, MGAT1) and parental gene hnRNPU via repression of nuclear NONO-mediated c-Myc transactivation or cytoplasmic NONO-facilitated mRNA stability. Rescue studies indicated that circ-hnRNPU inhibited the N- and O-glycosylation, growth, invasion, and metastasis of gastric cancer cells via interacting with NONO protein. Pre-clinically, administration of lentivirus carrying circ-hnRNPU suppressed the protein glycosylation, tumorigenesis, and aggressiveness of gastric cancer xenografts. In clinical cases, low circ-hnRNPU levels and high NONO or c-Myc expression were associated with poor survival outcome of gastric cancer patients. CONCLUSIONS: These findings indicate that circ-hnRNPU inhibits NONO-mediated c-Myc transactivation and mRNA stabilization essential for glycosylation and cancer progression.

Metagenomic analysis of individual mosquitos reveals the ecology of insect viruses.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Using a meta-transcriptomic approach, we analysed the virome of 2,438 individual mosquitos (79 species), spanning ~4000 km along latitudes and longitudes in China. From these data we identified 393 core viral species associated with mosquitos, including seven (putative) arbovirus species. We identified potential species and geographic hotspots of viral richness and arbovirus occurrence, and demonstrated that host phylogeny had a strong impact on the composition of individual mosquito viromes. Our data revealed a large number of viruses shared among mosquito species or genera, expanding our knowledge of host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, possibly facilitated by long-distance mosquito migrations. Together, our results greatly expand the known mosquito virome, linked the viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the ecology of viruses of insect vectors.

[Regularity of ventilator-associated pneumonia induced by three common pathogens].

OBJECTIVE: To investigate the incidence and infection regularity of ventilator-associated pneumonia (VAP) in patients undergoing tracheal intubation and to provide reference for the prevention and treatment of VAP infection in the future. METHODS: A retrospective study was conducted to collect the microbial data of airway secretion cultures from 72 patients with endotracheal intubation admitted to the emergency ward of Shanghai Fifth People's Hospital from May 2020 to February 2021, and the species of microorganisms and intubation time were statistically analyzed. RESULTS: Among 72 patients with endotracheal intubation, males were more than females (58.33% vs. 41.67%); Patients over 60 years old accounted for 90.28%; pneumonia was the main primary disease, accounting for 58.33%. Pathogenic tests showed that: (1) 72 patients were infected with Acinetobacter baumannii (AB), Klebsiella pneumoniae (KP), and Pseudomonas aeruginosa (PA) 48 hours after intubation, 51.39% (37/72), 27.78% (20/72), and 26.39% (19/72), respectively. The infection rate of AB was significantly higher than that of KP and PA. Within 48 hours of intubation, the infection rates of AB, KP, and PA were 20.83% (15/72), 13.89% (10/72), and 4.17% (3/72), respectively. Of the 42 patients with primary pneumonia, 61.90% (26/42) were infected with one or more of the three pathogenic bacteria AB, KP, and PA 48 hours after intubation, indicating a change in the etiology of the pathogenic bacteria, with the main pathogenic bacteria transitioning from other pathogenic bacteria to AB, KP, and PA. (2) AB, KP, and PA were prone to cause late onset VAP (i.e., intubation ≥ 5 days). Respectively, among VAP patients infected with AB, late onset VAP accounted for 59.46% (22/37). Among patients infected with KP, 75.00% (15/20) had late onset VAP. Among patients infected with PA, late onset VAP accounted for 94.74% (18/19), indicating a higher proportion of late onset VAP caused by PA and KP. (3) Infection was closely related to intubation time, and the pipeline can be replaced according to the peak period of infection. AB and KP infections peaked within 4 days after intubation, reaching 57.69% (30/52) and 50.00% (15/30), respectively. It is recommended to replace the tubes or undergo sensitive antimicrobial therapy around 3-4 days after starting the machine. The proportion of PA infection after 7 days of intubation was 72.73% (16/22), and it was considered to replace the pipeline after 7 days. (4) Most of the three pathogenic bacteria, AB, KP, and PA were carbapenem resistant pathogens with multiple drug resistance. Except for PA, the infection rate of carbapenem resistant bacteria (CRAB, CRKP) was significantly higher than that of non-carbapenem resistant bacteria (AB, KP), accounting for 86.54% (45/52) and 66.67% (20/30) of the corresponding infection cases, respectively, while CRPA only accounts for 18.18% (4/22). CONCLUSIONS: The main differences in VAP infection caused by AB, KP, and PA pathogens are infection time, infection probability, and carbapenem resistance. Targeted prevention and treatment measures can be implemented for patients with intubation.

Single-cell sequencing in primary intraocular tumors: understanding heterogeneity, the microenvironment, and drug resistance.

Retinoblastoma (RB) and uveal melanoma (UM) are the most common primary intraocular tumors in children and adults, respectively. Despite continued increases in the likelihood of salvaging the eyeball due to advancements in local tumor control, prognosis remains poor once metastasis has occurred. Traditional sequencing technology obtains averaged information from pooled clusters of diverse cells. In contrast, single-cell sequencing (SCS) allows for investigations of tumor biology at the resolution of the individual cell, providing insights into tumor heterogeneity, microenvironmental properties, and cellular genomic mutations. SCS is a powerful tool that can help identify new biomarkers for diagnosis and targeted therapy, which may in turn greatly improve tumor management. In this review, we focus on the application of SCS for evaluating heterogeneity, microenvironmental characteristics, and drug resistance in patients with RB and UM.

The impact of subclinical hypothyroidism on growth and development in infants and young children aged 0 to 5 years.

INTRODUCTION: The objective was to investigate the growth and development of infants and young children with mild subclinical hypothyroidism aged 0 to 5 years, especially those aged 0 to 2 years. MATERIAL AND METHODS: The study was a retrospective analysis of the birth status, physical growth, and neuromotor development of patients aged 0 to 5 years, who were diagnosed with subclinical hypothyroidism during newborn screening (NBS) in Zhongshan between 2016 and 2019. Based on preliminary results, we compared 3 groups: with thyroid-stimulating factor (TSH) value of 5-10 mIU/L (442 cases), TSH value of 10-20 mIU/L (208 cases), and TSH above 20 mIU/L (77 cases). Patients with TSH value above 5 mIU/L were called back for repeat testing and were divided into 4 groups as follows: mild subclinical hypothyroidism group 1 with a TSH value of 5-10 mIU/L in both initial screening and repeat testing; mild subclinical hypothyroidism group 2 with TSH value above 10 mIU/L in initial screening; and TSH value of 5-10 mIU/L in repeat testing; the severe subclinical hypothyroidism group with TSH value of 10-20 mIU/L in both the initial screening and repeat testing and the congenital hypothyroidism group. RESULTS: There were no significant differences in the maternal age, type of delivery, gender, length, and weight at birth between the preliminary groups; however, the gestational age at birth was significantly different (F = 5.268, p = 0.005). The z-score for length at birth was lower in the congenital hypothyroidism group compared to the other 3 groups but showed no difference at 6 months of age. The z-score for length in mild subclinical hypothyroidism group 2 was lower compared to the other 3 groups but showed no difference at 2-5 years of age. At 2 years of age there was no significant difference in the developmental quotient (DQ) of the Gesell Developmental Scale between the groups. CONCLUSION: The gestational age at birth affected the neonatal TSH level. Intrauterine growth in infants with congenital hypothyroidism was retarded compared to that of infants with subclinical hypothyroidism. Neonates with a TSH value of 10-20 mIU/L in the initial screening and a TSH value of 5-10 mIU/L in the repeat testing showed developmental delay at 18 months but caught up at age 2 years. There was no difference in neuromotor development between the groups. Levothyroxine in patients with mild subclinical hypothyroidism is not required, but we recommend that the growth and development of such infants and young children continues to be monitored.

LSM14B is an Oocyte-Specific RNA-Binding Protein Indispensable for Maternal mRNA Metabolism and Oocyte Development in Mice.

Mammalian oogenesis features reliance on the mRNAs produced and stored during early growth phase. These are essential for producing an oocyte competent to undergo meiotic maturation and embryogenesis later when oocytes are transcriptionally silent. The fate of maternal mRNAs hence ensures the success of oogenesis and the quality of the resulting eggs. Nevertheless, how the fate of maternal mRNAs is determined remains largely elusive. RNA-binding proteins (RBPs) are crucial regulators of oogenesis, yet the identity of the full complement of RBPs expressed in oocytes is unknown. Here, a global view of oocyte-expressed RBPs is presented: mRNA-interactome capture identifies 1396 RBPs in mouse oocytes. An analysis of one of these RBPs, LSM family member 14 (LSM14B), demonstrates that this RBP is specific to oocytes and associated with many networks essential for oogenesis. Deletion of Lsm14b results in female-specific infertility and a phenotype characterized by oocytes incompetent to complete meiosis and early embryogenesis. LSM14B serves as an interaction hub for proteins and mRNAs throughout oocyte development and regulates translation of a subset of its bound mRNAs. Therefore, RNP complexes tethered by LSM14B are found exclusively in oocytes and are essential for the control of maternal mRNA fate and oocyte development.

Reconstruction of Solid Electrolyte Interphase with SrI2 Reactivates Dead Li for Durable Anode-Free Li-Metal Batteries.

Without excess Li, anode-free Li-metal batteries (AFLMBs) have been proposed as the most likely solution to realizing highly-safe and cost-effective Li-metal batteries. Nevertheless, short cyclic life puzzles conventional AFLMBs due to anodic dead Li accumulation with a local current concentration induced by irreversible electrolyte depletion, insufficient active Li reservoir and slow Li+ transfer at the solid electrolyte interphase (SEI). Herein, SrI2 is introduced into carbon paper (CP) current collector to effectively suppress dead Li through synergistic mechanisms including reversible I- /I3 - redox reaction to reactivate dead Li, dielectric SEI surface with SrF2 and LiF to prevent electrolyte decomposition and highly ionic conductive (3.488 mS cm-1 ) inner layer of SEI with abundant LiI to enable efficient Li+ transfer inside. With the SrI2 -modified current collector, the NCM532/CP cell delivers unprecedented cyclic performances with a capacity of 129.2 mAh g-1 after 200 cycles.

Functionalized protein microparticles targeting hACE2 as a novel preventive strategy for SARS-CoV-2 infection.

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), resulting in a serious burden on public health and social economy worldwide. SARS-CoV-2 infection is mainly initialized in the nasopharyngeal cavity through the binding of viral spike (S) protein to human angiotensin-converting enzyme 2 (hACE2) receptors which are widely expressed in many human cells. Thus, blockade of the interaction between viral S protein and hACE2 receptor in the primary entry site is a promising prevention strategy for the management of COVID-19. Here we showed protein microparticles (PMPs) decorated with hACE2 could bind and neutralize SARS-CoV-2 S protein-expressing pseudovirus (PSV) and protect host cells from infection in vitro. In the hACE2 transgenic mouse model, administration of intranasal spray with hACE2-decorated PMPs markedly decreased the viral load of SARS-CoV-2 in the lungs though the inflammation was not attenuated significantly. Our results provided evidence for developing functionalized PMPs as a potential strategy for preventing emerging air-borne infectious pathogens, such as SARS-CoV-2 infection.