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Background Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by mutations within the dystrophin gene. DMD is characterized by progressive skeletal muscle degeneration and atrophy and progressive cardiomyopathy. It has been observed the severity of cardiomyopathy varies in patients with DMD. Methods and Results A cohort of male patients with DMD and female DMD carriers underwent whole exome sequencing. Potential risk factor variants were identified according to their functional annotations and frequencies. Cardiac function of 15 male patients with DMD was assessed by cardiac magnetic resonance imaging, and various cardiac magnetic resonance imaging parameters and circulating biomarkers were compared between genotype groups. Five subjects carrying potential risk factor variants in the cystic fibrosis transmembrane regulator gene demonstrated lower left ventricular ejection fraction, larger left ventricular end-diastolic volume, and higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels compared with 10 subjects who did not carry the potential risk factor variants (P=0.023, 0.019 and 0.028, respectively). Conclusions This study revealed heterozygous cystic fibrosis transmembrane regulator gene missense variants were associated with worse cardiac function in patients with DMD. The cystic fibrosis transmembrane regulator gene may serve as a genetic modifier that accounts for more severe cardiomyopathy in patients with DMD, who would require more aggressive management of the cardiomyopathy.

Single-cell ATAC-seq (scATAC-seq) profiles the chromatin accessibility landscape at single cell level, thus revealing cell-to-cell variability in gene regulation. However, the high dimensionality and sparsity of scATAC-seq data often complicate the analysis. Here, we introduce a method for analyzing scATAC-seq data, called Single-Cell ATAC-seq analysis via Latent feature Extraction (SCALE). SCALE combines a deep generative framework and a probabilistic Gaussian Mixture Model to learn latent features that accurately characterize scATAC-seq data. We validate SCALE on datasets generated on different platforms with different protocols, and having different overall data qualities. SCALE substantially outperforms the other tools in all aspects of scATAC-seq data analysis, including visualization, clustering, and denoising and imputation. Importantly, SCALE also generates interpretable features that directly link to cell populations, and can potentially reveal batch effects in scATAC-seq experiments.

Carbon nanotubes (CNTs) are promising blocks for building advanced yarns with unique structural and functional attributes. However, the complexity of fabrication and high cost has hindered the widespread adoption of CNT yarns. In this study, a rapid and continuous twisting wet spun yarn strategy to produce highly densified CNT yarns is presented. The method involves effectively dispersing CNTs in the surfactant dispersion, swiftly removing the surfactant in the coagulation bath and twisting treatment to effectively improve the density of yarn and the orientation of CNT. Detailed characterizations on the influence of each spinning conditions reveal that twisting treatment significantly enhances the packing density of yarns, improves the orientation of CNTs, and mitigates the impact of impurities on conductivity. The resulting CNT yarns exhibit a remarkable tensile strength of 600 MPa, a Young's modulus of ≈40 GPa, and a high conductivity of 8990 S cm−1. When utilized as a yarn heater, the CNT yarn demonstrates an ultra‐fast electrothermal response of over 1000 °C s−1 at a low operating voltage of 5 V. Impressively, the mechanical properties of CNT yarns show good stability during heating. This study provides a perspective of structural engineering for the large‐scale preparation of high‐performance CNT yarns. [ABSTRACT FROM AUTHOR]

Multiple genetic loci have been reported for progeroid syndromes. However, the molecular defects in some extremely rare forms of progeria have yet to be elucidated. Here, we report a 21-year-old man of Chinese ancestry who has an autosomal recessive form of progeria, characterized by severe dwarfism, mandibular hypoplasia, hyperopia, and partial lipodystrophy. Analyses of exome sequencing data from the entire family revealed only 1 rare homozygous missense variant (c.86C>T; p.Pro29Leu) in TOMM7 in the proband, while the parents and 2 unaffected siblings were heterozygous for the variant. TOMM7, a nuclear gene, encodes a translocase in the outer mitochondrial membrane. The TOMM complex makes up the outer membrane pore, which is responsible for importing many preproteins into the mitochondria. A proteomic comparison of mitochondria from control and proband-derived cultured fibroblasts revealed an increase in abundance of several proteins involved in oxidative phosphorylation, as well as a reduction in abundance of proteins involved in phospholipid metabolism. We also observed elevated basal and maximal oxygen consumption rates in the fibroblasts from the proband as compared with control fibroblasts. We concluded that altered mitochondrial protein import due to biallelic loss-of-function TOMM7 can cause severe growth retardation and progeroid features., Introduction In the last 2 decades, considerable progress has been made in identifying the molecular genetic basis of several progeroid syndromes, including mandibuloacral dysplasia (MAD), mandibular hypoplasia, deafness and progeroid [...]

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in Japan for adult patients with plaque (PP), generalized pustular (GPP), and erythrodermic (EP) psoriasis who have had an inadequate response to conventional systemic therapies. This approval is based on results from the global phase 3 POETYK PSO‐1 and PSO‐2 trials in which deucravacitinib was associated with significantly improved efficacy outcomes compared with placebo in adults with moderate to severe plaque psoriasis, and results described here from POETYK PSO‐4, an open‐label, single‐arm, phase 3 trial (NCT03924427), which evaluated the efficacy and safety of deucravacitinib 6 mg once daily in adult Japanese patients with PP, GPP, or EP. The coprimary endpoints were the proportion of patients achieving a ≥75% reduction from baseline in the Psoriasis Area and Severity Index (PASI 75) and a static Physician's Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1) with at least a two‐point improvement from baseline at week 16. Nonresponder imputation was used for missing data. Efficacy responses, adverse events (AEs), and serious AEs (SAEs) were recorded for up to 52 weeks. Seventy‐four patients were treated (PP, n = 63; GPP, n = 3; EP, n = 8). At week 16, 76.2%, 66.7%, and 37.5% of patients with PP, GPP, and EP, respectively, had achieved PASI 75, and 82.5%, 0.0%, and 50.0% had achieved sPGA 0/1. Responses were overall maintained through week 52. AEs occurred in 74.6% of patients with PP, 100% of patients with GPP, and 87.5% of patients with EP. The most common AEs were nasopharyngitis and acne. Rates of SAEs and discontinuations were low. There were no deaths. Deucravacitinib was effective and well tolerated in Japanese patients with moderate to severe PP and in a limited number of patients with GPP or EP. [ABSTRACT FROM AUTHOR]

Zinc oxide (ZnO) has been widely acknowledged as a highly effective photocatalyst for the degradation of organic pollutants. In this study, we presented silver nanoparticles (AgNPs) embedded ZnO foam photocatalyst (Ag−ZnO) on glass substrates by the chemical bath in‐situ co‐deposition method. Our findings demonstrat that at low Ag‐loading content, metallic Ag0 NPs are embedded within the ZnO foam, while at high Ag‐loading content, they accumulates increasingly from inside to the surface of the foam. With the increase of AgNPs loading from 0.1 mM to 1.5 mM, the absorption of Ag−ZnO foams in the visible light region gradually enhances. The photocatalytic degradation efficiency of rhodamine B (RhB) is the highest in Ag−ZnO foams when the Ag loading concentration reaches 0.8 mM, suggesting an optimal content of Ag for enhanced performance. This trend is attributed to the photo‐induced charge transfer behavior of Ag−ZnO samples. The AgNPs embedded inside the ZnO foam enhance the separation of photo‐induced charges and prevent their recombination. As a result, Ag−ZnO(0.8 mM) foam with more photo‐induced holes participate in the photocatalytic reaction, leading to a remarkably high photocatalytic activity. [ABSTRACT FROM AUTHOR]

Wearable strain–humidity sensors are increasingly recognized for their role in healthcare and detecting human motion signals. However, many strain–humidity sensors require complex manufacturing processes and have limited applicability. In this study, based on the good miscibility between natural rubber latex (NRL) and poly (3,4‐ethylenedioxythiophene):poly (4‐styrenesulfonate) (PEDOT:PSS), PEDOT:PSS/NRL composite conductors are transferred onto fabric substrate through screen printing and prepared high‐performance strain–humidity sensor. The PEDOT:PSS/NRL blends strain–humidity sensor exhibited good stability and durability (500 cycles) at 10% strain, achieves a gauge factor (GF) of 123.8 with excellent linearity, making it operational in detecting various human motions, such as finger bending, elbow bending, wrist bending, and so on. In addition, the PEDOT:PSS and water molecules interaction results in a humidity response time as low as 0.72 s and recovery time as low as 0.85 s for the PEDOT:PSS/NRL composite strain–humidity sensor, and a wide relative humidity detection range (6–83%), allowing it to be utilized for precise detection of human breathing. Furthermore, it can monitor the use's joint movement, facial muscle movement, and respiratory rate, which show its potential application prospect in health monitoring. [ABSTRACT FROM AUTHOR]

A novel multi‐color emitting Na2YMg2V3O12:Sm3+ phosphor was synthesized using a solid‐state reaction, and its crystal structure, luminescence properties, and thermal stability were studied. Charge transfer within the (VO4)3− groups in the Na2YMg2V3O12 host led to a broad emission band between 400 and 700 nm, with a maximum at 530 nm. The Na2Y1−xMg2V3O12:xSm3+ phosphors exhibited a multi‐color emission band under 365 nm near‐ultraviolet (near‐UV) light, consisting of the green emission of the (VO4)3− groups and sharp emission peaks at 570 nm (yellow), 618 nm (orange), 657 nm (red), and 714 nm (deep red) of Sm3+ ions. The optimal doping concentration of Sm3+ ions was found to be 0.05 mol%, and the dipole–dipole (d–d) interaction was primarily responsible for the concentration quenching phenomenon. Using the acquired Na2YMg2V3O12:Sm3+ phosphors, commercial BaMgAl10O17:Eu2+ blue phosphor, and a near‐UV light‐emitting diode (LED) chip, a white‐LED lamp was designed and packaged. It produced bright neutral white light, manifesting a CIE coordinate of (0.314, 0.373), a color rendering index (CRI) of 84.9, and a correlated color temperature (CCT) of 6377 K. These findings indicate the potential of Na2YMg2V3O12:Sm3+ phosphor to be used as a multi‐color component for solid‐state illumination. [ABSTRACT FROM AUTHOR]

TRIM33 is a chromatin reader required for mammalian mesendoderm differentiation after activation of Nodal signaling, while its role in mESCs is still elusive. Here, we report that TRIM33 co‐localizes with promyelocytic leukemia nuclear bodies (PML‐NBs) specifically in mESCs, to mediate Nodal signaling‐directed transcription of Lefty1/2. We show that TRIM33 puncta formation in mESCs depends on PML and on specific assembly of PML‐NBs. Moreover, TRIM33 and PML co‐regulate Lefty1/2 expression in mESCs, with both PML protein and formation of mESCs‐specific PML‐NBs being required for TRIM33 recruitment to these loci, and PML‐NBs directly associating with the Lefty1/2 loci. Finally, a TurboID proximity‐labeling experiment confirmed that TRIM33 is highly enriched only in mESCs‐specific PML‐NBs. Thus, our study supports a model in which TRIM33 condensates regulate Nodal signaling‐directed transcription in mESCs and shows that PML‐NBs can recruit distinct sets of client proteins in a cell‐context‐dependent manner. Synopsis: The chromatin reader TRIM33 is involved in cell fate decisions under different cell contexts, but the molecular details are still elusive. Here, TRIM33 is found to co‐condense with PML nuclear bodies (PML‐NBs) in mESCs to transcriptionally regulate Lefty1/2 expression upon Nodal signaling. TRIM33 is recruited into PML‐NBs selectively in mESCs, but not in differentiated cells.PML‐NB client protein composition differs between mESCs, oxidative stress‐treated mESCs, and differentiated cells.PML‐NBs regulate expression of gene clusters, including Lefty1/2 loci in mESCs.PML‐NBs form a regulatory hub for TRIM33 control of Lefty1/2 expression upon Nodal signaling. [ABSTRACT FROM AUTHOR]

Background. An in-silico screen identified mebendazole with potential antiviral activity that could be a repurposed drug against SARS-CoV-2. Mebendazole is a well-tolerated and cheap antihelminthic agent that is readily available worldwide and thus could be a therapeutic tool in the fight against COVID-19. Methods. This is an observational retrospective study of PCR-confirmed COVID-19 patients who received mebendazole with the intention-to-treat. The study included an inpatient cohort (157 inpatients) and an outpatient cohort (185 outpatients). Of the 157 inpatients and 185 outpatients, 68 (43.3%) and 94 (50.8%) received mebendazole, respectively. Patients who presented within the same timeframe but did not receive mebendazole were used as controls. Patients received standard-of-care treatment including remdesivir, dexamethasone, and anticoagulants as deemed necessary by the treating physician. The following clinical outcomes were evaluated: for the inpatient cohort, length of stay (LOS) at the hospital, need for ventilation (combined invasive and noninvasive), and mortality; for the outpatient cohort, time to symptom resolution, need for hospitalization, and mortality. Results. For the inpatient cohort, the median age did not differ between the treatment and control groups; 62 (56, 67) vs. 62 (56, 68), P , and there was a comparable proportion of males in both groups; 43 (63%) vs. 55 (62%), P = 0.85. The hospital LOS was 3.5 days shorter in the treatment group compared to the control group (P < 0.001). There were fewer patients who required invasive or noninvasive ventilation in the treatment group, 2 (2.9%) vs. 7 (7.9%), and the mortality rate is lower in the treatment group, 3 (4.4%) vs. 8 (9.0%), though the differences did not reach statistical significance. For the outpatient cohort, the median age was lower in the treatment group compared with the control group; 40 (34, 48) vs. 48 (41, 54), P < 0.001. There was a comparable proportion of males between both groups; 50 (53%) vs. 52 (57%), P = 0.59. Patients in the treatment group were 3.3 days closer to symptom resolution (P < 0.001). There were numerically fewer patients requiring hospitalization in the treatment group compared with the control group, 3 (3.2%) vs. 6 (6.6%), though this did not reach statistical significance (P = 0.33). Conclusion. In this retrospective observational study, the use of mebendazole in COVID-19 patients was associated with shorter hospitalizations in the inpatient cohort and shorter durations of symptom resolution in the outpatient cohort. The findings from this small observational study are hypothesis-generating and preclude drawing conclusions about clinical efficacy. Further studies are needed to examine the role of mebendazole in the treatment of COVID-19 patients. [ABSTRACT FROM AUTHOR]

In this study, an efficient nano-zero-valent iron supported by alkali-modified sludge biochar (nZVI@NaOH-SBC) composites were synthesized by a liquid-phase reduction method for Cu2+ removal. The preparation conditions (sodium hydroxide concentration, pyrolysis temperature, solid–liquid ratio, and modification time) of sludge biochar (SBC) were optimized by orthogonal experiments. The results showed that the best SBC was prepared under the conditions of sodium hydroxide concentration of 3 mol/L, pyrolysis temperature of 500 °C, a solid–liquid ratio of 1:20, and modification time of 24 h, and a maximum adsorption capacity was 183.22 mg/g, which is 2.43 times that of the pristine sludge biochar. The adsorption behavior was in accordance with a pseudo-second-order kinetic model, indicating that the removal of Cu2+ was mainly affected by chemisorption. The adsorption isotherm conformed to the Langmuir model, and the maximum adsorption capacity of Cu2+ was 358.42 mg/g at pH = 5, and 25 °C. Reusability tests confirmed the good reusability and stability of the material. Batch experiments and characterization reveal that the mechanism of Cu removal by nZVI@NaOH-SBC composites involves multiple processes: adsorption, precipitation, electrostatic attraction, and reduction. This study proposes a new biochemical adsorbent, which provides a good choice for the treatment of copper-containing wastewater and the resource utilization of sludge. [ABSTRACT FROM AUTHOR]

Organic components in atmospheric fine particulate matter have attracted much attention and several scientific studies have been performed, although most of the sample extraction methods are time consuming and laborious. Accelerated solvent extraction (ASE) is a new sample extraction method offering number of advantages, such as low extraction cost, reduced solvent and time consumption, and simplified extraction protocols. In order to optimize ASE methods to determine the concentrations of organic compounds in atmospheric fine particulate matter, different parameters were set out for the experiment, and the optimal method was selected according to the recoveries of the standard (i.e., n−alkanes and polycyclic aromatic hydrocarbons (PAHs)). This study also involves a comparison of the optimal method with the traditional method of ultrasonic extraction (USE). In addition, the optimized method was applied to measure the mass concentrations of organic compounds (n−alkanes and PAHs) in fine particulate matter samples collected in Beijing. The findings showed that the average recovery of target compounds using ASE was 96%, with the majority of compounds falling within the confidence levels, and the ASE recoveries and precision were consistent with the USE method tested. Furthermore, ASE combines the advantages of high extraction efficiency, automation, and reduced solvent use. In conclusion, the optimal ASE methods can be used to extract organic components in atmospheric particulate matter and serve as a point of reference for the development of analytical methodologies for assessing organic compounds in atmospheric particulate matter in China. [ABSTRACT FROM AUTHOR]

Owing to energy shortages and environmental pollution, green energy sources such as polymer electrolyte fuel cells and metal–air batteries play a more and more important role, whereby the oxygen reduction reaction (ORR) is the rate‐determining step. Development of high‐efficiency and stable catalysts to facilitate the ORR is of importance. Graphene is a new type of material with two‐dimensional structure and high surface area, which has wide‐ranging applications in many fields. However, graphene with zero band gap shows low electrocatalytic activity toward the ORR. Introduction of nonmetal atoms can change the electronic arrangement, generate active sites, and further improve the catalytic activity of graphene. Some nonmetal‐doping strategies (e.g. N, S, and P doping) can promote ORR activity. Herein, the recent development of nonmetal‐doped graphene catalysts for ORR is reviewed. Some common synthetic methods for nonmetal‐doped graphene materials are summarized, and the active sites and possible reaction mechanisms for ORR on various nonmetal‐doped graphene catalysts are discussed. [ABSTRACT FROM AUTHOR]

Sewage treatment plants are known as repositories of antibiotic resistance genes (ARGs). Adding biochar and inoculating with exogenous microbial agents are common ways to improve the quality of compost. However, little is known about the effects of these exogenous additives on the fate of ARGs during composting and the related mechanisms. In this study, municipal sludge was taken as the research object to study the ARG-removal effects of four composting methods: ordinary compost (CT), compost with hyperthermophiles (HT), compost with hyperthermophiles and 2.0% biochar (HT2C) and compost with hyperthermophiles and 5.0% biochar (HT5C). Real-time quantitative PCR (qPCR) and 16S rRNA high-throughput sequencing were conducted to analyze the ARGs, MGEs and bacterial community. After composting, the abundance of ARGs in CT was reduced by 72.7%, while HT, HT2C and HT5C were reduced by 80.7%, 84.3% and 84.8%, respectively. Treatments with different proportions of biochar added (HT2C, HT5C) had no significant effect on the abundance of ARGs. Network analysis showed that Firmicutes and Nitrospirae were positively associated with most ARGs and may be potential hosts for them. In addition, redundancy analysis further showed that the class 1 integrase gene (intI1), pH and organic carbon had a greater effect on ARGs. Our findings suggested that the combination of hyperthermophiles and biochar during the composting process was an effective way to control ARGs and mobile genetic elements (MGEs), thus inhibiting the spread and diffusion of ARGs in the environment and improving the efficiency of treating human and animal diseases. [ABSTRACT FROM AUTHOR]

In this study, a type of alkaline solid polyelectrolyte (ASPE) membrane was developed via the introduction of microcrystalline cellulose (MCC) and its modified product (QMCC) into the polyvinyl alcohol (PVA) matrix. In this process, green NaOH/urea-based solvent was used to achieve a good dispersion of MCC in the PVA matrix; meanwhile, the OH− groups in the NaOH/urea-based solvent provided an alkaline environment for good ion conductivity. Compared to the MCC-incorporated ASPE, further improved conductivity was achieved when the MCC was modified with quantitative quaternary ammonium salt. TGA showed that the addition of QMCC improved the water retention of the matrix, which was beneficial to the OH− conduction in the system. Compared to the control (50 mS cm−1), a maximum conductivity of 238 mS cm−1 was obtained after the incorporation of QMCC in the PVA matrix. Moreover, the tensile strength of the polymer electrolyte were also significantly increased with the addition of QMCC. Finally, this developed ASPE membrane was used in assembling a flexible Zn–air battery and showed a promising potential in the development of flexible electronic devices. [ABSTRACT FROM AUTHOR]