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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.

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

Single-cell ATAC-seq data is challenging to analyse for reasons such as high dimensionality and sparsity. Here, the authors develop SCALE, a deep learning method that leverages latent feature extraction for various tasks of scATACseq data analysis.

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.

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.

Incorporating fluorine (–F) substituents along the main-chains of polymer donors and acceptors is an effective strategy toward efficient bulk-heterojunction (BHJ) solar cells. Specifically, F-substituted polymers often exhibit planar conformations, leading to favorable packing, and electronic coupling. However, the effects of fluorine substituents on the charge generation and recombination characteristics that determine the overall efficiency of BHJ active layers remain critically important issues to examine. In this report, two PBDT[2X]T polymer analogs –poly[4,8-bis((2-ethylhexyl)oxy)benzo[1,2-b:4, 5-b′]dithiophene-thiophene] [PBDT[2H]T] and its F-substituted counterpart poly[4,8-bis((2-ethylhexyl)oxy)benzo[1,2-b:4,5-b′]dithiophene-3,4-difluoro-thiophene] [PBDT[2F]T]—are studied to systematically examine how –F substituents impact the blend morphology, charge generation, carrier recombination and extraction in BHJ solar cells. Considering the large efficiency differences between PBDT[2H]T- and PBDT[2F]T-based BHJ devices, significant emphasis is given to characterizing the out-of-plane morphology of the blend films as vertical phase-separation characteristics are known to have dramatic effects on charge transport and carrier extraction in polymer-fullerene BHJ solar cells. Herein, we use electron energy loss spectroscopy (EELS) in tandem with charge transport characterization to examine PBDT[2X]T-fullerene blend films. Our analyses show that PBDT[2H]T and PBDT[2F]T possess very different charge generation, recombination and extraction characteristics, resulting from distinct aggregation, and phase-distribution within the BHJ blend films.

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.

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.