KEGG orthology prediction of bacterial proteins using natural language processing.

BACKGROUND: The advent of high-throughput technologies has led to an exponential increase in uncharacterized bacterial protein sequences, surpassing the capacity of manual curation. A large number of bacterial protein sequences remain unannotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology, making it necessary to use auto annotation tools. These tools are now indispensable in the biological research landscape, bridging the gap between the vastness of unannotated sequences and meaningful biological insights. RESULTS: In this work, we propose a novel pipeline for KEGG orthology annotation of bacterial protein sequences that uses natural language processing and deep learning. To assess the effectiveness of our pipeline, we conducted evaluations using the genomes of two randomly selected species from the KEGG database. In our evaluation, we obtain competitive results on precision, recall, and F1 score, with values of 0.948, 0.947, and 0.947, respectively. CONCLUSIONS: Our experimental results suggest that our pipeline demonstrates performance comparable to traditional methods and excels in identifying distant relatives with low sequence identity. This demonstrates the potential of our pipeline to significantly improve the accuracy and comprehensiveness of KEGG orthology annotation, thereby advancing our understanding of functional relationships within biological systems.

The effects of Atractylodes macrocephala extract BZEP self-microemulsion based on gut-liver axis HDL/LPS signaling pathway to ameliorate metabolic dysfunction-associated fatty liver disease in rats.

OBJECTIVES: To elucidate the therapeutic effects and mechanisms of Atractylodes macrocephala extract crystallize (BZEP) and BZEP self-microemulsion (BZEPWR) on metabolic dysfunction-associated fatty liver disease (MAFLD) induced by "high sugar, high fat, and excessive alcohol consumption" based on the gut-liver axis HDL/LPS signaling pathway. METHODS: In this study, BZEP and BZEPWR were obtained via isolation, purification, and microemulsification. Furthermore, an anthropomorphic MAFLD rat model of "high sugar, high fat, and excessive alcohol consumption" was established. The therapeutic effects of BZEPWR and BZEP on the model rats were evaluated in terms of liver function, lipid metabolism (especially HDL-C), serum antioxidant indexes, and liver and intestinal pathophysiology. To determine the lipoproteins in the serum sample, the amplitudes of a plurality of NMR spectra were derived via deconvolution of the composite methyl signal envelope to yield HDL-C subclass concentrations. The changes in intestinal flora were detected via 16 S rRNA gene sequencing. In addition, the gut-liver axis HDL/LPS signaling pathway was validated using immunohistochemistry, immunofluorescence, and western blot. RESULTS: The findings established that BZEPWR and BZEP improved animal signs, serum levels of liver enzymes (ALT and AST), lipid metabolism (TC, TG, HDL-C, and LDL-C), and antioxidant indexes (GSH, SOD, and ROS). In addition, pathological damage to the liver, colon, and ileum was ameliorated, and the intestinal barrier function of the model rats was restored. At the genus level, BZEPWR and BZEP exerted positive effects on beneficial bacteria, such as Lactobacillus and norank_f__Muribaculaceae, and inhibitory effects on harmful bacteria, such as unclassified_f__Lachnospiraceae and Blautia. Twenty HDL-C subspecies were detected, and their levels were differentially increased in both BZEPWR and BZEP groups, with BZEPWR exhibiting a stronger elevating effect on specific HDL-C subspecies. Also, the gut-liver axis HDL/LPS signaling pathway was studied, which indicated that BZEPWR and BZEP significantly increased the expressions of ABCA1, LXR, occludin, and claudin-1 proteins in the gut and serum levels of HDL-C. Concomitantly, the levels of LPS in the serum and TLR4, Myd88, and NF-κB proteins in the liver were decreased. CONCLUSION: BZEPWR and BZEP exert restorative and reversal effects on the pathophysiological damage to the gut-liver axis in MAFLD rats, and the therapeutic mechanism may be related to the regulation of the intestinal flora and the HDL/LPS signaling pathway.

Cardiovascular mortality risk in patients with ovarian cancer: a population-based study.

OBJECTIVES: Ovarian cancer (OC) can occur at different ages and is affected by a variety of factors. In order to evaluate the risk of cardiovascular mortality in patients with ovarian cancer, we included influencing factors including age, histological type, surgical method, chemotherapy, whether distant metastasis, race and developed a nomogram to evaluate the ability to predict occurrence. At present, we have not found any correlation studies on cardiovascular death events in patients with ovarian cancer. This study was designed to provide targeted measures for effective prevention of cardiovascular death in patients with ovarian cancer. METHODS: Kaplan-Meier analysis and multivariable Cox proportional model were performed to evaluate the effectiveness of cardiovascular diseases on overall survival (OS) and ovarian cancer-specific survival (OCSS). We compared multiple groups including clinical, demographic, therapeutic characteristics and histological types. Cox risk regression analysis, Kaplan-Meier survival curves, and propensity score matching were employed for analyzing the data. RESULTS: A total of 88,653 ovarian cancer patients were collected, of which 2,282 (2.57%) patients died due to cardiovascular-related diseases. Age, chemotherapy and whether satisfactory cytoreduction surgery is still the most important factors affecting the prognosis of ovarian cancer patients, while different histological types, diagnosis time, and race also have a certain impact on the prognosis. The newly developed nomogram model showed excellent predictive performance, with a C-index of 0.759 (95%CI: 0.757-0.761) for the group. Elderly patients with ovarian cancer are still a high-risk group for cardiovascular death [HR: 21.07 (95%CI: 5.21-85.30), p < 0.001]. The calibration curve showed good agreement from predicted survival probabilities to actual observations. CONCLUSION: This study found that age, histology, surgery, race, chemotherapy, and tumor metastasis are independent prognostic factors for cardiovascular death in patients with ovarian cancer. The nomogram-based model can accurately predict the OS of ovarian cancer patients. It is expected to inform clinical decision-making and help develop targeted treatment strategies for this population.

Monolayer 1T-Ag6S2 with Excellent Thermoelectric Properties.

We obtained a new material called monolayer 1T-Ag6S2 by replacing metal atoms in 1T phase transition-metal dichalcogenide sulfides (TMDs) with octahedral Ag6 clusters. Subsequently, the thermoelectric transport properties of monolayer 1T-Ag6S2 were systematically investigated using first-principles calculations and the generalized gradient approximation (GGA-PBE) exchange correlation functional. The findings demonstrate that monolayer 1T-Ag6S2 displays characteristics of a wide-bandgap semiconductor, with a bandgap of 2.48 eV. Notably, the incorporation of Ag6 clusters disrupts the structural symmetry, effectively enhancing the electronic structure and phonon properties of the material. Due to the flat valence band near the Fermi level, the extended relaxation time of the hole results in a greater effective mass compared to the electron, leading to a significant increase in the Seebeck coefficient. Under optimal doping conditions, the power factor of monolayer 1T-Ag6S2 can achieve 14.9 mW/mK2 at 500 K. The intricate crystal structure induces phonon path bending, reduces the overall frequency of phonon vibrations (<10 THz), and causes hybridization of low-frequency optical and acoustic branches, resulting in remarkably low lattice thermal conductivity (0.20 and 0.17 W/mK along the x and y axes at 500 K, respectively). The monolayer 1T-Ag6S2 demonstrates a remarkably high figure of merit ZT of 3.14 (3.15) on the x (y) axis at 500 K, significantly higher than those of conventional TMD materials. Such excellent thermoelectric properties suggest that monolayer 1T-Ag6S2 is a promising thermoelectric (TE) material. Our work reveals the deep mechanism of cluster substitution to optimize the thermoelectric properties of materials and provides a useful reference for subsequent research.

Genome-wide characterization of DNA methyltransferase family genes implies GhDMT6 improving tolerance of salt and drought on cotton.

BACKGROUND: DNA methylation is an important epigenetic mode of genomic DNA modification and plays a vital role in maintaining epigenetic content and regulating gene expression. Cytosine-5 DNA methyltransferase (C5-MTase) are the key enzymes in the process of DNA methylation. However, there is no systematic analysis of the C5-MTase in cotton so far, and the function of DNMT2 genes has not been studied. METHODS: In this study, the whole genome of cotton C5-MTase coding genes was identified and analyzed using a bioinformatics method based on information from the cotton genome, and the function of GhDMT6 was further validated by VIGS experiments and subcellular localization analysis. RESULTS: 33 C5-MTases were identified from three cotton genomes, and were divided into four subfamilies by systematic evolutionary analysis. After the protein domain alignment of C5-MTases in cotton, 6 highly conserved motifs were found in the C-terminus of 33 proteins involved in methylation modification, which indicated that C5-MTases had a basic catalytic methylation function. These proteins were divided into four classes based on the N-terminal difference, of which DNMT2 lacks the N-terminal regulatory domain. The expression of C5-MTases in different parts of cotton was different under different stress treatments, which indicated the functional diversity of cotton C5-MTase gene family. Among the C5-MTases, the GhDMT6 had a obvious up-regulated expression. After silencing GhDMT6 with VIGS, the phenotype of cotton seedlings under different stress treatments showed a significant difference. Compared with cotton seedlings that did not silence GhDMT6, cotton seedlings silencing GhDMT6 showed significant stress resistance. CONCLUSION: The results show that C5-MTases plays an important role in cotton stress response, which is beneficial to further explore the function of DNMT2 subfamily genes.

A Novel DNA Synthesis Platform Design with High-Throughput Paralleled Addressability and High-Density Static Droplet Confinement.

Using DNA as the next-generation medium for data storage offers unparalleled advantages in terms of data density, storage duration, and power consumption as compared to existing data storage technologies. To meet the high-speed data writing requirements in DNA data storage, this paper proposes a novel design for an ultra-high-density and high-throughput DNA synthesis platform. The presented design mainly leverages two functional modules: a dynamic random-access memory (DRAM)-like integrated circuit (IC) responsible for electrode addressing and voltage supply, and the static droplet array (SDA)-based microfluidic structure to eliminate any reaction species diffusion concern in electrochemical DNA synthesis. Through theoretical analysis and simulation studies, we validate the effective addressing of 10 million electrodes and stable, adjustable voltage supply by the integrated circuit. We also demonstrate a reaction unit size down to 3.16 × 3.16 µm2, equivalent to 10 million/cm2, that can rapidly and stably generate static droplets at each site, effectively constraining proton diffusion. Finally, we conducted a synthesis cycle experiment by incorporating fluorescent beacons on a microfabricated electrode array to examine the feasibility of our design.

A Novel Microfluidic Strategy for Efficient Exosome Separation via Thermally Oxidized Non-Uniform Deterministic Lateral Displacement (DLD) Arrays and Dielectrophoresis (DEP) Synergy.

Exosomes, with diameters ranging from 30 to 150 nm, are saucer-shaped extracellular vesicles (EVs) secreted by various type of human cells. They are present in virtually all bodily fluids. Owing to their abundant nucleic acid and protein content, exosomes have emerged as promising biomarkers for noninvasive molecular diagnostics. However, the need for exosome separation purification presents tremendous technical challenges due to their minuscule size. In recent years, microfluidic technology has garnered substantial interest as a promising alternative capable of excellent separation performance, reduced reagent consumption, and lower overall device and operation costs. In this context, we hereby propose a novel microfluidic strategy based on thermally oxidized deterministic lateral displacement (DLD) arrays with tapered shapes to enhance separation performance. We have achieved more than 90% purity in both polystyrene nanoparticle and exosome experiments. The use of thermal oxidation also significantly reduces fabrication complexity by avoiding the use of high-precision lithography. Furthermore, in a simulation model, we attempt to integrate the use of dielectrophoresis (DEP) to overcome the size-based nature of DLD and distinguish particles that are close in size but differ in biochemical compositions (e.g., lipoproteins, exomeres, retroviruses). We believe the proposed strategy heralds a versatile and innovative platform poised to enhance exosome analysis across a spectrum of biochemical applications.

Impact of immediate postrecanalization cooling on outcome in acute ischemic stroke patients with a large ischemic core: prospective cohort study.

BACKGROUND: Patients with large acute ischemic strokes (AIS) often have a poor prognosis despite successful recanalization due to multiple factors including reperfusion injury. The authors aim to describe our preliminary experience of endovascular cooling in patients with a large AIS after recanalization. METHODS: From January 2021 to July 2022, AIS patients presenting with large infarcts (defined as ASPECTS ≤5 on noncontrast CT or ischemic core ≥50 ml on CT perfusion) who achieved successful recanalization after endovascular treatment were analyzed in a prospective registry. Patients were divided into targeted temperature management (TTM) and non-TTM group. Patients in the TTM group received systemic cooling with a targeted core temperature of 33° for at least 48 h. The primary outcome is 90-day favorable outcome [modified Rankin Scale (mRS) 0-2]. The secondary outcomes are 90-day good outcome (mRS 0-3), mortality, intracranial hemorrhage and malignant cerebral edema within 7 days or at discharge. RESULTS: Forty-four AIS patients were recruited (15 cases in the TTM group and 29 cases in the non-TTM group). The median Alberta Stroke Program Early CT Score (ASPECTS) was 3 (2-5). The median time for hypothermia duration was 84 (71.5-147.6) h. The TTM group had a numerically higher proportion of 90-day favorable outcomes than the non-TTM group (46.7 vs. 27.6%, P=0.210), and no significant difference were found regarding secondary outcomes (all P>0.05). The TTM group had a numerically higher rates of pneumonia (66.7 vs. 58.6%, P=0.604) and deep vein thrombosis (33.3 vs. 13.8%, P=0.138). Shivering occurred in 4/15 (26.7%) of the TTM patients and in none of the non-TTM patients (P=0.009). CONCLUSIONS: Postrecanalization cooling is feasible in patients with a large ischemic core. Future randomized clinical trials are warranted to validate its efficacy.

STING Agonist cGAMP Attenuates Sleep Deprivation-Induced Neuroinflammation and Cognitive Deficits via TREM2 Up-Regulation.

Sleep deprivation (SD) has been associated with several adverse effects, including cognitive deficit. Emerging evidence suggests microglia-associated neuroinflammation is a potential trigger of cognitive deficit after SD. Stimulator of interferon genes (STING) constitutes an important factor in host immune response to pathogenic organisms and is found in multiple cells, including microglia. STING is involved in neuroinflammation during neuronal degeneration, although how STING signaling affects SD-induced neuroinflammation remains unexplored. In the present study, the chronic sleep restriction (CSR) model was applied to examine the effects of STING signaling on cognition. The results revealed that cGAMP, a high-affinity and selective STING agonist, significantly improved cognitive deficit, alleviated neural injury, and relieved neuroinflammation in CSR mice by activating the STING-TBK1-IRF3 pathway. Moreover, triggering receptor expressed on myeloid cells 2 (TREM2) was upregulated in CSR mice treated with cGAMP, and this effect was abolished by STING knockout. TREM2 upregulation induced by cGAMP regulated the microglia from pro-inflammatory state to anti-inflammatory state, thereby relieving neuroinflammation in CSR mice. These findings indicate cGAMP-induced STING signaling activation alleviates SD-associated neuroinflammation and cognitive deficit by upregulating TREM2, providing a novel approach for the treatment of SD-related nerve injury.

High-Performance Thermoelectric Fibers from Metal-Backboned Polymers for Body-Temperature Wearable Power Devices.

Metal-backboned polymers (MBPs), with a unique backbone consisting of bonded metal atoms, are promising for optic, electric, magnetic, and thermoelectric fields. However, the application of MBP remains relatively understudied. Here, we develop a shear-induced orientation method to construct a flexible nickel-backboned polymer/carbon nanotube (NBP/CNT) thermoelectric composite fiber. It demonstrated a power factor of 719.48 µW ⋅m-1 K-2, which is ca. 3.5 times as high as the bare CNT fiber. Remarkably, with the regulation of carrier mobility and carrier concentration of NBP, the composite fiber further showed simultaneous increases in electrical conductivity and Seebeck coefficient in comparison to the bare CNT fiber. The NBP/CNT fiber can be integrated into fabrics to harvest thermal energy of human body to generate an output voltage of 3.09 mV at a temperature difference of 8 K. This research opens a new avenue for the development of MBPs in power supply.

[Retracted] Tremella polysaccharides inhibit cellular apoptosis and autophagy induced by Pseudomonas aeruginosa lipopolysaccharide in A549 cells through sirtuin 1 activation.

[This retracts the article DOI: 10.3892/ol.2018.8554.].

Poly (vinyl alcohol)/sodium alginate/carboxymethyl chitosan multifunctional hydrogel loading HKUST-1 nanoenzymes for diabetic wound healing.

Bacterial infection, hyperinflammation and hypoxia, which can lead to amputation in severe cases, are frequently observed in diabetic wounds, and this has been a critical issue facing the repair of chronic skin injuries. In this study, a copper-based MOF (TAX@HKUST-1) highly loaded with taxifolin (TAX) with a drug loading of 41.94 ±â€¯2.60 % was prepared. In addition, it has excellent catalase activity, and by constructing an oxygen-releasing hydrogel (PTH) system with calcium peroxide (CaO2), it can be used as a nano-enzyme to promote the generation of oxygen from hydrogen peroxide (H2O2) to provide sufficient oxygen to the wound, and at the same time, solve the problem of the oxidative stress damage caused by excess H2O2 to the cells during the oxygen-releasing process. On the other hand, TAX and HKUST-1 in PTH synergistically promoted antimicrobial and anti-oxidative stress properties, and the bacterial inhibition rate against Staphylococcus aureus and Escherichia coli reached 90 %. In vivo experiments have shown that PTH hydrogel is able to treat diabetic skin repair by inhibiting the expression of inflammation-related proteins and promoting epidermal neogenesis, angiogenesis and collagen deposition.

Exceptional Stability against Water, UV Light, and Heat for CsPbBr3@Pb-MOF Composites.

All-inorganic lead halide perovskite nanocrystals (NCs) have been widely applied in optoelectronic devices owing to their excellent photoluminescence (PL) properties. However, poor stability upon exposure to water, UV light or heat strongly limits their practical application. Herein, CsPbBr3@Pb-MOF composites with exceptional stability against water, UV light, and heat are synthesized by ultrasonic processing the precursors of lead-based MOF (Pb-MOF), oleylammonium bromide (OAmBr) and cesium oleate (Cs-OA) solutions at room temperature. Pb-MOF can not only provide the lead source for the in situ growth of CsPbBr3 NCs, but also the protective layer of perovskites NCs. The formed CsPbBr3@Pb-MOF composites show a considerable PL quantum yield (PLQY) of 67.8%, and can maintain 90% of the initial PL intensity when immersed in water for 2 months. In addition, the outstanding PL stability against UV light and heat is demonstrated with CsPbBr3 NCs synthesized by the conventional method as a comparison. Finally, a green (light-emitting diode) LED is fabricated using green-emitting CsPbBr3@Pb-MOF composites and exhibits excellent stability without packaging when immersed in water for 30 days. This study provides a practical approach to improve the stability in aqueous phase, which may pave the way for future applications for various optoelectronic devices.

An approach to evaluating seasonal responses to acute toxicity of antibiotic nitrofurazone on periphytic ciliated protist communities in marine environments.

Periphytic protists including ciliates are the primary components of microbial communities in which they play a vital role in the progression of food webs by moving resources from lower to higher trophic levels. However, the toxic effects of veterinary antibiotics on periphytic protists across four seasons are minimally understood. Therefore, in this study, a 1-year survey was conducted with the antibiotic nitrofurazone (NFZ) applied at concentrations of 0.0, 1.5, 3.0, 6.0, and 12.0 mg/L. Samples of protist communities were collected using microscope glass slides during four seasons in the coastal waters of the Yellow Sea, Qingdao, northern China. The abundance of protists dropped with an increase in NFZ concentrations, and almost all species were dead at a concentration of 12.0 mg/L. The 12 h-LC50 values of NFZ for the protist biota were similar among the four seasons, despite significant seasonal variability in the community structure. The present results suggest that the periphytic protist biota may be used as a biomarker for assessing the ecotoxicity of NFZ in marine environments regardless of the year season.

Domino Michael/Oxa-Michael Reactions of the Unsymmetric Double Michael Acceptor for Access to Bicyclic Furo[2,3-b]pyrrole.

By creating an unsymmetric double Michael acceptor 1, we were able to synthesize the nonaromatic-fused bicyclic furo[2,3-b]pyrrole nucleus using a domino Michael/oxa-Michael reaction. Adopting benzoyl acetonitrile 2d (CN as the electron-withdrawing group) as a substrate, we discovered a (DHQ)2AQN-catalyzed method for high diastereo- and enantioselectivity of those products. The reaction path has been determined by isolating the reaction intermediates, and density functional theory calculations support these findings. Beyond providing a synthetic approach, this work illustrated the compounds' possible use in antitumor activity.

Insight into the role of reactive species on catalyst surface underlying peroxymonosulfate activation by P-Fe2MnO4 loaded on bentonite for trichloroethylene degradation.

In this study, bentonite supporting phosphorus-doped Fe2MnO4 (BPF) was synthesized and applied for PMS activation to degrade TCE. Morphology and structure characterization results indicated the successfully synthesized of BPF, and the BPF/PMS system not only featured high TCE removal (97.4%) but also high reaction rate constant (kobs = 0.0554 min-1) and PMS utilization (70.4%, kobs = 0.0228 min-1). According to the results of various experiments, massive oxygen vacancies on P-Fe2MnO4 alter its charge balance and facilitate the electron transfer process named adjacent transfer (direct electron capture by adsorbed PMS from adjacent TCE). Mn(III) is the main adsorption site for PMS, and the hydroxyl groups on the catalyst (Fe sites of P-Fe2MnO4, Si and Al sites of bentonite) can also offer binding sites for PMS. The hydrogen-bonded PMS on Fe(III) and Mn(III) sites will subsequently accept the discharged electrons to generate free radicals and high-valent metal species. Meanwhile, electron loss of HSO5- that chemically bonded to hydroxyl groups on bentonite will generate SO5•-, which will further produce 1O2 through self-bonding. the active species on the catalyst surface contribute 65% of TCE degradation in the heterogeneous catalytic oxidation system.

[Evaluation of the feasibility of endoscopic tympanoplasty in two-person three-hand operation].

Objective:To study the difference of postoperative efficacy between two-person three-hand ear endoscopy and microscopic tympanoplasty in patients with chronic suppurative otitis media, and to explore the advantages and disadvantages of two-person three-hand ear endoscopy. Methods:A retrospective study was conducted on 100 patients who underwent tympanoplasty in the Department of Otolaryngology and Head and Neck Surgery of Hunan People's Hospital from April 2019 to March 2023, and they were divided into 2 groups with 50 cases each according to random number table method. Among them, 50 cases underwent endoscopic tympanoplasty in two-person three-hand（group A） and 50 cases underwent routine microscopic tympanoplasty（group B）. The operation and postoperative conditions of the two groups were followed up. Results:In group A, the mean operation time was（65.78±18.21） min, the mean intraoperative blood loss was（12.94±4.46） mL, the postoperative pain score was（1.82±0.60） points, and the mean postoperative hospital stay was（2.76±0.72） d. The mean operation time of group B was（89.45±20.38） min, the mean intraoperative blood loss was（22.78±5.74） mL, the postoperative pain score was（2.98±0.85） points, and the mean postoperative hospital stay was（3.82±0.75） d, which with statistical significance between the two groups（P<0.05）. Hearing in both groups was significantly improved 6 months after surgery, and the difference was statistically significant before and after surgery（P<0.05）, but there was no significant difference between the two groups before surgery and 6 months after surgery（P>0.05）. There were 2 cases in group A（4%） and 1 case in group B（2%） complicated with tympanic cord injury during operation, and the difference was not statistically significant（P>0.05）. There were 47 cases of A group（94%） of one-time healing of tympanic membrane after operation, 48 cases（96%） of group B, and the difference was not statistically significant（P>0.05）. Conclusion:There is no significant difference in cure rate and hearing improvement between two-person three-hand ear endoscopic tympanoplasty and conventional microscope surgery, and the operation time is significantly shortened, the amount of blood loss is less, and the postoperative recovery is faster. It has the advantages of clear operating field, two-person three-hand operation, minimally invasive, and can reach the range of middle ear tympanic sinus and mastoid apex, and the surgical complications are seldom, which is worth promoting.

Correction of human nonsense mutation via adenine base editing for Duchenne muscular dystrophy treatment in mouse.

Duchenne muscular dystrophy (DMD) is the most prevalent herediatry disease in men, characterized by dystrophin deficiency, progressive muscle wasting, cardiac insufficiency, and premature mortality, with no effective therapeutic options. Here, we investigated whether adenine base editing can correct pathological nonsense point mutations leading to premature stop codons in the dystrophin gene. We identified 27 causative nonsense mutations in our DMD patient cohort. Treatment with adenine base editor (ABE) could restore dystrophin expression by direct A-to-G editing of pathological nonsense mutations in cardiomyocytes generated from DMD patient-derived induced pluripotent stem cells. We also generated two humanized mouse models of DMD expressing mutation-bearing exons 23 or 30 of human dystrophin gene. Intramuscular administration of ABE, driven by ubiquitous or muscle-specific promoters could correct these nonsense mutations in vivo, albeit with higher efficiency in exon 30, restoring dystrophin expression in skeletal fibers of humanized DMD mice. Moreover, a single systemic delivery of ABE with human single guide RNA (sgRNA) could induce body-wide dystrophin expression and improve muscle function in rotarod tests of humanized DMD mice. These findings demonstrate that ABE with human sgRNAs can confer therapeutic alleviation of DMD in mice, providing a basis for development of adenine base editing therapies in monogenic diseases.

Aneurinibacillus uraniidurans sp. nov., a uranium-resistant bacterium isolated from uranium-contaminated soil.

A novel Gram-positive strain, B1T, was isolated from uranium-contaminated soil. The strain was aerobic, rod-shaped, spore-forming, and motile. The strain was able to grow at 20-45 °C, at pH 6.0-9.0, and in the presence of 0-3 % (w/v) NaCl. The complete genome size of the novel strain was 3 853 322 bp. The genomic DNA G+C content was 45.5 mol%. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain B1T has the highest similarity to Aneurinibacillus soli CB4T (96. 71 %). However, the novel strain showed an average nucleotide identity value of 89.02 % and a digital DNA-DNA hybridization value of 37.40 % with strain CB4T based on the genome sequences. The major fatty acids were iso-C15 : 0 and C16 : 0. The predominate respiratory quinone was MK7. Diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylglycerol, unidentified phospholipids, an unidentified aminolipid and an unidentified lipid were identified as the major polar lipids. The phylogenetic, phenotypic, and chemotaxonomic analyses showed that strain B1T represents a novel species of the genus Aneurinibacillus, for which the name Aneurinibacillus uraniidurans sp. nov. is proposed. The type strain is B1T (=GDMCC 1.4080T=JCM 36228T). Experiments have shown that strain B1T demonstrates uranium tolerance.

E3 ubiquitin ligase NEDD4L negatively regulates skin tumorigenesis by inhibiting of IL-6/GP130 signaling pathway.

Interleukin (IL)-6 signaling plays a crucial role in the survival and metastasis of skin cancer. Neural precursor cell expressed developmentally downregulated 4-Like (NEDD4L) acts as a suppressor of IL-6 signaling by targeting glycoprotein 130 (GP130) degradation. However, the effects of the NEDD4L-regulated IL-6/GP130 signaling pathway on skin cancer remain unclear. In this study, protein expression levels of NEDD4L and GP130 were measured in tumor tissues from patients with cutaneous squamous cell carcinoma (cSCC). Skin tumors were induced in wild type (WT) and Nedd4l knockout (KO) mice, and activation of the IL-6/GP130/STAT3 signaling pathway was detected. The results indicated a negative correlation between the protein expression levels of NEDD4L and GP130 in cSCC tissues from patients. Nedd4l deficiency significantly promoted DMBA/TPA-induced skin tumorigenesis and benign-to-malignant conversion by activating the IL-6/GP130/STAT3 signaling pathway, which was abrogated by supplementation with the GP130 inhibitor SC144. Furthermore, our findings suggested that NEDD4L can interact with GP130 and promote its ubiquitination in skin tumors. In conclusion, our results indicate that NEDD4L could act as a tumor suppressor in skin cancer, and inhibition of GP130 could be a potential therapeutic method for treating this disease.