Erlotinib suppresses tumorigenesis in a mouse model of colitis-associated cancer.

Colitis-associated cancer (CAC) in inflammatory bowel diseases exhibits more aggressive behavior than sporadic colorectal cancer; however, the molecular mechanisms remain unclear. No definitive preventative agent against CAC is currently established in the clinical setting. We investigated the molecular mechanisms of CAC in the azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model and assessed the antitumor efficacy of erlotinib, a small molecule inhibitor of the epidermal growth factor receptor (EGFR). Erlotinib premixed with AIN-93 G diet at 70 or 140 parts per million (ppm) inhibited tumor multiplicity significantly by 96%, with ∼60% of the treated mice exhibiting zero polyps at 12 weeks. Bulk RNA-sequencing revealed more than a thousand significant gene alterations in the colons of AOM/DSS-treated mice, with KEGG enrichment analysis highlighting 46 signaling pathways in CAC development. Erlotinib altered several signaling pathways and rescued 40 key genes dysregulated in CAC, including those involved in the Hippo and Wnt signaling. These findings suggest that the clinically-used antitumor agent erlotinib might be repurposed for suppression of CAC, and that further studies are warranted on the crosstalk between dysregulated Wnt and EGFR signaling in the corresponding patient population.

Biochar derivation at low temperature: A novel strategy for harmful resource usage of antibiotic mycelial dreg.

Antibiotic mycelial dreg (AMD) has been categorized as hazardous waste due to the high residual hazardous contaminants. Inappropriate management and disposal of AMD can cause potential environmental and ecological risks. In this study, the potential of pleuromutilin mycelial dreg (PMD) as a novel feedstock for preparing tetracycline hydrochloride (TC) adsorbent was explored to achieve safe management of PMD. The results suggested that residual hazardous contaminants were completely eliminated after pyrolysis. With the increase of pyrolysis temperature, the yields, H/C, O/C, (O + N)/C, and pore size in PMD-derived biochars (PMD-BCs) decreased, while BET surface area and pore volume increased, resulting in the higher stability of the PMD-BCs prepared from higher temperatures. The TC adsorption of the PMD-BCs increased from 27.3 to 46.9 mg/g with the increase of the pyrolysis temperature. Surprisingly, pH value had a strong impact on the TC adsorption, the adsorption capacity of BC-450 increased from 6.5 to 71.1 mg/g when the solution pH value increased from 2 to 10. Lewis acid-base interaction, pore filling, π-π interaction, hydrophobic interaction, and charge-assisted hydrogen bond (CAHB) are considered to drive the adsorption. This work provides a novel pathway for the concurrent detoxification and reutilization of AMD.

Phonon stability boundary and deep elastic strain engineering of lattice thermal conductivity.

Recent studies have reported the experimental discovery that nanoscale specimens of even a natural material, such as diamond, can be deformed elastically to as much as 10% tensile elastic strain at room temperature without the onset of permanent damage or fracture. Computational work combining ab initio calculations and machine learning (ML) algorithms has further demonstrated that the bandgap of diamond can be altered significantly purely by reversible elastic straining. These findings open up unprecedented possibilities for designing materials and devices with extreme physical properties and performance characteristics for a variety of technological applications. However, a general scientific framework to guide the design of engineering materials through such elastic strain engineering (ESE) has not yet been developed. By combining first-principles calculations with ML, we present here a general approach to map out the entire phonon stability boundary in six-dimensional strain space, which can guide the ESE of a material without phase transitions. We focus on ESE of vibrational properties, including harmonic phonon dispersions, nonlinear phonon scattering, and thermal conductivity. While the framework presented here can be applied to any material, we show as an example demonstration that the room-temperature lattice thermal conductivity of diamond can be increased by more than 100% or reduced by more than 95% purely by ESE, without triggering phonon instabilities. Such a framework opens the door for tailoring of thermal-barrier, thermoelectric, and electro-optical properties of materials and devices through the purposeful design of homogeneous or inhomogeneous strains.

Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma.

Despite that the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved patients' survival and became the first-line treatment for advanced nasopharyngeal carcinoma (NPC), not all patients could benefit from this therapy. The mechanism underlying the TPF chemoresistance remains unclear. Here, by analyzing gene-expression microarray data and survival of patients who received TPF chemotherapy, we identify transcription factor ATMIN as a chemoresistance gene in response to TPF chemotherapy in NPC. Mass spectrometry and Co-IP assays reveal that USP10 deubiquitinates and stabilizes ATMIN protein, resulting the high-ATMIN expression in NPC. Knockdown of ATMIN suppresses the cell proliferation and facilitates the docetaxel-sensitivity of NPC cells both in vitro and in vivo, while overexpression of ATMIN exerts the opposite effect. Mechanistically, ChIP-seq combined with RNA-seq analysis suggests that ATMIN is associated with the cell death signaling and identifies ten candidate target genes of ATMIN. We further confirm that ATMIN transcriptionally activates the downstream target gene LCK and stabilizes it to facilitate cell proliferation and docetaxel resistance. Taken together, our findings broaden the insight into the molecular mechanism of chemoresistance in NPC, and the USP10-ATMIN-LCK axis provides potential therapeutic targets for the management of NPC.

Effects of landscape pattern on land surface temperature in Nanchang, China.

The composition and configuration of landscapes are critical important to design effective approaches to mitigate urban thermal environment in the urbanization process. In this research, land use maps and land surface temperature (LST) retrieval were derived in Nanchang city of central China based on product datasets and the thermal infrared band of Landsat. The results showed that the thermal environment of Nanchang had become worse over the past two decades, that is, the proportion of area of the extremely low temperature zone (ELTZ) decreased from 4.39 to 0.77% from 2001 to 2020, and that of medium temperature zone (MTZ) reduced by 20%, whereas those of the high temperature zone (HTZ) and the extremely high temperature zone (EHTZ) increased sharply after 2001, and by 2020, the area ratio increased by 11% and 7.16%, respectively. The agricultural land (AL) area decreased from 68.44 to 49.69%, was gradually replaced by construction land (CL). The CL occupied the largest proportion in EHTZ, HTZ and slight high temperature zone (SHTZ); water landscape (WL) and green land (GL) occupied the largest proportion in ELTZ, low temperature zone (LTZ); and AL occupied the largest proportion in SHTZ, MTZ, and slight low temperature zone (SLTZ). Landscape configuration also obviously impacted on LST. The model fitting was well (R = 0.87) between land use area and LST by multiple regression analysis. The significant correlation between LST and six landscape pattern indices of CL (p < 0.01) indicated that the larger percent (PLANT, R = 0.78) and the more concentrate (LPI, R = 0.73) of CL implied the higher LST, while the more fragment (NP, R = - 0.45), dispersed and complex shape (R = - 0.35) were benefit to relieve LST. Contrastively, the larger percent and the more concentrated and complex shape distribution of AL, GL and WL, the lower LST (p < 0.01). In addition, LST had closely correlation with landscape level indices such as aggregation degree (AI, R = 0.44) and diversity (SHDI, R = - 0.60) (p < 0.01).

Asymmetric Cyclodextrin-Dimer-Involved Nanoassemblies by Selective Host-Guest Interactions: Concentration-Dependent Morphology Evolution and Light-Regulated Biomedical Applications.

Supramolecular assembly has attracted significant attention and has been applied to various applications. Herein, a ß-γ-CD dimer was synthesized to complex different guest molecules, including single-strand polyethylene glycol (PEG)-modified C60 (PEG-C60), photothermal conversion reagent (IR780), and dexamethasone (Dexa), according to the complexation constant-dependent specific selectivity. Spherical or cylindrical nanoparticles, monolayer or bilayer vesicles, and bilayer fusion vesicles were discovered in succession if the concentration of PEG-C60 was varied. Moreover, if near-infrared light was employed to irradiate these nanoassemblies, the thermo-induced morphological evolution, subsequent cargo release, photothermal effect, and singlet oxygen (1O2) generation were successfully achieved. The in vitro cell experiments confirmed that these nanoparticles possessed excellent biocompatibility in a normal environment and achieved superior cytotoxicity by light regulation. Such proposed strategies for the construction of multilevel structures with different morphologies can open a new window to obtain various host-guest functional materials and achieve further use for disease treatment.

Oral chemotherapy versus observation alone in nasopharyngeal carcinoma patients with persistently detected circulating cell-free Epstein-Barr virus DNA during follow-up.

AIM: Despite the high risk of tumor recurrence, patients with nasopharyngeal carcinoma (NPC) with persistently (at least twice) detected circulating cell-free Epstein-Barr virus (EBV) DNA levels during follow-up are routinely recommended to keep observation. For these patients, whether administering more aggressive treatment could improve survival outcomes remains unknown. MATERIALS AND METHODS: We retrospectively included 431 patients with nonmetastatic NPC with persistently detected EBV DNA during follow-up, who do not have clinical or imaging evidence of recurrence. Among these patients, 79 were administered oral chemotherapy, and the remaining 352 underwent observation alone. Baseline characteristics were balanced with propensity score matching (PSM) analysis. The primary endpoint was modified disease-free survival (mDFS), defined as time from detectable EBV DNA result to tumor recurrence or death. The secondary endpoints were disease-free survival (DFS) and overall survival (OS). RESULTS: One-to-three PSM resulted in 251 eligible patients (oral chemotherapy group, 73; observation group, 178). In the matched cohort, the oral chemotherapy group had higher median mDFS (12.9 months [95 % confidence interval [CI] 9.6-16.3] vs. 6.8 months [95 % CI 5.8-7.8], p = 0.009) and DFS (24.1 months [95 % CI 18.5-29.7] vs. 16.7 months [95 % CI 14.4-19.1], p = 0.035) than the observation group. The median OS was numerically higher in the oral chemotherapy group than in the observation group (57.9 months [95 % CI 42.5-73.3] vs. 50.8 months [95 % CI 39.7-61.9], p = 0.71). A consistent benefit favoring oral chemotherapy was observed for mDFS in all subgroups analyses for male, <45 years, stage III-IVa disease, pretreatment EBV DNA load ≥ 4,000 copies/mL, no induction chemotherapy, or a detectable EBV DNA load ≥ 1,200 copies/mL. After adjusting for other confounders in the multivariate analysis, oral chemotherapy remained a significantly favorable factor for both mDFS (hazard ratio [HR] 0.67, 95 % CI 0.50-0.89; p = 0.006) and DFS (HR 0.68, 95 % CI 0.51-0.91; p = 0.01), but not a significant factor for OS (HR 0.89, 95 % CI 0.62-1.27; p = 0.52). CONCLUSIONS: In patients with NPC having persistently detected EBV DNA levels but without clinical or imaging evidence of recurrence during follow-up, oral chemotherapy significantly prolongs mDFS and DFS. Employing oral chemotherapy as a more aggressive treatment option, as opposed to mere observation, could potentially benefit these patients, although further prospective validation is necessitated.

Evaluation and analysis of risk factors of hearing impairment for nasopharyngeal carcinoma treated using intensity-modulated radiotherapy.

BACKGROUND: Treating nasopharyngeal carcinoma (NPC) with radiotherapy frequently causes hearing impairment (HI). HI risk data haven't been evaluated quantitatively. This study aimed to analyze the probability of HI and sever HI (SHI), develop a nomogram to quantify individual prediction, and provide dose limitation suggestions. METHODS AND MATERIALS: This single-center, retrospective study was conducted based on 588 adolescents and young adults with non-metastatic NPC treated using intensity modulated radiation therapy (IMRT) at Sun Yat-sen University Cancer Center between 2010 and 2016. A least absolute shrinkage and selection operator (LASSO) logistic regression model and univariate analysis were used to screen potential risk factors. The concordance index and a calibration curve evaluated the nomogram models' predictive ability, with bootstrap resampling validation. RESULTS: We analyzed 588 patients with NPC, with a median follow-up of 103.4 months. HI occurred in 39.5 % of patients, with 29.7 % experiencing SHI. Two factors were classified as precursors for HI (volume 45 Gy of the inner ear (IEV45) and volume 50 Gy of the internal auditory canal (IACV50)), and IACmin and IACV60 for SHI, respectively. Prognostic nomograms were developed to predict HI and SHI probabilities, showing excellent discriminative abilities (c-index values = 0.806 and 0.793, respectively). We also suggested IEV45 < 50 % and/or IACV50 < 40 % as rational dose limitations for HI, and IACmin < 44 Gy and/or the IACV60 < 40 % for SHI. CONCLUSION: Comprehensive analysis could predict the risk of HI and SHI in NPC after IMRT, proposing rational dose limitations and improving long-term quality of life.

Six-Electron-Redox Iodine Electrodes for High-Energy Aqueous Batteries.

Iodine (I2 ) shows great promising as the active material in aqueous batteries due to its distinctive merits of high abundance in ocean and low cost. However, in conventional aqueous I2 -based batteries, the energy storage mechanism of I- /I2 conversion is only two-electron redox reaction, limiting their energy density. Herein, six-electron redox chemistry of I2 electrodes is achieved via the synergistic effect of redox-ion charge-carriers and halide ions in electrolytes. The redox-active Cu2+ ions in electrolytes induce the conversion between Cu2+ ions and I2 to CuI at low potential. Simultaneously, the Cl- ions in electrolytes activate the I2 /ICl redox couple at high potential. As a result, in our case, I2 -based battery system with six-electron redox is developed. Such energy storage mechanism with six-electron redox leads to high discharge potential and capacity, excellent rate capability, as well as stable cycling behavior of I2 electrodes. Impressively, six-electron-redox I2 cathodes can match various aqueous metal (e.g. Zn, Mn and Fe) anodes to construct metal||I2 hybrid batteries. These hybrid batteries not only deliver enhanced capacities, but also exhibit higher operate voltages, which contributes to superior energy densities. Therefore, this work broadens the horizon for the design of high-energy aqueous I2 -based batteries.

Quercitrin Is a Novel Inhibitor of Salmonella enterica Serovar Typhimurium Type III Secretion System.

The purpose was to screen type III secretory system (T3SS) inhibitors of Salmonella enterica serovar Typhimurium (S. Typhimurium) from natural compounds. The pharmacological activities and action mechanisms of candidate compounds in vivo and in vitro were systematically studied and analyzed. Using a SipA-ß-lactamase fusion reporting system, we found that quercitrin significantly blocked the translocation of SipA into eukaryotic host cells without affecting the growth of bacteria. Adhesion and invasion assay showed that quercitrin inhibited S. Typhimurium invasion into host cells and reduced S. Typhimurium mediated host cell damage. ß-galactosidase activity detection and Western blot analysis showed that quercitrin significantly inhibited the expression of SPI-1 genes (hilA and sopA) and effectors (SipA and SipC). The results of animal experiments showed that quercitrin significantly reduced colony colonization and alleviated the cecum pathological injury of the infected mice. Small molecule inhibitor quercitrin directly inhibited the function of T3SS and provided a potential antibiotic alternative against S. Typhimurium infection. Importance: T3SS plays a crucial role in the bacterial invasion and pathogenesis of S. Typhimurium. Compared with conventional antibiotics, small molecules could inhibit the virulence factors represented by S. Typhimurium T3SS. They have less pressure on bacterial vitality and a lower probability of producing drug resistance. Our results provide strong evidence for the development of novel inhibitors against S. Typhimurium infection.

Synergistic chemo-photo anticancer therapy by using reversible Diels-Alder dynamic covalent bond mediated polyprodrug amphiphiles and immunoactivation investigation.

Highly efficient endocytosis and multi-approach integrated therapeutic tactics are important factors in oncotherapy. With the aid of thermally reversible furan-maleimide dynamic covalent bonds and the "polyprodrug amphiphiles" concept, thermo- and reduction-responsive PEG(-COOH)Fu/MI(-SS-)CPT copolymers were fabricated by the Diels-Alder (D-A) coupling of hydrophilic Fu(-COOH)-PEG and hydrophobic MI(-SS-)-CPT building blocks. The copolymers could self-assemble to form composite nanoparticles with a photothermal conversion reagent (IR780) and maintain excellent stability. In the in vitro simulated environments, the composite nanoparticles could detach Fu(-COOH)-PEG chains by a retro-D-A reaction upon near-infrared light (NIR) irradiation and reduce the size to facilitate endocytosis. Once in the intracellular environment, glutathione (GSH) could trigger a cascade reaction to release active CPT drugs to achieve chemotherapy, which could be further promoted by NIR light induced photothermal therapy. The in vivo mouse tumor model experiments demonstrated that these nanoparticles had an excellent therapeutic effect on solid tumors and inhibited their recurrence. Not only that, the synergistic chemical and optical therapy induced body immune response was also systematically evaluated; the maturation of dendritic cells, the proliferation of T cells, the increase of high mobility group box protein 1, and the decrease of immunosuppressive regulatory T cells confirmed that such synergistic therapy could effectively provide immune protection to the body. We believe such in situ generation of small-sized therapeutic units brought by a dynamically reversible D-A reaction could expand the pathway to design next generation drug delivery systems possessing superior design philosophy and excellent practice effects compared to currently available ones.

Cardiovascular manifestations of inflammatory bowel diseases and the underlying pathogenic mechanisms.

Inflammatory bowel disease (IBD), consisting of ulcerative colitis and Crohn's disease, mainly affects the gastrointestinal tract but is also known to have extraintestinal manifestations because of long-standing systemic inflammation. Several national cohort studies have found that IBD is an independent risk factor for the development of cardiovascular disorders. However, the molecular mechanisms by which IBD impairs the cardiovascular system are not fully understood. Although the gut-heart axis is attracting more attention in recent years, our knowledge of the organ-to-organ communication between the gut and the heart remains limited. In patients with IBD, upregulated inflammatory factors, altered microRNAs and lipid profiles, as well as dysbiotic gut microbiota, may induce adverse cardiac remodeling. In addition, patients with IBD have a three- to four times higher risk of developing thrombosis than people without IBD, and it is believed that the increased risk of thrombosis is largely due to increased procoagulant factors, platelet count/activity, and fibrinogen concentration, in addition to decreased anticoagulant factors. The predisposing factors for atherosclerosis are present in IBD and the possible mechanisms may involve oxidative stress system, overexpression of matrix metalloproteinases, and changes in vascular smooth muscle phenotype. This review focuses mainly on 1) the prevalence of cardiovascular diseases associated with IBD, 2) the potential pathogenic mechanisms of cardiovascular diseases in patients with IBD, and 3) adverse effects of IBD drugs on the cardiovascular system. Also, we introduce here a new paradigm for the gut-heart axis that includes exosomal microRNA and the gut microbiota as a cause for cardiac remodeling and fibrosis.

Identification of key genes and pathways in atherosclerosis using integrated bioinformatics analysis.

BACKGROUND: Atherosclerosis (AS) is a chronic inflammatory disease that might induce severe cardiovascular events, such as myocardial infarction and cerebral infarction. These risk factors in the pathogenesis of AS remain uncertain and further research is needed. This study aims to explore the potential molecular mechanisms of AS by bioinformatics analyses. METHODS: GSE100927 gene expression profiles, including 69 AS samples and 35 healthy controls, were downloaded from Gene Expression Omnibus database and indenfied for key genes and pathways in AS. RESULTS: A total of 443 differentially expressed genes (DEGs) between control and AS were identified, including 323 down-regulated genes and 120 up-regulated genes. The Gene ontology terms enriched by the up-regulated DEGs were associated with the regulation of leukocyte activation, endocytic vesicle, and cytokine binding, while the down-regulated DEGs were associated with negative regulation of cell growth, extracellular matrix, and G protein-coupled receptor binding. KEGG pathway analysis showed that the up-regulated DEGs were enriched in Osteoclast differentiation and Phagosome, while the down-regulated DEGs were enriched in vascular smooth muscle contraction and cGMP-PKG signaling pathway. Using the modular analysis of Cytoscape, we identified 3 modules mainly involved in Leishmaniasis and Osteoclast differentiation. The GSEA analysis showed the up-regulated gene sets were enriched in the ribosome, ascorbated metabolism, and propanoate metabolism. The LASSO Cox regression analysis showed the top 3 genes were TNF, CX3CR1, and COL1R1. Finally, we found these immune cells were conferred significantly higher infiltrating density in the AS group. CONCLUSIONS: Our data showed the pathway of Osteoclast differentiation and Leishmaniasis was involved in the AS process and we developed a three-gene model base on the prognosis of AS. These findings clarified the gene regulatory network of AS and may provide a novel target for AS therapy.

Increased Neuromedin B is Associated with a Favorable Prognosis in Glioblastoma.

BACKGROUND: Neuromedin B (NMB) is a neuropeptide that plays a key role in many physiological processes and is involved in the pathology of various diseases. Increased levels of NMB have been reported in solid tumors. Therefore, we investigated the prognostic value of NMB in glioblastoma (GBM). METHODS: Expression profiles of NMB mRNA were investigated in GBM and normal tissues using data from the cancer genome atlas (TCGA). NMB protein expression was obtained using data from the Human Protein Atlas. Receiver operating characteristic (ROC) curves were evaluated in GBM and normal tissues. The survival effect of NMB in GBM patients was evaluated using the Kaplan-Meier method. Protein-protein interaction networks were constructed using STRING, and the functional enrichment analyses were performed. The relationship between NMB expression and tumor-infiltrating lymphocytes was analyzed using the Tumor Immune Estimation Resource (TIMER) and the Tumor-Immune System Interaction database (TISIDB). RESULTS: NMB was overexpressed in GBM relative to normal biopsy specimens. The ROC analysis showed that the sensitivity and specificity of NMB in GBM were 96.4% and 96.2%, respectively. Kaplan-Meier survival analysis showed that GBM patients with high NMB expression had a better prognosis than those with low NMB expression (16.3 vs. 12.7 months, p = 0.002). Correlation analysis showed that NMB expression was associated with tumor-infiltrating lymphocytes and tumor purity. CONCLUSIONS: High expression of NMB was associated with increased GBM patient survival. Our study indicated that the NMB expression may be a biomarker for prognosis and that NMB may be an immunotherapy target in GBM.

Prognostic value of the immunohistochemical score based on four markers in head and neck squamous cell carcinoma.

Purpose: Head and neck squamous cell carcinoma (HNSCC) ranks sixth among all cancers globally regarding morbidity, and it has a poor prognosis, high mortality, and highly aggressive properties. In this study, we established a model for predicting prognosis based on immunohistochemical (IHC) scores. Methods: Data on 402 HNSCC cases were collected, the glmnet Cox proportional hazards model was used, risk factors were analyzed for predicting the prognosis of survival, and the IHC score was established. We used the IHC score to predict disease-free survival (DFS) using training and independent validation cohorts, including 264 cases in total. Additionally, the accuracy of the IHC score and the TNM system (8th edition) was compared. A DFS prediction nomogram was established by combining the prognostic factors. Results: The IHC scores included CK, Ki-67, p16, and p40 staining intensity. The concordance index and the Kaplan-Meier survival analysis showed that the IHC scores had high predictive power for HNSCC. Our results showed that the IHC score is an independent factor that can predict prognosis in a multivariate Cox regression analysis. When predicting DFS, the IHC score had a significantly higher value for the area under the ROC curve (AUC) than that of the TNM system. A nomogram was established and included the IHC score, age, tumor location, and the TNM stage. The calibration curves exhibited high consistency between the prognosis predicted by our nomogram and the actual prognosis. Conclusions: The IHC score was more accurate than the eighth edition of the TNM system in predicting HNSCC prognosis. Therefore, combining the two methods can facilitate individualized patient consultation and care.

TRIM21 inhibits irradiation-induced mitochondrial DNA release and impairs antitumour immunity in nasopharyngeal carcinoma tumour models.

Although radiotherapy can promote antitumour immunity, the mechanisms underlying this phenomenon remain unclear. Here, we demonstrate that the expression of the E3 ubiquitin ligase, tumour cell-intrinsic tripartite motif-containing 21 (TRIM21) in tumours, is inversely associated with the response to radiation and CD8+ T cell-mediated antitumour immunity in nasopharyngeal carcinoma (NPC). Knockout of TRIM21 modulates the cGAS/STING cytosolic DNA sensing pathway, potentiates the antigen-presenting capacity of NPC cells, and activates cytotoxic T cell-mediated antitumour immunity in response to radiation. Mechanistically, TRIM21 promotes the degradation of the mitochondrial voltage-dependent anion-selective channel protein 2 (VDAC2) via K48-linked ubiquitination, which inhibits pore formation by VDAC2 oligomers for mitochondrial DNA (mtDNA) release, thereby inhibiting type-I interferon responses following radiation exposure. In patients with NPC, high TRIM21 expression was associated with poor prognosis and early tumour relapse after radiotherapy. Our findings reveal a critical role of TRIM21 in radiation-induced antitumour immunity, providing potential targets for improving the efficacy of radiotherapy in patients with NPC.

Current advances in neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a rare but probably underdiagnosed neurodegenerative disorder due to pathogenic GGC expansions in the NOTCH2NLC gene. In this review, we summarize recent developments in the inheritance features, pathogenesis, and histopathologic and radiologic features of NIID that subvert the previous perceptions of NIID. GGC repeat sizes determine the age of onset and clinical phenotypes of NIID patients. Anticipation may be absent in NIID but paternal bias is observed in NIID pedigrees. Eosinophilic intranuclear inclusions in skin tissues once considered pathological hallmarks of NIID can also present in other GGC repeat diseases. Diffusion-weighted imaging (DWI) hyperintensity along the corticomedullary junction once considered the imaging hallmark of NIID can frequently be absent in muscle weakness and parkinsonism phenotype of NIID. Besides, DWI abnormalities can appear years after the onset of predominant symptoms and may even disappear completely with disease progression. Moreover, continuous reports of NOTCH2NLC GGC expansions in patients with other neurodegenerative diseases lead to the proposal of a new concept of NOTCH2NLC-related GGC repeat expansion disorders (NRED). However, by reviewing the previous literature, we point out the limitations of these studies and provide evidence that these patients are actually suffering from neurodegenerative phenotypes of NIID.

A population of stem cells with strong regenerative potential discovered in deer antlers.

The annual regrowth of deer antlers provides a valuable model for studying organ regeneration in mammals. We describe a single-cell atlas of antler regrowth. The earliest-stage antler initiators were mesenchymal cells that express the paired related homeobox 1 gene (PRRX1+ mesenchymal cells). We also identified a population of "antler blastema progenitor cells" (ABPCs) that developed from the PRRX1+ mesenchymal cells and directed the antler regeneration process. Cross-species comparisons identified ABPCs in several mammalian blastema. In vivo and in vitro ABPCs displayed strong self-renewal ability and could generate osteochondral lineage cells. Last, we observed a spatially well-structured pattern of cellular and gene expression in antler growth center during the peak growth stage, revealing the cellular mechanisms involved in rapid antler elongation.

Microplastic load of benthic fauna in Jiaozhou Bay, China.

The prevalence of microplastic pollution in the ocean has caused widespread concern. Many studies have focused on the occurrence of microplastics in the marine environment and organisms, but the fate of microplastics in the ocean is still unclear, and the factors affecting the distribution of microplastics have not yet been consistently concluded. The aims of this study were to estimate the load of microplastics in benthic organisms as a temporary storage and to analyze the factors affecting microplastic ingestion by benthic organisms. For the purpose of this study, the benthic organisms in Jiaozhou Bay, China, were collected quarterly and were divided into the following six groups: polychaetes, mollusks, crustaceans, echinoderms, fish, and others. We concluded that the microplastic abundance in the benthos in Jiaozhou Bay was 1.00 ± 0.11 items/ind. (15.5 ± 3.5 items/g). The total load of microplastics in the benthic fauna in the bay with an area of 374 km2 was estimated to be 36.4 kg. On an individual basis, the fish contained significantly more microplastics than the other taxa. Furthermore, the characteristics of the microplastics in the benthic organisms were mainly fibrous, black, polyethylene, and <500 µm in size. In addition, the microplastic ingestion by benthic organisms was regulated by multiple factors, including biological characteristics and the environment. The masses of the organisms, the ambient seawater and sediment, and the spatial variations all influenced the microplastic ingestion by the organisms. The results of this study demonstrate that benthic organisms are an important storage for microplastics as they transferred through the ocean, and they provide an unbiased comparison of microplastic pollution among multiple organisms and the relevant pollution factors.

A New Zinc Salt Chemistry for Aqueous Zinc-Metal Batteries.

Aqueous zinc-ion batteries (ZIBs) are promising energy storage solutions with low cost and superior safety, but they suffer from chemical and electrochemical degradations closely related to the electrolyte. Here, a new zinc salt design and a drop-in solution for long cycle-life aqueous ZIBs are reported. The salt Zn(BBI)2 with a rationally designed anion group, N-(benzenesulfonyl)benzenesulfonamide (BBI- ), has a special amphiphilic molecular structure, which combines the benefits of hydrophilic and hydrophobic groups to properly tune the solubility and interfacial condition. This new zinc salt does not contain fluorine and is synthesized via a high-yield and low-cost method. It is shown that 1 m Zn(BBI)2 aqueous electrolyte with a widened cathodic stability window effectively stabilizes Zn metal/H2 O interface, mitigates chemical and electrochemical degradations, and enables both symmetric and full cells using a zinc-metal electrode.