Sulfonium-Stapled Peptides-Based Neoantigen Delivery System for Personalized Tumor Immunotherapy and Prevention.

Neoantigen peptides hold great potential as vaccine candidates for tumor immunotherapy. However, due to the limitation of antigen cellular uptake and cross-presentation, the progress with neoantigen peptide-based vaccines has obviously lagged in clinical trials. Here, a stapling peptide-based nano-vaccine is developed, comprising a self-assembly nanoparticle driven by the nucleic acid adjuvant-antigen conjugate. This nano-vaccine stimulates a strong tumor-specific T cell response by activating antigen presentation and toll-like receptor signaling pathways. By markedly improving the efficiency of antigen/adjuvant co-delivery to the draining lymph nodes, the nano-vaccine leads to 100% tumor prevention for up to 11 months and without tumor recurrence, heralding the generation of long-term anti-tumor memory. Moreover, the injection of nano-vaccine with signal neoantigen eliminates the established MC-38 tumor (a cell line of murine carcinoma of the colon without exogenous OVA protein expression) in 40% of the mice by inducing potent cytotoxic T lymphocyte infiltration in the tumor microenvironment without substantial systemic toxicity. These findings represent that stapling peptide-based nano-vaccine may serve as a facile, general, and safe strategy to stimulate a strong anti-tumor immune response for the neoantigen peptide-based personalized tumor immunotherapy.

Macroscale Superlubricity on Nanoscale Graphene Moiré Structure-Assembled Surface via Counterface Hydrogen Modulation.

Interlayer incommensurateness slippage is an excellent pathway to realize superlubricity of van der Waals materials; however, it is instable and heavily depends on twisted angle and super-smooth substrate which pose great challenges for the practical application of superlubricity. Here, macroscale superlubricity (0.001) is reported on countless nanoscale graphene moiré structure (GMS)-assembled surface via counterface hydrogen (H) modulation. The GMS-assembled surface is formed on grinding balls via sphere-triggered strain engineering. By the H modulation of counterface diamond-like carbon (25 at.% H), the wear of GMS-assembled surface is significantly reduced and a steadily superlubric sliding interface between them is achieved, based on assembly face charge depletion and H-induced assembly edge weakening. Furthermore, the superlubricity between GMS-assembled and DLC25 surfaces holds true in wide ranges of normal load (7-11 N), sliding velocity (0.5-27 cm -1s), contact area (0.4×104-3.7×104 µm2), and contact pressure (0.19-1.82 GPa). Atomistic simulations confirm the preferential formation of GMS on a sphere, and demonstrate the superlubricity on GMS-assembled surface via counterface H modulation. The results provide an efficient tribo-pairing strategy to achieve robust superlubricity, which is of significance for the engineering application of superlubricity.

G-quadruplexes on chromosomal DNA negatively regulates topoisomerase 1 activity.

Human DNA topoisomerase 1 (Top1) is a crucial enzyme responsible for alleviating torsional stress on DNA during transcription and replication, thereby maintaining genome stability. Previous researches had found that non-working Top1 interacted extensively with chromosomal DNA in human cells. However, the reason for its retention on chromosomal DNA remained unclear. In this study, we discovered a close association between Top1 and chromosomal DNA, specifically linked to the presence of G-quadruplex (G4) structures. G4 structures, formed during transcription, trap Top1 and hinder its ability to relax neighboring DNAs. Disruption of the Top1-G4 interaction using G4 ligand relieved the inhibitory effect of G4 on Top1 activity, resulting in a further reduction of R-loop levels in cells. Additionally, the activation of Top1 through the use of a G4 ligand enhanced the toxicity of Top1 inhibitors towards cancer cells. Our study uncovers a negative regulation mechanism of human Top1 and highlights a novel pathway for activating Top1.

Depletion of PHLDB2 Suppresses Epithelial-Mesenchymal Transition and Enhances Anti-Tumor Immunity in Head and Neck Squamous Cell Carcinoma.

The role of Pleckstrin homology-like domain family B member 2 (PHLDB2) in the regulation of cell migration has been extensively studied. However, the exploration of PHLDB2 in head and neck squamous cell carcinoma (HNSCC) is still limited in terms of expression, function, and therapeutic potential. In this study, we discovered an upregulation of PHLDB2 expression in HNSCC tissues which was correlated with a negative prognosis in patients with HNSCC. Additionally, we determined that a high level of expression of PHLDB2 is crucial for maintaining cell migration through the regulation of the epithelial-mesenchymal transition (EMT). Furthermore, we demonstrated that the ablation of PHLDB2 in tumor cells inhibited tumorigenicity in a C3H syngeneic tumor-bearing mouse model. Mechanistically, PHLDB2 was found to be involved in the regulation of T cell anti-tumor immunity, primarily by enhancing the activation and infiltration of CD8+ T cells. In light of these findings, PHLDB2 emerges as a promising biomarker and therapeutic target for interventions in HNSCC.

Covalent PROTAC design method based on a sulfonyl pyridone probe.

Covalent proteolysis-targeting chimeras (PROTACs) offer enhanced selectivity, prolonged action, and increased efficacy against challenging target proteins. The conventional approach relies on covalent ligands, but our study presents an innovative method employing an N-sulfonyl pyridone warhead to selectively target tyrosine (Tyr) residues. The von Hippel-Lindau (VHL) moiety is transferred from the warhead to the exposed Tyr, allowing us to design a STING degrader (DC50 0.53 µM, Dmax 56.65%). This approach showcases the potential of nucleophilic amino acid labeling probes, particularly for proteins lacking easily accessible cysteine residues, opening new possibilities for covalent PROTAC design and targeted protein degradation therapies.

Covalent Peptide LSD1 Inhibitor Specifically Recognizes Cys360 in the Enzyme-Active Region.

Lysine-specific demethylase 1 (LSD1) is a promising therapeutic target, especially in cancer treatment. Despite several LSD1 inhibitors being discovered for the cofactor pocket, none are FDA-approved. We aimed to develop stabilized peptides for irreversible LSD1 binding, focusing on unique cysteine residue Cys360 in LSD1 and SNAIL1. We created LSD1 C360-targeting peptides, like cyclic peptide S9-CMC1, using our Cysteine-Methionine cyclization strategy. S9-CMC1 effectively inhibited LSD1 at the protein level, as confirmed by MS analysis showing covalent bonding to Cys360. In cells, S9-CMC1 inhibited LSD1 activity, increasing H3K4me1 and H3K4me2 levels, leading to G1 cell cycle arrest and apoptosis and inhibiting cell proliferation. Remarkably, S9-CMC1 showed therapeutic potential in A549 xenograft animal models, regulating LSD1 activity and significantly inhibiting tumor growth with minimal organ damage. These findings suggest LSD1 C360 as a promising site for covalent LSD1 inhibitors' development.

Exploring temporal trends and influencing factors for thyroid cancer in Guangzhou, China: 2004-2018.

PURPOSE: Describe and analyze the trends of thyroid cancer incidence and mortality in Guangzhou, explore the potential influencing factors, and provide evidence for the government to formulate prevention and treatment measures. METHODS: Incident and death cases of thyroid cancer were retrieved from the Guangzhou cancer registry. The joinpoint regression models were used to estimate the incidence and mortality trends. Age-period-cohort models were used to estimate the age, period, and cohort effects on the time trends. Grey correlation analysis was performed to explore possible connections between thyroid cancer and social factors. RESULTS: A total of 15,955 new cases of thyroid cancer were registered in Guangzhou during 2004-2018, the age-standardized incidence rate (ASIR) of thyroid cancer increased from 4.29/105 in 2004 to 22.36/105 in 2018, with the average annual percentage change (AAPC) of 13.40%. The overall increase can be attributed to the increase in the incidence of papillary thyroid carcinoma (PTC), which was dominated by tumors <2 cm. The ASIR was higher in women (16.12/105) compared to men (5.46/105), and young and middle-aged individuals had higher incidence rates than older people. The number of thyroid cancer deaths registered between 2010 and 2018 was 356, and the age-standardized mortality rates (ASMRs) were stable (approximately 0.42/105). Men's ASMR (0.34/105) and women's (0.49/105) were similar, and those 60 and older had greater mortality. The period and cohort relative risks showed an overall increasing trend. Furthermore, there was a strong positive correlation between the ASIRs and social determinants. CONCLUSIONS: During the study period, the incidence rate of thyroid cancer among young and middle-aged people in Guangzhou showed a rapidly increasing trend, and the mortality was relatively stable. In the future, more effective preventive measures should be taken for this age group to reduce the burden of disease and avoid overdiagnosis.

Targeted Biomolecule Regulation Platform: A Split-and-Mix PROTAC Approach.

The development of bifunction al molecules, which can enable targeted RNA degradation, targeted protein acetylation, or targeted protein degradation, remains a time-consuming process that requires tedious optimization. We propose a split-and-mix nanoplatform that serves as a self-adjustable platform capable of facile screening, programmable ligand ratios, self-optimized biomolecule spatial recognition, and multifunctional applications. Herein, we demonstrate the potential of our proposed nanoplatform by showcasing proteolysis-targeting chimeras (PROTACs), namely, split-and-mix PROTAC (SM-PROTAC). We highlight the scope of our platform through the targeted disruption of intracellular therapeutic targets involving ERα, CDK4/6, AR, MEK1/2, BRD2/4, BCR-ABL, etc. These studies confirm the effectiveness and universality of the SM-PROTAC platform for proximity-induced applications. This platform is programmable, with significant potential applications to biomolecule regulation, including the fields of epigenetics, gene editing, and biomolecule modification regulation.

Amyotrophic lateral sclerosis in seven provinces of Chinese mainland: A cross-sectional survey from 2015 to 2016.

Background: The large-scale survey about amyotrophic lateral sclerosis (ALS) based on both population and hospitals in the Chinese mainland has been deficient at present. To this end, we conducted a cross-sectional survey about ALS based on the population and hospitals in seven provinces of the Chinese mainland in 2015-2016. Methods: We surveyed patients with ALS in seven provinces in eastern, middle, and western China. Among them, 13 prefecture-level cities, 13 municipal districts, 13 counties, 26 streets, 52 communities, 39 towns, and 78 administrative villages were selected for the population-based survey. Totally, 13 class-3 general hospitals, 13 class-2 general hospitals, and 26 street health centers or community health service centers in urban districts, and 13 county-level general hospitals, 39 township health centers, and 78 village clinics in rural districts were recruited for the hospital-based survey. Results: Among the Chinese mainland, the total prevalence of ALS was slightly lower than that of the world's other nations or districts. The male patients were more than female patients. The prevalence of rural residents was more than that of urban residents. The prevalence of farmers was higher than that of other professions. The majority of ALS was not accompanied by other chronic diseases. The peak onset age of ALS was higher, familial ALS (fALS) cases were slightly more, and the average survival duration of sporadic ALS (sALS) was slightly lower compared with the previous investigation data. The hospitalization expenses of almost 60% of ALS were not more than 10,000 Chinese Yuan. Conclusion: Hospitalization expenses in our survey objectives were the lowest in the current reported countries and districts. A farmer was a possible higher risk profession for ALS, the majority of ALS were not accompanied by other chronic diseases. Our survey provided more information on the epidemiology of ALS worldwide and supplied the deficiency of epidemiology survey about ALS from the Chinese mainland.

Polymorphisms of adiponectin gene and gene-lipid interaction with hypertension risk in Chinese coal miners: A matched case-control study.

OBJECTIVE: Low serum adiponectin level can predict hypertension development, and adiponectin gene (ADIPOQ) polymorphisms have been reported to be linked with hypertension risk. Whereas, the interaction between ADIPOQ polymorphisms and environmental factors on the susceptibility of hypertension remained unclear. The purpose of this study was to explore the relationship of ADIPOQ polymorphisms with hypertension risk and their interaction with lipid levels in coal miners. METHODS: A matched case-control study with 296 case-control pairs was performed in a large coal mining group located in North China. The participants were questioned by trained interviewers, and their ADIPOQ genotype and lipid levels were determined. Logistic regression, stratified analysis, and crossover analysis were applied to evaluate the effects of rs2241766, rs1501299, and rs266729 genotypes and gene-lipid interaction on hypertension risk. RESULTS: In this matched case-control study, the genotypes of rs2241766 TG+GG, rs1501299 GT+TT, and rs266729 CG+GG were marginally related to hypertension risk. Individuals with high total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) level were susceptible to hypertension (TC: odds ratio [OR] = 1.807, 95% confidence intervals [95%CI] = 1.266-2.581; LDL-C: OR = 1.981, 95%CI = 1.400-2.803; HDL-C: OR = 1.559, 95%CI = 1.093-2.223). Antagonistic interactions were detected between rs2241766 and TC, rs1501299 and TC, rs2241766 and LDL-C, and rs1501299 and HDL-C (rs2241766 and TC: OR = 0.393, 95%CI = 0.191-0.806; rs1501299 and TC: OR = 0.445, 95%CI = 0.216-0.918; rs2241766 and LDL-C: OR = 0.440, 95%CI = 0.221-0.877; rs1501299 and HDL-C: OR = 0.479, 95%CI = 0.237-0.967). Stratified analysis showed that hypertension risk was high for the subjects with rs2241766 TG+GG or rs1501299 GG under the low lipid level but low for those under the high lipid level. In the case group, the TC and LDL-C levels for rs2241766 TG+GG were lower than those for rs2241766 GG, and the TC and HDL-C levels for rs1501299 GT+TT were higher than those for rs1501299 GG. CONCLUSIONS: Although the effects of ADIPOQ polymorphisms alone were not remarkable, an antagonistic interaction was observed between ADIPOQ polymorphisms and lipid levels.

Potential proteomic alteration in the brain of Tg(SOD1*G93A)1Gur mice: A new pathogenesis insight of amyotrophic lateral sclerosis.

The pathogenesis of amyotrophic lateral sclerosis (ALS) remains unclear. The recent studies have suggested that the protein abnormalities could play some important roles in ALS because several protein mutations were found in individuals with this disease. However, proteins that are currently known to be associated with ALS only explain the pathogenesis of this disease in a minority of cases, thus, further screening is needed to identify other ALS-related proteins. In this study, we systematically analyzed and compared the brain proteomic alterations between a mouse model of ALS, the Tg(SOD1*G93A)1Gur model, and wild-type mice using isobaric tags for relative and absolute quantitation (iTRAQ) as well as bioinformatics methods. The results revealed some significant up- and downregulated proteins at the different developmental stages in the ALS-like mice as well as the possibly related cellular components, molecular functions, biological processes, and pathways in the development of ALS. Our results identified some possible proteins that participate in the pathogenesis of ALS as well as the cellular components that are damaged by these proteins, we additionally identified the molecular functions, the biological processes, and the pathways of these proteins as well as the molecules that are associated with these pathways. This study represents an important preliminary investigation of the role of proteomic abnormalities in the pathogenesis of ALS, both in human patients and other animal models. We present some novel findings that may serve as a basis for further investigation of abnormal proteins that are involved in the pathogenesis of ALS.

Baicalin attenuate diet-induced metabolic syndrome by improving abnormal metabolism and gut microbiota.

In this work, we examined whether baicalin (BC), a bioactive flavonoid in Scutellaria baicalensis Georgi, can reduce high-fat diet (HFD)-induced metabolic syndrome (MetS) in mice. The UPLC-QTOF/MS was used for metabolome profiles analysis, and an analysis of bacterial 16S rDNA in feces was used to examine the effects of BC on gut microbiota composition. Our results showed that BC (400 mg/kg) could reduce the body weight gain, decrease hepatic fat accumulation and abnormal blood lipids, and increase insulin sensitivity after 8 weeks of treatment. BC could reverse the alteration of 7 metabolites induced by HFD and the metabolic pathways responsive to BC intervention including citrate cycle, alanine, aspartate and glutamate metabolism, glycerophospholipid metabolism, and aminoacyl-tRNA biosynthesis. 16S rDNA analysis demonstrated that BC altered the composition and function of gut microbiota in MetS mice. Notably, we found that the change in succinic acid was negatively associated with the changes in Bacteroides and Sutterella, and positively associated with the change in Mucispirillum. Moreover, we confirmed that succinic acid displayed a metabolic protective effect on MetS mice. The antibiotic treatment verified that BC exerts metabolic protection through gut microbiota. Our findings suggested BC may be a potential therapeutic drug to ameliorate diet induced MetS and gut microbiome may be a novel mechanistic target of BC for treatment of MetS.

Mammalian eIF4E2-GSK3ß maintains basal phosphorylation of p53 to resist senescence under hypoxia.

Hypoxia modulates senescence, but their physiological link remains unclear. Here, we found that eIF4E2, a hypoxia-activated translation initiation factor, interacted with GSK3ß to maintain phosphorylation of p53, thus resisting senescence under hypoxia. RNA-binding protein RBM38 interacted with eIF4E to inhibit the translation of p53, but GSK3ß-mediated Ser195 phosphorylation disrupted the RBM38-eIF4E interaction. Through investigation of RBM38 phosphorylation, we found that the eIF4E2-GSK3ß pathway specifically regulated proline-directed serine/threonine phosphorylation (S/T-P). Importantly, peptides e2-I or G3-I that blocking eIF4E2-GSK3ß interaction can inhibit the basal S/T-P phosphorylation of p53 at multiple sites, therby inducing senescence through transcriptional inhibition. Additionally, a nanobody was screened via the domain where eIF4E2 bound to GSK3ß, and this nanobody inhibited S/T-P phosphorylation to promote senescence. Furthermore, hypoxia inhibited eIF4E2-GSK3ß pathway by mediating S-Nitrosylation of GSK3ß. Blocking eIF4E2-GSK3ß interaction promoted liver senescence under hypoxia, thus leading to liver fibrosis, eventually accelerating N, N-diethylnitrosamine (DEN)-induced tumorigenesis. Interestingly, eIF4E2 isoforms with GSK3ß-binding motif exclusively exist in mammals, which protect zebrafish heart against hypoxia. Together, this study reveals a mammalian eIF4E2-GSK3ß pathway that prevents senescence by maintaining basal S/T-P phosphorylation of p53, which underlies hypoxia adaptation of tissues.

Spectrum-Effect Relationships Between High-Performance Liquid Chromatography Fingerprints and Hepatoprotective Activities of Cuscutae Semen.

BACKGROUND: Cuscutae Semen (CS) is a commonly used hepatoprotective traditional Chinese medicine, but the chemical components responsible for its hepatoprotective activity are unclear. OBJECTIVE: The purpose of this study was to evaluate the spectrum-effect relationships between HPLC fingerprints and hepatoprotective effects of CS, and to identify its bioactive components. METHODS: Phytochemical isolation of CS extracts was first carried out and 14 potential bioactive compounds were obtained. Chemical fingerprinting was performed on 27 batches of CS from different sources by HPLC, and further analyzed by similarity analysis (SA) and hierarchical clustering analysis (HCA). Pharmacodynamic testing was performed in a CCl4-induced, acute liver injury cell model to assess the hepatoprotective activity of CS by measuring the cell viability and levels of alanine transaminase (ALT) and aspartate aminotransferase (AST). Bivariate correlations analysis (BCA) and orthogonal projections to latent structures (OPLS) were used to analyze the spectrum-effect relationships of CS. RESULTS: The results showed that the chemical fingerprints of CS were closely correlated with its hepatoprotective activity. Peaks 1, 10, 18, 19, 21, 22, and 24 might be potential hepatoprotective compounds in CS, and the validation experiments of isolated compounds indicated that chlorogenic acid (P10), hyperoside (P21), isoquercitrin (P22), and astragalin (P24) were the main hepatoprotective components. CONCLUSION: By combining chemical fingerprints with hepatoprotective evaluation, the present study provides important guidance for QC and clinical use of CS. HIGHLIGHTS: (1) Ten potential bioactive compounds were isolated from CS; (2) The spectrum-effect relationship of CS was molded by HPLC and analysed by OPLS and BCA. (3) Four compounds including chlorogenic acid were the main hepatoprotective components.

Regulation of PDGFR-ß gene expression by targeting the G-vacancy bearing G-quadruplex in promoter.

G-quadruplex is an essential element in gene transcription that serves as a promising drug target. Guanine-vacancy-bearing G-quadruplex (GVBQ) is a newly identified G-quadruplex that has distinct structural features from the canonical G-quadruplex. Potential GVBQ-forming motifs are widely distributed in gene promoter regions. However, whether GVBQ can form in genomic DNA and be an effective target for manipulating gene expression is unknown. Using photo-crosslinking, dimethyl sulfate footprinting, exonuclease digestion and in vitro transcription, we demonstrated the formation of a GVBQ in the G-rich nuclease hypersensitivity element within the human PDGFR-ß gene promoter region in both single-stranded and double-stranded DNA. The formation of GVBQ in dsDNA could be induced by negative supercoiling created by downstream transcription. We also found that the PDGFR-ß GVBQ was specifically recognized and stabilized by a new synthetic porphyrin guanine conjugate (mPG). Targeting the PDGFR-ß GVBQ in human cancer cells using the mPG could specifically alter PDGFR-ß gene expression. Our work illustrates that targeting GVBQ with mPG in human cells can regulate the expression level of a specific gene, thus indicating a novel strategy for drug development.

Urinary Metabolite Signatures for Predicting Elderly Stroke Survivors with Depression.

BACKGROUND: Post-stroke depression (PSD) is a major complication in stroke survivors, especially in elderly stroke survivors. But there are still no objective methods to diagnose depression in elderly stroke survivors. Thus, this study was conducted to identify potential biomarkers for diagnosing elderly PSD subjects. METHODS: Elderly (60 years or older) stroke survivors with depression were assigned into the PSD group, and elderly stroke survivors without depression and elderly healthy controls (HCs) were assigned into the non-depressed group. Urinary metabolite signatures obtained from gas chromatography-mass spectrometry (GC-MS)-based metabolomic platform were collected. Both univariate and multivariate statistical analysis were used to find the differential urinary metabolites between the two groups. RESULTS: The 78 elderly HCs, 122 elderly stroke survivors without depression and 124 elderly PSD subjects were included. A set of 13 differential urinary metabolites responsible for distinguishing PSD subjects from non-depressed subjects were found. The Phenylalanine, tyrosine and tryptophan biosynthesis, Phenylalanine metabolism and Galactose metabolism were found to be significantly changed in elderly PSD subjects. The phenylalanine was significantly negatively correlated with age and depressive symptoms. Meanwhile, a biomarker panel consisting of 3-hydroxyphenylacetic acid, tyrosine, phenylalanine, sucrose, palmitic acid, glyceric acid, azelaic acid and α-aminobutyric acid was identified. CONCLUSION: These results provided candidate molecules for developing objective methods to diagnose depression in elderly stroke survivors, suggested that taking supplements of phenylalanine might be an effective method to prevent depression in elderly stroke survivors, and would be helpful for future revealing the pathophysiological mechanism of PSD.

Recovery of gold from waste mobile phone circuit boards and synthesis of nanomaterials using emulsion liquid membrane.

In recent years, waste mobile phones have become popular as electronic waste due to the huge amount, serious pollution with improper disposal and high resource value. It is imperative to realize the recycling of resources in waste mobile phones. The application of emulsion liquid membrane in the recovery of gold and synthesis of nanomaterials from waste mobile phone printed circuit boards (WMPCBs) was studied. The components of the emulsion liquid membrane, effects of 7 factors on the extraction rate and the morphology of the synthesized nanomaterials were explored. The results show that it is possible to extract 99.79% of Au(III) from WMPCBs leachate with kerosene as diluent, Span80 as surfactant, methyl isobutyl ketone(MIBK) as carrier, ascorbic acid solution as stripping agent and liquid paraffin as membrane stabilizer. The external phase pH and the internal phase concentration had a greater influence on the extraction efficiency of Au(III) among 7 factors. The morphology of the synthesized product was affected by the concentration and type of the surfactant. It provides a new idea to connect recovery from waste with deep processing, extending the waste mobile phone recycling process chain and achieving high-value utilization of waste mobile phone secondary metal resource products.

Adsorption of gold from waste mobile phones by biochar and activated carbon in gold iodized solution.

The application of laboratory-generated biochar and activated carbon adsorbents in gold iodized solution for the recycling of waste mobile phone printed circuit boards (WMPCBs) is investigated. This research aims to solve problems associated with the existing gold recovery technologies of WMPCBs. Currently, the disposal of WMPCBs is expensive, involves complex processes, and contributes to secondary pollution. In this study, laboratory-generated biochar is produced from corn straw, wheat straw, and wood chips by pyrolysis. The effects of factors on the adsorption efficiency are investigated, and the optimal operating conditions for biochar and activated carbon adsorption are determined. The following optimal parameters were found for activated carbon: temperature = 25 °C, particle size = 40-60 mesh, dosage = 0.05 g/10 mL, pH = 7, reaction time = 2 h, and oscillation frequency = 200 r/min. The adsorption efficiency reached 98.6%. For biochar, optimization involved: raw material from corn straw at a pyrolysis temperature = 700 °C, reaction time = 5 h, oscillation frequency = 200 r/min, pH = 3, dosage = 0.15 g/10 mL, and temperature = 50 °C. An adsorption efficiency of 98% was achieved. The two adsorbents were compared, and results demonstrated that the adsorption properties of the laboratory-generated biochar were slightly inferior to those of the activated carbon; however, they were similar. Biochar adsorption can reuse waste, which may not only solve the current problems related to WMPCB recycling, but can help to achieve a "win-win" situation of increased environmental protection and sustainable utilization of resources.

Clinical and pathological features in adult-onset NIID patients with cortical enhancement.

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in multiple organs. On conventional MRI, high signals on diffused weight image (DWI) along the corticomedullary junction have demonstrated great diagnostic values for adult-onset NIID. However, changes of contrast MRI in the acute period of the encephalopathy-like episode have rarely been investigated. METHODS: Patients with enhanced lesions were retrieved in our database including 35 patients with adult-onset NIID between October 2017 and December 2019. Conventional and contrast MRI were conducted in all patients. Standard procedures of skin biopsy were performed in all patients. Repeat-primed PCR and amplicon length PCR were used to screen the GGC expansion in the 5'UTR of the NOTCH2NLC gene. RESULTS: Four of 35 patients (11.4%) were identified to have a cortical enhancement in this study. The enhanced lesions were selectively spread along the surface of posterior cortex and were clinically associated with encephalopathy-like episodes. These patients had a younger age of onset, shorter duration of disease, and a higher incidence of a headache than those without enhancement. Typical p62-postive intranuclear inclusions were observed in all patients, while patient 1 simultaneously had many nuclei full of abnormal substance immunopositive to p62, as well as short-curly filament materials on electron microscopy. All patients were identified to have GGC repeat expansion in the NOTCH2NLC gene. CONCLUSION: Post-contrast MRI should be routinely performed in the adult-onset NIID patients. Some patients with adult-onset NIID showed cortical enhancement and edema along the surface of posterior cortex, indicating that dehydrate and anti-inflammatory drugs might be potential therapies for these patients.