Fast and accurate variant identification tool for sequencing-based studies.

BACKGROUND: Accurate identification of genetic variants, such as point mutations and insertions/deletions (indels), is crucial for various genetic studies into epidemic tracking, population genetics, and disease diagnosis. Genetic studies into microbiomes often require processing numerous sequencing datasets, necessitating variant identifiers with high speed, accuracy, and robustness. RESULTS: We present QuickVariants, a bioinformatics tool that effectively summarizes variant information from read alignments and identifies variants. When tested on diverse bacterial sequencing data, QuickVariants demonstrates a ninefold higher median speed than bcftools, a widely used variant identifier, with higher accuracy in identifying both point mutations and indels. This accuracy extends to variant identification in virus samples, including SARS-CoV-2, particularly with significantly fewer false negative indels than bcftools. The high accuracy of QuickVariants is further demonstrated by its detection of a greater number of Omicron-specific indels (5 versus 0) and point mutations (61 versus 48-54) than bcftools in sewage metagenomes predominated by Omicron variants. Much of the reduced accuracy of bcftools was attributable to its misinterpretation of indels, often producing false negative indels and false positive point mutations at the same locations. CONCLUSIONS: We introduce QuickVariants, a fast, accurate, and robust bioinformatics tool designed for identifying genetic variants for microbial studies. QuickVariants is available at https://github.com/caozhichongchong/QuickVariants .

Ultrafine Pt Nanoparticles Anchored on 2D Metal-Organic Frameworks as Multifunctional Electrocatalysts for Water Electrolysis and Zinc-Air Batteries.

Multifunctional electrocatalysts are crucial to cost-effective electrochemical energy conversion and storage systems requiring mutual enhancement of disparate reactions. Embedding noble metal nanoparticles in 2D metal-organic frameworks (MOFs) are proposed as an effective strategy, however, the hybrids usually suffer from poor electrochemical performance and electrical conductivity in operating conditions. Herein, ultrafine Pt nanoparticles strongly anchored on thiophenedicarboxylate acid based 2D Fe-MOF nanobelt arrays (Pt@Fe-MOF) are fabricated, allowing sufficient exposure of active sites with superior trifunctional electrocatalytic activity for hydrogen evolution, oxygen evolution, and oxygen reduction reactions. The interfacial Fe─O─Pt bonds can induce the charge redistribution of metal centers, leading to the optimization of adsorption energy for reaction intermediates, while the dispersibility of ultrafine Pt nanoparticles contributes to the high mass activity. When Pt@Fe-MOF is used as bifunctional catalysts for water-splitting, a low voltage of 1.65 V is required at 100 mA cm-2 with long-term stability for 20 h at temperatures (65 °C) relevant for industrial applications, outperforming commercial benchmarks. Furthermore, liquid Zn-air batteries with Pt@Fe-MOF in cathodes deliver high open-circuit voltages (1.397 V) and decent cycling stability, which motivates the fabrication of flexible quasisolid-state rechargeable Zn-air batteries with remarkable performance.

Suppressing ion migration in metal halide perovskite via interstitial doping with a trace amount of multivalent cations.

Cations with suitable sizes to occupy an interstitial site of perovskite crystals have been widely used to inhibit ion migration and promote the performance and stability of perovskite optoelectronics. However, such interstitial doping inevitably leads to lattice microstrain that impairs the long-range ordering and stability of the crystals, causing a sacrificial trade-off. Here, we unravel the evident influence of the valence states of the interstitial cations on their efficacy to suppress the ion migration. Incorporation of a trivalent neodymium cation (Nd3+) effectively mitigates the ion migration in the perovskite lattice with a reduced dosage (0.08%) compared to a widely used monovalent cation dopant (Na+, 0.45%). The photovoltaic performances and operational stability of the prototypical perovskite solar cells are enhanced with a trace amount of Nd3+ doping while minimizing the sacrificial trade-off.

Risk factors for the mortality of hepatitis B virus-associated acute-on-chronic liver failure: a systematic review and meta-analysis.

BACKGROUND: Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) has been confirmed as a prevalent form of end-stage liver disease in people subjected to chronic HBV infection. However, there has been rare in-depth research on the risk factors for the mortality of HBV-ACLF. This study aimed at determining the risk factors for the mortality of HBV-ACLF. METHODS: The relevant research was selected from four electronic databases that have been published as of August 2023. The existing research was reviewed in accordance with the inclusion and exclusion criteria. The level of quality of previous research was evaluated using the Newcastle-Ottawa scale. Moreover, a pooled estimate of the odds ratios (ORs) with their associated 95% confidence intervals (CIs) was provided through a meta-analysis. The data were combined, and the risk variables that at least two studies had considered were analyzed. The publication bias was examined through Egger's test and Begg's test. RESULTS: Twenty two studies that conformed to the inclusion criteria were selected from 560 trials. Eight risk variables in terms of HBV-ACLF mortality were determined, which covered INR (OR = 1.923, 95% CI = 1.664-2.221, P < 0.001), Monocytes (OR = 1.201, 95% CI = 1.113-1.296, P < 0.001), Cirrhosis (OR = 1.432, 95% CI = 1.210-1.696, P < 0.001), HE (OR = 2.553, 95% CI = 1.968-3.312, P < 0.001), HE grade (OR = 2.059, 95% CI = 1.561-2.717, P < 0.001), SBP (OR = 1.383, 95% CI = 1.080-1.769, P = 0.010), Hyponatremia (OR = 1.941, 95% CI = 1.614-2.334, P < 0.001), as well as HRS (OR = 2.610, 95% CI = 1.669-4.080, P < 0.001). CONCLUSION: The most significant risk factors for HBV-ACLF mortality comprise HRS, HE, and HE grade, followed by INR and hyponatremia. The Monocytes, cirrhosis, and SBP have been confirmed as the additional key risk factors for HBV-ACLF mortality.

Transcriptome analysis reveals key developmental and metabolic regulatory aspects of oil palm (Elaeis guineensis Jacq.) during zygotic embryo development.

BACKGROUND: Oil palm is the most efficient oil-producing crop in the world, and the yield of palm oil is associated with embryonic development. However, a comprehensive understanding of zygotic embryo development at the molecular level remains elusive. In order to address this issue, we report the transcriptomic analysis of zygotic embryo development in oil palm, specifically focusing on regulatory genes involved in important biological pathways. RESULTS: In this study, three cDNA libraries were prepared from embryos at S1 (early-stage), S2 (middle-stage), and S3 (late-stage). There were 16,367, 16,500, and 18,012 genes characterized at the S1, S2, and S3 stages of embryonic development, respectively. A total of 1522, 2698, and 142 genes were differentially expressed in S1 vs S2, S1 vs S3, and S2 vs S3, respectively. Using Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to identify key genes and pathways. In the hormone signaling pathway, genes related to auxin antagonize the output of cytokinin which regulates the development of embryo meristem. The genes related to abscisic acid negatively regulating the synthesis of gibberellin were strongly up-regulated in the mid-late stage of embryonic development. The results were reported the early synthesis and mid-late degradation of sucrose, as well as the activation of the continuous degradation pathway of temporary starch, providing the nutrients needed for differentiation of the embryonic cell. Moreover, the transcripts of genes involved in fatty acid synthesis were also abundantly accumulated in the zygotic embryos. CONCLUSION: Taken together, our research provides a new perspective on the developmental and metabolic regulation of zygotic embryo development at the transcriptional level in oil palm.

Seasonal Prevalence of Ammonia-Oxidizing Archaea in a Full-Scale Municipal Wastewater Treatment Plant Treating Saline Wastewater Revealed by a 6-Year Time-Series Analysis.

Although several molecular-based studies have demonstrated the involvement of ammonia-oxidizing archaea (AOA) in ammonia oxidation in wastewater treatment plants (WWTPs), factors affecting the persistence and growth of AOA in these engineered systems have not been resolved. Here, we show a seasonal prevalence of AOA in a full-scale WWTP (Shatin, Hong Kong SAR) over a 6-year period of observation, even outnumbering ammonia-oxidizing bacteria in the seasonal peaks in 3 years, which may be due to the high bioavailable copper concentrations. Comparative analysis of three metagenome-assembled genomes of group I.1a AOA obtained from the activated sludge and 16S rRNA gene sequences recovered from marine sediments suggested that the seawater used for toilet flushing was the primary source of the WWTP AOA. A rare AOA population in the estuarine source water became transiently abundant in the WWTP with a metagenome-based relative abundance of up to 1.3% over three seasons of observation. Correlation-based network analysis revealed a robust co-occurrence relationship between these AOA and organisms potentially active in nitrite oxidation. Moreover, a strong correlation between the dominant AOA and an abundant proteobacterial organism suggested that capacity for extracellular polymeric substance production by the proteobacterium could provide a niche for AOA within bioaggregates. Together, the study highlights the importance of long-term observation in identifying biotic and abiotic factors governing population dynamics in open systems such as full-scale WWTPs.

Dosage delivery of sensitive reagents enables glove-box-free synthesis.

Contemporary organic chemists employ a broad range of catalytic and stoichiometric methods to construct molecules for applications in the material sciences, and as pharmaceuticals, agrochemicals, and sensors. The utility of a synthetic method may be greatly reduced if it relies on a glove box to enable the use of air- and moisture-sensitive reagents or catalysts. Furthermore, many synthetic chemistry laboratories have numerous containers of partially used reagents that have been spoiled by exposure to the ambient atmosphere. This is exceptionally wasteful from both an environmental and a cost perspective. Here we report an encapsulation method for stabilizing and storing air- and moisture-sensitive compounds. We demonstrate this approach in three contexts, by describing single-use capsules that contain all of the reagents (catalysts, ligands, and bases) necessary for the glove-box-free palladium-catalysed carbon-fluorine, carbon-nitrogen, and carbon-carbon bond-forming reactions. This strategy should reduce the number of error-prone, tedious and time-consuming weighing procedures required for such syntheses and should be applicable to a wide range of reagents, catalysts, and substrate combinations.

Molecular Interaction Regulates the Performance and Longevity of Defect Passivation for Metal Halide Perovskite Solar Cells.

Defect passivation constitutes one of the most commonly used strategies to fabricate highly efficient perovskite solar cells (PSCs). However, the durability of the passivation effects under harsh operational conditions has not been extensively studied regardless of the weak and vulnerable secondary bonding between the molecular passivation agents and perovskite crystals. Here, we incorporated strategically designed passivating agents to investigate the effect of their interaction energies on the perovskite crystals and correlated these with the performance and longevity of the passivation effects. We unraveled that the passivation agents with a stronger interaction energy are advantageous not only for effective defect passivation but also to suppress defect migration. The prototypical PSCs treated with the optimal passivation agent exhibited superior performance and operational stability, retaining 81.9 and 85.3% of their initial performance under continuous illumination or nitrogen at 85 °C after 1008 h, respectively, while the reference device completely degraded during that time. This work provides important insights into designing operationally durable defect passivation agents for perovskite optoelectronic devices.

ARGs-OAP: online analysis pipeline for antibiotic resistance genes detection from metagenomic data using an integrated structured ARG-database.

MOTIVATION: Environmental dissemination of antibiotic resistance genes (ARGs) has become an increasing concern for public health. Metagenomics approaches can effectively detect broad profiles of ARGs in environmental samples; however, the detection and subsequent classification of ARG-like sequences are time consuming and have been severe obstacles in employing metagenomic methods. We sought to accelerate quantification of ARGs in metagenomic data from environmental samples. RESULTS: A Structured ARG reference database (SARG) was constructed by integrating ARDB and CARD, the two most commonly used databases. SARG was curated to remove redundant sequences and optimized to facilitate query sequence identification by similarity. A database with a hierarchical structure (type-subtype-reference sequence) was then constructed to facilitate classification (assigning ARG-like sequence to type, subtype and reference sequence) of sequences identified through similarity search. Utilizing SARG and a previously proposed hybrid functional gene annotation pipeline, we developed an online pipeline called ARGs-OAP for fast annotation and classification of ARG-like sequences from metagenomic data. We also evaluated and proposed a set of criteria important for efficiently conducting metagenomic analysis of ARGs using ARGs-OAP. AVAILABILITY AND IMPLEMENTATION: Perl script for ARGs-OAP can be downloaded from https://github.com/biofuture/Ublastx_stageone ARGs-OAP can be accessed through http://smile.hku.hk/SARGs CONTACT: zhangt@hku.hk or tiedjej@msu.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

[Inhibition of connexin 43-mediated hemichannel activity promotes odontoblast differentiation of human dental pulp cells induced by lipopolysaccharide].

PURPOSE: To investigate the role and mechanism of connexin 43（Cx43）in odontoblast differentiation of human dental pulp cells (hDPCs) induced by lipopolysaccharide (LPS). METHODS: The maxillary first molar injury model of SD rats was established. The expression pattern of Cx43 in dental pulp repair after injury was detected by immunofluorescence(IF) staining. hDPCs was respectively stimulated with 0, 1, 10, 100 and 1 000 ng/mL LPS for 6 h to screen the optimal concentration, and then the expression of Cx43 was inhibited and overexpressed in hDPCs. Quantitative real-time PCR(qRT-PCR) and Western blot(WB) were used to detect the expression of Cx43 and dentin sialophosphoprotein (DSPP), dental matrix protein-1 (DMP-1), osterix (Osx) and extracellular signal-regulated kinase (ERK) activity. Furthermore, hDPCs were treated with specific Cx43 channel inhibitors to investigate the effect of Cx43-mediated channel activity in odontoblast differentiation of hDPCs, and to explore the role and mechanism of Cx43 in regulating odontoblast differentiation of hDPCs induced by LPS. Statistical analysis was performed with SPSS 26.0 software package. RESULTS: IF results showed that Cx43 was mainly expressed in the odontoblast layer in healthy dental pulp tissues. At 3-24 h after tooth injury, the expression of Cx43 decreased and then gradually increased to the normal level; from 3 days to 2 weeks after injury, the expression of Cx43 tended to be down-regulated which was in the odontoblast layer and pulp proper. The expression of DSPP mRNA was significantly up-regulated in the hDPCs stimulated with 10 ng/mL LPS for 6 h(P＜0.01). Inhibition of Cx43 significantly up-regulated the expression of DSPP, DMP-1 and Osx mRNA induced by LPS in hDPCs(P＜0.05), while overexpression of Cx43 obviously inhibited the expression of factors related to LPS-induced odontoblast differentiation(P＜0.01) and the fluorescence intensity of DSPP. 10 ng/mL LPS activated ERK signal in hDPCs, and overexpression of Cx43 significantly attenuated the activity of ERK signal induced by LPS(P＜0.01). Inhibition of Cx43-mediated hemichannel (HC) promoted mRNA expression of factors related to odontoblast differentiation in hDPCs and the activity of ERK signal induced by LPS(P＜0.05), while blocking Cx43-mediated gap junction channel (GJC) inhibited odontoblast differentiation. CONCLUSIONS: Cx43 participates in the regulation of dental pulp repair after injury, and its expression shows a downward trend as a whole. Inhibition of Cx43 or blocking of HC promotes LPS-induced ERK signal activity and odontoblast differentiation of hDPCs.

Automatic prediction of non-iodine-avid status in lung metastases for radioactive I131 treatment in differentiated thyroid cancer patients.

Objectives: The growing incidence of differentiated thyroid cancer (DTC) have been linked to insulin resistance and metabolic syndrome. The imperative need for developing effective diagnostic imaging tools to predict the non-iodine-avid status of lung metastasis (LMs) in differentiated thyroid cancer (DTC) patients is underscored to prevent unnecessary radioactive iodine treatment (RAI). Methods: Primary cohort consisted 1962 pretreated LMs of 496 consecutive DTC patients with pretreated initially diagnosed LMs who underwent chest CT and subsequent post-treatment radioiodine SPECT. After automatic lesion segmentation by SE V-Net, SE Net deep learning was trained to predict non-iodine-avid status of LMs. External validation cohort contained 123 pretreated LMs of 24 consecutive patients from other two hospitals. Stepwise validation was further performed according to the nodule's largest diameter. Results: The SE-Net deep learning network yielded area under the receiver operating characteristic curve (AUC) values of 0.879 (95% confidence interval: 0.852-0.906) and 0.713 (95% confidence interval: 0.613-0.813) for internal and external validation. With the LM diameter decreasing from ≥10mm to ≤4mm, the AUCs remained relatively stable, for smallest nodules (≤4mm), the model yielded an AUC of 0.783. Decision curve analysis showed that most patients benefited using deep learning to decide radioactive I131 treatment. Conclusion: This study presents a noninvasive, less radioactive and fully automatic approach that can facilitate suitable DTC patient selection for RAI therapy of LMs. Further prospective multicenter studies with larger study cohorts and related metabolic factors should address the possibility of comprehensive clinical transformation.

Temporal dynamics of gut microbiomes in non-industrialized urban Amazonia.

Increasing levels of industrialization have been associated with changes in gut microbiome structure and loss of features thought to be crucial for maintaining gut ecological balance. The stability of gut microbial communities over time within individuals seems to be largely affected by these changes but has been overlooked among transitioning populations from low- to middle-income countries. Here, we used metagenomic sequencing to characterize the temporal dynamics in gut microbiomes of 24 individuals living an urban non-industrialized lifestyle in the Brazilian Amazon. We further contextualized our data with 165 matching longitudinal samples from an urban industrialized and a rural non-industrialized population. We show that gut microbiome composition and diversity have greater variability over time among non-industrialized individuals when compared to industrialized counterparts and that taxa may present diverse temporal dynamics across human populations. Enterotype classifications show that community types are generally stable over time despite shifts in microbiome structure. Furthermore, by tracking genomes over time, we show that levels of bacterial population replacements are more frequent among Amazonian individuals and that non-synonymous variants accumulate in genes associated with degradation of host dietary polysaccharides. Taken together, our results suggest that the stability of gut microbiomes is influenced by levels of industrialization and that tracking microbial population dynamics is important to understand how the microbiome will adapt to these transitions.IMPORTANCEThe transition from a rural or non-industrialized lifestyle to urbanization and industrialization has been linked to changes in the structure and function of the human gut microbiome. Understanding how the gut microbiomes changes over time is crucial to define healthy states and to grasp how the gut microbiome interacts with the host environment. Here, we investigate the temporal dynamics of gut microbiomes from an urban and non-industrialized population in the Amazon, as well as metagenomic data sets from urban United States and rural Tanzania. We showed that healthy non-industrialized microbiomes experience greater compositional shifts over time compared to industrialized individuals. Furthermore, bacterial strain populations are more frequently replaced in non-industrialized microbiomes, and most non-synonymous mutations accumulate in genes associated with the degradation of host dietary components. This indicates that microbiome stability is affected by transitions to industrialization, and that strain tracking can elucidate the ecological dynamics behind such transitions.

Aramid Nanodielectrics for Ultraconformal Transparent Electronic Skins.

On-skin electronics require minimal thicknesses and decent transparency for conformal contact, imperceptible wearing, and visual aesthetics. It is challenging to search for advanced ultrathin dielectrics capable of supporting the active components while maintaining bending softness, easy handling, and wafer-scale processability. Here, self-delaminated aramid nanodielectrics (ANDs) are demonstrated, enabling any skin-like electronics easily exfoliated from the processing substrates after complicated nanofabrication. In addition, ANDs are mechanically strong, chemically and thermally stable, transparent and breathable, therefore are ideal substrates for soft electronics. As demonstrated, compliant epidermal electrodes comprising silver nanowires and ANDs can successfully record high-quality electromyogram signals with low motion artifacts and satisfying sweat and water resistance. Furthermore, ANDs can serve as both substrates and dielectrics in single-walled carbon nanotube field-effect transistors (FETs) with a merely 160-nm thickness, which can be operated within 4 V with on/off ratios of 1.4 ± 0.5 × 105 , mobilities of 39.9 ± 2.2 cm2 V-1 s-1 , and negligible hysteresis. The ultraconformal FETs can function properly when wrapped around human hair without any degradation in performance.

Biomimetic wafer-scale alignment of tellurium nanowires for high-mobility flexible and stretchable electronics.

Flexible and stretchable thin-film transistors (TFTs) are crucial in skin-like electronics for wearable and implantable applications. Such electronics are usually constrained in performance owing to a lack of high-mobility and stretchable semiconducting channels. Tellurium, a rising semiconductor with superior charge carrier mobilities, has been limited by its intrinsic brittleness and anisotropy. Here, we achieve highly oriented arrays of tellurium nanowires (TeNWs) on various substrates with wafer-scale scalability by a facile lock-and-shear strategy. Such an assembly approach mimics the alignment process of the trailing tentacles of a swimming jellyfish. We further apply these TeNW arrays in high-mobility TFTs and logic gates with improved flexibility and stretchability. More specifically, mobilities over 100 square centimeters per volt per second and on/off ratios of ~104 are achieved in TeNW-TFTs. The TeNW-TFTs on polyethylene terephthalate can sustain an omnidirectional bending strain of 1.3% for more than 1000 cycles. Furthermore, TeNW-TFTs on an elastomeric substrate can withstand a unidirectional strain of 40% with no performance degradation.

Differential analysis of transcriptomic and metabolomic of free fatty acid rancidity process in oil palm (Elaeis guineensis) fruits of different husk types.

Introduction: Oil palm is the world's highest yielding oil crop and its palm oil has high nutritional value, making it an oilseed plant with important economic value and application prospects. After picking, oil palm fruits exposed to air will gradually become soft and accelerate the process of fatty acid rancidity, which will not only affect their flavor and nutritional value, but also produce substances harmful to the human body. As a result, studying the dynamic change pattern of free fatty acids and important fatty acid metabolism-related regulatory genes during oil palm fatty acid rancidity can provide a theoretical basis for improving palm oil quality and extending its shelf life. Methods: The fruit of two shell types of oil palm, Pisifera (MP) and Tenera (MT), were used to study the changes of fruit souring at different times points of postharvesting, combined with LC-MS/MS metabolomics and RNA-seq transcriptomics techniques to analyze the dynamic changes of free fatty acids during fruit rancidity, and to find out the key enzyme genes and proteins in the process of free fatty acid synthesis and degradation according to metabolic pathways. Results and discussion: Metabolomic study revealed that there were 9 different types of free fatty acids at 0 hours of postharvest, 12 different types of free fatty acids at 24 hours of postharvest, and 8 different types of free fatty acids at 36 hours of postharvest. Transcriptomic research revealed substantial changes in gene expression between the three harvest phases of MT and MP. Combined metabolomics and transcriptomics analysis results show that the expression of SDR, FATA, FATB and MFP four key enzyme genes and enzyme proteins in the rancidity of free fatty acids are significantly correlated with Palmitic acid, Stearic acid, Myristic acid and Palmitoleic acid in oil palm fruit. In terms of binding gene expression, the expression of FATA gene and MFP protein in MT and MP was consistent, and both were expressed higher in MP. FATB fluctuates unevenly in MT and MP, with the level of expression growing steadily in MT and decreasing in MP before increasing. The amount of SDR gene expression varies in opposite directions in both shell types. The above findings suggest that these four enzyme genes and enzyme proteins may play an important role in regulating fatty acid rancidity and are the key enzyme genes and enzyme proteins that cause differences in fatty acid rancidity between MT and MP and other fruit shell types. Additionally, differential metabolite and differentially expressed genes were present in the three postharvest times of MT and MP fruits, with the difference occurring 24 hours postharvest being the most notable. As a result, 24 hours postharvest revealed the most obvious difference in fatty acid tranquility between MT and MP shell types of oil palm. The results from this study offer a theoretical underpinning for the gene mining of fatty acid rancidity of various oil palm fruit shell types and the enhancement of oilseed palm acid-resistant germplasm cultivation using molecular biology methods.

Hyperinsulinemia acts via acinar insulin receptors to initiate pancreatic cancer by increasing digestive enzyme production and inflammation.

The rising pancreatic cancer incidence due to obesity and type 2 diabetes is closely tied to hyperinsulinemia, an independent cancer risk factor. Previous studies demonstrated reducing insulin production suppressed pancreatic intraepithelial neoplasia (PanIN) pre-cancerous lesions in Kras-mutant mice. However, the pathophysiological and molecular mechanisms remained unknown, and in particular it was unclear whether hyperinsulinemia affected PanIN precursor cells directly or indirectly. Here, we demonstrate that insulin receptors (Insr) in KrasG12D-expressing pancreatic acinar cells are dispensable for glucose homeostasis but necessary for hyperinsulinemia-driven PanIN formation in the context of diet-induced hyperinsulinemia and obesity. Mechanistically, this was attributed to amplified digestive enzyme protein translation, triggering of local inflammation, and PanIN metaplasia in vivo. In vitro, insulin dose-dependently increased acinar-to-ductal metaplasia formation in a trypsin- and Insr-dependent manner. Collectively, our data shed light on the mechanisms connecting obesity-driven hyperinsulinemia and pancreatic cancer development.

Clinical Profile and Treatment Outcome in MOGAD: A Single-Center Case-Series Study in Guiyang, China.

Background: The clinical spectrum of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is expanding over time. However, the long-term management and prognosis of this disorder are still controversial. Therefore, this study aimed to report the clinical profiles and treatment outcomes of MOGAD in our center. Methods: This was a single-center case-series study. Clinical and para-clinical data, along with treatment outcomes of patients with MOGAD were analyzed. Results: A total of 27 patients were identified, of which 19 (70%) patients were women, and the median age at disease onset was 40 years (range 20-67). A total of 47 episodes were observed, with optic neuritis (53%) being the most frequent presentation and 60% of them were unilateral. Other presentations included rhombencephalitis (RE) (17%), limbic encephalitis (9%), simultaneous optic neuritis and myelitis (9%), acute disseminated encephalomyelitis (ADEM)-like presentation (6%), myelitis (4%), and ADEM (2%). One patient presenting with RE also met the diagnostic criteria of area postrema syndrome (APS). Another patient with RE presented with imaging characteristics of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). A total of 29 lumbar punctures were recorded, among which an elevated protein level was found in 34% of the samples, pleocytosis was found in 14% of the samples, and positive intrathecal oligoclonal bands were found in 19% of the patients. One patient was found to have anti-N-methyl-D-aspartate receptor antibodies both in his serum and cerebrospinal fluid. Intravenous methylprednisolone (IVMP) was administrated for 85% of the attacks while both IVMP and intravenous immunoglobulin were for 6% of the attacks. Moreover, nine patients received maintenance therapy. Among them, six patients were treated with mycophenolate mofetil, three patients were treated with prednisone, rituximab, and teriflunomide, respectively. The median follow-up period was 20 months (range 6-127). At follow-up, twelve (44%) patients experienced a relapsing course, and the median time to the first relapse was 9.5 months (range 2-120). The median Expanded Disability Status Scale score at nadir was 3.5 (range 2-8) and was 0 (range 0-3) at the last follow-up. Conclusion: The clinical spectrum of MOGAD is heterogenous, wherein APS and CLIPPERS-form can occur. The long-term outcome of MOGAD seems benign. Further studies are warranted to determine the risk factors of relapse and identify the optimal steroid-sparing agents.

Amyotrophic lateral sclerosis with primary progressive aphasia: a case report and literature review.

The association between amyotrophic lateral sclerosis (ALS) and primary progressive aphasia (PPA) is rarely seen in patients. A case of ALS-PPA with a possible reticulon 2 (RTN2) mutation was reported in this study. Moreover, we systematically reviewed the previous reports of 28 ALS cases with progressive non-fluent aphasia (PNFA) and semantic dementia (SD) to identified the unique pathologic features and strong heritability of ALS-PPA. There is a different heritability among the ALS-SD, ALS-PNFA, and the ALS-unclassified PPA groups (p=0.003). Males are more prone to have ALS-PPA than females in all the three groups (p=0.028). PPA-ALS usually starts with cognitive impairment, and the onset most often involves the bulbar. In addition, chromosome 9 open reading frame 72(C9ORF72) and TANK-binding kinase 1 (TBK1) are important pathogenic genes of PPA-ALS. Overall, heritability is of high certainty in ALS-SD, ALS-PNFA, and the ALS-unclassified PPA groups. TAR (Trans-Activator Regulatory) DNA-binding Protein 43 (TDP43) is a 100% predictive pathologic protein of ALS-PPA. C9ORF72 and TBK1 are important pathogenic genes of PPA-ALS.

Coexisting amyotrophic lateral sclerosis and chorea: A case report and literature review.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) coexisting with chorea is very rare. CASE REPORT: We present the case of a 48-year-old man with ALS and chorea; the diagnostic certainty was high based on clinical examination results. Combining the data from literature, we analyzed the characteristics of patients with ALS and chorea. We found that ALS coexisting with chorea is very rare, but is often hereditary with a genetic mutation. Most patients with ALS and chorea are caused by abnormal amplification of a CAG sequence in the HTT gene, and these patients have a mild course of disease. The FUS, VCP, and SETX genes also have low mutation frequencies in patients with ALS and chorea. CONCLUSION: The abnormal amplification of a CAG sequence in the HTT gene in ALS with chorea has an obvious familial genetic tendency, and most patients have a mild disease course.

Correlation analysis of carotid artery intima-media thickness, serum 25(OH)D and men with erectile dysfunction.

Our goal is to investigate the connection between serum 25(OH)D and carotid artery intima-media thickness (CIMT) in men with erectile dysfunction (ED).Serum 25(OH)D and CIMT were measured in 124 participants with erectile dysfunction and 39 healthy controls. The relationship between them and different patient-related parameters and disease-related parameters was studied. Compared with the control group and mild ED group, the level of serum 25(OH)D in moderate ED group and severe ED group decreased significantly(P<0.05). The CIMT values of moderate ED group and severe ED group were higher than those of the control group(P<0.05). The CIMT value of severe ED group was significantly higher than that of mild ED group(P<0.05). IIEF-5 score was positively correlated with serum 25(OH)D level, but negatively correlated with CIMT value(P<0.05). After adjusting for the influence of confounding factors, The CIMT values, 25(OH)D and IIEF-5 score were substantially associated(P<0.05). The serum level of 25(OH)D and IIEF-5 score were positively correlated, while the CIMT values and IIEF-5 score were negatively correlated. The level of serum 25(OH)D should be analyzed in men with ED, especially in patients with vasculogenic ED, and supplementation is recommended for those who were with vitamin D deficiency.