Roles of pyroptosis and immune infiltration in aortic dissection.

Introduction: Aortic dissection (AD) is often fatal, and its pathogenesis involves immune infiltration and pyroptosis, though the molecular pathways connecting these processes remain unclear. This study aimed to investigate the role of immune infiltration and pyroptosis in AD pathogenesis using bioinformatics analysis. Methods: Two Gene Expression Omnibus datasets and a Gene Cards dataset of pyroptosis-related genes (PRGs) were utilized. Immunological infiltration was assessed using CIBERSORT, and AD diagnostic markers were identified through univariate logistic regression and least absolute shrinkage and selection operator regression. Interaction networks were constructed using STRING, and weighted gene correlation network analysis (WGCNA) was employed to identify important modules and essential genes. Single-sample gene set enrichment analysis determined immune infiltration, and Pearson correlation analysis assessed the association of key genes with infiltrating immune cells. Results: Thirty-one PRGs associated with inflammatory response, vascular epidermal growth factor receptor, and Rap1 signaling pathways were identified. WGCNA revealed seven important genes within a critical module. CIBERSORT detected immune cell infiltration, indicating significant changes in immune cell infiltration and pyroptosis genes in AD and their connections. Discussion: Our findings suggest that key PRGs may serve as indicators for AD or high-risk individuals. Understanding the role of pyroptosis and immune cell infiltration in AD pathogenesis may lead to the development of novel molecular-targeted therapies for AD. Conclusion: This study provides insights into the molecular mechanisms underlying AD pathogenesis, highlighting the importance of immune infiltration and pyroptosis. Identification of diagnostic markers and potential therapeutic targets may improve the management of AD and reduce associated morbidity and mortality.

CancerProteome: a resource to functionally decipher the proteome landscape in cancer.

Advancements in mass spectrometry (MS)-based proteomics have greatly facilitated the large-scale quantification of proteins and microproteins, thereby revealing altered signalling pathways across many different cancer types. However, specialized and comprehensive resources are lacking for cancer proteomics. Here, we describe CancerProteome (http://bio-bigdata.hrbmu.edu.cn/CancerProteome), which functionally deciphers and visualizes the proteome landscape in cancer. We manually curated and re-analyzed publicly available MS-based quantification and post-translational modification (PTM) proteomes, including 7406 samples from 21 different cancer types, and also examined protein abundances and PTM levels in 31 120 proteins and 4111 microproteins. Six major analytical modules were developed with a view to describe protein contributions to carcinogenesis using proteome analysis, including conventional analyses of quantitative and the PTM proteome, functional enrichment, protein-protein associations by integrating known interactions with co-expression signatures, drug sensitivity and clinical relevance analyses. Moreover, protein abundances, which correlated with corresponding transcript or PTM levels, were evaluated. CancerProteome is convenient as it allows users to access specific proteins/microproteins of interest using quick searches or query options to generate multiple visualization results. In summary, CancerProteome is an important resource, which functionally deciphers the cancer proteome landscape and provides a novel insight for the identification of tumor protein markers in cancer.

The effect of reinforcement particle size on the mechanical and fracture properties of glass matrix composites.

The strength and toughness of sealing glass are currently unable to meet increasingly severe application conditions, and composites are an effective way to solve this problem. The size of reinforcement particles significantly affects the material properties, while the underlying mechanism still eludes deeper understanding. In this paper, the influence of the embedded alumina size is investigated from the perspectives of mechanical and fracture properties by mechanical tests, fracture toughness tests and the finite element method. The results of the experiment and simulation indicate that the fracture energy is mainly consumed by interface debonding and particle breakage, and the former consumes more energy. Materials with large particles have better mechanical properties, while those with small particles have better fracture properties. This difference could be ascribed to the curvature of the particles rather than the size. Therefore, an ideal reinforcement particle shape with both mechanical and fracture advantages is proposed. The results shed light on the nature of particle enhancement and point out a new direction for the design of sealing glass composites.

Assessing real-world safety concerns of Sacituzumab govitecan: a disproportionality analysis using spontaneous reports in the FDA adverse event reporting system.

Aim: The aim of this study was to identify potential safety concerns associated with Sacituzumab Govitecan (SG), an antibody-drug conjugate targeting trophoblastic cell-surface antigen-2, by analyzing real-world safety data from the largest publicly available worldwide pharmacovigilance database. Methods: All data obtained from the FDA Adverse Event Reporting System (FAERS) database from the second quarter of 2020 to the fourth quarter of 2022 underwent disproportionality analysis and Bayesian analysis to detect and assess the adverse event signals of SG, considering statistical significance when the lower limit of the 95% CI >1, based on at least 3 reports. Results: Total of 1072 cases were included. The main safety signals were blood and lymphatic system disorders [ROR(95CI)=7.23 (6.43-8.14)], gastrointestinal disorders [ROR(95CI)=2.01 (1.81-2.22)], and relative infection adverse events, such as neutropenic sepsis [ROR(95CI)=46.02 (27.15-77.99)] and neutropenic colitis [ROR(95CI)=188.02 (120.09-294.37)]. We also noted unexpected serious safety signals, including large intestine perforation [ROR(95CI)=10.77 (3.47-33.45)] and hepatic failure [ROR(95CI)=3.87 (1.45-10.31)], as well as a high signal for pneumonitis [ROR(95CI)=9.93 (5.75-17.12)]. Additionally, age sub-group analysis revealed that geriatric patients (>65 years old) were at an increased risk of neutropenic colitis [ROR(95CI)=282.05 (116.36-683.66)], neutropenic sepsis [ROR(95CI)=101.11 (41.83-244.43)], acute kidney injury [ROR(95CI)=3.29 (1.36-7.94)], and atrial fibrillation [ROR(95CI)=6.91 (2.86-16.69)]. Conclusion: This study provides crucial real-world safety data on SG, complementing existing clinical trial information. Practitioners should identify contributing factors, employ monitoring and intervention strategies, and focus on adverse events like neutropenic sepsis, large intestine perforation, and hepatic failure. Further prospective studies are needed to address these safety concerns for a comprehensive understanding and effective management of associated risks.

Spatial transcriptome analysis of long non-coding RNAs reveals tissue specificity and functional roles in cancer.

Long non-coding RNAs (lncRNAs) play a significant role in maintaining tissue morphology and functions, and their precise regulatory effectiveness is closely related to expression patterns. However, the spatial expression patterns of lncRNAs in humans are poorly characterized. Here, we constructed five comprehensive transcriptomic atlases of human lncRNAs covering thousands of major tissue samples in normal and disease states. The lncRNA transcriptomes exhibited high consistency within the same tissues across resources, and even higher complexity in specialized tissues. Tissue-elevated (TE) lncRNAs were identified in each resource and robust TE lncRNAs were refined by integrative analysis. We detected 1 to 4684 robust TE lncRNAs across tissues; the highest number was in testis tissue, followed by brain tissue. Functional analyses of TE lncRNAs indicated important roles in corresponding tissue-related pathways. Moreover, we found that the expression features of robust TE lncRNAs made them be effective biomarkers to distinguish tissues; TE lncRNAs also tended to be associated with cancer, and exhibited differential expression or were correlated with patient survival. In summary, spatial classification of lncRNAs is the starting point for elucidating the function of lncRNAs in both maintenance of tissue morphology and progress of tissue-constricted diseases.

IEAtlas: an atlas of HLA-presented immune epitopes derived from non-coding regions.

Cancer-related epitopes can engage the immune system against tumor cells, thus exploring epitopes derived from non-coding regions is emerging as a fascinating field in cancer immunotherapies. Here, we described a database, IEAtlas (http://bio-bigdata.hrbmu.edu.cn/IEAtlas), which aims to provide and visualize the comprehensive atlas of human leukocyte antigen (HLA)-presented immunogenic epitopes derived from non-coding regions. IEAtlas reanalyzed publicly available mass spectrometry-based HLA immunopeptidome datasets against our integrated benchmarked non-canonical open reading frame information. The current IEAtlas identified 245 870 non-canonical epitopes binding to HLA-I/II allotypes across 15 cancer types and 30 non-cancerous tissues, greatly expanding the cancer immunopeptidome. IEAtlas further evaluates the immunogenicity via several commonly used immunogenic features, including HLA binding affinity, stability and T-cell receptor recognition. In addition, IEAtlas provides the biochemical properties of epitopes as well as the clinical relevance of corresponding genes across major cancer types and normal tissues. Several flexible tools were also developed to aid retrieval and to analyze the epitopes derived from non-coding regions. Overall, IEAtlas will serve as a valuable resource for investigating the immunogenic capacity of non-canonical epitopes and the potential as therapeutic cancer vaccines.

Exploring the Mystery of the Tetrahydrobiopterin Synthetic Defect Lethal Mutant leml from Birth to Death in the Silkworm Bombyx mori.

Tetrahydrobiopterin (BH4) is a vital coenzyme for several enzymes involved in diverse enzymatic reactions in animals, and BH4 deficiency can lead to metabolic and neurological disorders due to dysfunction in its metabolism. In the silkworm natural homozygous mutant leml, the key enzyme sepiapterin reductase (BmSPR) in the de novo synthesis pathway of BH4 is inactivated, resulting in severe deficiency of BH4 synthesis. However, it is not known why the leml larvae can survive to the second-instar stage and which pathways lead to their death when BH4 is deficient. Here, we quantified BH4 and found that the fertilized eggs contained large amounts of BH4 transferred from the mother to the offspring, maintaining its normal development in the embryo and the first instar. Subsequently, we investigated the multiple pathways in which BH4 is involved as a cofactor. The results showed that BH4 deficiency in silkworms blocked the melanin synthesis pathway, caused an insufficient degree of epidermal sclerosis, disordered tyrosine metabolism, and damaged mitochondria. On the other hand, BH4 deficiency led to the uncoupling of nitric oxide synthase (BmNOS), a reduced NO production, and a significantly reduced fat in fat body catalyzation by phospholipase A2, resulting in an impaired immune system. Meanwhile, the uncoupling of BmNOS increased the O2- content, damaged the DNA, and caused the apoptosis of the body cells. Taken together, BH4 is critical for the life and death of leml mutants. This study lays a foundation for the further exploration of lepidopteran insects and provides an important basis for the treatment of human BH4 deficiency-related diseases.

PRES: a webserver for decoding the functional perturbations of RNA editing sites.

Rapid progresses in RNA-Seq and computational methods have assisted in quantifying A-to-I RNA editing and altered RNA editing sites have been widely observed in various diseases. Nevertheless, functional characterization of the altered RNA editing sites still remains a challenge. Here, we developed perturbations of RNA editing sites (PRES; http://bio-bigdata.hrbmu.edu.cn/PRES/) as the webserver for decoding functional perturbations of RNA editing sites based on editome profiling. After uploading an editome profile among samples of different groups, PRES will first annotate the editing sites to various genomic elements and detect differential editing sites under the user-selected method and thresholds. Next, the downstream functional perturbations of differential editing sites will be characterized from gain or loss miRNA/RNA binding protein regulation, RNA and protein structure changes, and the perturbed biological pathways. A prioritization module was developed to rank genes based on their functional consequences of RNA editing events. PRES provides user-friendly functionalities, ultra-efficient calculation, intuitive table and figure visualization interface to display the annotated RNA editing events, filtering options and elaborate application notebooks. We anticipate PRES will provide an opportunity for better understanding the regulatory mechanisms of RNA editing in human complex diseases.

Identification and functional analysis of carbonyl reductases related to tetrahydrobiopterin synthesis in the silkworm, Bombyx mori.

The superfamily of short-chain dehydrogenases/reductases (SDRs) is crucial in biosynthetic and signalling pathways, in which the carbonyl reductases (CBRs) subfamily is important in the biosynthesis of tetrahydrobiopterin (BH4). BH4 is an essential coenzyme for animals, and its deficiency can lead to neurological diseases. There are few reports on CBRs involved in BH4 synthesis of silkworms, Bombyx mori. Here, we identified 67 SDR genes in B. mori (BmSDR) through whole genome survey for the first time. Based on bioinformatics analyses and KEGG verification, four BmCBRs that may be related to BH4 synthesis were further characterized and functionally analysed. The results showed these four genes were high expressed in the head and gonads of ah09 (a lem mutant with defective BH4 synthesis). Enzyme activity, BH4 content and the related gene expression levels after intracellular interference with BmCBR and the main catalytic enzymes sepiapterin reductase of B. mori (BmSpr) in the de novo pathway of BH4 showed BmCBR2 plays a role in the salvage pathway. BmCBR3 and BmCBR4 regulate BH4 synthesis through the alternative pathway. Among the four pathways of silkworm BH4 synthesis, the de novo pathway occupies the dominant position, followed by the alternative pathway and salvage pathway. According to the overexpression of BmCBR3 after interference with BmSpr, the BH4 content did not change significantly. It is speculated that BmCBR3 is located upstream of BmSpr. These results provide a theoretical basis for in-depth exploration of the role of BmSDR in B. mori and also provide clues for the research of other animal-related diseases.

TransLnc: a comprehensive resource for translatable lncRNAs extends immunopeptidome.

LncRNAs are not only well-known as non-coding elements, but also serve as templates for peptide translation, playing important roles in fundamental cellular processes and diseases. Here, we describe a database, TransLnc (http://bio-bigdata.hrbmu.edu.cn/TransLnc/), which aims to provide comprehensive experimentally supported and predicted lncRNA peptides in multiple species. TransLnc currently documents approximate 583 840 peptides encoded by 33 094 lncRNAs. Six types of direct and indirect evidences supporting the coding potential of lncRNAs were integrated, and 65.28% peptides entries were with at least one type of evidence. Considering the strong tissue-specific expression of lncRNAs, TransLnc allows users to access lncRNA peptides in any of the 34 tissues involved in. In addition, both the unique characteristic and homology relationship were also predicted and provided. Importantly, TransLnc provides computationally predicted tumour neoantigens from peptides encoded by lncRNAs, which would provide novel insights into cancer immunotherapy. There were 220 791 and 237 915 candidate neoantigens binding by major histocompatibility complex (MHC) class I or II molecules, respectively. Several flexible tools were developed to aid retrieve and analyse, particularly lncRNAs tissue expression patterns, clinical relevance across cancer types. TransLnc will serve as a valuable resource for investigating the translation capacity of lncRNAs and greatly extends the cancer immunopeptidome.

Gene Expression, Biochemical Characterization of a sn-1, 3 Extracellular Lipase From Aspergillus niger GZUF36 and Its Model-Structure Analysis.

In this study, a sn-1, 3 extracellular lipases from Aspergillus niger GZUF36 (PEXANL1) was expressed in Pichia pastoris, characterized, and the predicted structural model was analyzed. The optimized culture conditions of P. pastoris showed that the highest lipase activity of 66.5 ± 1.4 U/mL (P < 0.05) could be attained with 1% methanol and 96 h induction time. The purified PEXANL1 exhibited the highest activity at pH 4.0 and 40°C temperature, and its original activity remained unaltered in the majority of the organic solvents (20% v/v concentration). Triton X-100, Tween 20, Tween 80, and SDS at a concentration of 0.01% (w/v) enhanced, and all the metal ions tested inhibited activity of purified PEXANL. The results of ultrasound-assisted PEXANL1 catalyzed synthesis of 1,3-diaglycerides showed that the content of 1,3-diglycerides was rapidly increased to 36.90% with 25 min of ultrasound duration (P < 0.05) and later decreased to 19.93% with 35 min of ultrasound duration. The modeled structure of PEXANL1 by comparative modeling showed α/ß hydrolase fold. Structural superposition and molecular docking results validated that Ser162, His274, and Asp217 residues of PEXANL1 were involved in the catalysis. Small-angle X-ray scattering analysis indicated the monomer properties of PEXANL1 in solution. The ab initio model of PEXANL1 overlapped with its modeling structure. This work presents a reliable structural model of A. niger lipase based on homology modeling and small-angle X-ray scattering. Besides, the data from this study will benefit the rational design of suitable crystalline lipase variants in the future.

Effect of cross-linked enzyme aggregate strategy on characterization of sn-1,3 extracellular lipase from Aspergillus niger GZUF36.

The sn-1,3 extracellular lipase from Aspergillus niger GZUF36 (EXANL1) has important potential applications. The cross-linked enzyme aggregate (CLEA) of purified EXANL1 (CLEA-EXANL1) achieved optimum activity recovery (148.5 ± 0.9%), immobilization yield (100 ± 0%), and recovered activity (99.7 ± 0.6%) with 80% tert-butanol as the precipitant, glutaraldehyde (GA) concentration of 30 mM, GA treatment time of 1.5 h, and centrifugal speed of 6000×g. The effect of CLEA strategy on the characterization of EXANL1 was evaluated in this work. CLEA-EXANL1 exhibited a broader optimum pH range (4-6) compared with free EXANL1 (6.5). CLEA-EXANL1 presented optimum activity at 40 °C, which was 5 °C higher than that of free EXANL1. CLEA strategy decreased the maximum reaction rate and increased the Michaelis-Menten constant of EXANL1 when olive oil emulsion was used as a substrate. Moreover, after 30 days, free EXANL1 lost more than 80.0% of its activity, whereas CLEA-EXANL1 retained more than 90.0% of its activity. CLEA strategy improved the tolerance of EXANL1 in polar organic solvents. Fourier transform infrared spectroscopy results showed that the CLEA technique increased the contents of ß-sheets and ß-turns in EXANL1 and reduced those of α-helixes and irregular crimps. CLEA strategy caused no change in the sn-1,3 selectivity of EXANL1. Therefore, EXANL1 in the form of CLEA is a valuable catalyst in the synthesis of 1,3-diacylglycerol. KEY POINTS: • Cross-linked enzyme aggregate (CLEA) strategy broadened the optimum pH range of sn-1,3 extracellular lipase from Aspergillus niger GZUF36 (EXANL1). • CLEA strategy improved the tolerance of EXANL1 in polar organic solvents. • CLEA strategy caused no change in the positional selectivity of EXANL1.

Primary role of increasing urea-N concentration in a novel Microcystis densa bloom: Evidence from ten years of field investigations and laboratory experiments.

A novel Microcystis bloom caused by Microcystis densa has occurred in a typical subtropical reservoir every spring and summer since 2012, and it has caused several ecological and economic losses. To determine the environmental factors that influence the growth and physiological characteristics of M. densa, we investigated the variations in physicochemical factors and M. densa cell density from 2007 to 2017. The results showed that the urea-N concentration increased significantly (from 0.02 ± 0.00-0.20 ± 0.01 mg N l-1), whereas other factors did not vary significantly. NO3--N and urea-N concentrations were higher than the NH4+-N concentration during the M. densa bloom. The nitrogen composition changed, and urea-N and NO3--N became a major nitrogen sources in the reservoir. Water temperature and increased urea-N concentrations were the primary factors that influenced variations in M. densa cell density (45.5%, p < 0.05). Laboratory experiments demonstrated that M. densa cultured with urea-N exhibited a higher maximum cell density (9.8 ± 0.5 × 108 cells l-1), more cellular pigments for photosynthesis (chlorophyll a and phycocyanin) and photoprotection (carotenoid), and more proteins than those cultured with NH4+-N and NO3--N. These results suggested that M. densa cultured with urea-N exhibited preferable growth and physiological conditions. Moreover, M. densa exhibited an increased maximum specific uptake rate (0.93 pg N cell-1 h-1) and reduced half-saturation constant (0.03 mg N l-1) for urea-N compared with NH4+-N and NO3--N, suggesting that M. densa preferred urea-N as its major nitrogen source. These results collectively indicated that the increasing urea-N concentration was beneficial for the growth and physiological conditions of M. densa. This study provided ten years of field data and detailed physiological information supporting the critical effect of urea-N on the growth of a novel bloom species M. densa. These findings helped to reveal the mechanism of M. densa bloom formation from the perspective of dissolved organic nitrogen.

A Rapid Immunochromatographic Method Based on a Secondary Antibody-Labelled Magnetic Nanoprobe for the Detection of Hepatitis B preS2 Surface Antigen.

Hepatitis B is a globally prevalent viral infectious disease caused by the hepatitis B virus (HBV). In this study, an immunochromatographic assay (ICA) for the rapid detection of hepatitis B preS2 antigen (preS2Ag) was established. The magnetic nanoparticles (MNPs) indirectly labelled with goat anti-mouse (GAM) secondary antibody were applied as a nanoprobe for free preS2 antibody (preS2Ab) capturing and signal amplification. By employing sample pre-incubation processing as well, preS2Ag-preS2Ab was sufficiently caught by the GAM-MNPs probe in 5 min. A qualitative sensitivity of 625 ng/mL was obtained by naked-eye observation within 15-20 min. A standard curve (0-5000 ng/mL) was established, with a quantitative limit of detection (LOD) of 3.6 ng/mL, based on the stability and penetrability of the magnetic signal characteristics. The proposed method for preS2Ag was rapid (~25 min, cf. ELISA ~4 h) and had a good accuracy, which was verified using an ELISA kit (relative error < 15%). Large equipment and skilled technicians were not required. The sensitivity and specificity of the developed GAM-MNPs-ICA method were 93.3% and 90% in clinical serum samples (n = 25), respectively. A good detection consistency (84%) was observed between the developed ICA method and 2 types of commercial ELISA kits, indicating that the GAM-MNPs-ICA has a potential application in large-scale screening for and point-of-care diagnosis of hepatitis B or other infectious diseases.

Considerations in treating patients with advance lung cancer during the epidemic outbreak of novel coronavirus (SARS-CoV-2).

The outbreak of pneumonia caused by novel coronavirus (SARS-CoV-2) in Wuhan, China, at the end of 2019 quickly escalated into a global health emergency. Since its outbreak until the 29th of April 2020, the pandemic has affected more than 3 million of people and caused 207,973 deaths globally. SARS-CoV-2 belongs to the ß-coronavirus genus of the Coronavirus family, and it shares the same subfamily with severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and Middle East respiratory syndrome-associated coronavirus (MERS-CoV), all of which lead to severe pneumonia. For cancer patients, especially those with lung cancers, their immune systems are compromised due to the disease itself as well as the treatment for cancer. The weakened immunity of these patients puts them at a higher risk of not only developing diseases but severe diseases. In this study, through a literature review and data collection, we focus on the selection and consideration of antitumor treatment strategies for advanced lung cancer during the coronavirus disease 2019 (COVID-19) epidemic.

Whole exome sequencing of lung adenocarcinoma and lung squamous cell carcinoma in one individual: A case report.

Multiple primary lung cancers (MPLCs) refers to two or more primary malignant tumors that occur simultaneously or successively in the lung of the same patient. Distinguishing MPLCs from intrapulmonary metastases is important for treatment strategy and prognosis. MPLCs have been considered as having different origins and clonal evolutionary processes. Whole genome sequencing (WGS) and whole exome sequencing (WES) are regarded as an effective way to identify the relationship and differentiation among MPLC nodules. Here, we report the case of a 63-year-old MPLC male patient who smoked for 40 years. Two nodules were found on chest computed tomography (CT) scan, which were further confirmed by pathology to be lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SCC), respectively. WES of the two different nodules was performed, and the results showed that there was a significant genetic difference between the two nodules. Further analysis of the tumor mutation burden (TMB) of the two tumor lesions showed that the TMB of the squamous cell carcinoma was higher than that of the adenocarcinoma, indicating that the squamous cell carcinoma had a higher mutation frequency. According to the pathology and WES sequencing results, MPLCs for this case were regarded as independent of each other, with different origins and clonal evolutionary processes. In this case report, we emphasize that WES should play an important role in determining the origin of MPLC clones, and also make some explorations for the further discovery of new potential driver genes and therapeutic targets.

Successful treatment of a patient with NSCLC carrying uncommon compound EGFR G719X and S768I mutations using osimertinib: A case report.

The discovery of epidermal growth factor receptor (EGFR) somatic mutations and the availability of tyrosine kinase inhibitors (TKIs) as targeted therapies have altered the therapeutic prospects of advanced non-small-cell lung cancer (NSCLC). G719X and S768I are uncommon mutations, and they often exist as compound mutations. A few reports have described the efficacy of first- and second-generation EGFR-TKIs. However, the efficacy of osimertinib in patients with these uncommon compound mutations is unknown. In this study, we reported the postoperative outcome of a patient with NSCLC and uncommon compound EGFR G719X and S768I mutations. After postoperative recurrence, the patient was treated with osimertinib, and an excellent and long-lasting clinical response was achieved. The patient has taken osimertinib for 31.0 months and exhibited a partial response, and her follow-up is ongoing.

Transcriptomic Analyses for Identification and Prioritization of Genes Associated With Alzheimer's Disease in Humans.

Long non-coding RNAs (lncRNAs), as important ncRNA regulators, play crucial roles in the regulation of various biological processes, and their aberrant expression is related to the occurrence and development of diseases, which is gradually validated by more and more studies. Alzheimer's disease (AD) is a chronic neurodegenerative disease that often develops slowly and gradually deteriorates over time. However, which functions the lncRNAs perform in AD are almost unknown. In this study, we performed transcriptome analysis in AD, containing 12,892 known lncRNAs and 19,053 protein-coding genes (PCGs). Further, 14 down-regulated and 39 up-regulated lncRNAs were identified, compared with normal brain samples, which indicated that these lncRNAs might play critical roles in the pathogenesis of AD. In addition, 19 down-regulated and 28 up-regulated PCGs were also detected. Using the differentially expressed lncRNAs and PCGs through the WGCNA method, an lncRNA-mRNA co-expressed network was constructed. The results showed that lncRNAs RP3-522J7, MIR3180-2, and MIR3180-3 were frequently co-expressed with known AD risk PCGs. Interestingly, PCGs in the network are significantly enriched in brain- or AD-related biological functions, including the brain renin-angiotensin system, cell adhesion, neuroprotective role of THOP1 in AD, and so on. Furthermore, it was shown that 18 lncRNAs and 7 PCGs were highly expressed in normal brain tissue relative to other normal tissue types, suggesting their potential as diagnostic markers of AD, especially RP3-522J7, MIR3180-2, MIR3180-3, and CTA-929C8. In total, our study identified a compendium of AD-related dysregulated lncRNAs and characterized the corresponding biological functions of these lncRNAs in AD, which will be helpful to understand the molecular basis and pathogenesis of AD.

Aggravation of depigmentation for a non-small-cell lung cancer patient with pre-existing vitiligo using anti-programmed cell death-1 therapy: case report.

Immune checkpoint inhibitors can enhance the antitumor activity of the immune system by mainly promoting CD8+ T lymphocyte immune function. However, they can also induce immune-related adverse events, especially skin toxicity. Some studies found that patients with autoimmune or inflammatory disease are susceptible to immune checkpoint inhibitors and were associated with a significantly increased risk of immune-related adverse events. In our present report, we described a newly diagnosed non-small-cell lung cancer patient who suffered from focal vitiligo for approximately ten years and was treated with the anti-programmed cell death-1 receptor antibody camrelizumab (SHR-1210), which accelerated the aggravation of depigmentation of the skin over the whole body in just half a year.