Protective Effect of Prunetin on Isoproterenol-Induced Myocardial Infarction in Wistar Rats via Biochemical Characterization.

BACKGROUND: The development of MI following ischemia damage is influenced by oxidative stress. Myocardial Infarction (MI) generates myocardial ischemia injury, which damages the cardiomyocytes. Ischemia builds up to a critical level over time in MI, causing permanent myocardial cell damage or death. AIM: The current study sought to determine whether Prunetin (PRU) could protect against Isoproterenol (ISO)-induced cardiac heart failure in rats by examining cardiac diagnostic markers, lipid peroxidation products, enzymatic and non-enzymatic antioxidant levels, and histological changes. METHODS: PRU (20 mg/kg bwt) was orally administered for 19 days to rats, and after the treatment, ISO (85 mg/kg bwt) was subcutaneously administered with an intermission of 24 h for a couple of days to induce myocardial infarction on 20th and 21st days. ISO-treated rats exhibited considerable alterations in cardiac-sensitive markers in the serum. The levels of lipid peroxidation markers augmented drastically in the plasma and myocardium. Enzymatic antioxidant levels in erythrocytes and myocardium and the states of non-enzymatic antioxidants were diminished in the plasma and heart tissue of ISO-treated rats. The histopathological examination of heart tissue exhibited cardiac damage in ISO-induced rats. RESULTS: The oral administration of PRU significantly lowered the levels of lipid peroxidation and biochemical indicators, while significantly improving the antioxidant system function of ISO-interposed rats. In PRU-treated ISO-injected rats, histological examinations revealed suppressed myocardial destruction. CONCLUSION: Our research shows that oral pretreatment of PRU prevented ISO-induced oxidative stress in MI.

Nerve growth factor (Ngf) gene-driven semaphorin 3a (Sema3a) expression exacerbates thoracic aortic aneurysm dissection in mice.

Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease and currently there is no pharmacological therapy. Sympathetic nerve overactivity plays an important role in the development of TAAD. Sympathetic innervation is mainly controlled by nerve growth factor (NGF, a key neural chemoattractant) and semaphoring 3A (Sema3A, a key neural chemorepellent), while the roles of these two factors in aortic sympathetic innervation and especially TAAD are unknown. We hypothesized that genetically manipulating the NGF/Sema3A ratio by the Ngf -driven Sema3a expression approach may reduce aortic sympathetic nerve innervation and mitigate TAAD progression. A mouse strain of Ngf gene-driven Sema3a expression (namely NgfSema3a/Sema3a mouse) was established by inserting the 2A-Sema3A expression frame to the Ngf terminating codon using CRISPR/Cas9 technology. TAAD was induced by ß-aminopropionitrile monofumarate (BAPN) both in NgfSema3a/Sema3a mice and wild type (WT) littermates. Contrary to our expectation, the BAPN-induced TAAD was severer in NgfSema3a/Sema3a mice than in wild-type (WT) mice. In addition, NgfSema3a/Sema3a mice showed higher aortic sympathetic innervation, inflammation and extracellular matrix degradation than the WT mice after BAPN treatment. The aortic vascular smooth muscle cells isolated from NgfSema3a/Sema3a mice and pretreated with BAPN in vivo for two weeks showed stronger capabilities of proliferation and migration than that from the WT mice. We conclude that the strategy of Ngf -driven Sema3a expression cannot suppress but worsens the BAPN-induced TAAD. By investigating the aortic phenotype of NgfSema3a/Sema3a mouse strain, we unexpectedly find a path to exacerbate BAPN-induced TAAD which might be useful in future TAAD studies.

Structure Evolution of Iron (Hydr)oxides under Nanoconfinement and Its Implication for Water Treatment.

In the development of nanoenabled technologies for large-scale water treatment, immobilizing nanosized functional materials into the confined space of suitable substrates is one of the most effective strategies. However, the intrinsic effects of nanoconfinement on the decontamination performance of nanomaterials, particularly in terms of structural modulation, are rarely unveiled. Herein, we investigate the structure evolution and decontamination performance of iron (hydr)oxide nanoparticles, a widely used material for water treatment, when confined in track-etched (TE) membranes with channel sizes varying from 200 to 20 nm. Nanoconfinement drives phase transformation from ferrihydrite to goethite, rather than to hematite occurring in bulk systems, and the increase in the nanoconfinement degree from 200 to 20 nm leads to a significant drop in the fraction of the goethite phase within the aged products (from 41% to 0%). The nanoconfinement configuration is believed to greatly slow down the phase transformation kinetics, thereby preserving the specific adsorption of ferrihydrite toward As(V) even after 20-day aging at 343 K. This study unravels the structure evolution of confined iron hydroxide nanoparticles and provides new insights into the temporospatial effects of nanoconfinement on improving the water decontamination performance.

Recent progress in 2D bipolar magnetic semiconductors.

Bipolar magnetic semiconductor (BMS) is a class of magnetic semiconductors, whose valence band maximum and conduction band minimum are fully spin-polarized with opposite spin directions. Due to the special energy band, half-metallicity can be easily obtained in BMS by gate voltage, and the spin polarization can be reversed between spin-up and down when the gate voltage switches from positive to negative. BMSs have great potential applications in spintronic devices, such as the field-effect spin valves, spin filters and spin transistors,etc. With the rapid progress of the two-dimensional (2D) magnetic materials, researchers have identified a series of potential intrinsic 2D BMS materials using high-throughput computational methods. Additionally, methods such as doping, application of external stress, introduction of external fields, stacking of interlayer antiferromagnetic semiconductors, and construction of Janus structures have endowed existing materials with BMS properties. This paper reviews the research progress of 2D BMS. These advancements provide crucial guidance for the design and synthesis of BMS materials and offer innovative pathways for the future development of spintronics.

Bilateral Pectoralis Major Muscle Flaps in Treating Deep Sternal Wound Infection following CABG in Diabetic Patients: Two Case Reports.

Deep sternal wound infection (DSWI) is a life-threatening complication after cardiac operations, especially after coronary artery bypass grafting (CABG) in diabetic patients. Bilateral pectoralis major muscle flaps have been performed to treat DSWI. Two diabetic patients suffering from DSWI after CABG were treated by bilateral pectoralis major muscle flaps in our hospital. Both patients were discharged with full recovery. Satisfactory results can be obtained with bilateral pectoralis major muscle flaps following tissue debridement and drainage. This procedure should be performed when DSWI occurs in diabetic patients after CABG.

A 106-year-old patient with unexpected COVID-19 pneumonia: A case report.

The fast spread of COVID-19, which was caused by SARS-CoV-2 infection, has posed a major challenge to public health systems around the world. Morbidity and mortality are higher in the elderly than in the young, due to a loss in immune function and more comorbidities. In this case, we describe a 106-year-old female patient, the oldest COVID-19 patient since 2019, who had not previously received the SARS-CoV-2 vaccine. Her clinical symptoms included cough and sputum production. Images of her chest CT showed double lung pneumonia, and laboratory tests revealed elevated serum KL-6 levels. She was mostly on oral medication during her hospitalization and recovered well. With the case, we discuss the risk factors and biomarkers correlated to COVID-19 severity. Following the COVID outbreak, it's vital to explore the possible risk factors that can help with disease risk stratification, identifying high-risk individuals, developing precise treatment regimens, and lowering mortality rates.

MALT1 Positively Relates to T Helper 1 and T Helper 17 cells, and Serves as a Potential Biomarker for Predicting 30-Day Mortality in Stanford Type A Aortic Dissection Patients.

Mucosa-associated lymphoid tissue 1 (MALT1) regulates inflammation and T helper (Th) cell differentiation, which may participate in the progression of Stanford type A aortic dissection (TAAD). This study intended to assess the association of MALT1 expression with prognosis in TAAD patients. In this prospective study, MALT1 expression was measured by reverse transcription-quantitative polymerase chain reaction assay from peripheral blood samples in 100 TAAD patients and 100 non-AD controls (non-AD patients with chest pain) before treatment. Besides, Th1, Th2, and Th17 cells of TAAD patients before treatment were measured by flow cytometry assay, and their 30-day mortality was recorded. MALT1 expression was ascended in TAAD patients vs. non-AD controls (P < 0.001). In TAAD patients, elevated MALT1 expression was linked with hypertension complication (P = 0.009), increased systolic blood pressure (r = 0.291, P = 0.003), C-reactive protein (CRP) (r = 0.286, P = 0.004), and D-dimer (r = 0.359, P < 0.001). Additionally, MALT1 expression was positively correlated with Th1 cells (r = 0.312, P = 0.002) and Th17 cells (r = 0.397, P < 0.001), but not linked with Th2 cells (r = -0.166, P = 0.098). Notably, the 30-day mortality of TAAD patients was 28.0%. MALT1 expression [odds ratio (OR) = 1.936, P = 0.004], CRP (OR = 1.108, P = 0.002), D-dimer (OR = 1.094, P = 0.003), and surgery timing (emergency vs. selective) (OR = 8.721, P = 0.024) independently predicted increased risk of death within 30 days in TAAD patients. Furthermore, the combination of the above-mentioned independent factors had an excellent ability in predicting 30-day mortality with the area under curve of 0.949 (95% confidence interval: 0.909-0.989). MALT1 expression relates to increased Th1 cells, Th17 cells, and 30-day mortality risk in TAAD patients.

[ST266 inhibits neointimal hyperplasia after arterial balloon injury in rats].

Objective    To examine the effect of Human Amnion-Derived Multipotent Progenitor (AMP) cells and their novel ST266 secretome on neointimal hyperplasia after arterial balloon injury in rats.Material and Methods    Sprague-Dawley male rats were randomly divided into four groups (n=7): Control (PBS) group, systemic ST266 group, systemic AMP group and local AMP implant group. Neointimal hyperplasia was induced in the iliac using a 2F Fogarty embolectomy catheter. After surgery, the rats in the ST266 group were treated with 0.1, 0.5, or 1ml ST266 iv daily. In the systemic AMP groups, a single dose (SD) of 0.5 ×106 or 1×106 AMP cells was injected via the inferior vena cava after arterial balloon injury. In local AMP implant groups, 1×106, 5×106, or 20×106 AMP cells were implanted in 300 µl Matrigel (Mtgl) around the iliac artery after balloon injury. The iliac arteries were removed for histologic analysis at 28 days after the surgery. Re-endothelialization index was measured at 10 days after balloon injury.Results    ST266 (1 ml) group had a lower level of the Neointima / Neointima+Media ratio (N / N+M) 0.3±0.1 vs 0.5±0.1, p=0.004) and luminal stenosis (LS) percentage (18.2±1.9 % vs 39.2±5.8 %, p=0.008) compared with the control group. Single-dose AMP (1×106) decreased LS compared to the control group (19.5±5.4 % vs 39.2±5.8 %, p=0.033). Significant reduction in N / N+M were found between implanted AMPs (20×106) and the control group (0.4±0.1 vs 0.5±0.1, p=0.003) and the Mtgl-only group (0.5±0.1, p=0.007). Implanted AMPs (20×106) decreased the LS compared with both the control (39.2±5.8 %, p=0.001) and Mtgl-only group (37.5±8.6 %, p=0.016). ST266 (1 ml) significantly increased the re-endothelialization index compared to the control (0.4±0.1 vs 0.1±0.1, p=0.002).Conclusion    ST266 and AMP cells reduce neointimal formation and increase the re-endothelialization index after arterial balloon injury. ST266 is potentially a novel, therapeutic agent to prevent vascular restenosis in human.

Specific pupylation as IDEntity reporter (SPIDER) for the identification of protein-biomolecule interactions.

Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired. By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin (SA)-biotin system, we developed the Specific Pupylation as IDEntity Reporter (SPIDER) method for identifying protein-biomolecule interactions. Using SPIDER, we validated the interactions between the known binding proteins of protein, DNA, RNA, and small molecule. We successfully applied SPIDER to construct the global protein interactome for m6A and mRNA, identified a variety of uncharacterized m6A binding proteins, and validated SRSF7 as a potential m6A reader. We globally identified the binding proteins for lenalidomide and CobB. Moreover, we identified SARS-CoV-2-specific receptors on the cell membrane. Overall, SPIDER is powerful and highly accessible for the study of protein-biomolecule interactions.

Hyperuricemia Predicts the Progression of Type 2 Diabetic Kidney Disease in Chinese Patients.

INTRODUCTION: Diabetic kidney disease (DKD) has a high global disease burden and substantially increases the risk of end-stage renal disease and cardiovascular events. High levels of serum uric acid (SUA), or hyperuricemia, may indicate patients with type 2 diabetes (T2D) at risk for kidney disease. METHODS: This study explored the association between SUA levels and progression of kidney disease among patients with T2D. A cross-sectional study of 993 Chinese patients aged 20-75 years with T2D and DKD was conducted. Patients were stratified by progression risk of kidney disease based on estimated glomerular filtration rate and ratio of urinary albumin to creatinine, according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Ordinal logistic regression was used to assess associations between SUA and different KDIGO risk categories. RESULTS: Among 768 patients in the final analysis, those with hyperuricemia and higher SUA were more likely to be assigned to higher KDIGO risk categories. Patients with SUA > 420 µmol/L were ninefold more likely to be in a higher KDIGO risk category than those with SUA < 300 µmol/L (odds risk 9.74, 95% confidence interval 5.47-17.33, P < 0.001). CONCLUSIONS: Hyperuricemia may be associated with higher risk of DKD progression in individuals with T2D.

Elevated serum uric acid is not an independent risk factor for the occurrence of Type 2 diabetic kidney disease in Chinese populations.

Previous studies suggested that increased serum uric acid (SUA) level is an independent risk factor for albuminuria in Type 2 diabetes (T2D) patients. However, the association between SUA and onset of Type 2 DKD (T2DKD) remained to be clarified. This was a cross-sectional clinical study in which 1210 Chinese T2D patients were enrolled. According to the urine albumin-to-creatinine ratio (UACR), the cohort was divided into normal-albuminuria (UACR < 30 mg/g), micro-albuminuria (UACR 30-300 mg/g) and macro-albuminuria (UACR > 300 mg/g). The micro- and macro-albuminuria groups were combined into albuminuria category. Results showed that T2D patients with macro-albuminuria have significantly higher SUA than the other 2 groups (P < .001). In the binary logistic regression model, the subjects with SUA higher than 420 µmol/L were associated with a 2-fold increase in the odds of albuminuria (odds ratio = 2.024, 95% confidence interval: 1.232-3.325, P = .005), as compared with those with SUA lower than 300 µmol/L. Moreover, the multinomial regression analysis revealed that the subjects with SUA higher than 420 µmol/L had about 3-fold increase in the odds of macro-albuminuria (odds ratio = 3.758, 95% confidence interval: 2.051-6.885, P < .001), as compared with those with SUA lower than 300 µmol/L. However, SUA was not significantly associated with the presence of micro-albuminuria. Although the SUAwas not independently risk factor for micro-albuminuria, it was closely correlated with the development of macro-albuminuria in Chinese T2DKD patients. Elevated SUA may be useful for predicting the occurrence of macro-albuminuria but not onset of micro-albuminuria at the early stage of T2DKD.

Age- and Severity-Associated Humoral Immunity Response in COVID-19 Patients: A Cohort Study from Wuhan, China.

Age has been found to be the single most significant factor in COVID-19 severity and outcome. However, the age-related severity factors of COVID-19 have not been definitively established. In this study, we detected SARS-CoV-2-specific antibody responses and infectious disease-related blood indicators in 2360 sera from 783 COVID-19 patients, with an age range of 1−92 years. In addition, we recorded the individual information and clinical symptoms of the patients. We found that the IgG responses for S1, N, and ORF3a and the IgM for NSP7 were associated with severe COVID-19 at different ages. The IgM responses for the S-protein peptides S1-113 (aa 673−684) and S2-97 (aa 1262−1273) were associated with severe COVID-19 in patients aged <60. Furthermore, we found that the IgM for S1-113 and NSP7 may play a protective role in patients aged <60 and >80, respectively. Regarding clinical parameters, we analyzed the diagnostic ability of five clinical parameters for severe COVID-19 in six age groups and identified three-target panel, glucose, IL-6, myoglobin, IL-6, and NT proBNP as the appropriate diagnostic markers for severe COVID-19 in patients aged <41, 41−50, 51−60, 61−70, 71−80, and >80, respectively. The age-associated severity factors revealed here will facilitate our understanding of COVID-19 immunity and diagnosis, and eventually provide meaningful information for combating the pandemic.

Antimicrobial Biosynthetic Potential and Phylogenetic Analysis of Culturable Bacteria Associated with the Sponge Ophlitaspongia sp. from the Yellow Sea, China.

Sponge-derived bacteria are considered to be a promising source of novel drugs, owing to their abundant secondary metabolites that have diverse biological activities. In this study, we explored the antimicrobial biosynthetic potential and phylogenetics of culturable bacteria associated with the sponge Ophlitaspongia sp. from the Yellow Sea, China. Using culture-dependent methods, we obtained 151 bacterial strains, which were then analysed for their antimicrobial activities against seven indicator strains. The results indicate that 94 (62.3%) of the 151 isolated strains exhibited antimicrobial activities and inhibited at least one of the indicator strains. Fifty-two strains were selected for further phylogenetic analysis using 16S rRNA gene sequencing, as well as for the presence of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes. These 52 strains belonged to 20 genera from 18 families in 4 phyla, including Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. Five strains with PKS genes and ten strains with NRPS genes were detected. Among them, two strains contained both PKS and NRPS genes. Notoacmeibacter sp. strain HMA008 (class Alphaproteobacteria) exhibited potent antimicrobial activity; thus, whole genome sequencing methods were used to analyse its secondary metabolite biosynthetic gene clusters. The genome of HMA008 contained 12 biosynthetic gene clusters that potentially encode secondary metabolites belonging to compound classes such as non-ribosomal peptides, prodigiosin, terpene, ß-lactones, and siderophore, among others. This study indicates that the sponge Ophlitaspongia sp. harbours diverse bacterial strains with antimicrobial properties and may serve as a potential source of bioactive compounds.

Identification of sitagliptin binding proteins by affinity purification mass spectrometry.

Type 2 diabetes mellitus (T2DM) is recognized as a serious public health concern with increasing incidence. The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin has been used for the treatment of T2DM worldwide. Although sitagliptin has excellent therapeutic outcome, adverse effects are observed. In addition, previous studies have suggested that sitagliptin may have pleiotropic effects other than treating T2DM. These pieces of evidence point to the importance of further investigation of the molecular mechanisms of sitagliptin, starting from the identification of sitagliptin-binding proteins. In this study, by combining affinity purification mass spectrometry (AP-MS) and stable isotope labeling by amino acids in cell culture (SILAC), we discover seven high-confidence targets that can interact with sitagliptin. Surface plasmon resonance (SPR) assay confirms the binding of sitagliptin to three proteins, i. e., LYPLAL1, TCP1, and CCAR2, with binding affinities (K D) ranging from 50.1 µM to 1490 µM. Molecular docking followed by molecular dynamic (MD) simulation reveals hydrogen binding between sitagliptin and the catalytic triad of LYPLAL1, and also between sitagliptin and the P-loop of ATP-binding pocket of TCP1. Molecular mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis indicates that sitagliptin can stably bind to LYPLAL1 and TCP1 in active sites, which may have an impact on the functions of these proteins. SPR analysis validates the binding affinity of sitagliptin to TCP1 mutant D88A is ~10 times lower than that to the wild-type TCP1. Our findings provide insights into the sitagliptin-targets interplay and demonstrate the potential of sitagliptin in regulating gluconeogenesis and in anti-tumor drug development.

Total Arch Replacement Combined with Stented Elephant Trunk Implantation for Acute Type A Aortic Dissection in an Octogenarian Patient.

BACKGROUND: The indications and outcome of surgery for Acute type A aortic dissection (ATAAD) in elderly patients are still debated, especially when they were above 80 years old.  Case presentation: This report describes the case of an octogenarian patient with ATAAD who underwent total arch replacement (TAR) combined with stented elephant trunk (SET) implantation. CONCLUSION: Emergent surgery should be performed on the ATAAD octogenarians without serious preoperative complications. Acceptable outcomes could be received by total arch replacement combined with SET implantation.

Bagging Strategy and Identification of Coloring Mode of 'Xinqihong' Pear.

'Xinqihong' is a recently selected and well-colored red pear (Pyrus bretschneideri Rehd.) cultivar that is popular in the marketplace owing to the bright red color and high quality of the fruit. The red pigmentation is strongly associated with the light signal. However, its responses to bagging treatment and to light exposure after shading are unknown. In this study, the fruit were treated with three types of fruit bags. 'Xinqihong' fruit colored rapidly in response to light stimulation. A white fruit bag was optimal for bagging of 'Xinqihong' fruit. To ensure satisfactory red pigmentation, the fruit required exposure to 30 days of light after bag removal. A transcriptome analysis was conducted to screen light-signal-related genes and identify their possible functions. PbCRY1 activated the promoter of PbHY5.2 and enhanced its expression. PbHY5.2 activated the promoter activity of PbUFGT and induced anthocyanin synthesis, and also showed self-activation characteristics. Both PbCRY2 and PbPHY1 induced anthocyanin accumulation. Thus, blue-light receptors played an important role in anthocyanin synthesis. This study provides a theoretical basis for the bagging cultivation of new varieties of 'Xinqihong', and lays a foundation for the study of the mechanisms of red pear fruit coloring in response to light signals.

A group of CLE peptides regulates de novo shoot regeneration in Arabidopsis thaliana.

Known for their regulatory roles in stem cell homeostasis, CLAVATA3/ESR-RELATED (CLE) peptides also function as mediators of external stimuli such as hormones. De novo shoot regeneration, representing the remarkable plant cellular plasticity, involves reconstitution of stem cells under control of stem-cell regulators. Yet whether and how stem cell-regulating CLE peptides are implicated in plant regeneration remains unknown. By CRISPR/Cas9-induced loss-of-function studies, peptide application, precursor overexpression, and expression analyses, the role of CLE1-CLE7 peptides and their receptors in de novo shoot regeneration was studied in Arabidopsis thaliana. CLE1-CLE7 are induced by callus-induction medium and dynamically expressed in pluripotent callus. Exogenously-applied CLE1-CLE7 peptides or precursor overexpression effectively leads to shoot regeneration suppression, whereas their simultaneous mutation results in enhanced regenerative capacity, demonstrating that CLE1-CLE7 peptides redundantly function as negative regulators of de novo shoot regeneration. CLE1-CLE7-mediated shoot regeneration suppression is impaired in loss-of-function mutants of callus-expressed CLAVATA1 (CLV1) and BARELY ANY MERISTEM1 (BAM1) genes, indicating that CLV1/BAM1 are required for CLE1-CLE7-mediated shoot regeneration signaling. CLE1-CLE7 signaling resulted in transcriptional repression of WUSCHEL (WUS), a stem cell-promoting transcription factor known as a principal regulator of plant regeneration. Our results indicate that functionally-redundant CLE1-CLE7 peptides genetically act through CLV1/BAM1 receptors and repress WUS expression to modulate shoot-regeneration capacity, establishing the mechanistic basis for CLE1-CLE7-mediated shoot regeneration and a novel role for CLE peptides in hormone-dependent developmental plasticity.

Non-coding RNAs Regulate the Pathogenesis of Aortic Dissection.

Aortic dissection (AD) is a fatal cardiovascular disease. It is caused by a rupture of the aortic intima or bleeding of the aortic wall that leads to the separation of different aortic wall layers. Patients with untreated AD have a mortality rate of 1-2% per hour after symptom onset. Therefore, effective biomarkers and therapeutic targets are needed to reduce AD-associated mortality. With the development of molecular technology, researchers have begun to explore the pathogenesis of AD at gene and protein levels, and have made some progress, but the pathogenesis of AD remains unclear. Non-coding RNAs, such as microRNAs, lncRNAs, and circRNAs, have been identified as basic regulators of gene expression and are found to play a key role in the pathogenesis of AD. Thus, providing a theoretical basis for developing these non-coding RNAs as clinical biomarkers and new therapeutic targets for AD in the future. Previous studies on the pathogenesis of AD focused on miRNAs, but recently, there have been an increasing number of studies that explore the role of lncRNAs, and circRNAs in AD. This review summarizes the existing knowledge on the roles of various non-coding RNAs in the pathogenesis of AD, discusses their potential role as clinical biomarkers and therapeutic targets, states the limitations of existing evidence, and recommends future avenues of research on the pathogenesis of AD.

SARS-CoV-2-specific antibody response characteristics in COVID-19 patients of different ages.

Age has been found to be one of the main risk factors for the severity and outcome of COVID-19. However, differences in SARS-CoV-2 specific antibody responses among COVID-19 patients of different age groups remain largely unknown. In this study, we analyzed the IgG/IgM responses to 21 SARS-CoV-2 proteins and 197 peptides that fully cover the spike protein against 731 sera collected from 731 COVID-19 patients aged from 1 to We show that there is no overall difference in SARS-CoV-2 antibody responses in COVID-19 patients in the 4 age groups. By antibody response landscape maps, we find that the IgG response profiles of SARS-CoV-2 proteins are positively correlated with age. The S protein linear epitope map shows that the immunogenicity of the S-protein peptides is related to peptide sequence, disease severity and age of the COVID-19 patients. Furthermore, the enrichment analysis indicates that low S1 IgG responses are enriched in patients aged <50 and high S1 IgG responses are enriched in mild COVID-19 patients aged >60. In addition, high responses of non-structural/accessory proteins are enriched in severe COVID-19 patients aged >70. These results suggest the distinct immune response of IgG/IgM to each SARS-CoV-2 protein in patients of different age, which may facilitate a deeper understanding of the immune responses in COVID-19 patients.