The actin polymerization factor Diaphanous and the actin severing protein Flightless I collaborate to regulate sarcomere size.

The sarcomere is the basic contractile unit of muscle, composed of repeated sets of actin thin filaments and myosin thick filaments. During muscle development, sarcomeres grow in size to accommodate the growth and function of muscle fibers. Failure in regulating sarcomere size results in muscle dysfunction; yet, it is unclear how the size and uniformity of sarcomeres are controlled. Here we show that the formin Diaphanous is critical for the growth and maintenance of sarcomere size: Dia sets sarcomere length and width through regulation of the number and length of the actin thin filaments in the Drosophila flight muscle. To regulate thin filament length and sarcomere size, Dia interacts with the Gelsolin superfamily member Flightless I (FliI). We suggest that these actin regulators, by controlling actin dynamics and turnover, generate uniformly sized sarcomeres tuned for the muscle contractions required for flight.

Comparative analysis of the endophytic bacteria inhabiting the phyllosphere of aquatic fern Azolla species by high-throughput sequencing.

BACKGROUND: Azolla is a small floating fern living in symbiosis with nitrogen-fixing cyanobacteria and provides a variety of important ecosystem benefits. Previous studies have presented that Azolla harbors diverse bacteria that may play a key role in host fitness and productivity. However, the characteristics of endophytic bacteria inhabiting the phyllosphere of different species of Azolla have not yet been fully understood. RESULTS: In this study, the 16S ribosomal DNA (rDNA) V5-V7 region of bacteria was determined by Illumina high-throughput sequencing platform to study the diversity and richness of endophytic bacterial communities in the phyllosphere of five Azolla species collected from different countries. A total of 1150 operational taxonomic units (OTUs) were detected for the endophytic bacteria community. According to the α diversity indices, the diversity of bacteria was ordered as Azolla imbricata > A. pinnata > A. filiculoides > A. mexicana > A. caroliniana. The PCoA results displayed that the bacterial communities of A. mexicana and A. caroliniana shared the highest similarity, followed by the similarity between A. pinnata and A. imbricata, and they were significantly distinct from the community of A. filiculoides. The dominant bacteria of Azolla mainly belonged to the phylum of Proteobacteria, followed by Actinobacteria, Chlorobillobacteria, and Firmicutes. In detail, the relative abundance of Proteobacteria in A. imbricata was 52.23%, whereas it was more than 80.00% in the other four species of Azolla. Notably, Herbaspirillum (45.91%, 44.08%) and Methylophilus (29.97%, 37.96%) were the main genera inhabiting A. mexicana and A. caroliniana respectively. Ferrovibrio (18.54%) and Rhizobium (16.68%) were the dominant genera inhabiting A. filiculoides. The group of unidentified genera (41.63%, 44.92%) consisted most of the bacteria in A. imbricata and A. pinnata respectively. Further analysis suggested that the significant different bacteria identified in LDA Effect Size analysis existed Azolla species-specific patterns. CONCLUSIONS: In summary, all results suggested that the diversity and composition of the endophytic bacterial communities were different in Azolla species.

Chronic cough in asthma is associated with increased airway inflammation, more comorbidities, and worse clinical outcomes.

Background: Cough is often the most prominent and intractable symptom reported by patients with asthma, but few studies have explored the characteristics of patients with asthma and with chronic cough (CC) in a real-world setting. Methods: In a prospective cohort study, patients ages ≥ 18 years with stable asthma were consecutively recruited at the West China Hospital, Sichuan University. The patients were classified as having asthma with CC (the CC group) or asthma with non-CC (the non-CC group) after 3 months of optimized asthma therapy according to standard guidelines. Multidimensional assessment was performed at baseline, followed by a 12-month follow-up to assess asthma exacerbations. Results: Of 323 patients with asthma, 127 patients were assigned to the CC group and 196 patients were assigned to the non-CC group. The participants with CC were older and had more airflow obstruction; worse asthma control and quality of life; increased airway inflammation; upper respiratory tract infection as a trigger; and more comorbidities, such as psychological dysfunction, rhinitis, chronic obstructive pulmonary disease, and bronchiectasis. They reported greater work productivity loss and daily activity impairment, and increased moderate-to-severe exacerbations. Conclusion: The participants with asthma and with CC had a significant disease burden, with increased exacerbations, health-care utilization, and impaired work productivity and daily activity. These observations indicated potential clinical implications in patients with asthma and with CC, and call for more attention to this aspect of asthma.

Glomerular Parietal Epithelial Cells Infection Is Associated With Poor Graft Outcome in Kidney Transplant Recipients With BK Polyomavirus-Associated Nephropathy.

BACKGROUND: The purpose of this study was to investigate the effect of BK polyomavirus (BKPyV infection of glomerular parietal epithelial cells (GPECs) on graft outcome in kidney transplant recipients with BKPyV-associated nephropathy (BKPyVAN). METHODS: A total of 152 kidney transplant recipients with BKPyVAN were divided into 31 with (GPEC-positive group) and 121 without (GPEC-negative group) BKPyV-infected GPECs. Clinicopathological characteristics and allograft survival were compared between the groups. RESULTS: The GPEC-positive group had more patients with advanced-stage BKPyVAN than the GPEC-negative group (P < .001). At the last follow-up, the GPEC-positive group had a significantly higher serum creatinine level than the GPEC-negative group. The graft loss rate in the GPEC-positive group was higher than that in the GPEC-negative group (32.3% vs 12.4%; P = .008). Kaplan-Meier analysis showed that the graft survival rate in the GPEC-positive group was lower than that in the GPEC-negative group (log-rank test, P = .004). Multivariate Cox regression analysis demonstrated that BKPyV infection of GPECs was an independent risk factor for graft survival (hazard ratio, 3.54; 95% confidence interval, 1.43-8.76; P = .006). CONCLUSIONS: GPEC infection in patients with BKPyVAN indicates more-severe pathological damage and a rapid decline in renal function. BKPyV infection of GPECs is an independent risk factor for allograft loss.

Acting on identity: Myoblast fusion and the formation of the syncytial muscle fiber.

The study of Drosophila muscle development dates back to the middle of the last century. Since that time, Drosophila has proved to be an ideal system for studying muscle development, differentiation, function, and disease. As in humans, Drosophila muscle forms via a series of conserved steps, starting with muscle specification, myoblast fusion, attachment to tendon cells, interactions with motorneurons, and sarcomere and myofibril formation. The genes and mechanisms required for these processes share striking similarities to those found in humans. The highly tractable genetic system and imaging approaches available in Drosophila allow for an efficient interrogation of muscle biology and for application of what we learn to other systems. In this article, we review our current understanding of muscle development in Drosophila, with a focus on myoblast fusion, the process responsible for the generation of syncytial muscle cells. We also compare and contrast those genes required for fusion in Drosophila and vertebrates.

The Formin Diaphanous Regulates Myoblast Fusion through Actin Polymerization and Arp2/3 Regulation.

The formation of multinucleated muscle cells through cell-cell fusion is a conserved process from fruit flies to humans. Numerous studies have shown the importance of Arp2/3, its regulators, and branched actin for the formation of an actin structure, the F-actin focus, at the fusion site. This F-actin focus forms the core of an invasive podosome-like structure that is required for myoblast fusion. In this study, we find that the formin Diaphanous (Dia), which nucleates and facilitates the elongation of actin filaments, is essential for Drosophila myoblast fusion. Following cell recognition and adhesion, Dia is enriched at the myoblast fusion site, concomitant with, and having the same dynamics as, the F-actin focus. Through analysis of Dia loss-of-function conditions using mutant alleles but particularly a dominant negative Dia transgene, we demonstrate that reduction in Dia activity in myoblasts leads to a fusion block. Significantly, no actin focus is detected, and neither branched actin regulators, SCAR or WASp, accumulate at the fusion site when Dia levels are reduced. Expression of constitutively active Dia also causes a fusion block that is associated with an increase in highly dynamic filopodia, altered actin turnover rates and F-actin distribution, and mislocalization of SCAR and WASp at the fusion site. Together our data indicate that Dia plays two roles during invasive podosome formation at the fusion site: it dictates the level of linear F-actin polymerization, and it is required for appropriate branched actin polymerization via localization of SCAR and WASp. These studies provide new insight to the mechanisms of cell-cell fusion, the relationship between different regulators of actin polymerization, and invasive podosome formation that occurs in normal development and in disease.

[Dynamical Analysis of the Inhibitory Effect of Aspirin and Clopidogrel on Platelet Adhesion and Aggregation for Healthy People under Physiological Flow Condition by Microfluidic Chip Technology].

Objective To explore the inhibitory effect of aspirin and clopidogrel on platelet adhesion and aggregation behaviors under the physiological flow condition using microfluidic chip technology for health volunteers. Methods Peripheral venous blood samples collected from twelve randomly recruited health volunteers were treated with 20 µmol/L acetylsalicylic acid,50 µmol/L 2-methlthioadenosine-5'-monophosphate triethylammonium salt,and their combination,respectively,with untreated blood samples being control group. The blood samples were flowed through a microchannel modified with type I collagen protein at a physiological relevant shear rate of 1000 s-1 for 300 s,while the fluorescent images of platelet aggregations were dynamic captured using a microscope. Based on the images,the platelet coverage rates were calculated and used as quantitative parameters for evaluating platelet adhesion and aggregation behaviors. Results Under a flow condition of 1000 s-1 shear rate,an expected in vivo-like platelet adhesion and aggregation behaviors were observed at the surfaces of collagen proteins for control blood samples. Aspirin alone or clopidogrel alone suppressed platelet adhesion and aggregation at the later period of flow(200-300 s),while the combination of aspirin and clopidogrel reduced the adhesion numbers of platelets at the earlier stage of flow(≤150 s) and compromised the stability of platelet aggregation at the later period of flow(200-300 s). The combination showed synergistic effect in inhibiting platelet aggregation. Furthermore,such inhibitory effect was heterogeneous among 12 volunteers. Conclusion This simple microfluidic technology can offer a new technical platform for analyzing the inhibitory effect of antiplatelet drugs.

PI(4,5)P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site.

Cell-cell fusion is a regulated process that requires merging of the opposing membranes and underlying cytoskeletons. However, the integration between membrane and cytoskeleton signaling during fusion is not known. Using Drosophila, we demonstrate that the membrane phosphoinositide PI(4,5)P2 is a crucial regulator of F-actin dynamics during myoblast fusion. PI(4,5)P2 is locally enriched and colocalizes spatially and temporally with the F-actin focus that defines the fusion site. PI(4,5)P2 enrichment depends on receptor engagement but is upstream or parallel to actin remodeling. Regulators of actin branching via Arp2/3 colocalize with PI(4,5)P2 in vivo and bind PI(4,5)P2 in vitro. Manipulation of PI(4,5)P2 availability leads to impaired fusion, with a reduction in the F-actin focus size and altered focus morphology. Mechanistically, the changes in the actin focus are due to a failure in the enrichment of actin regulators at the fusion site. Moreover, improper localization of these regulators hinders expansion of the fusion interface. Thus, PI(4,5)P2 enrichment at the fusion site encodes spatial and temporal information that regulates fusion progression through the localization of activators of actin polymerization.

En bloc kidney transplantation from infant donors younger than 10 months into pediatric recipients.

Early graft loss and poor graft function limit the use of kidneys from infant donors. Six en bloc kidney transplantations were performed from infant donors younger than 10 months into pediatric recipients between November 2012 and September 2015 at our center. We retrospectively analyzed recipient and donor demographics, surgery procedures, complications, graft function and size, and patient and graft survival with a follow-up of 6-39 months (median 15.5 months). Donor age ranged from 1 to 10 months with weight ranging from 3.5 to 10 kg. Recipient age ranged from 10 to 16 years with weight ranging from 30 to 39 kg. One kidney was removed due to arterial thrombosis during surgery, while the other kidney of this en bloc graft remained viable. Urine leak followed by bilateral ureteral obstruction occurred in one recipient. All of the recipients showed immediate graft function. The size of the en bloc kidney increased from 4.2±0.6 cm to 7.6±0.6 cm 6 months after surgery. Patient and graft survival were both 100% at the last follow-up. Our results show that en bloc kidney transplantation from infant donors younger than 10 months into pediatric recipients is effective under the condition of experienced surgical techniques and perioperative management.

Molecular detection and genome characterization of porcine circovirus type 2 in rats captured on commercial swine farms.

Porcine circovirus type 2 (PCV2) is considered the major etiological pathogen of porcine circovirus-associated diseases (PCVADs) in pigs. Recently, PCV2 was also found in non-porcine animals such as cattle, rats, and mice. However, there was no record of PCV2 in rats in China. The goal of this study was to investigate whether PCV2 was present in rats (Rattus norvegicus, RN) on three swine farms, using molecular tools. PCR results showed that 30 of 95 (31.6 %) rat samples were positive for PCV2. Moreover, further genotype analysis suggested that 10 of 30 (33.3 %) were positive for PCV2a, 19 of 30 (63.3 %) were positive for PCV2b, and only one sample (1/30, 3.33 %) was co-infected by PCV2a and PCV2b. To determine the possible origin of PCV2, 60 serum samples were also collected from weaned pigs on those swine farms, and 23 out of 60 samples were positive for PCV2. In addition, two distinct RN-origin and two distinct porcine-origin PCV2 full-length nucleotide sequences were obtained from the farms. Sequence and phylogenetic analysis indicated that they had the highest nucleotide similarity and closest genetic relationships to each other. In this study, we report the infection and genome characterization of PCV2 in rats and compare RN-origin and porcine-origin PCV2 sequences obtained from the same pig farm, revealing possible cross-species transmission of PCV2.

Mining the bladder cancer-associated genes by an integrated strategy for the construction and analysis of differential co-expression networks.

BACKGROUND: Bladder cancer is the most common malignant tumor of the urinary system and it is a heterogeneous disease with both superficial and invasive growth. However, its aetiological agent is still unclear. And it is indispensable to find key genes or modules causing the bladder cancer. Based on gene expression microarray datasets, constructing differential co-expression networks (DCNs) is an important method to investigate diseases and there have been some relevant good tools such as R package 'WGCNA', 'DCGL'. RESULTS: Employing an integrated strategy, 36 up-regulated differentially expressed genes (DEGs) and 356 down-regulated DEGs were selected and main functions of those DEGs are cellular physiological precess(24 up-regulated DEGs; 167 down-regulated DEGs) and cellular metabolism (19 up-regulated DEGs; 104 down-regulated DEGs). The up-regulated DEGs are mainly involved in the the pathways related to "metabolism". By comparing two DCNs between the normal and cancer states, we found some great changes in hub genes and topological structure, which suggest that the modules of two different DCNs change a lot. Especially, we screened some hub genes of a differential subnetwork between the normal and the cancer states and then do bioinformatics analysis for them. CONCLUSIONS: Through constructing and analyzing two differential co-expression networks at different states using the screened DEGs, we found some hub genes associated with the bladder cancer. The results of the bioinformatics analysis for those hub genes will support the biological experiments and the further treatment of the bladder cancer.

SFAPS: an R package for structure/function analysis of protein sequences based on informational spectrum method.

The R package SFAPS has been developed for structure/function analysis of protein sequences based on information spectrum method. The informational spectrum method employs the electron-ion interaction potential parameter as the numerical representation for the protein sequence, and obtains the characteristic frequency of a particular protein interaction after computing the Discrete Fourier Transform for protein sequences. The informational spectrum method is often used to analyze protein sequences, so we developed this software tool, which is implemented as an add-on package to the freely available and widely used statistical language R. Our package is distributed as open source code for Linux, Unix and Microsoft Windows. It is released under the GNU General Public License. The R package along with its source code and additional material are freely available at http://mlsbl.tongji.edu.cn/DBdownload.asp.

Prediction of protein-protein interactions from amino acid sequences using a novel multi-scale continuous and discontinuous feature set.

BACKGROUND: Identifying protein-protein interactions (PPIs) is essential for elucidating protein functions and understanding the molecular mechanisms inside the cell. However, the experimental methods for detecting PPIs are both time-consuming and expensive. Therefore, computational prediction of protein interactions are becoming increasingly popular, which can provide an inexpensive way of predicting the most likely set of interactions at the entire proteome scale, and can be used to complement experimental approaches. Although much progress has already been achieved in this direction, the problem is still far from being solved and new approaches are still required to overcome the limitations of the current prediction models. RESULTS: In this work, a sequence-based approach is developed by combining a novel Multi-scale Continuous and Discontinuous (MCD) feature representation and Support Vector Machine (SVM). The MCD representation gives adequate consideration to the interactions between sequentially distant but spatially close amino acid residues, thus it can sufficiently capture multiple overlapping continuous and discontinuous binding patterns within a protein sequence. An effective feature selection method mRMR was employed to construct an optimized and more discriminative feature set by excluding redundant features. Finally, a prediction model is trained and tested based on SVM algorithm to predict the interaction probability of protein pairs. CONCLUSIONS: When performed on the yeast PPIs data set, the proposed approach achieved 91.36% prediction accuracy with 91.94% precision at the sensitivity of 90.67%. Extensive experiments are conducted to compare our method with the existing sequence-based method. Experimental results show that the performance of our predictor is better than several other state-of-the-art predictors, whose average prediction accuracy is 84.91%, sensitivity is 83.24%, and precision is 86.12%. Achieved results show that the proposed approach is very promising for predicting PPI, so it can be a useful supplementary tool for future proteomics studies. The source code and the datasets are freely available at http://csse.szu.edu.cn/staff/youzh/MCDPPI.zip for academic use.

Porcine circovirus type 2 in China: an update on and insights to its prevalence and control.

Currently, porcine circovirus type 2 (PCV2) is considered the major pathogen of porcine circovirus associated-diseases (PCVAD) that causes large economic losses for the swine industry in the world annually, including China. Since the first report of PCV2 in 1998, it has been drawing tremendous attention for the government, farming enterprises, farmers, and veterinary practitioners. Chinese researchers have conducted a number of molecular epidemiological work on PCV2 by molecular approaches in the past several years, which has resulted in the identification of novel PCV2 genotypes and PCV2-like agents as well as the description of new prevalence patterns. Since late 2009, commercial PCV2 vaccines, including the subunit vaccines and inactivated vaccines, have already been used in Chinese swine farms. The aim of this review is to update the insights into the prevalence and control of PCV2 in China, which would contribute to understanding the epidemiology, control measures and design of novel vaccines for PCV2.

UBE2J1 is the E2 ubiquitin-conjugating enzyme regulating androgen receptor degradation and antiandrogen resistance.

Prostate cancer (PCa) is primarily driven by aberrant Androgen Receptor (AR) signaling. Although there has been substantial advancement in antiandrogen therapies, resistance to these treatments remains a significant obstacle, often marked by continuous or enhanced AR signaling in resistant tumors. While the dysregulation of the ubiquitination-based protein degradation process is instrumental in the accumulation of oncogenic proteins, including AR, the molecular mechanism of ubiquitination-driven AR degradation remains largely undefined. We identified UBE2J1 as the critical E2 ubiquitin-conjugating enzyme responsible for guiding AR ubiquitination and eventual degradation. The absence of UBE2J1, found in 5-15% of PCa patients, results in disrupted AR ubiquitination and degradation. This disruption leads to an accumulation of AR proteins, promoting resistance to antiandrogen treatments. By employing a ubiquitination-based AR degrader to adeptly restore AR ubiquitination, we reestablished AR degradation and inhibited the proliferation of antiandrogen-resistant PCa tumors. These findings underscore the fundamental role of UBE2J1 in AR degradation and illuminate an uncharted mechanism through which PCa maintains heightened AR protein levels, fostering resistance to antiandrogen therapies.

ZNF397 Deficiency Triggers TET2-driven Lineage Plasticity and AR-Targeted Therapy Resistance in Prostate Cancer.

Cancer cells exhibit phenotypical plasticity and epigenetic reprogramming, which allows them to evade lineage-dependent targeted treatments by adopting lineage plasticity. The underlying mechanisms by which cancer cells exploit the epigenetic regulatory machinery to acquire lineage plasticity and therapy resistance remain poorly understood. We identified Zinc Finger Protein 397 (ZNF397) as a bona fide coactivator of the androgen receptor (AR), essential for the transcriptional program governing AR-driven luminal lineage. ZNF397 deficiency facilitates the transition of cancer cell from an AR-driven luminal lineage to a Ten-Eleven Translocation 2 (TET2)-driven lineage plastic state, ultimately promoting resistance to therapies inhibiting AR signaling. Intriguingly, our findings indicate that a TET2 inhibitor can eliminate the resistance to AR targeted therapies in ZNF397-deficient tumors. These insights uncover a novel mechanism through which prostate cancer acquires lineage plasticity via epigenetic rewiring and offer promising implications for clinical interventions designed to overcome therapy resistance dictated by lineage plasticity.

Clinical characteristics and influencing factors of infectious diarrhea in preschool children: An observational study.

Infectious diarrhea is a common disease in preschool children, but the pathogenic species, origins, and influencing factors remain debatable. Therefore, more studies are required to solve these debatable topics. A number of 260 eligible preschool children diagnosed with infectious diarrhea in our hospital were enrolled in the infection group. Meanwhile, a number of 260 matched healthy children from the health center were enrolled in the control group. The pathogenic species and origins, the time of onset of infectious diarrhea in the infection group, demographic data, exposure history, hygiene habits, dietary habits, and other variables in both groups were initially collected from medical documents. In addition, a questionnaire was used to complete and confirm study variables through face-to-face or telephone interviews. Then, the univariate and multivariate regression analyses were used to screen the influencing factors of infectious diarrhea. Among 260 infected children, salmonella (15.77%), rotavirus (13.85%), shigella (11.54%), vibrio (10.38%), and norovirus (8.85%) were the top 5 common pathogens; January (13.85%), December (12.69%), August (12.31%), February (11.92%), and July (8.46%) were the top 5 frequent times of infectious diarrhea. The distribution of onset time for infectious diarrhea was commonly found in winter and summer, and the pathogens always originated from foods. The results of multivariate regression analysis showed that recent exposure to diarrhea, flies, and/or cockroaches indoors were the 2 risk factors for infectious diarrhea; Meanwhile, rotavirus vaccination, regular hand-washing, tableware disinfection, separate preparation of cooked and raw foods, and regular intake of lactobacillus products were the 5 protective factors for infectious diarrhea in preschool children. Infectious diarrhea has a diversity of pathogenic species, origins, and influencing factors in preschool children. Activities focusing on these influencing factors such as rotavirus vaccination, consumption of lactobacillus products, and other conventional factors would be beneficial to preschool children's health.

[Study on Platelet Adhesion and Aggregation Induced by Gradient Shear Stress Using Microfluidic Chip Technology].

OBJECTIVE: To study the effect of gradient shear stress on platelet aggregation by microfluidic chip Technology. METHODS: Microfluidic chip was used to simulate 80% fixed stenotic microchannel, and the hydrodynamic behavior of the stenotic microchannel model was analyzed by the finite element analysis module of sollidwork software. Microfluidic chip was used to analyze the adhesion and aggregation behavior of platelets in patients with different diseases, and flow cytometry was used to detect expression of the platelet activation marker CD62p. Aspirin, Tirofiban and protocatechuic acid were used to treat the blood, and the adhesion and aggregation of platelets were observed by fluorescence microscope. RESULTS: The gradient fluid shear rate produced by the stenosis model of microfluidic chip could induce platelet aggregation, and the degree of platelet adhesion and aggregation increased with the increase of shear rate within a certain range of shear rate. The effect of platelet aggregation in patients with arterial thrombotic diseases were significantly higher than normal group (P<0.05), and the effect of platelet aggregation in patients with myelodysplastic disease was lower than normal group (P<0.05). CONCLUSION: The microfluidic chip analysis technology can accurately analyze and evaluate the platelet adhesion and aggregation effects of various thrombotic diseases unde the environment of the shear rate, and is helpful for auxiliary diagnosis of clinical thrombotic diseases.

Cucurbit[n]uril-based fluorescent indicator-displacement assays for sensing organic compounds.

The widespread conversion of synthetic receptors into luminescent sensors has been achieved via the use of fluorescent-indicator displacement assays (F-IDAs). Due to their rigid structures and efficient binding affinities, cucurbit[n]urils, combined with a variety of fluorescent guests, have gained extensive utilization in fluorescent-indicator displacement assays for sensing non-fluorescent or weakly fluorescent organic compounds (analytes) in a selective and specific manner. This mini-review summarizes recent advances in the design of cucurbit[n]uril-based fluorescent-indicator displacement assays and discusses the current challenges and future prospects in this area.

Interaction effect of chronic cough and ageing on increased risk of exacerbation in patients with asthma: a prospective cohort study in a real-world setting.

Background: Older adults with asthma have the greatest burden and worst outcomes, and there is increasing evidence that chronic cough (CC) is associated with asthma severity and poor prognosis. However, the clinical characteristics of older adult patients with both asthma and CC remain largely unknown. Methods: Participants with stable asthma underwent two cough assessments within 3 months to define the presence of CC. Patients were divided into four groups based on CC and age (cut-off ≥60 years). Multidimensional assessment was performed at baseline, followed by a 12-month follow-up to investigate asthma exacerbations. Logistic regression models were used to explore the interaction effect of CC and age on asthma control and exacerbations. Results: In total, 310 adult patients were prospectively recruited and divided into four groups: older CC group (n=46), older non-CC group (n=20), younger CC group (n=112) and younger non-CC group (n=132). Compared with the younger non-CC group, the older CC group had worse asthma control and quality of life and increased airflow obstruction. The older CC group showed an increase in moderate-to-severe exacerbations during the 12-month follow-up. There was a significant interaction effect of CC and ageing on the increased moderate-to-severe exacerbations (adjusted risk ratio 2.36, 95% CI 1.47-3.30). Conclusion: Older asthma patients with CC have worse clinical outcomes, including worse asthma control and quality of life, increased airway obstruction and more frequent moderate-to-severe exacerbations, which can be partly explained by the interaction between CC and ageing.