The association of physical activity and sedentary behavior with depression in US adults: NHANES 2007-2018.

Objectives: Depression is largely preventable, and strategies that can effectively suppress its development are imperative. We aimed to examine whether physical activity and sedentary behavior were associated with depression and explore the possible mediatory role of complete blood count in this association. Methods: In this cross-sectional study, data were integrated from the National Health and Nutrition Examination Study (2007-2018). Depression was defined using the Patient Health Questionnaire-9. The risk for depression, expressed as odds ratio (OR) and 95% confidence interval (CI), was quantified by survey-weighted logistic regression analyses. Results: A total of 31,204 respondents were analyzed. Significance was identified for all, except walking or bicycling per week, types of physical activity, and sedentary behavior. Per 1 standard deviation (SD) increment in metabolic equivalent of task (MET) of weekly vigorous recreational physical activity was associated with 31.3% decreased depression risk (adjusted OR: 0.687, 95% CI: 0.5663-0.840). Per 1 SD increment in sitting time can increase depression risk by 22.4% (adjusted OR: 1.224, 95% CI: 1.131-1.325). In subsidiary analyses, the association with depression was reinforced in respondents aged ≤65 years and those overweight or obese. Mediation analyses revealed significant effects for red blood cell (RBC) on total MET (19.4%) and moderate work-related physical activity (MWPA) (22.0%), and for red cell distribution wide (RCDW) on vigorous work-related physical activity (17.7%), moderate work-related physical activity (13.1%), total MET (11.2%), and sitting time (16.4%) (p < 0.01). Conclusion: Our findings indicate that more physical activity and less sitting time were associated with a lower likelihood of having depression among US adults, and this association was probably mediated by RBC and RCDW.

Heterozygous variants in USP25 cause genetic generalized epilepsy.

USP25 encodes ubiquitin-specific proteases 25, a key member of deubiquitinating enzyme family and is involved in neural fate determination. Although abnormal expression in Down's syndrome was reported previously, the specific role of USP25 in human diseases has not been defined. In this study, we performed trio-based whole exome sequencing in a cohort of 319 cases (families) with generalized epilepsy of unknown etiology. Five heterozygous USP25 variants including two de novo and three co-segregated variants were determined in eight individuals affected by generalized seizures and/or febrile seizures from five unrelated families. The frequency of USP25 variants showed a significantly high aggregation in this cohort compared to the East Asian population and all populations in the gnomAD database. The mean onset ages of febrile and afebrile seizures were 10 months (infancy) and 11.8 years (juvenile), respectively. The patients achieved seizure freedom except one had occasional nocturnal seizures at the last follow-up. Two patients exhibited intellectual disability. Usp25 was ubiquitously expressed in mouse brain with two peaks on embryonic days (E14‒E16) and postnatal day 21, respectively. Similarly, USP25 expressed in fetus/early childhood stage with a second peak at approximately 12‒20 years old in human brain, consistent with the seizure onset age at infancy and juvenile in the patients. To investigate the functional impact of USP25 deficiency in vivo, we established Usp25 knock-out mice, which showed increased seizure susceptibility compared to wild-type mice in pentylenetetrazol-induced seizure test. To explore the impact of USP25 variants, we employed multiple functional detections. In HEK293T cells, the severe phenotype associated variant (p.Gln889Ter) led to a significant reduction of mRNA and protein expressions but formed a stable truncated dimers with increment of deubiquitinating enzyme activities and abnormal cellular aggregations, indicating a gain-of-function effect. The p.Gln889Ter and p.Leu1045del increased neuronal excitability in mice brain, with a higher firing ability in p.Gln889Ter. These functional impairments align with the severity of the observed phenotypes, suggesting a genotype-phenotype correlation. Hence, a moderate association between USP25 and epilepsy was noted, indicating USP25 is potentially a predisposing gene for epilepsy. Our results from Usp25 null mice and the patient-derived variants indicated that USP25 would play epileptogenic role via loss-of-function or gain-of-function effects. The truncated variant p.Gln889Ter would have profoundly different effect on epilepsy. Together, our results underscore the significance of USP25 heterozygous variants in epilepsy, thereby highlighting the critical role of USP25 in the brain.

The receptor kinase OsANX limits precocious flowering and inflorescence over-branching and maintains pollen tube integrity in rice.

CrRLK1L subfamily members are involved in diverse growth- and development-related processes in Arabidopsis. However, the functions of their counterparts in rice are unknown. Here, OsANX expression was detected in developing inflorescences, mature pollen grains, and growing pollen tubes, and it was localized to the plasma membrane in pollen grains and tobacco epidermal cells. Homozygous osanx progeny could not be segregated from the CRISPR/Cas9-edited mutants osanx-c1+/- and osanx-c2+/-, and such progeny were segregated only occasionally from osanx-c3+/-. Further, all three alleles showed osanx male but not female gamete transmission defects, in line with premature pollen tube rupture in osanx-c3. Additionally, osanx-c3 exhibited precocious flowering, excessively branched inflorescences, and an extremely low seed setting rate of 1.4 %, while osanx-c2+/- and osanx-c3+/- had no obvious defects in inflorescence development or the seed setting rate compared to wild-type Nipponbare (Nip). Consistent with this, the complemented line pPS1:OsANX-GFP/osanx-c2 (PSC), in which the lack of OsANX expression was inflorescence-specific, showed slightly earlier flowering and overly-branched panicles. Multiple inflorescence meristem transition-related and inflorescence architecture-related genes were expressed at higher levels in osanx-c3 than in Nip; thus, they may partially account for the aforementioned mutant phenotypes. Our findings broaden our understanding of the biological functions of OsANX in rice.

The roles of bacteria and viruses in COPD-Bronchiectasis association: A prospective cohort study.

BACKGROUND: Exacerbations are implicated in bronchiectasis and COPD, which frequently co-exist [COPD-Bronchiectasis association (CBA)]. We aimed to determine the bacterial and viral spectrum at stable-state and exacerbation onset of CBA, and their association with exacerbations and clinical outcomes of CBA as compared with bronchiectasis. METHODS: We prospectively collected spontaneous sputum from adults with CBA, bronchiectasis with (BO) and without airflow obstruction (BNO) for bacterial culture and viral detection at stable-state and exacerbations. RESULTS: We enrolled 76 patients with CBA, 58 with BO, and 138 with BNO (711 stable and 207 exacerbation visits). Bacterial detection rate increased from BNO, CBA to BO at steady-state (P = 0.02), but not at AE onset (P = 0.91). No significant differences in viral detection rate were found among BNO, CBA and BO. Compared with steady-state, viral isolations occurred more frequently at exacerbation in BNO (15.8 % vs 32.1 %, P = 0.001) and CBA (19.5 % vs 30.6 %, P = 0.036) only. In CBA, isolation of viruses, human metapneumovirus and bacteria plus viruses was associated with exacerbation. Repeated detection of Pseudomonas aeruginosa (PA) correlated with higher modified Reiff score (P = 0.032) in CBA but not in BO (P = 0.178). Repeated detection of PA yielded a shorter time to the first exacerbation in CBA [median: 4.3 vs 11.1 months, P = 0.006] but not in BO (median: 8.4 vs 7.6 months, P = 0.47). CONCLUSIONS: Isolation of any viruses, human metapneumovirus and bacterialplus viruses was associated with CBA exacerbations. Repeated detection of PA confers greater impact of future exacerbations on CBA than on BO.

Squaramide-catalyzed enantioselective Michael addition of nitromethane to 2-enoylazaarenes: synthesis of chiral azaarene-containing γ-nitroketones.

Bifunctional chiral squaramide-catalyzed highly enantioselective Michael addition of nitromethane to diverse 2-enoylazaarenes was successfully performed. This protocol provided a set of chiral azaarene-containing γ-nitroketones with up to 98% yield and 98% ee in a solvent-free catalytic system under mild conditions. Furthermore, gram-scale synthetic utility was also showcased.

Oxidative stress mediated decrement of spinal endomorphin-2 contributes to lumbar disc herniation sciatica in rats.

Increasing evidence supported that oxidative stress induced by herniated lumbar disc played important role in the formation of lumbar disc herniation sciatica (LDHS), however, the neural mechanisms underlying LDHS need further clarification. Endomorphin-2 (EM2) is the endogenous ligand for mu-opioid receptor (MOR), and there is increasing evidence implicating the involvement of spinal EM2 in neuropathic pain. In this study, using an nucleus pulposus implantation induced LDHS rat model that displayed obvious mechanical allodynia, it was found that the expression of EM2 in dorsal root ganglion (DRG) and spinal cord was significantly decreased. It was further found that oxidative stress in DRG and spinal cord was significantly increased in LDHS rats, and the reduction of EM2 in DRG and spinal cord was determined by oxidative stress dominated increment of dipeptidylpeptidase IV activity. A systemic treatment with antioxidant could prevent the forming of mechanical allodynia in LDHS rats. In addition, MOR expression in DRG and spinal cord remained unchanged in LDHS rats. Intrathecal injection of MOR antagonist promoted pain behavior in LDHS rats, and the analgesic effect of intrathecal injection of EM2 was stronger than that of endomorphin-1 and morphine. Taken together, our findings suggest that oxidative stress mediated decrement of EM2 in DRG and spinal cord causes the loss of endogenous analgesic effects and enhances the pain sensation of LDHS.

Clinical Characteristics and Outcomes of the Phenotypes of COPD-Bronchiectasis Association.

INTRODUCTION: Although COPD may frequently co-exist with bronchiectasis [COPD-bronchiectasis associated (CBA)], little is known regarding the clinical heterogeneity. We aimed to identify the phenotypes and compare the clinical characteristics and prognosis of CBA. METHODS: We conducted a retrospective cohort study involving 2928 bronchiectasis patients, 5158 COPD patients, and 1219 patients with CBA hospitalized between July 2017 and December 2020. We phenotyped CBA with a two-step clustering approach and validated in an independent retrospective cohort with decision-tree algorithms. RESULTS: Compared with patients with COPD or bronchiectasis alone, patients with CBA had significantly longer disease duration, greater lung function impairment, and increased use of intravenous antibiotics during hospitalization. We identified five clusters of CBA. Cluster 1 (N=120, CBA-MS) had predominantly moderate-severe bronchiectasis, Cluster 2 (N=108, CBA-FH) was characterized by frequent hospitalization within the previous year, Cluster 3 (N=163, CBA-BI) had bacterial infection, Cluster 4 (N=143, CBA-NB) had infrequent hospitalization but no bacterial infection, and Cluster 5 (N=113, CBA-NHB) had no hospitalization or bacterial infection in the past year. The decision-tree model predicted the cluster assignment in the validation cohort with 91.8% accuracy. CBA-MS, CBA-BI, and CBA-FH exhibited higher risks of hospital re-admission and intensive care unit admission compared with CBA-NHB during follow-up (all P<0.05). Of the five clusters, CBA-FH conferred the worst clinical prognosis. CONCLUSION: Bronchiectasis severity, recent hospitalizations and sputum culture findings are three defining variables accounting for most heterogeneity of CBA, the characterization of which will help refine personalized clinical management.

The Receptor Kinases DRUS1 and DRUS2 Behave Distinctly in Osmotic Stress Tolerance by Modulating the Root System Architecture via Auxin Signaling.

Receptor kinases DRUS1 (Dwarf and Runtish Spikelet1) and DRUS2 are orthologues of the renowned Arabidopsis thaliana gene FERONIA, which play redundant roles in rice growth and development. Whether the two duplicated genes perform distinct functions in response to environmental stress is largely unknown. Here, we found that osmotic stress (OS) and ABA increased DRUS1 expression while decreasing DRUS2. When subjected to osmotic stress, the increased DRUS1 in drus2 mutants suppresses the OsIAA repressors, resulting in a robust root system with an increased number of adventitious and lateral roots as well as elongated primary, adventitious, and lateral roots, conferring OS tolerance. In contrast, the decreased DRUS2 in drus1-1 mutants are not sufficient to suppress OsIAA repressors, leading to a feeble root system with fewer adventitious and lateral roots and hindering seminal root growth, rendering OS intolerance. All these findings offer valuable insights into the biological significance of the duplication of two homologous genes in rice, wherein, if one is impaired, the other one is able to continue auxin-signaling-mediated root growth and development to favor resilience to environmental stress, such as water shortage.

Genome-wide analysis and expression profiling of the HD-ZIP gene family in kiwifruit.

The homeodomain-leucine zipper (HD-Zip) gene family plays a pivotal role in plant development and stress responses. Nevertheless, a comprehensive characterization of the HD-Zip gene family in kiwifruit has been lacking. In this study, we have systematically identified 70 HD-Zip genes in the Actinidia chinensis (Ac) genome and 55 in the Actinidia eriantha (Ae) genome. These genes have been categorized into four subfamilies (HD-Zip I, II, III, and IV) through rigorous phylogenetic analysis. Analysis of synteny patterns and selection pressures has provided insights into how whole-genome duplication (WGD) or segmental may have contributed to the divergence in gene numbers between these two kiwifruit species, with duplicated gene pairs undergoing purifying selection. Furthermore, our study has unveiled tissue-specific expression patterns among kiwifruit HD-Zip genes, with some genes identified as key regulators of kiwifruit responses to bacterial canker disease and postharvest processes. These findings not only offer valuable insights into the evolutionary and functional characteristics of kiwifruit HD-Zips but also shed light on their potential roles in plant growth and development.

DNA-functionalized MOF fluorescent probes for the enzyme-free and pretreatment-free detection of MicroRNA in serum.

MicroRNA (miRNA) is a promising biomarker that plays an important role in various biomedical applications, especially in cancer diagnosis. However, the current miRNA detection technology has inherent limitations such as complex operation, expensive testing cost and excessive detection time. In this study, a dual signal amplification biosensor based on DNA-functionalized metal-organic frameworks (MOFs) fluorescent probes, MFPBiosensor, was established for the enzyme-free and pretreatment-free detection of the colon cancer (CC) marker miR-23a. DNA-functionalized MOFs NH2-MIL-53(Al) (DNA@MOFs) were synthesized as fluorescent probes with specific recognition functions. A single DNA@MOF carries a large number of fluorescent ligands 2-aminoterephthalic acid (NH2-H2BDC), which can generate strong fluorescence signals after alkaline hydrolysis. Combined with catalyzed hairpin assembly (CHA), an efficient isothermal amplification technique, the dual signal enhancement strategy reduced matrix interference and sensitized the signal response. The established MFPBiosensor successfully detected extremely low levels of miRNA in complex biological samples with acceptable sensitivity and specificity. With a single detection cost of $0.583 and a test time of 50 min, the excellent inexpensive and rapid advantage of the MFPBiosensor is highlighted. More importantly, the subtle design enables the MFPBiosensor to achieve convenient batch detection, where miRNA in serum can be directly detected without any pretreatment process or enzyme. In conclusion, MFPBiosensor is a promising biosensor with substantial potential for commercial miRNA detection and clinical diagnostic applications of CC.

Tumor vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA): Suppresses macrophage capping protein beyond STING activation.

The vascular disrupting agent (VDA) 5,6-dimethylxanthenone-4-acetic acid (DMXAA) induces apoptosis in vascular endothelial cells and leads to tumor hemorrhagic necrosis. While DMXAA has been proven to be a potent agonist of murine stimulator of interferon genes (mSTING), it has little effect on human-STING (hSTING). This species selectivity of DMXAA may explain its effectiveness against solid tumors in mice and its failure in clinical trials. However, DMXAA did reduce tumor volume in some patients during clinical trials. These paradoxical results have prompted us to investigate the anti-tumor mechanism of DMXAA beyond STING in the destruction of tumor vasculature in humans. In this study, we demonstrated that DMXAA binds to both human and mouse macrophage capping protein (CapG), with a KD of 5.839 µM for hCapG and a KD of 2.867 µM for mCapG, as determined by surface plasmon resonance (SPR) analysis. Homology modeling and molecular docking analysis of hCapG indicated that the critical residues involved in the hydrogen bond interaction of DMXAA with hCapG were Arg153, Thr151, and GLN141, Asn234. In addition, electrostatic pi-cation interaction occurred between DMXAA and hCapG. Further functional studies revealed that CapG protein plays a crucial role in the effects of DMXAA on human umbilical endothelial vein cell (HUEVC) angiogenesis and migration, as well as the expression of cytoskeletal proteins actin and tubulin, and the invasion of A549 lung adenocarcinoma cells. Our study has originally uncovered a novel cross-species pathway underlying the antitumor vascular disruption of DMXAA extends beyond STING activation. This finding deepens our understanding of the multifaceted actions of flavonoid VDAs in animal models and in clinical settings, and may provide insights for the precise therapy of DMXAA based on the biomarker CapG protein.

[Determination of 21 organophosphate esters and their metabolites in drinking water by automatic solid phase extraction-liquid chromatography-tandem mass spectrometry].

OBJECTIVE: To establish a method for simultaneous determination of 21 organophosphate esters(OPEs) and their metabolites in drinking water by automatic solid phase extraction-liquid chromatography-tandem mass spectrometry. METHODS: The drinking water was purified by automatic solid phase extraction with HLB column, eluted by methanol, determined by liquid chromatography tandem mass spectrometry with ACQUITY UPLC BEH(100 mm×2.1mm, 1.7 µm) column, and quantified by internal standard method. RESULTS: The optimized method could simultaneously detect 21 organophosphate esters and their metabolites in drinking water. The detection limit was 0.01-0.24 ng/L, the quantitation limit was 0.03-0.77 ng/L. The recovery range was 57.6%-121.2% and the relative standard deviation is 1.2%-11.1% when the concentration was 0.8-20 ng/L. Senventeen tap water and 30 packaged drinking water collected by the supermarket were measured. The ΣOPEs range was 16.8-177 ng/L, and the Σdi-OPEs range was 0.328-16.3ng/L, indicating the exposure risk of organophosphates and their metabolites in water. CONCLUSION: The pretreatment of the method is simple, automatic and sensitive, and is suitable for simultaneous high-throughput determination of organophosphate esters and their metabolites in large quantities of drinking water.

Development and implementation of a high-fidelity simulation training course for medical and nursing collaboration based on the Fink integrated course design model.

Aim: The purpose of this study is to examine the design and implementation of a high-fidelity simulation training course for medical and nursing collaboration, based on the Fink integrated course design model. Additionally, the study aims to validate the teaching effectiveness of the course. Background: Previous empirical studies have highlighted the effectiveness of collaborative healthcare education in institutional teaching and hospital training. However, the development of healthcare collaborative education in China has been slow to develop in China. In recent years, Chinese nursing educators and researchers have shown interest in utilizing high-fidelity simulators for healthcare collaborative education. These simulators help address the limitations of traditional nursing teaching and healthcare separation simulation. Nevertheless, a standardized simulation interprofessional education curriculum is still lacking. Therefore, nursing educators need to develop a standardized high-fidelity simulation training curriculum for healthcare collaboration, guided by established science curriculum development theories. Methods: A high-fidelity simulation training course on healthcare collaboration was designed based on the Fink integrated curriculum design model. The course was taught to 14 nursing students and 8 clinical medicine students from March to July 2022. To comprehensively evaluate the effectiveness of the healthcare collaboration high-fidelity simulation training course, several assessment tools were used. These included course grades, satisfaction and self-confidence scales, simulation teaching practice scales, healthcare collaboration attitude scales, critical thinking skills scales, and semi-structured interviews. Results: After the course was implemented, students demonstrated high overall scores (79.19 ± 5.12) and reported high satisfaction ratings (4.44 ± 0.37). They also exhibited increased self-confidence (4.16 ± 0.33). Additionally, students evaluated all four dimensions of the course teaching practice scale positively. Furthermore, the study demonstrated significant improvements in various aspects, such as attitudes toward medical and nursing collaboration (t = -7.135, P < 0.01), shared education and teamwork (t = -3.247, P = 0.002), job autonomy for nurses (t = -1.782, P = 0.000), and reduced physician dominance (t = -6.768, P = 0.000). The critical thinking skills of the students showed significant improvement, with higher scores in truth-seeking (t = -3.052, P = 0.004), analytical ability (t = -2.561, P = 0.014), systematic ability (t = -3.491, P = 0.001), self-confidence in critical thinking (t = -4.024, P = 0.000), and curiosity (t = -5.318, P = 0.000) compared to their scores before the course (all P < 0.05). The interviews showed that the course's student-centered approach enabled active learning. Students suggested enhancing teaching cases and allocating more time for reflection and summarization. Conclusion: The study successfully designed a high-fidelity simulation training course for healthcare collaboration by utilizing the Fink integrated curriculum design model. The findings provide valuable insights for the development of standardized curricula and healthcare collaboration education in China. Moreover, the course adheres to best practice principles, fostering improved attitudes toward healthcare collaboration and enhancing students' healthcare collaboration and clinical thinking skills.

NUS1 Variants Cause Lennox-Gastaut Syndrome Related to Unfolded Protein Reaction Activation.

NUS1 encodes the Nogo-B receptor, a critical regulator for unfolded protein reaction (UPR) signaling. Although several loss-of-function variants of NUS1 have been identified in patients with developmental and epileptic encephalopathy (DEE), the role of the NUS1 variant in Lennox-Gastaut syndrome (LGS), a severe child-onset DEE, remains unknown. In this study, we identified two de novo variants of NUS1, a missense variant (c.868 C > T/p.R290C) and a splice site variant (c.792-2 A > G), in two unrelated LGS patients using trio-based whole-exome sequencing performed in a cohort of 165 LGS patients. Both variants were absent in the gnomAD population and showed a significantly higher observed number of variants than expected genome-wide. The R290C variant was predicted to damage NUS1 and decrease its protein stability. The c.792-2 A > G variant caused premature termination of the protein. Knockdown of NUS1 activated the UPR pathway, resulting in apoptosis of HEK293T cells. Supplementing cells with expression of wild-type NUS1, but not the mutant (R290C), rescued UPR activation and apoptosis in NUS1 knockdown cells. Compared to wild-type Drosophila, seizure-like behaviors and excitability in projection neurons were significantly increased in Tango14 (homolog of human NUS1) knockdown and Tango14R290C/+ knock-in Drosophila. Additionally, abnormal development and a small body size were observed in both mutants. Activated UPR signaling was also detected in both mutants. Thus, NUS1 is a causative gene for LGS with dominant inheritance. The pathogenicity of these variants is related to the UPR signaling activation, which may be a common pathogenic mechanism of DEE.

Adverse childhood experiences and mental health disorder in China: A nationwide study from CHARLS.

OBJECTIVES: Mental health disorder is highly prevalent worldwide, and factors attributable to its development have not been fully understood. We aimed to explore the association of adverse childhood experiences (ACEs) with mental health disorder using data from the China Health and Retirement Longitudinal Study (CHARLS). METHODS: CHARLS is an ongoing nationwide survey enrolling 17,708 residents aged ≥45 years in China. Total 20 ACE indicators were extracted. Unmeasured confounding and potential mediation were assessed, and effect-size estimates are expressed as odds ratio (OR) with 95 % confidence interval (CI). RESULTS: Of 10,961 assessable participants with complete information, 3652 were reported to have mental health disorder. The risk for mental health disorder was increased by 20.7 % for participants with one to less than four events of ACEs (OR: 1.207, 95 % CI: 0.711 to 2.049), and this number reached 102.7 % for participants with four or more events (OR: 2.027, 95 % CI: 1.196 to 3.436) relative to those with no ACE. In subgroup analyses, between-group risk estimates differed significantly for residence, marital status, personal asset, life satisfaction, and living standard. The E-value of 2.35 for ACEs of 4 or more events indicated the low likelihood of unmeasured confounders. In mediation analyses, the proportion eliminated was 5.1 % for continuous ACEs and 6.1 % for categorical ACEs (both P < 0.001). DISCUSSION: Our findings indicate that ACEs, especially with four or more events, can predict the significant risk of mental health disorder, underscoring the necessity of screening mental illness based on ACEs to reduce the resultant morbidity and mortality in China.

Corrigendum: ATP6V0C is associated with febrile seizures and epilepsy with febrile seizures plus.

[This corrects the article DOI: 10.3389/fnmol.2022.889534.].

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis: ERASE.

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.

Genetic control of thermomorphogenesis in tomato inflorescences.

Understanding how plants alter their development and architecture in response to ambient temperature is crucial for breeding resilient crops. Here, we identify the quantitative trait locus qMULTIPLE INFLORESCENCE BRANCH 2 (qMIB2), which modulates inflorescence branching in response to high ambient temperature in tomato (Solanum lycopersicum). The non-functional mib2 allele may have been selected in large-fruited varieties to ensure larger and more uniform fruits under varying temperatures. MIB2 gene encodes a homolog of the Arabidopsis thaliana transcription factor SPATULA; its expression is induced in meristems at high temperature. MIB2 directly binds to the promoter of its downstream gene CONSTANS-Like1 (SlCOL1) by recognizing the conserved G-box motif to activate SlCOL1 expression in reproductive meristems. Overexpressing SlCOL1 rescue the reduced inflorescence branching of mib2, suggesting how the MIB2-SlCOL1 module helps tomato inflorescences adapt to high temperature. Our findings reveal the molecular mechanism underlying inflorescence thermomorphogenesis and provide a target for breeding climate-resilient crops.

Bacteria and viruses and clinical outcomes of asthma-bronchiectasis overlap syndrome: A cohort study.

BACKGROUND: Despite the high prevalence of co-existing bronchiectasis and asthma (asthma-bronchiectasis overlap syndrome [ABOS]), little is known regarding the dominant pathogens and clinical correlates. OBJECTIVE: To investigate the bacteria and viruses which differentially dominate in ABOS (including its subtypes) compared with bronchiectasis alone, and determine their relevance with bronchiectasis severity and exacerbations. METHODS: This was a prospective observational cohort study conducted between March 2017 and August 2023. We included 81 patients with ABOS and 107 patients with bronchiectasis alone. At steady-state baseline, patients underwent comprehensive assessments and sputum collection for bacterial culture and viral detection (quantitative polymerase-chain-reaction). Patients were followed-up to record exacerbation and spirometry. RESULTS: Patients with ABOS had significantly higher symptom burden and exacerbation frequency than those with bronchiectasis alone. Despite similar pathogen spectrum, the rate of bacteria-virus co-detection increased less substantially at acute exacerbations (AE) onset than at steady-state compared with bronchiectasis alone. Pathogenic bacteria (particularly Pseudomonas aeruginosa) were detected fairly common (exceeding 50%) in ABOS and were associated with greater severity of bronchiectasis when stable and conferred greater exacerbation risks at follow-up. Viral but not bacterial compositions changed substantially at AE onset compared with clinical stability. Higher blood eosinophil count, moderate-to-severe bronchiectasis and non-atopy were associated with higher odds of bacterial, but not viral, detection (all p < 0.05). CONCLUSION: Detection of bacteria or virus is associated with bronchiectasis severity or clinical outcomes in ABOS. This highlights the importance of integrating sputum microbial assessment for ascertaining the dominant pathophysiology (atopy vs. infection) and longitudinal trajectory prediction in ABOS.