The productive performance of intercropping.

Crop diversification has been put forward as a way to reduce the environmental impact of agriculture without penalizing its productivity. In this context, intercropping, the planned combination of two or more crop species in one field, is a promising practice. On an average, intercropping saves land compared with the component sole crops, but it remains unclear whether intercropping produces a higher yield than the most productive single crop per unit area, i.e., whether intercropping achieves transgressive overyielding. Here, we quantified the performance of intercropping for the production of grain, calories, and protein in a global meta-analysis of several production indices. The results show that intercrops outperform sole crops when the objective is to achieve a diversity of crop products on a given land area. However, when intercropping is evaluated for its ability to produce raw products without concern for diversity, intercrops on average generate a small loss in grain or calorie yield compared with the most productive sole crop (-4%) but achieve similar or higher protein yield, especially with maize/legume combinations grown at moderate N supply. Overall, although intercropping does not achieve transgressive overyielding on average, our results show that intercropping performs well in producing a diverse set of crop products and performs almost similar to the most productive component sole crop to produce raw products, while improving crop resilience, enhancing ecosystem services, and improving nutrient use efficiency. Our study, therefore, confirms the great interest of intercropping for the development of a more sustainable agricultural production, supporting diversified diets.

Reduced circ_lrrc49 in trigeminal ganglion contributes to neuropathic pain in mice by downregulating Ist1 and impairing autophagy.

Orofacial neuropathic pain is a common symptom induced by orofacial nerve injury caused by a range of trauma or dental and maxillofacial procedures but lacks effective treatment. Circular RNAs (circRNAs) participate in the regulatory processes of neuropathic pain. Nevertheless, the biological roles of circRNAs in orofacial neuropathic pain remain unexplored. In this study, circRNA sequencing and Real-time quantitative polymerase chain reaction (RT-qPCR) were carried out. Notably, a novel circRNA named circ_lrrc49 was identified to be downregulated following chronic constriction injury of the infraorbital nerve (CCI-ION) in mice on day 14. Subsequent RNA Antisense Purification (RAP)-mass spectrometry and RNA immunoprecipitation found a direct interaction between circ_lrrc49 and increased sodium tolerance 1 homolog (Ist1). Western blot (WB) identified decreased expression of Ist1 on day 14 post-CCI-ION. Considering the known relationship between Ist1 and autophagy, LC3-II and p62 were detected to be upregulated, and an accumulation of autophagosomes were observed at the same time point. Besides, the knockdown of circ_lrrc49 by small interfering RNA (siRNA) reduced Ist1 expression, increased LC3-II, p62 levels and autophagosomes amount, and evoked orofacial mechanical hypersensitivity, which could be counteracted by the Ist1 overexpression. Similarly, the knockdown of Ist1 by siRNA also increased LC3-II and p62 levels and evoked orofacial mechanical hypersensitivity without influence on circ_lrrc49. Moreover, autophagy activation by rapamycin alleviated orofacial mechanical hypersensitivity evoked by CCI-ION or circ_lrrc49 knockdown. In conclusion, our data revealed the existence of a circ_lrrc49/Ist1/autophagy signaling axis contributing to the progression of orofacial neuropathic pain. These discoveries reveal the intricate molecular processes that drive orofacial neuropathic pain and identify circ_lrrc49 as a promising target for potential therapeutic interventions.

Evidence linking COVID-19 and the health/well-being of children and adolescents: an umbrella review.

BACKGROUND: Experiences during childhood and adolescence have enduring impacts on physical and mental well-being, overall quality of life, and socioeconomic status throughout one's lifetime. This underscores the importance of prioritizing the health of children and adolescents to establish an impactful healthcare system that benefits both individuals and society. It is crucial for healthcare providers and policymakers to examine the relationship between COVID-19 and the health of children and adolescents, as this understanding will guide the creation of interventions and policies for the long-term management of the virus. METHODS: In this umbrella review (PROSPERO ID: CRD42023401106), systematic reviews were identified from the Cochrane Database of Systematic Reviews; EMBASE (OvidSP); and MEDLINE (OvidSP) from December 2019 to February 2023. Pairwise and single-arm meta-analyses were extracted from the included systematic reviews. The methodological quality appraisal was completed using the AMSTAR-2 tool. Single-arm meta-analyses were re-presented under six domains associated with COVID-19 condition. Pairwise meta-analyses were classified into five domains according to the evidence classification criteria. Rosenberg's FSN was calculated for both binary and continuous measures. RESULTS: We identified 1551 single-arm and 301 pairwise meta-analyses from 124 systematic reviews that met our predefined criteria for inclusion. The focus of the meta-analytical evidence was predominantly on the physical outcomes of COVID-19, encompassing both single-arm and pairwise study designs. However, the quality of evidence and methodological rigor were suboptimal. Based on the evidence gathered from single-arm meta-analyses, we constructed an illustrative representation of the disease severity, clinical manifestations, laboratory and radiological findings, treatments, and outcomes from 2020 to 2022. Additionally, we discovered 17 instances of strong or highly suggestive pairwise meta-analytical evidence concerning long-COVID, pediatric comorbidity, COVID-19 vaccines, mental health, and depression. CONCLUSIONS: The findings of our study advocate for the implementation of surveillance systems to track health consequences associated with COVID-19 and the establishment of multidisciplinary collaborative rehabilitation programs for affected younger populations. In future research endeavors, it is important to prioritize the investigation of non-physical outcomes to bridge the gap between research findings and clinical application in this field.

Systemic and Local Administration of a Dual-siRNA Complex Efficiently Inhibits Tumor Growth and Bone Invasion in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of oral and oropharyngeal cancer cases and is characterized by high mortality and poor prognosis. RNA-based gene therapies have been developed as an emerging option for cancer treatment, but it has not been widely explored in OSCC. In this work, we developed an efficient siRNA cationic micelle DOTAP-mPEG-PCL (DMP) by self-assembling the cationic lipid DOTAP and monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) polymer. We tested the characteristics and transformation efficiency of this micelle and combined DMP with siRNA targeting STAT3 and TGF-ß to evaluate the antitumor effect and bone invasion interfering in vitro and in vivo. The average size of the DMP was 28.27 ± 1.62 nm with an average zeta potential of 54.60 ± 0.29 mV. The DMP/siRNA complex showed high delivery efficiency, with rates of 97.47 ± 0.42% for HSC-3. In vitro, the DMP/siSTAT3 complex exhibited an obvious cell growth inhibition effect detected by MTT assay (an average cell viability of 25.1%) and clonogenic assay (an average inhibition rate of 51.9%). Besides, the supernatant from HSC-3 transfected by DMP/siTGF-ß complexes was found to interfere with osteoclast differentiation in vitro. Irrespective of local or systemic administration, DMP/siSTAT3+siTGF-ß showed antitumor effects and bone invasion inhibition in the OSCC mice mandibular invasion model according to tumor volume assays and Micro-CT scanning. The complex constructed by DMP cationic micelles and siSTAT3+siTGF-ß represents a potential RNA-based gene therapy delivery system for OSCC.

Endophytes Alleviate Drought-Derived Oxidative Damage in Achnatherum inebrians Plants Through Increasing Antioxidants and Regulating Host Stress Responses.

Endophytes generally increase antioxidant contents of plants subjected to environmental stresses. However, the mechanisms by which endophytes alter the accumulation of antioxidants in plant tissues are not entirely clear. We hypothesized that, in stress situations, endophytes would simultaneously reduce oxidative damage and increase antioxidant contents of plants and that the accumulation of antioxidants would be a consequence of the endophyte ability to regulate the expression of plant antioxidant genes. We investigated the effects of the fungal endophyte Epichloë gansuensis (C.J. Li & Nan) on oxidative damage, antioxidant contents, and expression of representative genes associated with antioxidant pathways in Achnatherum inebrians (Hance) Keng plants subjected to low (15%) and high (60%) soil moisture conditions. Gene expression levels were measured using RNA-seq. As expected, the endophyte reduced the oxidative damage by 17.55% and increased the antioxidant contents by 53.14% (on average) in plants subjected to low soil moisture. In line with the accumulation of antioxidants in plant tissues, the endophyte increased the expression of most plant genes associated with the biosynthesis of antioxidants (e.g., MIOX, crtB, gpx) while it reduced the expression of plant genes related to the metabolization of antioxidants (e.g., GST, PRODH, ALDH). Our findings suggest that endophyte ability of increasing antioxidant contents in plants may reduce the oxidative damage caused by stresses and that the fungal regulation of plant antioxidants would partly explain the accumulation of these compounds in plant tissues.

N6-Methyladenosine (m6A) Sequencing Reveals Heterodera glycines-Induced Dynamic Methylation Promoting Soybean Defense.

Unraveling the intricacies of soybean cyst nematode (Heterodera glycines) race 4 resistance and susceptibility in soybean breeding lines-11-452 (highly resistant) and Dongsheng1 (DS1, highly susceptible)-was the focal point of this study. Employing cutting-edge N6-methyladenosine (m6A) and RNA sequencing techniques, we delved into the impact of m6A modification on gene expression and plant defense responses. Through the evaluation of nematode development in both resistant and susceptible roots, a pivotal time point (3 days postinoculation) for m6A methylation sequencing was identified. Our sequencing data exhibited robust statistics, successful soybean genome mapping, and prevalent m6A peak distributions, primarily in the 3' untranslated region and stop codon regions. Analysis of differential methylation peaks and differentially expressed genes revealed distinctive patterns between resistant and susceptible genotypes. In the highly resistant line (11-452), key resistance and defense-associated genes displayed increased expression coupled with inhibited methylation, encompassing crucial players such as R genes, receptor kinases, and transcription factors. Conversely, the highly susceptible DS1 line exhibited heightened expression correlated with decreased methylation in genes linked to susceptibility pathways, including Mildew Locus O-like proteins and regulatory elements affecting defense mechanisms. Genome-wide assessments, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, and differential methylation peak/differentially expressed gene overlap emphasized the intricate interplay of m6A modifications, alternative splicing, microRNA, and gene regulation in plant defense. Protein-protein interaction networks illuminated defense-pivotal genes, delineating divergent mechanisms in resistant and susceptible responses. This study sheds light on the dynamic correlation between methylation, splicing, and gene expression, providing profound insights into plant responses to nematode infection.

Electronic symptom monitoring for home-based palliative care: A systematic review.

BACKGROUND: Coordination and communication challenges in home-based palliative care complicate transitions from hospital care. Electronic symptom monitoring enables real-time data collection, enhancing patient-provider communication. However, a systematic evaluation of its effectiveness in home-based palliative care is lacking. AIM: To analyze the feasibility, effectiveness, and limitations of electronic symptom monitoring in home-based palliative care, assess the evidence quality, identify the evidence gap, and suggest implications for future research and practice. DESIGN: This study uses systematic review, meta-analysis, and narrative synthesis (CRD42023457977) to analyze relevant studies until September 2023. DATA SOURCES: Electronic searches in MEDLINE, CENTRAL, and Embase until September 2023, complemented by hand-searching of references and citations. RESULTS: This study included twenty studies. The majority of patients positively engage in electronic symptom monitoring, which could improve their quality of life, physical and emotional well-being, and symptom scores without a significant increase in costs. However, firm conclusions about the effects of electronic symptom monitoring on outcomes like survival, hospital admissions, length of stay, emergency visits, and adverse events were limited due to significant variability in the reported data or inadequate statistical power. CONCLUSION: Introducing electronic symptom monitoring in home-based palliative care holds potential for enhancing patient-reported outcomes, potentially decreasing hospital visits and costs. However, inconsistency in current studies arising from diverse monitoring systems obstructs comparability. To advance, future high-quality research should employ standardized follow-up periods and established scales to better grasp the benefits of electronic symptom monitoring in home-based palliative care.

Regulation of mineral elements in Hordeum brevisubulatum by Epichloë bromicola under Cd stress.

In this study, wild barley (Hordeum brevisubulatum) infected (E+) and uninfected (E-) by Epichloë bromicola were used for hydroponic experiments during the seedling stage. Various attributes, such as the effect of fungal endophyte on the growth and development of wild barley, the absorption of cadmium (Cd) and mineral elements (Ca, Mg, Fe, Mn, Cu, Zn), subcellular distribution, and chemical forms were investigated under CdCl2 stress. The results showed that the fungal endophy significantly reduced the Ca content and percentage of plant roots under Cd stress. The Fe and Mn content of roots, the mineral element content of soluble fractions, and the stems in the pectin acid or protein-chelated state increased significantly in response to fungal endophy. Epichloë endophyte helped Cd2+ to enter into plants; and reduced the positive correlation of Ca-Fe and Ca-Mn in roots. In addition, it also decreased the correlation of soluble components Cd-Cu, Cd-Ca, Cd-Mg in roots, and the negative correlation between pectin acid or protein-chelated Cd in stems and mineral elements, to increase the absorbance of host for mineral elements. In conclusion, fungal endophy regulated the concentration and distribution of mineral elements, while storing more Cd2+ to resist the damage caused by Cd stress. The study could provide a ground for revealing the Cd tolerance mechanism of endophytic fungal symbionts.

The present study is the first to study the effect of fungal endophy on essential mineral elements of plants under heavy metal stress, filling a gap in the existing research. The study could be helpful to reveal the mechanism of endophytic fungi to improve the host's tolerance to heavy metals and provide a foundation for the grass-endophyte symbionts to improve heavy metal-contaminated soils as ecological grasses.

Mandibular Gorham-Stout Disease With Implanted Fibular Resorption.

Gorham-Stout disease is an extremely rare disease characterized by progressive massive osteolysis with different clinical manifestations. The pathology is characterized by vascular proliferation, leading to destruction and resorption of the bone matrix, but the exact etiology is unknown. It can occur in any part of the body, with few reports of cases involving the maxillofacial region. Herein, the authors report a case of Gorham-Stout disease of the mandible, which started by affecting the alveolar bone and progressed to the mandibular marginal branches and even to the implanted vascularized free fibula.

Reconstruction of Extensive Maxillary Defects Using Flow-Through Fibula Free Flap With Anterolateral Thigh Free Flap.

BACKGROUND: The maxillary defects left unreconstructed or inadequately reconstructed often result in significant functional and esthetic impairments. Adequate reconstruction of extensive maxillary defects requires a sufficient volume of hard and soft tissues. METHODS: A 48-year-old male presenting bilateral extensive maxillary defects underwent secondary reconstruction with a flow-through fibula free flap in combination with an anterolateral thigh free flap. RESULTS: The use of flow-through technique allowed minimizing the problem of limited recipient vessels and the length of free flap vascular pedicle usually encountered in secondary reconstruction. The bilateral maxillary defects were successfully reconstructed, and the postoperative outcomes were uneventful. The patient was satisfied with the treatment outcomes. He is being followed up and was referred to the implantology department for the placement of osseointegrated dental implants. CONCLUSIONS: The flow-through fibula free flap, in combination with the anterolateral thigh free flap, was found reliable and feasible for this case of secondary reconstruction of bilateral maxillary defects. This technique has provided satisfactory functional and esthetic outcomes and effectively improved the patient's self-esteem.

Application of Oral Retractor for Lip Injury Protection in Oral and Maxillofacial Surgeries: A Randomized Controlled Trial.

PURPOSE: Iatrogenic lip injury may occur during oral and maxillofacial surgical procedures. This study aimed to evaluate the effect of oral retractors on iatrogenic lip injury prevention during intraoral procedures of oral and maxillofacial surgery. METHODS: We conducted a randomized controlled trial and included patients who underwent intraoral procedures of oral and maxillofacial surgery. Patients were randomly allocated to receive oral retractor (intervention group) or traditional procedure without lip protection (control group). The incidence of lip injury was the outcome variable. Other study variables included surgical time and satisfaction of patients and surgeons with treatment experience evaluated by visual analog scale (VAS). Student t test and χ 2 test were used to compare both groups' variables and measure the relationship between the predictor variable and the outcome variable. P <0.05 was considered significant for all analyses. RESULTS: A total of 114 patients were included, with 56 allocated to intervention group and 58 to control group. The results showed that the application of an oral retractor did not significantly increase surgical time ( P =0.318). A total of 12 patients had lip injury, with 1 in the intervention group and 11 in the control group ( P =0.003). For the assessment of satisfaction with treatment experience, the intervention group had significantly higher VAS scores for doctors and patients ( P <0.05). CONCLUSIONS: We found that the oral retractor was a good tool for iatrogenic lip injury prevention in oral and maxillofacial surgical procedures and could be considered in clinical treatment.

A New Definition for Alar Flare Based on "Alar Flare Angle".

BACKGROUND: An accurate diagnosis and an appropriate treatment are important parts of successful rhinoplasty. We proposed a new definition for alar flares to guide our clinical work. METHODS: A retrospective study was conducted on patients with alar flares from July 2017 to July 2021, and the follow-up time ranged from 12 to 27 months, mean of 16 months. We defined the alar flare angle by the formation of two lines: the line that connects the alar to the alar root point and line that connects the alar to the pronasale. The alar flare angle, interalar distance and nasal base width were measured, and alar wedge excision or alar base excision and tip elevation were performed. Scars, complications and satisfaction scales were evaluated after surgery. Through an analysis of the database, we found that the ideal alar flare angle was between 130 degrees and 140 degrees. If it was less than 130 degrees, it represented alar flares, and patients asked for alar surgery. RESULTS: A total of 33 patients were included. All patients underwent tip elevation, 12 patients underwent external alar wedge excision, and 5 patients underwent external alar wedge excision and alar base excision. External alar wedge excision can be used to completely correct alar flares, and in our study, the alar flare angles were more than 130 degrees after surgery. One patient complained of an acceptable scar, and there was no infection or alar deformity. All patients were satisfied. CONCLUSIONS: We proposed a new definition in which an alar flare angle less than 130 degrees can be diagnosed as an alar flare. This new definition is valuable for the clinical diagnosis and treatment of alar flares. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

LncRNA Anxa10-203 enhances Mc1r mRNA stability to promote neuropathic pain by recruiting DHX30 in the trigeminal ganglion.

BACKGROUND: Trigeminal nerve injury is one of the most serious complications in oral clinics, and the subsequent chronic orofacial pain is a consumptive disease. Increasing evidence demonstrates long non-coding RNAs (lncRNAs) play an important role in the pathological process of neuropathic pain. This study aims to explore the function and mechanism of LncRNA Anxa10-203 in the development of orofacial neuropathic pain. METHODS: A mouse model of orofacial neuropathic pain was established by chronic constriction injury of the infraorbital nerve (CCI-ION). The Von Frey test was applied to evaluate hypersensitivity of mice. RT-qPCR and/or Western Blot were performed to analyze the expression of Anxa10-203, DHX30, and MC1R. Cellular localization of target genes was verified by immunofluorescence and RNA fluorescence in situ hybridization. RNA pull-down and RNA immunoprecipitation were used to detect the interaction between the target molecules. Electrophysiology was employed to assess the intrinsic excitability of TG neurons (TGNs) in vitro. RESULTS: Anxa10-203 was upregulated in the TG of CCI-ION mice, and knockdown of Anxa10-203 relieved neuropathic pain. Structurally, Anxa10-203 was located in the cytoplasm of TGNs. Mechanistically, Mc1r expression was positively correlated with Anxa10-203 and was identified as the functional target of Anxa10-203. Besides, Anxa10-203 recruited RNA binding protein DHX30 and formed the Anxa10-203/DHX30 complex to enhance the stability of Mc1r mRNA, resulting in the upregulation of MC1R, which contributed to the enhancement of the intrinsic activity of TGNs in vitro and orofacial neuropathic pain in vivo. CONCLUSIONS: LncRNA Anxa10-203 in the TG played an important role in orofacial neuropathic pain and mediated mechanical allodynia in CCI-ION mice by binding with DHX30 to upregulate MC1R expression.

Hourly Air Pollutants and Acute Coronary Syndrome Onset in 1.29 Million Patients.

BACKGROUND: Short-term exposure to ambient air pollution has been linked with daily hospitalization and mortality from acute coronary syndrome (ACS); however, the associations of subdaily (hourly) levels of criteria air pollutants with the onset of ACS and its subtypes have rarely been evaluated. METHODS: We conducted a time-stratified case-crossover study among 1 292 880 patients with ACS from 2239 hospitals in 318 Chinese cities between January 1, 2015, and September 30, 2020. Hourly concentrations of fine particulate matter (PM2.5), coarse particulate matter (PM2.5-10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3) were collected. Hourly onset data of ACS and its subtypes, including ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, and unstable angina, were also obtained. Conditional logistic regressions combined with polynomial distributed lag models were applied. RESULTS: Acute exposures to PM2.5, NO2, SO2, and CO were each associated with the onset of ACS and its subtypes. These associations were strongest in the concurrent hour of exposure and were attenuated thereafter, with the weakest effects observed after 15 to 29 hours. There were no apparent thresholds in the concentration-response curves. An interquartile range increase in concentrations of PM2.5 (36.0 µg/m3), NO2 (29.0 µg/m3), SO2 (9.0 µg/m3), and CO (0.6 mg/m3) over the 0 to 24 hours before onset was significantly associated with 1.32%, 3.89%, 0.67%, and 1.55% higher risks of ACS onset, respectively. For a given pollutant, the associations were comparable in magnitude across different subtypes of ACS. NO2 showed the strongest associations with all 3 subtypes, followed by PM2.5, CO, and SO2. Greater magnitude of associations was observed among patients older than 65 years and in the cold season. Null associations of exposure to either PM2.5-10 or O3 with ACS onset were observed. CONCLUSIONS: The results suggest that transient exposure to the air pollutants PM2.5, NO2, SO2, or CO, but not PM2.5-10 or O3, may trigger the onset of ACS, even at concentrations below the World Health Organization air quality guidelines.

Association between Coronary Artery Disease Reporting and Data System-recommended Post-Coronary CT Angiography Management and Clinical Outcomes in Patients with Stable Chest Pain from a Chinese Registry.

Background Coronary Artery Disease Reporting and Data System (CAD-RADS) was developed to standardize and optimize disease management in patients after coronary CT angiography (CCTA), but the impact of CAD-RADS management recommendations on clinical outcomes remains unclear. Purpose To retrospectively assess the association between the appropriateness of post-CCTA management according to CAD-RADS version 2.0 and clinical outcomes. Materials and Methods From January 2016 to January 2018, consecutive participants with stable chest pain referred for CCTA were prospectively included in a Chinese registry and followed for 4 years. Retrospectively, CAD-RADS 2.0 classification and the appropriateness of post-CCTA management were determined. Propensity score matching (PSM) was used to adjust for confounding variables. Hazard ratios (HRs) for a major adverse cardiovascular event (MACE), relative risks for invasive coronary angiography (ICA), and the corresponding number needed to treat were estimated. Results Of the 14 232 included participants (mean age, 61 years ± 13 [SD]; 8852 male), 2330, 2756, and 2614 were retrospectively categorized in CAD-RADS 1, 2, and 3, respectively. Only 26% of participants with CAD-RADS 1-2 disease and 20% with CAD-RADS 3 received appropriate post-CCTA management. After PSM, appropriate post-CCTA management was associated with lower risk of MACEs (HR, 0.34; 95% CI: 0.22, 0.51; P < .001), corresponding to a number needed to treat of 21 in CAD-RADS 1-2 but not CAD-RADS 3 (HR, 0.86; 95% CI: 0.49, 1.85; P = .42). Appropriate post-CCTA management was associated with decreased use of ICA in CAD-RADS 1-2 (relative risk, 0.40; 95% CI: 0.29, 0.55; P < .001) and 3 (relative risk, 0.33; 95% CI: 0.28, 0.39; P < .001), resulting in a number needed to treat of 14 and 2, respectively. Conclusion In this retrospective secondary analysis, appropriate disease management after CCTA according to CAD-RADS 2.0 was associated with lower risk of MACEs and more prudent use of ICA. ClinicalTrials.gov registration no. NCT04691037 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Leipsic and Tzimas in this issue.

Hourly air pollution exposure and the onset of symptomatic arrhythmia: an individual-level case-crossover study in 322 Chinese cities.

BACKGROUND: Few studies have explored the relationship between air pollution and arrhythmia onset at the hourly level. We aimed to examine the association of exposure to air pollution with the onset of acute symptomatic arrhythmia at an hourly level. METHODS: We conducted a nationwide, time-stratified, case-crossover study in China between 2015 and 2021. We obtained hourly information on the onset of symptomatic arrhythmia (including atrial fibrillation, atrial flutter, atrial and ventricular premature beats and supraventricular tachycardia) from the Chinese Cardiovascular Association Database - Chest Pain Center (including 2025 certified hospitals in 322 cities). We obtained data on hourly concentrations of 6 air pollutants from the nearest monitors, including fine particles (PM2.5), coarse particles (PM2.5-10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO) and ozone. For each patient, we matched the case period to 3 or 4 control periods during the same hour, day of week, month and year. We used conditional logistic regression models to analyze the data. RESULTS: We included a total of 190 115 patients with acute onset of symptomatic arrhythmia. Air pollution was associated with increased risk of onset of symptomatic arrhythmia within the first few hours of exposure; this risk attenuated substantially after 24 hours. An interquartile range increase in PM2.5, NO2, SO2 and CO in the first 24 hours after exposure (i.e., lag period 0-24 h) was associated with significantly higher odds of atrial fibrillation (1.7%-3.4%), atrial flutter (8.1%-11.4%) and supraventricular tachycardia (3.4%-8.9%). Exposure to PM2.5-10 was associated with significantly higher odds of atrial flutter (8.7%) and supraventricular tachycardia (5.4%), and exposure to ozone was associated with higher odds of supraventricular tachycardia (3.4%). The exposure-response relationships were approximately linear, without discernible concentration thresholds. INTERPRETATION: Exposure to air pollution was associated with the onset of symptomatic arrhythmia shortly after exposure. This finding highlights the importance of further reducing air pollution and taking prompt protective measures for susceptible populations during periods of elevated levels of air pollutants.

Comparison of two diagnostic strategies for patients with stable chest pain suggestive of chronic coronary syndrome: rationale and design of the double-blind, pragmatic, randomized and controlled OPERATE Trial.

BACKGROUND: To achieve potential financial savings and avoid exposing the patients to unnecessary risk, an optimal diagnostic strategy to identify low risk individual who may derive minimal benefit from further cardiac imaging testing (CIT) is important for patients with stable chest pain (SCP) suggestive of chronic coronary syndrome (CCS). Although several diagnostic strategies have been recommended by the most recent guidelines, few randomized controlled trials (RCTs) have prospectively investigated the actual effect of applying these strategies in clinical practice. METHODS: OPERATE (OPtimal Evaluation of stable chest pain to Reduce unnecessAry utilization of cardiac imaging TEsting) trial is an investigator-initiated, multicenter, coronary computed tomography angiography (CCTA)-based, 2-arm parallel-group, double-blind, pragmatic and confirmative RCT planning to include 800 subjects with SCP suggestive of CCS. After enrollment, all subjects will be randomized to two arms (2016 U.K. National Institute of Health and Care Excellence guideline-determined and 2019 European Society of Cardiology guideline-determined diagnostic strategy) on a 1:1 basis. According to each strategy, CCTA should be referred and deferred for a subject in high and low risk group, respectively. The primary (effectiveness) endpoint is CCTA without obstructive coronary artery disease. Safety of each strategy will be mainly assessed by 1-year major adverse cardiovascular event rates. DISCUSSION: The OPERATE trial will provide comparative effectiveness and safety evidences for two different diagnostic strategies for patients with SCP suggestive of CCS, with the intension of improving the diagnostic yield of CCTA at no expense of safety. CLINICAL TRIAL REGISTRATION: ClinicalTrial.org Identifier NCT05640752.

Oxidation-responsive G-quadruplex ligand for selective inhibition of the proliferation of tumour cells.

Tumour cells show a higher level of reactive oxygen species (ROS) than normal cells. On the basis of this difference, we designed an oxidation-responsive G-quadruplex proligand PDS-B by installing borolanylbenzyls on a well-known pyridostatin (PDS) ligand PDS-S to response high level ROS in tumour cells. The rapid oxidative degradation of the proligand to its active form PDS-S in the presence of H2O2 confirms the oxidation-responsive design. According to Förster resonance energy transfer (FRET) assays, circular dichroism (CD) spectra and confocal fluorescence imaging, PDS-B stabilizes telomeric G4 structures after oxidation with H2O2 or intracellular ROS. Apoptosis assays and cell cycle assays showed significant selectivity of PDS-B in inhibiting the proliferation of tumour cells over normal cells through responses to a high level of ROS in the formers. Further assays confirmed higher level of relative Caspase-3 activity in tumour cells than normal cells, consequently the enhanced apoptosis of the tumour cells induced by PDS-B. In summary, the results demonstrate a modification approach to solve the poor selectivity of the G4 ligand in tumour cells and cytotoxicity in normal cells.

Occurrence of Crown Rot Caused by Fusarium pseudograminearum in Oat (Avena sativa) in China.

Oats (Avena sativa) are an important fodder crop for grazing livestock in northern and northwestern China (Chen et al. 2021; Yang et al. 2010). In May 2019, a crown rot disease was observed in a field where oat has been grown continuously for 5 years in Yongchang County (37.52° N, 101.16° E), Gansu Province, with an average disease incidence of 3%. Affected plants were stunted and displayed crown and basal stem rot. The basal stem showed chocolate brown discoloration and several basal stems appeared slightly constricted. Three disease plots were surveyed and at least 10 plants were collected from each plot. Infected basal stems were disinfested by immersion in 75% ethanol for 30 s and 1% NaClO for 2 min, rinsed three times in sterilized water. Then they were placed on potato dextrose agar (PDA) medium, incubated at 20°C in the dark. Isolates were purified by single spore cultures (Leslie and Summerell, 2006). Ten monosporic cultures were consistently isolated with similar phenotypes. Then those isolates were transferred onto carnation leaf agar (CLA) and incubated at 20°C under blacklight blue lamps. On PDA, isolates produced abundant aerial mycelium, densely floccose, reddish-white to white with deep-red to reddish-white reverse pigmentation. On CLA, macroconidia of the strains were formed in sporodochia, but no microconidia were found. Macroconidia (n=50) were relatively slender, curved to almost straight, commonly 3-7 septate, 22.2 to 43.7 × 3.0 to 4.8 µm (averag 28.5 × 3.9 µm). The morphological characteristics of this fungus fully fit the description of Fusarium species (Aoki and O'Donnell, 1999). For molecular identification, total genomic DNA of representative strain Y-Y-L was extracted by using an HP Fungal DNA Kit (D3195), and the elongation factor 1 alpha (EF1-α) gene and RNA polymerase II second largest subunit (RPB2) gene were amplified using primers EF1 and EF2 (O'Donnell et al. 1998) and RPB2-5f2 and RPB2-7cr (O'Donnell et al. 2010), respectively. The sequences were deposited in GenBank (Accession numbers: OP113831 for EF1-α and OP113828 for RPB2). A nucleotide BLAST search revealed RPB2 and EF1-α sequences to be 99.78% and 100% similar to the corresponding sequences of the ex-type strain NRRL 28062 Fusarium pseudograminearum accessions numbers MW233433 and MW233090, respectively. In the maximum-likelihood phylogenetic tree, three Chinese strains (Y-Y-L, C-F-2 and Y-F-3) were grouped with the reference sequences of F. pseudograminearum with a high bootstrap supporting values of 98%. For pathogenicity tests, millet seed-based inoculum of F. pseudograminearum was prepared using a modified procedure (Chen et al. 2021). Healthy oat seedlings (4 weeks old) were transplanted into plastic pots containing pasteurized potting mix infested with millet seed-based inoculum of strain Y-Y-L F. pseudograminearum at a rate of 2% by mass fraction. Control seedlings for comparison were transplanted into pots containing potting mix without inoculum. Each treatment was inoculated with 5 pots each, with 3 plants per pot. Plants were maintained for 20 days under greenhouse conditions at 17 to 25℃ with all the inoculated plants developing symptoms similar to those observed in the field, while control plants remained healthy. The fungus was re-isolated from the basal stems of inoculated plants, and confirmed phenotypically and molecularly as F. pseudograminearum. F. pseudograminearum has been reported associated with crown rot in oat in Tunisia (Chekali et al. 2019). To our knowledge, this is the first report of F. pseudograminearum causing crown rot in oat in China. This study provides a basis for identifying pathogens causing oat root rot and managing the disease.

First Report of Bipolaris zeae Causing Leaf Spot on Setaria viridis in China.

Green bristlegrass (Setaria viridis) is an annual dominant herb in arid sandy grasslands with strong drought resistance to water stress (Valença et al. 2020). In August 2021, brown or dark tan spots on the leaves of S. viridis were observed on natural grassland in Qingyang city, Gansu Province, China (36.55°N, 107.32°E). Leaf disease incidence was around 13%, and the infected area of each leaf was about 20%. For isolation, 30 tissue pieces (5×5 mm) from 10 symptomatic leaf samples were surface-sterilized with 70% ethanol for 30 seconds and rinsed three times with steriled distilled water. Then these tissues were placed on the potato dextrose agar (PDA) at 25 °C, and incubated in dark from 2 to 5 days. Sixteen single-spored cultures with consistent colony characteristics were obtained by single spore isolation as described in Manamgoda et al. (2012). Colonies on PDA were irregular shapes with black color and white edge; conidia were dark brown with septate, cylindrical, straight or flexuous geniculate at the upper end, 22.7 to 69.38×9.2 to 17.6 µm (n = 50; average size 40.8×13.2 µm) under microscope (40X). The internal transcribed spacer (ITS) and glyceraldehyde-3-phosphate dehydrogenase (GPD) regions of the representative isolate 83HXGWC, 84HXGWC and 85HXGWC were amplified using the primers of ITS1/ITS4 and GPD1/GPD2 (Manamgoda et al. 2012). All the amplified gene sequences were deposited into GenBank with accession numbers ITS (OP703331, OQ978850, and OQ978851) and GPD (OQ559683, OQ992505, and OQ992506). BLAST analysis of both the two segments showed 100% identity with those reported sequences of ex-type isolate BRIP 11512 (KJ415538 and KJ415408) of B. zeae Sivan (Tan et al. 2014; Bhunjun et al. 2020), respectively. In the maximum-likelihood phylogenetic tree, 83-HXGWC, 84HXGWC and 85HXGWC strains were grouped with the reference sequences of B. zeae with a high bootstrap supporting values of 100%. Five healthy green bristlegrass (6 weeks) plants in pots were sprayed with conidial suspensions (1×106 conidia ml-1). Another five pots were sprayed with sterilized distilled water (controls). Then all pots were individually covered with transparent polyethylene bags for 5 days to maintain high relative humidity and placed in a greenhouse maintained at 18 to 25 °C. After incubation for 14 days, the typical symptoms of leaf spots developed from brown to dark brown on the plants inoculated with conidial suspension, whereas no symptoms were observed on the control plants. The measurement of pathogenicity was carried out three times. The same pathogens were consistently reisolated from inoculated leaves, and was confirmed as B. zeae based on morphological and molecular analyses, fulfilling Koch's postulates. This study provides a new record of B. zeae on green bristlegrass on natural grassland in China, which can potentially impose disease challenges to other crops. Since, B. oryzae has been known to cause disease in cereal crops (Manamgoda et al. 2014), this can be a potential alternate source of survival of this pathogen.