The Mechanism of Ovule Abortion in Self-Pollinated 'Hanfu' Apple Fruits and Related Gene Screening.

Apples exhibit S-RNase-mediated self-incompatibility and typically require cross-pollination in nature. 'Hanfu' is a cultivar that produces abundant fruit after self-pollination, although it also shows a high rate of seed abortion afterwards, which greatly reduces fruit quality. In this study, we investigated the ovule development process and the mechanism of ovule abortion in apples after self-pollination. Using a DIC microscope and biomicroscope, we found that the abortion of apple ovules occurs before embryo formation and results from the failure of sperm-egg fusion. Further, we used laser-assisted microdissection (LAM) cutting and sperm and egg cell sequencing at different periods after pollination to obtain the genes related to ovule abortion. The top 40 differentially expressed genes (DEGs) were further verified, and the results were consistent with switching the mechanism at the 5' end of the RNA transcript (SMART-seq). Through this study, we can preliminarily clarify the mechanism of ovule abortion in self-pollinated apple fruits and provide a gene reserve for further study and improvement of 'Hanfu' apple fruit quality.

Positive effect of deep diaphragmatic breathing training on gastroesophageal reflux-induced chronic cough: a clinical randomized controlled study.

BACKGROUND AND OBJECTIVE: To explore the efficacy of deep diaphragmatic breathing training (DEP) in patients with gastroesophageal reflux-induced chronic cough (GERC). METHODS: A randomized controlled study was conducted involving 60 GERC patients who were divided into the intervention group and the control group (each with 30 patients). Both groups received routine medication treatment for GERC, while the intervention group received DEP training additionally. Both groups were evaluated by cough symptom scores, Hull airway reflux questionnaire (HARQ), gastroesophageal reflux diagnostic questionnaire (GerdQ), generalized anxiety disorder scale-7 (GAD-7), patient health questionnaire-9 (PHQ-9), Pittsburgh sleep quality index (PSQI), the Leicester cough questionnaire (LCQ), as well as capsaicin cough sensitivity testing, B-ultrasound and surface electromyography (sEMG) of the diaphragmatic muscles before and after treatment. The cough resolution rate and changes of the above indictors was compared between the two groups after eight weeks of treatment. RESULTS: After eight weeks of treatment, cough symptoms improved in both groups, but the cough resolution rate in the intervention group of 94% was significantly higher than that in the control group of 77% (χ2 = 6.402, P = 0.041). The intervention group showed significant improvements to the control group in GerdQ (6.13(0.35) VS 6.57(0.77)), GAD-7 (0(0;1) VS 1(0;3)), PSQI (2(1;3) VS 4(3;6)), LCQ (17.19(1.56) VS 15.88(1.92)) and PHQ-9 (0(0;0) VS 0(0;3)) after treatment. Compared to control group, sEMG activity of the diaphragmatic muscle was significantly increased in the intervention group after treatment, measured during DEP (79.00(2.49) VS 74.65 (1.93)) and quiet breathing (72.73 (1.96) VS 67.15 (2.48)). CONCLUSION: DEP training can improve cough symptoms as an adjunctive treatment in GERC patients. TRIAL REGISTRATION: The protocol was registered in February 2, 2022 via the Chinese Clinical Trials Register ( http://www.chictr.org.cn/ ) [ChiCTR2200056246].

Enriched oxygen improves age-related cognitive impairment through enhancing autophagy.

Age-related cognitive impairment represents a significant health concern, with the understanding of its underlying mechanisms and potential interventions being of paramount importance. This study aimed to investigate the effects of hyperbaric oxygen therapy (HBOT) on cognitive function and neuronal integrity in aged (22-month-old) C57BL/6 mice. Male mice were exposed to HBOT for 2 weeks, and spatial learning and memory abilities were assessed using the Morris water maze. We employed transcriptome sequencing and Gene Ontology (GO) term enrichment analysis to examine the effects of HBOT on gene expression profiles, with particular attention given to synapse-related genes. Our data indicated a significant upregulation of postsynapse organization, synapse organization, and axonogenesis GO terms, likely contributing to improved cognitive performance. Moreover, the hyperphosphorylation of tau, a hallmark of many neurodegenerative diseases, was significantly reduced in the HBO-treated group, both in vivo and in vitro. Transmission electron microscopy revealed significant ultrastructural alterations in the hippocampus of the HBOT group, including an increase in the number of synapses and the size of the active zone, a reduction in demyelinated lesions, and a decreased number of "PANTHOS." Furthermore, Western blot analyses confirmed the upregulation of PSD95, BDNF, and Syn proteins, suggesting enhanced synaptic plasticity and neurotrophic support. Moreover, HBOT increased autophagy, as evidenced by the elevated levels of Beclin-1 and LC3 proteins and the reduced level of p62 protein. Finally, we demonstrated that HBOT activated the AMPK-mTOR signaling pathway, a critical regulator of autophagy. Notably, our findings provide novel insights into the mechanisms by which HBOT ameliorates age-related cognitive impairment, suggesting the potential therapeutic value of this approach.

Microglia in brain aging: An overview of recent basic science and clinical research developments.

Aging is characterized by progressive degeneration of tissues and organs, and it is positively associated with an increased mortality rate. The brain, as one of the most significantly affected organs, experiences age-related changes, including abnormal neuronal activity, dysfunctional calcium homeostasis, dysregulated mitochondrial function, and increased levels of reactive oxygen species. These changes collectively contribute to cognitive deterioration. Aging is also a key risk factor for neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. For many years, neurodegenerative disease investigations have primarily focused on neurons, with less attention given to microglial cells. However, recently, microglial homeostasis has emerged as an important mediator in neurological disease pathogenesis. Here, we provide an overview of brain aging from the perspective of the microglia. In doing so, we present the current knowledge on the correlation between brain aging and the microglia, summarize recent progress of investigations about the microglia in normal aging, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, and then discuss the correlation between the senescent microglia and the brain, which will culminate with a presentation of the molecular complexity involved in the microglia in brain aging with suggestions for healthy aging.

A comparison between a gastroesophageal reflux disease questionnaire-based algorithm and multichannel intraluminal impedance-pH monitoring for the treatment of gastroesophageal reflux-induced chronic cough.

BACKGROUND: Empiric therapy with multichannel intraluminal impedance-pH monitoring (MII-pH) has been used for the initial treatment of gastroesophageal reflux-induced chronic cough (GERC). However, an algorithm based on the gastroesophageal reflux disease questionnaire (GerdQ) has the potential to achieve a simple, structured, and effective treatment approach for patients with GERC. OBJECTIVES: This study compared the efficacy of anti-reflux therapy based on GerdQ (new structured pathway, NSP) with medical treatment after MII-pH examination (ordinary clinical pathway, OCP) in the management of GERC. DESIGN: For the NSP, we adapted the GerdQ score to establish the basis for a treatment algorithm. For the OCP, treatment was determined using the MII-pH examination results. METHODS: The non-inferiority (NI) hypothesis was used to evaluate NSP versus OCP. RESULTS: Overall, the NSP and OCP-based therapeutic algorithms have similar efficacy for GERC [NI analysis: 95% confidence interval (CI), -4.97 to 17.73, p = 0.009; superiority analysis: p = 0.420]. Moreover, the cough symptom scores and cough threshold improved faster in the NSP group than in the OCP group at week 8 (p < 0.05). In the subgroup analyses using the GerdQ and GerdQ impact scale (GIS) scores, patients with low-likelihood GERC (GerdQ < 8) were more likely to benefit from OCP (NI analysis: 95% CI, -19.73 to 18.02, p = 0.213). On the other hand, in patients with high-likelihood and low-reflux impact GERC patients (GerdQ > 8 and GIS < 4), the NSP arm was not inferior to the standard treatment of OCP (NI analysis: 95% CI, -8.85 to 28.21%, p = 0.04; superiority analysis: p = 0.339), indicating that GerdQ- and GIS-guided diagnosis and management of patients with GERC could be an alternative to MII-pH management, especially in settings with reduced medical resources. CONCLUSIONS: The use of the GerdQ algorithm should be considered when handling patients with GERC in the primary care setting. TRIAL REGISTRATION: This research was registered in the Chinese Clinical Trials Registry (ChiCTR-ODT-12001899).

Post-reflux swallow-induced peristaltic wave index: a new parameter for the identification of non-acid gastroesophageal reflux-related chronic cough.

BACKGROUND: The current available diagnostic criteria for gastroesophageal reflux-related chronic cough (GERC) dominated by non-acid reflux is imperfect. The post-reflux swallow-induced peristaltic wave index (PSPWI) is a parameter reflecting esophageal clearance function. OBJECTIVES: This study aims to investigate its diagnostic value for non-acid GERC. DESIGN: This study sought to compare the diagnostic value of PSPWI in different types of GERC, particularly non-acid GERC, and explore the clinical significance of PSPWI in the diagnosis of non-acid GERC through diagnostic experiments. METHODS: A retrospective analysis was performed based on 223 patients with suspected GERC who underwent multichannel intraluminal impedance-pH monitoring (MII-pH) in the outpatient clinic of our department from August 2016 to June 2021. Their clinical information, laboratory test results, and treatment responses were assessed and the underlying etiologies of chronic cough were categorized. The predictive value of the PSPWI in diagnosing different types of GERC, especially non-acid GERC, was analyzed and compared. RESULTS: A total of 195 patients with chronic cough who met the inclusion criteria underwent MII-pH monitoring. 143 patients had a definitive diagnosis of GERC, including 98 with acid GERC and 45 with non-acid GERC. The diagnostic value of PSPWI alone was moderate for GERC with an area under the working curve (AUC) 0.760, but poor for non-acid GERC with an AUC of 0.569. However, PSPWI < 39.8% combining with acid exposure time (AET) ⩽ 6.2% demonstrated a moderate diagnostic value for non-acid GERC, with an AUC of 0.722. When PSPWI < 39.8% combined with a non-acid reflux ratio >68.75%, the diagnostic value for non-acid GERC was improved (AUCROC = 0.80 versus AUCROC = 0.722, p < 0.05), which was significantly superior to non-acid symptom index (AUCROC = 0.804 versus AUCROC = 0.550, p < 0.05) and non-acid symptom association probability (AUCROC = 0.804 versus AUCROC = 0.571, p < 0.05). CONCLUSION: PSPWI < 39.8% and AET ⩽ 6.2% have demonstrated good diagnostic value for non-acid GERC. The diagnostic value was further improved when combined with non-acid reflux ratio >68.75%.

The association between blue light exposure and incidence of type 2 diabetes: A prospective study of UK biobank.

BACKGROUND: Type 2 diabetes (T2D) is the most common type of diabetes. However, research on the relationship between blue light exposure and diabetes development is limited. OBJECTIVE: The present study aimed to investigate the relationship between blue light exposure and T2D incidence and whether it is affected by sleep duration, physical activity, outdoor activity time, and genetic susceptibility. METHODS: A total of 471,686 participants without diabetes were recruited from the UK Biobank cohort. T2D incidence was assessed using hospital inpatient records. Blue light exposure was calculated based on the time spent watching TV, using a computer, and playing computer games, which was determined using an online questionnaire. Cox proportional hazards regression models were used to assess the survival relationship between blue light exposure and T2D, as well as the potential modification effects. RESULT: A total of 18,738 cases of T2D were documented during the median follow-up of 13.04 years. After adjusting for potential confounders, the participants with heavy blue light exposure had a greater risk of T2D compared to those with mild blue light exposure (hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.12-1.23). A significant association between blue light exposure and T2D risk was observed among the participants with heavy physical activity (HR = 1.39, 95%CI: 1.25-1.55), healthy sleep habits (HR = 1.23, 95%CI: 1.10-1.36), higher outdoor activity time (HR = 1.14, 95%CI: 1.07-1.22), or high genetic susceptibility (HR = 1.24, 95%CI: 1.14-1.35). However, this association became non-significant among the participants with low genetic susceptibility (HR = 1.05, 95%CI: 0.97-1.15). CONCLUSION: The present study showed that blue light exposure is associated with a greater risk of T2D independent of classical T2D risk factors.

High-fat diet induces cognitive impairment through repression of SIRT1/AMPK-mediated autophagy.

AIMS: Recent evidence suggests an association between a high-fat diet (HFD) and cognitive decline. HFD may reduce synaptic plasticity and cause tau hyperphosphorylation, but the mechanisms involved remain unclear. The purpose of this study was to explore whether Sirtuin1 (SIRT1)/AMP-activated protein kinase (AMPK) pathway was involved in this pathogenic effect in the HFD exposed mice. METHODS: C57BL/6 mice at 12 months of age were fed a standard (9% kcal fat) or high-fat (60% kcal fat) diet for 22 weeks, and Neuro-2a (N2a) cells were treated with normal culture medium or a palmitic acid (PA) medium (100uM) for 40 h. After that, cognitive function was tested by Morris water maze (MWM). The levels of proteins involved in SIRT1/AMPK pathway and autophagy were measured using western blotting and immunofluorescence. We also assessed the phosphorylation of tau protein and synapse. RESULTS: The mice presented impaired learning and memory abilities. We further found decreased levels of synaptophysin (Syn) and brain-derived neurotrophic factor (BDNF), increased tau46 and phosphorylated tau protein, and damaged neurons in mice after HFD or in N2a cells treated with PA medium. Moreover, HFD can also reduce the expression of SIRT1, inhibit AMPK phosphorylation, and block autophagic flow in both mice and cells. After treating the cells with the SIRT1 agonist SRT1720, SIRT1/AMPK pathway and autophagy-related proteins were partially reversed and the number of PA-induced positive cells was alleviated in senescence-associated ß-galactosidase (SA-ß-gal) staining. CONCLUSIONS: HFD may inhibit the expression of SIRT1/AMPK pathway and disrupt autophagy flux, and result in tau hyperphosphorylation and synaptic dysfunction during aging, which ultimately lead to cognitive decline.

New Insights Into Refractory Chronic Cough and Unexplained Chronic Cough: A 6-Year Ambispective Cohort Study.

PURPOSE: Only limited studies have depicted the unique features and management of refractory chronic cough (RCC) and unexplained chronic cough (UCC). These led to the initiation of this study, which reported the demographic characteristics, manifestations, and long-term outcomes on a large series of consecutive RCC/UCC patients, providing a guideline-led real-world clinical experience. METHODS: Retrospective baseline information was obtained from Clinical Research Database (January 2016 to May 2021). At least 6 months after the last clinic visit, included subjects were prospectively followed up. RESULTS: Three hundred and sixty-nine RCC and UCC patients (199 females, 53.9%) were analyzed. The median cough duration was 24.0 (12.0-72.0) months. Laryngeal symptoms were reported in 95.9% of the patients. The common triggers for coughing were talking (74.9%), pungent odors (47.3%), eating (45.5%), and cold air (42.8%). RCC was considered in 38.2%, and the remainder of 228 patients had UCC, with an equal sex distribution (P = 0.66). Among the 141 RCCs, 90.8% (128) had refractory reflux cough, which was more responsive to current treatments (P < 0.01). Although most features and test results between RCC and UCC were similar, UCC was more commonly inappropriately treated (P < 0.01). Nineteen (7.7-41.1) months after the final clinic visit, 31.2% still coughed persistently, while 68.8% reported cough improvement or remission. RCC reported more favorable treatment outcomes (including cough improvement, control, and spontaneous remission) than UCC (P < 0.01). Coughs with long duration before the initial cough clinic visit (P < 0.01), frequent urinary incontinence (P < 0.01), and being sensitive to "talking" (P < 0.01) or "cold air" (P < 0.01) were less likely to be solved. CONCLUSIONS: The current treatments only improve cough symptoms in two-thirds of patients. Clinical indicators for treatment failure were those coughing for long duration and being sensitive to "talking" or "cold air."

A randomized, double-blinded, placebo-controlled clinical trial of duloxetine hydrochloride enteric-coated tablets in the treatment of refractory chronic cough.

INTRODUCTION: Refractory cough, a chronic cough with an unclear diagnosis or poor treatment response. The symptoms are often stubborn and persistent, causing serious complications and lowering the patient's quality of life. Cough hypersensitivity syndrome (CHS) is proposed as a potential cause, and reducing sensory nerve hyperresponsiveness is suggested as an effective treatment. However, current drugs have low efficacy and benefit rates and numerous side effects. This trail proposes using duloxetine, a selective 5-HT and norepinephrine reuptake inhibitor, as a potential treatment for refractory cough, which has shown promise in treating pain and depression. Duloxetine may inhibit pain conduction and oxidative stress in peripheral nerves by inhibiting the activity of TRPV1 channels, which play an important role in the peripheral afferent pathway of refractory cough. Meanwhile, the antidepressant effects of duloxetine may also play a role in the treatment of refractory cough. METHODS AND ANALYSIS: This is a single-center, prospective, randomized, double-blind, and controlled trial. A total of 98 individuals will be randomized in a 1:1 ratio to duloxetine group and placebo control group (starting with 20 mg QD, increasing 20 mg daily until 20 mg TID). After a screening period, the second stage runs from baseline to the 42nd (last) day of treatment, with follow-up visits on the 3rd, 7th, 14th, 21st, 28th, 35th, 42nd and 49th days. The main end-stage observation indicators include objective cough frequency, cough visual analog scale (VAS), cough symptom score, Leicester Cough Questionnaire (LCQ), and cough evaluation test (CET); the secondary end-stage observation indicators include capsaicin cough sensitivity, Patient Health Questionnaire-9 (PHQ-9), Major Depression Inventory (MDI), the Generalized Anxiety Disorder-7 scale (GAD-7), Life Events Scale (LES-32), induced sputum supernatant. The safety measures will be AEs/SAEs, vital signs, liver and kidney function, fecal occult blood test. DISCUSSION: This study is the first randomized, double-blind, and controlled clinical trial investigating the use of duloxetine in the treatment of refractory coughs. The study aims to provide a high-quality basis for evaluating the efficacy and safety of duloxetine for this condition. TRIAL REGISTRATION: Our study was registered in the Chinese Clinical Trials Register ( www.chictr.org.cn/ ) (ChiCTR2000037429) in 28/08/2020.

A systematic review: on the mercaptoacid metabolites of acrylamide, N-acetyl-S-(2-carbamoylethyl)-L-cysteine.

Acrylamide is widely found in a variety of fried foods and cigarettes and is not only neurotoxic and carcinogenic, but also has many potential toxic effects. The current assessment of acrylamide intake through dietary questionnaires is confounded by a variety of factors, which poses limitations to safety assessment. In this review, we focus on the levels of AAMA, the urinary metabolite of acrylamide in humans, and its association with other diseases, and discuss the current research gaps in AAMA and the future needs. We reviewed a total of 25 studies from eight countries. In the general population, urinary AAMA levels were higher in smokers than in non-smokers, and higher in children than in adults; the highest levels of AAMA were found in the population from Spain, compared with the general population from other countries. In addition, AAMA is associated with several diseases, especially cardiovascular system diseases. Therefore, AAMA, as a biomarker of internal human exposure, can reflect acrylamide intake in the short term, which is of great significance for tracing acrylamide-containing foods and setting the allowable intake of acrylamide in foods.

Psychological morbidity and chronic cough: which is predominant? A comparison of clinical characteristics.

Background: The clinical characteristics of chronic cough with pre-existing psychological co-morbidity (PCC) and chronic cough with secondary anxiety and depression (SCC) were compared to provide a basis for diagnosing and treating psychological co-morbidities in people with chronic cough. Methods: A prospective study was conducted to analyze the general clinical data between the PCC, SCC, and the chronic cough without anxiety and depression (CC) groups. A total of 203 patients with chronic cough were enrolled in the study. The final diagnosis was made in all cases using a combination of psychosomatic and respiratory diagnoses. The three groups' general clinical data, capsaicin cough sensitivity, cough symptom score, Leicester cough questionnaire (LCQ), and psychosomatic scale scores were compared among the three groups. The diagnostic value of the patient health questionnaire (PHQ)-9 and general anxiety disorder (GAD)-7 in patients with PCC and the follow-up information were analyzed. Results: Compared with the SCC group, the duration of cough in the PCC group was shorter (H = -3.54, p = 0.001), the night cough symptoms were milder (H = -4.60, p < 0.001), the total LCQ score was lower (H = -2.97, p = 0.009), and the PHQ-9 (H = 2.90, p = 0.011) and GAD-7 scores (H = 2.71, p = 0.002) were higher. When using PHQ-9 and GAD-7 scores for the combined prediction and diagnosis of PCC, the area under the curve (AUC) was 0.88, and the sensitivity and specificity were 90.0% and 73.85%, respectively. After 8 weeks of psychosomatic treatment, cough symptoms improved in the PCC group, but the psychological improvement was not significant. The psychological status of the SCC group improved after cough symptoms were ameliorated by etiologic or empirical treatment. Conclusion: The clinical characteristics of patients with PCC and SCC are different. The evaluation of psychosomatic scales is of value to distinguish between the two groups. Chronic cough patients with psychological co-morbidity benefit from the combined diagnosis of psychosomatic medicine in a timely fashion. PCC requires more attention in psychological therapy, but for SCC, targeting etiological treatment of the cough is preferred. Trial registration: The protocol was registered in the Chinese Clinical Trials Register (http://www.chictr.org.cn/) [ChiCTR2000037429].

Potential applications of P2X3 receptor antagonists in the treatment of refractory cough.

Refractory chronic cough is defined as a clinical condition in which the cause of the cough remains unclear after comprehensive examination and treatment, or the cause is clear but symptomatic treatment is ineffective. Patients with refractory chronic cough experience a variety of physiological and psychological issues that significantly lower their quality of life and place a significant socio-economic burden on society. As a result, research both domestically and internationally has turned heavily toward these patients. Recently, several studies have identified P2X3 receptor antagonists for the treatment of refractory chronic cough, and this paper reviews the background, mechanism of action, evidence-based proof and application prospects of this class of drugs. KEY MESSAGE: There were plenty of studies about P2X3 receptor antagonists in the past, and in recent years this series of drugs are effective in refractory chronic cough. Although review articles summarizing have been published previously, most have focused on their chemical properties rather than their clinical aspects, with some omitting drugs that have been in clinical studies for nearly two years such as Eliapixant and Sivopixant. Focusing on four P2X3 receptor antagonists with proven efficacy in clinical studies, we analyzed the characteristics and disadvantages of each drug by comparing their clinical results of them and theoretically explained the common side effects of these drugs, as well as their potential for treating refractory chronic cough. This article can be used as a reference for the follow-up studies of P2X3 receptor antagonists in chronic cough. Additionally, it also has implications for the clinical focus of the drug and the approaches to relieve some side effects.

The ß-1,3-Glucanase Degrades Callose at Plasmodesmata to Facilitate the Transport of the Ribonucleoprotein Complex in Pyrus betulaefolia.

Grafting is widely used to improve the stress tolerance and the fruit yield of horticultural crops. Ribonucleoprotein complexes formed by mRNAs and proteins play critical roles in the communication between scions and stocks of grafted plants. In Pyrus betulaefolia, ankyrin was identified previously to promote the long-distance movement of the ribonucleoprotein complex(PbWoxT1-PbPTB3) by facilitating callose degradation at plasmodesmata. However, the mechanism of the ankyrin-mediated callose degradation remains elusive. In this study, we discovered a ß-1,3-glucanase (EC 3.2.1.39, PbPDBG) using ankyrin as a bait from plasmodesmata by co-immunoprecipitation and mass spectrometry. Ankyrin was required for the plasmodesmata-localization of PbPDBG. The grafting and bombardment experiments indicated that overexpressing PbPDBG resulted in decreased callose content at plasmodesmata, and thereby promoting the long-distance transport of the ribonucleoprotein complex. Altogether, our findings revealed that PbPDBG was the key factor in ankyrin-mediated callose degradation at plasmodesmata.

Constructing a prognostic risk model for Alzheimer's disease based on ferroptosis.

Introduction: The aim of this study is to establish a prognostic risk model based on ferroptosis to prognosticate the severity of Alzheimer's disease (AD) through gene expression changes. Methods: The GSE138260 dataset was initially downloaded from the Gene expression Omnibus database. The ssGSEA algorithm was used to evaluate the immune infiltration of 28 kinds of immune cells in 36 samples. The up-regulated immune cells were divided into Cluster 1 group and Cluster 2 group, and the differences were analyzed. The LASSO regression analysis was used to establish the optimal scoring model. Cell Counting Kit-8 and Real Time Quantitative PCR were used to verify the effect of different concentrations of Aß1-42 on the expression profile of representative genes in vitro. Results: Based on the differential expression analysis, there were 14 up-regulated genes and 18 down-regulated genes between the control group and Cluster 1 group. Cluster 1 and Cluster 2 groups were differentially analyzed, and 50 up-regulated genes and 101 down-regulated genes were obtained. Finally, nine common differential genes were selected to establish the optimal scoring model. In vitro, CCK-8 experiments showed that the survival rate of cells decreased significantly with the increase of Aß1-42 concentration compared with the control group. Moreover, RT-qPCR showed that with the increase of Aß1-42 concentration, the expression of POR decreased first and then increased; RUFY3 was firstly increased and then decreased. Discussion: The establishment of this research model can help clinicians make decisions on the severity of AD, thus providing better guidance for the clinical treatment of Alzheimer's disease.

Similarities and differences between the cough suppression test and the cough challenge test.

In recent years, a new test method namely the cough suppression test has been proposed to measure cough suppression in patients with chronic cough. The cough suppression test is a modified test based on capsaicin tussive challenge. There are similarities and differences between it and the more established cough challenge test in detection method, purpose and clinical significance. In this article, we will introduce and compare the concepts, application and methodology of the cough suppression test and the cough challenge test, summarize this research progress and problems of the two methods, and predict the possible role of both in the further study of chronic cough.

Antitussive efficacy of the current treatment protocol for refractory chronic cough: our real-world experience in a retrospective cohort study.

BACKGROUND: The management of refractory chronic cough (RCC) is a great challenge. Neuromodulators have long been used for RCC with imperfect efficacy. OBJECTIVES: We summarized the outcomes of the current treatments used at our specialist cough clinic, which provides a guideline-led service and real-world experience for the future management of RCC. DESIGN: This is a single-centre retrospective observational cohort study. METHODS: Consecutive RCC patients (the first clinic visit between January 2016 and May 2021) were included into this observational cohort study. Medical records in the Chronic Cough Clinical Research Database were fully reviewed using uniform criteria. The included subjects were followed-up for at least 6 months after the final clinic visit via instant messages with the link to self-scaled cough-associated questionnaires. RESULTS: Overall, 369 RCC patients were analysed with a median age of 46.6 years and a cough duration of 24.0 months. A total of 10 different treatments were offered. However, 96.2% of patients had been prescribed at least one neuromodulator. One-third of patients had alternative treatments prescribed given the poor response to the initial therapy and 71.3% favourably responded to at least one of the treatments. Gabapentin, deanxit, and baclofen had comparable therapeutic efficacy (56.0%, 56.0%, and 62.5% respectively; p = 0.88) and overall incidences of adverse effects (28.3%, 22.0%, and 32.3% respectively; p = 0.76). However, 19.1 (7.7-41.8) months after the last clinic visit, 65.0% reported improvement (24.9%) or control of their cough (40.1%); 3.8% reported a spontaneous remission and 31.2% still had a severe cough. Both HARQ (n = 97; p < 0.001) and LCQ (n = 58; p < 0.001) demonstrated marked improvement. CONCLUSION: Trying different neuromodulators is a pragmatic strategy for RCC, which helped around two-thirds of patients. Relapse is common on withdrawal or reduction of dosage. Novel medication for RCC is an urgent clinical need. PLAIN LANGUAGE SUMMARY: This is the first report that fully represented a guideline-led treatment protocol for refractory chronic cough (RCC) based on a large series of patients, which evaluated the short- and long-term effects of the currently available treatments for RCC. We found that the therapeutic trial of different neuromodulators is a pragmatic strategy, which helped around two-thirds of patients. Gabapentin, deanxit (flupentixol/melitracen), and baclofen had similar therapeutic outcomes. This study may offer real-world experience for the future management of RCC.

Preliminary Study on Insecticidal Potential and Chemical Composition of Five Rutaceae Essential Oils against Thrips flavus (Thysanoptera: Thripidae).

To meet the demand for novel pest management strategies to combat the development of insecticide resistance, plant essential oils may be a promising alternative source. This study investigated the insecticidal activity of five essential oils from the Rutaceae plant family against Thrips flavus Schrank (Thysanoptera: Thripidae) under laboratory conditions. The plant essential oils were citrus oil (Citrus reticulata Blanco), Chuan-shan pepper oil (Zanthoxylum piasezkii Maxim.), zanthoxylum oil (Zanthoxylum bungeanum Maxim.), pomelo peel oil (Citrus maxima (Burm.) Merr.) and orange leaf oil (Citrus sinensis (L.) Osbeck). Among the essential oils evaluated, orange leaf oil (LC50 = 0.26 g/L), zanthoxylum oil (LC50 = 0.27 g/L), and pomelo peel oil (LC50 = 0.44 g/L) resulted in a higher gastric toxicity under laboratory conditions. The results of the pot experiment also showed that orange leaf oil (93.06 ± 3.67% at 540.00 g a.i.·hm-2, 97.22 ± 1.39% at 720 g a.i.·hm-2, 100.00% at 900.00 g a.i.·hm-2) zanthoxylum oil (98.73 ± 1.27% at 900 g a.i.·hm-2), and pomelo peel oil (100.00% at 900 g a.i.·hm-2) exhibited a higher control efficacy, being the most effective against T. flavus after 7 days of treatment. The essential oil components were then identified by gas chromatography-mass spectrometry (GC-MS). The insecticidal activity of orange leaf oil, pomelo peel oil, and zanthoxylum oil could be attributed to their main constituents, such as methyl jasmonate (50.92%), D-limonene (76.96%), and linalool (52.32%), respectively. In the olfactory test, adult T. flavus were attracted by zanthoxylum oil and Chuan-shan pepper oil. We speculated that linalool might be the key signaling compound that attracts T. flavus. These results showed that orange leaf oil, zanthoxylum oil, and pomelo peel oil exhibited insecticidal activities under controlled conditions. They can be implemented as effective and low-toxicity botanical insecticides and synergistic agents against T. flavus.

Long-distance transport of the pear HMGR1 mRNA via the phloem is associated with enhanced salt tolerance.

Grafting is the main asexual propagation method for horticultural crops and can enhance their resistance to biotic or abiotic stress. Many mRNAs can be transported over long distances through the graft union, however, the function of mobile mRNAs remains poorly understood. Here, we exploited lists of candidate mobile mRNAs harboring potential 5-methylcytosine (m5C) modification in pear (Pyrus betulaefolia). dCAPS RT-PCR and RT-PCR were employed to demonstrate the mobility of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase1 (PbHMGR1) mRNA in grafted plants of both pear and tobacco (Nicotiana tabacum). Overexpressing PbHMGR1 in tobacco plants enhanced salt tolerance during seed germination. In addition, both histochemical staining and GUS expression analysis showed that PbHMGR1 could directly respond to salt stress. Furthermore, it was found that the relative abundance of PbHMGR1 increased in heterografted scion, which avoided serious damage under salt stress. Collectively, these findings established that PbHMGR1 mRNA could act as a salt-responsive signal and move through the graft union to enhance salt tolerance of scion, which might be used as a new plant breeding technique to improve resistance of scion through a stress-tolerant rootstock.

Molecular Characteristics and Pathogenicity of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) 1 in Taiwan during 2019-2020.

Two variants of porcine reproductive and respiratory syndrome virus (PRRSV), PRRSV 1 and PRRSV 2, have caused abortion in pregnant sows and respiratory distress in nursery pigs worldwide. PRRSV 2 has been thoroughly researched in Taiwan since 1993; however, the first case of PRRSV 1 was not reported until late 2018. To decipher the genetic characteristics of PRRSV 1 in Taiwan, open reading frame 5 (ORF5) genes of PRRSV 1 strains collected from 11 individual pig farms in 2019-2020 were successfully sequenced. All Taiwanese ORF5 sequences were closely related to Spanish-like PRRSV strains, which are considered to share a common evolutionary origin with the strain used for the PRRSV 1 vaccine. Analyses of amino acid (aa) and non-synonymous substitutions showed that genetic variations resulted in numerously specific codon mutations scattered across the neutralizing epitopes within the ORF5 gene. The PRRSV 1 challenge experiment disclosed the pathogenetic capability of the NPUST2789 isolate in nursery pigs. These findings provide comprehensive knowledge of the molecular diversity of the PRRSV 1 variant in local Taiwanese fields and facilitate the development of suitable immunization programs against this disease.