Bioinformatics and system biology approach to identify potential common pathogenesis for COVID-19 infection and sarcopenia.

Sarcopenia is a condition characterized by age-related loss of muscle mass and strength. Increasing evidence suggests that patients with sarcopenia have higher rates of coronavirus 2019 (COVID-19) infection and poorer post-infection outcomes. However, the exact mechanism and connections between the two is unknown. In this study, we used high-throughput data from the GEO database for sarcopenia (GSE111016) and COVID-19 (GSE171110) to identify common differentially expressed genes (DEGs). We conducted GO and KEGG pathway analyses, as well as PPI network analysis on these DEGs. Using seven algorithms from the Cytoscape plug-in cytoHubba, we identified 15 common hub genes. Further analyses included enrichment, PPI interaction, TF-gene and miRNA-gene regulatory networks, gene-disease associations, and drug prediction. Additionally, we evaluated immune cell infiltration with CIBERSORT and assessed the diagnostic accuracy of hub genes for sarcopenia and COVID-19 using ROC curves. In total, we identified 66 DEGs (34 up-regulated and 32 down-regulated) and 15 hub genes associated with sarcopenia and COVID-19. GO and KEGG analyses revealed functions and pathways between the two diseases. TF-genes and TF-miRNA regulatory network suggest that FOXOC1 and hsa-mir-155-5p may be identified as key regulators, while gene-disease analysis showed strong correlations with hub genes in schizophrenia and bipolar disorder. Immune infiltration showed a correlation between the degree of immune infiltration and the level of infiltration of different immune cell subpopulations of hub genes in different datasets. The ROC curves for ALDH1L2 and KLF5 genes demonstrated their potential as diagnostic markers for both sarcopenia and COVID-19. This study suggests that sarcopenia and COVID-19 may share pathogenic pathways, and these pathways and hub genes offer new targets and strategies for early diagnosis, effective treatment, and tailored therapies for sarcopenia patients with COVID-19.

Identification of risk factors for acute exacerbation of idiopathic pulmonary fibrosis based on baseline high-resolution computed tomography: a prospective observational study.

BACKGROUND: This study aimed to investigate risk factors for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) based on baseline high-resolution computed tomography (HRCT). METHODS: This prospective observational study enrolled patients with IPF treated at the General Hospital of Ningxia Medical University between January 2019 and January 2021. HRCT-derived quantitative parameters at baseline were analyzed. RESULTS: A total of 102 patients [92 (90.2%) males with a mean age of 67 years] with IPF were included, with a median follow-up of 32 (24-40.5) months. AE occurred in 30 (29.4%) IPF patients. Multivariable logistic regression analysis identified Doppler transthoracic echocardiography suggestive of pulmonary hypertension (PH) (13.43; 95% CI: 4.18-41.09; P < 0.001), honeycombing (OR 1.08; 95% CI: 1.02-1.14; P = 0.013), and whole lung volume (OR 0.99; 95% CI: 0.99-1.00; P = 0.037) as independent risk factors for AE-IPF. The combination of PH, honeycombing, whole lung volume, and the percentage of predicted forced vital capacity (FVC% pred) showed a high area under the curve from receiver operating characteristic curves of 0.888, with a sensitivity of 90% and specificity of 78%. CONCLUSIONS: This study emphasizes that quantitative CT parameters (honeycombing, whole lung volume) may serve as risk factors for AE-IPF. The combination of honeycombing, whole lung volume, FVC% pred, and PH may aid in predicting AE-IPF.

The modified suture-bridge technique for treating avulsion fracture of minors tibial eminence of anterior cruciate ligament: a retrospective study.

PURPOSE: This study aimed to evaluate the clinical and radiological outcomes of modified suture-bridge technique fixation for anterior cruciate ligament (ACL) tibial avulsion fracture. METHOD: Minors who underwent arthroscopic reduction and modified suture bridge fixation of ACL tibial avulsion fracture between January 2018 and January 2022 were retrospectively analyzed. Postoperative MRI and X-ray examinations were performed to evaluate the presence of epiphyseal plate injury and fracture healing. Moreover, KT-1000 side-to-side difference, Lachman test, range of motion (ROM), the subjective Knee score of the International Knee Documentation Committee (IKDC), Lysholm Knee score, and Tegner activity grade score were evaluated preoperatively and at the minimum 1-year follow-up visit. RESULTS: A total of 16 participants met the inclusion criteria. They had a mean age of 12.6 years (range, 9-16 years); mean time to surgery, 6.9 days (range, 2-13 days) and had a minimum of 12 months clinical follow-up (mean, 25.4 months; range, 12-36 months) after surgery. Postoperative radiographs and MRI showed no injury to the epiphyseal plate, optimal reduction immediately after the operation, and bone union within three months in all patients. All of the following showed significant improvements (pre- vs. postoperatively): mean KT-1000 side-to-side difference (8.6 vs. 1.5; p < 0.05), Lachman tests (2 grade 9 and 3 grade 7 vs. 0 grade 12 and 1 grade 4; p < 0.05), IKDC subjective score (48.3 vs. 95.0; p < 0.05), mean Lysholm score (53.9 vs. 92.2; p < 0.05), mean Tegner activity score (3.2 vs. 8.3; p < 0.05) and mean ROM (42.9°vs 133.1°; p < 0.05). CONCLUSION: Arthroscopic reduction and modified suture bridge fixation for ACL tibial avulsion fracture is a dependable and recommended treatment that can effectively restore the stability and function of the knee and is worthy of clinical promotion.

Rational Design of Loop Dynamics for a Barrel-Shaped Enzyme by Introducing Disulfide Bonds.

Loop dynamics redesign is an important strategy to manipulate protein function. Cellobiose 2-epimerase (CE) and other members of its superfamily are widely used for diverse industrial applications. The structural feature of the loops connecting barrel helices contributes greatly to the differences in their functional characteristics. Inspired by the in-silico mutation with molecular dynamics (MD) simulation analysis, we propose a strategy for identifying disulfide bond mutation candidates based on the prediction of protein flexibility and residue-residue interaction. The most beneficial mutant with the newly introduced disulfide bond would simultaneously improve both its thermostability and its reaction propensity to the targeting isomerization product. The ratio of the isomerization/epimerization catalytic rate was improved from 4:103 to 9:22. MD simulation and binding free energy calculations were applied to provide insights into molecular recognition upon mutations. The comparative analysis of enzyme/substrate binding modes indicates that the altered catalytic reaction pathway is due to less efficient binding of the native product. The key residue responsible for the observed phenotype was identified by energy decomposition and was further confirmed by the mutation experiment. The rational design of the key loop region might be a promising strategy to alter the catalytic behavior of all (α/α)6-barrel-like proteins.

Synergy level of urban resilience and urban land use efficiency in the Yellow River Basin: Spatial-temporal evolution characteristics and driving factors.

The complex global context, including globalization, rapid urbanization, and climate change, poses significant challenges to urban stability and development. Balancing urban land use efficiency and resilience is crucial for sustainable progress. Focusing on the vulnerable Yellow River Basin (YRB), this study examines the interplay between urban resilience and land use efficiency. Panel data from 2013 to 2020 for 54 cities in the YRB were used, it quantifies the Coupling Coordination Degree of Urban Resilience and Urban Land Use Efficiency (CCDUU), explores its spatiotemporal evolution and influencing factors. Key findings include: The CCDUU exhibits a sustained and discernible growth trend. Notably, CCDUU is higher in downstream areas in comparison to the middle reaches, reaching its lowest point in the upstream areas; however, the increase in CCDUU in the upstream areas surpasses that observed in other regions. Concurrently, regional disparities in CCDUU are diminishing. Despite the presence of a notable positive spatial correlation in CCDUU within the YRB, the strength of this spatial association is not sufficiently robust. Of paramount importance factor is the role of regional innovation, which significantly influences the enhancement of CCDUU. Following closely is the degree of openness, whereas the positive effects of government support and population density are concentrated predominantly in the upper YRB region. In contrast, urban-rural disparity exerts an adverse impact on CCDUU in most regions. Policy recommendations for enhancing CCDUU in YRB cities include strengthening government support and planning control, particularly in upstream regions, to achieve efficient resource utilization and environmental protection. Implementing population density management policies, encouraging rational movement, and promoting population migration to upstream areas can alleviate pressure in downstream cities. Enhancing openness, attracting foreign investment, and promoting innovation and industrial upgrading will drive economic structural upgrades and improve CCDUU.

Mitochondrial calcium uniporter knockdown in hippocampal neurons alleviates anxious and depressive behavior in the 3XTG Alzheimer's disease mouse model.

Alzheimer's disease (AD) is a progressive and degenerative disorder accompanied by emotional disturbance, especially anxiety and depression. More and more evidence shows that the imbalance of mitochondrial Ca2+ (mCa2+) homeostasis has a close connection with the pathogenesis of anxiety and depression. The Mitochondrial Calcium Uniporter (MCU), a key channel of mCa2+ uptake, induces the imbalance of mCa2+ homeostasis and may be a therapeutic target for anxiety and depression of AD. In the present study, we revealed for the first time that MCU knockdown in hippocampal neurons alleviated anxious and depressive behaviors of APP/PS1/tau mice through elevated plus-maze (EPM), elevated zero maze (EZM), sucrose preference test (SPT) and tail suspension test (TST). Western blot analysis results demonstrated that MCU knockdown in hippocampal neurons increased levels of glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (vGAT) and GABAA receptor α1 (GABRA1) and activated the PKA-CREB-BDNF signaling pathway. This study indicates that MCU inhibition has the potential to be developed as a novel therapy for anxiety and depression in AD.

NtARF11 positively regulates cadmium tolerance in tobacco by inhibiting expression of the nitrate transporter NtNRT1.1.

Heavy metal cadmium (Cd) is widespread in contaminated soil and an important factor limiting plant growth. NO3- (nitrate) affects Cd uptake and thus changes Cd tolerance in plants; however, the underlying molecular regulatory mechanisms have not yet been elucidated. Here, we analyzed a novel gene, NtARF11 (auxin response factor), which regulates Cd tolerance in tobacco via the NO3- uptake pathway, through experiments with NtARF11-knockout and NtARF11-overexpression transgenic tobacco lines. NtARF11 was highly expressed under Cd stress in tobacco plants. Under Cd stress, overexpression of NtARF11 enhanced Cd tolerance in tobacco compared to that in wild-type tobacco, as shown by the low Cd concentration, high chlorophyll concentration, and low accumulation of reactive oxygen species in NtARF11-overexpressing tobacco. Moreover, low NO3- concentrations were observed in NtARF11-overexpressing tobacco plants. Further analyses revealed direct binding of NtARF11 to the promoter of the nitrate transporter NtNRT1.1, thereby negatively regulating its expression in tobacco. Notably, NtNRT1.1 knockout reduced NO3- uptake, which resulted in low Cd concentrations in tobacco. Altogether, these results demonstrate that the NtARF11-NtNRT1.1 module functions as a positive regulator of Cd tolerance by reducing the Cd uptake in tobacco, providing new insights for improving Cd tolerance of plants through genetic engineering.

NtHD9 modulates plant salt tolerance by regulating the formation of glandular trichome heads in Nicotiana tabacum.

Salt stress is one of the main abiotic factor affecting plant growth. We have previously identified a key gene (NtHD9) in Nicotiana tabacum L. that positively regulates the formation of long glandular trichomes (LGTs). Here, we verified that both abiotic stress (aphids, drought and salt stress) could restore the phenotype lacking LGTs in NtHD9-knockout (NtHD9-KO) plants. The abiotic stress response assays indicated that NtHD9 is highly sensitive to salt stress. Compared with cultivated tobacco "K326" (CK) plants, NtHD9-overexpressing (NtHD9-OE) plants with more LGTs exhibited stronger salt tolerance, whereas NtHD9-KO with no LGTs showed weaker tolerance to salt. The densities and sizes of the glandular heads gradually increased with increasing NaCl concentrations in NtHD9-KO plants. Mineral element determination showed that leaves and trichomes of NtHD9-OE plants accumulated less Na+ but had higher K+ contents under salt stress, thus maintaining ion homeostasis in plants, which could contribute to a robust photosynthetic and antioxidant system under salt stress. Therefore, NtHD9-OE plants maintained a larger leaf area and root length under high-salt conditions than CK and NtHD9-KO plants. We verified that NtHD9 could individually interact with NtHD5, NtHD7, NtHD12, and NtJAZ10 proteins. Salt stress led to an increase in jasmonic acid (JA) levels and activated the expression of NtHDs while inhibiting the expression of NtJAZ. This study suggests that the glandular heads play an important role in plant resistance to salt stress. The activation of JA signaling leading to JAZ protein degradation may be key factors regulating the glandular heads development under salt stress.

Process of mercury accumulation in urban strip river artificial wetland ecosystems: a case study of Changchun, a typical industrial city in Northeast China.

Mercury (Hg), as a global pollutant, is persistent, migratory, insidious, highly biotoxic and highly enriched, and is widely distributed in the atmosphere, hydrosphere, biosphere and lithosphere. Wetland ecosystems, as active mercury reservoirs, have become the most important sources and sinks of heavy metal mercury. Distinguished from natural wetlands, artificial wetlands located in urban sections of rivers face problems such as diverse urban pollution sources and complex spatial and temporal changes. Therefore, in this study, five intermittently distributed artificial wetlands were selected from the upstream to the downstream of the Changchun section of the Yitong River, a tributary of the Songhua River basin in the old industrial base of Northeast China. The mercury levels in the water bodies, sediments and plants of the artificial wetlands were collected and tested in four quarters from April 2023 to analyse the spatial and temporal distribution characteristics of total mercury. The results showed that the mercury levels in the water bodies, sediments and plants of the five wetlands showed a fluctuating trend with the river flow direction and had certain spatial and temporal distribution characteristics. This phenomenon was attributed to the sinking of external mercury pollution sources. In general, the wetland ecosystems showed a decreasing trend in the total Hg output of the downstream watershed. This may be due to the retention of particulate matter by aquatic plants in artificial wetlands to regular salvage of dead aquatic plants. At the same time urbanization and industrialization affect mercury levels in aquatic environments, so the risk of residential exposure needs to be looked at.

Assessing trends and burden of occupational exposure to asbestos in the United States: a comprehensive analysis from 1990 to 2019.

BACKGROUND: This study aimed to analyze the trends and burden of occupational exposure to asbestos in the United States (U.S.) from 1990 to 2019, focusing on mortality rates, geographic distribution, age and sex patterns, and causes of death. METHODS: Data on the number of deaths attributable to occupational exposure to asbestos were collected from 1990 to 2019 in the U.S. Joinpoint analysis was conducted to assess trends over time, and regression models were applied to calculate annual percentage changes (APC) and annual average percentage changes (AAPC). Geographic distribution was examined using mapping techniques. Age and sex patterns were analyzed, and causes of death were identified based on available data. RESULTS: From 1990 to 2019, the overall number of deaths due to occupational exposure to asbestos in the U.S. increased by 20.2%. However, age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life years (DALYs) rates (ASDR) exhibited a decline over the same period. Geographic analysis revealed differences in the number of deaths across states in 2019, with California reporting the highest number of fatalities. Age-specific mortality and DALYs showed an increase with age, peaking in older age groups. Tracheal, bronchus, and lung cancer were the leading causes of death attributed to asbestos exposure, with increasing trends observed over the past five years. CONCLUSION: The study highlights significant trends and burden in occupational exposure to asbestos in the U.S., including overall increases in mortality rates, declining ASMR and ASDR, geographic disparities, age and sex patterns, and shifts in causes of death. These findings underscore the importance of continued monitoring and preventive measures to mitigate the burden of asbestos-related diseases.

Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

Annular Conductive Hydrogel-Mediated Wireless Electrical Stimulation for Augmenting Neurogenesis.

Electrical stimulation (ES) has a remarkable capacity to regulate neuronal differentiation and neurogenesis in the treatment of various neurological diseases. However, wired devices connected to the stimulating electrode and the mechanical mismatch between conventional rigid electrodes and soft tissues restrict their motion and cause possible infections, thereby limiting their clinical utility. An approach integrating the advantages of wireless techniques and soft hydrogels provides new insights into ES-induced nerve regeneration. Herein, a flexible and implantable wireless ES-responsive electrode based on an annular gelatin methacrylate-polyaniline (Gel/Pani) hydrogel is fabricated and used as a secondary coil to achieve wireless ES via electromagnetic induction in the presence of a primary coil. The Gel/Pani hydrogels exhibit favorable biocompatibility, biodegradability, conductivity, and compression resistance. The annular electrode of the Gel/Pani conductive hydrogel (AECH) supports neural stem cell growth, while the applied wireless ES facilitates neuronal differentiation and the formation of functional neural networks in vitro. Furthermore, AECH is implanted in vivo in rats with ischemic stroke and the results reveal that AECH-mediated wireless ES significantly ameliorates brain impairment and neurological function by activating endogenous neurogenesis. This novel flexible hydrogel system addresses wireless stimulation and implantable technical challenges, holding great potential for the treatment of neurodegenerative diseases.

A retrospective investigation on clinical and radiographic outcomes of distal tibial fractures after intramedullary nailing using the lateral parapatellar extra-articular approach.

INTRODUCTION: According to reports, the modified extra-articular parapatellar approach allows the performance of tibial nailing in the semi-extended position without the concern of joint violation. However, there remains no special study that has provided a detailed assessment of the benefits and risks of this approach for treating distal tibial fractures (DTFs). The aim of this retrospective study was to investigate the clinical and radiological outcomes of patients with DTFs after intramedullary nailing using a lateral parapatellar extra-articular (LPE) approach in comparison to using the suprapatellar (SP) and transpatellar (TP) approaches. METHODS: Data were collected from 99 patients with a minimum follow-up period of 12 months. Comparisons were conducted between the groups regarding the number of intraoperative fluoroscopies, complications, knee pain, knee range of motion (ROM), the Lysholm Knee Scale (LKS), the Olerud-Molander Ankle Score (OMAS) and radiological findings. RESULTS: The demographic characteristics were comparable between the groups. Fewer intraoperative fluoroscopies were performed in the LPE (27.47 ± 4.98) and SP (26.03 ± 5.12) groups than in the TP group (30.20 ± 7.42; P<0.001). When compared with the other two approaches, the LPE approach was associated with less knee pain (P<0.001) and better knee ROM (P<0.001) at one week postoperative. No significant intergroup differences were detected in the incidence of complications, LKS scores (P = 0.687) and OMAS (P = 0.926). Radiological findings demonstrated that postoperative tibial alignment (P = 0.853), the time of bony union and rate of non-union were similar between the groups. CONCLUSION: The LPE approach can serve as a safe and effective option for tibial nailing, as it offers favourable outcomes in knee pain relief and knee ROM in the early postoperative period and is equivalent to the other two approaches in terms of the incidence of complications, fracture healing, functional recovery and postoperative alignment for patients with DTFs.

Selective Orexin 2 Receptor Blockade Alleviates Cognitive Impairments and the Pathological Progression of Alzheimer's Disease in 3xTg-AD Mice.

The orexin system is closely related to the pathogenesis of Alzheimer's disease (AD). Orexin-A aggravates cognitive dysfunction and increases amyloid ß (Aß) deposition in AD model mice, but studies of different dual orexin receptor (OXR) antagonists in AD have shown inconsistent results. Our previous study revealed that OX1R blockade aggravates cognitive deficits and pathological progression in 3xTg-AD mice, but the effects of OX2R and its potential mechanism in AD have not been reported. In the present study, OX2R was blocked by oral administration of the selective OX2R antagonist MK-1064, and the effects of OX2R blockade on cognitive dysfunction and neuropsychiatric symptoms in 3xTg-AD mice were evaluated via behavioral tests. Then, immunohistochemistry, western blotting, and ELISA were used to detect Aß deposition, tau phosphorylation, and neuroinflammation, and electrophysiological and wheel-running activity recording were recorded to observe hippocampal synaptic plasticity and circadian rhythm. The results showed that OX2R blockade ameliorated cognitive dysfunction, improved LTP depression, increased the expression of PSD-95, alleviated anxiety- and depression-like behaviors and circadian rhythm disturbances in 3xTg-AD mice, and reduced Aß pathology, tau phosphorylation, and neuroinflammation in the brains of 3xTg-AD mice. These results indicated that chronic OX2R blockade exerts neuroprotective effects in 3xTg-AD mice by reducing AD pathology at least partly through improving circadian rhythm disturbance and the sleep-wake cycle and that OX2R might be a potential target for the prevention and treatment of AD; however, the potential mechanism by which OX2R exerts neuroprotective effects on AD needs to be further investigated.

Overexpression of the WRKY transcription factor gene NtWRKY65 enhances salt tolerance in tobacco (Nicotiana tabacum).

BACKGROUND: Salt stress severely inhibits plant growth, and the WRKY family transcription factors play important roles in salt stress resistance. In this study, we aimed to characterize the role of tobacco (Nicotiana tabacum) NtWRKY65 transcription factor gene in salinity tolerance. RESULTS: This study characterized the role of tobacco (Nicotiana tabacum) NtWRKY65 transcription factor gene in salinity tolerance using four NtWRKY65 overexpression lines. NtWRKY65 is localized to the nucleus, has transactivation activity, and is upregulated by NaCl treatment. Salinity treatment resulted in the overexpressing transgenic tobacco lines generating significantly longer roots, with larger leaf area, higher fresh weight, and greater chlorophyll content than those of wild type (WT) plants. Moreover, the overexpressing lines showed elevated antioxidant enzyme activity, reduced malondialdehyde content, and leaf electrolyte leakage. In addition, the Na+ content significantly decreased, and the K+/Na+ ratio was increased in the NtWRKY65 overexpression lines compared to those in the WT. These results suggest that NtWRKY65 overexpression enhances salinity tolerance in transgenic plants. RNA-Seq analysis of the NtWRKY65 overexpressing and WT plants revealed that NtWRKY65 might regulate the expression of genes involved in the salt stress response, including cell wall component metabolism, osmotic stress response, cellular oxidant detoxification, protein phosphorylation, and the auxin signaling pathway. These results were consistent with the morphological and physiological data. These findings indicate that NtWRKY65 overexpression confers enhanced salinity tolerance. CONCLUSIONS: Our results indicated that NtWRKY65 is a critical regulator of salinity tolerance in tobacco plants.

Towards an actionable One Health approach.

BACKGROUND: Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. MAIN TEXT: This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. CONCLUSIONS: By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.

Shenqi Fuzheng injection alleviates chemotherapy-induced cachexia by restoring glucocorticoid signaling in hypothalamus.

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Transcriptome disclosure of hormones inducing stigma exsertion in Nicotiana tabacum by corolla shortening.

BACKGROUND: Stigma exsertion is an essential agricultural trait that can promote cross-pollination to improve hybrid seed production efficiency. However, the molecular mechanism controlling stigma exsertion remains unknown. RESULTS: In this study, the Nicotiana tabacum cv. K326 and its two homonuclear-heteroplasmic lines, MSK326 (male-sterile) and MSK326SE (male-sterile and stigma exserted), were used to investigate the mechanism of tobacco stigma exsertion. A comparison of the flowers between the three lines showed that the stigma exsertion of MSK326SE was mainly due to corolla shortening. Therefore, the corollas of the three lines were sampled and presented for RNA-seq analysis, which found 338 candidate genes that may cause corolla shortening. These genes were equally expressed in K326 and MSK326, but differentially expressed in MSK326SE. Among these 338 genes, 15 were involved in hormone synthesis or signal transduction pathways. Consistently, the content of auxin, dihydrozeatin, gibberellin, and jasmonic acid was significantly decreased in the MSK326SE corolla, whereas abscisic acid levels were significantly increased. Additionally, seven genes involved in cell division, cell cycle, or cell expansion were identified. Protein-protein interaction network analysis identified 45 nodes and 79 protein interactions, and the largest module contained 20 nodes and 52 protein interactions, mainly involved in the hormone signal transduction and pathogen defensive pathways. Furthermore, a putative hub gene coding a serine/threonine-protein kinase was identified for the network. CONCLUSIONS: Our results suggest that hormones may play a key role in regulating tobacco stigma exsertion induced by corolla shortening.

Inhibition of lysyl oxidase by pharmacological intervention and genetic manipulation alleviates epilepsy-associated cognitive disorder.

Epilepsy-associated cognitive disorder (ECD), a prevalent comorbidity in epilepsy patients, has so far uncharacterized etiological origins. Our prior work revealed that lysyl oxidase (Lox) acted as a novel contributor of ferroptosis, a recently discovered cell death mode in the regulation of brain function. However, the role of Lox-mediated ferroptosis in ECD remains unknown. ECD mouse model was established 2 months later following a single injection of kainic acid (KA) for. After chronic treatment with KA, mice were treated with different doses (30 mg/kg, 100 mg/kg and 300 mg/kg) of Lox inhibitor BAPN. Additionally, hippocampal-specific Lox knockout mice was also constructed and employed to validate the role of Lox in ECD. Cognitive functions were assessed using novel object recognition test (NOR) and Morris water maze test (MWM). Protein expression of phosphorylated cAMP-response element binding (CREB), a well-known molecular marker for evaluation of cognitive performance, was also detected by Western blot. The protein distribution of Lox was analyzed by immunofluorescence. In KA-induced ECD mouse model, ferroptosis process was activated according to upregulation of 4-HNE protein and a previously discovered ferroptosis in our group, namely, Lox was remarkably increased. Pharmacological inhibition of Lox by BAPN at the dose of 100 mg/kg significantly increased the discrimination index following NOR test and decreased escape latency as well as augmented passing times within 60 s following MWM test in ECD mouse model. Additionally, deficiency of Lox in hippocampus also led to pronounced improvement of deficits in ECD model. These findings indicate that the ferroptosis regulatory factor, Lox, is activated in ECD. Ablation of Lox by either pharmacological intervention or genetic manipulation ameliorates the impairment in ECD mouse model, which suggest that Lox serves as a promising therapeutic target for treating ECD in clinic.