Transcriptome differential expression analysis of defoliation of two different lemon varieties.

'Allen Eureka' is a bud variety of Eureka lemon with excellent fruiting traits. However, it suffers from severe winter defoliation that leads to a large loss of organic nutrients and seriously affects the tree's growth and development as well as the yield of the following year, and the mechanism of its response to defoliation is still unclear. In order to investigate the molecular regulatory mechanisms of different leaf abscission periods in lemon, two lemon cultivars ('Allen Eureka' and 'Yunning No. 1') with different defoliation traits were used as materials. The petiole abscission zone (AZ) was collected at three different defoliation stages, namely, the pre-defoliation stage (CQ), the mid-defoliation stage (CZ), and the post-defoliation stage (CH). Transcriptome sequencing was performed to analyze the gene expression differences between these two cultivars. A total of 898, 4,856, and 3,126 differentially expressed genes (DEGs) were obtained in CQ, CZ, and CH, respectively, and the number of DEGs in CZ was the largest. GO analysis revealed that the DEGs between the two cultivars were mainly enriched in processes related to oxidoreductase, hydrolase, DNA binding transcription factor, and transcription regulator activity in the defoliation stages. KEGG analysis showed that the DEGs were concentrated in CZ and involved plant hormone signal transduction, phenylpropanoid biosynthesis, glutathione metabolism, and alpha-linolenic acid metabolism. The expression trends of some DEGs suggested their roles in regulating defoliation in lemon. Eight gene families were obtained by combining DEG clustering analysis and weighted gene co-expression network analysis (WGCNA), including ß-glucosidase, AUX/IAA, SAUR, GH3, POD, and WRKY, suggesting that these genes may be involved in the regulation of lemon leaf abscission. The above conclusions enrich the research related to lemon leaf abscission and provide reliable data for the screening of lemon defoliation candidate genes and analysis of defoliation pathways.

Transcriptome differential expression analysis of defoliation in different lemon varieties under drought treatment.

'Allen Eureka' is a bud variety of Eureka lemon with excellent fruiting traits, but severe winter defoliation affects the following year's yield, and the response mechanism of lemon defoliation is currently unknown. Two lemon cultivars ('Allen Eureka' and 'Yunning No. 1') with different defoliation traits were used as materials to investigate the molecular regulatory mechanisms of different leaf abscission periods in lemons. The petiole abscission zone was collected at three different defoliation stages, namely, the predefoliation stage (k15), the middefoliation stage (k30), and the postdefoliation stage (k45). Transcriptome sequencing was performed to analyze the gene expression differences between these two cultivars. A total of 1141, 2695, and 1433 differentially expressed genes (DEGs) were obtained in k15, k30, and k45, respectively, and the number of DEGs in k30 was the largest. GO analysis revealed that the DEGs between the two cultivars were mainly enriched in processes related to hydrolase activity, chitinase activity, oxidoreductase activity, and transcription regulator activity in the defoliation stages. KEGG analysis showed that the DEGs were concentrated in k30, which involved plant hormone signal transduction, phenylpropanoid biosynthesis, and biosynthesis of amino acids. The expression trends of some DEGs suggested their roles in regulating defoliation in Lemon. Seven genes were obtained by WGCNA, including sorbitol dehydrogenase (CL9G068822012_alt, CL9G068820012_alt, CL9G068818012_alt), abscisic acid 8'-hydroxylase (CL8G064053012_alt, CL8G064054012_alt), and asparagine synthetase (CL8G065162012_alt, CL8G065151012_alt), suggesting that these genes may be involved in the regulation of lemon leaf abscission.

Au nano-cone array for SERS detection of associated miRNA in lymphoma patients.

Based on Au nano-cone array (Au-NCA) and a three-segment hybridization strategy, a novel SERS biosensor is proposed for the ultrasensitive detection of the microRNA miR-21. The uniform, stable, and reproducible Au-NCA was prepared by the single-layer colloidal ball template method. Subsequently, the target was hybridized with sequence 2. The resulting target-sequence 2 complex was then hybridized with sequence 1 anchored on Au-NCA. Thus, a three-segment sequence complex was formed. SERS measurements can be performed without the need for complex purification and amplification steps. Due to the ability of miR-21 to perform specific complementary hybridization with two sequences, SERS biosensors have superior specificity for miR-21 without interference from other miRNAs. Under the optimal conditions, the SERS biosensor was applied and the limit of detection (LOD) was as low as 3.02 aM. This method has been successfully used to the detection of miR-21 in the serum of lymphoma patients and healthy volunteers. The results are consistent with the traditional test methods. Therefore, this novel SERS biosensor shows excellent clinical translational potential in the detection of lymphoma.

The role of blood pressure variability indicators combined with cerebral blood flow parameters in predicting intraventricular hemorrhage in very low birth weight preterm infants.

Background: Hemodynamic instability is the main factor responsible for the development of intraventricular hemorrhage (IVH) in premature newborns. Herein, we evaluated the predictive ability of blood pressure variability (BPV) and anterior cerebral artery (ACA) blood flow parameters in IVH in premature infants with gestational age (GA) ≤32 weeks and birth weight (BW) ≤ 1,500 g. Methods: Preterm infants with GA ≤32 weeks and BW ≤ 1,500 g admitted to the neonatal intensive care unit (NICU) of the hospital affiliated to Yangzhou University from January 2020 to January 2023 were selected as the research subjects. All preterm infants were admitted within 1 h after birth, and systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MABP) were monitored at 1-h intervals. The difference between maximum and minimum values (max-min), standard deviation (SD), coefficient of variation (CV), and successive variation (SV) were used as BPV indicators. On the 1st, 3rd, and 7th day after birth, transcranial ultrasound examination was performed to screen for the occurrence of IVH. On the 24 ± 1 h after birth, systolic velocity (Vs), diastolic velocity (Vd), and resistance index (RI) of the ACA were measured simultaneously. Preterm infants were divided into the IVH group and non-IVH group based on the results of transcranial ultrasound examination, and the correlation between BPV indicators, ACA blood flow parameters, and development of IVH was analyzed. Results: A total of 92 premature infants were enrolled, including 49 in the IVH group and 43 in the non-IVH group. There was no statistically significant difference in baseline characteristics such as BW, GA, sex, and perinatal medical history between the two groups of preterm infants (P > 0.05). The SBP SD (OR: 1.480, 95%CI: 1.020-2.147) and ACA-RI (OR: 3.027, 95%CI: 2.769-3.591) were independent risk factors for IVH in premature newborns. The sensitivity and specificity of combined detection of SBP SD and ACA-RI in predicting IVH were 61.2% and 79.1%, respectively. Conclusion: High BPV and ACA-RI are related to IVH in premature infants with GA ≤32 w and BW ≤1,500 g. Combined detection of SBP SD and ACA-RI has a certain predictive effect on early identification of IVH.

Pangenome analysis provides insight into the evolution of the orange subfamily and a key gene for citric acid accumulation in citrus fruits.

The orange subfamily (Aurantioideae) contains several Citrus species cultivated worldwide, such as sweet orange and lemon. The origin of Citrus species has long been debated and less is known about the Aurantioideae. Here, we compiled the genome sequences of 314 accessions, de novo assembled the genomes of 12 species and constructed a graph-based pangenome for Aurantioideae. Our analysis indicates that the ancient Indian Plate is the ancestral area for Citrus-related genera and that South Central China is the primary center of origin of the Citrus genus. We found substantial variations in the sequence and expression of the PH4 gene in Citrus relative to Citrus-related genera. Gene editing and biochemical experiments demonstrate a central role for PH4 in the accumulation of citric acid in citrus fruits. This study provides insights into the origin and evolution of the orange subfamily and a regulatory mechanism underpinning the evolution of fruit taste.

Enhancement of neural regeneration as a therapeutic strategy for Alzheimer's disease (Review).

Alzheimer's disease (AD), the most common cause of dementia worldwide, has gradually become a global health concern for society and individuals with the process of global ageing. Although extensive research has been carried out on AD, the etiology and pathological mechanism of the disease are still unclear, and there is no specific drug to cure or delay AD progression. The exploration of enhancing nerve regeneration in AD has gradually attracted increasing attention. In the current review, the existing therapeutic strategies were summarized to induce nerve regeneration which can increase the number of neurons, and improve the survival of neurons, the plasticity of synapses and synaptic activity. The strategies include increasing neurotrophic expression (such as brain-derived neurotrophic factor and nerve growth factor), inhibiting acetylcholinesterase (such as donepezil, tacrine, rivastigmine and galanthamine), elevating histone deacetylase levels (such as RGFP-966, Tasquinimod, CM-414 and 44B), stimulating the brain by physiotherapy (such as near-infrared light, repetitive transcranial magnetic stimulation, and transcranial direct current stimulation) and transplanting exogenous neural stem cells. However, further evaluations need to be performed to determine the optimal treatment. The present study reviews recent interventions for enhancing adult neurogenesis and attempts to elucidate their mechanisms of action, which may provide a theoretical basis for inducing nerve regeneration to fight against AD.

Characteristics of large vestibular aqueduct syndrome in wideband acoustic immittance.

Objective: To describe the characteristics of large vestibular aqueduct syndrome (LVAS) in wideband acoustic immittance (WAI) and to explore whether inner ear deformity has an impact on WAI results. Methods: Subjects with typical LVAS (LVAS group) and control subjects with a normal anatomical structure of the inner ear (control group) were screened from pediatric patients with cochlear implants using thin-slice computed tomography (CT) images of the temporal bone. With inflammation of the auditory canal and middle ear excluded by routine ear examination and 226 Hz acoustic immittance, WAI data were acquired. Then, the maximum absorbance as the major observation indicator on the mean tympanogram was compared between the LVAS group and control group, and a descriptive comparison of the mean tympanogram and frequency-absorbance curve at peak pressure was performed between the two groups. Results: The LVAS group included 21 cases (38 ears), and the control group included 27 cases (45 ears). All LVAS subjects met the Valvassori criteria, and the VA at the horizontal semicircular canal displayed flared expansion. On the mean tympanogram, the maximum absorbance in the LVAS group (0.542 ± 0.087) was significantly higher than that in the control group (0.455 ± 0.087) (p < 0.001). The tympanogram in the LVAS group showed an overall elevation, and the absorbance at all pressure sampling points was significantly higher than that in the control group (p < 0.001). The frequency-absorbance curve at peak pressure first increased and then decreased in both groups, and the LVAS group showed higher absorbance than the control group in the frequency range below 2,828 Hz. The absorbance at 343-1,124 Hz was significantly different between the two groups (p < 0.001), and 343-1,124 Hz was the major frequency range at which the maximum absorbance on the mean tympanogram increased in the LVAS group. Conclusion: Large vestibular aqueduct syndrome (LVAS) shows increased absorbance in low and medium frequency ranges in WAI. The maximum absorbance on the mean tympanogram can serve as a reliable evaluation indicator. Inner ear factors must be considered when middle ear lesions are analyzed by WAI.

[Long-term hearing outcomes of children with cochlear implant].

Objective:To investigate the long-term rehabilitation outcomes of children with cochlear implants（CI） and provide constructive guidance for clinical application. Methods:Fifteen children with unilateral CI over 5 years（CI group） were recruited. Ten children with normal hearing were recruited as the healthy control group. The project collected aided sound-field hearing thresholds and speech recognition scores using disyllabic words and C-HINT sentences with and without speech noise for 15 children with unilateral CI. In addition, children's guardians were requested to fill out the Mandarin Parental Perspectives questionnaire（MPP） in order to evaluate the hearing aspects of quality of life. MPP results from the 15 children were then compared with previous responses from 17 unilateral CI children whose overall CI wearing time was one year（CI control group）. Results:The aided pure-tone average（PTA） of the recruited children was below 35 dB HL, all children reached 80% for the speech recognition test in a quiet environment, yet their performance decreased in a noisy environment. Regarding the hearing aspects of the MPP questionnaire results, recruited children demonstrated better results than those from CI control group（P<0.05）. Speech noise had a significant impact on the recognition rate, and the CI group had higher recognition rate scores in the quiet environment than in the noise environment（two-syllable words t=18.81, P<0.001, short sentences t=16.48, P<0.001）. In the comparison of quality of life, in the dimension of "support for children", both the CI group and the CI control group can obtain better benefits, and there is no statistically significant difference between the groups（P>0.05）. The CI group benefited more significantly, and the scores were higher than those of the CI control group（P<0.05）. Conclusion:The long-term hearing outcome of children with CI is adequate for daily communication, but there is still a gap compared with hearing children of the same age, and they still need support from the entire society.

[Effect of cochlear implantation on speech recognition under different listening modes in children].

Objective:To investigate speech recognition among children with a unilateral cochlear implant（CI）, bilateral CI, and bimodal hearing and identify the benefits of binaural hearing. Methods:A total of 67 children with severe sensorineural hearing loss who received bilateral CI, bimodal hearing, and unilateral CI from 2012 to 2021 were recruited, including 23 cases with unilateral CI, 25 cases of bimodal hearing, and 19 cases of bilateral CI. The aided hearing threshold at 250-4000 Hz and speech recognition performance of two-syllable words and short sentences in quiet and noisy environments were tested, respectively. Results:There was no significant difference in the hearing threshold results of the bilateral CI group, the bimodal hearing group, and the unilateral CI group by ANOVA（P>0.05）. According to the paired t-test within the group, the speech recognition of disyllabic words and short sentences in quiet and noisy environments were significantly different among the three groups（P<0.05）. There was no significant difference in the speech recognition rates of disyllabic words and short sentences among the three groups in a quiet environment（P>0.05）, but there was a statistically significant difference in a noisy environment（P<0.05）. Additional multiple linear regression analysis showed no significant difference in the recognition rates of disyllabic words and short sentences between the bimodal group and the bilateral CI group in quiet and noisy environments（ß=-0.567, P>0.05; ß=-0.643, P>0.05）. There was a statistically significant difference in speech recognition of disyllabic words and short sentences between the bimodal group and the unilateral CI group in the noise environment（ß=-0.124, P<0.05）, but the difference was not statistically significant in a quiet environment（ß=-0.671, P>0.05）; there was a statistically significant difference in the recognition rate of disyllabic words and short sentences between the bilateral CI group and the unilateral CI group in the noise environment（ß=-0.226, P<0.05）, but the difference was not statistically significant in a quiet environment（ß=-0.341, P>0.05）. Conclusion:Clinicians and guardians are encouraged to provide the most comprehensive audiological evaluation for children with hearing loss. Bilateral CI and bimodal hearing have demonstrated enormous advantages over unilateral CI regarding speech recognition in noise. Bimodal hearing deems a strong recommendation if the contralateral ear has sufficient speech recognition capability. Bilateral CI should be warranted if hearing aids deemed to be ineffective.

Dock4 is required for the maintenance of cochlear hair cells and hearing function.

Auditory hair cells (HCs) are the mechanosensory receptors of the cochlea, and HC loss or malfunction can result from genetic defects. Dock4, a member of the Dock180-related protein superfamily, is a guanine nucleotide exchange factor for Rac1, and previous reports have shown that Dock4 mutations are associated with autism spectrum disorder, myelodysplastic syndromes, and tumorigenesis. Here, we found that Dock4 is highly expressed in the cochlear HCs of mice. However, the role of Dock4 in the inner ear has not yet been investigated. Taking advantage of the piggyBac transposon system, Dock4 knockdown (KD) mice were established to explore the role of Dock4 in the cochlea. Compared to wild-type controls, Dock4 KD mice showed significant hearing impairment from postnatal day 60. Dock4 KD mice showed hair bundle deficits and increased oxidative stress, which eventually led to HC apoptosis, late-onset HC loss, and progressive hearing loss. Furthermore, molecular mechanism studies showed that Rac1/ß-catenin signaling was significantly downregulated in Dock4 KD cochleae and that this was the cause for the disorganized stereocilia and increased oxidative stress in HCs. Overall, our work demonstrates that the Dock4/Rac1/ß-catenin signaling pathway plays a critical role in the maintenance of auditory HCs and hearing function.

Study on the Densification of Osmium by Experiment and First Principle Calculations.

The sintering of osmium is critical for the preparation of raw material targets for film coating, which is the main application area of osmium. In order to get a better understanding of the intrinsic mechanism of densification of osmium, a serial study on the sintering behavior of osmium has been made in this study. By the master sintering curve (MSC) and constant heating rate (CHR) method, the sintering activation energy of nanosized osmium is evaluated to be about 340 kJ/mol, which is higher than most other metals. The density-functional theory calculation indicates the higher energy barrier of the surface atom and vacancy migration and lacking migration tunnel of inner point vacancies. For example, the diffusion of osmium atoms on the surface of particles is mainly limited by Os (1010), which has an energy barrier as high as 1.14 eV, that is higher than the W atom on W (110) of 0.99 eV. The vacancy migration energy barrier inside osmium's grains is higher than 3.0 eV, while that of W is only 1.7 eV. This means that it is more difficult for osmium to achieve a high density compared with W, which is consistent with the experimental results. Accordingly, the proposed strategy provides a new opportunity to design a sintering process for target fabrication with excellent properties for various applications.

Influence of cochlear implants on hearing-related quality of life: results from Chinese children with cochlear implants entering mainstream education.

OBJECTIVES: This study aimed to 1) assess the hearing-related Quality of Life (QoL) of children with cochlear implants (CIs) in China and 2) investigate the impact of CI in children and of the socio-demographic backgrounds of their guardians on the hearing-related QoL of children with CIs in the Chinese mainstream education system. METHODS: This study used the Mandarin Children with Cochlear Implants: Parental Perspectives questionnaire (MPP), which assessed the communication capability, auditory perception, self-independence, level of happiness with family, social interaction, academic performance, outcome assessment for CI, and level of family support in children with CIs. Both univariate and multiple linear regression analyses were performed to identify the relationship of CI in children and the socio-demographic backgrounds of their guardians with hearing-related QoL in children with CI. RESULT: A total of 124 responses were collected, and they indicated satisfaction and improvement across all aspects of the MPP Questionnaire. Statistical analysis revealed that an earlier age of cochlear implantation (≤3 years old) could improve the communication capabilities, self-independence, social interaction performance, and academic performance of children with CIs. In addition, children with CI from the urban regions demonstrated better social interaction performance than that by those from the rural regions of China. CONCLUSION: CIs can improve hearing-related QoL in children with pre-lingual or congenital hearing loss entering the mainstream education system in China. This study showed that early age of cochlear implantation was critical for successful long-term auditory development and academic achievement in children with CIs in China. Therefore, healthcare professionals and educators in China should advocate for CI for children with severe congenital or pre-lingual hearing loss.

Total flavonoids of Rhizoma drynariae promote angiogenesis and osteogenesis in bone defects.

Bone defects are difficult to heal, which conveys a heavy burden to patients' lives and their economy. The total flavonoids of Rhizoma drynariae (TFRD) can promote the osteogenesis of distraction osteogenesis. However, the dose effect is not clear, the treatment period is short, and the quality of bone formation is poor. In our study, we observed the long-term effects and dose effects of TFRD on bone defects, verified the main ingredients of TFRD in combination with network pharmacology for the first time, explored its potential mechanism, and verified these findings. We found that TFRD management for 12 weeks regulated osteogenesis and angiogenesis in rats with 4-mm tibial bone defects through the PI3K/AKT/HIF-1α/VEGF signaling pathway, especially at high doses (135 mg kg-1  d-1 ). The vascularization effect of TFRD in promoting human umbilical vein endothelial cells was inhibited by PI3K inhibitors. These results provide a reference for the clinical application of TFRD.

The effect of decitabine-combined minimally myelosuppressive regimen bridged allo-HSCT on the outcomes of pediatric MDS from 10 years' experience of a single center.

BACKGROUND: Myelodysplastic syndrome (MDS) is a rare disease in children and the treatment option before the allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rarely reported. Our main objective was to report our single-center experience with the DNA-hypomethylating agent, decitabine-combined minimally myelosuppressive regimen (DAC + MMR) bridged allo-HSCT in children with MDS. METHODS: Twenty-eight children with de novo MDS who underwent allo-HSCT between 2011 and 2020 were enrolled. Patients were divided into subgroups (refractory cytopenia of childhood [RCC] and advanced MDS [aMDS]) and treated by HSCT alone or pre-transplant combination treatment based on risk stratification. The patients' clinical characteristics, treatment strategies and outcomes were retrospectively evaluated. RESULTS: Twenty patients with aMDS had received pre-transplant treatment (three were treated with decitabine alone, thirteen with DAC + MMR, and four with acute myeloid leukemia type [AML-type] induction therapy). DAC + MMR was well tolerated and the most common adverse events were myelosuppression and gastrointestinal reaction. DAC + MMR had shown an improved marrow complete remission (mCR) compared with AML-type chemotherapy (13/13, 100% versus 2/4, 50%, P = 0.044). The median follow-up for total cohort was 53.0 months (range, 2.3-127.0 months) and the 4-year overall survival (OS) was 71.4 ± 8.5%. In the subgroup of aMDS, pretreatment of DAC + MMR resulted in a much better survival rate than AML-type chemotherapy (84.6 ± 10.0% versus 0.0 ± 0.0%, P < 0.001). CONCLUSIONS: The DAC + MMR bridged allo-HSCT may be recommended as a novel and effective approach.

Effects of Involuntary and Voluntary Exercise in Combination with Acousto-Optic Stimulation on Adult Neurogenesis in an Alzheimer's Mouse Model.

Single-factor intervention, such as physical exercise and auditory and visual stimulation, plays a positive role on the prevention and treatment of Alzheimer's disease (AD); however, the therapeutic effects of single-factor intervention are limited. The beneficial effects of these multifactor combinations on AD and its molecular mechanism have yet to be elucidated. Here, we investigated the effect of multifactor intervention, voluntary wheel exercise, and involuntary treadmill running in combination with acousto-optic stimulation, on adult neurogenesis and behavioral phenotypes in a mouse model of AD. We found that 4 weeks of multifactor intervention can significantly increase the production of newborn cells (BrdU+ cells) and immature neurons (DCX+ cells) in the hippocampus and lateral ventricle of Aß oligomer-induced mice. Importantly, the multifactor intervention could promote BrdU+ cells to differentiate into neurons (BrdU+ DCX+ cells or BrdU+ NeuN+ cells) and astrocytes (BrdU+GFAP+ cells) in the hippocampus and ameliorate Aß oligomer-induced cognitive impairment and anxiety- and depression-like behaviors in mice evaluated by novel object recognition, Morris water maze tests, elevated zero maze, forced swimming test, and tail suspension test, respectively. Moreover, multifactor intervention could lead to an increase in the protein levels of PSD-95, SYP, DCX, NeuN, GFAP, Bcl-2, BDNF, TrkB, and pSer473-Akt and a decrease in the protein levels of BAX and caspase-9 in the hippocampal lysates of Aß oligomer-induced mice. Furthermore, sequencing analysis of serum metabolites revealed that aberrantly expressed metabolites modulated by multifactor intervention were highly enriched in the biological process associated with keeping neurons functioning and neurobehavioral function. Additionally, the intervention-mediated serum metabolites mainly participated in glutamate metabolism, glucose metabolism, and the tricarboxylic acid cycle in mice. Our findings suggest the potential of multifactor intervention as a non-invasive therapeutic strategy for AD to anti-Aß oligomer neurotoxicity.

Effects of involuntary treadmill running in combination with swimming on adult neurogenesis in an Alzheimer's mouse model.

Physical exercise plays a role on the prevention and treatment of Alzheimer's disease (AD), but the exercise mode and the mechanism for these positive effects is still ambiguous. Here, we investigated the effect of an aerobic interval exercise, running in combination with swimming, on behavioral dysfunction and associated adult neurogenesis in a mouse model of AD. We demonstrate that 4 weeks of the exercise could ameliorate Aß42 oligomer-induced cognitive impairment in mice utilizing Morris water maze tests. Additionally, the exercised Aß42 oligomer-induced mice exhibited a significant reduction of anxiety- and depression-like behaviors compared to the sedentary Aß42 oligomer-induced mice utilizing an Elevated zero maze and a Tail suspension test. Moreover, by utilizing 5'-bromodeoxyuridine (BrdU) as an exogenous cell tracer, we found that the exercised Aß42 oligomer-induced mice displayed a significant increase in newborn cells (BrdU+ cells), which differentiated into a majority of neurons (BrdU+ DCX+ cells or BrdU+NeuN+ cells) and a few of astrocytes (BrdU+GFAP+ cells). Likewise, the exercised Aß42 oligomer-induced mice also displayed the higher levels of NeuN, PSD95, synaptophysin, Bcl-2 and lower level of GFAP protein. Furthermore, alteration of serum metabolites in transgenic AD mice between the exercised and sedentary group were significantly associated with lipid metabolism, amino acid metabolism, and neurotransmitters. These findings suggest that combined aerobic interval exercise-mediated metabolites and proteins contributed to improving adult neurogenesis and behavioral performance after AD pathology, which might provide a promising therapeutic strategy for AD.

Disruption of the autism-related gene Pak1 causes stereocilia disorganization, hair cell loss, and deafness in mice.

Several clinical studies have reported that hearing loss is correlated with autism in children. However, little is known about the underlying mechanism between hearing loss and autism. p21-activated kinases (PAKs) are a family of serine/threonine kinases that can be activated by multiple signaling molecules, particularly the Rho family of small GTPases. Previous studies have shown that Pak1 mutations are associated with autism. In the present study, we take advantage of Pak1 knockout (Pak1-/-) mice to investigate the role of PAK1 in hearing function. We find that PAK1 is highly expressed in the postnatal mouse cochlea and that PAK1 deficiency leads to hair cell (HC) apoptosis and severe hearing loss. Further investigation indicates that PAK1 deficiency downregulates the phosphorylation of cofilin and ezrin-radixin-moesin and the expression of ßII-spectrin, which further decreases the HC synapse density in the basal turn of cochlea and disorganized the HC stereocilia in all three turns of cochlea in Pak1-/- mice. Overall, our work demonstrates that the autism-related gene Pak1 plays a crucial role in hearing function. As the first candidate gene linking autism and hearing loss, Pak1 may serve as a potential target for the clinical diagnosis of autism-related hearing loss.

Characterization of the complete chloroplast genome of 'Yunning No.1' lemon (Citrus limon).

'Yunning No.1' lemon, a mutant of Eureka lemon, is originally found in Yunnan province of China and is the main cultivated lemon variety there. In this study, we assembled and annotated its chloroplast genome using Illumina Hiseq-2500 whole genome re-sequencing data. Its chloroplast genome is 160,141 bp in size, containing a 87,754 bp large single copy region, a 18,385 bp small single copy region and a pair of 27,001 bp inverted repeat region. Like many citrus species, 114 unique genes (including 80 protein-coding genes, 30 tRNAs and 4 rRNAs) could be identified from the chloroplast genome of 'Yunning No.1'. Phylogenetic analysis revealed that the 'Yunning No.1' chloroplast genome was closest to Citrus maxima.

Exploring the treatment of COVID-19 with Yinqiao powder based on network pharmacology.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In China, Yinqiao powder is widely used to prevent and treat COVID-19 patients with Weifen syndrome. In this study, the screening and verification of active ingredients, target selection and DisGeNET scoring, drug-ingredient-gene network construction, protein-protein interaction network construction, molecular docking and surface plasmon resonance (SPR) analysis, gene ontology (GO) functional analysis, gene tissue analysis, and kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were used to explore the active ingredients, targets, and potential mechanisms of Yinqiao powder in the treatment of COVID-19. We also predicted the therapeutic effect of Yinqiao powder using TCM anti-COVID-19 (TCMATCOV). Yinqiao powder has a certain therapeutic effect on COVID-19, with an intervention score of 20.16. Hesperetin, eriodictyol, luteolin, quercetin, and naringenin were the potentially effective active ingredients against COVID-19. The hub-proteins were interleukin-6 (IL-6), mitogen-activated protein kinase 3 (MAPK3), tumor necrosis factor (TNF), and tumor protein P53 (TP53). The potential mechanisms of Yinqiao powder in the treatment of COVID-19 are the TNF signaling pathway, T-cell receptor signaling pathway, Toll-like receptor signaling pathway, and MAPK signaling pathway. This study provides a new perspective for discovering potential drugs and mechanisms of COVID-19.

IFI27 may predict and evaluate the severity of respiratory syncytial virus infection in preterm infants.

BACKGROUND: Preterm infants are a special population that vulnerable to respiratory syncytial virus (RSV) infection and the lower respiratory tract infections (LRTIs) caused by RSV could be severe and even life-threating. The purpose of the present study was to identify candidate genes of preterm infants who are susceptible to RSV infection and provide a new insight into the pathogenesis of RSV infection. METHODS: Three datasets (GSE77087, GSE69606 and GSE41374) containing 183 blood samples of RSV infected patients and 33 blood samples of healthy controls from Gene Expression Omnibus (GEO) database were downloaded and the differentially expressed genes (DEGs) were screened out. The function and pathway enrichments were analyzed through Database for Annotation, Visualization and Integrated Discovery (DAVID) website. The protein-protein interaction (PPI) network for DEGs was constructed through Search Tool for the Retrieval of Interacting Genes (STRING). The module analysis was performed by Cytoscape software and hub genes were identified. Clinical verification was employed to verify the expression level of top five hub genes among 72 infants including 50 RSV infected patients and 22 non-RSV-infected patients hospitalized in our center. Further, the RSV infected infants with high-expression IFI27 and those with low-expression IFI27 were compared (defined as higher or lower than the median mRNA level). Finally, the gene set enrichment analysis (GSEA) focusing on IFI27 was carried out. RESULTS: Totally, 4028 DEGs were screened out and among which, 131 most significant DEGs were selected. Subsequently, 13 hub genes were identified, and function and pathway enrichments of hub genes mainly were: response to virus, defense response to virus, regulation of viral genome replication and regulation of viral life cycle. Furthermore, IFI27 was confirmed to be the most significantly expressed in clinical verification. Gene sets associated with calcium signaling pathway, arachidonic acid metabolism, extracellular matrix receptor interaction and so on were significantly enriched when IFI27 was highly expressed. Moreover, high-expression IFI27 was associated with more severe cases (p = 0.041), more requirements of mechanical ventilation (p = 0.034), more frequent hospitalization (p < 0.001) and longer cumulative hospital stay (p = 0.012). CONCLUSION: IFI27 might serve to predict RSV infection and evaluate the severity of RSV infection in preterm infants.