Lipid metabolism and hearing loss: association of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) with adolescent hearing health.

BACKGROUND: The ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) is a novel lipid measure for assessing the risk of cardiovascular disease. Lipid metabolism disorders are reportedly associated with hearing impairment. This study aimed to investigate the potential association between NHHR and hearing. METHODS: The data used in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) cycles of 2005-2010 and 2017-2018, including 4,296 participants aged 6-19 years. The NHHR was calculated from lipid profiles, and hearing was assessed using pure-tone audiometry. Weighted multivariate logistic regression analyses were used to investigate the association between the NHHR and hearing loss. Subgroup and sensitivity analyses were performed to verify the robustness of the results. RESULTS: Univariate analysis revealed significant associations between the NHHR and hearing threshold at all categorized frequency (low, speech, or high-frequency) (P < 0.001). Three models were used: an unadjusted model, a model adjusted for age, sex, and race, and a model further adjusted for PIR, BMI, and diabetes. Multiple regression analysis confirmed these associations consistently across all models. When considered as a continuous variable, NHHR had a significant association with enhanced hearing thresholds at all categorized frequencies: low-frequency (ß:0.56, 95% CI: 0.36-0.75), speech-frequency (ß:0.55, 95% CI: 0.36-0.7), and high-frequency (ß:0.55, 95% CI: 0.36-0.74). The adjusted models showed persistent positive correlations after controlling for covariates. The NHHR was consistently positively associated with hearing loss. The NHHR and auditory thresholds showed a general dose-response association across all frequencies. CONCLUSIONS: NHHR is a promising biomarker for predicting adolescent hearing threshold shifts and hearing loss. The study highlights the importance of early lipid monitoring and management as strategies to prevent or reduce hearing impairment.

Physiological and molecular mechanism of Populus pseudo-cathayana × Populus deltoides response to Hyphantria cunea.

Populus pseudo-cathayana × Populus deltoides is a crucial artificial forest tree species in Northeast China. The presence of the fall webworm (Hyphantria cunea) poses a significant threat to these poplar trees, causing substantial economic and ecological damage. This study conducted an insect-feeding experiment with fall webworm on P. pseudo-cathayana × P. deltoides, examining poplar's physiological indicators, transcriptome, and metabolome under different lengths of feeding times. Results revealed significant differences in phenylalanine ammonia-lyase activity, total phenolic content, and flavonoids at different feeding durations. Transcriptomic analysis identified numerous differentially expressed genes, including AP2/ERF, MYB, and WRKY transcription factor families exhibiting the highest expression variations. Differential metabolite analysis highlighted flavonoids and phenolic acid compounds of poplar's leaves as the most abundant in our insect-feeding experiment. Enrichment analysis revealed significant enrichment in the plant hormone signal transduction and flavonoid biosynthetic pathways. The contents of jasmonic acid and jasmonoyl-L-isoleucine increased with prolonged fall webworm feeding. Furthermore, the accumulation of dihydrokaempferol, catechin, kaempferol, and naringenin in the flavonoid biosynthesis pathway varied significantly among different samples, suggesting their crucial role in response to pest infestation. These findings provide novel insights into how poplar responds to fall webworm infestation.

Anti-inflammatory activity of a new lactone isolated from the leaves of Ardisia crenata Sims.

One new lactone (1) named Ardisicreolide C, together with three saponin compounds, Ardisiacrispin B (2), Ardisicrenoside A (3), Ardisiacrispin A (4) were isolated and identified from the leaves of Ardisia crenata Sims. The structures of 1-4 were elucidated by 1D, 2D-NMR and HR-MS spectra and together with the published data. In view of structures with lactone moieties showed good anti-inflammatory activity, the anti-inflammatory effects of Ardisicreolide C on LPS-induced RAW264.7 cells were evaluated by enzyme linked immunosorbent assay (ELISA) method. As a result, Ardisicreolide C could reduce release of nitric oxide (NO), tumour necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), interleukin 4 (IL-4) and interleukin 10 (IL-10) of the cell supernatant to exert anti-inflammatory activity. This indicates that the leaves as non-medicinal parts of Ardisia crenata Sims contain compounds with good anti-inflammatory activity, which provides a new direction for the discovery of anti-inflammatory drugs.

Discovery of Potential Anti-Microbial Molecules and Spectrum Correlation Effect of Ardisia crenata Sims via High-Performance Liquid Chromatography Fingerprints and Molecular Docking.

Ardisia crenata Sims, an important ethnic medicine, is recorded in the Chinese Pharmacopoeia for treating laryngeal diseases and upper respiratory tract infections. This study aimed to evaluate the antimicrobial effect of extracts and potential antimicrobial compounds of A. crenata Sims. It was found that the roots of A. crenata Sims have a potential inhibitory effect on Candida albicans and Aspergillus flavus, with MICs of 1.56 mg/mL and 0.39 mg/mL, and the leaves of A. crenata Sims have a potential inhibitory effect on Pseudomonas aeruginosa and Staphylococcus aureus, with MICs of 3.12 mg/mL and 6.77 mg/mL, respectively. Meanwhile, five compounds including one catechin and four bergenins were obtained from roots. These components were identified on the fingerprint spectrum, representing chromatographic peaks 16, 21, 22, 23, and 25, respectively. Among these, 11-ß-d-glucopyranosyl-bergenin and (-)-gallocatechin showed potential inhibition for Staphylococcus aureus and Pseudomonas aeruginosa with MIC of 0.26 and 0.33 mg/mL, respectively. The roots, stems, and leaves of A. crenata Sims are very similar in chemical composition, with large differences in content. Principal component analysis (PCA) and Hierarchical cluster analysis (HCA) showed that 16 batches of A. crenata Sims could be divided into four main production areas: Guizhou, Jiangsu, Guangxi, and Jiangxi. Furthermore, molecular docking results showed that 11-ß-d-glucopyranosyl-bergenin had a better affinity for Casein lytic proteinase P (ClpP), and (-)-gallocatechin possessed a strong affinity for LasA hydrolysis protease and LasB elastase. These findings suggest catechin and bergenins from A. crenata Sims can be used as antimicrobial activity molecules.

Early-life noise exposure causes cognitive impairment in a sex-dependent manner by disrupting homeostasis of the microbiota-gut-brain axis.

Epidemiological investigations show that noise exposure in early life is associated with health and cognitive impairment. The gut microbiome established in early life plays a crucial role in modulating developmental processes that subsequently affect brain function and behavior. Here, we examined the impact of early-life exposure to noise on cognitive function in adolescent rats by analyzing the gut microbiome and metabolome to elucidate the underlying mechanisms. Chronic noise exposure during early life led to cognitive deficits, hippocampal injury, and neuroinflammation. Early-life noise exposure showed significant difference on the composition and function of the gut microbiome throughout adolescence, subsequently causing axis-series changes in fecal short-chain fatty acid (SCFA) metabolism and serum metabolome profiles, as well as dysregulation of endothelial tight junction proteins, in both intestine and brain. We also observed sex-dependent effects of microbiota depletion on SCFA-related beneficial bacteria in adolescence. Experiments on microbiota transplantation and SCFA supplementation further confirmed the role of intestinal bacteria and related SCFAs in early-life noise-exposure-induced impairments in cognition, epithelial integrity, and neuroinflammation. Overall, these results highlight the homeostatic imbalance of microbiota-gut-brain axis as an important physiological response toward environmental noise during early life and reveals subtle differences in molecular signaling processes between male and female rats.

Synthesis and Photoluminescence Modulation of Cs4Cd1-xMnxBi2Cl12-Based Two-Dimensional Layered Double Perovskites.

Two-dimensional (2D) layered double perovskites have attracted much attention because of their excellent photoelectric properties. However, few reports have been published on the synthesis of 2D layered double perovskites from halide perovskites as precursors. Here, we report that CsCdCl3 and Cs3Bi2Cl9 were synthesized by the coprecipitation method, and a two-dimensional layered double perovskite Cs4CdBi2Cl12 was readily synthesized by mixing the two halide perovskites. We doped different amounts of Mn2+ into CsCdCl3 to form CsCd1-xMnxCl3, which introduced impurity states into the energy level and exhibited an orange-red light emission that is characteristic of Mn2+. A series of 2D layered double perovskites Cs4Cd1-xMnxBi2Cl12 were synthesized from CsCd1-xMnxCl3 and Cs3Bi2Cl9, which showed a bright orange-yellow luminescence under ultraviolet excitation. The presence of high concentrations of Cd2+ in the two-dimensional layered double perovskites weakened the strong Mn-Mn coupling and suppressed the energy transfer to defects, thus minimizing nonradiative decay and promoting efficient energy transfer. Our work provides a new concept for the synthesis of low-dimensional metal halide perovskites with unique optical properties.

Adenovirus-mediated SIRT1 protects cochlear strial marginal cells in a D-gal-induced senescent model in vitro.

BACKGROUND: A primary obstacle in age-related hearing loss (ARHL) study is the lack of accelerated senescent models in vitro that explore the precise underlying mechanism in different types of ARHL. The damage to strial marginal cells (SMCs) is a subset of strial presbycusis-associated pathological changes. We aimed to establish a D-galactose (D-gal)-induced SMCs senescent model and study the effect of deacetylase sirtuin 1 (SIRT1) on presbycusis in vitro. METHODS: SMCs from C57BL/6J neonatal mice were cultured and treated with D-gal to establish accelerated senescent models. And then D-gal-induced SMCs were transfected with adenovirus (Ad)-SIRT1-GFP or Ad-GFP. Oxidative stress and mitochondrial DNA (mtDNA) damage were determined by histological analysis or RT-PCR. Western blotting (WB) and RT-PCR were used to evaluate protein and mRNA levels of superoxide dismutase 2 (SOD2) and SIRT1, respectively. Additionally, apoptosis was investigated by WB and TUNEL staining. RESULTS: D-gal-induced SMCs exhibited several characteristics of senescence, including increased the level of 8-hydroxy-2'-deoxyguanosine, which is a marker of DNA oxidative damage, and elevated the amount of mtDNA 3860-bp deletion, which is a common type of mtDNA damage in the auditory system of mice. SIRT1 overexpression effectively inhibited these changes by upregulating the level of SOD2, thereby inhibiting cytochrome c translocation from mitochondria to cytoplasm, inhibiting cell apoptosis, and ultimately delaying aging in the D-gal-induced senescent SMCs. CONCLUSIONS: Altogether, the evidence suggests that the D-gal-induced SMCs accelerated aging model is successfully established, and SIRT1 overexpression protects SMCs against oxidative stress by enhancing SOD2 expression in ARHL.

Optimal Choice for Improving the Hearing in Children with Unilateral Microtia and Atresia: Softband or Adhesive Adapter?

INTRODUCTION: A nonsurgical bone conduction hearing aid (BCHA) is a well-established treatment for children with congenital unilateral microtia and atresia (UMA). To date, limited studies have evaluated the audiological characteristics of the different wearing modes in the same nonsurgical BCHA. METHODS: Eighteen patients with UMA aged 5-24 years were included. Warble tones at frequencies of 0.5, 1, 2, and 4 kHz were presented to determine functional hearing gain (FHG) of hearing thresholds (in dB HL) in the sound field. The speech perception abilities were assessed by the speech discrimination score (SDS, in %) of monosyllables, disyllables, and sentences in quiet and noise using the Chinese Mandarin speech test materials. Hearing outcomes were evaluated with the ADHEAR™ worn on a softband and with an adhesive adapter. A correlational analysis was conducted to analyze the correlations between variables (e.g., age, height, weight, body mass index [BMI], bone conduction pure-tone threshold, and air conduction pure-tone threshold) and the differences in the two wearing modes. RESULTS: The mean FHG (standard deviation, SD) at 0.5-4 kHz was 20.63 (3.94) dB HL with the adhesive adapter and 26.39 (3.15) dB HL with the softband. When aided with the BCHA, significant improvements in SDS were revealed in all Mandarin speech test material lists either in quiet or noise for both wearing modes. Compared with the adapter mode, the softband provided higher aided SDS values. Correctional analyses revealed that higher BMI values were positively associated with larger delta outcomes between the two coupling methods of the softband and adhesive adapter in patients with UMA. Furthermore, a larger delta average FHG of 0.5-4 kHz was consistently associated with larger delta monosyllabic SDS in quiet, disyllabic SDS in quiet, and disyllabic SDS in noise. DISCUSSION: To the best of our knowledge, this is the first study to compare the hearing benefits of coupling methods using novel adhesive adapters and conventional softbands with the same audio processor (ADHEAR™). Under uniform internal settings, softband integration provided more hearing benefits than adhesive adapter integration, and the differences were more obvious in patients with higher BMI values. Besides, a brief measurement of FHG can be utilized to predict individualized speech perception levels.

SIRT3-mediated deacetylation protects inner hair cell synapses in a H2O2-induced oxidative stress model in vitro.

Oxidative stress is considered a driving event in the damage to inner hair cell (IHC) synapses. Mitochondrial deacetylase sirtuin 3 (SIRT3) is an important regulator of reactive oxygen species (ROS) production. However, the effect of SIRT3 on IHC synapses remains elusive. In this study, we treated cochlear basilar membrane (CBM) with hydrogen peroxide (H2O2) to establish an oxidative stress model in vitro. The H2O2-induced CBM exhibited decreased the number of IHC synapses with low levels of ATP and mitochondrial membrane potential. Additionally, H2O2-induced CBM showed markedly reduced levels of forkhead box protein O 3a (FOXO3a), superoxide dismutase 2 (SOD2), and isocitrate dehydrogenase 2 (IDH2), thereby increasing ROS generation. SIRT3 overexpression via administrating nicotinamide riboside in the H2O2-induced CBM protected IHC synapses against oxidative stress and inhibited hair cell apoptosis. We further demonstrated that SIRT3 overexpression led to upregulation of IDH2, and hypoacetylation of several proteins, such as FOXO3a and SOD2, which in turn reduced the levels of ROS and improved mitochondrial function. Collectively, these findings reveal that overexpressing SIRT3 may be a potential therapeutic approach for damaged IHC synapses induced by oxidative stress.

Optimized Design of Distributed Quasi-Cyclic LDPC Coded Spatial Modulation.

We propose a distributed quasi-cyclic low-density parity-check (QC-LDPC) coded spatial modulation (D-QC-LDPCC-SM) scheme with source, relay and destination nodes. At the source and relay, two distinct QC-LDPC codes are used. The relay chooses partial source information bits for further encoding, and a distributed code corresponding to each selection is generated at the destination. To construct the best code, the optimal information bit selection algorithm by exhaustive search in the relay is proposed. However, the exhaustive-based search algorithm has large complexity for QC-LDPC codes with long block length. Then, we develop another low-complexity information bit selection algorithm by partial search. Moreover, the iterative decoding algorithm based on the three-layer Tanner graph is proposed at the destination to carry out joint decoding for the received signal. The recently developed polar-coded cooperative SM (PCC-SM) scheme does not adopt a better encoding method at the relay, which motivates us to compare it with the proposed D-QC-LDPCC-SM scheme. Simulations exhibit that the proposed exhaustive-based and partial-based search algorithms outperform the random selection approach by 1 and 1.2 dB, respectively. Because the proposed D-QC-LDPCC-SM system uses the optimized algorithm to select the information bits for further encoding, it outperforms the PCC-SM scheme by 3.1 dB.

A Modified Method for Transient Transformation via Pollen Magnetofection in Lilium Germplasm.

Lily (Lilium spp.) is a popular ornamental plant. Traditional genetic transformation methods have low efficiency in lily, thus development of a high-efficiency genetic transformation system is important. In this study, a novel transient transformation method involving pollen magnetofection was established and optimized pollen viability, and exogenous gene expression in magnetofected pollen and that of different germplasm were assessed. The highest germination percentage of Lilium regale pollen was 85.73% in medium containing 100 g/L sucrose, 61.5 mg/L H3BO3, and 91.5 mg/L CaCl2. A 1:4 ratio of nanomagnetic beads to DNA plasmid and transformation time of 0.5 h realized the highest transformation efficiency (88.32%). The GFP activity in transformed pollen averaged 69.66%, while that of the control pollen was 0.00%. In contrast to the control, transgenic seedlings obtained by pollination with magnetofected pollen showed strong positive GUS activity with 56.34% transformation efficiency. Among the lily germplasm tested, 'Sweet Surrender' and L. leucanthum had the highest transformation efficiency (85.80% and 54.47%), whereas L. davidii var. willmottiae was not successfully transformed. Transformation efficiency was positively correlated with pollen equatorial diameter and negatively correlated with polar axis/equatorial diameter ratio. The results suggest that pollen magnetofection-mediated transformation can be applied in Lilium but might have species or cultivar specificity.

AAV-ie-mediated UCP2 overexpression accelerates inner hair cell loss during aging in vivo.

BACKGROUND: Uncoupling protein 2 (UCP2), activated by excessive reactive oxygen species (ROS) in vivo, has the dual effect of reducing ROS to protect against oxidative stress and reducing ATP production to regulate cellular metabolism. Both the UCP2 and ROS are increased in cochleae in age-related hearing loss (ARHL). However, the role of UCP2 in sensory hair cells in ARHL remains unclear. METHODS: Male C57BL/6 J mice were randomly assigned to an 8-week-old group (Group 1), a 16-week-old group (Group 2), a 16-week-old + adeno-associated virus-inner ear (AAV-ie) group (Group 3), and a 16-week-old + AAV-ie-UCP2 group (Group 4). Mice aged 8 weeks were administrated with AAV-ie-GFP or AAV-ie-UCP2 via posterior semicircular canal injection. Eight weeks after this viral intervention, hearing thresholds and wave-I amplitudes were tested by auditory brainstem response (ABR). Subsequently, the cochlear basilar membrane was dissected for investigation. The number of hair cells and inner hair cell (IHC) synapses, the level of ROS, and the expression of AMP-activated protein kinase α (AMPKα), were assessed by immunofluorescence staining. In addition, mitochondrial function was determined, and the expression of AMPKα and UCP2 proteins was further evaluated using western blotting. RESULTS: Mice with early-onset ARHL exhibited enhanced oxidative stress and loss of outer hair cells and IHC synapses, while UCP2 overexpression aggravated hearing loss and cochlear pathophysiological changes in mice. UCP2 overexpression resulted in a notable decrease in the number of IHCs and IHC synapses, caused ATP depletion and excessive ROS generation, increased AMPKα protein levels, and promoted IHC apoptosis, especially in the apical and middle turns of the cochlea. CONCLUSION: Collectively, our data suggest that UCP2 overexpression may cause mitochondrial dysfunction via energy metabolism, which activates mitochondrion-dependent cellular apoptosis and leads to IHC loss, ultimately exacerbating ARHL.

Aronia melanocarpa polysaccharide ameliorates liver fibrosis through TGF-ß1-mediated the activation of PI3K/AKT pathway and modulating gut microbiota.

The purpose of this experiment was to investigate the anti-hepatic fibrosis effect of Aronia melanocarpa polysaccharide (AMP) on TAA-induced liver fibrosis mice and its mechanism, as well as the changes in intestinal flora in vivo. This was established with a dose of 200 mg/kg TAA (i.p) once every three days, lasting for eight weeks. Colchicine with 0.4 mg/kg, and AMP (200 and 400 mg/kg) were given by intragastric administration (i.g) after 28 days of intraperitoneal injection of TAA. AMP treatment significantly inhibited the activities of liver injury markers ALT and AST in serum. Histopathological staining demonstrated that AMP significantly reversed TAA-induced hepatocyte necrosis and collagen deposition. In addition, AMP treatment block TGF- ß1/Smads pathway inhibited the production of ECM and alleviates liver fibrosis. Furthermore, AMP treatment enhanced the phosphorylation of PI3K/AKT and decreased the expression of its downstream apoptosis-related proteins in liver, thus effectively alleviating TAA-induced liver fibrosis. In addition, 16S rDNA gene sequencing analysis showed that AMP treatment helped restore the imbalanced ecosystem of gut microbes, increased the proportion of Bacteroidetes and Proteobacteria, and increased species richness. Above findings clearly show that AMP is an effective method for treating liver fibrosis, possibly by improving the gut microbiota.

Audiological and subjective benefit with a new adhesive bone conduction hearing aid in children with congenital unilateral microtia and atresia.

PURPOSE: This study aimed to evaluate the audiological benefits and subjective satisfaction in using a new adhesive bone conduction hearing aid in children with congenital unilateral microtia and atresia. METHODS: We evaluated the effectiveness of the hearing aid using the sound field hearing threshold, speech recognition ability under quiet and noise, and subjective questionnaires in 13 children (5-15 years old). RESULTS: The mean sound field hearing threshold significantly improved with a gain of 25.4 ± 4.9 dB HL. Mean word recognition scores were ameliorated in quiet and noise by 1.9 ± 2.5% and 7.3 ± 5.3%, respectively. Speech recognition ability results in noise varied; when the speech signal and noise were presented from the front, the mean speech recognition ability improved by 2.5 ± 1.6 dB signal-to-noise ratios (SNR). When noise was presented towards the normal hearing side, speech understanding was improved by 2.9 ± 1.6 dB SNR. When the speech signal was presented from the atretic side with noise from the normal hearing side, an improvement of 5.7 ± 3.4 dB SNR (p < 0.001) was noted. However, when noise was presented towards the newly aided atretic ear, no statistical significance was found. The questionnaire results indicated that the hearing device provided benefits in speech recognition ability in different complex situations, with high satisfaction rates. CONCLUSION: The adhesive bone conduction hearing aid investigated here offers a concealed and aesthetic method to improve hearing in children with congenital unilateral microtia and atresia during their early years, with high subjective satisfaction.

Optimized Distributed Generalized Reed-Solomon Coding with Space-Time Block Coded Spatial Modulation.

We present a well-known generalized Reed-Solomon (GRS) code incorporated with space-time block coded spatial modulation (STBC-SM) for wireless networks, which is capable of enjoying coded cooperation between the source and the relay. In the proposed distributed GRS-coded STBC-SM (DGRSC-STBC-SM) scheme, the source and relay nodes use distinct GRS codes. At the relay, we employ the concept of information selection to choose the message symbols from the source for further encoding. Thus, the codewords jointly constructed by the source and relay are generated at the destination. For achieving the best codeword set at the destination, we propose an optimal algorithm at the relay to select partial symbols from the source. To reduce the computational complexity, we propose a more practical algorithm with low complexity. Monte Carlo simulation results show that the proposed scheme using the low-complexity algorithm can achieve near-optimal error performance. Furthermore, our proposed scheme provides better error performance than its corresponding coded non-cooperative counterpart and the existing Reed-Solomon coded cooperative SM (RSCC-SM) scheme under identical conditions.

Functional and structural analysis of cytokine-selective IL6ST defects that cause recessive hyper-IgE syndrome.

BACKGROUND: Biallelic variants in IL6ST, encoding GP130, cause a recessive form of hyper-IgE syndrome (HIES) characterized by high IgE level, eosinophilia, defective acute phase response, susceptibility to bacterial infections, and skeletal abnormalities due to cytokine-selective loss of function in GP130, with defective IL-6 and IL-11 and variable oncostatin M (OSM) and IL-27 levels but sparing leukemia inhibitory factor (LIF) signaling. OBJECTIVE: Our aim was to understand the functional and structural impact of recessive HIES-associated IL6ST variants. METHODS: We investigated a patient with HIES by using exome, genome, and RNA sequencing. Functional assays assessed IL-6, IL-11, IL-27, OSM, LIF, CT-1, CLC, and CNTF signaling. Molecular dynamics simulations and structural modeling of GP130 cytokine receptor complexes were performed. RESULTS: We identified a patient with compound heterozygous novel missense variants in IL6ST (p.Ala517Pro and the exon-skipping null variant p.Gly484_Pro518delinsArg). The p.Ala517Pro variant resulted in a more profound IL-6- and IL-11-dominated signaling defect than did the previously identified recessive HIES IL6ST variants p.Asn404Tyr and p.Pro498Leu. Molecular dynamics simulations suggested that the p.Ala517Pro and p.Asn404Tyr variants result in increased flexibility of the extracellular membrane-proximal domains of GP130. We propose a structural model that explains the cytokine selectivity of pathogenic IL6ST variants that result in recessive HIES. The variants destabilized the conformation of the hexameric cytokine receptor complexes, whereas the trimeric LIF-GP130-LIFR complex remained stable through an additional membrane-proximal interaction. Deletion of this membrane-proximal interaction site in GP130 consequently caused additional defective LIF signaling and Stüve-Wiedemann syndrome. CONCLUSION: Our data provide a structural basis to understand clinical phenotypes in patients with IL6ST variants.

A Novel Senescence-Specific Gene (ZmSAG39) Negatively Regulates Darkness and Drought Responses in Maize.

The papain-like cysteine proteases (PLCPs) is a subfamily of cysteine proteases that plays an important role in leaf senescence, and some of its members are involved in the regulation of plant growth and development under stress. In this study, we cloned a new gene, ZmSAG39, from maize. Expression profile analysis showed that ZmSAG39 was induced by darkness and drought treatments. In addition, the ZmSAG39 overexpression in maize accelerated the senescence of maize leaves under darkness and drought treatments. However, the knockout of ZmSAG39 in maize enhanced the resistance of maize to darkness and drought stresses and reduced the degree of senescence of maize leaves. Under drought stress, compared with WT plants, the knockout lines had a higher seed germination rate, seedling survival rate and chlorophyll content, and lower reactive oxygen species (ROS) level and malondialdehyde (MDA) content. In addition, quantitative real-time PCR (qRT-PCR) analysis showed that ZmSAG39 negatively regulated some stress-related genes but positively regulated senescence-related genes under darkness and drought stress conditions. To summarize, these results indicate that ZmSAG39 is a senescence-related gene and plays a negative role in response to darkness and drought stresses. This study laid a theoretical foundation for the innovation of maize germplasm resources with high quality, high yield and strong stress resistance.

Biallelic Mutations in ATP5F1D, which Encodes a Subunit of ATP Synthase, Cause a Metabolic Disorder.

ATP synthase, H+ transporting, mitochondrial F1 complex, δ subunit (ATP5F1D; formerly ATP5D) is a subunit of mitochondrial ATP synthase and plays an important role in coupling proton translocation and ATP production. Here, we describe two individuals, each with homozygous missense variants in ATP5F1D, who presented with episodic lethargy, metabolic acidosis, 3-methylglutaconic aciduria, and hyperammonemia. Subject 1, homozygous for c.245C>T (p.Pro82Leu), presented with recurrent metabolic decompensation starting in the neonatal period, and subject 2, homozygous for c.317T>G (p.Val106Gly), presented with acute encephalopathy in childhood. Cultured skin fibroblasts from these individuals exhibited impaired assembly of F1FO ATP synthase and subsequent reduced complex V activity. Cells from subject 1 also exhibited a significant decrease in mitochondrial cristae. Knockdown of Drosophila ATPsynδ, the ATP5F1D homolog, in developing eyes and brains caused a near complete loss of the fly head, a phenotype that was fully rescued by wild-type human ATP5F1D. In contrast, expression of the ATP5F1D c.245C>T and c.317T>G variants rescued the head-size phenotype but recapitulated the eye and antennae defects seen in other genetic models of mitochondrial oxidative phosphorylation deficiency. Our data establish c.245C>T (p.Pro82Leu) and c.317T>G (p.Val106Gly) in ATP5F1D as pathogenic variants leading to a Mendelian mitochondrial disease featuring episodic metabolic decompensation.

Efficacy and Safety Evaluation of Transurethral Resection of the Prostate versus Plasmakinetic Enucleation of the Prostate in the Treatment of Massive Benign Prostatic Hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common chronic progressive disease resulting in urinary obstruction in aging men. It comes to more and more patients with massive BPH with the aging of society and extension of life expectancy. OBJECTIVE: The aim of the study was to compare the clinical efficacy, safety, and complications between transurethral bipolar plasmakinetic enucleation of the prostate (PKEP) and transurethral resection of the prostate (TURP) in the treatment of massive BPH. DESIGN AND SETTING: Patients with BPH were divided into the PKEP group and the TURP group randomly. Intraoperative blood loss (BL), operation time (OT), resected tissue weight (RTW), gland resection ratio (GRR), postoperative indwelling ureter time (IUT), bladder fistula time (BFT) and hospital stay time (HST), preoperative and postoperative serum sodium concentration (SSC), hemoglobin concentration (HGB), prostate weight (PW), postvoid residual (PVR), maximum urinary flow rate (Qmax), international prostate symptom score (IPSS), quality of life (QOL), International Index of Erectile Function (IIEF), and other complications were analyzed and compared respectively. RESULTS: There was no statistical difference in preoperative IPSS, preoperative QOL score, preoperative PVR, preoperative Qmax, postoperative QOL score, postoperative PVR, postoperative Qmax, IPSS difference value (DV), Qmax DV, and PVR DV between the PKEP group and the TURP group (p > 0.05). OT, BL, IUT, BFT, HST, and postoperative IPSS in the PKEP group were significantly lower than that in the TURP group (p < 0.01). RTW and GRR in the PKEP group were significantly higher than that in the TURP group (p < 0.01). QOL DV in the PKEP group was higher than that in the TURP group (p < 0.05). There was statistical difference in SSC DV between the PKEP group and the TURP group (p < 0.05). There was significant statistical difference in postoperative PW, postoperative HGB, PW DV, and HGB DV between the PKEP group and the TURP group (p < 0.01). There was significant statistical difference in IPSS, QOL, PVR, and Qmax between postoperative value and preoperative value in both groups (p < 0.01). The incidence of transurethral resection syndrome, obturator nerve reflex, transient urinary incontinence, and retrograde ejaculation between the PKEP group and the TURP group has no statistical difference (p > 0.05). Capsule perforation, blood transfusion, secondary hemorrhage, bladder neck contracture, and urethral stricture in the PKEP group were lower than that in the TURP group (p < 0.05). Bladder spasm in the PKEP group was significantly lower than that in the TURP group (p < 0.01). There was no statistical difference in preoperative and postoperative IIEF-5, effective erectile frequency, telotism average tension, sustainable telotism average time, and sexual dissatisfaction between the PKEP group and the TURP group (p > 0.05). CONCLUSIONS: PKEP and TURP have similar clinical efficacy in the treatment of massive BPH. PKEP has advantages in shorter OT, less BL, more GRR, and fewer complications, but the long-term therapeutic effect of PKEP needs further follow-up.

Sound-localisation performance in patients with congenital unilateral microtia and atresia fitted with an active middle ear implant.

OBJECTIVE: This study assessed the safety and sound-localisation ability of the Vibrant Soundbridge (VSB) (Med-EL, Innsbruck, Austria) in patients with unilateral microtia and atresia (MA). METHODS: This was a single-centre retrospective research study. Twelve subjects with unilateral conductive hearing loss (UCHL) caused by ipsilateral MA were recruited, each of whom underwent VSB implantation and auricular reconstruction. The bone-conduction (BC) threshold was measured postoperatively, and the accuracy of sound localisation was evaluated at least 6 months after surgery. Horizontal sound-localisation performance was investigated with the VSB activated and inactivated, at varying sound stimuli levels (65, 70 and 75 dB SPL). Localisation benefit was analysed via the mean absolute error (MAE). RESULTS: There was no statistical difference in mean BC threshold of impaired ears measured preoperatively and postoperatively. When compared with VSB-inactivated condition, the MAE increased significantly in unilateral MA patients in the VSB-activated condition. Besides, sound-localisation performance worsened remarkably when sound was presented at 70 dB SPL and 75 dB SPL. Regarding the side of signal location, the average MAE with the VSB device was much higher than that without the VSB when sound was from the normal-hearing ear. However, no significant difference was observed when sound was located from the impaired ear. CONCLUSION: This study demonstrates that in patients with unilateral MA, the VSB device does not affect inner-ear function. Sound-localisation ability is not improved, but deteriorated at follow-up. Our results suggest that the VSB-aided localisation abilities may be related to the thresholds between the ears, plasticity of auditory system and duration of use of VSB.