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According to a recent epidemiological survey, the incidence of sudden sensorineural hearing loss (SSNHL) is increasing yearly. The cause of SSNHL is of great interest in research. To date, viral infection, vascular occlusion, abnormal cellular stress responses within the cochlea, and immune-mediated mechanisms are considered the most likely etiologies of this disease. Among these etiologies, the relationship between viral infection and sudden deafness has been unclear. In this review, we mainly discuss the viral hypothesis of SSNHL. There is little research proving or clearly indicating the pathogenesis of this disease. Further research is needed to elucidate the precise etiopathogenesis to better understand SSNHL and establish more suitable treatment to help restore hearing in affected patients.

Transition metal‐catalyzed direct decarboxylative transformations of aromatic carboxylic acids usually require high temperatures, which limit the substrate's scope, especially for late‐stage applications. The development of the selective decarbonylative of carboxylic acid derivatives, especially the most fundamental aroyl chlorides, with stable and cheap electrophiles under mild conditions is highly desirable and meaningful, but remains challenging. Herein, a strategy of nickel‐catalyzed decarbonylative alkylation of aroyl chlorides via phosphine/nitrogen ligand relay is reported. The simple phosphine ligand is found essential for the decarbonylation step, while the nitrogen ligand promotes the cross‐electrophile coupling. Such a ligand relay system can effectively and orderly carry out the catalytic process at room temperature, utilizing easily available aroyl chlorides as an aryl electrophile for reductive alkylation. This discovery provides a new strategy for direct decarbonylative coupling, features operationally simple, mild conditions, and excellent functional group tolerance. The mild approach is applied to the late‐stage methylation of various pharmaceuticals. Extensive experiments are carried out to provide insights into the reaction pathway and support the ligand relay process. A nickel‐catalyzed decarbonylative cross electrophiles coupling of aroyl chlorides with alkyl halides/pseudohalides via phosphine/nitrogen ligand relay is demonstrated. The phosphine ligand is useful in decarbonylation process and the nitrogen ligand is essential for cross‐coupling step. Such a ligand relay system can effectively and orderly carry out the catalytic process at room temperature.

This study employed traditional and advanced echocardiographic techniques to assess comprehensively age- and sex-related changes in cardiovascular structure and function in wildtype (WT) mice. Forty-five normal adult wildtype mice were apportioned to groups based on age and sex: 2-month (young) male or female, and 24-month (old) male or female ( n  = 13, 13, 13, and 6, respectively). Each underwent 2-dimensional (2D) imaging echocardiography, Doppler, tissue Doppler imaging echocardiography, and speckle-tracking echocardiography (STE) for comparison of cardiovascular structure and function parameters. Compared to the young mice, the old had significantly higher body weight (BW), and lower diastolic and mean arterial pressure. The left ventricular (LV) end-diastolic and end-systolic volumes, and left ventricular mass, were significantly higher in the old mice. Within each sex, the cardiac diastolic and systolic function parameters were comparable between the young and old. Isovolumetric relaxation time (IVRT)/diastolic time interval (DT) and the maximum drop rate of pressure in LV (− dP/dtmax) were significantly lower in the old mice, while the LV relaxation time constant (Tau) was significantly higher. Spearman’s rank correlation showed a positive association between IVRT/DT and − dp/dtmax (male r  = 0.663; female r  = 0.639). Among the males, the maximum rise rate of pressure in LV (+ dp/dtmax), and systolic global longitudinal strains and rates (S-GLS, S-GLSR) were significantly different between the young and old. Spearman’s rank correlation showed positive association between S-GLS, S-GLSR and + dp/dtmax (r = 0.709 and r = 0.499). Regarding vascular structure, the ascending aorta systolic and diastolic diameters were significantly higher in the old mice compared with the young. The male mice had progressive, age-related aortic stiffness. Ageing in mice leads to changes in cardiovascular structure and cardiac diastolic function, but systolic function is relatively well preserved in females. Changes in cardiac function and arterial stiffness were more significant in males than females. Traditional ECG is better than STE for evaluating LV diastolic function; STE is better for LV systolic function.

Background Vertebral augmentation is the first-line treatment for the osteoporosis vertebral compression fractures. Bone cement leakage is the most common complication of this surgery. This study aims to assess the risk factors for different types of cement leakage and provides a nomogram for predicting the cement intradiscal leakage. Methods We retrospectively reviewed 268 patients who underwent vertebral augmentation procedure between January 2015 and March 2019. The cement leakage risk factors were evaluated by univariate analysis. Different types of cement leakage risk factors were identified by the stepwise logistic analysis. We provided a nomogram for predicting the cement intradiscal leakage and used the concordance index to assess the prediction ability. Results A total of 295 levels of vertebrae were included, with a leakage rate of 32.5%. Univariate analysis showed delayed surgery and lower vertebral compression ratio were the independent risk factors of cement leakage. The stepwise logistic analysis revealed percutaneous vertebroplasty was a risk factor in vein cement leakage; delayed surgery, preoperative compression ratio, and upper endplate disruption were in intradiscal cement leakage; age, preoperative fracture severity, and intravertebral vacuum cleft were in perivertebral soft tissue cement leakage; no factor was in spinal canal cement leakage. The nomogram for intradiscal cement leakage had a precise prediction ability with an original concordance index of 0.75. Conclusions Delayed surgery and more vertebral compression increase the risk of cement leakage. Different types of cement leakage have different risk factors. We provided a nomogram for precise predicting the intradiscal cement leakage.

IgA nephropathy (IgAN), an immune-mediated chronic inflammatory kidney disease, is the most common primary glomerular disease in Asia, especially in China and Japan. The pathogenesis of IgAN is complex, and the main cause of IgAN is explained by the 'multiple hit' theory, which states that the deposition of immune complexes in renal mesangial cells induces chronic inflammation that leads to kidney damage. Chronic inflammation is associated with iron metabolism, which also plays an essential role in the pathogenesis, progression, diagnosis and prognosis of IgAN. Overall, this review aimed to explore the application of iron metabolism in IgAN by systematically elaborating the relationship between iron metabolism and chronic inflammation in IgAN to speculate on the possible diagnostic and therapeutic significance of iron metabolism indicators in IgAN.

Background Adipose-derived stem cells (ADSCs) promote tissue regeneration and repair. Cryoprotective agents (CPAs) protect cells from cryodamage during cryopreservation. Safe and efficient cryopreservation of ADSCs is critical for cell-based therapy in clinical applications. However, most CPAs are used at toxic concentrations, limiting their clinical application. Objective The aim of this study is to develop a non-toxic xeno-free novel CPA aiming at achieving high-efficiency and low-risk ADSC cryopreservation. Methods We explored different concentrations of trehalose (0.3 M, 0.6 M, 1.0 M, and 1.25 M) and glycerol (10%, 20%, and 30% v/v) for optimization and evaluated and compared the outcomes of ADSCs cryopreservation between a combination of trehalose and glycerol and the commonly used CPA DMSO (10%) + FBS (90%). All samples were slowly frozen and stored in liquid nitrogen for 30 days. The effectiveness was evaluated by the viability, proliferation, migration, and multi-potential differentiation of the ADSCs after thawing. Results Compared with the groups treated with individual reagents, the 1.0 M trehalose (Tre) + 20% glycerol (Gly) group showed significantly higher efficiency in preserving ADSC activities after thawing, with better outcomes in both cell viability and proliferation capacity. Compared with the 10% DMSO + 90% FBS treatment, the ADSCs preserved in 1.0 M Tre + 20% Gly showed similar cell viability, surface markers, and multi-potential differentiation but a significantly higher migration capability. The results indicated that cell function preservation can be improved by 1.0 M Tre + 20% Gly. Conclusions The 1.0 M Tre + 20% Gly treatment preserved ADSCs with a higher migration capability than 10% DMSO + 90% FBS and with viability higher than that with trehalose or glycerol alone but similar to that with 10% DMSO + 90% FBS and fresh cells. Moreover, the new CPA achieves stemness and multi-potential differentiation similar to those in fresh cells. Our results demonstrate that 1.0 M Tre + 20% Gly can more efficiently cryopreserve ADSCs and is a non-toxic CPA that may be suitable for clinical applications.

Toxoplasma gondii undergoes a complex life cycle characterized by alternating developmental stages. The genetic reprogramming mechanisms driving these stage transitions remain largely unknown. In this study, we identified the AP2 factor AP2X-1 as a critical regulator important for T. gondii growth and life cycle progression. Our findings suggest that AP2X-1 functions as a repressor by modulating the function or influencing the association of the HDAC3/MORC complex at the promoters of bradyzoite- and sexual stage-specific genes, leading to chromatin compaction, restricting DNA accessibility and thereby repressing the transcription of genes required for bradyzoite formation and sexual commitment. Deletion of ap2X-1 significantly reduced T. gondii virulence and its ability to form brain cysts. These findings reveal a previously unknown regulatory pathway controlling sexual development in T. gondii , providing new insights into its underlying mechanisms.

Background Soil salinization has become a global problem restricting the seed yield and quality of crops, including wheat ( Triticum aestivum L.). Salinity significantly alters plant morphology and severely disrupts physiological homeostasis. Salt tolerance of wheat has been widely studied whereas core ion transporters responsive to salt stress remain elusive. Results In this study, the wheat seedlings were subjected to salinity toxicity for morpho-physiological and transcriptomic analysis of wheat salt tolerance. There was a inversely proportional relationship between salt concentrations and morpho-physiological parameters. Under the condition of 100 mM NaCl, the H 2 O 2 , O 2 − , MDA content and membrane permeability were significantly increased whereas the chlorophyll content was markedly decreased. Under salt stress, a larger proportion of Na + was partitioned in the roots than in the shoots, which had a lower Na + /K + ratio and proline content. Salt stress also obviously affected the homeostasis of other cations. Genome-wide transcriptomic analysis showed that a total of 2,807 and 5,570 differentially expressed genes (DEGs) were identified in the shoots and roots, respectively. Functionality analysis showed that these DEGs were mainly enriched in the KEGG pathways related to carbon metabolism, phenylalanine, and amino acid biosynthesis, and were primarily enriched in the GO terms involving proline metabolism and redox processes. The Na + transporter genes were upregulated under salt stress, which repressed the gene expression of the K + transporters. Salt stress also significantly elevated the expression of the genes involved in osmoregulation substances biosynthesis, and obviously affected the expression profiling of other cation transporters. Co-expression network analysis identified TaNHX6-D5 / TaNHX4-B7 and TaP5CS2-B3 potentially as core members regulating wheat salt tolerance. Conclusions These results might help us fully understand the morpho-physiological and molecular responses of wheat seedlings to salt stress, and provide elite genetic resources for the genetic modification of wheat salt tolerance.

Background Oilseed rape ( B. napus L.) has great potential for phytoremediation of cadmium (Cd)-polluted soils due to its large plant biomass production and strong metal accumulation. Soil properties and the presence of other soluble compounds or ions, cause a heterogeneous distribution of Cd. Results The aim of our study was to reveal the differential responses of B. napus to different Cd abundances. Herein, we found that high Cd (50 μM) severely inhibited the growth of B. napus , which was not repressed by low Cd (0.50 μM) under hydroponic culture system. ICP-MS assays showed that the Cd 2+ concentrations in both shoots and roots under 50 μM Cd were over 10 times higher than those under 0.50 μM Cd. Under low Cd, the concentrations of only shoot Ca 2+ /Mn 2+ and root Mn 2+ were obviously changed (both reduced); under high Cd, the concentrations of most cations assayed were significantly altered in both shoots and roots except root Ca 2+ and Mg 2+ . High-throughput transcriptomic profiling revealed a total of 18,021 and 1408 differentially expressed genes under high Cd and low Cd conditions, respectively. The biological categories related to the biosynthesis of plant cell wall components and response to external stimulus were over-accumulated under low Cd, whereas the terms involving photosynthesis, nitrogen transport and response, and cellular metal ion homeostasis were highly enriched under high Cd. Differential expression of the transporters responsible for Cd uptake ( NRAMPs ), transport ( IRTs and ZIPs ), sequestration ( HMAs , ABCs , and CAXs ), and detoxification ( MTPs , PCR , MTs , and PCSs ), and some other essential nutrient transporters were investigated, and gene co-expression network analysis revealed the core members of these Cd transporters. Some Cd transporter genes, especially NRAMPs and IRTs , showed opposite responsive patterns between high Cd and low Cd conditions. Conclusions Our findings would enrich our understanding of the interaction between essential nutrients and Cd, and might also provide suitable gene resources and important implications for the genetic improvement of plant Cd accumulation and resistance through molecular engineering of these core genes under varying Cd abundances in soils.

The aim of this report is to provide international recommendations for functional ear reconstruction in patients with microtia and aural atresia. All patients with microtia and external auditory atresia should be seen in the setting of a multidisciplinary team and agreed treatment outcomes should be measured, so that techniques, approaches, and results can be compared. The methods are expert opinion from the members of the International Microtia and Atresia Workgroup (IMAW).The consensus recommendations reported herein take into account the variability in practice patterns present among experts in the field; the degree of consensus was quantified by presenting the percentage of above authors who agree or partially agree with each statement. Recommendations include the definition and classification of microtia/atresia, treatment of microtia, treatment of congenital aural atresia, flowchart of functional ear reconstruction, and future research directions. Patients with microtia and aural atresia can be guided by the consensus recommendations provided herein.