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Multifunctional magnetic materials have broad application prospects in molecular switches and information storage. In this study, four mononuclear Fe(II) complexes are synthesized using a series of pyrenylhydrazone ligands HL1-4. Two deprotonated ligands are coordinated to the iron(II) ions in an enolic form, leading to neutral complexes FeII(Lx)2·xsol with a FeIIN4O2 octahedral coordination environment. Magnetic measurements suggest that complex Fe(L1)2·2ACE (1·2ACE, ACE = acetone) is mainly low spin below 300 K and complex Fe(L3)2·ACE (3·ACE) is high spin, whereas complexes Fe(L2)2 (2) and Fe(L4)2·6H2O (4·6H2O) exhibit gradual spin crossover behavior. The spin states of complexes 1-4 are confirmed by single-crystal X-ray diffraction analysis. The substituent effect on the magnetic properties of the complexes is significant in this system. Temperature-dependent fluorescence emission spectra show the coexistence but no coupling effect of spin crossover and fluorescence for complexes 2 and 4·6H2O.

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Nurses are the largest group in the health care system. The current care shortage remains a global challenge in the healthcare system.The accelerated second-degree nursing (ABSN) program was first proposed by the University of St.Louis in 1971 and then vigorously developed in the United States. Its purpose is to train more nursing talents to solve the medical needs of the poor in the United States. In the past few decades, this project has been carried out by many countries around the world to solve their domestic nursing problems.As a strategy to address severe care shortages, ABSN is continuing to increase rapidly.China as the world's second most populous country, coupled with aging year by year, the demand for nursing talents, and the ABSN project just gave China effective inspiration.Therefore, this article introduces the basic design of the bachelor's degree in nursing at the University of Washington, summarizes the characteristics of the training model, and draws on experience from the basic situation, training objectives, courses and evaluation methods. It is urgent to provide guidance and reference for the acceleration of nursing education in China.

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Objective: The purpose of this study was to report a case of herpes simplex virus-1 (HSV-1) keratitis misdiagnosed as fungal keratitis due to its clinical presentation being similar to that of fungal keratitis, ultimately diagnosed by NGS. Patients and Methods: A 59-year-old male presented with reduced vision in the right eye, combined with a history of trauma with vegetative matter. The corneal ulcer was accompanied with feathery infiltration, satellite lesion, and endothelial plaques. In vivo confocal microscopy (IVCM) showed hyper-reflective linear, thin, and branching interlocking structures. Fungal keratitis was diagnosed. Voriconazole 100 mg orally daily, topical tobramycin and 1% voriconazole were initiated empirically right away. The condition was aggravated and penetrating keratoplasty was performed. Anterior segment optical coherence tomography (AS-OCT) demonstrated the presence of plaques with a clear boundary between plaques and endothelium, resembling the AS-OCT images observed in cases of viral keratitis. Next-generation sequencing (NGS) further detected HSV-1 deoxyribonucleic acid, and no fungal component was found. Antifungal agents were discontinued and antiviral treatments were added. Results: We successfully treated a patient with HSV-1 keratitis who was misdiagnosed due to clinical features and IVCM findings similar to fungal keratitis. The patient's infection was controlled. At 2 years after surgery, the cornea recovered well. Conclusions: HSV-1 keratitis with atypical clinical presentation can be easily misdiagnosed. This case report emphasizes the importance of NGS in diagnosing the pathogens of keratitis.

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Acute myeloid leukemia (AML) is a prevalent hematological malignancy among adults. Recent studies suggest that the length of telomeres could significantly affect both the risk of developing AML and the overall survival (OS). Despite the limited focus on the prognostic value of telomere-related genes (TRGs) in AML, our study aims at addressing this gap by compiling a list of TRGs from TelNet, as well as collecting clinical information and TRGs expression data through the Gene Expression Omnibus (GEO) database. The GSE37642 dataset, sourced from GEO and based on the GPL96 platform, was divided into training and validation sets at a 6:4 ratio. Additionally, the GSE71014 dataset (based on the GPL10558 platform), GSE12417 dataset (based on the GPL96 and GPL570 platforms), and another portion of the GSE37642 dataset (based on the GPL570 platform) were designated as external testing sets. Univariate Cox regression analysis identified 96 TRGs significantly associated with OS. Subsequent Lasso-Cox stepwise regression analysis pinpointed eight TRGs (MCPH1, SLC25A6, STK19, PSAT1, KCTD15, DNMT3B, PSMD5, and TAF2) exhibiting robust predictive potential for patient survival. Both univariate and multivariate survival analyses unveiled TRG risk scores and age as independent prognostic variables. To refine the accuracy of survival prognosis, we developed both a nomogram integrating clinical parameters and a predictive risk score model based on TRGs. In subsequent investigations, associations were emphasized not solely regarding the TRG risk score and immune infiltration patterns but also concerning the response to immune-checkpoint inhibitor (ICI) therapy. In summary, the establishment of a telomere-associated genetic risk model offers a valuable tool for prognosticating AML outcomes, thereby facilitating informed treatment decisions.

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Purpose: This study aimed to investigate the maintenance effect of two puncture methods using non-coring needles in children with totally implantable venous access device (TIVAD). Methods: The 110 children who received TIVAD implantation for short bowel syndrome and solid tumors in our department from 2021.12 to 2022.12 were selected as the study subjects. Blinded method was used and divided into experimental group and control group according to random number table The experimental group underwent painless surround puncture method to place the needles and compound lidocaine ointment for topical anesthesia, while the control group underwent traditional puncture method to complete this operation. The effects of the two puncture methods on pain, catheter seal fluid volume, and catheter occlusion rate were evaluated using the Facial Pain Scale Revised, Behavioral Assessment Scale, and in vitro digital subtraction angiography test. Results: In the control group, the degree of puncture pain was mild in 5 patients, moderate in 19 patients, and severe in 28 patients; the amount of catheter sealing solution was 9.32 ± 1.32 mL, and the catheter occlusion rate was 25.00%. In the experimental group, the degree of puncture pain was mild in 16 patients, moderate in 22 patients, and severe in 16 patients; the amount of sealing solution was 7.66 ± 1.08 mL, and the blocking rate was 9.26%. The total pain score in the experimental group was lower than that in the control group (5.23±6.17 VS 7.89±2.38). The difference between the two groups had statistical significance (P < 0.05). Conclusion: The use of the painless surround puncture method can effectively reduce the pain experienced by children during puncture, decrease the volume of catheter sealing fluid, reduce the rate of catheter blockage, provide a valuable basis for enhancing the maintenance effect of TIVAD in clinical practice for children.

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Mechanically interlocked molecules (MIMs) including famous catenanes show switchable physical properties and attract continuous research interest due to their potential application in molecular devices. The advantages of using spin crossover (SCO) materials here are enormous, allowing for control through diverse stimuli and highly specific functions, and enabling the transfer of the internal dynamics of MIMs from solution to solid state, leading to macroscopic applications. Herein, we report the efficient self-assembly of catenated metal-organic frameworks (termed catena-MOFs) induced by stacking interactions, through the combination of rationally selected flexible and conjugated naphthalene diimide-based bis-pyridyl ligand (BPND), [MI(CN)2]- (M = Ag or Au) and Fe2+ in a one-step strategy. The obtained bimetallic Hofmann-type SCO-MOFs [FeII(BPND){Ag(CN)2}2]·3CHCl3 (1Ag) and [FeII(BPND{Au(CN)2}2]·2CHCl3·2H2O (1Au) possess a unique three-dimensional (3D) catena-MOF constructed from the polycatenation of two-dimensional (2D) layers with hxl topology. Both complexes undergo thermal- and light-induced SCO. Significantly, abnormal increases in the maximum emission intensity and dielectric constant can be detected simultaneously with the switching of spin states. This research opens up SCO-actuated bistable MIMs that afford dual functionality of coupled fluorescence emission and dielectricity.

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This study aims to investigate the mechanism of total saponins of Paridis Rhizoma in inducing the ferroptosis of MCF-7 cells and provide a theoretical basis for the clinical treatment of breast cancer with total saponins of Paridis Rhizoma. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the effects of different concentrations of total saponins of Paridis Rhizoma on the proliferation of MCF-7 cells. A phase contrast inverted microscope was used to observe the morphological changes of MCF-7 cells. The colony formation assay was employed to test the colony formation of MCF-7 cells. The lactate dehydrogenase(LDH) release test was conducted to determine the cell membrane integrity of MCF-7 cells. The cell scratch assay was employed to examine the migration of MCF-7 cells. After that, the level of reactive oxygen species(ROS) in MCF-7 cells was observed by an inverted fluorescence microscope, and the content of Fe~(2+) in MCF-7 cells was detected by the corresponding kit. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of MCF-7 cells. Western blot was employed to determine the expression of ferroptosis-related proteins, such as p53, solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long-chain family member 4(ACSL4), and transferrin receptor protein 1(TFR1) in MCF-7 cells. The results showed that 1.5, 3, 4.5, 6, 7.5, and 9 µg·mL~(-1) total saponins of Paridis Rhizoma significantly inhibited the proliferation of MCF-7 cells, with the IC_(50) of 4.12 µg·mL~(-1). Total saponins of Paridis Rhizoma significantly damaged the morphology of MCF-7 cells, leading to the formation of vacuoles and the gradual shrinkage and detachment of cells. Meanwhile, total saponins of Paridis Rhizoma inhibited the colony formation of MCF-7 cells, destroyed the cell membrane(leading to the release of LDH), and shortened the migration distance of MCF-7 cells. Total saponins of Paridis Rhizoma treatment significantly increased the content of ROS, induced oxidative damage, and led to the accumulation of Fe~(2+) in MCF-7 cells. Furthermore, total saponins of Paridis Rhizoma changed the mitochondrial structure, increased the mitochondrial membrane density, led to the decrease or even disappear of ridges, promoted the expression of p53 protein, down-regulated the expression of SLC7A11 and GPX4, and up-regulated the expression of ACSL4 and TFR1. In summary, total saponins of Paridis Rhizoma can significantly inhibit the proliferation and migration of MCF-7 cells and destroy the cell structure by inducing ferroptosis.

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Asari Radix et Rhizoma is a common drug for relieving exterior syndrome in clinics, but its toxicity limits its use. In this study, the mechanism of hepatic damage of Asari Radix et Rhizoma was studied by network pharmacology and metabolomics. The hepatic damage-related dataset, namely GSE54257 was downloaded from the GEO database. The Limma package was used to analyze the differentially expressed genes in the dataset GSE54257. Toxic components and target genes of Asari Radix et Rhizoma were screened by TCMSP, ECTM, and TOXNET. The hepatic damage target genes of Asari Radix et Rhizoma were obtained by mapping with the differentially expressed gene of GSE54257, and a PPI network was constructed. GO and KEGG enrichment analysis of target genes were performed, and a "miRNA-target gene-signal pathway" network was drawn with upstream miRNA information. Thirty rats were divided into a blank group, a high-dose Asari Radix et Rhizoma group, and a low-dose Asari Radix et Rhizoma group, which were administered once a day. After continuous administration for 28 days, liver function indexes and liver pathological changes were detected. Five liver tissue samples were randomly collected from the blank group and high-dose Asari Radix et Rhizoma group, and small molecule metabolites were analyzed by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS). The orthogonal partial least squares-discriminant analysis(OPLS-DA) method was used to screen differential metabolites, and enrichment analysis, correlation analysis, and cluster analysis were conducted for differential metabolites. Finally, the MetaboAnalyst platform was used to conduct pathway enrichment analysis for differential metabolites. It was found that there were 14 toxic components in Asari Radix et Rhizoma, corresponding to 37 target genes, and 12 genes related to liver toxicity of Asari Radix et Rhizoma were obtained by mapping to differentially expressed genes of GSE54257. The animal test results showed that Asari Radix et Rhizoma could significantly increase the liver function index, reduce the activity of the free radical scavenging enzyme, change the liver oxidative stress level, and induce lipid peroxidation damage in rats. The results of untargeted metabolomics analysis showed that compared with the blank group, nine metabolites were up-regulated, and 16 metabolites were down-regulated in the liver tissue of the Asari Radix et Rhizoma group. These 25 metabolites had strong correlations and good clustering. Pathway enrichment analysis showed that these differential metabolites and the 12 hepatotoxic target genes of Asari Radix et Rhizoma were mainly involved in purine metabolism, as well as the biosynthesis and metabolism of valine, leucine, glycine, serine, and threonine. The study confirmed that the hepatica damage effect of Asari Radix et Rhizoma was the result of multi-component, multi-target, and multi-signaling pathways, and its mechanism may be related to inhibiting nucleotide synthesis and affecting protein metabolism.

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Polymyxin is a lipopeptide antibiotic that is effective against multidrug-resistant Gram-negative bacteria. However, its clinical development is limited due to low titer and the presence of homologs. To address this, the polymyxin gene cluster was integrated into Bacillus subtilis, and sfp from Paenibacillus polymyxa was expressed heterologously, enabling recombinant B. subtilis to synthesize polymyxin B. Regulating NRPS domain inhibited formation of polymyxin B2 and B3. The production of polymyxin B increased to 329.7 mg/L by replacing the native promoters of pmxA, pmxB, and pmxE with PfusA, C2up, and PfusA, respectively. Further enhancement in this production, up to 616.1 mg/L, was achieved by improving the synthesis ability of 6-methyloctanoic acid compared to the original strain expressing polymyxin heterologously. Additionally, incorporating an anikasin-derived domain into the hybrid nonribosomal peptide synthase of polymyxin increased the B1 ratio in polymyxin B from 57.5% to 62.2%. Through optimization of peptone supply in the fermentation medium and fermentation in a 5.0-L bioreactor, the final polymyxin B titer reached 962.1 mg/L, with a yield of 19.24 mg/g maltodextrin and a productivity of 10.02 mg/(L·h). This study demonstrates a successful approach for enhancing polymyxin B production and increasing the B1 ratio through combinatorial metabolic engineering.

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This study aims to explore the associations and the underlying mechanism among dry eye disease (DED), air pollution, and meteorological conditions. DED is positively correlated with air pollutants (i.e., PM2.5, PM10, O3, NO2, CO, and SO2) and meteorological conditions (i.e., high altitude and wind speed), while negatively associated with relative humidity. Both low and high air temperatures effect DED. Atmospheric pollutants affect DED mainly through necroptosis or autophagy, inflammatory responses, and oxidative stress. Meteorological factors affect DED not only by their own affects but also by dispersing the concentration of air pollutants, and then reducing the negative exposure. In summary, this review may expand the understanding of the effects of air pollution and meteorological factors on DED and emphasize the importance of air environmental protection.

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Novel lead thiazole aminoguanidines exhibited strong activity against Gram-positive bacteria. The potential targets of these substances are undecaprenyl diphosphate synthase (UPPS) and undecaprenyl diphosphate phosphatase (UPPP). Here, we report the synthesis and antibacterial evaluation of a library of thiazole aminoguanidines analogues, wherein the rotatable bond is inserted between the C2 position of thiazole and hydrophobic group. The molecular flexibility is increased, and new analogues with strong activity against MRSA and E. coli are produced. The best compound 4i showed rapid sterilization and low tendency to induce bacterial resistance. The IC50 of compound 4i to EcUPPS enzyme is 145 µmol L-1 (58 µg mL-1). Compound 4i can also inhibit and destroy bacterial biofilms. These thiazole aminoguanidines can be developed as potential therapeutic candidates in the future.

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Polymyxin B, produced by Paenibacillus polymyxa, is used as the last line of defense clinically. In this study, exogenous mixture of precursor amino acids increased the level and proportion of polymyxin B1 in the total of polymyxin B analogs of P. polymyxa CJX518-AC (PPAC) from 0.15 g/L and 61.8 % to 0.33 g/L and 79.9 %, respectively. The co-culture of strain PPAC and recombinant Corynebacterium glutamicum-leu01, which produces high levels of threonine, leucine, and isoleucine, increased polymyxin B1 production to 0.64 g/L. When strains PPAC and C. glu-leu01 simultaneously inoculated into an optimized medium with 20 g/L peptone, polymyxin B1 production was increased to 0.97 g/L. Furthermore, the polymyxin B1 production in the co-culture of strains PPAC and C. glu-leu01 increased to 2.21 g/L after optimized inoculation ratios and fermentation medium with 60 g/L peptone. This study provides a new strategy to improve polymyxin B1 production.

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Heptanuclear {GdIII7} (complex 1) and tetradecanuclear {GdIII14} (complex 2) were synthesized using the rhodamine 6G ligand HL (rhodamine 6G salicylaldehyde hydrazone) and characterized. Complex 1 has a rare disc-shaped structure, where the central Gd ion is connected to the six peripheral GdIII ions via CH3O-/µ3-OH- bridges. Complex 2 has an unexpected three-layer double sandwich structure with a rare µ6-O2- ion in the center of the cluster. Magnetic studies revealed that complex 1 exhibits a magnetic entropy change of 17.4 J kg-1 K-1 at 3 K and 5 T. On the other hand, complex 2 shows a higher magnetic entropy change of 22.3 J kg-1 K-1 at 2 K and 5 T.

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OBJECTIVE: To explore the difference in temperature recovery following cold stimulation between participants with and without diabetes mellitus (DM). MATERIALS AND METHODS: The participants without (control group; n = 25) and with (DM group; n = 26) DM were subjected to local cold stimulation (10º C for 90 s). The thermal images of their hands were continuously captured using a thermal camera within 7 min following cold stimulation, and the highest temperature of each fingertip was calculated. According to the temperature values at different timepoints, the temperature recovery curves were drawn, and the baseline temperature (T-base), initial temperature after cooling (T0), temperature decline amplitude (T-range), and area under the temperature recovery curve > T0 (S) were calculated. Finally, symmetry differences between the two groups were analysed. RESULTS: No statistical differences in the T-base, T0, and T-range were observed between the DM and control groups. After drawing the rewarming curve according to the temperature of the fingertips of the patients following cold stimulation, the S in the DM group was significantly lower than that in the control group (p < 0.05). Furthermore, the asymmetry of the base temperature of the hand was observed in the DM group. CONCLUSIONS: Following cold stimulation, the patients with DM exhibited a different rewarming pattern than those without DM. Thus, cold stimulation tests under infrared thermography may contribute to the early screening of diabetic peripheral neuropathy in future.

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BACKGROUND: Cancer cell survival, proliferation, and metabolism are all intertwined with mitochondria. However, a complete description of how the features of mitochondria relate to the tumor microenvironment (TME) and immunological landscape of colorectal cancer (CRC) has yet to be made. We performed subgroup analysis on CRC patient data obtained from the databases using non-negative matrix factorization (NMF) clustering. Construct a prognostic model using the mitochondrial-related gene (MRG) risk score, and then compare it to other models for accuracy. Comprehensive analyses of the risk score, in conjunction with the TME and immune landscape, were performed, and the relationship between the model and different types of cell death, radiation and chemotherapy, and drug resistance was investigated. Results from immunohistochemistry and single-cell sequencing were utilized to verify the model genes, and a drug sensitivity analysis was conducted to evaluate possible therapeutic medicines. The pan-cancer analysis is utilized to further investigate the role of genes in a wider range of malignancies. METHODS AND RESULTS: We found that CRC patients based on MRG were divided into two groups with significant differences in survival outcomes and TME between groups. The predictive power of the risk score was further shown by building a prognostic model and testing it extensively in both internal and external cohorts. Multiple immune therapeutic responses and the expression of immunological checkpoints demonstrate that the risk score is connected to immunotherapy success. The correlation analysis of the risk score provide more ideas and guidance for prognostic models in clinical treatment. CONCLUSION: The TME, immune cell infiltration, and responsiveness to immunotherapy in CRC were all thoroughly evaluated on the basis of MRG features. The comparative validation of multiple queues and models combined with clinical data ensures the effectiveness and clinical practicality of MRG features. Our studies help clinicians create individualized treatment programs for individuals with cancer.

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Objective:To explore the effects of staged thematic painting therapy on positive emotions, alexithymia and self-efficacy in children with emotional disorders.Methods:This was a quasi-experimental study. By convenient sampling, 61 children with emotional disorders admitted from January 2022 to December 2022 to the Department of Child and Adolescent Psychology, Affiliated Psychological Hospital of Anhui Medical University were selected as the research objects, 31 patients admitted from January 2022 to June 2022 were listed as the control group and 30 patients admitted from July 2022 to December 2022 were listed as the observation group according to the time of admission.The control group was given routine psychiatric care, and the observation group was given staged thematic painting therapy on this basis. The intervention time was 6 weeks. The intervention effect was evaluated by Positive and Negative Affect Scale,Toronto Alexithymia Scale, and General Self-Efficacy Scale.Results:There were 15 males and 16 females in the control group, aged (14.19 ± 1.79) years old. There were 13 males and 17 females in the observation group, aged (14.47 ± 1.55) years old. The difference in baseline data between the two groups was not statistically significant ( P>0.05) and was comparable. There was no significant difference in the score of positive emotions, alexithymia and self-efficacy before intervention between the two groups (all P>0.05). After intervention, the scores of positive emotions and self-efficacy in the observation group were (43.20±7.41), (31.88 ± 5.42) points, which were higher than those in the control group (33.81 ± 6.92), (21.24 ± 5.41) points, the differences were statistically significant ( t=-6.19, -5.63, both P<0.05). After intervention, the scores of alexithymia in the observation group was (53.44 ± 4.68) points, which was lower than that in the control group (60.44 ± 5.52) points, the difference was statistically significant ( t=-8.72, P<0.05). Conclusions:Staged thematic painting therapy can effectively improve the positive emotions, self-efficacy and alexithymia level of children with emotional disorders, help the patients establish confidence to overcome the disease. It is valuable in clinical practice.

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As a new strategy for the application of sacubitril/valsartan (LCZ696) in patients with CKD, much evidence showed that it improved the prognosis of patients with CKD. This review summarizes the efficacy and safety of sacubitril/valsartan in physiology, pathology, pharmacology and clinical application by searching Wanfang, CNKI, PubMed and other databases for related articles on the application of sacubitril/valsartan in CKD patients. Although LBQ657, the active product of sacubitril, has a high drug accumulation in patients with moderate, severe renal injury, and ESRD, it is not cleared in hemodialysis, and has very little eliminated in peritoneal dialysis, which does not affect its safety. Compared with angiotensin converting enzyme inhibitor and angiotensin receptor blocker drugs, LCZ696 could increase the blood pressure control rate, improve cardiac function, slow down the decline of glomerular filtration rate, and significantly improve cardiovascular outcomes without more adverse events. Sacubitril/valsartan can be used in all levels of CKD patients complicated with hypertension and/or heart failure, with reliable safety and tolerance.

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Objective:To observe the effects of warming triple needling plus Chinese medication on inflammatory responses and daily functioning ability in patients with knee osteoarthritis(KOA)due to wind-cold-dampness Bi-impediment. Methods:A total of 101 patients with KOA due to wind-cold-dampness Bi-impediment were divided into an acupuncture-medication group and a Chinese medication group using the random number table method.Fifty cases in the Chinese medication group took oral Fang Feng Xi Bi Tang for treatment,and 51 cases in the acupuncture-medication group received additional warming triple needling therapy.The symptom score of traditional Chinese medicine(TCM),inflammatory factor levels,and motor function of the knee joint were compared before and after treatment.The clinical efficacy was also compared between the two groups after treatment. Results:Three cases in the acupuncture-medication group and 2 cases in the Chinese medication group dropped out during the study,and the two groups each had 48 cases being included in statistical analysis ultimately.The total effective rate was 95.8%in the acupuncture-medication group,higher than 79.2%in the Chinese medication group,and the between-group difference was statistically significant(P<0.05).After treatment,the TCM symptom score dropped in both groups(P<0.05)and was lower in the acupuncture-medication group than in the Chinese medication group(P<0.05).The levels of interleukin(IL)-6,tumor necrosis factor(TNF)-α,and IL-1β dropped after the intervention in both groups(P<0.05)and were lower in the acupuncture-medication group than in the Chinese medication group(P<0.05).The scores of knee pain intensity,knee joint stiffness,and diurnal functioning decreased after treatment in the two groups(P<0.05)and were lower in the acupuncture-medication group than in the Chinese medication group(P<0.05). Conclusion:Warming triple needling plus Fang Feng Xi Bi Tang can reduce inflammatory responses,improve daily functioning ability,and enhance the quality of life in patients with KOA due to wind-cold-dampness Bi-impediment.

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Hyperlipidemia is characterized by elevated levels of blood lipids. The clinical manifestations are mainly atherosclerosis caused by the deposition of lipids in the vascular endothelium. The link between abnormal lipid metabolism and sudden hearing loss remains unclear. This article presents a case study of sudden hearing loss accompanied by familial hyperlipidemia. Pure tone audiometry indicated intermediate frequency hearing loss in one ear. Laboratory tests showed abnormal lipid metabolism, and genetic examination identified a heterozygous mutation in theAPOA5 gene. Diagnosis: Sudden hearing loss; hypercholesterolemia. The patient responded well to pharmacological treatment. This paper aims to analyze and discuss thepotential connection between abnormal lipid metabolism and sudden hearing loss.

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As a major neuron type in the brain, the excitatory neuron (EN) regulates the lifespan in C. elegans. How the EN acquires senescence, however, is unknown. Here, we show that growth differentiation factor 11 (GDF11) is predominantly expressed in the EN in the adult mouse, marmoset and human brain. In mice, selective knock-out of GDF11 in the post-mitotic EN shapes the brain ageing-related transcriptional profile, induces EN senescence and hyperexcitability, prunes their dendrites, impedes their synaptic input, impairs object recognition memory and shortens the lifespan, establishing a functional link between GDF11, brain ageing and cognition. In vitro GDF11 deletion causes cellular senescence in Neuro-2a cells. Mechanistically, GDF11 deletion induces neuronal senescence via Smad2-induced transcription of the pro-senescence factor p21. This work indicates that endogenous GDF11 acts as a brake on EN senescence and brain ageing.

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