Tsunami Squares: Leapfrog scheme implementation and benchmark study on wave-shore interaction of solitary waves.

Impulse waves are generated by rapid subaerial mass movements including landslides, avalanches and glacier break-offs, which pose a potential risk to public facilities and residents along the shore of natural lakes or engineered reservoirs. Therefore, the prediction and assessment of impulse waves are of considerable importance to practical engineering. Tsunami Squares, as a meshless numerical method based on a hybrid Eulerian-Lagrangian algorithm, have focused on the simulation of landslide-generated impulse waves. An updated numerical scheme referred to as Tsunami Squares Leapfrog, was developed which contains a new smooth function able to achieve space and time convergence tests as well as the Leapfrog time integration method enabling second-order accuracy. The updated scheme shows improved performance due to a lower wave decay rate per unit propagation distance compared to the original implementation of Tsunami Squares. A systematic benchmark testing of the updated scheme was conducted by simulating the run-up, reflection and overland flow of solitary waves along a slope for various initial wave amplitudes, water depths and slope angles. For run-up, the updated scheme shows good performance when the initial relative wave amplitude is smaller than 0.4. Otherwise, the model tends to underestimate the run-up height for mild slopes, while an overestimation is observed for steeper slopes. With respect to overland flow, the prediction error of the maximum flow height can be limited to ± 50% within a 90% confidence interval. However, the prediction of the front propagation velocity can only be controlled to ± 100% within a 90% confidence interval. Furthermore, a sensitivity analysis of the dynamic friction coefficient of water was performed and a suggested range from 0.01 to 0.1 was given for reference.

Meteorin­like/meteorin­ß protects against cardiac dysfunction after myocardial infarction in mice by inhibiting autophagy.

Meteorin-ß (Metrnß) is a protein that is secreted by skeletal muscle and adipose tissue, and participates in cardiovascular diseases. However, its role in myocardial infarction (MI) has not been fully elucidated to date. The aim of the present study was to investigate the role and underlying mechanism of Metrnß in MI. In the present study, mice were subjected to left coronary ligation to induce a MI model before being injected with adeno-associated virus 9 (AAV9)-Metrnß to overexpress Metrnß. Mice were subjected to echocardiography and pressure-volume measurements 2 weeks after ligation. Cardiac injury was measured from the levels of cardiac troponin T and pro-inflammatory factors, which were detected using ELISA kits. Cardiac remodelling was determined from the cross-sectional areas detected using H&E and wheat germ agglutinin staining as well as from the transcriptional levels of hypertrophic and fibrosis markers detected using reverse transcription-quantitative PCR. Cardiac function was detected using echocardiography and pressure-volume measurements. In addition, H9c2 cardiomyocytes were transfected with Ad-Metrnß to overexpress Metrnß, before being exposed to hypoxia to induce ischaemic injury. Apoptosis was determined using TUNEL staining and caspase 3 activity. Cell inflammation was detected using ELISA assays for pro-inflammatory factors. Autophagy was detected using LC3 staining and assessing the protein level of LC3II using western blotting. H9c2 cells were also treated with rapamycin to induce autophagy. It was revealed that Metrnß expression was reduced in both mouse serum and heart tissue 2 weeks post-MI. Metrnß overexpression using AAV9-Metrnß delivery reduced the mortality rate, decreased the infarction size and reduced the extent of myocardial injury 2 weeks post-MI. Furthermore, Metrnß overexpression inhibited cardiac hypertrophy, fibrosis and inflammation post-MI. In ischaemic H9c2 cells, Metrnß overexpression using adenovirus also reduced cell injury, cell death and inflammatory response. Metrnß overexpression suppressed MI-induced autophagy in vitro. Following autophagy activation using rapamycin in vitro, the protective effects induced by Metrnß were reversed. Taken together, these results indicated that Metrnß could protect against cardiac dysfunction post-MI in mice by inhibiting autophagy.

Prediction of cross-border spread of the COVID-19 pandemic: A predictive model for imported cases outside China.

The COVID-19 pandemic has been present globally for more than three years, and cross-border transmission has played an important role in its spread. Currently, most predictions of COVID-19 spread are limited to a country (or a region), and models for cross-border transmission risk assessment remain lacking. Information on imported COVID-19 cases reported from March 2020 to June 2022 was collected from the National Health Commission of China, and COVID-19 epidemic data of the countries of origin of the imported cases were collected on data websites such as WHO and Our World in Data. It is proposed to establish a prediction model suitable for the prevention and control of overseas importation of COVID-19. Firstly, the SIR model was used to fit the epidemic infection status of the countries where the cases were exported, and most of the r2 values of the fitted curves obtained were above 0.75, which indicated that the SIR model could well fit different countries and the infection status of the region. After fitting the epidemic infection status data of overseas exporting countries, on this basis, a SIR-multiple linear regression overseas import risk prediction combination model was established, which can predict the risk of overseas case importation, and the established overseas import risk model overall P <0.05, the adjusted R2 = 0.7, indicating that the SIR-multivariate linear regression overseas import risk prediction combination model can obtain better prediction results. Our model effectively estimates the risk of imported cases of COVID-19 from abroad.

Associations of Heavy Metals with Cognitive Function: An Epigenome-Wide View of DNA Methylation and Mediation Analysis.

OBJECTIVE: Exposure to heavy metals has been reported to be associated with impaired cognitive function, but the underlying mechanisms remain unclear. This pilot study aimed to identify key heavy metal elements associated with cognitive function and further explore the potential mediating role of metal-related DNA methylation. METHODS: Blood levels of arsenic, cadmium, lead, copper, manganese, and zinc and genome-wide DNA methylations were separately detected in peripheral blood in 155 older adults. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE). Least absolute shrinkage and selection operator penalized regression and Bayesian kernel machine regression were used to identify metals associated with cognitive function. An epigenome-wide association study examined the DNA methylation profile of the identified metal, and mediation analysis investigated its mediating role. RESULTS: The MMSE scores showed a significant decrease of 1.61 (95% confidence interval [CI]: -2.64, -0.59) with each 1 standard deviation increase in ln-transformed arsenic level; this association was significant in multiple-metal models and dominated the overall negative effect of 6 heavy metal mixture on cognitive function. Seventy-three differentially methylated positions were associated with blood arsenic (p < 1.0 × 10-5). The methylation levels at cg05226051 (annotated to TDRD3) and cg18886932 (annotated to GAL3ST3) mediated 24.8% and 25.5% of the association between blood arsenic and cognitive function, respectively (all p < 0.05). INTERPRETATION: Blood arsenic levels displayed a negative association with the cognitive function of older adults. This finding shows that arsenic-related DNA methylation alterations are critical partial mediators that may serve as potential biomarkers for further mechanism-related studies. ANN NEUROL 2024.

Melanoma differentiation-associated protein 5 prevents cardiac hypertrophy via apoptosis signal-regulating kinase 1-c-Jun N-terminal kinase/p38 signaling.

Pathological cardiac hypertrophy (CH) is driven by maladaptive changes in myocardial cells in response to pressure overload or other stimuli. CH has been identified as a significant risk factor for the development of various cardiovascular diseases, ultimately resulting in heart failure. Melanoma differentiation-associated protein 5 (MDA5), encoded by interferon-induced with helicase C domain 1 (IFIH1), is a cytoplasmic sensor that primarily functions as a detector of double-stranded ribonucleic acid (dsRNA) viruses in innate immune responses; however, its role in CH pathogenesis remains unclear. Thus, the aim of this study was to examine the relationship between MDA5 and CH using cellular and animal models generated by stimulating neonatal rat cardiomyocytes with phenylephrine and by performing transverse aortic constriction on mice, respectively. MDA5 expression was upregulated in all models. MDA5 deficiency exacerbated myocardial pachynsis, fibrosis, and inflammation in vivo, whereas its overexpression hindered CH development in vitro. In terms of the underlying molecular mechanism, MDA5 inhibited CH development by promoting apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, thereby suppressing c-Jun N-terminal kinase/p38 signaling pathway activation. Rescue experiments using an ASK1 activation inhibitor confirmed that ASK1 phosphorylation was essential for MDA5-mediated cell death. Thus, MDA5 protects against CH and is a potential therapeutic target.

Administration with curcumin alleviates spinal cord ischemia-reperfusion injury by regulating anti-oxidative stress and microglia activation-mediated neuroinflammation via Nrf2/NF-κB axis.

Spinal cord ischemia-reperfusion injury (SCII) ranks as the common complication after aortic surgery, usually leading to devastating post-operative paraplegia. Microglia over-activation and neuronal cell loss are key pathological features of SCII. Curcumin is involved in several I/R injuries. However, its underlying mechanism in SCII remains elusive. Here, curcumin attenuated oxygen and glucose deprivation/reoxygenation (OGD/R)-induced oxidative injury in PC12 neuronal cells by increasing cell viability, inhibiting cell apoptosis, lactate dehydrogenase, malondialdehyde levels, but elevating anti-oxidative superoxide dismutase and glutathione peroxidase levels. Furthermore, curcumin restrained OGD/R-evoked microglia M1 activation by decreasing microglia M1 polarization marker IBA-1 and iNOS transcripts. Moreover, the increased inflammatory cytokine levels of TNF-α and IL-6 in microglia under OGD/R conditions were suppressed after curcumin treatment. Importantly, neuronal cells incubated with a conditioned medium from OGD/R-treated microglia exhibited lower cell viability and higher apoptotic ratio, which were overturned when microglia were treated with curcumin. Intriguingly, curcumin could inhibit the activation of the NF-κB pathway by Nrf2 enhancement in OGD/R-treated PC12 cells and microglia. Notably, targeting Nrf2 signaling reversed the protective efficacy of curcumin against OGD/R-evoked oxidative insult in neuronal, microglia M1 activation, inflammatory response, and microglial activation-evoked neuronal death. In vivo, curcumin improved histopathologic injury and neurologic motor function in SCII rats and attenuated oxidative stress, microglia activation and neuroinflammation in spinal cord tissues, and activation of the Nrf2/NF-κB pathway. Thus, curcumin may alleviate SCII by mitigating I/R-evoked oxidative injury in neuron and microglia activation-induced neuroinflammation and neuron death through Nrf2/NF-κB signaling, supporting a promising therapeutic agent for SCII.

Identification of prosthetic joint infection by Candida using metagenomic shotgun sequencing.

Background: Periprosthetic joint infection (PJI) is a serious complication after total knee arthroplasty. Fungal infections are prone to biofilm formation, which makes it hard to diagnose and clarify the pathogenic species. Case Presentation: This case study provides evidence of a novel PJI pathogen that is otherwise difficult to detect using conventional methods. A patient was reviewed with persistent postoperative pain, swelling and eventually drainage around the left knee after undergoing a bilateral total knee arthroplasty 2 years previously for progressive osteoarthritis. By using metagenomic shotgun sequencing to analyse both bacterial and fungal agent sequences, we were able to identify fungal strains of Candida tropicalis, a rarely reported and difficult-to-culture PJI pathogen. Conclusion: Metagenomic shotgun sequencing enables the detection of difficult-to-detect pathogens and the formulation of treatment recommendations for fungal infections with low positive rates based on gene content analysis.

Deciphering the Mechanism of Xijiao Dihuang Decoction in Treating Psoriasis by Network Pharmacology and Experimental Validation.

Purpose: This study aims to confirm the efficacy of Xijiao Dihuang decoction (XJDHT), a classic prescription, in treating psoriasis and to explore the potential therapeutic mechanism. Methods: For pharmacodynamic analysis, a mouse model of imiquimod cream (IMQ)-induced psoriasis was constructed. Active ingredients and genes of XJDHT, as well as psoriasis-related targets, were obtained from public databases. Intersecting genes (IGEs) of XJDHT and psoriasis were collected by Venn Diagram. A protein-protein interaction (PPI) network of IGEs is constructed through the STRING database. The Molecular Complex Detection (MCODE) and Cytohubba plug-ins of Cytoscape software were used to identified hub genes. In addition, we conducted enrichment analysis of IGEs using the R package clusterProfiler. Hub genes were validated via external GEO databases. The influence of XJDHT on Hub gene expression was examined by qPCR and ELISA, and molecular docking was used to evaluate the binding efficacy between active ingredients and hub genes. Results: The results revealed that XJDHT possesses 92 potential genes for psoriasis, and 8 Hub genes were screened. Enrichment analysis suggested that XJDHT ameliorate psoriasis through multiple pathways, including AGE-RAGE, HIF-1, IL-17 and TNF signaling pathway. Validation data confirmed the differential expression of IL6, VEGFA, TNF, MMP9, STAT3, and TLR4. Molecular docking revealed a strong affinity between active ingredients and Hub genes. The efficacy of XJDHT in improving psoriatic lesions in model mice was demonstrated by PASI score and HE staining, potentially attributed to the down-regulation of VEGFA, MMP9, STAT3, TNF, and IL-17A, as evidenced by ELISA and qPCR. Conclusion: This study employed network pharmacology and in vitro experiments to identify the potential mechanisms underlying the therapeutic effects of XJDHT on psoriasis, providing a new theoretical basis for its clinical application in the treatment of psoriasis.

TRIM-containing 44 aggravates cardiac hypertrophy via TLR4/NOX4-induced ferroptosis.

TRIM-containing 44 (TRIM44) is a promoter of multiple cancers. However, its role in cardiac hypertrophy has not been elucidated. This study explored the role of TRIM44 on pressure overload-induced cardiac hypertrophy in mice. Mice were subjected to aortic banding to establish an adverse cardiac hypertrophy model, followed by the administration of AAV9-TRIM44 or AAV9shTRIM44 to overexpress or knock down TRIM44. Echocardiography was used to assess cardiac function. H9c2 cells were cultured and transfected with either Ad-TRIM44 or TRIM44 siRNA to overexpress or silence TRIM44. Cells were also stimulated with angiotensin II to establish a cardiomyocyte hypertrophy model. Results indicated that TRIM44 was downregulated in mice hearts and cardiomyocytes that were treated with aortic banding or angiotensin II. TRIM44 overexpression in mice hearts aggravated cardiac hypertrophy and fibrosis, as well as inhibited cardiac function post-aortic banding. Moreover, mice with TRIM44 overexpression displayed increased ferroptosis post-aortic banding. Mice with TRIM44 knockdown revealed ameliorated cardiac hypertrophy, ferroptosis, and fibrosis, as well as improved cardiac function post-aortic banding. In H9c2 cells transfected with Ad-TRIM44, angiotensin II-induced ferroptosis was enhanced, while cells with silenced TRIM44 reported reduced ferroptosis post-angiotensin II administration. Furthermore, TRIM44 interacted with TLR4, which increased the expression of NOX4 and subsequently augmented ferroptosis-associated protein levels. By using TLR4 knockout mice, the inhibitory role of TRIM44 was reduced post-aortic banding. Taken together, TRIM44 aggravated pressure overload-induced cardiac hypertrophy via increased TLR4/NOX4-associated ferroptosis. KEY MESSAGES: TRIM44 could aggregate pressure overload-induced cardiac hypertrophy via increasing TLR4-NOX4 associated ferroptosis. Target TRIM44 may become a new therapeutic method for preventing or treating pressure overload-induced cardiac hypertrophy.

Never in mitosis gene A-related kinase-6 deficiency deteriorates diabetic cardiomyopathy via regulating heat shock protein 72.

NIMA (never in mitosis, gene A)-related kinase-6 (NEK6), a cell cycle regulatory gene, was found to regulate cardiac hypertrophy. However, its role in diabetes-induced cardiomyopathy has not been fully elucidated. This research was designed to illustrate the effect of NEK6 involved in diabetic cardiomyopathy. Here we used a streptozotocin (STZ)-induced mice diabetic cardiomyopathy model and NEK6 knockout mice to explore the role and mechanism of NEK6 in diabetic-induced cardiomyopathy. NEK6 knockout mice and wild-type littermates were subjected to STZ injection (50 mg/kg/day for 5 days) to induce a diabetic cardiomyopathy model. As a result, 4 months after final STZ injection, DCM mice revealed cardiac hypertrophy, fibrosis, and systolic and diastolic dysfunction. NEK6 deficiency causes deteriorated cardiac hypertrophy, fibrosis, and cardiac dysfunction. Furthermore, we observed inflammation and oxidative stress in the hearts of NEK6 deficiency mice under diabetic cardiomyopathy pathology. Adenovirus was used to upregulate NEK6 in neonatal rat cardiomyocytes, and it was found that NEK6 ameliorated high glucose-induced inflammation and oxidative stress. Our findings revealed that NEK6 increased the phosphorylation of heat shock protein 72 (HSP72) and increased the protein level of PGC-1α and NRF2. Co-IP assay experiment confirmed that NEK6 interacted with HSP72. When HSP72 was silenced, the anti-inflammation and anti-oxidative stress effects of NEK6 were blurred. In summary, NEK6 may protect diabetic-induced cardiomyopathy by interacting with HSP72 and promoting the HSP72/PGC-1α/NRF2 signaling. KEY MESSAGES: NEK6 knockout deteriorated cardiac dysfunction, cardiac hypertrophy, fibrosis as well as inflammation response, and oxidative stress. NEK6 overexpression attenuated high glucose induced inflammation and oxidative stress. The underlying mechanisms of the protective role of NEK6 in the development of diabetic cardiomyopathy seem to involve the regulation of HSP72-NRF2- PGC-1α pathway. NEK6 may become a new therapeutic target for diabetic cardiomyopathy.

Research trends of platelet-rich plasma therapy on knee osteoarthritis from 2011 to 2021: A review.

BACKGROUND: Platelet-rich plasma (PRP) has been widely used to alleviate osteoarthritis of the knee, and research results are abundant. However, there are no bibliometric reports in publications in this field. Therefore, the current status of PRP for the treatment of osteoarthritis of the knee from 2011 to 2021 was analyzed using Citespace 6.1.R2 software. METHODS: Publications regarding PRP treating Knee Osteoarthritis between 2011 and 2021 were extracted from the Web of Science database. CiteSpace was used to analyze the number of publications, countries, institutions, journals, authors, cited references, and keywords by using standard bibliometric indicators. RESULTS: A total of 988 publications were searched from 2011 to 2021. In the last decade, the number of publications has increased in the field. Brian J. Cole was the author with the most output, with 31 relevant articles, and Giuseppe Filardo ranked first in cited authors. Am J Sport Med was the most cited journal. In this field, the most prolific country is the United States and the most prolific institution is Rush University. An article published by Sandeep Patel ranked first in cited references with 118 citations. "Randomized controlled trial" was the most bursting keyword and other more popular keywords about PRP for knee osteoarthritis: "hyaluronic acid," "double-blind," and "mesenchymal stem cell." CONCLUSION: This bibliometric study provides a decade of current clinical research on PRP for the treatment of osteoarthritis of the knee, which can help researchers understand the hot spots in the field and provide a new direction for their research.

HMGB1 accumulation in cytoplasm mediates noise-induced cochlear damage.

Damage-associated molecular pattern molecules (DAMPs) play a critical role in mediating cochlear cell death, which leads to noise-induced hearing loss (NIHL). High-mobility group box 1 (HMGB1), a prototypical DAMP released from cells, has been extensively studied in the context of various diseases. However, whether extracellular HMGB1 contributes to cochlear pathogenesis in NIHL and the potential signals initiating HMGB1 release from cochlear cells are not well understood. Here, through the transfection of the adeno-associated virus with HMGB1-HA-tag, we first investigated early cytoplasmic accumulation of HMGB1 in cochlear hair cells after noise exposure. We found that the cochlear administration of HMGB1-neutralizing antibody immediately after noise exposure significantly alleviated hearing loss and outer hair cells (OHCs) death induced by noise exposure. In addition, activation of signal transducer and activators of transcription 1 (STAT1) and cellular hyperacetylation were verified as potential canonical initiators of HMGB1 cytoplasmic accumulation. These findings reveal the adverse effects of extracellular HMGB1 on the cochlea and the potential signaling events mediating HMGB1 release in hair cells, indicating multiple potential pharmacotherapeutic targets for NIHL.

Cross-sectional and longitudinal associations of urinary zinc with glucose-insulin homeostasis traits and type 2 diabetes: Exploring the potential roles of systemic inflammation and oxidative damage in Chinese urban adults.

The link between zinc exposure and glucose metabolism or the development of type 2 diabetes (T2D) is controversial, and underlying mechanisms are unclear. This study aimed to explore the associations of zinc exposure with glucose-insulin homeostasis traits and the long-term effects of zinc on the development of T2D, and further to estimate the potential roles of inflammation and oxidative damage in such relationships. We investigated 3890 urban adults from the Wuhan-Zhuhai cohort, and followed up every three years. Mixed linear model was applied to estimate dose-response associations between urinary zinc and glycemia traits [fasting plasma insulin (FPI), fasting plasma glucose (FPG), insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR), and ß-cell dysfunction (homeostasis model assessment of ß-cell function, HOMA-B)], as well as zinc and biomarkers for systemic inflammation (C-reactive protein) and oxidative damage (8-isoprostane and 8-hydroxy-2'-deoxyguanosine). Logistic regression model and Cox regression model were conducted to evaluate the relationships between urinary zinc and prevalence and incidence of T2D, respectively. We further performed mediation analysis to assess the roles of inflammation and oxidative damage biomarkers in above associations. At baseline, we observed significant dose-response relationships of elevated urinary zinc with increased FPI, FPG, HOMA-IR, and T2D prevalence and decreased HOMA-B, and such associations could be strengthened by increased C-reactive protein, 8-isoprostane, and 8-hydroxy-2'-deoxyguanosine. Elevated C-reactive protein significantly mediated 9.09% and 17.67% of the zinc-related FPG and HOMA-IR increments, respectively. In longitudinal analysis, a significantly positive association between urinary zinc and T2D incidence was observed among subjects with persistent high urinary zinc levels when compared with those with persistent low zinc levels. Our results suggested that high levels of zinc exposure adversely affected on glucose-insulin homeostasis and further contributed to increased risk of T2D cross-sectionally and longitudinally. Moreover, inflammatory response might play an important role in zinc-related glucose metabolic disorder.

The complete chloroplast genome sequence of Litsea coreana var. lanuginosa (Lauraceae): genome structure and phylogenetic analysis.

Litsea coreana var. lanuginose is a perennial, indeciduous, and broad-leaved tree used as an essential medicinal and edible plant. In addition, this species is well-known for its leaves are rich in aromatic oil. In this study, we firstly assembled and characterized the complete chloroplast genome of L. coreana var. lanuginose using Illumina pair-end sequencing and performed a phylogenetic analysis with other 13 species in Lauraceae. The results revealed that its chloroplast genome was 152,859 bp in total length with 39% of GC content, containing a pair of inverted repeats of 20,084 bp (IRA and IRB), separated by a large single-copy (LSC) region of 93,795 bp and a small single-copy (SSC) region of 18,896 bp. The plastid genome of L. coreana var. lanuginose encoded 125 genes, including 81 protein-coding genes, 36 transfer RNA (tRNA), and eight ribosomal RNA (rRNA) genes. The phylogenetic analysis suggested that L. coreana var. lanuginose was closely related to the clade of Litsea monopetala, Litsea garrettii, and Litsea elongate in Lauraceae family.

Bone-turnover biomarkers as potential prognostic factors in sudden sensorineural hearing loss: A prospective cohort study.

Objectives: This study aims to explore the relationship between bone-turnover biomarkers and the recovery of SSNHL to provide clues for further improvements in etiological research and predictors. Methods: The medical history, hearing thresholds, biomarkers of bone-turnover, and related hormones of 117 SSNHL patients were collected prospectively between August 2018 and December 2021. Linear correlation and logistic regression models were applied to examine the association between bone-turnover biomarkers and the prognosis of SSNHL. Results: Age, the incidence of vertigo, pure tone average of the impaired frequencies (PTAimpairedfre), and the levels of bone turnover [including alkaline phosphatase (ALP), ß-carboxy terminal crosslinked telopeptide of type 1 collagen (ß-CTX), and N-terminal-midfragment of osteocalcin (N-MID)] were higher in the nonresponders than responders (P < 0.05). Logistic regression showed that the age (OR = 1.035, P = 0.027), time to treatment (OR = 1.157, P = 0.038), PTAimpairedfre (OR = 1.031, P = 0.008), and ß-CTX (OR = 1.004, P = 0.001) were independent risk factors for the prognosis of SSNHL. In the women SSNHL subgroup, age, postmenopause percentage, PTAimpairedfre, the activity of ALP, levels of ß-CTX, and N-MID were significantly higher in the nonresponders than the responders (P < 0.05). Compared to the men SSNHL subgroup, ß-CTX has a higher correlation coefficient and predictive efficiency in the women SSNHL subgroup, and logistic regression showed that ß-CTX (OR = 1.004, P = 0.004) was an independent risk factor for the women SSNHL. Conclusions: Bone-turnover biomarkers are risk factors for poor prognosis in SSNHL, especially ß-CTX. The differences were significant in women SSNHL, which may be related to the rapid regression of estrogen after menopause that leads to the occurrence of osteoporosis with a high conversion rate.

Associations of Heavy Metals with Activities of Daily Living Disability: An Epigenome-Wide View of DNA Methylation and Mediation Analysis.

BACKGROUND: Exposure to heavy metals has been reported to be associated with multiple diseases. However, direct associations and potential mechanisms of heavy metals with physical disability remain unclear. OBJECTIVES: We aimed to quantify associations of heavy metals with physical disability and further explore the potential mechanisms of DNA methylation on the genome scale. METHODS: A cross-sectional study of 4,391 older adults was conducted and activities of daily living (ADL) disability were identified using a 14-item scale questionnaire including basic and instrumental activities to assess the presence of disability (yes or no) rated on a scale of dependence. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated to quantify associations between heavy metals and ADL disability prevalence using multivariate logistic regression and Bayesian kernel machine regression (BKMR) models. Whole blood-derived DNA methylation was measured using the HumanMethylationEPIC BeadChip array. An ADL disability-related epigenome-wide DNA methylation association study (EWAS) was performed among 212 sex-matched ADL disability cases and controls, and mediation analysis was further applied to explore potential mediators of DNA methylation. RESULTS: Each 1-standard deviation (SD) higher difference in log10-transformed manganese, copper, arsenic, and cadmium level was significantly associated with a 14% (95% CI: 1.05, 1.24), 16% (95% CI:1.07, 1.26), 22% (95% CI:1.13, 1.33), and 15% (95% CI:1.06, 1.26) higher odds of ADL disability, which remained significant in the multiple-metal and BKMR models. A total of 85 differential DNA methylation sites were identified to be associated with ADL disability prevalence, among which methylation level at cg220000984 and cg23012519 (annotated to IRGM and PKP3) mediated 31.0% and 31.2% of manganese-associated ADL disability prevalence, cg06723863 (annotated to ESRP2) mediated 32.4% of copper-associated ADL disability prevalence, cg24433124 (nearest to IER3) mediated 15.8% of arsenic-associated ADL disability prevalence, and cg07905190 and cg17485717 (annotated to FREM1 and TCP11L1) mediated 21.5% and 30.5% of cadmium-associated ADL disability prevalence (all p<0.05). DISCUSSION: Our findings suggested that heavy metals contributed to higher prevalence of ADL disability and that locus-specific DNA methylation are partial mediators, providing potential biomarkers for further cellular mechanism studies. https://doi.org/10.1289/EHP10602.

Hyperbranched Tetraphenylethylene Derivatives with Low Non-specific Aggregation-Induced Emission for Fluorescence Recognition of Proteins with Hydrophobic Pockets.

Proteins play an important role in the physiological process of many organisms, and their abnormal level often indicates the occurrence of some diseases. Therefore, protein analysis has important reference value and clinical significance for early diagnosis and therapy of disease. Using human serum albumin (HSA) as a model protein, a series of super-branched tetraphenylethylene (TPE) derivatives with different branching structures and terminal groups are reported herein for highly sensitive and specific recognition of proteins with hydrophobic cages. Benefiting from the hyperbranched structures, these probes showed much higher critical micelle concentrations (CMCs) than most linear TPE-based amphiphilic molecules since the hyperbranched structure not only improved their solubility but also amplified the steric hindrance effect and electrostatic repulsive force to prevent their aggregation. Dynamic light scattering experiments proved that these probes formed dense aggregates at CMC, and such aggregate structures would lead to a higher background fluorescence noise. Hence, a higher CMC is more conducive to the detection of the target with low backgrounds. Among them, P3-COOH with -COOH as the terminal unit and a relatively longer branch showed the highest CMC and the best signal to background ratio (S/N). Mechanism studies showed that P3-COOH was bound to HSA mainly through a hydrophobic force, resulting in a limited P3-COOH molecular movement and less attack from quenchers in solutions, thus leading to greatly enhanced fluorescence intensity. In addition, P3-COOH was also applied to the determination of HSA content in actual human serum samples.

The nickel phosphate rods derived from Ni-MOF with enhanced electrochemical activity for non-enzymatic glucose sensing.

In this work, spherical Ni-based metal-organic frameworks (Ni-MOFs) were used as precursors for preparing nanorod-like nickel phosphate (r-NiPO) with enhanced electro-catalytic properties in detection of glucose. It was found that the addition of nickel ion has a profound effect on construction of nickel phosphate with flower-like, rod-like, and ribbon-like structure in presence of H2PO2-. The r-NiPO consisted of multiple phases of nickel phosphate showed porous, interconnected structure and abundant active Ni(II)/Ni(III) pairs, which was beneficial to facilitate glucose oxidation. In comparison with Ni-MOF, r-NiPO exhibited the superior electrocatalytic property on oxidation of glucose because of the exposing more active Ni sites in r-NiPO than that of Ni-MOF precursor. r-NiPO modified glassy carbon electrode (r-NiPO/GCE) showed a good linear response to glucose from 1.0 µM to 3.0 mM with a high sensitivity of 3169 µA mM-1 cm-2. In addition, r-NiPO/GCE can be used to detect glucose in human serum with satisfactory recoveries (90-97%).

Salubrinal Protects Against Cisplatin-Induced Cochlear Hair Cell Endoplasmic Reticulum Stress by Regulating Eukaryotic Translation Initiation Factor 2α Signalling.

Objective: Cisplatin is a broad-spectrum anti-tumour drug commonly used in clinical practice. However, its ototoxicity greatly limits its clinical application, and no effective method is available to prevent this effect. Endoplasmic reticulum stress (ERS) is reportedly involved in cisplatin ototoxicity, but the exact mechanism remains unclear. Therefore, this study aimed to investigate the role of eukaryotic translation initiation factor 2α (eIF2α) signalling and its dephosphorylation inhibitor salubrinal in cisplatin ototoxicity. Methods: We evaluated whether salubrinal could protect against cisplatin-induced damage in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and mouse cochlear explants. By knocking down eIF2α, we elucidated the vital role of eIF2α in cisplatin-induced damage in HEI-OC1 cells. Whole-mount immunofluorescent staining and confocal microscopy of mouse cochlear explants and HEI-OC1 cells were performed to analyse cisplatin-induced damage in cochlear hair cells and the auditory cell line. Results: Data suggested salubrinal attenuated cisplatin-induced hair cell injury by inhibiting apoptosis. In addition, salubrinal significantly reduced ERS levels in hair cells via eIF2α signalling, while eIF2α knockdown inhibited the protective effect of salubrinal. Significance: Salubrinal and eIF2α signalling play a role in protecting against cisplatin-induced ototoxicity, and pharmacological inhibition of eIF2α-mediated ERS is a potential treatment for cisplatin-induced damage in the cochlea and HEI-OC1 cells.

Effect Analysis of Clinical Pathway Nursing Combined with Humanized Nursing in Cerebral Infarction.

Objective: To make the application effect of clinical pathway nursing combined with humanized nursing clear in cerebral infarction. Methods: Hundred patients who suffered from cerebral infarction had been hospitalized in our hospital and they become our study objects. By means of the random number table, they were separated into 50 cases both in the control group and in the observation group. The control group accepted the routine nursing, and the observation group accepted the clinical pathway nursing mixed with humanized nursing. The followings were compared including the hospitalization expenses and length of stay, National Institutes of Health Stroke Scale (NIHSS), Barthel index rating scale (BI), Fugl-Meyer Assessment (FMA), and the incidence of complications and recurrence rate. A comparison was made between the two groups about satisfaction with nursing. Results: In contrast with the control group, the treatment expenses and length of stay in the observation group were considerably reduced (P < 0.05). In contrast, before nursing, the NIHSS marks of the two groups decreased considerably after nursing, and the scores of BI and FMA increased considerably, the NIHSS scores of the observation group were considerably lower than those of the control group, and the scores of BI and FMA were considerably higher than those of the control group (P < 0.05). In contrast with the control group (44.00%, 12.00%), the incidence of complications (22.00%) and recurrence rate (2.00%) in the observation group were considerably lower (P < 0.05). In contrast with the control group (72.00%), the satisfaction of nursing in the observation group (96.00%) was considerably higher (P < 0.05). Conclusion: The application effect of clinical pathway nursing combined with humanized nursing in cerebral infarction is significant. It can not only effectively reduce hospitalization expenses and hospitalization time, improve neurological function, ability of daily living, and limb motor function but also reduce complications and recurrence and improve patients' satisfaction with nursing, which has a high clinical reference value.