Evolution of the Moral Lexicon.

Morality is central to social well-being and cognition, and moral lexicon is a key device for human communication of moral concepts and experiences. How was the moral lexicon formed? We explore this open question and hypothesize that words evolved to take on abstract moral meanings from concrete and grounded experiences. We test this hypothesis by analyzing semantic change and formation of over 800 words from the English Moral Foundations Dictionary and the Historical Thesaurus of English over the past hundreds of years. Across historical text corpora and dictionaries, we discover concrete-to-abstract shifts as words acquire moral meaning, in contrast with the broad observation that words become more concrete over time. Furthermore, we find that compound moral words tend to be derived from a concrete-to-abstract shift from their constituents, and this derivational property is more prominent in moral words compared to alternative compound words when word frequency is controlled for. We suggest that evolution of the moral lexicon depends on systematic metaphorical mappings from concrete domains to the moral domain. Our results provide large-scale evidence for the role of metaphor in shaping the historical development of the English moral lexicon.

Study on the differentiation of sensory quality of mainstream Jiang-flavor baijiu in the Chinese market based on Pivot Profile.

Jiang-flavor baijiu (JFB) is a prominent type of Chinese baijiu, known for its unique flavor attributes, sensory experience, and high tasting value. Previous research has mainly focused on the detection and identification of its flavor substances, but in-depth studies on the precise sensory description and differentiation of its flavor qualities are still lacking. In this study, a rapid sensory analysis method, Pivot Profile (PP), was applied to 30 mainstream JFBs in the Chinese market, generating 91 sensory attributes with independent definitions, from which 29 main sensory attributes were established that were easy to perceive and descriptive, as well as convenient for transmitting their sensory qualities and distinguishing differences in price and production region, including color (one descriptor), aroma (21 descriptors), taste, and mouthfeel (seven descriptors). The nine key sensory attributes that distinguish JFB quality are as follows: Jiang, Grain, Chen, Qu, Rancid, Acid, Sweet, Fullness, and Harmony. It was found that price was positively correlated with sensory quality, with greater variation in the quality of samples within the medium price range (RMB 500-1000). All samples from MTCQ1 (the core production area of Maotai Town) performed better in sensory quality. In addition, salted vegetable showed a high degree of regional characteristics, concentrated in most of the production regions of Guizhou Province. Aroma attributes were more suitable than taste and mouthfeel as sensory indicators for distinguishing production regions. This study has opened the direction of systematic construction of sensory description of JFB and provided a successful case for the evaluation of Chinese baijiu using novel sensory analysis techniques.

Unsupervised Hyperspectral and Multispectral Image Blind Fusion Based on Deep Tucker Decomposition Network With Spatial-Spectral Manifold Learning.

Hyperspectral image (HSI) and multispectral image (MSI) fusion aims to generate high spectral and spatial resolution hyperspectral image (HR-HSI) by fusing high-resolution multispectral image (HR-MSI) and low-resolution hyperspectral image (LR-HSI). However, existing fusion methods encounter challenges such as unknown degradation parameters, and incomplete exploitation of the correlation between high-dimensional structures and deep image features. To overcome these issues, in this article, an unsupervised blind fusion method for LR-HSI and HR-MSI based on Tucker decomposition and spatial-spectral manifold learning (DTDNML) is proposed. We design a novel deep Tucker decomposition network that maps LR-HSI and HR-MSI into a consistent feature space, achieving reconstruction through decoders with shared parameters. To better exploit and fuse spatial-spectral features in the data, we design a core tensor fusion network (CTFN) that incorporates a spatial-spectral attention mechanism for aligning and fusing features at different scales. Furthermore, to enhance the capacity to capture global information, a Laplacian-based spatial-spectral manifold constraint is introduced in shared-decoders. Sufficient experiments have validated that this method enhances the accuracy and efficiency of hyperspectral and multispectral fusion on different remote sensing datasets. The source code is available at https://github.com/Shawn-H-Wang/DTDNML.

The Predictive Value of SII Combined with UHR for Contrast-Induced Acute Kidney Injury in Patients with Acute Myocardial Infarction After Percutaneous Coronary Intervention.

Background: Contrast-induced acute kidney injury (CI-AKI) refers to the acute renal dysfunction caused by the injection of contrast agents. CI-AKI is currently a common complication after percutaneous coronary intervention (PCI). Objective: To investigate the predictive value of the combined systemic inflammatory index (SII) and urate/high-density lipoprotein cholesterol ratio (UHR) for CI-AKI after PCI in patients with AMI. Methods: A total of 1222 patients with AMI who underwent PCI were randomly divided into a training group and a validation group in an 8:2 ratio. According to the definition of CI-AKI diagnostic criteria, the training group was divided into CI-AKI group and non-CI-AKI group. Collect patient's blood and biochemical data, then calculate SII and UHR. The risk factors for CI-AKI were identified using LASSO and multivariate logistic regression analyses. A predictive column was created by using R language.Evaluate the predictive value of SII, UHR and their combination for CI-AKI after PCI using the area under the ROC curve (AUC). Results: Diabetes, Cystatin C, Diuretics, UHR, and LnSII were independent risk factors for CI-AKI in AMI patients after PCI. The ROC curve showed that the AUC of UHR and SII combined for predicting CI-AKI in AMI patients after PCI was 0.761 (95% CI: 0.709-0.812), with a sensitivity of 65.20% and a specificity of 76.70%, which was better than the prediction by either factor alone. Conclusion: High SII and high UHR are risk factors for AMI, and their combination can improve the accuracy of predicting CI-AKI in AMI patients after PCI.The prognosis of CI-AKI in AMI patients is worse than in the general population.

Systematic screening of protein-coding gene expression identified VWF as a potential key regulator in anthracycline-based chemotherapy-exacerbated metastasis of breast cancer.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer worldwide. Although major treatments represented by chemotherapy have shown effectiveness at the initial period, recurrence and metastasis still occur later after treatments. The alternation of the tumor microenvironment by chemotherapy is confirmed as a trigger of the elevated proliferation and migration of the remaining tumor cells. METHODS: Using bioinformatic methods, differential gene expression analysis was used to determine DEGs between post-chemotherapy and pre-chemotherapy samples of breast cancer patients, followed by survival analysis and ELISA analysis of the potential key genes. An in vitro model of 2 breast cancer cells lines was used to demonstrate the role of VWF in the evasion and migration of breast cancer cells, using cell migration, evasion and wound healing assays, PCR and molecular docking analysis. RESULTS: 19 hub genes were further identified using GO and KEGG pathway analyses and WGCNA. The 5 secreted protein-coding genes with reported carcinogenesis effects (VWF, SVEP1, DPT, ADIPOQ, and LPL) were further analyzed in breast cancer patients and VWF was identified as a potential key regulator in the anthracycline-based chemotherapy-exacerbated metastasis. It was further confirmed that anthracycline-based chemotherapeutics doxorubicin exacerbated VWF upregulation and the evasion and migration of breast cancer cells. Based on molecular docking analysis and previous study, berberine was used as an inhibitor of VWF, and showed an effective inhibition of the doxorubicin-exacerbated VWF upregulation, migration and evasion in breast cancer. CONCLUSIONS: Doxorubicin-exacerbated evasion and migration through VWF upregulation. Berberine as an inhibitor of VWF was able to reversed the doxorubicin-exacerbated VWF upregulation and evasion and migration in breast cancer cells.

HDAC inhibitor SAHA enhances antitumor immunity via the HDAC1/JAK1/FGL1 axis in lung adenocarcinoma.

BACKGROUND: Histone deacetylase (HDAC), a kind of protease that regulates gene expression by modifying protein acetylation levels, is usually aberrantly activated in tumors. The approved pan-HDAC inhibitors (HDACi) have exhibited clinical benefits for hematopoietic malignancies. Recently, HDACis have emerged as enhancers of antitumor immunity. However, the effect of HDACs on the tumor immune microenvironment of lung adenocarcinoma (LUAD) and the underlying mechanism is largely unknown. METHODS: C57BL/6J and BALB/c nude mice with subcutaneous tumors were used for in vivo therapeutic effects and mechanistic investigations. Flow cytometry was used to measure the toxicity and exhaustion of human CD8+T cells after co-culturing with tumor cells and to determine the immunophenotype of tumor-infiltrating CD8+T cells. A series of experimental techniques, including RNA sequencing, quantitative PCR, western blot, ELISA, mass spectrometry, co-immunoprecipitation, chromatin immunoprecipitation and immunohistochemistry, were used to explore the underlying molecular mechanism. RESULTS: The pan-HDACi vorinostat (SAHA) promoted CD8+T cell infiltration and effector function in LUAD through suppressing FGL1, a newly identified major ligand of LAG-3. Mechanistically, SAHA inhibited the activity of HDAC1, an essential deacetylase of JAK1. This increased the acetylation level of JAK1 at lysine 1109, thus promoting its proteasomal degradation and subsequently reducing STAT3-driven FGL1 transcription. The combination regimen of SAHA and anti-LAG-3 therapy was further explored in an immunocompetent LUAD mouse model. Compared with those receiving control or single agent treatments, mice receiving combination therapy exhibited a lower tumor burden and superior CD8+T-cell-killing activity. CONCLUSIONS: Our results revealed a novel mechanism by which the HDACi SAHA potentiates CD8+T-cell-mediated antitumor activity through the HDAC1/JAK1/FGL1 axis, providing a rationale for the combined use of HDACis and immunotherapy.

Hyperkalemia and maintenance of renin-angiotensin system inhibitor therapy after initiating SGLT-2 or DPP-4 inhibitors.

BACKGROUND: Post-hoc analyses of clinical trials suggest that sodium-glucose cotransporter-2 inhibitors (SGLT-2i) lower the risk of hyperkalemia and facilitate the use of renin-angiotensin system inhibitors (RASi) in people with type 2 diabetes. Whether this is also observed in routine care is unclear. We investigated whether SGLT-2i lowered the risk of hyperkalemia and RASi discontinuation as compared to dipeptidyl peptidase 4 inhibitors (DPP-4i). METHODS: Using the target trial emulation framework, we studied adults with type 2 diabetes (T2D) who started SGLT-2i or DPP-4i in Stockholm, Sweden (2014-2021). The outcomes were incident hyperkalaemia (potassium > 5.0 mmol/L), mild hyperkalemia (potassium > 5-≤5.5 mmol/L) and moderate to severe hyperkalemia (potassium > 5.5 mmol/L). Among RASi users, we studied time to RASi discontinuation through evaluation of pharmacy fills. Cox regression with inverse probability of treatment weighting was used to estimate per-protocol hazard ratios (HRs). RESULTS: 29 849 individuals (15 326 SGLT-2i and 14 523 DPP-4i initiators) were included (mean age 66 years, 37% women). About one third of participants in each arm discontinued treatment within a year. Compared with DPP-4i, SGLT-2i use was associated with a lower rate of hyperkalemia (HR 0.77; 95% CI: 0.64-0.93), including both mild (0.76; 0.62-0.93) and moderate/severe (0.53; 0.40-0.69) hyperkalemia events. Of 19.116 participants that used RASi at baseline, 7% discontinued therapy. Initiation of SGLT-2i vs. DPP-4i was not associated with the rate of RASi discontinuation (0.97; 0.83-1.14). Results were consistent in intention-to-treat analyses and across strata of age, sex, cardiovascular comorbidity, and baseline kidney function. CONCLUSIONS: In patients with diabetes managed in routine clinical care, the use of SGLT-2i was associated with lower rates of hyperkalemia compared with DPP-4i. Possibly because of a relatively high rate of treatment discontinuations, this was not accompanied by higher persistence on RASi therapy.

Heterogeneous Uptake of Al 18 F-NOTA-FAPI and 18 F-FDG in Apical Aneurysm in Apical Hypertrophic Cardiomyopathy.

ABSTRACT: Apical aneurysm in apical hypertrophic cardiomyopathy (HCM) is a very rare condition in clinical practice. Some studies have reported abnormal uptake of 18 F-FDG and 18 F-FAPI in HCM, respectively. We presented a case of FAPI and FDG imaging in a patient with apical aneurysm in apical HCM, and further analyzed the discrepancy of spatial distribution pattern of these 2 radiotracers.

Caudal-Type Homeobox Transcription Factor 2 is a Favorable Prognostic Indicator in Stage II and III Gastric Cancer Following Curative Surgery.

Background: The study explored the prognostic value of caudal-type homeobox transcription factor 2 (CDX2) in stage II and III gastric cancer. Methods: This study evaluated the expression level of CDX2 in gastric cancer in a hospital cohort (n=197) using immunohistochemistry. According to a semiquantitative score used to determine CDX2 expression, the cases were divided into a low CDX2 group (116 cases) and a high CDX2 group (81 cases). The RNA-seq expression data from 291 patients with stage II and III gastric cancer from The Cancer Genome Atlas (TCGA) cohort were used to verify the immunohistochemistry results. Based on the median CDX2 expression value, the TCGA patients were divided into a low CDX2 group (145 cases) and a high CDX2 group (146 cases). The relationships among CDX2 expression and clinicopathological features were determined using the Chi-square test. Cox proportional hazards regression models were applied to estimate the independent prognostic factors. The probability of survival was determined using the Kaplan-Meier method and Log rank tests. Results: Based on the Cox multivariate analysis, CDX2 was the independent prognostic factor in the hospital and TCGA cohorts. In the hospital cohort, CDX2 expression was associated with an improved DFS (hazard ratio [HR] = 0.4076, 95% CI, 0.2675-0.6210, P = 0.0001) and OS (HR = 0.4183, 95% CI, 0.2744-0.6375, P = 0.0002). In the TCGA cohort, CDX2 expression also was associated with an improved DFS (HR = 0.5948, 95% CI, 0.4153-0.8521, P = 0.0054) and OS (HR = 0.5976, 95% CI, 0.4172-0.8561, P = 0.0058). Furthermore, the CDX2 expression level was correlated with an improved DFS (P = 0.0025) and OS (P = 0.0015) using the Kaplan-Meier Plotter database for gastric cancer. Conclusion: CDX2 is a potential prognostic biomarker for stage II and III gastric cancer. In addition, CDX2 positive cancer patients are more likely to have resectable tumors and exhibit better survival rates.

Enhancing the corrosion inhibition of copper sheets in oil-in-water (O/W) emulsions by combining two organic heterocyclic derivatives.

Copper sheets corrode easily when exposed to oil-in-water (O/W) emulsions during metal-forming processes. The quest for identifying novel, high-efficiency copper inhibitors and realizing the effective protection of copper surfaces from emulsion corrosion has gradually attracted considerable attention. In this study, two organic heterocyclic derivatives, N,N-bis(2-ethylhexyl)-4-methyl-1H-benzotriazol-1-methanamine (NBTAH) and 2,5-bis(octyldithio)-1,3,4-thiadiazole (BTDA), were introduced as copper inhibitors into O/W emulsions. Their corrosion inhibition performance was investigated in-depth using electrochemical measurements, surface characterization, adsorption isotherms and wetting techniques. The results indicated that both inhibitors generated anodic passive films on the copper surface, and thus enhanced the corrosion resistance. The maximum corrosion inhibition efficiency achieved was 94.0% with combination of 5 mM NBTAH and 8 mM BTDA. From the surface analysis, it was confirmed that the composite inhibitors could successfully adsorb onto the copper surface via the polar atoms of the benzene, azole, and thiazole rings. The adsorption formed multilayer inhibitor films comprised of Cu-NBTAH and Cu-BTDA chelates. In addition, these films significantly reduced the wettability of the O/W emulsions on the copper surface, thus isolating copper from the corrosive medium. The anti-corrosion mechanism for adsorption and shielding of the composite inhibitors on the copper surface is preliminarily proposed.

Cell membrane-camouflaged nanoarchitectonics of photosensitizer nanoparticles for enhanced phototherapy in surgery.

Surgical risk and wound area can be reduced by diminishing tumor volume before surgery. The chemotherapy and radiotherapy currently used that can reduce the tumor volume generally cause severe systemic side effects. Phototherapy has recently emerged as an effective treatment modality for superficial cancers. However, phototherapy is limited by the low utilization of photosensitizer, the tumor hypoxia, and the low photothermal conversion efficiency. Herein, we report the cancer membrane biomimetic nanoparticles assembled by Chlorin e6 (Ce6) and chlorambucil (CRB). Ce6@CRB nanoparticles (CCNPs) show excellent photothermal conversion efficiency, which is 2 times higher than free Ce6. Meanwhile, CCNPs can produce singlet oxygen stably compared to free Ce6 thereby reducing the dependence on oxygen. Furthermore, the coating of 4 T1 cancer membrane on the surface of CCNPs endows them with the ability of homologous targeting, not only improving the utilization of Ce6, but also effectively activating the immune system in vivo when combined photodynamic therapy (PDT) and photothermal therapy (PTT). Intriguingly, surgical resection is performed after phototherapy in this treatment regimen, which can effectively reduce the wound area. Together, this work provided a feasible and creative method for tumor clinical therapy for its patient-centric and humanitarian focus.

Silver Nanoparticles Exhibit Ecotoxicological Effects via Oxidative Stress, Inflammation, and Reproductive Toxicity in Asian Clam (Corbicula fluminea).

Silver nanoparticles (AgNPs) are pervasive environmental pollutants capable of inducing toxicological impacts on benthic organisms. In this study, the effects of AgNPs on the antioxidant enzyme activities, tissue damage, inflammatory responses, and reproductive toxicity of Corbicula fluminea were investigated. C. fluminea was exposed to four concentrations of AgNPs (0, 5 mg/L, 10 mg/L, and 125 mg/L) for 48 h. The results showed that the higher concentrations of AgNPs caused severe tissue damage in multiple organs of C. fluminea, induced oxidative stress and an imbalance of the antioxidant enzyme activities (such as SOD, CAT, MDA), and increased the inflammatory immune response involving NFκB, TLR2/4, HSP70/90, IL1ß, and TNFα. Notably, further transmission electron microscopy and cytological analyses revealed that AgNPs exposure induced apoptosis in the gonad tissues, resulting in significant loss and damage in the oocytes and spermatids. The present study demonstrates the ecotoxicological impacts of AgNPs on freshwater bivalves, particularly highlighting their reproductive toxicity on germ cells, signifying the potential toxic effects of heavy metal pollution on aquatic ecosystems.

Systematic evaluation of multifactorial causal associations for Alzheimer's disease and an interactive platform MRAD developed based on Mendelian randomization analysis.

Alzheimer's disease (AD) is a complex degenerative disease of the central nervous system, and elucidating its pathogenesis remains challenging. In this study, we used the inverse-variance weighted (IVW) model as the major analysis method to perform hypothesis-free Mendelian randomization (MR) analysis on the data from MRC IEU OpenGWAS (18,097 exposure traits and 16 AD outcome traits), and conducted sensitivity analysis with six models, to assess the robustness of the IVW results, to identify various classes of risk or protective factors for AD, early-onset AD, and late-onset AD. We generated 400,274 data entries in total, among which the major analysis method of the IVW model consists of 73,129 records with 4840 exposure traits, which fall into 10 categories: Disease, Medical laboratory science, Imaging, Anthropometric, Treatment, Molecular trait, Gut microbiota, Past history, Family history, and Lifestyle trait. More importantly, a freely accessed online platform called MRAD (https://gwasmrad.com/mrad/) has been developed using the Shiny package with MR analysis results. Additionally, novel potential AD therapeutic targets (CD33, TBCA, VPS29, GNAI3, PSME1) are identified, among which CD33 was positively associated with the main outcome traits of AD, as well as with both EOAD and LOAD. TBCA and VPS29 were negatively associated with the main outcome traits of AD, as well as with both EOAD and LOAD. GNAI3 and PSME1 were negatively associated with the main outcome traits of AD, as well as with LOAD, but had no significant causal association with EOAD. The findings of our research advance our understanding of the etiology of AD.

"A diamond-shaped" penoplasty technique with or without concurrent suprapubic liposuction for adult-acquired buried penis: clinical outcomes and patient satisfaction rates.

Various techniques have been described for reconstructing the skin of the penile shaft; however, no universally accepted standard exists for correcting buried penis in adults. We aimed to describe a new technique for correcting an adult-acquired buried penis through a diamond-shaped incision at the penopubic junction. We retrospectively analyzed data from patients treated with our technique between March 2019 and June 2023 in the Department of Andrology, Nanjing Drum Tower Hospital (Nanjing, China). Forty-two adult males with buried penises, with a mean (±standard deviation [s.d.]) age of 26.6 (±6.6) years, underwent surgery. All patients were obese, with an average (±s.d.) body mass index of 35.56 (±3.23) kg m-2. In addition to phalloplasty, 32 patients concurrently underwent circumcision, and 28 underwent suprapubic liposuction. The mean (±s.d.) duration of the operation was 98.02 (±13.28) min. The mean (±s.d.) duration of follow-up was 6.71 (±3.43) months. The length in the flaccid unstretched state postoperatively was significantly greater than that preoperatively (mean ± s.d: 5.55±1.19 cm vs 1.94±0.59 cm, P < 0.01). Only minor complications, such as wound disruption (7.1%) and infection (4.8%), were observed. The mean (±s.d.) score of patient satisfaction was 4.02 (±0.84) on a scale of 5. This technique provides excellent cosmetic and functional outcomes with a minimal risk of complications. However, additional clinical studies are needed to evaluate the long-term effects of this procedure.

Does Disaster Severity Have a Long-Term Effect on Survivors' Disaster Preparedness? A Survey a Decade after the 2008 Wenchuan Earthquake in China.

OBJECTIVES: Disaster experiences have long-term effects on disaster preparedness. This study examined the long-term (10-y) effect of disaster severity of the 2008 Wenchuan earthquake on survivors' disaster preparedness and the moderating effects of household vulnerability. METHODS: The data were collected in January 2018 covering 30 counties in Wenchuan earthquake-stricken areas. The dependent variable was survivors' disaster preparedness (including overall, material, knowledge and awareness, and action preparedness) in 2018. Disaster severity included survivors' housing damage and county death rate caused by the earthquake in 2008. Household vulnerability is a set of conditions that negatively affects the ability of people to prepare for and withstand disaster, proxied by households' per-capita income and the highest years of schooling of household members. We performed multivariable linear regression models to answer the research questions. RESULTS: A higher county death rate was associated with better overall preparedness (ß = 0.043; P < 0.05) and knowledge and awareness preparedness (ß = 0.018; P < 0.05), but housing damage was not significantly associated with disaster preparedness. The positive association of county death rate with overall preparedness (ß = -0.065; P < 0.05) becomes weaker when a household has a higher per-capita income. Also, with the household per-capita income increasing, the associations of county death rate with material preparedness (ß = -0.037; P < 0.05) and action preparedness (ß = -0.034; P < 0.01) become weaker. CONCLUSIONS: Disaster severity has positive and long-term effects on survivors' disaster preparedness. Also, the positive and long-term effects are affected by household vulnerability. Specifically, the positive and long-term effects of disaster severity on disaster preparedness are more substantial when a household is more vulnerable.

Bivalves under extreme weather events: A comparative study of five economically important species in the South China sea during marine heatwaves.

Marine heatwaves (MHWs) are increasing in frequency and intensity, threatening marine organisms and ecosystems they support. Yet, little is known about impacts of intensifying MHWs on ecologically and economically important bivalves cultured in the South China Sea. Here, we compared survival and physiological responses of five bivalve species, Pinctada fucata, Crassostrea angulata, Perna viridis, Argopecten irradians and Paphia undulata, to two consecutive MHWs events (3 days of thermal exposure to + 4 °C or + 8 °C, following 3 days of recovery under ambient conditions). While P. fucata, P. viridis, and P. undulata are native to the South China Sea region, C. angulata and A. irradians are not. Individuals of P. fucata, C. angulata and P. viridis had higher stress tolerance to MHWs than A. irradians and P. undulata, the latter already experiencing 100% mortality under +8 °C conditions during the first event. With increasing intensity of MHWs, standard metabolic rates of all five species increased significantly, in line with significant depressions of function-related energy-metabolizing enzymes (CMA, NKA, and T-ATP). Likewise, activities of antioxidant enzymes (SOD, CAT, and MDA) and shell mineralization-related enzymes (AKP and ACP) responded significantly to MHWs, despite species-specific performances observed. These findings demonstrate that some bivalve species can likely fail to accommodate intensifying MHWs events in the South China Sea, but some may persist. If this is the case, then one would expect substantial loss of fitness in bivalve aquaculture in the South China Sea under intensifying MHWs conditions.

BRCA1 promotes repair of DNA damage in cochlear hair cells and prevents hearing loss.

Cochlear hair cells (HCs) sense sound waves and allow us to hear. Loss of HCs will cause irreversible sensorineural hearing loss. It is well known that DNA damage repair plays a critical role in protecting cells in many organs. However, how HCs respond to DNA damage and how defective DNA damage repair contributes to hearing loss remain elusive.In this study, we showed that cisplatin induced DNA damage in outer hair cells (OHCs) and promoted OHC loss, leading to hearing loss in mice of either sex. Cisplatin induced the expression of Brca1, a DNA damage repair factor, in OHCs. Deficiency of Brca1 induced OHC and hearing loss, and further promoted cisplatin-induced DNA damage in OHCs, accelerating OHC loss. This study provides the first in vivo evidence demonstrating that cisplatin mainly induces DNA damage in OHCs and that BRCA1 promotes repair of DNA damage in OHCs and prevents hearing loss. Our findings not only demonstrate that DNA-damage inducible agent generates DNA damage in postmitotic HCs, but also suggest that DNA repair factors, like BRCA1, protect postmitotic HCs from DNA-damage induced cell death and hearing loss.Significance statement Sensorineural hearing loss is the most severe hearing loss caused by irreversible loss of cochlear hair cells. Hair cells are vulnerable to aging and ototoxic drug. Though DNA damage repair plays a critical role in protecting cells in many organs, it is poorly understood how DNA damage is repaired in hair cells. This study provides the first in vivo evidence demonstrating that cisplatin mainly induces DNA damage in outer hair cells and that BRCA1 promotes repair of DNA damage in outer hair cells and prevents outer hair cell loss as well as hearing loss.

Circular RNA HMGCS1 sponges MIR4521 to aggravate type 2 diabetes-induced vascular endothelial dysfunction.

Noncoding RNA plays a pivotal role as novel regulators of endothelial cell function. Type 2 diabetes, acknowledged as a primary contributor to cardiovascular diseases, plays a vital role in vascular endothelial cell dysfunction due to induced abnormalities of glucolipid metabolism and oxidative stress. In this study, aberrant expression levels of circHMGCS1 and MIR4521 were observed in diabetes-induced human umbilical vein endothelial cell dysfunction. Persistent inhibition of MIR4521 accelerated development and exacerbated vascular endothelial dysfunction in diabetic mice. Mechanistically, circHMGCS1 upregulated arginase 1 by sponging MIR4521, leading to decrease in vascular nitric oxide secretion and inhibition of endothelial nitric oxide synthase activity, and an increase in the expression of adhesion molecules and generation of cellular reactive oxygen species, reduced vasodilation and accelerated the impairment of vascular endothelial function. Collectively, these findings illuminate the physiological role and interacting mechanisms of circHMGCS1 and MIR4521 in diabetes-induced cardiovascular diseases, suggesting that modulating the expression of circHMGCS1 and MIR4521 could serve as a potential strategy to prevent diabetes-associated cardiovascular diseases. Furthermore, our findings provide a novel technical avenue for unraveling ncRNAs regulatory roles of ncRNAs in diabetes and its associated complications.

Feasibility and safety of transarterial chemoembolization in patients with liver cancer via the distal radial approach: a single-center retrospective cohort study.

Background: The femoral artery is the standard route for transarterial chemoembolization (TACE); however, it is negatively associated with the quality of life of patients, and carries an increased risk of deep vein thrombosis in the lower limbs. We employed the distal radial approach to TACE to assess its feasibility and safety. Methods: We conducted a retrospective study at the First Hospital of Jilin University from August 1, 2020 to October 31, 2023. To be eligible for inclusion in the study, the patients had to meet the following main inclusion criteria: (I) have undergone a preoperative imaging (abdominal computed tomography enhancement or magnetic resonance dynamic enhancement) examination, or have a pathologically confirmed diagnosis of primary liver cancer, and a Child-Pugh score of A or B; and (II) have undergone distal radial artery puncture. The primary endpoint of this study was the success rate of distal radial artery puncture. The secondary endpoints were complications and the duration of the puncture. Results: Among the 343 patients with primary liver cancer (of whom 236 were male and 107 were female), a total of 1,315 distal radial artery punctures were attempted. The success rate was remarkably high at 95.13% (1,251/1,315), with only 64 cases requiring an alternative approach due to failed puncture. The average puncture duration was 20±7.43 minutes. No bleeding and hematoma, no arterial dissection and pseudoaneurysm formation were observed on ultrasound, and the radial pulse was palpable in all patients, highlighting the safety of the procedure. Further, no adverse events of vascular occlusion were observed among the 12 patients who received 6 or more punctures, indicating the sustainability of the distal radial artery access under the premise of adequate vascular protection. The development of this technique requires a learning curve of at least 50 cases to break through the learning baseline and be proficient in distal radial artery blind puncture. This may be the reason why many interventional physicians are reluctant to perform this procedure, adapting to the femoral approach with a shorter learning curve. Conclusions: The distal radial artery approach is feasible and safe in hepatic arterial chemoembolization, and should be widely promoted in TACE.