Amplifying hepatic L-aspartate levels suppresses CCl4-induced liver fibrosis by reversing glucocorticoid receptor ß-mediated mitochondrial malfunction.

Liver fibrosis is a determinant-stage process of many chronic liver diseases and affected over 7.9 billion populations worldwide with increasing demands of ideal therapeutic agents. Discovery of active molecules with anti-hepatic fibrosis efficacies presents the most attacking filed. Here, we revealed that hepatic L-aspartate levels were decreased in CCl4-induced fibrotic mice. Instead, supplementation of L-aspartate orally alleviated typical manifestations of liver injury and fibrosis. These therapeutic efficacies were alongside improvements of mitochondrial adaptive oxidation. Notably, treatment with L-aspartate rebalanced hepatic cholesterol-steroid metabolism and reduced the levels of liver-impairing metabolites, including corticosterone (CORT). Mechanistically, L-aspartate treatment efficiently reversed CORT-mediated glucocorticoid receptor ß (GRß) signaling activation and subsequent transcriptional suppression of the mitochondrial genome by directly binding to the mitochondrial genome. Knockout of GRß ameliorated corticosterone-mediated mitochondrial dysfunction and hepatocyte damage which also weakened the improvements of L-aspartate in suppressing GRß signaling. These data suggest that L-aspartate ameliorates hepatic fibrosis by suppressing GRß signaling via rebalancing cholesterol-steroid metabolism, would be an ideal candidate for clinical liver fibrosis treatment.

The correlation between the MYBL2/CDCA8 signaling pathway of malignant melanoma.

Objective: Investigating the effects of MYB proto-oncogene like 2 (MYBL2)-mediated regulation of Cell division cycle associated 8 (CDCA8) expression on the biological activity of cutaneous malignant melanoma cells. Methods: A375 cells with MYBL2 and CDCA8 overexpression and knockdown were evaluated using migration, invasion, and proliferation assays. Besides, cell apoptosis was quantified by flow cytometry. To investigate the tumorigenic effects of MYBL2 knockdown in vivo, A375 cells with MYBL2 knockdown were injected in BALB/C nude mice. Results: The levels of MYBL2 and CDCA8 gene expression were notably elevated in A375 cells in comparison to HaCat cells (P < 0.05). Downregulation of MYBL2 led to a notable reduction in the migratory and invasive capability of A375 cells in vitro (P < 0.001). On the contrary, overexpression of MYBL2 enhanced migration and invasion ability (P < 0.001). There existed a positive correlation between CDCA8 and MYBL2 gene and protein expression levels after overexpression or knockdown of MYBL2 (P < 0.001). In the in vivo tumorigenic study, the MYBL2 knockdown group displayed a substantial decrease in tumor volume (P < 0.01) and exhibited decreased CDCA8 expression in tumors in comparison to the control group. Conclusion: We arrived at such a conclusion that MYBL2 promoted the migration, invasion and proliferation ability of cutaneous malignant melanoma cells by targeted regulation of CDCA8 expression in this study.

Metabolic Engineering of Corynebacterium glutamicum for the High-Level Production of l-Valine under Aerobic Conditions.

l-Valine, an essential amino acid, serves as a valuable compound in various industries. However, engineering strains with both high yield and purity are yet to be delivered for microbial l-valine production. We engineered a Corynebacterium glutamicum strain capable of highly efficient production of l-valine. We initially introduced an acetohydroxy acid synthase mutant from an industrial l-valine producer and optimized a cofactor-balanced pathway, followed by the activation of the nonphosphoenolpyruvate-dependent carbohydrate phosphotransferase system and the introduction of an exogenous Entner-Doudoroff pathway. Subsequently, we weakened anaplerotic pathways, and attenuated the tricarboxylic acid cycle via start codon substitution in icd, encoding isocitrate dehydrogenase. Finally, to balance bacterial growth and l-valine production, an l-valine biosensor-dependent genetic circuit was established to dynamically repress citrate synthase expression. The engineered strain Val19 produced 103 g/L of l-valine with a high yield of 0.35 g/g glucose and a productivity of 2.67 g/L/h. This represents the highest reported l-valine production in C. glutamicum via direct fermentation and exhibits potential for its industrial-scale production, leveraging the advantages of C. glutamicum over other microbes.

A multi-orientation system for characterizing microstructure changes and mechanical responses of fine-grained gassy sediments associated with gas hydrates.

Fine-grained marine sediments containing veiny and nodular gas hydrates will evolve into fine-grained gassy sediments after hydrate dissociation due to climate-driven ocean warming. The mechanical properties of the fine-grained gassy sediments are basically acquired by ocean engineering design. However, they have not been fully understood, largely due to the lack of microstructure visualization. In this paper, a new system is developed to jointly conduct x-ray computed tomography scans, oedometer tests, and seismic wave testing on a single specimen with temperature being well controlled, allowing varieties of experimental data to be acquired effectively and automatically. The results show that stress history can hardly affect the undrained stiffness of fine-grained gassy sediments, while the drained stiffness of fine-grained sediments without gas bubbles is stress history dependent. After being unloaded, many microstructure changes remain, and examples include the free gas distribution being more concentrated and the connectivity among gas bubbles becoming much better. The multi-orientation system lays the foundation for further studies on the microstructure changes and mechanical responses of fine-grained gassy sediments associated with gas hydrates.

Tannic acids and proanthocyanidins in tea inhibit SARS-CoV-2 variants infection.

The COVID-19 pandemic has caused hundreds million cases and millions death as well as continues to infect human life in the world since late of 2019. The breakthrough infection caused from mutation of SARS-CoV-2 is rising even the vaccinated population has been increasing. Currently, the severe threat posed by SARS-CoV-2 has been alleviated worldwide, and the situation has transitioned to coexisting with the virus. The dietary food with antiviral activities may improve to prevent virus infection for living with COVID-19 pandemic. Teas containing enriched phenolic ingredients such as tannins have been reported to be antitumor agents as well as be good inhibitors for coronavirus. This study developed a highly sensitive and selective ultra-high performance liquid chromatography-high resolution mass spectrometric method for quantification of tannic acids, a hydrolysable tannin, and proanthocyanidins, a condense tannin, in teas with different levels of fermentation. The in vitro pseudoviral particles (Vpp) infection assay was used to evaluate the inhibition activities of various teas. The results of current research demonstrate that the tannins in teas are effective inhibitors against infection of SARS-CoV-2 and its variants.

Tailoring silk fibroin fibrous architecture by a high-yield electrospinning method for fast wound healing possibilities.

In this study, a novel array electrospinning collector was devised to generate two distinct regenerated silk fibroin (SF) fibrous membranes: ordered and disordered. Leveraging electrostatic forces during the electrospinning process allowed precise control over the orientation of SF fiber, resulting in the creation of membranes comprising both aligned and randomly arranged fiber layers. This innovative approach resulted in the development of large-area membranes featuring exceptional stability due to their alternating patterned structure, achievable through expansion using the collector, and improving the aligned fiber membrane mechanical properties. The study delved into exploring the potential of these membranes in augmenting wound healing efficiency. Conducting in vitro toxicity assays with adipose tissue-derived mesenchymal stem cells (AD-MSCs) and normal human dermal fibroblasts (NHDFs) confirmed the biocompatibility of the SF membranes. We use dual perspectives on exploring the effects of different conditioned mediums produced by cells and structural cues of materials on NHDFs migration. The nanofibers providing the microenvironment can directly guide NHDFs migration and also affect the AD-MSCs and NHDFs paracrine effects, which can improve the chemotaxis of NHDFs migration. The ordered membrane, in particular, exhibited pronounced effectiveness in guiding directional cell migration. This research underscores the revelation that customizable microenvironments facilitated by SF membranes optimize the paracrine products of mesenchymal stem cells and offer valuable physical cues, presenting novel prospects for enhancing wound healing efficiency.

Influence of Normal-to-High Anodizing Voltage on AAO Surface Hardness from 1050 Aluminum Alloy in Oxalic Acid.

Anodic aluminum oxide (AAO) has been widely applied for the surface protection of electronic component packaging through a pore-sealing process, with the enhanced hardness value reaching around 400 Vickers hardness (HV). However, the traditional AAO fabrication at 0~10 °C for surface protection takes at least 3-6 h for the reaction or other complicated methods used for the pore-sealing process, including boiling-water sealing, oil sealing, or salt-compound sealing. With the increasing development of nanostructured AAO, there is a growing interest in improving hardness without pore sealing, in order to leverage the characteristics of porous AAO and surface protection properties simultaneously. Here, we investigate the effect of voltage on hardness under the same AAO thickness conditions in oxalic acid at room temperature from a normal level of 40 V to a high level of 100 V and found a positive correlation between surface hardness and voltage. The surface hardness values of AAO formed at 100 V reach about 423 HV without pore sealing in 30 min. By employing a hybrid pulse anodization (HPA) method, we are able to prevent the high-voltage burning effect and complete the anodization process at room temperature. The mechanism behind this can be explained by the porosity and photoluminescence (PL) intensity of AAO. For the same thickness of AAO from 40~100 V, increasing the anodizing voltage decreases both the porosity and PL intensity, indicating a reduction in pores, as well as anion and oxygen vacancy defects, due to rapid AAO growth. This reduction in defects in the AAO film leads to an increase in hardness, allowing us to significantly enhance AAO hardness without a pore-sealing process. This offers an effective hardness enhancement in AAO under economically feasible conditions for the application of hard coatings and protective films.

High prevalence of exon-13 variants in USH2A-related retinal dystrophies in Taiwanese population.

BACKGROUND: Biallelic pathogenic variants in USH2A lead to Usher syndrome or non-syndromic retinitis pigmentosa, and shown to have geographical and ethnical distribution in previous studies. This study provided a deeper understanding of the detailed clinical features using multimodal imaging, genetic spectrum, and genotype-phenotype correlations of USH2A-related retinal dystrophies in Taiwan. RESULTS: In our cohort, the mean age at first visit was 47.66 ± 13.54 years, and the mean age at symptom onset, which was referred to the onset of nyctalopia and/or visual field constriction, was 31.21 ± 15.24 years. Among the variants identified, 23 (50%) were missense, 10 (22%) were splicing variants, 8 (17%) were nonsense, and 5 (11%) were frameshift mutations. The most predominant variant was c.2802T>G, which accounted for 21% of patients, and was located in exon 13. Patients with truncated alleles had significantly earlier symptom onset and seemly poorer disease progression regarding visual acuity, ellipsoid zone line length, and hypofluorescent lesions in the macula than those who had the complete gene. However, the clinical presentation revealed similar progression between patients with and without the c.2802T>G variant. During long-term follow-up, the patients had different ellipsoid zone line progression rates and were almost evenly distributed in the fast, moderate, and slow progression subgroups. Although a younger onset age and a smaller baseline intact macular area was observed in the fast progression subgroup, the results showed no significant difference. CONCLUSIONS: This is the first cohort study to provide detailed genetic and longitudinal clinical analyses of patients with USH2A-related retinal dystrophies in Taiwan. The mutated allele frequency in exon 13 was high in Taiwan due to the predominant c.2802T>G variant. Moreover, truncated variants greatly impacted disease progression and determined the length of therapeutic windows. These findings provide insight into the characteristics of candidates for future gene therapies.

Validation of the Chinese Version of the Speech, Spatial, and Qualities of Hearing Scale for Parents and Children.

OBJECTIVES: To translate and validate the Chinese version of the Speech, Spatial, and Qualities of Hearing Scale (SSQ) for children with hearing impairment (C-SSQ-C) and for their parents (C-SSQ-P). DESIGN: We translated the SSQ for children into Chinese and verified its readability and comprehensibility. A total of 105 participants with moderate-to-profound hearing loss (HL) and 54 with normal hearing were enrolled in the validation process. The participants with HL were fitted with bilateral hearing aids, bimodal hearing, or bilateral cochlear implants. The C-SSQ-P was administered to the parents of participants aged 3 to 6.9 years, and the C-SSQ-C was administered to participants aged 7 to 18 years. The internal consistency, test-retest reliability, and validity were evaluated for both questionnaires. RESULTS: Both C-SSQ-P and C-SSQ-C demonstrated high internal consistency (Cronbach's α >0.8) and good validity (generalized linear model revealed significant negative relationships between the C-SSQ-P subscales with aided better-hearing threshold [ß = -0.08 to -0.12, p ≤ 0.001] and between the C-SSQ-C subscales with worse-hearing threshold [ß = -0.13 to -0.14, p < 0.001]). Among the children with HL, the participants with bilateral cochlear implants had demonstrated better performance than those with bimodal hearing and bilateral hearing aids, as evidenced by the highest mean scores in three subscales. CONCLUSIONS: Both C-SSQ-P and C-SSQ-C are reliable and valid for assessing HL in children and adolescents. The C-SSQ-P is applicable in evaluating young children aged 3 to 6.9 years after a 7-day observation period, while the C-SSQ-C is appropriate for children and adolescents aged 7 to 18 years.

Effects of polymer matrix and temperature on pyrolysis of tetrabromobisphenol A: Product profiles and transformation pathways.

Plastics are crucial constituents in electronic waste (e-waste) and part of the issue in e-waste recycling and environmental protection. However, previous studies have mostly focused on plastic recovery or thermal behavior of flame retardants, but not both simultaneously. The present study simulated the process of e-waste thermal treatment to explore tetrabromobisphenol A (TBBPA) pyrolysis at various temperatures using polystyrene (PS), polyvinyl chloride (PVC), and e-waste plastics as polymer matrices. Pyrolysis of TBBPA produced bromophenol, bromoacetophenone, bromobenzaldehyde, and bromobisphenol A. Co-pyrolysis with the polymer matrices increased emission factors by 1 - 2 orders of magnitude. The pyrolytic products of TBBPA, TBBPA+PS, and TBBPA+PVC were mainly low-brominated bisphenol A, while that of TBBPA in e-waste plastics was consistently bromophenol. Increasing temperature drove up the proportions of gaseous and particulate products, but lowered the relative abundances of inner wall adsorbed and residual products in pyrolysis of pure TBBPA. In co-pyrolysis of TBBPA with polymer matrix, the proportions of products in different phases were no longer governed solely by temperature, but also by polymer matrix. Co-pyrolysis of TBBPA with PS generated various bromophenols, while that with PVC produced chlorophenols and chlorobrominated bisphenol A. Transformation pathways, deduced by ab initio calculations, include hydrogenation-debromination, isopropylphenyl bond cleavage, oxidation, and chlorination.

Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets.

Tumorigenesis is a multistep process, with oncogenic mutations in a normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic mutations and clonal expansion in normal tissues, their transformation into cancer remains a rare event, indicating the presence of additional driver events for progression to an irreversible, highly heterogeneous, and invasive lesion. Recently, researchers are emphasizing the mechanisms of environmental tumor risk factors and epigenetic alterations that are profoundly influencing early clonal expansion and malignant evolution, independently of inducing mutations. Additionally, clonal evolution in tumorigenesis reflects a multifaceted interplay between cell-intrinsic identities and various cell-extrinsic factors that exert selective pressures to either restrain uncontrolled proliferation or allow specific clones to progress into tumors. However, the mechanisms by which driver events induce both intrinsic cellular competency and remodel environmental stress to facilitate malignant transformation are not fully understood. In this review, we summarize the genetic, epigenetic, and external driver events, and their effects on the co-evolution of the transformed cells and their ecosystem during tumor initiation and early malignant evolution. A deeper understanding of the earliest molecular events holds promise for translational applications, predicting individuals at high-risk of tumor and developing strategies to intercept malignant transformation.

Nomogram based on immune-inflammatory indicators and age-adjusted charlson comorbidity index score to predict prognosis of postoperative parotid gland carcinoma patients.

BACKGROUND: Parotid gland carcinoma (PGC) is a rare malignant tumor. The purpose of this study was to investigate the role of immune-inflammatory-nutrition indicators and age-adjusted Charlson comorbidity index score (ACCI) of PGC and develop the nomogram model for predicting prognosis. METHOD: All patients diagnosed with PGC in two tertiary hospitals, treated with surgical resection, from March 2012 to June 2018 were obtained. Potential prognostic factors were identified by univariate and multivariate Cox regression analyses. The nomogram models were established based on these identified independent prognostic factors. The performance of the developed prognostic model was estimated by related indexes and plots. RESULT: The study population consisted of 344 patients with PGC who underwent surgical resection, 285 patients without smoking (82.8%), and 225 patients (65.4%) with mucoepidermoid carcinoma, with a median age of 50.0 years. American Joint Committee on Cancer (AJCC) stage (p < 0.001), pathology (p = 0.019), tumor location (p < 0.001), extranodal extension (ENE) (p < 0.001), systemic immune-inflammation index (SII) (p = 0.004), prognostic nutrition index (PNI) (p = 0.003), ACCI (p < 0.001), and Glasgow prognostic Score (GPS) (p = 0.001) were independent indicators for disease free survival (DFS). Additionally, the independent prognostic factors for overall survival (OS) including AJCC stage (p = 0.015), pathology (p = 0.004), tumor location (p < 0.001), perineural invasion (p = 0.009), ENE (p < 0.001), systemic immune-inflammation index (SII) (p = 0.001), PNI (p = 0.001), ACCI (p = 0.003), and GPS (p = 0.033). The nomogram models for predicting DFS and OS in PGC patients were generated based on these independent risk factors. All nomogram models show good discriminative capability with area under curves (AUCs) over 0.8 (DFS 0.802, and OS 0.825, respectively). Decision curve analysis (DCA), integrated discrimination improvement (IDI), and net reclassification index (NRI) show good clinical net benefit of the two nomograms in both training and validation cohorts. Kaplan-Meier survival analyses showed superior discrimination of DFS and OS in the new risk stratification system compared with the AJCC stage system. Finally, postoperative patients with PGC who underwent adjuvant radiotherapy had a better prognosis in the high-, and medium-risk subgroups (p < 0.05), but not for the low-risk subgroup. CONCLUSION: The immune-inflammatory-nutrition indicators and ACCI played an important role in both DFS and OS of PGC patients. Adjuvant radiotherapy had no benefit in the low-risk subgroup for PGC patients who underwent surgical resection. The newly established nomogram models perform well and can provide an individualized prognostic reference, which may be helpful for patients and surgeons in proper follow-up strategies.

KRAS Promotes GLI2-Dependent Transcription during Pancreatic Carcinogenesis.

Aberrant activation of GLI transcription factors has been implicated in the pathogenesis of different tumor types including pancreatic ductal adenocarcinoma. However, the mechanistic link with established drivers of this disease remains in part elusive. In this study, using a new genetically engineered mouse model overexpressing constitutively active mouse form of GLI2 and a combination of genome-wide assays, we provide evidence of a novel mechanism underlying the interplay between KRAS, a major driver of pancreatic ductal adenocarcinoma development, and GLI2 to control oncogenic gene expression. These mice, also expressing KrasG12D, show significantly reduced median survival rate and accelerated tumorigenesis compared with the KrasG12D only expressing mice. Analysis of the mechanism using RNA sequencing demonstrate higher levels of GLI2 targets, particularly tumor growth-promoting genes, including Ccnd1, N-Myc, and Bcl2, in KrasG12D mutant cells. Furthermore, chromatin immunoprecipitation sequencing studies showed that in these cells KrasG12D increases the levels of trimethylation of lysine 4 of the histone 3 (H3K4me3) at the promoter of GLI2 targets without affecting significantly the levels of other major active chromatin marks. Importantly, Gli2 knockdown reduces H3K4me3 enrichment and gene expression induced by mutant Kras. In summary, we demonstrate that Gli2 plays a significant role in pancreatic carcinogenesis by acting as a downstream effector of KrasG12D to control gene expression.

[Dynamic Response of Aerobic Denitrification Bacteria to Water Quality in Baiyangdian Lake Under Different Hydrological Scenarios].

In order to explore the evolution law and driving mechanism of aerobic denitrification bacteria in Baiyangdian Lake under different hydrological scenarios, based on water quality survey and high-throughput sequencing technology, this study conducted a water quality factor analysis and aerobic denitrification bacteria α-diversity analysis, species composition, and network analysis. The results showed that the water body of Baiyangdian Lake was weakly alkaline, with the highest T and the lowest DO in the rainy season and the lowest T and the highest DO in the freezing season. There were significant differences between NH4+-N, NO2--N, NO3--N, TN, permanganate index, Fe, and Mn in Baiyangdian water under different hydrological scenarios (P < 0.01), and there was no significant difference in TP under different hydrological scenarios (P > 0.05). The largest category in water bodies under different hydrological scenarios was Proteobacteria, and the genera with a higher relative abundance were Magnetospirillum, Aeromonas, Pseudomonas, Azospirillum, and Bradyrhizobium. In addition, within the aerobic denitrifying bacteria community, there were significant differences in α-diversity (P < 0.001), with the highest abundance of microbial communities occurring during the freezing period, and the highest diversity and evenness of microbial communities during the dry and freezing periods. According to the RDA and Mantel analyses, the water quality driving factors of flora were different under different hydrological scenarios. The water quality driving factors of flora in the dry season were pH, NO3--N, NO2--N, and permanganate index; the driving factors of flora in the rainy season were pH, T, DO, NO2--N, and TP; the driving factors of flora in the normal season were NO2--N, Fe, and permanganate index; and the driving factors of flora in the freezing season were NO3--N and NONO2--N. Network analysis showed that there were temporal differences in species related to water quality driving factors. The genera related to water quality driving factors during the dry season were Magnetospirillum, Aeromonas, and Azoarcus, whereas the genera related to the rainy season were Magnetospirillum, Pseudomonas, and Aeromonas. The genera related to the normal season were Magnetospirillum, Pseudomonas, and Limnohabitans, and the genera related to the freezing period were Magnetospirillum, Azoarcus, and Pseudomonas. The relationship between key water quality factors (mainly T, DO, NO3--N, and permanganate index) and aerobic denitrification flora in different hydrological scenarios was gradually changing with time. In conclusion, the study on the evolution characteristics of aerobic denitrification bacteria in Baiyangdian Lake under different hydrological scenarios and the driving mechanism of environmental factors could provide a basis for understanding the evolution mechanism of aerobic denitrification bacteria in the natural environment.

Microalgae-loaded biocompatible alginate microspheres for tissue repair.

Hydrogel-based microcarriers have demonstrated effectiveness in wound repair treatments. The current research focus is creating and optimizing active microcarriers containing natural ingredients capable of conforming to diverse wound shapes and depths. Here, microalgae (MA)-loaded living alginate hydrogel microspheres were successfully fabricated via microfluidic electrospray technology, to enhance the effectiveness of wound healing. The stable living alginate hydrogel microspheres loaded with photoautotrophic MA were formed by cross-linking alginate with calcium ions. The combination of MA-loaded living alginate microspheres ensures high biocompatibility and efficient oxygen release, providing strong support for wound healing. Concurrently, vascular endothelial growth factor (VEGF) has been successfully introduced into the microspheres, further enhancing the comprehensive effectiveness of wound treatment. Covering the rat's wound with these MA-VEGF-loaded alginate microspheres further substantiated their significant role in promoting collagen deposition and vascular generation during the wound closure processes. These results confirm the outstanding value of microalgae-loaded live alginate hydrogel microspheres in wound healing, paving the way for new prospects in future clinical treatment methods.

Do the residual metals in multiple environmental media surrounding mines pose ecological and health risks? A case of an abandoned mining area in central south China.

Despite effective mining environmental regulations, residual metal pollution persists, leading to significant ecological harm and posing substantial risks to human well-being. This study employed multiple-criteria methods to investigate the ecological and health risks caused by metals in multiple environmental media (e.g., arable soil, indoor dust, PM10, homegrown vegetables, and rice) around abandoned mine areas (MA) in central south China. The study also aimed to identify predominant risk factors and the main exposure pathway. The findings revealed that metal levels and risks in the environmental media surrounding the MA were significantly higher than those in the control areas (away from abandoned mines, CA). This indicates that the accumulation of metals in the environmental media surrounding the MA was attributed to the previous mining activities. Variations in metal content were observed among different environmental media in MA, with Cd from mining source being the primary pollutant in arable soil, indoor dust, PM10, and vegetables, while As from agricultural source was the main pollutant in rice. Additionally, the consumption of Cd-contaminated vegetables and As-contaminated rice emerged as the primary routes of health hazards for the local population, leading to significant non-carcinogenic and carcinogenic risks. Consequently, it is imperative for the government and mining companies to promptly establish risk control and remedial strategies for mitigating residual metal levels in multiple environmental media surrounding the MA.

Neural representations of perspectival shapes and attentional effects: Evidence from fMRI and MEG.

Does the human brain represent perspectival shapes, i.e., viewpoint-dependent object shapes, especially in relatively higher-level visual areas such as the lateral occipital cortex? What is the temporal profile of the appearance and disappearance of neural representations of perspectival shapes? And how does attention influence these neural representations? To answer these questions, we employed functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and multivariate decoding techniques to investigate spatiotemporal neural representations of perspectival shapes. Participants viewed rotated objects along with the corresponding objective shapes and perspectival shapes (i.e., rotated round, round, and oval) while we measured their brain activities. Our results revealed that shape classifiers trained on the basic shapes (i.e., round and oval) consistently identified neural representations in the lateral occipital cortex corresponding to the perspectival shapes of the viewed objects regardless of attentional manipulations. Additionally, this classification tendency toward the perspectival shapes emerged approximately 200 ms after stimulus presentation. Moreover, attention influenced the spatial dimension as the regions showing the perspectival shape classification tendency propagated from the occipital lobe to the temporal lobe. As for the temporal dimension, attention led to a more robust and enduring classification tendency towards perspectival shapes. In summary, our study outlines a spatiotemporal neural profile for perspectival shapes that suggests a greater degree of perspectival representation than is often acknowledged.

Machine learning-based longitudinal prediction for GJB2-related sensorineural hearing loss.

BACKGROUND: Recessive GJB2 variants, the most common genetic cause of hearing loss, may contribute to progressive sensorineural hearing loss (SNHL). The aim of this study is to build a realistic predictive model for GJB2-related SNHL using machine learning to enable personalized medical planning for timely intervention. METHOD: Patients with SNHL with confirmed biallelic GJB2 variants in a nationwide cohort between 2005 and 2022 were included. Different data preprocessing protocols and computational algorithms were combined to construct a prediction model. We randomly divided the dataset into training, validation, and test sets at a ratio of 72:8:20, and repeated this process ten times to obtain an average result. The performance of the models was evaluated using the mean absolute error (MAE), which refers to the discrepancy between the predicted and actual hearing thresholds. RESULTS: We enrolled 449 patients with 2184 audiograms available for deep learning analysis. SNHL progression was identified in all models and was independent of age, sex, and genotype. The average hearing progression rate was 0.61 dB HL per year. The best MAE for linear regression, multilayer perceptron, long short-term memory, and attention model were 4.42, 4.38, 4.34, and 4.76 dB HL, respectively. The long short-term memory model performed best with an average MAE of 4.34 dB HL and acceptable accuracy for up to 4 years. CONCLUSIONS: We have developed a prognostic model that uses machine learning to approximate realistic hearing progression in GJB2-related SNHL, allowing for the design of individualized medical plans, such as recommending the optimal follow-up interval for this population.