Clinical efficacy of vestibular assessment and rehabilitation training in peripheral vestibular vertigo.

Objective: To evaluate the clinical efficacy of vestibular assessment and rehabilitation training in patients with peripheral vestibular vertigo. Method: This was a retrospective study. A total of 169 patients diagnosed with peripheral vestibular vertigo, admitted to Cangzhou People's Hospital between January 2020 and January 2023 were divided into control group (83 cases) and observation group (86 cases). The control group received medication-based treatment, while the observation group was provided with combined treatment of medication and vestibular rehabilitation training. Assessment of recovery included the Dizziness Handicap Inventory (DHI), Vestibular Symptom Index (VSI), and Activities-specific Balance Confidence (ABC) scale before and at two, four, and eight weeks post-treatment. Psychological status, sleep quality, and life quality were evaluated. Both groups underwent the Fukuda stepping test and timed balance test. Result: At two, four, and eight weeks post-treatment, both groups exhibited significantly lower DHI-P, DHI-F, DHI-E, VSI, and ABC scores compared to pre-treatment (p<0.05). The observation group showed significantly lower DHI-P, DHI-F, DHI-E, VSI, and ABC scores than the control group at two and four weeks post-treatment (p<0.05). After treatment, both groups demonstrated reduced body deviation angles and increased time without falling in the Fukuda stepping test (p<0.05). Notably, the observation group had significantly better outcomes (p<0.05). Conclusion: In comparison to medication-based treatment alone, a combined approach involving medication treatment and vestibular rehabilitation training may demonstrate early improvements in vertigo symptoms, enhance balance capabilities, and ameliorate psychological well-being, sleep quality, and overall quality of life for patients.

Pan-cancer analyses reveal the molecular and clinical characteristics of TET family members and suggests that TET3 maybe a potential therapeutic target.

The Ten-Eleven Translocation (TET) family genes are implicated in a wide array of biological functions across various human cancers. Nonetheless, there is a scarcity of studies that comprehensively analyze the correlation between TET family members and the molecular phenotypes and clinical characteristics of different cancers. Leveraging updated public databases and employing several bioinformatics analysis methods, we assessed the expression levels, somatic variations, methylation levels, and prognostic values of TET family genes. Additionally, we explored the association between the expression of TET family genes and pathway activity, tumor microenvironment (TME), stemness score, immune subtype, clinical staging, and drug sensitivity in pan-cancer. Molecular biology and cytology experiments were conducted to validate the potential role of TET3 in tumor progression. Each TET family gene displayed distinct expression patterns across at least ten detected tumors. The frequency of Single Nucleotide Variant (SNV) in TET genes was found to be 91.24%, primarily comprising missense mutation types, with the main types of copy number variant (CNV) being heterozygous amplifications and deletions. TET1 gene exhibited high methylation levels, whereas TET2 and TET3 genes displayed hypomethylation in most cancers, which correlated closely with patient prognosis. Pathway activity analysis revealed the involvement of TET family genes in multiple signaling pathways, including cell cycle, apoptosis, DNA damage response, hormone AR, PI3K/AKT, and RTK. Furthermore, the expression levels of TET family genes were shown to impact the clinical staging of tumor patients, modulate the sensitivity of chemotherapy drugs, and thereby influence patient prognosis by participating in the regulation of the tumor microenvironment, cellular stemness potential, and immune subtype. Notably, TET3 was identified to promote cancer progression across various tumors, and its silencing was found to inhibit tumor malignancy and enhance chemotherapy sensitivity. These findings shed light on the role of TET family genes in cancer progression and offer insights for further research on TET3 as a potential therapeutic target for pan-cancer.

Mapping of a novel locus Ra conferring extreme resistance against potato virus A in cultivated potato (Solanum tuberosum L.).

KEY MESSAGE: The Ra extreme resistance against potato virus A was mapped to the upper of chromosome 4 in tetraploid potato. Potato virus A (PVA) is one of the major viruses affecting potato worldwide and can cause serious disease symptoms and yield losses. Previously, we determined that potato cultivar Barbara harbors Rysto (genotype: Ryryryry) and Ra (genotype: Rararara) that each independently confer extreme resistance to PVA. In this study, employing a combination of next-generation sequencing and bulked-segregant analysis, we further located this novel Ra on chromosome 4 using a tetraploid BC1 potato population derived from a Ry-free progeny (Rararararyryryry) of Barbara (RarararaRyryryry) × F58050 (rararararyryryry). Using 29 insertion-deletion (InDel) markers spanning chromosome 4, Ra was delimited by the InDel markers M8-83 and M10-8 within a genetic interval of 1.46 cM, corresponding to a 1.86-Mb genomic region in the potato DM reference genome. The InDel marker M10-8, which is closely linked with the resistance against PVA in the Ry-free segregating populations, was then used to screen 43 selected Rysto-free tetraploid potato breeding clones. The phenotype to PVA was significantly correlated with the present/absent of the marker, albeit with a 9.3% false positive rate and a 14.0% false negative rate. These findings are of importance in furthering the cloning of Ra and employing the marker-assisted selection for PVA resistance.

End-of-life vehicle dismantling activity emits large quantities of phthalates and their alternatives: New insights on environmental sources and co-exposure risks.

Automotive interiors have been identified as significant sources of various chemicals, yet their occupational hazards for end-of-life vehicle (ELV) dismantlers remain poorly characterized. Herein, eight classes of plasticizers, including 11 phthalates esters (PAEs) and 16 non-phthalates esters (NPAEs), were detected in dust samples from inside and outside ELV dismantling workshops. Moreover, indoor dust from ordinary households and university dormitories was compared. The indoor dust from the ELV dismantling workshops contained the highest concentrations of plasticizers (median: 594 µg/g), followed by ordinary households (296 µg/g), university dormitories (186 µg/g), and outdoor dust (157 µg/g). PAEs remained the dominant plasticizers, averaging 11.7-fold higher than their NPAE alternatives. Specifically, diisononyl phthalate and trioctyl trimellitate were notably elevated in workshop dust, being 15.5 and 4.78 times higher, respectively, than in ordinary household dust, potentially indicating their association with ELV dismantling activities. The estimated daily intake of occupational ELV dismantling workers was up to five times higher than that of the general population. Moreover, certain dominant NPAEs demonstrated nuclear receptor interference abilities comparable to typical PAEs, suggesting potential toxic effects. This study is the first to demonstrate that ELV dismantling activities contribute to the co-emission of PAEs and NPAEs, posing a substantial risk of exposure to workers, which warrants further investigation.

Sanfeng Tongqiao Dripping Pills alleviate House Dust Mite-induced allergic rhinitis in mice by inhibiting Th2 differentiation and repairing the nasal epithelial barrier.

BACKGROUND: Sanfeng Tongqiao Dripping Pills (SFTQ) has clinically demonstrated a promising therapeutic effect on allergic rhinitis (AR). However, the active ingredients and underlying mechanisms of SFTQ remain unclear. PURPOSE: Exploring the effects, mechanisms, and active ingredients of SFTQ in the treatment of AR is valuable. STUDY DESIGN: The mechanisms of SFTQ and its active ingredients in treating AR were investigated through in vivo and in vitro studies. METHODS: A HDM-induced AR model was established in BALB/c mice. The effects of SFTQ in treating AR were evaluated by AR-like symptoms, EOS count, and pathological changes in the nasal tissue in vivo. The effects of SFTQ active components on epithelial cells (ECs) were evaluated in Poly(I:C) and TNF-α co-stimulated human nasal ECs (RPMI-2650). Additionally, the effects of SFTQ active components on splenocytes proliferation and Th cell differentiation were assessed. A co-culture system of ECs and T lymphocytes was established to investigate the impact of Th2 cells on the structure and function of ECs. The effects of SFTQ ingredients on ECs, T lymphocytes, and the HDM-induced AR model were further confirmed through in vivo and in vivo studies, respectively. RESULTS: SFTQ significantly alleviated AR-like symptoms and pathological changes in the nasal tissue of AR mice. The treatment elevated the expression of Occludin and E-cadherin in the nasal epithelium and reduced the percentage of Th2 cells in cervical lymph nodes (CLN). Among the active compounds of SFTQ, L-Menthone and Pulegone notably downregulated IL-33 levels in activated ECs, while Hesperetin significantly decreased TSLP and IL-33 levels. In the co-culture system of ECs and Th2 cells, exposure to Baicalin, Wogonin, and Pulegone increased the TEER value of ECs, while notably inhibiting the production of TSLP and IL-33. Furthermore, in HDM-induced AR mice, treatments with Baicalin, Luteolin, and Hesperetin effectively inhibited AR-like symptoms. Additionally, Luteolin and Hesperetin significantly reduced the inflammatory cells infiltration and the population of Th2 cells in AR mice. CONCLUSION: SFTQ and its active ingredients effectively alleviated HDM-induced AR in mice by inhibiting Th2 cell differentiation and repairing the nasal epithelial barrier. Our study can provide a scientific basis for SFTQ to be used in clinical treatment of AR.

Association of social determinants, lifestyle, and metabolic factors with mortality in Chinese adults: A nationwide 10-year prospective cohort study.

Nationwide estimates of the impact of common modifiable risk factors on mortality remain crucial. We aim to assess the influence of social determinants, lifestyle, and metabolic factors on mortality in 174,004 adults aged ≥40 years from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We reveal that 17 modifiable factors are independently associated with mortality, accounting for 64.8% of all-cause mortality, 77.4% of cardiovascular mortality, and 44.8% of cancer mortality. Low education emerges as the leading factor for both all-cause and cancer mortality, while hypertension is predominant for cardiovascular mortality. Moreover, low gross domestic product per capita and high ambient particulate matter with a diameter of <2.5 µm (PM2.5) air pollution account for 7.8% and 4.3% for all-cause mortality, respectively, using a different method. Gender-specific analyses reveal distinct patterns, with women's mortality primarily associated with social determinants and men exhibiting stronger associations with lifestyle factors. Targeted health interventions are essential to mitigate mortality risks effectively in China.

Gold Nanoparticle Transport in the Injured Kidneys with Elevated Renal Function Biomarkers.

Renal function biomarkers such as serum blood urea nitrogen (BUN) and creatinine (Cr) serve as key indicators for guiding clinical decisions before administering kidney-excreted small-molecule agents. With engineered nanoparticles increasingly designed to be renally clearable to expedite their clinical translation, understanding the relationship between renal function biomarkers and nanoparticle transport in diseased kidneys becomes crucial to their biosafety in future clinical applications. In this study, renal-clearable gold nanoparticles (AuNPs) are used as X-ray contrast agents to noninvasively track their transport and retention in cisplatin-injured kidneys with varying BUN and Cr levels. The findings reveal that AuNP transport is significantly slowed in the medulla of severely injured kidneys, with BUN and Cr levels elevated to 10 times normal. In mildly injured kidneys, where BUN and Cr levels only four to five times higher than normal, AuNP transport and retention are not predictable by BUN and Cr levels but correlate strongly with the degree of tubular injury due to the formation of gold-protein casts in the Henle's loop of the medulla. These results underscore the need for caution when employing renal-clearable nanomedicines in compromised kidneys and highlight the potential of renal-clearable AuNPs as X-ray probes for assessing kidney injuries noninvasively.

The Expression of Non B Cell-Derived Immunoglobulins.

Although V(D)J recombination and immunoglobulin (Ig) production are traditionally recognised to occur only in B lymphocytes and plasma cells, the expression of Igs in non-lymphoid cells, which we call non B cell-derived Igs (non B Igs), has been documented by growing studies. It has been demonstrated that non B-Igs can be widely expressed in most cell types, including, but not limited to, epithelial cells, cardiomyocytes, hematopoietic stem/progenitor cells, myeloid cells, and cells from immune-privileged sites, such as neurons and spermatogenic cells. In particular, malignant tumour cells express high level of IgG. Moreover, different from B-Igs that mainly localised on the B cell membrane and in the serum and perform immune defence function mainly, non B-Igs have been found to distribute more widely and play critical roles in immune defence, maintaining cell proliferation and survival, and promoting progression. The findings of non B-Igs may provide a wealthier breakthrough point for more therapeutic strategies for a wide range of immune-related diseases.

A novel causative factor of injury: Severe burns related to fires and explosions of lithium-ion batteries of electric motorcycles.

Severe burns related to fires and explosions of lithium-ion batteries of electric motorcycles have not been reported to date. We retrospectively studied 419 patients admitted to our burn intensive care unit from January 2016 to December 2021. Of these 419 patients, 26 (22 male, 4 female; median age, 42 years) had burns related to lithium-ion battery fires and explosions, and all of their injury characteristics were similar to those of traditional flame burns. Lithium-ion battery-related burns were the eighth most common cause of burn injuries among all hospitalized patients. The 26 patients comprised 10 unemployed and 16 employed individuals. Twenty-three patients were injured at home during the battery charging process, and three were injured outdoors (one by a fire while the electric motorcycle was stationary and the others two by a fire while riding the motorcycle). The burn sites were distributed over the whole body; the burn area ranged from 10 % to 100 % of the total body surface area, and the burn depth ranged from superficial second-degree burns to third-degree burns. Twenty-three patients had inhalation injuries, and ten underwent prophylactic tracheostomy and intubation. Multiple operations were required for wound repair. Although convenient, lithium-ion electric motorcycles can also cause severe burns. To prevent these injuries, we must increase public safety awareness and education, develop new battery energy storage systems and battery management systems, and ensure the safety of batteries. Consumers should be aware of the potential dangers of lithium-ion batteries and comply with related security measures.

Effects of different pretreatment methods on the degree of substitution, structure, and physicochemical properties of synthesized malic acid sweet potato starch ester.

BACKGROUND: The preparation of malic acid starch ester (MSE) is mostly carried out using a high temperature method, but there are problems such as high energy consumption, long preparation time, and uneven heating. Microwave technology can be used to overcome these limitations. The semi-crystalline structure of starch granules hinders the modifier's access to the matrix, thus limiting the esterification reaction. Physical techniques can act on the interior of the starch to create a number of active sites, thereby facilitating the reaction of the starch with esterification reagents. Therefore, this study investigated the effect of starch pretreatment by microwave, heat-moisture, and ultrasonic techniques on the degree of substitution (DS), structure, and physicochemical properties of MSE synthesized by the microwave method. RESULTS: The DS of MSE was increased after pretreatments. The modified starch obtained by different pretreatment methods did not show new characteristic peaks, while the MSE synthesized showed new absorption peaks near 1735 cm-1. The granular structure and morphology of the modified starch obtained by microwave and heat-moisture pretreatment were gelatinized and aggregated, while some of the starch particles of the modified starch obtained by ultrasonic pretreatment appeared pore-sized. The relative crystallinity and gelatinization enthalpy of the MSE were reduced, but the crystallization pattern remained as A-type. CONCLUSION: Overall, the results suggest that various pretreatment methods can enhance the DS of MSE by disrupting the structure of starch. The findings of this study provide theoretical support for improving the DS of esterified starch. © 2024 Society of Chemical Industry.

Periphery Biomarkers Predicting Conversion of Type 2 Diabetes to Pre-Alzheimer-Like Cognitive Decline: A Multicenter Follow-Up Study.

Background: The prevalence of Alzheimer's disease (AD) is increasing, therefore, identifying biomarkers to predict those vulnerable to AD is imperative. Type 2 diabetes (T2D) serves as an independent risk factor for AD. Early prediction of T2D patients who may be more susceptible to AD, so as to achieve early intervention, is of great significance to reduce the prevalence of AD. Objective: To establish periphery biomarkers that could predict conversion of T2D into pre-AD-like cognitive decline. Methods: A follow-up study was carried out from 159 T2D patients at baseline. The correlations of cognitive states (by MMSE score) with multi-periphery biomarkers, including APOE genotype, plasma amyloid-ß level, platelet GSK-3ß activity, and olfactory score were analyzed by logistic regression. ROC curve was used for establishing the prediction model. Additionally, MRI acquired from 38 T2D patients for analyzing the correlation among cognitive function, biomarkers and brain structure. Results: Compared with the patients who maintained normal cognitive functions during the follow-up period, the patients who developed MCI showed worse olfactory function, higher platelet GSK-3ß activity, and higher plasma Aß42/Aß40 ratio. We conducted a predictive model which T2D patients had more chance of suffering from pre-AD-like cognitive decline. The MRI data revealed MMSE scores were positively correlated with brain structures. However, platelet GSK-3ß activity was negatively correlated with brain structures. Conclusions: Elevated platelet GSK-3ß activity and plasma Aß42/Aß40 ratio with reduced olfactory function are correlated with pre-AD-like cognitive decline in T2D patients, which used for predicting which T2D patients will convert into pre-AD-like cognitive decline in very early stage.

Analysis of BK Virus Infection in Children After Hematopoietic Cell Transplantation: A Retrospective Single-Center Study.

BACKGROUND: BK virus (BKV) is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT). Viruses can be found in urine and serum of immunocompromised patients. OBJECTIVE: This study aimed to evaluate the incidence, clinical course, and risk factors for BKV infection in children undergoing HSCT. METHODS: Retrospectively analyzed children who underwent HSCT at Beijing Children's Hospital, Capital Medical University from June 2020 to June 2022. Data related to the clinical manifestations, engraftment, and prognosis were extracted from medical records. Patients were divided into the case group and the control group, according to the BKV infection or not after HSCT. RESULTS: A total of 149 patients were enrolled in this study, and 61 (40.9%) patients developed BKV infection after HSCT. Among the 61 patients, BKV load was detected in all patients in urine samples and 22 patients in blood samples. The median value of BKV DNA copies in urine and plasma were 9.50×107 (5.37×102 to 6.84×109) copies/mL and 2.97×103 (9.96×102 to 3.58×108) copies/mL, respectively. The median time from beginning of the conditioning regimen to BKV infection was 23 (0 to 273) days, and the first positive time of urinary BKV was earlier than that of blood (13.5 d [0.0 to 123.0 d] vs. 30.5 d [7.0 to 165.0 d], P=0.003). Among the patients with BKV infection, 36 (59.0%) patients met the diagnosis of hemorrhagic cystitis (HC), and the incidence was higher than that in the control group (P<0.001). Similarly, 15 (24.6%) patients developed renal function damage in the case group and the proportion was higher than that in the control group. The median follow-up was 5.67 (0.03 to 24.90) months, and there was no significant difference in 1-year overall survival rate between the case group and the control group (84.2%±5.7% vs. 95.3%±2.3%, P=0.688), but the incidence of TA-TMA/VOD (31.1%) and diffuse alveolar hemorrhage (9.8%) in the case group was higher than that in the control group (P=0.002 and 0.038, respectively). Multivariate analysis showed that age above 5 years old (OR=9.039, 95% CI: 3.561-24.333, P<0.001) and use of MMF (OR=2.708, 95% CI: 1.041-7.044, P<0.05) were independent risk factors for BKV infection after HSCT. CONCLUSION: Among children after HSCT, the incidence of BKV infection was high and BKV infection was associated with an increased incidence of TA-TMA/VOD and diffuse alveolar hemorrhage. Patients older than 5 years of age at the time of HSCT and treated with MMF were more likely to develop BKV infection.

Genetic Analysis of Cotton Fiber Traits in Gossypium Hybrid Lines.

Cotton plays a crucial role in the progress of the textile industry and the betterment of human life by providing natural fibers. In our study, we explored the genetic determinants of cotton architecture and fiber yield and quality by crossbreeding Gossypium hirsutum and Gossypium barbadense, creating a recombinant inbred line (RIL) population. Utilizing SNP markers, we constructed an extensive genetic map encompassing 7,730 markers over 2,784.2 cM. We appraised two architectural and seven fiber traits within six environments, identifying 58 QTLs, of which 49 demonstrated stability across these environments. These encompassed QTLs for traits such as lint percentage (LP), boll weight (BW), fiber strength (STRENGTH), seed index (SI), and micronaire (MIC), primarily located on chromosomes chr-A07, chr-D06, and chr-D07. Notably, chr-D07 houses a QTL region affecting SI, corroborated by multiple studies. Within this region, the genes BZIP043 and SEP2 were identified as pivotal, with SEP2 particularly showing augmented expression in developing ovules. These discoveries contribute significantly to marker-assisted selection, potentially elevating both the yield and quality of cotton fiber production. These findings provide valuable insights into marker-assisted breeding strategies, offering crucial information to enhance fiber yield and quality in cotton production.

Minimal effect of scanning parameters on ultrasound shear wave elastography variability in tendons.

PURPOSE: Ultrasound shear wave elastography has potential use in assessing tendon tissue; however, reducing measurement variability remains challenging. The primary purpose of this study was to identify the amount of variability accounted for by ultrasound parameter (frequency, harmonics and CrossXBeam) settings on shear wave speed at two testing sites. METHODS: Shear wave elastography images of the Achilles tendon were obtained from individuals with healthy tendons (n = 28) at two testing sites with standardised image acquisition/postprocessing protocols. Images were acquired at a range of frequencies (7-15 MHz) with CrossXBeam (a filtering technique) and harmonics settings toggled on and off. Variance decomposition analysis was performed to identify the amount of variability in shear wave speed accounted for by scan acquisition settings and testing sites. RESULTS: Shear wave speed variance was primarily attributed to participants (56.87% of variance; residual error: 35%). All scanning parameters, testing site and interaction terms each accounted for less than 2.5% of the variance. A statistically significant, negative relationship was observed between shear wave speed and image quality (p = 0.001) suggesting poor image quality yields higher shear wave speed estimates. CONCLUSION: The findings of this study suggest that natural variation in Achilles tendon mechanics between individuals without tendon pathology accounts for most of the shear wave speed variability. Optimising image quality, which may be observed in higher frequencies, should be considered to improve shear wave speed estimation. Clinically, this study highlights the need to take multiple images, maintain consistent ultrasound settings when tracking patient progress over time and use caution when comparing raw values from tendon scans performed in different clinics with shear wave elastography. LEVEL OF EVIDENCE: Level III.

Dynamic Covalent Bonds Enabled Carbon Fiber Reinforced Polymers Recyclability and Material Circularity.

Due to their remarkable features of lightweight, high strength, stiffness, high-temperature resistance, and corrosion resistance, carbon fiber reinforced polymers (CFRPs) are extensively used in sports equipment, vehicles, aircraft, windmill blades, and other sectors. The urging need to develop a resource-saving and environmentally responsible society requires the recycling of CFRPs. Traditional CFRPs, on the other hand, are difficult to recycle due to the permanent covalent crosslinking of polymer matrices. The combination of covalent adaptable networks (CANs) with carbon fibers (CFs) marks a new development path for closed-loop recyclable CFRPs and polymer resins. This review summarizes the most recent developments of closed-loop recyclable CFRPs from the unique paradigm of dynamic crosslinking polymers, CANs. These sophisticated materials with diverse functions, oriented towards CFs recycling and resin sustainability, are further categorized into several active domains of dynamic covalent bonds, including ester bonds, imine bonds, disulfide bonds, boronic ester bonds, and acetal linkages, etc. Finally, the possible strategies for the future design of recyclable CFPRs by combining dynamic covalent chemistry innovation with materials interface science are proposed.

The Gene Rearrangement and Transcriptional Regulation of Non B Cell-Derived Immunoglobulin.

Traditionally, immunoglobulin (Ig) expression has been attributed solely to B cells/plasma cells with well-documented and accepted regulatory mechanisms governing Ig expression in B cells. Ig transcription is tightly controlled by a series of transcription factors. However, increasing evidence has recently demonstrated that Ig is not only produced by B cell lineages but also by various types of non-B cells (non-B-Ig). Under physiological conditions, non-B-Ig not only exhibits antibody activity but also regulates cellular biological activities (such as promoting cell proliferation, adhesion, and cytoskeleton protein activity). In pathological conditions, non-B-Ig is implicated in the development of various diseases including tumour, kidney disease, and other immune-related disorders. The mechanisms underline Ig gene rearrangement and transcriptional regulation of Ig genes in non-B cells are not fully understood. However, existing evidence suggests that these mechanisms in non-B cells differ from those in B cells. For instance, non-B-Ig gene rearrangement occurs in an RAG-independent manner; and Oct-1 and Oct-4, rather than Oct-2, are required for the transcriptional regulation of non-B derived Igs. In this chapter, we will describe and compare the mechanisms of gene rearrangement and expression regulation between B-Ig and non-B-Ig.

Phase separation of RNF214 promotes the progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and the expression and function of an uncharacterized protein RNF214 in HCC are still unknown. Phase separation has recently been observed to participate in the progression of HCC. In this study, we investigated the expression, function, and phase separation of RNF214 in HCC. We found that RNF214 was highly expressed in HCC and associated with poor prognosis. RNF214 functioned as an oncogene to promote the proliferation, migration, and metastasis of HCC. Mechanically, RNF214 underwent phase separation, and the coiled-coil (CC) domain of RNF214 mediated its phase separation. Furthermore, the CC domain was necessary for the oncogenic function of RNF214 in HCC. Taken together, our data favored that phase separation of RNF214 promoted the progression of HCC. RNF214 may be a potential biomarker and therapeutic target for HCC.

Dominant activities of fear engram cells in the dorsal dentate gyrus underlie fear generalization in mice.

Over-generalized fear is a maladaptive response to harmless stimuli or situations characteristic of posttraumatic stress disorder (PTSD) and other anxiety disorders. The dorsal dentate gyrus (dDG) contains engram cells that play a crucial role in accurate memory retrieval. However, the coordination mechanism of neuronal subpopulations within the dDG network during fear generalization is not well understood. Here, with the Tet-off system combined with immunostaining and two-photon calcium imaging, we report that dDG fear engram cells labeled in the conditioned context constitutes a significantly higher proportion of dDG neurons activated in a similar context where mice show generalized fear. The activation of these dDG fear engram cells encoding the conditioned context is both sufficient and necessary for inducing fear generalization in the similar context. Activities of mossy cells in the ventral dentate gyrus (vMCs) are significantly suppressed in mice showing fear generalization in a similar context, and activating the vMCs-dDG pathway suppresses generalized but not conditioned fear. Finally, modifying fear memory engrams in the dDG with "safety" signals effectively rescues fear generalization. These findings reveal that the competitive advantage of dDG engram cells underlies fear generalization, which can be rescued by activating the vMCs-dDG pathway or modifying fear memory engrams, and provide novel insights into the dDG network as the neuronal basis of fear generalization.