Vestibular Migraine and Recurrent Vertigo in Children: A Diagnostic Focus From a Tertiary Hospital Study.

BACKGROUND: To improve diagnostic precision in pediatric vertigo, particularly in Vestibular Migraine of Childhood (VMC), probable VMC (pVMC), Recurrent Vertigo of Childhood (RVC), and unspecified categories, by delineating clinical characteristics and prevalence to refine diagnostics and treatments. METHODS: Retrospective analysis of 102 pediatric patients (five to 18 years; 46 females, 56 males) at the Dizziness Center of the Otolaryngology Department in a tertiary-level hospital from January 2019 to December 2023. Patients were classified into VMC, pVMC, RVC, and indeterminate groups. Evaluations included audiometry and vestibular tests (video head impulse test [vHIT] or caloric testing), conducted in the audiology unit and vestibular testing laboratory. Data were analyzed using IBM SPSS 20.0. RESULTS: Diagnoses were 8.8% VMC, 31.4% pVMC, 51.0% RVC, and 8.8% indeterminate. Nausea and vomiting were common in VMC and pVMC; cochlear symptoms like tinnitus and hearing loss predominated in VMC. Although vestibular testing showed no significant group differences, VMC had more vHIT abnormalities and RVC had more caloric test anomalies. CONCLUSIONS: This study highlights the need for comprehensive diagnostics in pediatric vestibular disorders, revealing unique and overlapping traits across VMC, pVMC, and RVC. Insights call for further research to refine diagnostic criteria and improve treatment methods.

Self-healing, antibacterial, and conductive double network hydrogel for strain sensors.

Multifunctional hydrogels have great potential in smart wearable technology, flexible electronic devices, and biomedical research. However, it is highly challenging to prepare unique conductive hydrogels with combined properties such as self-healing, self-adhesive, and antibacterial activity. In this regard, herein, a conductive double network hydrogel (ACBt-PAA/CMCs) was fabricated using carboxymethyl chitosan (CMCs), acrylic acid (AA), and alkaline calcium bentonite (ACBt) via a convenient approach. Owing to the hydrogen bond interaction between PAA and CMCs, the ACBt-PAA/CMCs double network structured hydrogels exhibited excellent self-healing (the tensile strength recovered to 74.3 % after 1 h) and adjustable mechanical properties, in which the fracture stress and strain can be easily adjusted in the range of 0.039 to 0.93 MPa and 564 to 2900 %, respectively. In addition, the ACBt-PAA/CMCs hydrogels exhibited the remarkable antibacterial activities against Escherichia coli (bacterial inhibition efficiency of ~99.99 %) and Staphylococcus aureus (bacterial inhibition efficiency of ~99.98 %). Furthermore, the ACBt-PAA/CMCs hydrogel based wearable skin exhibited an excellent real-time sensing performance for monitoring various motions, signifying outstanding sensing and self-adhesion properties. Considering the unique features such as self-healing, excellent adhesion, highly active strain sensing, and antibacterial activities making the ACBt-PAA/CMCs hydrogel is an excellent multifunctional conductive hydrogel. Hence, we believe that this proposed design method for the fabrication of smart and multifunctional conductive hydrogels, and this ACBt-PAA/CMCs hydrogel could be a promising candidate for flexible wearable materials, health monitoring, and beyond.

Wide Grain 3, a GRAS Protein, Interacts with DLT to Regulate Grain Size and Brassinosteroid Signaling in Rice.

BACKGROUND: Grain size is a direct determinant of grain weight and yield in rice; however, the genetic and molecular mechanisms determining grain size remain largely unknown. FINDINGS: We identified a mutant, wide grain 3 (wg3), which exhibited significantly increased grain width and 1000-grain weight. Cytological analysis showed that WG3 regulates grain size by affecting cell proliferation. MutMap-based gene cloning and a transgenic experiment demonstrated that WG3 encodes a GRAS protein. Moreover, we found that WG3 directly interacts with DWARF AND LOW-TILLERING (DLT), a previously reported GRAS protein, and a genetic experiment demonstrated that WG3 and DLT function in a common pathway to regulate grain size. Additionally, a brassinosteroid (BR) sensitivity test suggested that WG3 has a positive role in BR signaling in rice. Collectively, our results reveal a new genetic and molecular mechanism for the regulation of grain size in rice by the WG3-DLT complex, and highlight the important functions of the GRAS protein complex in plants. CONCLUSION: WG3 functions directly in regulating grain size and BR signaling in rice.

OsBSK2, a putative brassinosteroid-signalling kinase, positively controls grain size in rice.

Grain size is an important trait that directly affects grain yield in rice; however, the genetic and molecular mechanisms regulating grain size remain unclear. In this study, we identified a mutant, grain length and grain weight 10 (glw10), which exhibited significantly reduced grain length and grain weight. Histological analysis demonstrated that GLW10 affects cell expansion, which regulates grain size. MutMap-based gene mapping and transgenic experiments demonstrated that GLW10 encodes a putative brassinosteroid (BR) signalling kinase, OsBSK2. OsBSK2 is a plasma membrane protein, and an N-myristoylation site is needed for both membrane localization and function. OsBSK2 directly interacts with the BR receptor kinase OsBRI1; however, genetic experiments have demonstrated that OsBSK2 may regulate grain size independent of the BR signalling pathway. OsBSK2 can form a homodimer or heterodimer with OsBSK3 and OsBSK4, and silencing OsBSK2, OsBSK3, and OsBSK4 reduce grain size. This indicates that OsBSKs seem to function as homodimers or heterodimers to positively regulate grain size in rice. OsBSK2/3/4 are all highly expressed in young panicles and spikelet hulls, suggesting that they control grain size. In summary, our results provide novel insights into the function of BSKs in rice, and identify novel targets for improving grain size during crop breeding.

Fine mapping and candidate gene analysis of qGSN5, a novel quantitative trait locus coordinating grain size and grain number in rice.

KEY MESSAGE: qGSN5, a novel quantitative trait locus coordinating grain size and grain number in rice, was fine-mapped to an 85.60-kb region. GS3 may be a suppressor of qGSN5. Grain size and grain number are two factors that directly determine rice grain yield; however, the underlying genetic mechanisms are complicated and remain largely unclear. In this study, a chromosome segment substitution line (CSSL), CSSL28, which showed increased grain size and decreased grain number per panicle, was identified in a set of CSSLs derived from a cross between 93-11 (recipient) and Nipponbare (donor). Four substitution segments were identified in CSSL28, and the substitution segment located on chromosome 5 was responsible for the phenotypes of CSSL28. Thus, we defined this quantitative trait locus (QTL) as grain size and grain number 5 (qGSN5). Cytological and quantitative PCR analysis showed that qGSN5 regulates the development of the spikelet hull by affecting cell proliferation. Genetic analysis showed that qGSN5 is a semi-dominant locus regulating grain size and grain number. Through map-based cloning and overlapping substitution segment analysis, qGSN5 was finally delimited to an 85.60-kb region. Based on sequence and quantitative PCR analysis, Os05g47510, which encodes a P-type pentatricopeptide repeat protein, is the most likely candidate gene for qGSN5. Pyramiding analysis showed that the effect of qGSN5 was significantly lower in the presence of a functional GS3 gene, indicating that GS3 may be a suppressor of qGSN5. In addition, we found that qGSN5 could improve the grain shape of hybrid rice. Together, our results lay the foundation for cloning a novel QTL coordinating grain size and grain number in rice and provide a good genetic material for long-grain hybrid rice breeding.

ILT4 in Colorectal Cancer Cells Induces Suppressive T Cell Contexture and Disease Progression.

PURPOSE: Immune checkpoint blockade (ICB) therapy shows little or no clinical benefit in most colorectal cancer (CRC) patients, due to the immunosuppressive T cell contexture in the tumor microenvironment (TME). Immunoglobulin-like transcript (ILT) 4 is an immunosuppressive molecule in myeloid cells. ILT4 is enriched in solid tumor cells, facilitating their proliferation, invasion, and metastasis. However, the regulatory role of ILT4 in T cell immunity of CRC is still undetermined. Here, we aimed to explore how tumor cell-derived ILT4 orchestrates T cell infiltration, subset distribution, and function in CRC. METHODS: A total of 145 paraffin-embedded cancer tissues and the corresponding clinicopathological information were collected from CRC patients. Immunohistochemical (IHC) staining and public database analyses determined the correlation of ILT4 expression with different T cell subset densities, IFN-γ levels, and patient outcomes. Paired Ig-like receptor B (PIR-B, ILT4 mouse ortholog)-overexpressing/-downregulated MC38 cells were subcutaneously injected into C57BL/6 mice as a CRC transplantation model. The frequencies, subsets, and IFN-γ levels of T cells in mouse blood and spleens were determined using flow cytometry and immunohistochemistry, respectively. RESULTS: High ILT4 expression in CRC cells was associated with decreased T cell infiltration, disease progression, and poor patient survival. T cell subset analyses indicated that ILT4-high patients showed reduced CD8+ T cell but elevated FOXP3+ regulatory T (Treg) cell frequencies in the TME. High ILT4 levels predicted lower IFN-γ production by tumor-infiltrating lymphocytes (TILs), especially by CD8+T cells in human CRC tissues. Moreover, PIR-B overexpression accelerated MC38 growth in mice, decreased CD3+/CD8+/IFN-γ+ T cell densities, and elevated Treg infiltration in the TME, blood, and spleens. PIR-B knockdown had the opposite effects. CONCLUSION: ILT4 in CRC cells induced immunosuppressive T cell subset infiltration and impaired IFN-γ production in TILs, suggesting that ILT4 might be a potential immunotherapeutic target and prognostic biomarker.

Sudden sensorineural hearing loss during pregnancy: etiology, treatment, and outcome.

OBJECTIVE: To analyze the etiologies, treatments, and outcomes of sensorineural hearing loss (SSNHL) during pregnancy. STUDY DESIGN: Retrospective chart review of 25 pregnant patients treated for SSNHL between January 2012 and September 2019. Forty-nine age matched non-pregnant women with severe and profound hearing loss diagnosed with SSNHL during the same period served as controls. Data were recorded on age, symptoms, onset of hearing loss, audiometric results, treatments, and outcomes. RESULTS: The mean age was 29.6 years (range 23-38 years). Intratympanic steroids (ITS) were administered in 15 (60.0%) pregnant women with SSNHL. Three women were treated with postauricular steroids only, while another woman was treated with intravenous ginkgo leaf extract and dipyridamole. The remaining six women received no medications. More than half (8/15, 53.3%) of pregnant women with SSNHL receiving ITS experienced hearing improvement. Pregnant women with profound hearing loss who received no medication had no hearing improvement. Most pregnant women with SSNHL (12/15, 80.0%) had higher fibrinogen levels than controls (mean values 3.77±0.71 g/L and 2.54±0.48 g/L, respectively). CONCLUSION: Fibrinogen could be a risk factor for SSNHL during pregnancy. ITS may benefit pregnant women with severe and profound SSNHL.

OsSPL18 controls grain weight and grain number in rice.

Grain weight and grain number are two important traits directly determining grain yield in rice. To date, a lot of genes related to grain weight and grain number have been identified; however, the regulatory mechanism underlying these genes remains largely unknown. In this study, we studied the biological function of OsSPL18 during grain and panicle development in rice. Knockout (KO) mutants of OsSPL18 exhibited reduced grain width and thickness, panicle length and grain number, but increased tiller number. Cytological analysis showed that OsSPL18 regulates the development of spikelet hulls by affecting cell proliferation. qRT-PCR and GUS staining analyses showed that OsSPL18 was highly expressed in developing young panicles and young spikelet hulls, in agreement with its function in regulating grain and panicle development. Transcriptional activation experiments indicated that OsSPL18 is a functional transcription factor with activation domains in both the N-terminus and C-terminus, and both activation domains are indispensable for its biological functions. Quantitative expression analysis showed that DEP1, a major grain number regulator, was significantly down-regulated in OsSPL18 KO lines. Both yeast one-hybrid and dual-luciferase (LUC) assays showed that OsSPL18 could bind to the DEP1 promoter, suggesting that OsSPL18 regulates panicle development by positively regulating the expression of DEP1. Sequence analysis showed that OsSPL18 contains the OsmiR156k complementary sequence in the third exon; 5' RLM-RACE experiments indicated that OsSPL18 could be cleaved by OsmiR156k. Taken together, our results uncovered a new OsmiR156k-OsSPL18-DEP1 pathway regulating grain number in rice.

Rapid induction of pancreatic cancer cells to cancer stem cells via heterochromatin modulation.

Mounting evidence supports that CSCs (cancer stem cells) play a vital role in cancer recurrence. Therefore elimination of CSCs is currently considered to be an important therapeutic strategy for complete remission. A major obstacle in CSC research is the obtainment of sufficient numbers of functional CSC populations. Here, we established a method to induce bulk pancreatic cancer cells to CSCs via heterochromatin modulation. Two pancreatic cancer cell lines Panc1 and Bxpc3 were cultured for 4 days in inducing medium (mTeSR containing FBS, B27, MEK inhibitor, GSK3 inhibitor, and VPA), and another 2 days in sphere culture medium (mTeSR supplemented with B27). Then the induced cells were dissociated into single cells and cultured in suspension in sphere culture medium. It was found that the majority of induced cells formed spheres which could grow larger and be passaged serially. Characterization of Panc1 sphere cells demonstrated that the sphere cells expressed increased pancreatic cancer stem cell surface markers and stem cell genes, were more resistant to chemotherapy, and were more tumorigenic in vivo, indicating that the induced sphere cells acquired CSC properties. Thus, the inducing method we developed may be used to obtain a sufficient number of CSCs from cancer cells, and contribute to the research for CSC-targeting therapy.

[Direct reprogramming from fibroblasts into cardiamyocytes].

Cardiac regenerative therapy has attracted much attention as a novel approach for heart diseases. Direct reprogramming of fibroblasts into cardiomyocytes without going through a pluripotent stem cell stage would provide a promising source of cells for cell transplantation in future. This review summarizes the research methods and problems of direct reprogramming of fibroblasts into cardiomyocytes in vitro and in vivo, and forecasts the future development of this new strategy.