Analysis of etiology and clinical features of spontaneous downbeat nystagmus: a retrospective study

ObjectiveTo investigate the topical diagnosis, possible etiology and mechanism of spontaneous downbeat nystagmus (sDBN) patients with dizziness/vertigo.MethodsThe clinical features of dizziness/vertigo patients accompanied with DBN were retrospectively reviewed in the Vertigo Center of our hospital from January 2018 to March 2021. The clinical features of dizziness/vertigo patients accompanied with DBN were reviewed. Comprehensive VNG, bithermal caloric testing, video-head-impulse test (vHIT), vestibular-evoked myogenic potentials (VEMP), head magnetic resonance imaging (MRI), three-dimensional fluid-attenuated incersion recovery magnetic resonance imaging (3D-FLAIR MRI) in the inner ear, serum immunology and other examinations were to determine the lesion site, and analyze its possible etiology and mechanism.ResultsA total of 54 patients were included. Among them, 70.4% (n = 38) of DBN patients were diagnosed with episodic vestibular syndrome (EVS), 22.2% (n = 12) with chronic vestibular syndrome (CVS), and 7.4% (n = 4) with acute vestibular syndrome (AVS). Among all the patients, 51.9% of DBN patients had clear etiology, with central lesions of 29.6% and peripheral diseases of 22.2%. The most common diseases in DBN patients were cerebellar lesions (13.0%, n = 7) and vestibular migraine (13.0%, n = 7), followed by benign positional paroxysmal vertigo (7.4%, n = 4) and drug-related dizziness/vertigo (5.6%, n = 3). The other 48.1% of the patients had unknown etiology. 53.8% (14/26) of patients with idiopathic DBN had decreased semicircular canal function, with 42.9% (6/14) decreased posterior semicircular canal function. The posterior semicircular canal gain in DBN patients decreased compared to the anterior semicircular canal in the same conjugate plane. Patients with peripheral DBN were more prone to horizontal/torsional nystagmus during positional testing.ConclusionIn our study, DBN patients have a relative decrease in posterior semicircular canal gain, which is possibly a particular result found in a subset of downbeat nystagmus patients. The changes in nystagmus during positional testing may be helpful in distinguishing between peripheral and central causes

Subseasonal processes of triple extreme heatwaves over the Yangtze River Valley in 2022

Historical extreme heatwaves struck the Yangtze River Valley (YRV) in the boreal summer of 2022, severely impacting agricultural production, electricity supply, and resident health in China. This study shows that extreme heatwaves recurred over the YRV with distinct subseasonal processes. In early summer, from 14 June to 18 July, two extreme heatwaves were embedded in a mid-latitude 10–25-day intraseasonal oscillation (ISO), and hot-and-wet anomalies persisted over the YRV. A self-sustaining mechanism between the “cold vortex” over Northeast China and the “heat dome” around the YRV maintained this bi-weekly ISO. It fueled the heatwaves by modulating the meridional advection of upper-tropospheric potential vorticity, which firstly warmed the air via adiabatic processes and then later by diabatic heating. In late summer, from 30 July to 29 August, a 30–50-day ISO impacted the heatwave and drought over the YRV. This ISO originated from monsoon convection in the tropics, which regulated the meridional monsoonal circulation and enhanced the heatwave by intensifying the descending air motion and adiabatic heating over the YRV. The alternation of the two ISOs accompanied the northward migration of the subtropical westerly jet over East Asia. The combination of the above-normal 10–25-day ISO and the moderate 30–50-day ISO led to the three consecutive extreme YRV heatwaves in 2022

Microbial Succession and the Dynamics of Chemical Compounds during the Solid-State Fermentation of Pu-erh Tea

An in-depth knowledge of the microbiota and metabolites in the solid-state fermentation (SSF) of Post-fermented Pu-erh tea (Pu-erh Shucha, PFPT), a Chinese traditional tea with various health benefits, is essential to develop modern fermentation technology. In this work, the microbial diversity and succession in two laboratory-developed SSF protocols for PFPT were investigated using pyrosequencing analyses of the bacterial 16S rRNA and fungal 18S rRNA genes. The active bacteria in the initial stages of SSF (seven days) were from the raw materials and environment, with a dominance of Proteobacteria in both the raw materials and SSF after seven days. The environmental bacteria were inoculated into the tea mass throughout the fermentation process and multiplied, with a dominance of Firmicutes at day 14 and 21, and then Firmicutes and Actinobacteria at the last stages of fermentation (day 28 and 35). The dominant fungi came from the raw material and were identified at the genus level as Aspergillus throughout the SSF process. The contents of tea polyphenols, free amino acids, gallic acid, theaflavin, thearubigin, and catechins decreased significantly (p < 0.05), while the level of theabrownin increased significantly (p < 0.05). The caffeine content showed no significant change (p > 0.05). In total, 30 bacterial and three fungal genera showed significant correlations to 1–8 and 3–4 identified tea compounds, respectively (p < 0.05). The dynamics of the microbiota and chemical compounds, and correlations between their changes in the SSF of PFPT were revealed, and present a foundation for further studies on the microbial effects on chemical compounds

Comparison of clinical characteristics and vestibular function test results in patients with vestibular migraine and Menière’s disease

Objectives: The differentiation between Vestibular Migraine (VM) and Meniere's Disease (MD) is difficult because of overlapping symptoms. The study aimed to compare the clinical characteristics and vestibular function test results between VM and MD patients. Methods: Seventy-one patients with definite VM and 31 patients with definite unilateral MD were included. All patients received Caloric Test (CT), Video Head Impulse Test (vHIT) and Vestibular Evoked Myogenic Potential (VEMP) test within 7 days after visiting the hospital. Results of these tests were compared between groups. Results: Most VM patients (64.0%) experienced spontaneous internal vertigo, while most MD patients (66.7%) experienced spontaneous external vertigo. MD patients had more severe vestibular symptoms and autonomic responses compared to VM patients during attacks (p =  0.03, p = 0.00, respectively). The nystagmus intensity of CT-induced was greater in VM patients than in MD patients (p = 0.003). More VM patients had CT intolerance and Central Positional Nystagmus (CPN) compared to MD patients (p = 0.002, p = 0.006, respectively). More MD patients had CT(+) and vHIT saccades wave compared to VM patients (p < 0.001, p = 0.002, respectively). The non-elicitation rate of cervical VEMP was higher, and the ocular VEMP amplitudes were lower in MD patients than in VM patients (p = 0.002, p = 0.018). Conclusions: Vestibular symptoms during attacks combined with the results of vestibular function tests may be used to differentiate between VM and MD. The diverse nature of vestibular symptoms (especially internal vertigo), history of motion sickness and CT intolerance may provide clues to the diagnosis of VM, whereas spontaneous external vertigo, CT(+) with vHIT(-), and the presence of saccades may provide clues to the diagnosis of MD. Level of evidence: 4

Alternative Splicing Regulation of Anthocyanin Biosynthesis in Camellia sinensis var. assamica Unveiled by PacBio Iso-Seq

Although the pathway and transcription factor regulation of anthocyanin biosynthesis in tea plants [Camellia sinensis (L.) O. Ktze] are known, post-transcriptional regulation mechanisms involved in anthocyanin accumulation have not been comprehensively studied. We obtained the full-length transcriptome of a purple cultivar (‘Zijuan’) and a normal green cultivar (‘Yunkang 10#) of C. sinensis var. asssamica (Masters) showing different accumulation of anthocyanins and catechins through PacBio isoform sequencing (Iso-Seq). In total, 577,557 mapped full-length cDNAs were obtained, and 2,600 average-length gene isoforms were identified in both cultivars. After gene annotations and pathway predictions, we found that 98 key genes in anthocyanin biosynthesis pathways could have undergone alternative splicing (AS) events, and identified a total of 238 isoforms involved in anthocyanin biosynthesis. We verified expression of the C4H, CHS, FLS, CCOM, F3′5’H, LAR, PAL, CCR, CYP73A13, UDP75L12, UDP78A15/UFGT, UDP94P1, GL3, MYB113, ANR, ANS, F3H, 4CL1, CYP98A3/C3H, CHI, DFR genes and their AS transcripts using qRT-PCR. Correlation analysis of anthocyanin biosynthesis and gene expression results revealed that C4H1, FLS1, PAL2, CCR2, UDP75L122 and MYB113-1 are crucial AS transcripts for regulating anthocyanin biosynthesis in C. sinensis var. assamica. Our results reveal post-transcriptional regulation of anthocyanin biosynthesis in tea plants, and provide more new insights into the regulation of secondary metabolism

Enhanced risk of record-breaking regional temperatures during the 2023–24 El Niño

Abstract In 2023, the development of El Niño is poised to drive a global upsurge in surface air temperatures (SAT), potentially resulting in unprecedented warming worldwide. Nevertheless, the regional patterns of SAT anomalies remain diverse, obscuring where historical warming records may be surpassed in the forthcoming year. Our study underscores the significant influence of El Niño and the persistence of climate signals on the inter-annual variability of regional SAT, both in amplitude and spatial distribution. The likelihood of global mean SAT exceeding historical records, calculated from July 2023 to June 2024, is estimated at 90%, contingent upon annual-mean sea surface temperature anomalies in the eastern equatorial Pacific exceeding 0.6 °C. Regions particularly susceptible to recording record-high SAT include coastal and adjacent areas in Asia such as the Bay of Bengal and the South China Sea, as well as Alaska, the Caribbean Sea, and the Amazon. This impending warmth heightens the risk of year-round marine heatwaves and escalates the threat of wildfires and other negative consequences in Alaska and the Amazon basin, necessitating strategic mitigation measures to minimize potential worst-case impacts

Anti-Tumor Effects of the Peptide TMTP1-GG-_D(KLAKLAK)² on Highly Metastatic Cancers

<div><p>The treatment of cancer such as oligonucleotides or peptides requires efficient delivery systems. A novel peptide, TMTP1, previously derived and identified in our laboratory showed remarkable ability to target highly metastatic tumors both <em>in vitro and in vivo</em>, even at the early stage of occult metastasis foci. TMTP1 moderately inhibited tumor cell viability, although not enough to deem it an efficient killer of tumor cells. In this study, we sought to enhance the anti-tumor activity of TMTP1. To do this, we fused it to an antimicrobial peptide, _D(KLAKLAK)², and termed the resulting peptide TMTP1-DKK. We found that TMTP1-DKK could trigger rapid apoptosis in human prostate and gastric cancer cells through both the mitochondrial-induced apoptosis pathway and the death receptor pathway. Furthermore, direct injection of TMTP1-DKK into mice with prostate and gastric xenograft cancers resulted in reduction of tumor volumes and a significant delay in tumor progression and metastasis <em>in vivo</em>. These results suggest that TMTP1-DKK may serve as a powerful therapeutic agent for metastatic tumors.</p> </div

Cytotoxicity of the TMTP1-DKK peptide in various cell lines. A, B, C

<p>Cell survival rates were determined by MTT assays performed in triplicate (<i>error bars</i>, ±SD). The data presented represent the percentage of cells surviving compared to untreated cells. Representative results are shown. The differences of survival rates between 10 µM and 20 µM TMTP1-DKK are more significant in either PC-3M-1E8 or MKN-45sci cells (<i>P</i><0.01). However, little or no effect was seen on murine fibroblast NIH/3T3 cell proliferation when they were treated with TMTP1-DKK. D Cells viability of MKN-45 and PC-3M-1E8 cancer cells treated different concentrations (0–20 µM) of svTMTP1-DKK for 24 hour was measured by MTT assay. E Morphological quantification of cellular apoptosis by inverted microscope in PC-3M-1E8 and MKN-45sci cells treated with 10 µM TMTP1-DKK. After treated with DKK, the cells showed cell shrinkage, membrane disintegration, and nuclear condensation/fragmentation. F Little Morphological change was observed by inverted microscope in PC-3M-1E8 and MKN-45sci treated with 10 µM svTMTP1-DKK for 24 hour.</p

TMTP1-DKK inhibits cell migration. A

<p>Cells were incubated with 2 µM TMTP1-DKK peptide for 12 h. Transwell migration assays of PC-3M-1E8 cells and MKN-45sci cells were performed. After 24 h incubation, cells from the upper side of the filter were removed and cells from the lower surface of the filter were fixed and stained. Data are the means ± SE of three independent experiments; each performed in triplicate. <b>B</b> Cellular migration was reduced by 52.38±3.3% in PC-3M-1E8 cells and 46.16±2.7% in MKN-45sci cells compared to the appropriate controls.</p