Removal of signal peptide variants by cation exchange chromatography: A case study.

Signal peptide (SP) is required for secretion of recombinant proteins and typically cleaved by signal peptidase at its C-region to generate the mature proteins. Miscleavage of the SP is reported occasionally, resulting in a truncated- or elongated-terminal sequence. In the present work, we demonstrated that cation exchange (CEX) chromatography is an effective means for removing SP variants with a case study. With the selected resin/conditions, the chromatographic performance is comparable between runs performed at the low end and high end of load density and elution range. The procedure described in this work can be used as a general approach for resin selection and optimization of chromatographic conditions to remove byproducts that bind more strongly than the product to the selected resin.

A pooled analysis of the incidence and mortality risk of atrial fibrillation in patients with COVID-19.

Background: There exist serious cardiovascular complications subsequent to SARS-Cov2 infection (COVID-19); however, the association between COVID-19 and atrial fibrillation (AF) remains to be elucidated. We aimed to assess the prevalence of AF among COVID-19 patients and its associated risk of death. Methods: The present systematic review was performed in accordance with the PRISMA guidelines. The protocol was registered with CRD42022306523. A comprehensive literature search was performed across PubMed, Embase, and Cochrane databases to identify studies reporting on the prevalence of pre-existing or new-onset fibrillation (AF), and/or the associated clinical outcomes in patients with COVID-19 from January 2020 to December 2023. The random-effect model was used to estimate the prevalence of AF and its related mortality. Results: A total of 80 studies, including 39,062,868 COVID-19 patients, were identified in the present investigation. The prevalence rates of pre-existing AF or new-onset AF were 10.5% (95% CI [9.3-11.7%]) or 10.3% (95% CI [6.2-14.5%]), respectively. Subgroup analysis revealed a two fold higher incidence of AF in older patients (≥65 years) compared to younger patients (<65 years) (14.4% vs. 6.4%). The highest rate of AF was observed in Europeans (10.7%, 95% CI [10.2-11.2%]), followed by Northern Americans (10.0%, 95% CI [8.2-11.7%]), while Asians demonstrated a lower prevalence (2.7%, 95% CI [2.2-3.3%]). Notably, severe COVID-19 patients displayed a significantly elevated prevalence of AF at 14.l% (95% CI [13.3-14.9%]), which was approximately 2.5-fold higher than that in non-severe patients (5.2%, 95% CI [4.8-5.5%]). Both pre-existing (HR: 1.83, 95% CI [1.49-2.17]) and new-onset AF (HR: 3.47, 95% CI [2.26-5.33]) were associated with an increased mortality risk among COVID-19 patients. Furthermore, the effect on mortality risk was more significant in Asians (HR: 5.33, 95% CI [1.62-9.04]), compared to Europeans (HR: 1.68, 95% CI [1.24-2.13]) and North Americans (HR: 2.01, 95% CI [1.18-2.83]). Conclusion: This study comprehensively investigated the association between AF and COVID-19 in a real-world setting. Notably, a high prevalence of AF was observed among older individuals, severe COVID-19 patients, and in Europe and Northern America. Moreover, co-existing AF was found to be associated with an increased risk for mortality. Further investigations are warranted to improve the management and outcomes of COVID-19 patients with AF.

Rethinking Kawasaki disease diagnosis: Continuing the search for new biomarkers.

Recent findings by Yamashita et al report a Kawasaki disease (KD) case with normal biomarker levels, challenging traditional diagnostic paradigms. This editorial explores the implications of such atypical KD presentations, emphasizing the need for novel biomarkers and revised diagnostic guidelines. The case underscores the limitations of current biomarkers, the importance of clinical judgment, and the necessity for comprehensive research to identify new diagnostic tools. Emerging technologies in proteomics and genomics offer potential avenues for discovering reliable biomarkers. Revisiting clinical guidelines to incorporate flexibility for atypical presentations is crucial. Ensuring timely and accurate KD diagnosis, even without elevated traditional biomarkers, prevents severe complications. Future advancements should focus on novel biomarkers to improve patient outcomes.

Will a plant germplasm accession conserved in a genebank change genetically over time?

The simplified question on the genetic change of a conserved plant germplasm accession over time is raised for a better understanding of the challenging mission of conserving more than 7.4 million germplasm accessions in 2000 genebanks worldwide for generations to come. Its answer will influence how these genebanks operate to ensure the continued survival and availability of the conserved plant genetic resources for future food security. Here, we explore the expected impact of evolutionary forces on plant germplasm in genebanks, search for the theoretical expectations and empirical evidence for such impacts from the literature, and discuss the ramifications of the evidence for long-term plant germplasm management and conservation. It is expected that genetic changes of long-term conserved germplasm under genebank conditions will occur commonly as an evolutionary rule, not as an exception. Incorporating evolutionary biology into the Genebank Standards and operational procedures will benefit the mission of long-term germplasm conservation.

Enhancement of cognitive function in mice with Alzheimer's disease through hyperbaric oxygen-induced activation of cellular autophagy.

Objective: In this study, we examined the effectiveness of hyperbaric oxygen (HBO) therapy in ameliorating cognitive deficits in mice with Alzheimer's disease (AD), while also assessing its impact on the autophagic pathway within the context of AD. Methods: 20 double-transgenic mice expressing the amyloid precursor protein and presenilin 1 (APP/PS1) were purposefully selected and randomly assigned to groups A and B. Concurrently, 20 C57BL/6 mice were chosen and randomly categorized into groups C and D, each consisting of 10 mice. Mice in groups B and D received HBO treatment. The Morris water maze assay was used to assess changes in mouse behavior. Immunohistochemistry techniques were used to quantify the expression levels of amyloid-beta 42 (Aß42) and microtubule-associated protein 1A/1B-light chain 3 (LC3) in hippocampal tissues, while western blot analysis was used to investigate the levels of LC3-II, p62, phosphoinositide 3-kinase (PI3K), and mammalian target of rapamycin (mTOR) proteins within hippocampal tissues. Results: Mice allocated to group B exhibited reduced escape latency and prolonged dwell time in the target quadrant compared to other groups. Histological examination revealed conspicuous plaque-like deposits of Aß42 in the hippocampal tissues of mice in groups A and B. Group B displayed diminished Aß42-positive reactants and augmented microtubule-associated protein 1A/1B-LC3-positive reactants compared to group A. LC3-positive reactants were also detected in the hippocampal tissues of mice in groups C and D, surpassing the levels observed in groups A and B. Furthermore, group B demonstrated significantly lower expression of mTOR protein and markedly higher expression of LC3-II protein in mouse hippocampal tissues when compared to group A (P < 0.05). Conversely, there were no significant disparities noted in PI3K and p62 protein expression between groups B and A. Notably, no discernible discrepancies were observed in the expression levels of mTOR, PI3K, LC3-II, and p62 proteins between groups C and D within mouse hippocampal tissues. Conclusion: HBO treatment demonstrates efficacy in enhancing cognitive function in mice with AD and holds promise as a potential therapeutic intervention for AD by facilitating the activation of the mTOR pathway-mediated autophagy.

Ultra-processed food consumption and renal cell carcinoma incidence and mortality: results from a large prospective cohort.

BACKGROUND: Growing evidence shows that ultra-processed food consumption is associated with the risk of cancer. However, prospective evidence is limited on renal cell carcinoma (RCC) incidence and mortality. In this study, we aimed to examine the association of ultra-processed food consumption and RCC incidence and mortality in a large cohort of US adults. METHODS: A population-based cohort of 101,688 participants were included from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Ultra-processed food items were confirmed by using the NOVA food classification system. The consumption of ultra-processed food was expressed as a percentage of total food intake (g/day). Prospective associations were calculated using Cox regression. Restricted cubic spline regression was used to assess nonlinearity. Subgroup analyses were performed to investigate the potential effect modifiers on the incidence and mortality of RCC. RESULTS: A total of 410 participants developed RCC during a total of 899,731 person-years of follow-up (median 9.41 years) and 230 RCC deaths during 1,533,930 person-years of follow-up (median 16.85 years). In the fully adjusted model, participants in the highest compared with the lowest quintiles of ultra-processed food consumption had a higher risk of RCC (HR quartile 4 vs 1:1.42; 95% CI: 1.06-1.91; Ptrend = 0.004) and mortality (HR quartile 4 vs. quartile 1: 1.64; 95% CI: 1.10-2.43; Ptrend = 0.027). Linear dose-response associations with RCC incidence and mortality were observed for ultra-processed food consumption (all Pnonlinearity > 0.05). The reliability of these results was supported by sensitivity and subgroup analyses. CONCLUSION: In conclusion, higher consumption of ultra-processed food is associated with an increased risk of RCC incidence and mortality. Limiting ultra-processed food consumption might be a primary prevention method of RCC.

Development of a staging system for hepatoid adenocarcinoma of the stomach based on multicenter data: A retrospective cohort study: A Staging System for Hepatoid Adenocarcinoma of the Stomach.

BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC) with a poor prognosis. Furthermore, the current pathological staging system for HAS does not distinguish it from that for common gastric cancer (CGC). METHODS: The clinicopathological data of 251 patients with primary HAS who underwent radical surgery at 14 centers in China from April 2004 to December 2019 and 5082 patients with primary CGC who underwent radical surgery at 2 centers during the same period were retrospectively analyzed. A modified staging system was established based on the differences in survival. RESULTS: After 1:4 propensity score matching (PSM), 228 patients with HAS and 828 patients with CGC were analyzed. Kaplan-Meier (K-M) analysis showed patients with HAS had a poorer prognosis compared with CGC. Multivariate analysis identified pN stage, CEA level, and perineural invasion (PNI) as independent prognostic factors in patients with HAS. A modified pT (mpT) staging was derived using recursive partitioning analysis (RPA) incorporating PNI and pT staging. The modified pathological staging system (mpTNM) integrated the mpT and the 8th American Joint Committee on Cancer (AJCC) pN definitions. Multivariate analysis showed that mpTNM stage outperformed other pathological variables as independent predictors of OS and RFS in patients with HAS. The mpTNM staging system exhibited significantly higher predictive accuracy for 3-year OS in patients with HAS (0.707, 95% CI: 0.650-0.763) compared to that of the 8th AJCC staging system (0.667, 95% CI: 0.610-0.723, P<0.05). Analysis using the Akaike information criterion favored the mpTNM staging system over the 8th AJCC staging system (824.69 vs. 835.94) regarding the goodness of fit. The mpTNM stages showed improved homogeneity in survival prediction (likelihood ratio: 41.51 vs. 27.10). Comparatively the mpTNM staging system outperformed the 8th AJCC staging system in survival prediction, supported by improvements in the net reclassification index (NRI: 47.7%) and integrated discrimination improvement (IDI: 0.083, P<0.05). Time-dependent ROC curve showed that the mpTNM staging system consistently outperformed the 8th AJCC staging system with increasing observation time. CONCLUSION: The mpTNM staging system exhibited superior postoperative prognostic accuracy for patients with HAS compared to the 8th AJCC staging system.

Glycated haemoglobin variability and risk of renal function decline in type 2 diabetes mellitus: An updated systematic review and meta-analysis.

OBJECTIVE: To assess the association between glycated haemoglobin (HbA1c) variability and risk of renal function decline in type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: A comprehensive search was carried out in PubMed, Embase, Web of Science and the Cochrane Library (until 12 March 2024). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines were followed for this meta-analysis. HbA1c variability was presented as indices of the standard deviation (SD), coefficient of variation (CV), HbA1c variability score (HVS) and haemoglobin glycation index (HGI). This meta-analysis was performed using random-effect models. RESULTS: Eighteen studies met the objectives of this meta-analysis. The analyses showed positive associations between HbA1c variability and kidney function decline, with hazard ratio (HR) 1.26 (95% confidence interval [CI] 1.15-1.38) for high versus low SD groups, HR 1.47 (95% CI 1.30-1.65) for CV groups, HR 1.32 (95% CI 1.10-1.57) for HVS groups and HR 1.53 (95% CI 1.05-2.23) for HGI groups. In addition, each 1% increase in SD and CV was linked to kidney function decline, with HR 1.26 (95% CI 1.17-1.35), and 1.13 (95% CI 1.03-1.23), respectively. Also, each 1-SD increase in SD of HbA1c was associated with deterioration in renal function, with HR 1.17 (95% CI 1.07-1.29). CONCLUSIONS: The four HbA1c variability indicators were all positively associated with renal function decline progression; therefore, HbA1c variability might play an important and promising role in guiding glycaemic control targets and predicting kidney function decline progression in T2DM.

Controlling bacterial growth and inactivation using thin film-based surface acoustic waves.

Formation of bacterial films on structural surfaces often leads to severe contamination of medical devices, hospital equipment, implant materials, etc., and antimicrobial resistance of microorganisms has indeed become a global health issue. Therefore, effective therapies for controlling infectious and pathogenic bacteria are urgently needed. Being a promising active method for this purpose, surface acoustic waves (SAWs) have merits such as nanoscale earthquake-like vibration/agitation/radiation, acoustic streaming induced circulations, and localised acoustic heating effect in liquids. However, only a few studies have explored controlling bacterial growth and inactivation behaviour using SAWs. In this study, we proposed utilising piezoelectric thin film-based SAW devices on a silicon substrate for controlling bacterial growth and inactivation with and without using ZnO micro/nanostructures. Effects of SAW powers on bacterial growth for two types of bacteria, i.e., E. coli and S. aureus, were evaluated. Varied concentrations of ZnO tetrapods were also added into the bacterial culture to study their effects and the combined antimicrobial effects along with SAW agitation. Our results showed that when the SAW power was below a threshold (e.g., about 2.55 W in this study), the bacterial growth was apparently enhanced, whereas the further increase of SAW power to a high power caused inactivation of bacteria. Combination of thin film SAWs with ZnO tetrapods led to significantly decreased growth or inactivation for both E. coli and S. aureus, revealing their effectiveness for antimicrobial treatment. Mechanisms and effects of SAW interactions with bacterial solutions and ZnO tetrapods have been systematically discussed.

Constitutive upregulation of transcription factors underlies permissive bradyzoite differentiation in a natural isolate of Toxoplasma gondii.

Toxoplasma gondii bradyzoites play a critical role in pathology due to their long-term persistence in intermediate hosts and their potential to reactivate, resulting in severe diseases in immunocompromised individuals. Currently, there is no effective treatment for eliminating bradyzoites. Hence, better in vitro models of T. gondii bradyzoite development would facilitate identification of therapeutic targets for bradyzoites. Herein, we characterized a natural isolate of T. gondii, called Tg68, which showed slower in vitro replication of tachyzoites, and permissive bradyzoite development under stress conditions in vitro. Transcriptional analysis revealed constitutive expression in Tg68 tachyzoites of the key regulators of bradyzoite development including BFD1, BFD2, and several AP2 factors. Consistent with this finding, Tg68 tachyzoites expressed high levels of bradyzoite-specific genes including BAG1, ENO1, and LDH2. Moreover, after stress-induced differentiation, Tg68 bradyzoites exhibited gene expression profiles of mature bradyzoites, even at early time points. These data suggest that Tg68 tachyzoites exist in a pre-bradyzoite stage primed to readily develop into mature bradyzoites under stress conditions in vitro. Tg68 presents a novel model for differentiation in vitro that will serve as a useful tool for the investigation of bradyzoite biology and the development of therapeutics. IMPORTANCE: Toxoplasma gondii is a widespread protozoan that chronically infects ~30% of the world's population. T. gondii can differentiate between the fast-growing life stage that causes acute infection and the slow-growing stage that persists in the host for extended periods of time. The slow-growing stage cannot be eliminated by the host immune response or currently known antiparasitic drugs. Studies on the slow-growing stage have been limited due to the limitations of in vivo experiments and the challenges of in vitro manipulation. Here, we characterize a natural isolate of T. gondii, which constitutively expresses factors that drive development and that is permissive to convert to the slow-growing stage under stress conditions in vitro. The strain presents a novel in vitro model for studying the chronic phase of toxoplasmosis and identifying new therapeutic treatments for chronic infections.

Flexible surface acoustic wave technology for enhancing transdermal drug delivery.

Transdermal drug delivery provides therapeutic benefits over enteric or injection delivery because its transdermal routes provide more consistent concentrations of drug and avoid issues of drugs affecting kidneys and liver functions. Many technologies have been evaluated to enhance drug delivery through the relatively impervious epidermal layer of the skin. However, precise delivery of large hydrophilic molecules is still a great challenge even though microneedles or other energized (such as electrical, thermal, or ultrasonic) patches have been used, which are often difficult to be integrated into small wearable devices. This study developed a flexible surface acoustic wave (SAW) patch platform to facilitate transdermal delivery of macromolecules with fluorescein isothiocyanates up to 2000 kDa. Two surrogates of human skin were used to evaluate SAW based energized devices, i.e., delivering dextran through agarose gels and across stratum corneum of pig skin into the epidermis. Results showed that the 2000 kDa fluorescent molecules have been delivered up to 1.1 mm in agarose gel, and the fluorescent molecules from 4 to 2000 kDa have been delivered up to 100 µm and 25 µm in porcine skin tissue, respectively. Mechanical agitation, localised streaming, and acousto-thermal effect generated on the skin surface were identified as the main mechanisms for promoting drug transdermal transportation, although micro/nanoscale acoustic cavitation induced by SAWs could also have its contribution. SAW enhanced transdermal drug delivery is dependent on the combined effects of wave frequency and intensity, duration of applied acoustic waves, temperature, and drug molecules molecular weights.

Application of artificial intelligence in the diagnosis and treatment of Kawasaki disease.

This editorial provides commentary on an article titled "Potential and limitations of ChatGPT and generative artificial intelligence (AI) in medical safety education" recently published in the World Journal of Clinical Cases. AI has enormous potential for various applications in the field of Kawasaki disease (KD). One is machine learning (ML) to assist in the diagnosis of KD, and clinical prediction models have been constructed worldwide using ML; the second is using a gene signal calculation toolbox to identify KD, which can be used to monitor key clinical features and laboratory parameters of disease severity; and the third is using deep learning (DL) to assist in cardiac ultrasound detection. The performance of the DL algorithm is similar to that of experienced cardiac experts in detecting coronary artery lesions to promoting the diagnosis of KD. To effectively utilize AI in the diagnosis and treatment process of KD, it is crucial to improve the accuracy of AI decision-making using more medical data, while addressing issues related to patient personal information protection and AI decision-making responsibility. AI progress is expected to provide patients with accurate and effective medical services that will positively impact the diagnosis and treatment of KD in the future.

Link between childhood obesity and gut microbiota.

Childhood obesity is a critical global health concern with rising prevalence and significant long-term health implications. Recent studies have implicated gut microbiota in the development and progression of obesity. This editorial analyzes the research conducted by Li et al, who utilized 16S rRNA gene sequencing to compare the gut microbiome of overweight and healthy-weight children. The study found significant differences in microbial diversity and composition between the two groups, with potential implications for understanding and managing childhood obesity. We analyzed the study's advantages and drawbacks, proposing potential areas for future research to better understand the connection between gut microbiota and obesity.

Survival predictor in emergency resuscitative thoracotomy for blunt trauma patients: Insights from a Chinese trauma center.

PURPOSE: Emergency resuscitative thoracotomy (ERT) is a final salvage procedure for critically injured trauma patients. Given its low success rate and ambiguous indications, its use in blunt trauma scenarios remains highly debated. Consequently, our study seeks to ascertain the overall survival rate of ERT in blunt trauma patients and determine which patients would benefit most from this procedure. METHODS: A retrospective case-control study was conducted for this research. Blunt trauma patients who underwent ERT between January 2020 and December 2023 in our trauma center were selected for analysis, with the endpoint outcome being in-hospital survival, divided into survival and non-survival groups. Inter-group comparisons were conducted using Chi-square and Fisher's exact tests, the Kruskal-Wallis test, Student's t-test, or the Mann-Whitney U test. Univariate and multivariate logistic regression analyses were conducted to assess potential predictors of survival. Then, the efficacy of the predictors was assessed through sensitivity and specificity analysis. RESULTS: A total of 33 patients were included in the study, with 4 survivors (12.12%). Multivariate logistic regression analysis indicated a significant association between cardiac tamponade and survival, with an adjusted odds ratio of 33.4 (95% CI: 1.31 - 850, p = 0.034). Additionally, an analysis of sensitivity and specificity, targeting cardiac tamponade as an indicator for survivor identification, showed a sensitivity rate of 75.0% and a specificity rate of 96.6%. CONCLUSION: The survival rate among blunt trauma patients undergoing ERT exceeds traditional expectations, suggesting that select individuals with blunt trauma can significantly benefit from the procedure. Notably, those presenting with cardiac tamponade are identified as the subgroup most likely to derive substantial benefits from ERT.

Optimizing sheep B-cell epitopes in Echinococcus granulosus recombinant antigen P29 for vaccine development.

Background: Echinococcus granulosus is a widespread zoonotic parasitic disease, significantly impacting human health and livestock development; however, no vaccine is currently available for humans. Our preliminary studies indicate that recombinant antigen P29 (rEg.P29) is a promising candidate for vaccine. Methods: Sheep were immunized with rEg.P29, and venous blood was collected at various time points. Serum was isolated, and the presence of specific antibodies was detected using ELISA. We designed and synthesized a total of 45 B cell monopeptides covering rEg.P29 using the overlap method. ELISA was employed to assess the serum antibodies of the immunized sheep for recognition of these overlapping peptides, leading to the preliminary identification of B cell epitopes. Utilizing these identified epitopes, new single peptides were designed, synthesized, and used to optimize and confirm B-cell epitopes. Results: rEg.P29 effectively induces a sustained antibody response in sheep, particularly characterized by high and stable levels of IgG. Eight B-cell epitopes of were identified, which were mainly distributed in three regions of rEg.P29. Finally, three B cell epitopes were identified and optimized: rEg.P2971-90, rEg.P29151-175, and rEg.P29211-235. These optimized epitopes were well recognized by antibodies in sheep and mice, and the efficacy of these three epitopes significantly increased when they were linked in tandem. Conclusion: Three B-cell epitopes were identified and optimized, and the efficacy of these epitopes was significantly enhanced by tandem connection, which indicated the feasibility of tandem peptide vaccine research. This laid a solid foundation for the development of epitope peptide vaccine for Echinococcus granulosus.

LncRNA H19 accelerates renal fibrosis by negatively regulating the let-7b-5p/TGF-ßR1/COL1A1 axis.

BACKGROUND: Transforming growth factor-beta1 (TGF-ß1)-mediated renal fibrosis is a critical pathological process of chronic kidney disease worsening to end-stage renal disease. Recent studies have shown that long noncoding RNA H19 (lncRNA H19) is widely involved in the formation and progression of fibrosis in multiple organs. However, its molecular events in renal fibrosis remain to be elucidated. METHODS: Rats were treated with adenine intragastrically and HK-2 cells were induced by TGF-ß1 to construct renal fibrosis models in vivo and in vitro, respectively. Renal histopathological examination was performed using HE and Masson staining. Gene expression levels of interleukin-1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), TGF-ß1, fibronectin (Fn), alpha-smooth muscle actin (α-SMA), H19, let-7b-5p, TGF-ß receptor 1 (TGF-ßR1), and type I collagen (COL1A1) were detected by qRT-PCR. Immunohistochemistry, immunofluorescence, and western blot analysis were used to evaluate the expression of renal fibrosis biomarkers. Dual-luciferase reporter assay was used to verify the presence of binding sites between H19 and let-7b-5p, and between let-7b-5p and TGF-ßR1 and COL1A1. RESULTS: H19 was overexpressed in both in vivo and in vitro renal fibrosis models. H19 knockdown significantly reversed TGF-ß1-induced upregulation of fibronectin, COL1A1, and α-SMA and downregulation of E-cadherin in HK-2 cells, accompanied by an increase in let-7b-5p. Let-7b-5p was bound to H19 in HK-2 cells, and its overexpression inhibited TGF-ß1-induced HK-2 cell fibrosis. Further experiments determined that let-7b-5p directly targets TGF-ßR1 and COL1A1 in HK-2 cells. In addition, inhibition of let-7b-5p reversed the reduction in HK-2 cell fibrosis induced by H19 knockdown. Finally, knockdown of H19 alleviated renal fibrosis in vivo and was associated with regulation of the let-7b-5p/TGF-ßR1/COL1A1 axis. CONCLUSION: Our results indicate that knockdown of H19 inhibits renal tubular epithelial fibrosis by negatively regulating the let-7b-5p/TGF-ßR1/COL1A1 axis, which may provide new mechanistic insights into CRF progression.

Supramolecular Channels Assembled within Intercellular Gaps.

Tubular structures exist broadly in biological systems and exhibit important functions including mediating cellular communications. The construction of artificial analogues in living cells would provide a new strategy for chemotherapy. In this report, a kind of supramolecular channel has been constructed within intercellular gaps by mimicking the assembly process and structure of natural gap junctional channels, which consist of hydrophobic tubular modules located in the adjacent cell membranes and hydrophilic modules within the extracellular space. The assembly of the channels was driven by electrostatic interactions. The channels could inhibit tumor cell invasion by preventing cell migration.

High-sensitivity narrow­band T-shaped cantilever Fabry-perot acoustic sensor for photoacoustic spectroscopy.

Photoacoustic spectroscopy (PAS) has been rapidly developed and applied to different detection scenarios. The acoustic pressure detection is an important part in the PAS system. In this paper, an ultrahigh sensitivity Fabry-Perot acoustic sensor with a T-shaped cantilever was proposed. To achieve the best acoustic pressure effect, the dimension of the cantilever structure was designed and optimized by finite element analysis using COMSOL Multiphysics. Simulation results showed that the sensitivity of such T-shaped cantilever was 1.5 times higher than that based on a rectangular cantilever, and the resonance frequency of T-shaped cantilever were able to modulate from 800 Hz to 1500 Hz by adjusting the multi-parameter characteristics. Experimental sensing results showed that the resonance frequency of T-shaped Fabry-Perot acoustic sensor was 1080 Hz, yielding a high sensitivity of 1.428 µm/Pa, with a signal-to-noise ratio (SNR) of 84.8 dB and a detectable pressure limit of 1.9 µPa/Hz1/2@1 kHz. We successfully used such acoustic sensor to measure acetylene (C2H2) concentration in the PAS. The sensitivity of PAS for C2H2 gas was 3.22 pm/ppm with a concentration range of 50 ppm ∼100 ppm, and the minimum detection limit was 24.91ppb.

[Prognosis of 109 cases of sudden sensorineural hearing loss in children].

Objective:To analyze the factors influencing the prognosis of sudden sensorineural deafness in children, and to provide theoretical basis for clinical prevention and treatment. Methods:The clinical data of 109 children with sudden deafness admitted to our hospital from 2016 to 2023 were retrospectively analyzed. The children were grouped according to eight related factors, including gender, age, climate, duration of hearing loss, concomitant symptoms, degree of hearing loss, sicken ear, and auditory curve. The chi-square test was used for univariate analysis, and logistic regression was employed to identify factors influencing prognosis. Results:After conventional treatment, 56 cases were ineffective（51.40%）, 30 cases were effective（27.5%）, 13 cases were effective（11.9%）, 10 cases were cured（9.2%）, and the total effective rate was 48.6%. Among concomitant symptoms, children with tinnitus had better treatment results（P<0.05）; In the degree of hearing loss, the effective rate of mild hearing loss was the highest（83.3%）, and the effective rate of very severe hearing loss was the lowest（40.0%）. The prognosis of low frequency decline and high frequency decline were better（P<0.05）; There was no significant correlation between gender, age, climate, duration of hearing loss, sicken ear and prognosis（P>0.05）. Conclusion:The auditory curve and the degree of hearing loss are the factors affecting the prognosis of children with sudden deafness. Additionally, children with tinnitus tend to have a better prognosis.

Clinical features and management strategies concerning auditory canal duplication anomalies in children with congenital first branchial cleft anomalies.

OBJECTIVE: This study aimed to summarise the clinical features and management strategies concerning auditory canal duplication anomalies in children with congenital first branchial cleft anomalies (CFBCAs), and to provide guidance for precise treatment. METHODS: We retrospectively analysed 84 children with CFBCAs who had complete data, diagnosed between December 2018 and February 2024. RESULTS: All the lesions identified were located around the external auditory canal or near the mandibular angle, manifested as pinhead-sized perforations in 10 cases, painless masses in 18 cases, recurrent swelling and pain with purulent discharge in 52 cases, and otorrhea in 4 cases. Otoscopy examinations revealed external auditory canal swelling in seven children, fistulas within the auditory canal in four children, and a myringa web in three children. Fifty-six children had a preoperative history of infection. Using Work's classification system, Work I and II in 70 (87.5%) and 14 (12.5%) children, respectively. Intraoperatively, 80 (95.2%) children had auditory canal duplication anomalies at the base of the lesion, closely associated with the cartilage of the inferior wall of external auditory canal(EAC), We then classified auditory canal duplication anomalies into three types: Type A (duplication anomalies of epithelial tissue structure between the skin of the EAC and the cartilage of the inferior wall, n = 16 children), Type B (duplication anomalies of the epithelial and/or skin tissue structure, sharing a wall with the cartilage of the inferior wall, n = 40), and Type C (duplication anomalies of the skin and cartilage tissue structure, connected to the cartilage of the inferior wall of EAC, n = 24). Sixty-eight children had lesions superficial to the facial nerve, 12 had lesions deep to the facial nerve, and four had lesions between branches. There were two cases of transient postoperative facial paralysis, three cases of CFBCA recurrence, and two cases of transient auditory canal stenosis. CONCLUSION: Auditory canal duplication anomalies are an important feature of first branchial cleft anomalies in children. Precise staging and accurate identification of the base of the lesion facilitate complete removal, thereby increasing the cure rate.