Highly Durable, Stretchable Multielectrode Array for Electro-mechanical Co-stimulation of Cells.

Electro-mechanical co-stimulation of cells can be a useful cue for tissue engineering. However, reliable co-stimulation platforms still have limitations due to low durability of the components and difficulty in optimizing the stimulation parameters. Although various electro-mechanical co-simulation systems have been explored, integrating materials and components with high durability is still limited. To tackle this problem, we designed an electro-mechanical co-stimulation system that facilitates uniaxial cyclic stretching, electrical stimulation, and optical monitoring. This system utilizes a robust and autoclavable stretchable multielectrode array housed within a compact mini-incubator. To illustrate its effectiveness, we conducted experiments that highlighted how electro-mechanical co-stimulation using this system can enhance the maturation of cardiomyocytes derived from human induced pluripotent stem cells. The results showed great potential of our co-stimulation platform as an effective tool for tissue engineering.

Lactiplantibacillus argentoratensis AGMB00912 alleviates salmonellosis and modulates gut microbiota in weaned piglets: a pilot study.

This study aimed to evaluate the efficacy of Lactiplantibacillus argentoratensis AGMB00912 (LA) in reducing Salmonella Typhimurium infection in weaned piglets. The investigation focused on the influence of LA on the gut microbiota composition, growth performance, and Salmonella fecal shedding. The results indicated that LA supplementation significantly improved average daily gain and reduced the prevalence and severity of diarrhea. Fecal analysis revealed reduced Salmonella shedding in the LA-supplemented group. Furthermore, LA notably altered the composition of the gut microbiota, increasing the levels of beneficial Bacillus and decreasing those of harmful Proteobacteria and Spirochaetes. Histopathological examination showed less intestinal damage in LA-treated piglets than in the controls. The study also observed that LA affected metabolic functions related to carbohydrate, amino acid, and fatty acid metabolism, thereby enhancing gut health and resilience against infection. Short-chain fatty acid concentrations in the feces were higher in the LA group, suggesting improved gut microbial activity. LA supplementation enriched the population of beneficial bacteria, including Streptococcus, Clostridium, and Bifidobacterium, while reducing the number of harmful bacteria, such as Escherichia and Campylobacter. These findings indicate the potential of LA as a probiotic alternative for swine nutrition, offering protective effects to the gut microbiota against Salmonella infection.

Limited Generalizability of Retrospective Single-Center Cohort Study in Comparison to Multicenter Cohort Study on Prognosis of Hepatocellular Carcinoma.

Introduction: We aimed to evaluate the generalizability of retrospective single-center cohort studies on prognosis of hepatocellular carcinoma (HCC) by comparing overall survival (OS) after various treatments between a nationwide multicenter cohort and a single-center cohort of HCC patients. Methods: Patients newly diagnosed with HCC between January 2008 and December 2018 were analyzed using data from the Korean Primary Liver Cancer Registry (multicenter cohort, n=16,443), and the Asan Medical Center HCC registry (single-center cohort, n=15,655). The primary outcome, OS after initial treatment, was compared between the two cohorts for both the entire population and for subcohorts with Child-Pugh A liver function (n=2797 and n=5151, respectively) treated according to the Barcelona-Clinic-Liver-Cancer (BCLC) strategy, using Log rank test and Cox proportional hazard models. Results: Patients of BCLC stages 0 and A (59.3% vs 35.2%) and patients who received curative treatment (42.1% vs 32.1%) were more frequently observed in the single-center cohort (Ps<0.001). Multivariable analysis revealed significant differences between the two cohorts in OS according to type of treatment: the multicenter cohort was associated with higher risk of mortality among patients who received curative (adjusted hazard ratio [95% confidence interval], 1.48 [1.39-1.59]) and non-curative (1.22 [1.17-1.27]) treatments, whereas the risk was lower in patients treated with systemic therapy (0.83 [0.74-0.92]) and best supportive care (0.85 [0.79-0.91]). Subcohort analysis also demonstrated significantly different OS between the two cohorts, with a higher risk of mortality in multicenter cohort patients who received chemoembolization (1.72 [1.48-2.00]) and ablation (1.44 [1.08-1.92]). Conclusion: Comparisons of single-center and multicenter cohorts of HCC patients revealed significant differences in OS according to treatment modality after adjustment for prognostic variables. Therefore, the results of retrospective single-center cohort studies of HCC treatments may not be generalizable to real-world practice.

Effects of Fu's Subcutaneous Needling on Postoperative Pain in Patients Receiving Surgery for Degenerative Lumbar Spinal Disorders: A Single-Blind, Randomized Controlled Trial.

Background: Fu's subcutaneous needling (FSN) is a novel acupuncture technique for pain treatment. This study investigated the effects of postsurgical FSN on postoperative pain in patients receiving surgery for degenerative spinal disorders. Methods: This single-center, single-blind, randomized-controlled study involved patients undergoing surgery for degenerative spinal disorders. Participants were randomized into either an FSN group or a control group that received sham FSN. The primary outcomes were scores on the Brief Pain Inventory Taiwan version (BPI-T) and Oswestry Disability Index before and at 1, 24, and 48 hours after surgery. Secondary outcomes were muscle hardness, pethidine use, and inflammatory biomarker presence. Results: Initially, 51 patients met the inclusion criteria and were allocated (26 in the FSN group and 25 in the control group). Two patients were lost to follow-up, and finally, 49 patients (25 in the FSN group and 24 in the control group) who completed the study were analyzed. The FSN group had significantly lower pain intensity measured on the BPI-T compared with the control group at 1, 24, 48, and 72 hours after surgical treatment (all p < 0.001). Additionally, pain interference as measured on the BPI-T was lower in the FSN group than in the control group 1 hour (p = 0.001), 24 hours (p = 0.018), 48 hours (p = 0.001), and 72 hours (p = 0.017) after surgical treatment. Finally, the FSN group exhibited less muscle hardness in the latissimus dorsi and gluteus maximus 24, 48, and 72 hours (all p < 0.05) after surgery compared with the control group; patients in the FSN group also exhibited less muscle hardness in the L3 paraspinal muscle 48 hours (p = 0.001) and 72 hours (p < 0.001) after surgery compared with the control group. There were no significant differences in serum CRP, IL-1ß, IL-2, IL-6, and TNF-α levels between the FSN and control groups at 24 hours, 72 hours, and 1-month post-surgery (all p > 0.05). Conclusion: FSN treatment can reduce postoperative pain in patients receiving surgery for degenerative spinal disorders. However, larger sample sizes and multicenter clinical trials are required to verify these findings.

Tumor phagocytosis-driven STING activation invigorates antitumor immunity and reprograms the tumor micro-environment.

Immunogenic cell death (ICD) holds the potential for in situ tumor vaccination while concurrently eradicating tumors and stimulating adaptive immunity. Most ICD inducers, however, elicit insufficient immune responses due to negative feedback against ICD biomarkers, limited infiltration of antitumoral immune cells, and the immunosuppressive tumor micro-environment (TME). Recent findings highlight the pivotal roles of stimulators of interferon gene (STING) activation, particularly in stimulating antigen-presenting cells (APCs) and TME reprogramming, addressing ICD limitations. Herein, we introduced 'tumor phagocytosis-driven STING activation', which involves the activation of STING in APCs during the recognition of ICD-induced cancer cells. We developed a polypeptide-based nanocarrier encapsulating both doxorubicin (DOX) and diABZI STING agonist 3 (dSA3) to facilitate this hypothesis in vitro and in vivo. After systemic administration, nanoparticles predominantly accumulated in tumor tissue and significantly enhanced anticancer efficacy by activating tumor phagocytosis-driven STING activation in MC38 and TC1 tumor models. Immunological activation of APCs occurred within 12 h, subsequently leading to the activation of T cells within 7 days, observed in both the TME and spleen. Furthermore, surface modification of nanoparticles with cyclic RGD (cRGD) moieties, which actively target integrin αvß3, enhances tumor accumulation and eradication, thereby verifying the establishment of systemic immune memory. Collectively, this study proposes the concept of tumor phagocytosis-driven STING activation and its effectiveness in generating short-term and long-term immune responses.

DNA-encoded probe-based assay for profiling plant kinase activities.

Elucidating kinase-substrate relationships is pivotal for deciphering cellular signaling mechanisms, yet it remains challenging due to the complexity of kinase networks. Herein, we report the development of a versatile DNA-based kinase assay platform for high-throughput profiling of plant protein kinase activities and substrate preferences. Our approach employs DNA-linked peptide substrates, facilitating quantitative and specific kinase activity detection through next-generation DNA sequencing. Leveraging DNA barcodes as quantitative readouts, our approach establishes a high-throughput, sensitive, and specific platform for dissecting kinase-substrate networks in plants, representing a powerful tool for elucidating signaling mechanisms in plants.

Transient elastography for significant fibrosis in treatment-naïve CHB patients: A systematic review and meta-analysis.

Background and Aims: Accurate diagnosis of significant liver fibrosis in patients with chronic hepatitis B (CHB) is crucial when determining whether to initiate antiviral treatment (AVT). We conduct a meta-analysis to assess the diagnostic performance of transient elastography (TE) for significant liver fibrosis in AVT-naïve CHB patients with serum alanine transaminase (ALT) levels within 5-fold the upper limit of normal (ULN). Methods: The Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases were searched to identify studies that compared the performance of TE and liver biopsy (reference standard) when diagnosing significant liver fibrosis (≥ F2) in AVT-naïve CHB patients with ALT within 5-fold the ULN. A hierarchical summary receiver operating characteristic curve (HSROC) and bivariate model were performed to evaluate the diagnostic performance of TE in the meta-analysis. Results: Eight studies (2,003 patients) were included. The summary sensitivity and specificity for diagnosis of significant liver fibrosis were 0.78 [95% confidence interval (CI), 0.66-0.86] and 0.72 (95% CI, 0.60-0.82), respectively. The HSROC for the diagnosis of significant liver fibrosis was 0.81 (95% CI, 0.72-0.86). The optimal cut-off value of TE for diagnosis of significant liver fibrosis was 7.7 kPa with a sensitivity of 0.64 (95% CI, 0.50-0.76) and specificity of 0.83 (95% CI, 0.72-0.90). Conclusions: Our study demonstrated that TE has an acceptable diagnostic performance for significant liver fibrosis in AVT-naïve CHB patients with ALT within 5-fold the ULN.

Risk Assessment of Hepatitis B virus-related Hepatocellular Carcinoma Development Using Transient Elastography: Systematic Review and Meta-analysis.

Background and Aims: Liver stiffness measurement (LSM) using transient elastography (TE) can assess fibrotic burden in chronic liver diseases. The systematic review and meta-analysis was conducted to determine whether LSM using TE can predict the risk of development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. Methods: A systematic literature search of the Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases (from January 2010 to June 2023) was conducted. Of the 1,345 individual studies identified, 10 studies that used TE were finally registered. Hazard ratios (HRs) and the 95% confidence interval (CIs) were considered summary estimates of treatment effect sizes of ≥ 11 kilopascal (kPa) standard for HCC development. Meta-analysis was performed using the restricted Maximum Likelihood random effects model. Results: Among the ten studies, data for risk ratios for HCC development could be obtained from nine studies. When analyzed for the nine studies, the HR for HCC development was high at 3.33 (95% CI, 2.45-4.54) in CHB patients with a baseline LSM of ≥ 11 kPa compared to patients who did not. In ten studies included, LSM of ≥ 11 kPa showed the sensitivity and specificity for predicting HCC development were 61% (95% CI, 50-71%) and 78% (95% CI, 66-86%), respectively, and the diagnostic accuracy was 0.74 (95% CI, 0.70-0.77). Conclusions: The risk of HCC development was elevated in CHB patients with TE-determined LSM of ≥11 kPa. This finding suggests that TE-determined LSM values may aid the risk prediction of HCC development in CHB patients.

Trends in Hospital Stay, Complication Rate, and Mortality in Hip Fracture Patients: A Two-Decade Comparison at a National Tertiary Referral Center.

Background: Since the turn of the century, the age-adjusted incidence of proximal femoral fractures has caused a plateau or fall. However, it was anticipated that the number of patients with proximal femoral fractures would rise as life expectancy rose and the population over 80 years old expanded. The aim of this study was to compare the length of hospital stay, complication rate, and mortality in patients with proximal femoral fractures between two different time periods: 20 years ago and the present. Methods: We conducted a retrospective review of medical records of patients aged 65 years and above who underwent surgery for proximal femoral fractures between January 2000 and December 2001 and between January 2020 and December 2021. We collected information on age, gender, fracture type, length of hospital stay, and complication rate. Dates of death were obtained from the Ministry of the Interior and Safety. Results: We included 136 patients who were operated on between 2000 and 2001 and 134 patients between 2020 and 2021. The average age increased significantly from 71.6 years to 79.0 years (p < 0.001). The length of hospital stay decreased dramatically from 15.1 days to 6.0 days (p < 0.001). There was no statistically significant difference in delirium, urinary tract infection, or pneumonia. No difference was found in 30-day or 1-year mortality between the two groups. Conclusions: The complication rate and mortality between the two time periods appeared comparable, although the length of hospital stay decreased substantially. Therefore, we recommend considering expedited discharge from the acute care hospital for elderly hip fracture patients while implementing an individualized approach for better outcomes.

Papillary tumor of the pineal region: analysis of DNA methylation profiles and clinical outcomes in 76 cases.

Papillary tumor of the pineal region (PTPR) is an uncommon tumor of the pineal region with distinctive histopathologic and molecular characteristics. Experience is limited with respect to its molecular heterogeneity and clinical characteristics. Here, we describe 39 new cases and combine these with 37 previously published cases for a cohort of 76 PTPR's, all confirmed by methylation profiling. As previously reported, two main methylation groups were identified (PTPR-A and PTPR-B). In our analysis we extended the subtyping into three subtypes: PTPR-A, PTPR-B1 and PTPR-B2 supported by DNA methylation profile and genomic copy number variations. Frequent loss of chromosome 3 or 14 was found in PTPR-B1 tumors but not in PTPR-B2. Examination of clinical outcome showed that nearly half (14/30, 47%) of examined patients experienced tumor progression with significant difference among the subtypes (p value = 0.046). Our analysis extends the understanding of this uncommon but distinct neuroepithelial tumor by describing its molecular heterogeneity and clinical outcomes, including its tendency towards tumor recurrence.

Differential effects of desvenlafaxine on hot flashes in women with breast cancer taking tamoxifen: a randomized controlled trial.

Hot flashes (HF) are a common adverse event of prolonged tamoxifen use in women with estrogen receptor-positive breast cancer, impacting psychiatric health and quality of life. While desvenlafaxine does not interact with tamoxifen, its efficacy and safety in breast cancer patients remain unstudied. This phase 3, four-week, multi-center, three-arm, parallel-group, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of desvenlafaxine for treating HF in women with breast cancer taking tamoxifen, assessing potential differential effects in patients with psychiatric and inflammatory conditions. Between December 2017 and February 2019, 57 women aged 19 or older, regularly taking tamoxifen as adjuvant therapy, experiencing moderate-to-severe HFs for more than a month, were randomized to receive desvenlafaxine 50 mg/day (D-50), desvenlafaxine 100 mg/day (D-100), or placebo for four weeks. The primary endpoint was the change rate in HF scores over four weeks, with adverse events as a secondary endpoint. Both desvenlafaxine arms demonstrated greater HF score reductions compared to placebo: D-50 (2.20 points/week, 95% CI: 0.71, 3.68) and D-100 (2.34 points/week, 95% CI: 0.92, 3.76). Notably, D-50 arm showed significantly greater efficacy in patients with depression or elevated inflammation. Desvenlafaxine offers an effective and safe treatment regimen for HF in women with breast cancer taking tamoxifen. The presence of depression and inflammation may guide optimal desvenlafaxine dosing. (Trial Registration: ClinicalTrials.gov Identifier: NCT02819921).

Morbidity and Mortality After Laparoscopy-Assisted Distal Gastrectomy and Totally Laparoscopic Distal Gastrectomy to Treat Gastric Cancer: An Interim Report: A Phase III Multicenter, Prospective, Randomized Trial (The KLASS-07 Trial).

PURPOSE: We conducted a randomized prospective trial (KLASS-07 trial) to compare laparoscopy-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG) for gastric cancer. In this interim report, we describe short-term results in terms of morbidity and mortality. METHODS AND METHODS: The sample size was 442 participants. At the time of the interim analysis, 314 patients were enrolled and randomized. After excluding patients who did not undergo planned surgeries, we performed a modified per-protocol analysis of 151 and 145 patients in the LADG and TLDG groups, respectively. RESULTS: The baseline characteristics, including comorbidity status, did not differ between the LADG and TLDG groups. Blood loss was somewhat higher in the LADG group, but statistical significance was not attained (76.76±72.63 vs. 62.91±65.68 mL; P=0.087). Neither the required transfusion level nor the operation or reconstruction time differed between the 2 groups. The mini-laparotomy incision in the LADG group was significantly longer than the extended umbilical incision required for specimen removal in the TLDG group (4.79±0.82 vs. 3.89±0.83 cm; P<0.001). There were no between-group differences in the time to solid food intake, hospital stay, pain score, or complications within 30 days postoperatively. No mortality was observed in either group. CONCLUSIONS: Short-term morbidity and mortality rates did not differ between the LADG and TLDG groups. The KLASS-07 trial is currently underway. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03393182.

Revisiting the steatosis-associated fibrosis estimator score in young Asian subjects with steatotic liver disease and consideration for population variability.

BACKGROUND AND AIM: The steatosis-associated fibrosis estimator (SAFE) score has been developed to distinguish clinically significant fibrosis in patients with steatotic liver disease (SLD). However, validation of its performance in Asian subjects is limited. This study aimed to evaluate the performance of the SAFE score in Asian subjects with biopsy-proven SLD and in different subgroups according to age, sex, and body mass index. METHODS: We retrospectively analyzed 6383 living liver donors who underwent a liver biopsy between 2005 and 2023. Of these, 1551 subjects with biopsy-proven SLD were included. The performance of the SAFE score was evaluated using areas under the curve and compared with those of the nonalcoholic fatty liver disease fibrosis score (NFS) and fibrosis-4 index (FIB-4). RESULTS: The prevalence of clinically significant fibrosis in the cohort was 2.2%. The proportion of subjects with a "low-risk" SAFE score was the highest (91.0%), followed by those with "intermediate-risk" (7.8%) and "high-risk" (1.2%) scores. The prevalence of fibrosis in subjects with low-risk, intermediate-risk, and high-risk scores was 1.6%, 6.6%, and 21.1%, respectively. The SAFE outperformed FIB-4 and NFS (area under the curve: 0.70 vs 0.64 for both NFS and FIB-4). However, it showed low diagnostic accuracy and sensitivity (27%) at the low cutoff (SAFE < 0) in subjects aged 30-39 years (fibrosis: 1.2%), despite having a high negative predictive value (0.99). CONCLUSION: While the SAFE score demonstrates superior performance compared with other noninvasive tests in Asian subjects with SLD, its performance varies across age groups. In younger subjects, particularly, its performance may be more limited.

Dried Blood Spot Postmortem Metabolic Autopsy With Genotype Validation for Sudden Unexpected Deaths in Infancy and Childhood in Hong Kong.

Background Inborn errors of metabolism (IEM) are collectively rare but potentially preventable causes of sudden unexpected death (SUD) in infancy or childhood, and metabolic autopsy serves as the final tool for establishing the diagnosis. We conducted a retrospective review of the metabolic and molecular autopsy on SUD and characterized the biochemical and genetic findings. Methodology A retrospective review of postmortem metabolic investigations (dried blood spot acylcarnitines and amino acid analysis, urine metabolic profiling where available, and next-generation sequencing on a panel of 75 IEM genes) performed for infants and children who presented with SUD between October 2016 and December 2021 with inconclusive autopsy findings or autopsy features suspicious of underlying IEM in our locality was conducted. Clinical and autopsy findings were reviewed for each case. Results A total of 43 infants and children aged between zero days to 10 years at the time of death were referred to the authors' laboratories throughout the study period. One positive case of multiple acyl-CoA dehydrogenase deficiency was diagnosed. Postmortem reference intervals for dried blood spot amino acids and acylcarnitines profile were established based on the results from the remaining patients. Conclusions Our study confirmed the importance of metabolic autopsy and the advantages of incorporating biochemical and genetic testing in this setting.

Assessment of Treatment Response in Patients With Severe Asthma Using Visual and Quantitative Analysis of Chest CT.

OBJECTIVE: To evaluate the role of visual and quantitative chest CT parameters in assessing treatment response in patients with severe asthma. MATERIALS AND METHODS: Korean participants enrolled in a prospective multicenter study, named the Precision Medicine Intervention in Severe Asthma study, from May 2020 to August 2021, underwent baseline and follow-up chest CT scans (inspiration/expiration) 10-12 months apart, before and after biologic treatment. Two radiologists scored bronchiectasis severity and mucus plugging extent. Quantitative parameters were obtained from each CT scan as follows: normal lung area (normal), air trapping without emphysema (AT without emph), air trapping with emphysema (AT with emph), and airway (total branch count, Pi10). Clinical parameters, including pulmonary function tests (forced expiratory volume in 1 s [FEV1] and FEV1/forced vital capacity [FVC]), sputum and blood eosinophil count, were assessed at initial and follow-up stages. Changes in CT parameters were correlated with changes in clinical parameters using Pearson or Spearman correlation. RESULTS: Thirty-four participants (female:male, 20:14; median age, 50.5 years) diagnosed with severe asthma from three centers were included. Changes in the bronchiectasis and mucus plugging extent scores were negatively correlated with changes in FEV1 and FEV1/FVC (ρ = from -0.544 to -0.368, all P < 0.05). Changes in quantitative CT parameters were correlated with changes in FEV1 (normal, r = 0.373 [P = 0.030], AT without emph, r = -0.351 [P = 0.042]), FEV1/FVC (normal, r = 0.390 [P = 0.022], AT without emph, r = -0.370 [P = 0.031]). Changes in total branch count were positively correlated with changes in FEV1 (r = 0.349 [P = 0.043]). There was no correlation between changes in Pi10 and the clinical parameters (P > 0.05). CONCLUSION: Visual and quantitative CT parameters of normal, AT without emph, and total branch count may be effective for evaluating treatment response in patients with severe asthma.

Anatomical Reference of the Femur after Distal Resection Is Reliable for Rotational Alignment in Total Knee Arthroplasty.

The rotational alignment of the femoral component in total knee arthroplasty (TKA) is considered an important factor, but it is still difficult to assess intraoperatively. This study was conducted to identify anatomical parameters for femoral rotational alignment. A total of 204 patients who underwent primary TKA between 2015 and 2019 were enrolled. The femoral lateral (FLAP) and femoral medial anteroposterior (FMAP) lengths were measured as the widest lengths in the anteroposterior (AP) axis after distal femoral resection. The difference between FLAP and FMAP was defined as dFAP. The concordance correlation coefficient (CCC) was assessed for agreement between the cTEA-PCA and the value of femoral rotation using the linear regression analysis equation. HKA, FLAP, FMAP, and dFAP were significantly associated with femoral rotational alignment. The prediction equation combining the novel intraoperative anatomical references showed improved association with rotational alignment. If dFAP was 6.0 mm, the femoral rotation angle was calculated as 4.9° using this univariate regression equation. The CCC was 0.483, indicating moderate agreement. The dFAP showed an association with distal femoral rotational alignment. A 6 mm dFAP could be a reference for around 5° of femoral rotation. The equation developed in this study may be a reliable tool for intraoperative distal femoral rotational alignment.

Estrogen-related receptor alpha promotes thyroid tumor cell survival via a tumor subtype-specific regulation of target gene networks.

Mortalin (encoded by HSPA9) is a mitochondrial chaperone often overexpressed in cancer through as-yet-unknown mechanisms. By searching different RNA-sequencing datasets, we found that ESRRA is a transcription factor highly correlated with HSPA9 in thyroid cancer, especially in follicular, but not C cell-originated, tumors. Consistent with this correlation, ESRRA depletion decreased mortalin expression only in follicular thyroid tumor cells. Further, ESRRA expression and activity were relatively high in thyroid tumors with oncocytic characteristics, wherein ESRRA and mortalin exhibited relatively high functional overlap. Mechanistically, ESRRA directly regulated HSPA9 transcription through a novel ESRRA-responsive element located upstream of the HSPA9 promoter. Physiologically, ESRRA depletion suppressed thyroid tumor cell survival via caspase-dependent apoptosis, which ectopic mortalin expression substantially abrogated. ESRRA depletion also effectively suppressed tumor growth and mortalin expression in the xenografts of oncocytic or ESRRA-overexpressing human thyroid tumor cells in mice. Notably, our Bioinformatics analyses of patient data revealed two ESRRA target gene clusters that contrast oncocytic-like and anaplastic features of follicular thyroid tumors. These findings suggest that ESRRA is a tumor-specific regulator of mortalin expression, the ESRRA-mortalin axis has higher significance in tumors with oncocytic characteristics, and ESRRA target gene networks can refine molecular classification of thyroid cancer.

Focused ion beam-fabricated nanorod substrate for label-free surface-enhanced Raman spectroscopy and enabling dual virus detection.

The COVID-19 pandemic presents global challenges, notably with co-infections in respiratory tract involving SARS-CoV-2 variants and influenza strains. Detecting multiple viruses simultaneously is crucial for accurate diagnosis, effective tracking infectious sources, and containment of the epidemic. This study uses a label-free surface-enhanced Raman spectroscopy (SERS) method using Au NPs/pZrO2 (250) and FIB-made Au NRs (100) to detect dual viruses, including SARS-CoV-2 Delta variant (D) and influenza A (A) or B (B) virus. Results demonstrate distinct peaks facilitating virus differentiation, especially between D and A or B, with clear disparities between substrates; specific peaks at 950 and 1337 cm-1 are pivotal for discerning viruses using Au NPs/pZrO2 (250), while those at 1050, 1394, and 1450 cm-1 and 1033, 1165, 1337, and 1378 cm-1 are key for validation using Au NRs (100). Differences in substrate surface morphology and spatial disposition of accommodating viruses significantly influence hotspot formation and Raman signal amplification efficiency, thereby affecting the ability to distinguish various viruses. Furthermore, both substrates offer insights, even in the presence of oxymetazoline hydrochloride (an interfering substance), with practical implications in viral diagnosis. The customized design and reproducibility underscore efficient Raman signal amplification, even in challenging environments, highlighting potential for widespread virus detection.