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1.
Article in English | MEDLINE | ID: mdl-38747488

ABSTRACT

This work reveals the correlation between the performance of triboelectric nanogenerators (TENGs) and the characteristics of deformable solid-state ionic conductors (referred to as ionogels). For this purpose, we modify ionogel characteristics by incorporating additional plasticizers (propylene carbonate) and solid salts (lithium bis(trifluoromethylsulfonyl)imide) into the ionogels. We conclude that the high capacitance of the ionogel is crucial for achieving a high-performance TENG platform. The optimized ionogel-based TENG (i-TENG) exhibits a power density of ∼372.4 mW·m-2 (based on 95 V and 36 mA·m-2 outputs) with outstanding long-term stability over 2 weeks. Additionally, successful demonstrations of wearable nanogenerators are performed by leveraging the high stretchability (up to ∼1000%) and optical transparency (∼90%) of the ionogels. Overall, the results provide insight into the design of deformable ionic conductors for high-performance, reliable, and wearable TENGs.

2.
Cell Death Discov ; 10(1): 222, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719807

ABSTRACT

Neutrophil heterogeneity is involved in autoimmune diseases, sepsis, and several cancers. However, the link between neutrophil heterogeneity and T-cell immunity in thyroid cancer is incompletely understood. We investigated the circulating neutrophil heterogeneity in 3 undifferentiated thyroid cancer (UTC), 14 differentiated thyroid cancer (DTC) (4 Stage IV, 10 Stage I-II), and healthy controls (n = 10) by transcriptomic data and cytometry. Participants with UTC had a significantly higher proportion of immature high-density neutrophils (HDN) and lower proportion of mature HDN in peripheral blood compared to DTC. The proportion of circulating PD-L1+ immature neutrophils were significantly increased in advanced cancer patients. Unsupervised analysis of transcriptomics data from circulating HDN revealed downregulation of innate immune response and T-cell receptor signaling pathway in cancer patients. Moreover, UTC patients revealed the upregulation of glycolytic process and glutamate receptor signaling pathway. Comparative analysis across tumor types and stages revealed the downregulation of various T-cell-related pathways, such as T-cell receptor signaling pathway and T-cell proliferation in advanced cancer patients. Moreover, the proportions of CD8+ and CD4+ T effector memory CD45RA+ (TEMRA) cells from peripheral blood were significantly decreased in UTC patients compared to DTC patients. Finally, we demonstrated that proportions of tumor-infiltrated neutrophils were increased and related with poor prognosis in advanced thyroid cancer using data from our RNA-seq and TCGA (The Cancer Genome Atlas) data. In conclusion, observed prevalence of circulating immature high-density neutrophils and their immunosuppressive features in undifferentiated thyroid cancers underscore the importance of understanding neutrophil dynamics in the context of tumor progression in thyroid cancer.

3.
Perit Dial Int ; : 8968608241252015, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38738926

ABSTRACT

BACKGROUND: Varying peritoneal dialysis (PD)-related clinical outcomes have been reported in different countries. As a participant of the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS), this study investigated the characteristics of Korean PD patients, PD facilities and the incidence rates of clinical outcomes including mortality and PD-related outcomes. METHODS: From July 2019 to December 2021, a total of 766 Korean PD patients were included for analysis. Poisson regression analysis was used to explore the incidence rates of various clinical events including mortality, modality transfer, exit site or catheter tunnel infection and peritonitis. RESULTS: Among the 766 patients (median age 55.5 years, males 59.5%), 276 were incident and 490 were prevalent PD patients. The incidence rates of events were as follows: all-cause mortality (0.048), modality transfer (0.051), exit site or catheter tunnel infection (0.054) and peritonitis (0.136) events per person year. The most common causative organism for exit site or tunnel infection was staphylococcus species (47%) and that for peritonitis was streptococcus (28%) followed by staphylococcus (27%) species. CONCLUSIONS: Up to now, PDOPPS Korea has recruited 766 Korean PD patients and started documentation of major PD-related outcomes which occurred during the follow-up period. The overall incidence rates of clinical outcomes in Korean PD patients were relatively favourable. There was no statistically significant difference in the incidence rates of clinical outcomes according to both facility and patient factors.

4.
Mol Med Rep ; 30(1)2024 Jul.
Article in English | MEDLINE | ID: mdl-38757344

ABSTRACT

Muscle atrophy is a debilitating condition with various causes; while aging is one of these causes, reduced engagement in routine muscle­strengthening activities also markedly contributes to muscle loss. Although extensive research has been conducted on microRNAs (miRNAs/miRs) and their associations with muscle atrophy, the roles played by miRNA precursors remain underexplored. The present study detected the upregulation of the miR­206 precursor in cell­free (cf)RNA from the plasma of patients at risk of sarcopenia, and in cfRNAs from the muscles of mice subjected to muscle atrophy. Additionally, a decline in the levels of the miR­6516 precursor was observed in mice with muscle atrophy. The administration of mimic­miR­6516 to mice immobilized due to injury inhibited muscle atrophy by targeting and inhibiting cyclin­dependent kinase inhibitor 1b (Cdkn1b). Based on these results, the miR­206 precursor appears to be a potential biomarker of muscle atrophy, whereas miR­6516 shows promise as a therapeutic target to alleviate muscle deterioration in patients with muscle disuse and atrophy.


Subject(s)
MicroRNAs , MicroRNAs/genetics , MicroRNAs/metabolism , Animals , Mice , Humans , Male , Female , Muscular Atrophy/genetics , Muscular Atrophy/metabolism , Muscular Atrophy/pathology , Disease Models, Animal , Middle Aged , Aged , Muscular Disorders, Atrophic/genetics , Muscular Disorders, Atrophic/metabolism , Muscular Disorders, Atrophic/pathology , Muscular Disorders, Atrophic/therapy , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Biomarkers , Sarcopenia/metabolism , Sarcopenia/genetics , Sarcopenia/pathology , Sarcopenia/therapy , Adult
5.
Sci Rep ; 14(1): 11005, 2024 05 14.
Article in English | MEDLINE | ID: mdl-38745021

ABSTRACT

The SUVmax is a measure of FDG uptake and is related with tumor aggressiveness in thyroid cancer, however, its association with molecular pathways is unclear. Here, we investigated the relationship between SUVmax and gene expression profiles in 80 papillary thyroid cancer (PTC) patients. We conducted an analysis of DEGs and enriched pathways in relation to SUVmax and tumor size. SUVmax showed a positive correlation with tumor size and correlated with glucose metabolic process. The genes that indicate thyroid differentiation, such as SLC5A5 and TPO, were negatively correlated with SUVmax. Unsupervised analysis revealed that SUVmax positively correlated with DNA replication(r = 0.29, p = 0.009), pyrimidine metabolism(r = 0.50, p < 0.0001) and purine metabolism (r = 0.42, p = 0.0001). Based on subgroups analysis, we identified that PSG5, TFF3, SOX2, SL5A5, SLC5A7, HOXD10, FER1L6, and IFNA1 genes were found to be significantly associated with tumor aggressiveness. Both high SUVmax PTMC and macro-PTC are enriched in pathways of DNA replication and cell cycle, however, gene sets for purine metabolic pathways are enriched only in high SUVmax macro-PTC but not in high SUVmax PTMC. Our findings demonstrate the molecular characteristics of high SUVmax tumor and metabolism involved in tumor growth in differentiated thyroid cancer.


Subject(s)
Thyroid Cancer, Papillary , Thyroid Neoplasms , Transcriptome , Humans , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/metabolism , Female , Male , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Thyroid Neoplasms/metabolism , Middle Aged , Adult , Fluorodeoxyglucose F18 , Gene Expression Regulation, Neoplastic , Aged , Gene Expression Profiling , Tumor Burden/genetics
6.
Article in English | MEDLINE | ID: mdl-38719137

ABSTRACT

OBJECTIVE: Residual aortic dissection (AD) following DeBakey type I AD repair is associated with a high rate of adverse events that need additional intervention or surgery. This study aimed to identify clinical and early post-operative computed tomography (CT) imaging factors associated with adverse events in patients with type I AD after ascending aorta replacement. METHODS: This single centre, retrospective cohort study included consecutive patients with type I AD who underwent ascending aorta replacement from January 2011 to December 2017 and post-operative CT within 3 months. The primary outcome was AD related adverse events, defined as AD related death and re-operation due to aortic aneurysm or impending rupture. The location and size of the primary intimal tears, aortic diameter, and false lumen status were evaluated. Regression analyses were performed to identify factors associated with AD related adverse events. A decision tree model was used to classify patients as high or low risk. RESULTS: Of 103 participants (55.43 ± 13.94 years; 49.5% males), 24 (23.3%) experienced AD related adverse events. In multivariable Cox regression analysis, connective tissue disease (hazard ratio [HR] 15.33; p < .001), maximum aortic diameter ≥ 40 mm (HR 4.90; p < .001), and multiple (three or more) intimal tears (HR 7.12; p < .001) were associated with AD related adverse events. The 3 year cumulative survival free from AD related events was lower in the high risk group with aortic diameter ≥ 40 mm and multiple intimal tears (41.7% vs. 90.9%; p < .001). CONCLUSION: Early post-operative CT findings indicating a maximum aortic diameter ≥ 40 mm and multiple intimal tears may predict a higher risk of adverse events. These findings suggest the need for careful monitoring and more vigilant management approaches in these cases.

7.
Cell Rep Med ; : 101570, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38749422

ABSTRACT

While an association between Parkinson's disease (PD) and viral infections has been recognized, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on PD progression remains unclear. Here, we demonstrate that SARS-CoV-2 infection heightens the risk of PD using human embryonic stem cell (hESC)-derived dopaminergic (DA) neurons and a human angiotensin-converting enzyme 2 (hACE2) transgenic (Tg) mouse model. Our findings reveal that SARS-CoV-2 infection exacerbates PD susceptibility and cellular toxicity in DA neurons pre-treated with human preformed fibrils (hPFFs). Additionally, nasally delivered SARS-CoV-2 infects DA neurons in hACE2 Tg mice, aggravating the damage initiated by hPFFs. Mice infected with SARS-CoV-2 display persisting neuroinflammation even after the virus is no longer detectable in the brain. A comprehensive analysis suggests that the inflammatory response mediated by astrocytes and microglia could contribute to increased PD susceptibility associated with SARS-CoV-2. These findings advance our understanding of the potential long-term effects of SARS-CoV-2 infection on the progression of PD.

8.
Br J Pharmacol ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38751203

ABSTRACT

BACKGROUND AND PURPOSE: Cytoplasmic fragile X mental retardation 1 (FMR1)-interacting protein 2 (CYFIP2), as a component of the Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE) regulatory complex, is involved in actin polymerization, contributing to neuronal development and structural plasticity. Mutating serine-968 to phenylalanine (S968F) in CYFIP2 causes an altered cocaine response in mice. The neuronal mechanisms underlying this response remain unknown. EXPERIMENTAL APPROACH: We performed cocaine reward-related behavioural tests and examined changes in synaptic protein phenotypes and neuronal morphology in the nucleus accumbens (NAc), using CYFIP2 S968F knock-in mice to investigate the role of CYFIP2 in regulating cocaine reward. KEY RESULTS: CYFIP2 S968F mutation attenuated cocaine-induced behavioural sensitization and conditioned place preference. Cocaine-induced c-Fos was not observed in the NAc of CYFIP2 S968F knock-in mice. However, c-Fos induction was still evident in the medial prefrontal cortex (mPFC). CYFIP2 S968F mutation altered cocaine-associated CYFIP2 signalling, glutamatergic protein expression and synaptic density in the NAc following cocaine exposure. To further determine the role of CYFIP2 in NAc neuronal activity and the mPFC projecting to the NAc activity-mediating reward response, we used optogenetic tools to stimulate the NAc or mPFC-NAc pathway and observed that optogenetic activation of the NAc or mPFC-NAc pathway induced reward-related behaviours. This effect was not observed in the S968F mutation in CYFIP2. CONCLUSION AND IMPLICATIONS: These results suggest that CYFIP2 plays a role in controlling cocaine-mediated neuronal function and structural plasticity in the NAc, and that CYFIP2 could serve as a target for regulating cocaine reward.

9.
Ann Diagn Pathol ; 71: 152317, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38642470

ABSTRACT

We report a series of patients with CSF3R-mutant (CSF3Rmut) atypical chronic myeloid leukemia (aCML), chronic neutrophilic leukemia (CNL) or other hematologic malignancies. We included 25 patients: 5 aCML and 4 CNL CSF3Rmut patients; 1 aCML, 2 CNL, and 2 myelodysplastic/myeloproliferative neoplasm, not otherwise specified patients without CSF3R mutation; and 11 CSF3Rmut patients with other diseases [8 acute myeloid leukemia (AML), 1 chronic myelomonocytic leukemia (CMML), 1 myelodysplastic syndrome (MDS), and 1 acute lymphoblastic leukemia (ALL)]. Patients with aCML or CNL were tested by Sanger sequencing and pyrosequencing to identify CSF3R T618I. Twenty-two patients underwent gene panel analysis. CSF3R mutations, mostly T618I (8/9), were found at high frequencies in both aCML and CNL patients [5/6 aCML and 4/6 CNL]. Two aCML patients in early adulthood with CSF3R T618I and biallelic or homozygous CEBPA mutations without other mutations presented with increased blasts and exhibited remission for >6 years after transplantation. The other 7 CSF3Rmut aCML or CNL patients were elderly adults who all had ASXL1 mutations and frequently presented with SEBP1 and SRSF2 mutations. Five AML patients had CSF3R exon 14 or 15 point mutations, and 6 other patients (3 AML, 1 CMML, 1 MDS, and 1 ALL) had truncating mutations, demonstrating differences in leukocyte counts and mutation status. In conclusion, CSF3R mutations were found at a higher frequency in aCML patients than in previous studies, which might reflect ethnic differences. Additional studies are needed to confirm these findings and the relationship between CSF3R and CEBPA mutations.

11.
Mol Med Rep ; 29(6)2024 Jun.
Article in English | MEDLINE | ID: mdl-38606516

ABSTRACT

Muscular atrophy, which results in loss of muscle mass and strength, is a significant concern for patients with various diseases. It is crucial to comprehend the molecular mechanisms underlying this condition to devise targeted treatments. MicroRNAs (miRNAs) have emerged as key regulators of gene expression, serving vital roles in numerous cellular processes, including the maintenance of muscle stability. An intricate network of miRNAs finely regulates gene expression, influencing pathways related to muscle protein production, and muscle breakdown and regeneration. Dysregulation of specific miRNAs has been linked to the development of muscular atrophy, affecting important signaling pathways including the protein kinase B/mTOR and ubiquitin­proteasome systems. The present review summarizes recent work on miRNA patterns associated with muscular atrophy under various physiological and pathological conditions, elucidating its intricate regulatory networks. In conclusion, the present review lays a foundation for the development of novel treatment options for individuals affected by muscular atrophy, and explores other regulatory pathways, such as autophagy and inflammatory signaling, to ensure a comprehensive overview of the multifarious nature of muscular atrophy. The objective of the present review was to elucidate the complex molecular pathways involved in muscular atrophy, and to facilitate the development of innovative and specific therapeutic strategies for the prevention or reversal of muscular atrophy in diverse clinical scenarios.


Subject(s)
MicroRNAs , Muscular Diseases , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Muscle, Skeletal/metabolism , Muscular Atrophy/genetics , Muscular Atrophy/therapy , Muscular Atrophy/metabolism , Signal Transduction/genetics
12.
Diagnostics (Basel) ; 14(7)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38611613

ABSTRACT

BACKGROUND/AIMS: Rapid and accurate diagnostic tools are essential for the timely recognition of Helicobacter pylori (H. pylori) in clinical practice. The rapid urease test (RUT) is a comparatively accurate and time-saving method recommended as a first-line diagnostic test. The primary objective of conducting the RUT is to obtain rapid results, thus enabling the initiation of an eradication therapy based on clarithromycin resistance testing. This study aimed to assess the reaction time and accuracy of a new liquid-type RUT. METHOD: In this prospective study, consecutive dyspeptic or check-up patients referred to our clinic for endoscopy were assessed to evaluate the rapidity and accuracy of a novel liquid-type RUT (Helicotest®, WON Medical, Bucheon, Republic of Korea) compared with another commercial RUT kit (HP kit, Chong Kun Dang, Seoul, Republic of Korea) and a real-time quantitative PCR-based assay (Seeplex® H.pylori-ClaR Detection, Seegene, Republic of Korea). RUTs were analyzed at 10 min, 30 min, 60 min, and 120 min. RESULTS: Among the 177 enrolled patients, 38.6% were infected with H. pylori. The positivity rates of the liquid-type RUT were 26.1, 35.8, 39.2%, and 41.5% at 10, 30, 60, and 120 min, respectively. When compared with the HP kit test, the time needed to confirm positivity was significantly reduced by 28.6 min (95% CI, 16.60-39.73, p < 0.0001). Helicotest® had a greater accuracy (96.02 ± 1.47), sensitivity (98.53 ± 1.46) and NPV (99.03 ± 0.97) compared to the HP kit. CONCLUSIONS: Compared to the commonly used RUT, the new liquid-type RUT presented faster and reliable results. Such findings could improve H. pylori treatment outcomes, particularly in outpatient clinical settings.

13.
Molecules ; 29(7)2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38611843

ABSTRACT

Methotrexate (MTX) has poor water solubility and low bioavailability, and cancer cells can become resistant to it, which limits its safe delivery to tumor sites and reduces its clinical efficacy. Herein, we developed novel redox-responsive hybrid nanoparticles (NPs) from hyaluronic acid (HA) and 3-mercaptopropionic acid (MPA)-coated gold NPs (gold@MPA NPs), which were further conjugated with folic acid (FA). The design of FA-HA-ss-gold NPs aimed at enhancing cellular uptake specifically in cancer cells using an active FA/HA dual targeting strategy for enhanced tumor eradication. MTX was successfully encapsulated into FA-HA-ss-gold NPs, with drug encapsulation efficiency (EE) as high as >98.7%. The physicochemical properties of the NPs were investigated in terms of size, surface charges, wavelength reflectance, and chemical bonds. MTX was released in a sustained manner in glutathione (GSH). The cellular uptake experiments showed effective uptake of FA-HA-ss-gold over HA-ss-gold NPs in the deep tumor. Moreover, the release studies provided strong evidence that FA-HA-ss-gold NPs serve as GSH-responsive carriers. In vitro, anti-tumor activity tests showed that FA-HA-ss-gold/MTX NPs exhibited significantly higher cytotoxic activity against both human cervical cancer (HeLa) cells and breast cancer (BT-20) cells compared to gold only and HA-ss-gold/MTX NPs while being safe for human embryonic kidney (HEK-293) cells. Therefore, this present study suggests that FA-HA-ss-gold NPs are promising active targeting hybrid nanocarriers that are stable, controllable, biocompatible, biodegradable, and with enhanced cancer cell targetability for the safe delivery of hydrophobic anticancer drugs.


Subject(s)
Folic Acid , Metal Nanoparticles , Humans , Gold , Hyaluronic Acid , HEK293 Cells , Methotrexate/pharmacology , Glutathione
14.
Gigascience ; 132024 Jan 02.
Article in English | MEDLINE | ID: mdl-38626723

ABSTRACT

BACKGROUND: Phenome-wide association studies (PheWASs) have been conducted on Asian populations, including Koreans, but many were based on chip or exome genotyping data. Such studies have limitations regarding whole genome-wide association analysis, making it crucial to have genome-to-phenome association information with the largest possible whole genome and matched phenome data to conduct further population-genome studies and develop health care services based on population genomics. RESULTS: Here, we present 4,157 whole genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest genomic resource of the Korean Genome Project. It encompasses most of the variants with allele frequency >0.001 in Koreans, indicating that it sufficiently covered most of the common and rare genetic variants with commonly measured phenotypes for Koreans. Korea4K provides 45,537,252 variants, and half of them were not present in Korea1K (1,094 samples). We also identified 1,356 new genotype-phenotype associations that were not found by the Korea1K dataset. Phenomics analyses further revealed 24 significant genetic correlations, 14 pleiotropic associations, and 127 causal relationships based on Mendelian randomization among 37 traits. In addition, the Korea4K imputation reference panel, the largest Korean variants reference to date, showed a superior imputation performance to Korea1K across all allele frequency categories. CONCLUSIONS: Collectively, Korea4K provides not only the largest Korean genome data but also corresponding health check-up parameters and novel genome-phenome associations. The large-scale pathological whole genome-wide omics data will become a powerful set for genome-phenome level association studies to discover causal markers for the prediction and diagnosis of health conditions in future studies.


Subject(s)
Genome-Wide Association Study , Polymorphism, Single Nucleotide , Humans , Phenotype , Genetic Association Studies , Gene Frequency , Republic of Korea , Genotype
15.
Br J Pharmacol ; 2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38644533

ABSTRACT

BACKGROUND AND PURPOSE: Methamphetamine (METH) use disorder has risen dramatically over the past decade, and there are currently no FDA-approved medications due, in part, to gaps in our understanding of the pharmacological mechanisms related to METH action in the brain. EXPERIMENTAL APPROACH: Here, we investigated whether transient receptor potential ankyrin 1 (TRPA1) mediates each of several METH abuse-related behaviours in rodents: self-administration, drug-primed reinstatement, acquisition of conditioned place preference, and hyperlocomotion. Additionally, METH-induced molecular (i.e., neurotransmitter and protein) changes in the brain were compared between wild-type and TRPA1 knock-out mice. Finally, the relationship between TRPA1 and the dopamine transporter was investigated through immunoprecipitation and dopamine reuptake assays. KEY RESULTS: TRPA1 antagonism blunted METH self-administration and drug-primed reinstatement of METH-seeking behaviour. Further, development of METH-induced conditioned place preference and hyperlocomotion were inhibited by TRPA1 antagonist treatment, effects that were not observed in TRPA1 knock-out mice. Similarly, molecular studies revealed METH-induced increases in dopamine levels and expression of dopamine system-related proteins in wild-type, but not in TRPA1 knock-out mice. Furthermore, pharmacological blockade of TRPA1 receptors reduced the interaction between TRPA1 and the dopamine transporter, thereby increasing dopamine reuptake activity by the transporter. CONCLUSION AND IMPLICATIONS: This study demonstrates that TRPA1 is involved in the abuse-related behavioural effects of METH, potentially through its modulatory role in METH-induced activation of dopaminergic neurotransmission. Taken together, these data suggest that TRPA1 may be a novel therapeutic target for treating METH use disorder.

16.
Nat Commun ; 15(1): 3459, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658566

ABSTRACT

Establishing dependable, cost-effective electrical connections is vital for enhancing device performance and shrinking electronic circuits. MXenes, combining excellent electrical conductivity, high breakdown voltage, solution processability, and two-dimensional morphology, are promising candidates for contacts in microelectronics. However, their hydrophilic surfaces, which enable spontaneous environmental degradation and poor dispersion stability in organic solvents, have restricted certain electronic applications. Herein, electrohydrodynamic printing technique is used to fabricate fully solution-processed thin-film transistors with alkylated 3,4-dihydroxy-L-phenylalanine functionalized Ti3C2Tx (AD-MXene) as source, drain, and gate electrodes. The AD-MXene has excellent dispersion stability in ethanol, which is required for electrohydrodynamic printing, and maintains high electrical conductivity. It outperformed conventional vacuum-deposited Au and Al electrodes, providing thin-film transistors with good environmental stability due to its hydrophobicity. Further, thin-film transistors are integrated into logic gates and one-transistor-one-memory cells. This work, unveiling the ligand-functionalized MXenes' potential in printed electrical contacts, promotes environmentally robust MXene-based electronics (MXetronics).

17.
Front Cell Infect Microbiol ; 14: 1287557, 2024.
Article in English | MEDLINE | ID: mdl-38577619

ABSTRACT

Despite extensive knowledge of antibiotic-targeted bacterial cell death, deeper understanding of antibiotic tolerance mechanisms is necessary to combat multi-drug resistance in the global healthcare settings. Regulatory RNAs in bacteria control important cellular processes such as cell division, cellular respiration, metabolism, and virulence. Here, we investigated how exposing Escherichia coli to the moderately effective first-generation antibiotic cephalothin alters transcriptional and post-transcriptional dynamics. Bacteria switched from active aerobic respiration to anaerobic adaptation via an FnrS and Tp2 small RNA-mediated post-transcriptional regulatory circuit. From the early hours of antibiotic exposure, FnrS was involved in regulating reactive oxygen species levels, and delayed oxygen consumption in bacteria. We demonstrated that bacteria strive to maintain cellular homeostasis via sRNA-mediated sudden respiratory changes upon sublethal antibiotic exposure.


Subject(s)
Anti-Bacterial Agents , RNA , Anti-Bacterial Agents/pharmacology , Anaerobiosis , Cell Respiration , Bacteria , Respiration , Gene Expression Regulation, Bacterial
18.
Eur J Surg Oncol ; 50(6): 108308, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38583214

ABSTRACT

BACKGROUND: Around 20% of rectal tumors are locally advanced with invasion into adjacent structures at presentation. These may require surgical resections beyond boundaries of total mesorectal excision (bTME) for radicality. Robotic bTME is under investigation. This study reports perioperative and oncological outcomes of robotic bTME for locally advanced rectal cancers. MATERIALS AND METHODS: A multicentre, retrospective analysis of prospectively collected robotic bTME resections (July 2015-November 2020). Demographics, clinicopathological features, short-term outcomes, recurrences, and survival were investigated. RESULTS: One-hundred-sixty-eight patients (eight centres) were included. Median age and BMI were 60.0 (50.0-68.7) years and 24.0 (24.4-27.7) kg/m2. Female sex was prevalent (n = 95, 56.8%). Fifty patients (29.6%) were ASA III-IV. Neoadjuvant chemoradiotherapy was given to 125 (74.4%) patients. Median operative time was 314.0 (260.0-450.0) minutes. Median estimated blood loss was 150.0 (27.5-500.0) ml. Conversion to laparotomy was seen in 4.8%. Postoperative complications occurred in 77 (45.8%) patients; 27.3% and 3.9% were Clavien-Dindo III and IV, respectively. Thirty-day mortality was 1.2% (n = 2). R0 rate was 92.9%. Adjuvant chemotherapy was offered to 72 (42.9%) patients. Median follow-up was 34.0 (10.0-65.7) months. Distant and local recurrences were seen in 35 (20.8%) and 15 patients (8.9%), respectively. Overall survival (OS) at 1, 3, and 5-years was 91.7, 82.1, and 76.8%. Disease-free survival (DFS) at 1, 3, and 5-years was 84.0, 74.5, and 69.2%. CONCLUSION: Robotic bTME is technically safe with relatively low conversion rate, good OS, and acceptable DFS in the hands of experienced surgeons in high volume centres. In selected cases robotic approach allows for high R0 rates during bTME.

19.
J Clin Med ; 13(5)2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38592109

ABSTRACT

(1) Introduction: The laparoscopic approach to low pelvic tumors is challenging and hindered by suboptimal tumor visualization and dissection, with possible oncological failure. Stereotactic navigation provides real-time image guidance that may optimize safety, accuracy, and precision when dissecting challenging low pelvic tumors. (2) Methods: Preoperative CT images were acquired with eight skin-fixed fiducials and loaded into a navigation system. A patient tracker was mounted on the bed side. Patient-to-image paired point registration was performed, and an instrument tracker was mounted on a laparoscopic instrument and calibrated for instrument tracking. Surgical operations were performed with real-time stereotactic navigation assistance. (3) Results: Three patients underwent stereotactic navigation surgery. Fiducial registration errors were good to optimal (±1.9, ±3.4, and ±3.4 mm). Lesions were easily identified and targeted with real-time navigation. Surgeries were uneventful. Histopathology examinations identified one retro-rectal schwannoma, one lateral pelvic recurrence from rectal adenocarcinoma, and one advanced anal canal carcinoma. No navigation-related complications, readmissions, or postoperative mortalities were observed. (4) Conclusions: The application of laparoscopic stereotactic navigation surgery to complex low pelvic tumors is feasible and could impact oncological surgical quality by enabling tumor targeting and ensuring resection margins. Further wider series are needed to confirm stereotactic navigation's impact on challenging low pelvic tumors.

20.
Adv Mater ; : e2313688, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38685135

ABSTRACT

Reliability of power supply for current implantable electronic devices is a critical issue for longevity and for reducing the risk of device failure. Energy harvesting is an emerging technology, representing a strategy for establishing autonomous power supply by utilizing biomechanical movements in human body. Here, a novel "Twistron energy cell harvester" (TECH), consisting of coiled carbon nanotube yarn that converts mechanical energy of the beating heart into electrical energy, is presented. The performance of TECH is evaluated in an in vitro artificial heartbeat system which simulates the deformation pattern of the cardiac surface, reaching a maximum peak power of 1.42 W kg-1 and average power of 0.39 W kg-1 at 60 beats per minute. In vivo implantation of TECH onto the left ventricular surface in a porcine model continuously generates electrical energy from cardiac contraction. The generated electrical energy is used for direct pacing of the heart as documented by extensive electrophysiology mapping. Implanted modified carbon nanotubes are applicable as a source for harvesting biomechanical energy from cardiac motion for power supply or cardiac pacing.

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