Dietary effects of vitamin C on antioxidant capacity, intestinal microbiota and the resistance of pathogenic bacteria in cultured Silver pomfret (Pampus argenteus).

As most teleosts are unable to synthesize vitamin C, supplemental diets containing vitamin C diets play a crucial role in fish health. The aim of this study was to investigate the effect of dietary vitamin C on the intestinal enzyme activity and intestinal microbiota of silver pomfre (Pampus argenteus). Four experimental diets were supplemented with basic diets containing 300 mg of vitamin C/kg (group tjl3), 600 mg of vitamin C/kg (group tjl6), and 1200 mg of vitamin C/kg (group tjl12), as well as vitamin C-free supplemental basic diet (group tjl0), respectively. The four diets were fed to juvenile P. argenteus (average initial weight: 4.68 ± 0.93 g) for 6 weeks. The results showed that the activity of SOD (superoxide dismutase) and CAT (catalase) increased significantly while that of MDA (malondialdehyde) decreased significantly in group tjl3 compared to vitamin group tjl0. At the genus level, groups tjl0, tjl6, and tjl12 contained the same dominant microbial community, Stenotrophomonas, Photobacterium, and Vibrio, whereas group tjl3 was dominated by Stenotrophomonas, Delftia, and Bacteroides. Among the fish fed with a basic diet containing 300 mg of vitamin C/kg, the intestines exhibited a notable abundance of probiotic bacteria, including lactic acid bacteria (Lactobacillus) and Bacillus. The abundance of Aeromonas in groups tjl3 and tjl6 was lower than that of the vitamin C-free supplemental basic diet group, whereas Aeromonas was not detected in group tjl12. In addition, a causative agent of the disease outbreak in cultured P. argenteus, Photobacterium damselae subsp. Damselae (PDD) was the dominant microbiota community in groups tjl0, tjl6 and tjl12, whereas the abundance of PDD in group tjl3 was the lowest among the diets. Taken together, the diets supplied with vitamin C could influence the composition microbial community of P. argenteus. The low level of vitamin C (300 mg of vitamin C/kg per basic diet) supplementation could not only improve the antioxidant capacity but also resist the invasion of pathogenic bacteria.

Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis.

The initiation of osteogenesis primarily occurs as mesenchymal stem cells undergo differentiation into osteoblasts. This differentiation process plays a crucial role in bone formation and homeostasis and is regulated by two intricate processes: cell signal transduction and transcriptional gene expression. Various essential cell signaling pathways, including Wnt, BMP, TGF-ß, Hedgehog, PTH, FGF, Ephrin, Notch, Hippo, and Piezo1/2, play a critical role in facilitating osteoblast differentiation, bone formation, and bone homeostasis. Key transcriptional factors in this differentiation process include Runx2, Cbfß, Runx1, Osterix, ATF4, SATB2, and TAZ/YAP. Furthermore, a diverse array of epigenetic factors also plays critical roles in osteoblast differentiation, bone formation, and homeostasis at the transcriptional level. This review provides an overview of the latest developments and current comprehension concerning the pathways of cell signaling, regulation of hormones, and transcriptional regulation of genes involved in the commitment and differentiation of osteoblast lineage, as well as in bone formation and maintenance of homeostasis. The paper also reviews epigenetic regulation of osteoblast differentiation via mechanisms, such as histone and DNA modifications. Additionally, we summarize the latest developments in osteoblast biology spurred by recent advancements in various modern technologies and bioinformatics. By synthesizing these insights into a comprehensive understanding of osteoblast differentiation, this review provides further clarification of the mechanisms underlying osteoblast lineage commitment, differentiation, and bone formation, and highlights potential new therapeutic applications for the treatment of bone diseases.

Reassessment of EUS features in preoperative diagnosis of pancreatic serous cystic neoplasm: Lessons to avoid misdiagnosis.

OBJECTIVES: Pancreatic serous cystic neoplasm (SCN) is a benign cystic neoplasm that is likely to be surgically resected due to preoperative misdiagnosis or tentative diagnosis even using endoscopic ultrasonography (EUS). We aimed to analyze EUS findings of SCN associated with misdiagnosis. METHODS: Between January 2012 and September 2023, histologically confirmed pancreatic SCN were included and EUS features were reviewed. RESULTS: Overall, 294 patients with 300 surgically resected SCNs were included. The median age of the patients was 51 years and 75.9% were females. The lesions were predominantly located in the body/neck/tail of the pancreas (63.0%). The overall preoperative diagnostic rate of SCN was 36.3%, with the most common misdiagnosis being intraductal papillary mucinous neoplasm (IPMN) (31.3%), while 16.3% remained undefined. The preoperative diagnostic rate of SCN varied across different endosonographic morphologies, with oligocystic, macrocystic, microcystic, and solid patterns yielding rates of 12.8%, 37.9%, 76.5%, and 19.2%, respectively. Notably, the presence of central scar and vascularity improved the diagnostic accuracy and correctly identified 41.4% and 52.3% of the lesions. While mucus or pancreatic duct (PD) communication significantly increased the likelihood of misdiagnosis, particularly as IPMN. Multivariate analysis revealed a morphological pattern, mucin-producing signs, wall thickening, vascularity, and PD communication were independent factors related to preoperative misdiagnosis, with an overall accuracy of 82.3%. CONCLUSIONS: Preoperative diagnosis of SCN remains challenging. The microcystic pattern emerged as a reliable feature, while mucin-producing signs, including mural nodules, mucus, and PD communication, pose diagnostic pitfalls despite the presence of typical central scar or vascularity commonly in SCN.

FABP3 Induces Mitochondrial Autophagy to Promote Neuronal Cell Apoptosis in Brain Ischemia-Reperfusion Injury.

This study elucidates the molecular mechanisms by which FABP3 regulates neuronal apoptosis via mitochondrial autophagy in the context of cerebral ischemia-reperfusion (I/R). Employing a transient mouse model of middle cerebral artery occlusion (MCAO) established using the filament method, brain tissue samples were procured from I/R mice. High-throughput transcriptome sequencing on the Illumina CN500 platform was performed to identify differentially expressed mRNAs. Critical genes were selected by intersecting I/R-related genes from the GeneCards database with the differentially expressed mRNAs. The in vivo mechanism was explored by infecting I/R mice with lentivirus. Brain tissue injury, infarct volume ratio in the ischemic penumbra, neurologic deficits, behavioral abilities, neuronal apoptosis, apoptotic factors, inflammatory factors, and lipid peroxidation markers were assessed using H&E staining, TTC staining, Longa scoring, rotation experiments, immunofluorescence staining, and Western blot. For in vitro validation, an OGD/R model was established using primary neuron cells. Cell viability, apoptosis rate, mitochondrial oxidative stress, morphology, autophagosome formation, membrane potential, LC3 protein levels, and colocalization of autophagosomes and mitochondria were evaluated using MTT assay, LDH release assay, flow cytometry, ROS/MDA/GSH-Px measurement, transmission electron microscopy, MitoTracker staining, JC-1 method, Western blot, and immunofluorescence staining. FABP3 was identified as a critical gene in I/R through integrated transcriptome sequencing and bioinformatics analysis. In vivo experiments revealed that FABP3 silencing mitigated brain tissue damage, reduced infarct volume ratio, improved neurologic deficits, restored behavioral abilities, and attenuated neuronal apoptosis, inflammation, and mitochondrial oxidative stress in I/R mice. In vitro experiments demonstrated that FABP3 silencing restored OGD/R cell viability, reduced neuronal apoptosis, and decreased mitochondrial oxidative stress. Moreover, FABP3 induced mitochondrial autophagy through ROS, which was inhibited by the free radical scavenger NAC. Blocking mitochondrial autophagy with sh-ATG5 lentivirus confirmed that FABP3 induces mitochondrial dysfunction and neuronal apoptosis by activating mitochondrial autophagy. In conclusion, FABP3 activates mitochondrial autophagy through ROS, leading to mitochondrial dysfunction and neuronal apoptosis, thereby promoting cerebral ischemia-reperfusion injury.

Yearly change in air pollution and brain aging among older adults: A community-based study in Taiwan.

BACKGROUND: Air pollution is recognized as a modifiable risk factor for dementia, and recent evidence suggests that improving air quality could attenuate cognitive decline and reduce dementia risk. However, studies have yet to explore the effects of improved air quality on brain structures. This study aims to investigate the impact of air pollution reduction on cognitive functions and structural brain differences among cognitively normal older adults. METHODS: Four hundred and thirty-one cognitively normal older adults were from the Epidemiology of Mild Cognitive Impairment study in Taiwan (EMCIT), a community-based cohort of adults aged 60 and older, between year 2017- 2021. Annual concentrations of PM2.5, NO2, O3, and PM10 at participants' residential addresses during the 10 years before enrollment were estimated using ensemble mixed spatial models. The yearly rate of change (slope) in air pollutants was estimated for each participant. Cognitive functions and structural brain images were collected during enrollment. The relationships between the rate of air pollution change and cognitive functions were examined using linear regression models. For air pollutants with significant findings in relation to cognitive function, we further explored the association with brain structure. RESULTS: Overall, all pollutant concentrations, except O3, decreased over the 10-year period. The yearly rates of change (slopes) in PM2.5 and NO2 were correlated with better attention (PM2.5: r = -0.1, p = 0.047; NO2: r = -0.1, p = 0.03) and higher white matter integrity in several brain regions. These regions included anterior thalamic radiation, superior longitudinal fasciculus, inferior longitudinal fasciculus, corticospinal tract, and inferior fronto-occipital fasciculus. CONCLUSIONS: Greater rate of reduction in air pollution was associated with better attention and attention-related white matter integrity. These results provide insight into the mechanism underlying the relationship between air pollution, brain health, and cognitive aging among older adults.

Global current research status and future hotspots in osteoporotic fracture based on bibliometric assessment and visualization techniques.

BACKGROUND: In the past decade, the evolution of themes in the field of osteoporotic fractures has changed from epidemiology and prediction of long-term morbidity, risk assessment of osteoporotic fractures, and zoledronic acid and denosumab in the treatment of osteoporosis to treatment guidelines for osteoporosis and the side effects caused by anti-osteoporotic drugs. AIM: To understand the trends and hotspots in osteoporotic fracture research. METHODS: Original articles were retrieved between January 1, 2010, and December 31, 2019, from the Web of Science Core Collection database. CiteSpace software facilitated the analysis and visualization of scientific productivity and emerging trends. RESULTS: Nine studies were identified using bibliometric indices, including citation, centrality, and sigma value, which might indicate a growing trend. Through clustering, we identified six major hot subtopics. Using burst analysis, top-5 references with the strongest bursting strength after 2017 were identified, indicating a future hotspot in this field. CONCLUSION: Current hot subtopics in osteoporotic fracture research include atypical femoral fractures, androgen deprivation therapy, denosumab discontinuation, hip fractures, trabecular bone score (TBS), and bone phenotype. Management and prevention of secondary fractures in patients with osteoporotic fractures, TBSs, and long-term administration strategy for zoledronic acid are expected to become research hotspots.

Wnt/ß-catenin signaling components and mechanisms in bone formation, homeostasis, and disease.

Wnts are secreted, lipid-modified proteins that bind to different receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways, which control various biological processes throughout embryonic development and adult life. Aberrant Wnt signaling pathway underlies a wide range of human disease pathogeneses. In this review, we provide an update of Wnt/ß-catenin signaling components and mechanisms in bone formation, homeostasis, and diseases. The Wnt proteins, receptors, activators, inhibitors, and the crosstalk of Wnt signaling pathways with other signaling pathways are summarized and discussed. We mainly review Wnt signaling functions in bone formation, homeostasis, and related diseases, and summarize mouse models carrying genetic modifications of Wnt signaling components. Moreover, the therapeutic strategies for treating bone diseases by targeting Wnt signaling, including the extracellular molecules, cytosol components, and nuclear components of Wnt signaling are reviewed. In summary, this paper reviews our current understanding of the mechanisms by which Wnt signaling regulates bone formation, homeostasis, and the efforts targeting Wnt signaling for treating bone diseases. Finally, the paper evaluates the important questions in Wnt signaling to be further explored based on the progress of new biological analytical technologies.

Deep brain stimulation of the Tbr1-deficient mouse model of autism spectrum disorder at the basolateral amygdala alters amygdalar connectivity, whole-brain synchronization, and social behaviors.

Autism spectrum disorders (ASDs) are considered neural dysconnectivity syndromes. To better understand ASD and uncover potential treatments, it is imperative to know and dissect the connectivity deficits under conditions of autism. Here, we apply a whole-brain immunostaining and quantification platform to demonstrate impaired structural and functional connectivity and aberrant whole-brain synchronization in a Tbr1+/-autism mouse model. We express a channelrhodopsin variant oChIEF fused with Citrine at the basolateral amygdala (BLA) to outline the axonal projections of BLA neurons. By activating the BLA under blue light theta-burst stimulation (TBS), we then evaluate the effect of BLA activation on C-FOS expression at a whole brain level to represent neural activity. We show that Tbr1 haploinsufficiency almost completely disrupts contralateral BLA axonal projections and results in mistargeting in both ipsilateral and contralateral hemispheres, thereby globally altering BLA functional connectivity. Based on correlated C-FOS expression among brain regions, we further show that Tbr1 deficiency severely disrupts whole-brain synchronization in the absence of salient stimulation. Tbr1+/-and wild-type (WT) mice exhibit opposing responses to TBS-induced amygdalar activation, reducing synchronization in WT mice but enhancing it in Tbr1+/-mice. Whole-brain modular organization and intermodule connectivity are also affected by Tbr1 deficiency and amygdalar activation. Following BLA activation by TBS, the synchronizations of the whole brain and the default mode network, a specific subnetwork highly relevant to ASD, are enhanced in Tbr1+/-mice, implying a potential ameliorating effect of amygdalar stimulation on brain function. Indeed, TBS-mediated BLA activation increases nose-to-nose social interactions of Tbr1+/-mice, strengthening evidence for the role of amygdalar connectivity in social behaviors. Our high-resolution analytical platform reveals the inter- and intrahemispheric connectopathies arising from ASD. Our study emphasizes the defective synchronization at a whole-brain scale caused by Tbr1 deficiency and implies a potential beneficial effect of deep brain stimulation at the amygdala for TBR1-linked autism.

DNA cytosine methyltransferases differentially regulate genome-wide hypermutation and interhomolog recombination in Trichoderma reesei meiosis.

Trichoderma reesei is an economically important enzyme producer with several unique meiotic features. spo11, the initiator of meiotic double-strand breaks (DSBs) in most sexual eukaryotes, is dispensable for T. reesei meiosis. T. reesei lacks the meiosis-specific recombinase Dmc1. Rad51 and Sae2, the activator of the Mre11 endonuclease complex, promote DSB repair and chromosome synapsis in wild-type and spo11Δ meiosis. DNA methyltransferases (DNMTs) perform multiple tasks in meiosis. Three DNMT genes (rid1, dim2 and dimX) differentially regulate genome-wide cytosine methylation and C:G-to-T:A hypermutations in different chromosomal regions. We have identified two types of DSBs: type I DSBs require spo11 or rid1 for initiation, whereas type II DSBs do not rely on spo11 and rid1 for initiation. rid1 (but not dim2) is essential for Rad51-mediated DSB repair and normal meiosis. rid1 and rad51 exhibit a locus heterogeneity (LH) relationship, in which LH-associated proteins often regulate interconnectivity in protein interaction networks. This LH relationship can be suppressed by deleting dim2 in a haploid rid1Δ (but not rad51Δ) parental strain, indicating that dim2 and rid1 share a redundant function that acts earlier than rad51 during early meiosis. In conclusion, our studies provide the first evidence of the involvement of DNMTs during meiotic initiation and recombination.

Extracellular Matrix Remodelling of the Periodontium under Orthodontic Force.

As the biological mechanisms of orthodontic tooth movement have been explored further, scholars have gradually focused on the remodelling mechanism of the extracellular matrix (ECM) in the periodontal ligament (PDL). The ECM of the PDL consists of various types of collagens and other glycoproteins. The specific process and mechanism of ECM remodelling during orthodontic tooth movement remains unclear. Collagen I and III, which constitute major components of the PDL, are upregulated under orthodontic force. The changes in the contents of ECM proteins also depend on the expression of ECM-related enzymes, which organise new collagen fibre networks to adapt to changes in tooth position. The matrix metalloproteinase family is the main enzyme that participates in collagen hydrolysis and renewal and changes its expression under orthodontic force. Moreover, ECM adhesion molecules, such as integrins, are also regulated by orthodontic force and participate in the dynamic reaction of cell adhesion and separation with the ECM. This article reviews the changes in ECM components, related enzymes and adhesion molecules in the PDL under orthodontic force to lay the foundation for the exploration of the regulatory mechanism of ECM remodelling during orthodontic tooth movement.

The impact of photobiomodulation on sleep and life quality in hemodialysis patients: A randomized controlled trial.

The quality of life (QoL) and sleep quality are closely linked to the physical and psychological health of end-stage renal disease (ESRD) patients, especially those underwent hemodialysis (HD) therapy. This study aims to investigate the impact of 830 nm laser treatment on improving QoL and sleep quality in HD patients. Forty ESRD patients participated in this study. 830 nm laser was used to radiate on the palm (at dose of 256.10 J/cm2), ST 36 and KI 1 acupoints (at dose of 109.76 J/cm2) of HD patients, and QoL and sleep quality questionnaires were utilized to assess changes following the treatment. After 830 nm laser radiation, lower global Pittsburgh Sleep Quality Index and Athens Insomnia Scale scores were observed, accompanied by higher physical and mental component summary scores in MOS 36-item short-form health survey version 2 and a global World Health Organization Quality of Life Brief Version score. The laser group also showed significant improvements in QoL and sleep quality indicators. Additionally, pain levels decreased on the third day and after one month according to visual analogue scale. This study revealed the positive effects of 830 nm laser on palm, KI 1 and ST 36 acupoints for improving the QoL and sleep quality in ESRD patients underwent HD treatment. The results suggest that 830 nm laser applied to specific targets could be used as a complementary and alternative approach to increase the QoL and sleep quality in ESRD patients.

Preliminary evidence for therapeutic impact of intravesical glucosamine on protamine sulfate and potassium chloride-induced bladder overactivity in rat model.

PURPOSE: To investigate the protective effect of intravesical glucosamine in treating overactive bladder (OAB). METHODS: Ninety-two female Sprague-Dawley (SD) rats were divided into 4 groups i.e. protamine sulfate (PS), N-acetylcysteine (NAC), and glucosamine-treated PS (GPS), and normal saline control (NC) were used. We induced hyperactivity in rats via intravesical infusion of PS and potassium chloride (KCl), whereas the NC group underwent a sustained intravesical saline infusion for 1 h. N-acetylcysteine (NAC), a potential antioxidant as well as anti-inflammatory agent was employed as positive control. Cystometrography (CMG) was then conducted to determine urodynamic parameters, i.e., leak point pressure (LPP, n = 48) and inter-contractile interval, the duration between two voids (ICI, n = 32). RESULTS: LPP was significantly elevated in the GPS group (mean ± SD: 110.9 ± 6.2 mmHg) compared to the NC (81.0 ± 32.5 mmHg), PS (40.3 ± 10.9 mmHg), and NAC group (70.3 ± 19.4 mmHg). The cystometrogram data also reveals a prolonged ICI in the GPS group (241.3 ± 40.2 s) compared to the NC group (216.0 ± 41.7 s), PS group (128.8 ± 23.6 s), and NAC group (193.8 ± 28.3 s). CONCLUSION: This preliminary study implies the ameliorative impact of GPS treatment on OAB in terms of improved urodynamic parameters, including LPP and ICI.

Role of TAP1 in the identification of immune-hot tumor microenvironment and its prognostic significance for immunotherapeutic efficacy in gastric carcinoma.

Background: Gastric cancer (GC), a multifaceted gastrointestinal malignancy, is the fourth most prevalent contributor to cancer-related fatalities globally. As a member of the ATP-binding cassette (ABC) family, transporter associated with antigen processing 1 (TAP1) is crucial for conveying antigen peptides from the cytoplasm to the lumen of the endoplasmic reticulum and subsequently loading them onto the major histocompatibility complex (MHC) class I molecules. Recent studies have established the biological significance of TAP1 in upholding tumor survival and facilitating immune evasion by remodeling the tumor microenvironment (TME) and orchestrating immune infiltration. The study was conducted to elucidate the association of TAP1 expression with immunological characteristics, and sought to exploit the value of TAP1 as a biomarker reflecting the inflamed TME and immunotherapeutic response. Methods: RNA-sequencing profiles and clinical annotations were obtained from The Cancer Genome Atlas-stomach adenocarcinoma (TCGA-STAD) cohort and Gene Expression Omnibus (GEO) portal. Preprocessing was conducting using the limma package. Weighted gene co-expression network analysis (WGCNA) was used to identify gene modules and TAP1 co-expressed genes (CEGs) based on correlation patterns. Consensus clustering and silhouette analysis determined the optimal number of TAP1-related groups. Gene expression profiles were integrated and classified using the pamr package. The Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm and single-sample gene set enrichment analysis (ssGSEA) were used to evaluate immunological characteristics. Differential expression analysis was conducted using the limma package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Single-cell RNA sequencing (scRNA-seq) datasets were analyzed using the Seurat toolkit to characterize cell types. Results: Within this investigation, no significant differences in TAP1 expression were observed among patients exhibiting various clinicopathological features, indicating that TAP1 expression was not specific to molecular subtypes. Subsequent analysis revealed a positive correlation between TAP1 and diverse immunological traits, encompassing immunomodulators, tumor-infiltrating immune cells, as well as immune checkpoints across multiple datasets. Besides, within a GC immunotherapy cohort, individuals displaying high TAP1 expression demonstrated an increased likelihood of achieving complete remission (CR) post-treatment, suggesting heightened sensitivity to immunotherapy. In the clinical cohort, TAP1 overexpression in GC patients was positively correlated with CD8. Conclusions: TAP1 appears linked to an inflamed TME and serves as a prospective biomarker for discerning immunological attributes and gauging immunotherapeutic responses in GC, particularly in identifying immune-reactive tumors.

Subgroups of relational job characteristics and their differences in turnover intention and subjective well-being among nurses: a latent profile analysis.

OBJECTIVE: Relational job characteristics include perceived social worth and perceived social influence. Good relational job characteristics mean that nurses have high prosocial behavior. The purpose of this study was to explore the potential profile of nurses' relational job characteristics, influencing factors and their differences in turnover intention and subjective well-being, thus finding the most suitable clinical relationship job characteristics. METHODS: A cross-sectional survey was conducted among 1013 clinical nurses using the general demographic data questionnaire, Relational Job Characteristics scale, Turnover Intention Questionnaire and Campbell index of well-being. A latent profile analysis was performed to explore relational job characteristics latent profiles. Multinomial logistic regression analysis was conducted to examine the predictors of profile membership, and a one-way analysis of variance was applied to compare the turnover intention and subjective well-being in each latent profile. RESULTS: Five latent profiles were identified and labeled 'High prosocial job characteristics' profile (20.7%), 'Moderate prosocial job characteristics' profile (41.7%), 'High social worth-low social impact perceived' profile (6.3%), 'Low social worth-high social impact perceived' profile (18.8%) and 'Low prosocial job characteristics' profile (12.5%). Factors affecting the different types of nurse relationship job characteristics include age, marital status, hospital department, nursing years, professional title and hospital position. Among them, chief nurse, nurses with more than 20 years of nursing experience and obstetrics and gynecology nurses were more likely to be 'high prosocial job characteristics' profile. The turnover intention of nurses in 'high prosocial job characteristics' profile was significantly lower than that of other profiles, and their subjective well-being was significantly higher than that of other profiles. CONCLUSION: Improving nurses' perception of social worth and social impact on clinical work can improve nurses' prosocial behavior and subjective well-being, and reduce their turnover intention. Nursing managers or policy makers can formulate targeted intervention measures according to the influencing factors of potential profiles.

Advanced Lung Adenocarcinoma with EGFR 19-del Mutation Transformed into SCC after EGFR-tyrosine Kinase inhibitors Treatment: A Case report.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly improve the survival of patients with Epidermal growth factor receptor (EGFR) sensitive mutations in non-small cell lung cancer (NSCLC). CASE SUMMARY: A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment. Secondary pathological tissue biopsy confirmed squamous cell carcinoma (SCC) transformation. Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time, while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC. Notably, EGFR-TKIs resistance includes primary and acquired. Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs, with SCC transformation being relatively rare. Our results provide more detailed results of the patient's diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma. CONCLUSION: Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations.

An SNP Marker Predicts Colorectal Cancer Outcomes with 5-Fluorouracil-Based Adjuvant Chemotherapy Post-Resection.

Colorectal cancer (CRC) is a global health concern, necessitating adjuvant chemotherapy post-curative surgery to mitigate recurrence and enhance survival, particularly in intermediate-stage patients. However, existing therapeutic disparities highlight the need for biomarker-guided adjuvant chemotherapy to achieve better CRC inhibition. This study explores the molecular mechanisms underlying the inhibition of CRC through a genome-wide association study (GWAS) focused on 5-fluorouracil (5-FU)-based adjuvant therapy in intermediate-stage CRC patients, a domain previously unexplored. We retrospectively included 226 intermediate-stage CRC patients undergoing surgical resection followed by 5-FU-based adjuvant chemotherapy. The exploration cohort comprised 31 patients, and the validation cohort included 195 individuals. Genotyping was carried out using either Axiom Genome-Wide TWB 2.0 Array Plate-based or polymerase chain reaction-based methods on genomic DNA derived from collected tissue samples. Statistical analyses involved descriptive statistics, Kaplan-Meier analyses, and Cox proportional hazard analyses. From the GWAS, potential genetic predictors, GALNT14-rs62139523 and DNMBP-rs10786578 genotypes, of 5-FU-based adjuvant therapy following surgery in intermediate-stage CRC patients were identified. Validation in a larger cohort of 195 patients emphasized the predictive significance of GALNT14-rs62139523 genotypes, especially the "A/G" genotype, for improved overall and progression-free survival. This predictive association remained robust across various subgroups, with exceptions for specific demographic and clinical parameters such as age < 58 years old, CEA ≤ 2.5 ng/mL, tumor diameter > 44.0 mm, and tumor-free margin ≥ 50 mm. This study identifies that the GALNT14-rs62139523 "A/G" genotype modulates therapeutic outcomes, establishing it as a promising biomarker for predicting favorable responses to 5-FU-based adjuvant chemotherapy in intermediate-stage CRC patients, although further investigations are needed to detail these mechanisms.

Specific and efficient knockdown of intracellular miRNA using partially neutralized phosphate-methylated DNA oligonucleic acid-loaded mesoporous silica nanoparticles.

Antisense oligonucleotides (ASOs) are molecules used to regulate RNA expression by targeting specific RNA sequences. One specific type of ASO, known as neutralized DNA (nDNA), contains site-specific methyl phosphotriester (MPTE) linkages on the phosphate backbone, changing the negatively charged DNA phosphodiester into a neutralized MPTE with designed locations. While nDNA has previously been employed as a sensitive nucleotide sequencing probe for the PCR, the potential of nDNA in intracellular RNA regulation and gene therapy remains underexplored. Our study aims to evaluate the regulatory capacity of nDNA as an ASO probe in cellular gene expression. We demonstrated that by tuning MPTE locations, partially and intermediately methylated nDNA loaded onto mesoporous silica nanoparticles (MSNs) can effectively knock down the intracellular miRNA, subsequently resulting in downstream mRNA regulation in colorectal cancer cell HCT116. Additionally, the nDNA ASO-loaded MSNs exhibit superior efficacy in reducing miR-21 levels over 72 hours compared to the efficacy of canonical DNA ASO-loaded MSNs. The reduction in the miR-21 level subsequently resulted in the enhanced mRNA levels of tumour-suppressing genes PTEN and PDCD4. Our findings underscore the potential of nDNA in gene therapies, especially in cancer treatment via a fine-tuned methylation location.

A single center analysis of long-term outcomes and survival related risk factors in liver retransplantation.

Background: Liver retransplant is the only option to save a patient with liver graft failure. However, it is controversial due to its poor survival outcome compared to primary transplantation. Insufficient deceased organ donation in Taiwan leads to high waitlist mortality. Hence, living-donor grafts offer a valuable alternative for retransplantation. This study aims to analyze the single center's outcome in living donor liver retransplantation (re-LDLT) and deceased donor liver retransplantation (re-DDLT) as well as the survival related confounding risk factors. Methods: This is a single center retrospective study including 32 adults who underwent liver retransplantation (re-LT) from June 2002 to April 2020. The cohort was divided into a re-LDLT and a re-DDLT group and survival outcomes were analyzed. Patient outcomes over different periods, the effect of timing on survival, and multivariate analysis for risk factors were also demonstrated. Results: Of the 32 retransplantations, the re-LDLT group (n=11) received grafts from younger donors (31.3 vs. 43.75 years, P=0.016), with lower graft weights (688 vs. 1,457.2 g, P<0.001) and shorter cold ischemia time (CIT) (45 vs. 313 min, P<0.001). The 5-year survival was significantly better in the re-LDLT group than in the re-DDLT group (100% vs. 70.8%, P=0.02). This difference was adjusted when only retransplantation after 2010 was analyzed. Further analysis showed that the timing of retransplantation (early vs. late) did not affect patient survival. Multivariate analysis revealed that prolonged warm ischemia time (WIT) and intraoperative blood transfusion were related to poor long-term survival. Conclusions: Retransplantation with living donor graft demonstrated good long-term outcomes with acceptable complications to both recipient and donor. It may serve as a choice in areas lacking deceased donors. The timing of retransplantation did not affect the long-term survival. Further effort should be made to reduce WIT and massive blood transfusion as they contributed to poor survival after retransplantation.

Low Prognostic Nutritional Index Predicts In-Hospital Complications and Case Fatality in Patients with Spontaneous Intracerebral Hemorrhage: A Retrospective Study.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is associated with high case fatality and significant healthcare costs. Recent studies emphasize the critical role of nutritional status in affecting outcomes in neurological disorders. This study investigates the relationship between the Prognostic Nutrition Index (PNI) and in-hospital complications and case fatality among patients with ICH. METHODS: A retrospective analysis was performed using data from the Changhua Christian Hospital Clinical Research Database between January 2015 and December 2022. Patients under 20 or over 100 years of age or with incomplete medical data were excluded. We utilized restricted cubic spline models, Kaplan-Meier survival analysis, and ROC analysis to assess the association between PNI and clinical outcomes. Propensity score matching analysis was performed to balance these clinical variables between groups. RESULTS: In this study, 2402 patients with spontaneous ICH were assessed using the median PNI value of 42.77. The cohort was evenly divided between low and high PNI groups, predominantly male (59.1%), with an average age of 64 years. Patients with lower PNI scores at admission had higher in-hospital complications and increased 28- and 90-day case fatality rates. CONCLUSIONS: Our study suggests that PNI could serve as a valuable marker for predicting medical complications and case fatality in patients with spontaneous ICH.

The Influence of Dynamic Taping on Landing Biomechanics after Fatigue in Young Football Athletes: A Randomized, Sham-Controlled Crossover Trial.

Fatigue is believed to increase the risk of anterior cruciate ligament (ACL) injury by directly promoting high-risk biomechanics in the lower limbs. Studies have shown that dynamic taping can help normalize inadequate biomechanics during landings. This study aims to examine the effects of dynamic taping on landing biomechanics in fatigued football athletes. Twenty-seven high-school football athletes were recruited and randomly allocated to groups of either active taping or sham taping, with a crossover allocation two weeks later. In each group, the participants underwent a functional agility short-term fatigue protocol and were evaluated using the landing error scoring system before and after the fatigue protocol. The landing error scoring system (LESS) scores in the sham taping group increased from 4.24 ± 1.83 to 5.36 ± 2.00 (t = -2.07, p = 0.04, effect size = 0.61). In contrast, the pre-post difference did not reach statistical significance in the active taping group (from 4.24 ± 1.69 to 4.52 ± 1.69, t = -1.50, p = 0.15, effect size 0.46). Furthermore, the pre-post changes between the sham and active taping groups were statistically significant (sham taping: 1.12 ± 1.20; active taping: 0.28 ± 0.94, p = 0.007). Dynamic taping, particularly using the spiral technique, appeared to mitigate faulty landing biomechanics in the fatigued athletes by reducing hip and knee flexion and increasing hip internal rotation during landing. These results suggest that dynamic taping can potentially offer protective benefits in landing mechanics, which could further be applied to prevent ACL injuries in fatigued athletes.