Chiou-Ying Yang

Oral cancer represents a significant global health burden owing to the limitations of current therapeutic approaches, including adverse effects and drug resistance. Phytochemicals have gained increasing attention as promising anticancer agents with multi‐target effects and low toxicity. This study evaluated the anticancer potential of Phyllanthus emblica water extract (PEWE) using in vitro and in vivo models. In vitro, PEWE exhibited dose‐dependent inhibition of DOK and OECM‐1 oral cancer cell proliferation while sparing non‐cancerous CGHNK2 cells. PEWE significantly suppressed cell migration and invasion, induced S‐phase cell cycle arrest, and promoted apoptosis associated with mitochondrial dysfunction. Morphological and molecular analyses confirmed the induction of autophagy as evidenced by increased LC3 expression, decreased p62 levels, and upregulation of Rab7. RNA sequencing revealed significant modulation of key autophagy‐related genes, including ITPR1, AMBRA1, and MAP1LC3B. In vivo, PEWE effectively inhibited tumor growth in xenograft and carcinogen‐induced mouse oral cancer models without any apparent systemic toxicity. These findings demonstrate that PEWE exerts anticancer effects through a coordinated mechanism involving cell cycle disruption, apoptosis, and autophagy, highlighting its potential as a novel and less toxic therapeutic agent for oral cancer.

Antimicrobial resistance (AMR) has become a crucial global health issue. Antibiotic-resistant bacteria can survive after antibiotic treatments, lowering drug efficacy and increasing lethal risks. A microfluidic water-in-oil emulsion droplet system can entrap microorganisms and antibiotics within the tiny bioreactor, separate from the surroundings, enabling independent assays that can be performed in a high-throughput manner. This study presents the development of a label-free dielectrophoresis (DEP)-based microfluidic platform to sort droplets that co-encapsulate Escherichia coli (E. coli) and ampicillin (Amp) and droplets that co-encapsulate Amp-resistant (AmpR) E. coli with Amp only based on the conductivity-dependent DEP force (F_DEP) without the assistance of optical analyses. The 9.4% low conductivity (LC) Luria–Bertani (LB) broth diluted with 170 mM mannitol can maintain E. coli and AmpR E. coli growth for 3 h and allow Amp to kill almost all E. coli, which can significantly increase the LCLB conductivity by about 100 μS/cm. Therefore, the AmpR E. coli/9.4%LCLB/Amp where no cells are killed and the E. coli/9.4%LCLB/Amp-containing droplets where most of the cells are killed can be sorted based on this conductivity difference at an applied electric field of 2 MHz and 100 V_pp that generates positive F_DEP. Moreover, the sorting ratio significantly decreased to about 50% when the population of AmpR E. coli was equal to or higher than 50% in droplets. The conductivity-dependent DEP-based sorting platform exhibits promising potential to probe the ratio of AmpR E. coli in an unknown bacterial sample by using the sorting ratio as an index.

Nasopharyngeal carcinoma (NPC) is an epithelial cancer originating in the nasopharynx epithelium. Nevertheless, annotating pathology slides remains a bottleneck in the development of AI-driven pathology models and applications. In the present study, we aim to demonstrate the feasibility of using immunohistochemistry (IHC) for annotation by non-pathologists and to develop an efficient model for distinguishing NPC without the time-consuming involvement of pathologists. For this study, we gathered NPC slides from 251 different patients, comprising hematoxylin and eosin (H&E) slides, pan-cytokeratin (Pan-CK) IHC slides, and Epstein–Barr virus-encoded small RNA (EBER) slides. The annotation of NPC regions in the H&E slides was carried out by a non-pathologist trainee who had access to corresponding Pan-CK IHC slides, both with and without EBER slides. The training process utilized ResNeXt, a deep neural network featuring a residual and inception architecture. In the validation set, NPC exhibited an AUC of 0.896, with a sensitivity of 0.919 and a specificity of 0.878. This study represents a significant breakthrough: the successful application of deep convolutional neural networks to identify NPC without the need for expert pathologist annotations. Our results underscore the potential of laboratory techniques to substantially reduce the workload of pathologists.

Carboxy-terminal processing protease (Ctp) is a serine protease that controls multiple cellular processes through posttranslational modification of proteins. Acinetobacter baumannii ATCC 17978 ctp mutant, namely MR14, is known to cause cell wall defects and autolysis. The objective of this study was to investigate the role of ctp mutation–driven autolysis in regulating biofilms in A. baumannii and to evaluate the vesiculation caused by cell wall defects. We found that in A. baumannii, Ctp is localized in the cytoplasmic membrane, and loss of Ctp function enhances the biofilm-forming ability of A. baumannii. Quantification of the matrix components revealed that extracellular DNA (eDNA) and proteins were the chief constituents of MR14 biofilm, and the transmission electron microscopy further indicated the presence of numerous dead cells compared with ATCC 17978. The large number of MR14 dead cells is potentially the result of compromised outer membrane integrity, as demonstrated by its high sensitivity to sodium dodecyl sulfate (SDS) and ethylenediaminetetraacetic acid (EDTA). MR14 also exhibited the hypervesiculation phenotype, producing outer-membrane vesicles (OMVs) of large mean size. The MR14 OMVs were more cytotoxic toward A549 cells than ATCC 17978 OMVs. Our overall results indicate that A. baumanniictp negatively controls pathogenic traits through autolysis and OMV biogenesis.

When a centrifugation-enriched sample of 100 μL containing the surface-enhanced Raman scattering (SERS) tag-bound bacteria (Salmonella in this study) is siphoned onto a glass slide next to an embedded thermoelectric heating chip, such a sessile droplet is quickly evaporated. As the size of the sample droplet is significantly reduced during the heating process, ionic wind streams from a corona discharge needle, stationed above the sample, sweep across the liquid surface to produce centrifugal vortex flow. Tag-bound Salmonella in the sample are then dragged and trapped at the center of droplet bottom. Finally, when the sample is dried, unlike the “coffee ring” effect, the SERS tag-bound Salmonella is concentrated in one small spot to allow sensitive detection of a Raman signal. Compared with our previous electrohydrodynamic concentration device containing only a corona discharge needle, this thermoelectric evaporation-assisted device is more time-effective, with the time of concentrating and drying about 100 μL sample reduced from 2 h to 30 min. Hence, sample throughput can be accelerated with this device for practical use. It is also more sensitive, with SERS detection of a few cells of Salmonella in neat samples achievable. We also evaluated the feasibility of using this device to detect Salmonella in food samples without performing the culturing procedures. Having spiked a few Salmonella cells into ice cubes and lettuce leaves, we use filtration and ultracentrifugation steps to obtain enriched tag-bound Salmonella samples of 200 μL. After loading an aliquot of 100 μL of sample onto this concentration device, the SERS tag signals from samples of 100 g ice cubes containing two Salmonella cells and 20 g lettuce leaf containing 5 Salmonella cells can be successfully detected.

Treatment of advanced hepatocellular carcinoma (HCC) has exhibited a poor overall survival rate of only six to ten months, and the urgency of the development of more effective novel agents is ever present. In this line of research, we aimed to investigate the effects and inhibitive mechanisms of aqueous Ocimum gratissimum leaf extract (OGE), the extract of Ocimum gratissimum, which is commonly used as a therapeutic herb for its numerous pharmacological properties, on malignant HCC cells. Our results showed that OGE decreased the cell viability of HCC SK-Hep1 and HA22T cells in a dose-dependent manner (from 400 to 800 µg/mL), while there is little effect on Chang liver cells. Moreover, cell-cycle analysis shows increased Sub-G1 cell count in SK-Hep1 and HA22T cells which is not observed in Chang liver cells. These findings raise suspicion that the OGE-induced cell death may be mediated through proteins that regulate cell cycle and apoptosis in SK-Hep1 and HA22T cells, and further experimentation revealed that OGE treatment resulted in a dose-dependent decrease in caspase 3 and PARP expressions and in CDK4and p-ERK1/2expressions. Moreover, animal tests also exhibited decreased HCC tumor growth by OGE treatment. We therefore suggest that the inhibition of cell viability and tumor growth induced by OGE may be correlated to the alteration of apoptosis-related proteins.

Adhesive capsulitis (AC) is a common chronic disorder for adult patients; however, whether a history of pre-existing shoulder diseases may affect the development of AC is still not fully understood. We aimed to investigate the incidence and prevalence of AC and to assess the association of pre-existing shoulder diseases and traumatic injuries of the shoulder with the development of AC in adults. This retrospective population-based cohort and nested case-control study used data from the National Health Institute Research Database of Taiwan. A total of 24,414 patients aged 20 years or older and with a diagnosis of AC were identified between 2000 and 2013. We calculated the incidence of AC for each year during the study period. In addition, these AC patients were matched with controls (n = 97,656) in a ratio of 1:4 based on age, gender, and index date. Univariate and multivariate logistic regression models were performed to identify variables associated with AC. Females and patients aged 50 to 69 years had higher age-gender standardized incidence and prevalence of AC than their counterparts. Multivariate analyses showed that after adjusting for relevant covariates, pre-existing shoulder diseases of calcific tendinitis (odds ratio [OR] = 8.74, 95% confidence interval [CI] = 5.66–13.5), biceps tendinitis (OR = 7.93, 95% CI = 5.33–11.79), rotator cuff syndrome (OR = 6, 95% CI = 5.26–6.85), osteoarthritis (OR = 4.27, 95% CI = 3.44–5.3), and impingement syndrome (OR = 3.13, 95% CI = 2.64–3.71), as well as fracture (OR = 4.51, 95% CI = 3.82–5.34) and dislocation (OR = 3.57, 95% CI = 2.35–5.45) of the shoulder were significantly associated with AC risk. Higher odds of AC were observed among patients with pre-existing shoulder conditions. This study highlights the need to consider differences in AC risk among patients with various types of shoulder diseases and traumatic injuries of the shoulder.