Nonlinear photoacoustic microscopy via a loss modulation technique: from detection to imaging

In order to achieve high-resolution deep-tissue imaging, multi-photon fluorescence microscopy and photoacoustic tomography had been proposed in the past two decades. However, combining the advantages of these two imaging systems to achieve optical-spatial resolution with an ultrasonic-penetration depth is still a field with challenges. In this paper, we investigate the detection of the two-photon photoacoustic ultrasound, and first demonstrate background-free two-photon photoacoustic imaging in a phantom sample. To generate the background-free two-photon photoacoustic signals, we used a high-repetition rate femtosecond laser to induce narrowband excitation. Combining a loss modulation technique, we successfully created a beating on the light intensity, which not only provides pure sinusoidal modulation, but also ensures the spectrum sensitivity and frequency selectivity. By using the lock-in detection, the power dependency experiment validates our methodology to frequency-select the source of the nonlinearity. This ensures our capability of measuring the background-free two-photon photoacoustic waves by detecting the 2nd order beating signal directly. Furthermore, by mixing the nanoparticles and fluorescence dyes as contrast agents, the two-photon photoacoustic signal was found to be enhanced and detected. In the end, we demonstrate subsurface two-photon photoacoustic bio-imaging based on the optical scanning mechanism inside phantom samples

106GBaud (200G PAM4) CWDM EML for 800G/1.6T Optical Networks and AI Applications

We report ultrahigh speed 106GBaud (200G PAM4) electro-absorption modulated laser (EML) for 800G and 1.6T optical transmission. Four CWDM EMLs of 1271, 1291, 1311 and 1331nm in 800G FR4 optical transceivers show clear eye diagram after 2km. Our 106GBaud EMLs show high bandwidth, high extinction ratio, low threshold current and high power, making it a suitable source laser for 800G/1.6T and AI applications.&nbsp

Mediating role of resilience in the relationships of physical activity and mindful self-awareness with peace of mind among college students

Abstract Peace of mind (PoM) is an index of mental health in Asian culture and emphasizes low arousal, happiness, harmony, and an internal state of peacefulness. While previous studies have found that mindful self-awareness can contribute to PoM, regular physical activity (PA) is also an important factor contributing to one’s PoM due to its function in promoting one's resilience. The study aims to investigate a hypothetical model that assumes PA is associated with resilience while controlling for mindful self-awareness, contributing to PoM. The PoM scale, Connor-Davidson Resilience Scale, Chinese translation of Mindful Attention Awareness Scale, and PA self-report questionnaire were used. A path analysis was applied to test the association between these variables and the mediating role of resilience. A total of 436 students from a university in Taiwan were recruited; the mean age was 20.87, with 46.3% female and 73.6% engaging in over 150 min/week of moderate PA. Gender and age negatively correlated with PA. After controlling for age and gender, there was no direct effect of physical activity on PoM; both mindful self-awareness and PA predict resilience, which in turn predicts PoM, suggesting that both cognitive (i.e., mindful self-awareness) and PA are important to cultivate resilience and thus PoM

Trypsin-induced proteome alteration during cell subculture in mammalian cells

<p>Abstract</p> <p>Background</p> <p>It is essential to subculture the cells once cultured cells reach confluence. For this, trypsin is frequently applied to dissociate adhesive cells from the substratum. However, due to the proteolytic activity of trypsin, cell surface proteins are often cleaved, which leads to dysregulation of the cell functions.</p> <p>Methods</p> <p>In this study, a triplicate 2D-DIGE strategy has been performed to monitor trypsin-induced proteome alterations. The differentially expressed spots were identified by MALDI-TOF MS and validated by immunoblotting.</p> <p>Results</p> <p>36 proteins are found to be differentially expressed in cells treated with trypsin, and proteins that are known to regulate cell metabolism, growth regulation, mitochondrial electron transportation and cell adhesion are down-regulated and proteins that regulate cell apoptosis are up-regulated after trypsin treatment. Further study shows that bcl-2 is down-regulated, p53 and p21 are both up-regulated after trypsinization.</p> <p>Conclusions</p> <p>In summary, this is the first report that uses the proteomic approach to thoroughly study trypsin-induced cell physiological changes and provides researchers in carrying out their experimental design.</p

Long-term results of intensity-modulated radiotherapy concomitant with chemotherapy for hypopharyngeal carcinoma aimed at laryngeal preservation

<p>Abstract</p> <p>Background</p> <p>The objective of this retrospective study is to investigate laryngeal preservation and long-term treatment results in hypopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) combined with chemotherapy.</p> <p>Methods</p> <p>Twenty-seven patients with hypopharyngeal carcinoma (stage II-IV) were enrolled and underwent concurrent chemoradiotherapy. The chemotherapy regimens were monthly cisplatin and 5-fluorouracil for six patients and weekly cisplatin for 19 patients. All patients were treated with IMRT with simultaneous integrated boost technique. Acute and late toxicities were recorded based on CTCAE 3.0 (Common Terminology Criteria for Adverse Events).</p> <p>Results</p> <p>The median follow-up time for survivors was 53.0 months (range 36-82 months). The initial complete response rate was 85.2%, with a laryngeal preservation rate of 63.0%. The 5-year functional laryngeal, local-regional control, disease-free and overall survival rates were 59.7%, 63.3%, 51.0% and 34.8%, respectively. The most common greater than or equal to grade 3 acute and late effects were dysphagia (63.0%, 17 of 27 patients) and laryngeal stricture (18.5%, 5 of 27 patients), respectively. Patients belonging to the high risk group showed significantly higher risk of tracheostomy compared to the low risk group (p = 0.014).</p> <p>Conclusions</p> <p>After long-term follow-up, our results confirmed that patients with hypopharyngeal carcinoma treated with IMRT concurrent with platinum-based chemotherapy attain high functional laryngeal and local-regional control survival rates. However, the late effect of laryngeal stricture remains a problem, particularly for high risk group patients.</p

Differential Proteomic Analysis of Human Placenta-Derived Mesenchymal Stem Cells Cultured on Normal Tissue Culture Surface and Hyaluronan-Coated Surface

Our previous results showed that hyaluronan (HA) preserved human placenta-derived mesenchymal stem cells (PDMSC) in a slow cell cycling mode similar to quiescence, the pristine state of stem cells in vivo, and HA was found to prevent murine adipose-derived mesenchymal stem cells from senescence. Here, stable isotope labeling by amino acid in cell culture (SILAC) proteomic profiling was used to evaluate the effects of HA on aging phenomenon in stem cells, comparing (1) old and young passage PDMSC cultured on normal tissue culture surface (TCS); (2) old passage on HA-coated surface (CHA) compared to TCS; (3) old and young passage on CHA. The results indicated that senescence-associated protein transgelin (TAGLN) was upregulated in old TCS. Protein CYR61, reportedly senescence-related, was downregulated in old CHA compared to old TCS. The SIRT1-interacting Nicotinamide phosphoribosyltransferase (NAMPT) increased by 2.23-fold in old CHA compared to old TCS, and is 0.48-fold lower in old TCS compared to young TCS. Results also indicated that components of endoplasmic reticulum associated degradation (ERAD) pathway were upregulated in old CHA compared to old TCS cells, potentially for overcoming stress to maintain cell function and suppress senescence. Our data points to pathways that may be targeted by HA to maintain stem cells youth

Leptospira santorosai serovar shermani detergent extract induces an increase in fibronectin production through a toll-like receptor 2-mediated pathway

Leptospirosis can activate inflammatory responses through Toll-like receptors (TLRs) and may cause renal tubulointerstitial fibrosis characterized by the accumulation of extracellular matrix (ECM). We have previously demonstrated that Leptospira santorosai serovar Shermani detergent extract stimulates ECM accumulation in vitro. The aim of this study was to examine the mechanistic basis of these previous observations and, in particular, to examine the potential involvement of TLRs. The addition of serovar Shermani detergent extract led to an increase in fibronectin gene expression and production. Inhibition of TLR2 but not TLR4 expression abrogated serovar Shermani detergent extract-mediated increases in fibronectin production. This response was also blocked by the knockdown of the gene expression of the TLR2 downstream transducers myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6). Serovar Shermani detergent extract also activated nuclear factor-κB, and its inhibition by curcumin-attenuated serovar Shermani detergent extract induced increases in fibronectin production. These effects were also mimicked by the specific TLR2 agonist, Pam(3)CsK(4), a response that was also abrogated by the knockdown of MyD88 and TRAF6. Similarly, the administration of live leptospires to cells also induced fibronectin production that was blocked by inhibition of TLR2 and MyD88 expression. In conclusion, serovar Shermani detergent extract can induce fibronectin production through the TLR2-associated cascade, providing evidence of an association between TLRs and leptospirosis-mediated ECM deposition

Efficacy and toxicities of doxorubicin plus ifosfamide in the second-line treatment of uterine leiomyosarcoma

PurposeUterine leiomyosarcoma is a rare and aggressive tumor known for its drug resistance and metastatic potential. The standard first-line treatment typically involves anthracycline-based chemotherapy or a combination of gemcitabine and docetaxel; however, there is currently no established second-line treatment. Therefore, the aim of this study was to evaluate the efficacy and toxicity of doxorubicin plus ifosfamide as a potential second-line treatment for uterine leiomyosarcoma.Materials and methodsThis is a retrospective, single-center, single-arm study. We reviewed the tumor registry data from January 2010 to December 2022 and identified patients with uterine leiomyosarcoma who had previously received first-line salvage or adjuvant treatment involving gemcitabine and taxotere, and later experienced tumor recurrence. Patients who met these criteria were included in the study. The primary endpoint was the efficacy of doxorubicin and ifosfamide as a second-line treatment for uterine leiomyosarcoma, as measured by progression-free survival, 1-year overall survival, and response rate. The secondary endpoint was the adverse events associated with this regimen.ResultsFifty-two patients were diagnosed with uterine leiomyosarcoma during the study period, nine of whom were included in the data analysis. All patients had previously received gemcitabine-docetaxel as first-line adjuvant therapy, with a median progression-free survival period of 8.4 months. Doxorubicin-ifosfamide was administered as second-line treatment, with a median progression-free survival of 6.0 months (range: 2.7-79.9 months). The clinical benefit rate of the second-line treatment was 66.7%, with a median overall survival of 33.0 months, and a 1-year overall survival rate of 83.3%. Previous reports have shown that the median progression-free survival for second-line treatments using other regimens ranged from 1.4-5.6 months. The most common adverse event was myelosuppression, with five patients requiring granulocyte colony-stimulating factor and one patient requiring a blood transfusion. No patient discontinued treatment due to unmanageable adverse events.ConclusionUse of doxorubicin with ifosfamide may be a promising and reasonable second-line treatment with manageable adverse events for patients with uterine leiomyosarcoma

Serologic and Molecular Biologic Methods for SARS-associated Coronavirus Infection, Taiwan

Severe acute respiratory syndrome (SARS) has raised a global alert since March 2003. After its causative agent, SARS-associated coronavirus (SARS-CoV), was confirmed, laboratory methods, including virus isolation, reverse transcriptase–polymerase chain reaction (RT-PCR), and serologic methods, have been quickly developed. In this study, we evaluated four serologic tests ( neutralization test, enzyme-linked immunosorbent assay [ELISA], immunofluorescent assay [IFA], and immunochromatographic test [ICT]) for detecting antibodies to SARS-CoV in sera of 537 probable SARS case-patients with correlation to the RT-PCR . With the neutralization test as a reference method, the sensitivity, specificity, positive predictive value, and negative predictive value were 98.2%, 98.7%, 98.7%, and 98.4% for ELISA; 99.1%, 87.8%, 88.1% and 99.1% for IFA; 33.6%, 98.2%, 95.7%, and 56.1% for ICT, respectively. We also compared the recombinant-based western blot with the whole virus–based IFA and ELISA; the data showed a high correlation between these methods, with an overall agreement of >90%. Our results provide a systematic analysis of serologic and molecular methods for evaluating SARS-CoV infection