The Protective Effects of Mcl-1 on Mitochondrial Damage and Oxidative Stress in Imiquimod-Induced Cancer Cell Death.

Mitochondria, vital organelles that generate ATP, determine cell fate. Dysfunctional and damaged mitochondria are fragmented and removed through mitophagy, a mitochondrial quality control mechanism. The FDA-approved drug IMQ, a synthetic agonist of Toll-like receptor 7, exhibits antitumor activity against various skin malignancies. We previously reported that IMQ promptly reduced the level of the antiapoptotic Mcl-1 protein and that Mcl-1 overexpression attenuated IMQ-triggered apoptosis in skin cancer cells. Furthermore, IMQ profoundly disrupted mitochondrial function, promoted mitochondrial fragmentation, induced mitophagy, and caused cell death by generating high levels of ROS. However, whether Mcl-1 protects mitochondria from IMQ treatment is still unknown. In this study, we demonstrated that Mcl-1 overexpression induced resistance to IMQ-induced apoptosis and reduced both IMQ-induced ROS generation and oxidative stress in cancer cells. Mcl-1 overexpression maintained mitochondrial function and integrity and prevented mitophagy in IMQ-treated cancer cells. Furthermore, IL-6 protected against IMQ-induced apoptosis by increasing Mcl-1 expression and attenuating IMQ-induced mitochondrial fragmentation. Mcl-1 overexpression ameliorates IMQ-induced ROS generation and mitochondrial fragmentation, thereby increasing mitochondrial stability and ultimately attenuating IMQ-induced cell death. Investigating the roles of Mcl-1 in mitochondria is a potential strategy for cancer therapy development.

Enhanced Carrier Transport Performance of Monolayer Hafnium Disulphide by Strain Engineering.

For semiconducting two-dimensional transition metal dichalcogenides (TMDs), the carrier transport properties of the material are affected by strain engineering. In this study, we investigate the carrier mobility of monolayer hafnium disulphide (HfS2) under different biaxial strains by first-principles calculations combined with the Kubo-Greenwood mobility approach and the compact band model. The decrease/increase in the effective mass of the conduction band (CB) of monolayer HfS2 caused by biaxial tensile/compressive strain is the major reason for the enhancement/degradation of its electron mobility. The lower hole effective mass of the valence bands (VB) in monolayer HfS2 under biaxial compressive strain improves its hole transport performance compared to that under biaxial tensile strain. In summary, biaxial compressive strain causes a decrease in both the effective mass and phonon scattering rate of monolayer HfS2, resulting in an increase in its carrier mobility. Under the biaxial compressive strain reaches 4%, the electron mobility enhancement ratio of the CB of monolayer HfS2 is ~90%. For the VB of monolayer HfS2, the maximum hole mobility enhancement ratio appears to be ~13% at a biaxial compressive strain of 4%. Our results indicate that the carrier transport performance of monolayer HfS2 can be greatly improved by strain engineering.

Low-level mosaic trisomy 14 at amniocentesis in a pregnancy associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, positive non-invasive prenatal testing for trisomy 14, perinatal progressive decrease of the trisomy 14 cell line and a favorable fetal outcome.

OBJECTIVE: We present low-level mosaic trisomy 14 at amniocentesis. CASE REPORT: A 37-year-old, gravida 2, para 1, woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization and embryo transfer (IVF-ET). Amniocentesis revealed a karyotype of 47,XX,+14 [4]/46,XX [27], consistent with 12.9% mosaicism for trisomy 14. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1-22, X) × 2 with no genomic imbalance. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling at 21 weeks of gestation and was offered expanded non-invasive prenatal testing (NIPT) which was positive for trisomy 14. At 24 weeks of gestation, she underwent repeat amniocentesis which revealed a karyotype of 47,XX,+14 [2]/46,XX [26], consistent with 7% mosaicism for trisomy 14. The parental karyotypes were normal. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed no genomic imbalance. Polymorphic marker analysis excluded uniparental disomy (UPD) 14. Interphase fluorescence in situ hybridization (FISH) analysis on 104 uncultured amniocytes detected no trisomy 14 cell. At 35 weeks of gestation, a 2315-g phenotypically normal baby was delivered. The umbilical cord and placenta had the karyotype of 46, XX (40/40 cells). aCGH analysis on the DNA extracted from peripheral blood and buccal mucosal cells at the age of three months revealed no genomic imbalance. The neonate was normal in phenotype and development during postnatal follow-ups. CONCLUSIONS: Low-level mosaic trisomy 14 at amniocentesis can be associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 14 cell line and a favorable fetal outcome.

Mosaic distal 13q duplication due to mosaic unbalanced translocation of 46,XY,der(14)t(13;14)(q32.2;p13)/46,XY at amniocentesis in a pregnancy associated with a favorable fetal outcome, perinatal progressive decrease of the aneuploid cell line and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes.

OBJECTIVE: We present mosaic distal 13q duplication due to mosaic unbalanced translocation 46,XY,der(14)t(13;14)(q32.2;p13)/46,XY at amniocentesis in a pregnancy associated with a favorable fetal outcome. CASE REPORT: A 37-year-old, gravida 2, para 0, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY, add(14) (p13)[17]/46,XY[13] (56.6% mosaicism). Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed arr 13q32.2q34 × 2∼3, consistent with 45% mosaicism for distal 13q duplication. Repeat amniocentesis at 24 weeks of gestation revealed a karyotype of 46,XY,der(14)t(13;14)(q32.2;p13)[14]/46,XY[16] (46.6% mosaicism). The parental karyotypes were normal. aCGH analysis on the DNA extracted from uncultured amniocytes revealed arr 13q32.2q34 × 2.38, consistent with 30-40% mosaicism for distal 13q duplication. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes detected 22.8% (23/101 cells) mosaicism for distal 13q duplication. Prenatal ultrasound findings were unremarkable. At 39 weeks of gestation, a 3616-g phenotypically normal baby was delivered. The karyotypes of cord blood, umbilical cord and placenta were 46,XY,der(14)t(13;14)(q32.2;p13)[20]/46,XY[20] (50% mosaicism), 46,XY,der(14)t(13;14)(q32.2;p13)[14]/46,XY[26] (35% mosaicism) and 46,XY (40/40 cells) (0% mosaicism), respectively. When follow-ups at the age of 4½ months and the age of one year, the peripheral blood had the karyotype of 46,XY,der(14)t(13;14)(q32.2;p13)[18]/46,XY[22] (45% mosaicism). Interphase FISH analysis on buccal mucosal cells at the age of 4½ months revealed 2.7% (3/110 cells) mosaicism for distal 13q duplication, compared with 1% (1/100 cells) in the normal control. The neonate was normal in phenotype and development. CONCLUSIONS: Mosaic unbalanced translocation at amniocentesis can be associated with a favorable fetal outcome, perinatal progressive decrease of the aneuploid cell line and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes.

The cold temperature associated with new-onset heart failure after incorporating dynamic status of multimorbidity: nationwide cohort, Taiwan 2012-2019.

AIMS: Cold temperatures are known to affect heart failure (HF) hospitalizations, but the dynamic status of multi-morbidity of HF was rarely incorporated. We investigated the relationship between temperature and new-onset HF by risk strata. METHODS AND RESULTS: This nationwide cohort study analysed daily data on ambient temperature, the dynamic status of risk factors (age, diabetes, chronic obstructive pulmonary disease, coronary artery disease, chronic kidney disease, hypertension, myocardial infarction, and atrial fibrillation), and new-onset HF among the Taiwan population from 2012 to 2019. Poisson regression, Austin's algorithm, and classification and regression tree (CART) were used to determine risk strata and obtain the predicted HF rate. 148 708 patients developed new-onset HF over 152.52 million person-years. Three risk strata for HF were identified: Stratum 1 was predominantly those without any comorbidity (89.9%); Stratum 2 was those aged 60-69 with 2-3 comorbidities or aged 70+ with 1-2 comorbidities (9.0%), and Stratum 3 was those aged 70+ and had four or more comorbidity (1.1%). The HF incidence rates for these three strata were 25.54, 555.27, and 2315.52 per 100 000 person-years, respectively. The R2 of the Poisson regression with the three risk strata and the daily minimum temperature on the ln HF incidence rates was 77.99%. The risk of HF increased as temperatures decreased, and the slopes were 1.032, 1.040, and 1.034 for Strata 1-3, respectively. The rate ratios of HF at the winter median temperature of 17°C vs. the summer median temperature of 29°C were 1.45, 1.58, and 1.49 for Strata 1-3, respectively. Cross-validation reveals a good fit and predicted HF rates by ambient temperature for the three strata were provided. CONCLUSION: Cold temperatures are associated with an increased risk of new-onset HF. Stratum 2 (aged 60-69 with 2-3 comorbidities or aged 70+ with 1-2 comorbidities) are particularly susceptible to cold-related new-onset HF.

Cold temperatures are known to affect heart failure (HF) hospitalizations, but the dynamic status of multi-morbidity of HF was rarely incorporated. Three risk strata for HF were determined for the Taiwan population from 2012 to 2019: Stratum 1 was predominantly young or without comorbidities (89.9%); Stratum 2 was those aged 60­69 with 2­3 comorbidities or aged 70+ with 1­2 comorbidities (9.0%), and Stratum 3 was those aged 70+ and had four or more risk factors (1.1%). The HF incidence rates for these three strata were 25.54, 555.27, and 2315.52 per 100 000 person-years, respectively. The rate ratios of HF at the winter median temperature of 17°C vs. the summer median temperature of 29°C were 1.45, 1.58, and 1.49 for Strata 1­3, respectively. Other than cold temperatures are associated with an increased risk of new-onset HF, Stratum 2 (those aged 60­69 with 2­3 comorbidities or aged 70+ with 1­2 comorbidities) are particularly susceptible to cold-related new-onset HF. Predicted HF rates by ambient temperature for the three strata were provided so that individuals can find their predicted HF rate based on the risk score and the current temperature and, therefore, be amenable to primary preventive efforts.

Arsenic-induced disruption of circadian rhythms and glutamine anaplerosis in human urothelial carcinoma.

Inorganic arsenic (iAs)-induced urothelial carcinoma (UC) develops into a poor-prognosis malignancy. Arsenic-induced oxidative stress contributes to circadian rhythm disruption altered metabolism. Glutamine anaplerosis is a common metabolic feature of rapidly proliferating malignant cells, in which glutaminase (GLS) is a key enzyme in this process. Therefore, this study intends to determine if arsenic-induced oxidative stress can alter circadian rhythms and promote glutamine anaplerosis. Exonic expression of core circadian molecules (CLOCK, ARNTL, and NR1D1) and GLS in varying grades of UC were assessed using 423 bladder cancer samples from the TCGA Urothelial Bladder Cancer (BLCA) dataset. The levels of circadian proteins and metabolic markers in 44 UC patients from non-black foot disease (BFD) and BFD areas were detected by immunohistochemistry. In vitro and in vivo experiments elucidated the regulatory mechanisms of arsenic-mediated circadian disturbance and metabolic alteration. Public database analysis showed that ARNTL, NR1D1, and GLS exhibited greater expression in more high-grade UC. Strong immunoreactivity for BMAL1, GLS, and low levels of NR1D1 were found in malignant urothelial lesions, especially in arsenic-exposed UC. Arsenic-induced overexpression of BMAL1 and GLS involves activation of NADH: quinone oxidoreductase 1 (NQO1), continuously altering the NADH oscillations to promote glutamate metabolism in SV-HUC-1, T24 and BFTC-905 cells. These phenomenon were also demonstrated in the urothelium of arsenic-exposed animals. The present findings highlight the potential clinical significance of BMAL1 and GLS in UC in the BFD region. Furthermore, these results suggest that arsenic interferes with circadian rhythm and glutamine anaplerosis by NADH oscillatory imbalance in urothelial cells and urothelial cancer cells, predisposing them to malignant development.

Zirconia and Crofer Joint Made by Reactive Air Brazing Using the Silver Base Paste and Cu-Ti Coating Layer.

This study proposes a method to enhance the airtightness of the joint between the ZrO2 and Crofer alloy using coating technology. With the aid of vacuum sputtering technology, a titanium-copper alloy layer with a thickness between 1.5 µm and 6 µm was first deposited on the surface of ZrO2 and Crofer, respectively. The chemical composition of the deposited reaction layer was 70.2 Cu and 29.8 Ti in at%. Then, using silver as the base material in the reactive air brazing (RAB) process, we explore the use of this material design to improve the microstructure and reaction mechanism of the joint surface between ceramics and metal, compare the effects of different pretreatment thicknesses on the microstructure, and evaluate its effectiveness through air tightness tests. The results show that a coating of Cu-Ti alloy on the ZrO2 substrate can significantly improve bonding between the Ag filler and ZrO2. The Cu-Ti metallization layer on the ZrO2 substrate is beneficial to the RAB. After the brazing process, the coated Cu-Ti layers form suitable reaction interfaces between the filler, the metal, the filler, and the ceramic. In terms of coating layer thickness, the optimized 3 µm coated Cu-Ti alloy layer is achieved from the experiment. Melting and dissolving the Cu-Ti coated layer into the ZrO2 substrate results in a defect-free interface between the Ag-rich braze and the ZrO2. The air tightness test result shows no leakage under 2 psig at room temperature for 28 h. The pressure condition can still be maintained even under high-temperature conditions of 600 °C for 24 h.

Impacts of Interleukin-10 Promoter Genotypes on Prostate Cancer.

Prostate cancer (PCa) is a multifactorial disease influenced by genetic, environmental, and immunological factors. Genetic polymorphisms in the interleukin-10 (IL-10) gene have been implicated in PCa susceptibility, development, and progression. This study aims to assess the contributions of three IL-10 promoter single nucleotide polymorphisms (SNPs), A-1082G (rs1800896), T-819C (rs3021097), and A-592C (rs1800872), to the risk of PCa in Taiwan. The three IL-10 genotypes were determined using PCR-RFLP methodology and were evaluated for their contributions to PCa risk among 218 PCa patients and 436 non-PCa controls. None of the three IL-10 SNPs were significantly associated with the risks of PCa (p all > 0.05) in the overall analyses. However, the GG at rs1800896 combined with smoking behavior was found to significantly increase the risk of PCa by 3.90-fold (95% confidence interval [95% CI] = 1.28-11.89, p = 0.0231). In addition, the rs1800896 AG and GGs were found to be correlated with the late stages of PCa (odds ratio [OR] = 1.90 and 6.42, 95% CI = 1.05-3.45 and 2.30-17.89, p = 0.0452 and 0.0003, respectively). The IL-10 promoter SNP, A-1082G (rs1800896), might be a risk factor for PCa development among smokers and those at late stages of the disease. These findings should be validated in larger and more diverse populations.

Targeting Bmi1 for Enhancing Anoikis Sensitivity and Inhibiting Metastasis in Colorectal Cancer.

BACKGROUND/AIM: Patients diagnosed with advanced metastatic colorectal cancer (CRC) confront a bleak prognosis characterized by low survival rates. Anoikis, the programmed apoptosis resistance exhibited by metastatic cancer cells, is a crucial factor in this scenario. MATERIALS AND METHODS: We employed bulk flow cytometry and RT-qPCR assays, conducted in vivo experiments with mice and zebrafish, and analyzed patient tissues to examine the effects of the B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1)-midkine (MDK) axis on the cellular response to anoikis. Bmi1 is pivotal in tumorigenesis. This study elucidated the involvement of Bmi1 in conferring anoikis resistance in CRC and explored its downstream targets associated with metastasis. RESULTS: Elevated levels of Bmi1 expression correlated with distant metastasis in CRC. Suppression of Bmi1 significantly diminished the metastatic potential of CRC cells. Inhibition of Bmi1 led to an increase in the proportion of apoptotic SW620 cells detached from the matrix. This effect was further enhanced by the addition of irinotecan, a topoisomerase I inhibitor. Furthermore, Bmi1 was found to synergize with MDK in modulating CRC viability, with consistent expression patterns observed in in vivo models and clinical tissue specimens. In summary, Bmi1 acted as a regulator of CRC metastatic capability by conferring anoikis resistance. Additionally, it collaborated with MDK to facilitate invasion and distant metastasis. CONCLUSION: Targeting Bmi1 may offer a promising adjunctive therapeutic strategy when administering traditional chemotherapy regimens to patients with advanced CRC.

Study of different pre-treatments in the comparison of the efficacy of photodynamic therapy for moderate to severe acne vulgaris.

OBJECTIVE: To evaluate the efficacy of CO2 fractional laser and microneedling pretreatment combined with ALA-PDT for moderate-to-severe acne, aiming to optimize clinical treatment. METHODS: Patients were randomly divided into three groups: Group A (CO2 fractional laser + ALA-PDT), Group B (microneedling + ALA-PDT), and Group C (ALA-PDT). Each group underwent photodynamic therapy once a week for 3 weeks. Efficacy was assessed at the end of the 4th week, and recurrence was assessed at the end of the 12th week. RESULTS: A total of 150 patients with moderate to severe acne were included in this study, with 50 patients in each group. Four weeks after the end of treatment, the effective rates were 88 % for Group A, 62 % for Group B, and 36 % for Group C. Statistically significant differences were found between the groups (P < 0.05), with Group A showing superior efficacy compared to Group B (P < 0.05). No serious systemic or local adverse reactions were observed in any group. No recurrence was seen in any group 12 weeks after the end of treatment, and some patients continued to show improvement in skin lesions over time. CONCLUSION: Both the CO2 fractional laser group and the microneedling group improved the efficacy of photodynamic therapy for moderate to severe acne compared to the control group, with the CO2 fractional laser group demonstrating better efficacy and fewer adverse effects.

Topology Optimization Enables High-Q Metasurface for Color Selectivity.

Nonlocal metasurfaces, exemplified by resonant waveguide gratings (RWGs), spatially and angularly configure optical wavefronts through narrow-band resonant modes, unlike the broad-band and broad-angle responses of local metasurfaces. However, forward design techniques for RWGs remain constrained at lower efficiency. Here, we present a topology-optimized metasurface resonant waveguide grating (MRWG) composed of titanium dioxide on a glass substrate capable of operating simultaneously at red, yellow, green, and blue wavelengths. Through adjoint-based topology optimization, while considering nonlocal effects, we significantly enhance its diffraction efficiency, achieving numerical efficiencies up to 78% and Q-factors as high as 1362. Experimentally, we demonstrated efficiencies of up to 59% with a Q-factor of 93. Additionally, we applied our topology-optimized metasurface to color selectivity, producing vivid colors at 4 narrow-band wavelengths. Our investigation represents a significant advancement in metasurface technology, with potential applications in see-through optical combiners and augmented reality platforms.

Targeting the CDK7-MDK axis to suppresses irinotecan resistance in colorectal cancer.

AIMS: Colorectal cancer (CRC) remains a major global health issue, with metastatic cases presenting poor prognosis despite advances in chemotherapy and targeted therapy. Irinotecan, a key drug for advanced CRC treatment, faces challenges owing to the development of resistance. This study aimed to understand the mechanisms underlying irinotecan resistance in colorectal cancer. MAIN METHODS: We created a cell line resistant to irinotecan using HT29 cells. These resistant cells were utilized to investigate the role of the CDK7-MDK axis. We employed bulk RNA sequencing, conducted in vivo experiments with mice, and analyzed patient tissues to examine the effects of the CDK7-MDK axis on the cellular response to irinotecan. KEY FINDINGS: Our findings revealed that HT29 cells resistant to irinotecan, a crucial colorectal cancer medication, exhibited significant phenotypic and molecular alterations compared to their parental counterparts, including elevated stem cell characteristics and increased levels of cytokines and drug resistance proteins. Notably, CDK7 expression was substantially higher in these resistant cells, and targeting CDK7 effectively decreased their survival and tumor growth, enhancing irinotecan sensitivity. RNA-seq analysis indicated that suppression of CDK7 in irinotecan-resistant HT29 cells significantly reduced Midkine (MDK) expression. Decreased CDK7 and MDK levels, achieved through siRNA and the CDK7 inhibitor THZ1, enhanced the sensitivity of resistant HT29 cells to irinotecan. SIGNIFICANCE: Our study sheds light on how CDK7 and MDK influence irinotecan resistance in colorectal and highlights the potential of MDK-targeted therapies. We hypothesized that irinotecan sensitivity and overall treatment efficacy would improve by inhibiting MDK. This finding encourages a careful yet proactive investigation of MDK as a therapeutic target to enhance outcomes in colorectal cancer patients.

Recurrent Occupational Hantavirus Infections Linked to Feeder Rodent Breeding Farm, Taiwan, 2022.

We investigated 2 acute cases and 1 previous case of Seoul hantavirus infection in workers in a feeder rodent breeding farm in Taiwan. Prevalence of hantavirus IgG among the tested feeder rats was 37.5%. Appropriate prevention measures, including using disinfection protocols and personal protective equipment, are crucial to lowering risk.

Development of a long-term care service integration self-assessment tool.

The World Health Organization emphasizes the importance of providing integrated care for older people. Taiwan is the fastest aging country in the world. In 2016, Taiwan implemented the Long-Term Care Plan 2.0 (TLTCP 2.0), aimed at providing integrated long-term care (LTC) services in communities. However, LTC service agencies have not been able to evaluate the level of integrated care they provide due to the lack of an effective assessment tool. To address this need, this study sets out to develop an integration assessment tool, namely the Self-Assessment for Service Integration in Long-Term Care (SASI-LTC), which will allow LTC agencies to self-evaluate their current level of integration from multiple perspectives. The SASI-LTC was developed based on Evashwick's framework, underwent two rounds of Delphi panels with twenty-six experts, and a pilot test with 243 valid questionnaires from administrators of Tier A agencies who are responsible for integrating LTC. The Delphi experts assessed the content with high levels of agreement using medians, the scale content validity index (SCVI) and item content validity index (ICVI). The SASI-LTC included four domains (inter-entity organization and management, integrated care coordination, integrated resources, and integrated information systems) with thirty items. The SASI-LTC showed good reliability (Cronbach's α = 0.94) and good validity, and a confirmatory factor analysis showed a good model fit index [χ2/df = 1.38; RMSEA = 0.040; CFI = 0.963; SRMR = 0.049] in pilot testing. While the SASI-LTC is a useful and feasible tool for Taiwan's LTC service agencies to evaluate their level of integration in providing LTC services, it could also be used in other countries with minor adjustments to localization of items related to financial integration.

Associations Between Obstructive Sleep Apnea Syndrome, Dry Eye Disease, and CPAP Usage Among Taiwanese Patients: A Retrospective Analysis.

Study Objectives: To evaluate the association between obstructive sleep apnea (OSA) and dry eye disease (DED) and analyze the impact of Continuous Positive Airway Pressure (CPAP) on DED. Methods: This is a retrospective population-based case-control study. Patients who underwent polysomnography in Taiwan from March 1, 2009, to March 1, 2020, were identified from the database of a sleep center. Patients who were diagnosed with keratoconjunctivitis sicca or tear film insufficiency were included. Patients without data from Schirmer's test, lacking tear break-up time values, or with a history of refractive surgery, Sjögren's syndrome, ocular injuries, or a disability in eyelid closure were excluded. All patients with DED enrolled had DED in both eyes. OSA severity between patients with and without DED was compared. Results: In total, 86 patients with DED and 86 age-matched patients without DED were enrolled. Significant differences in apnea-hypopnea index values (patients with DED: 29.1 ± 23.4, patients without DED: 17.9 ± 20.2, P < 0.001), OSA severity (P < 0.001), and lowest oxygen saturation (P = 0.040) between patients with and without DED were observed. A multivariate logistic regression model indicated that the use of CPAP was independently associated with DED after adjustments for OSA severity. Patients undergoing CPAP were at greater risk of developing DED than those not undergoing CPAP (Odds ratio: 3.93, 95% confidence interval: 1.47-10.49, P = 0.006). Conclusion: OSA severity is associated with DED and might be attributed to the use of CPAP.

Antimony-Platinum Modulated Contact Enabling Majority Carrier Polarity Selection on a Monolayer Tungsten Diselenide Channel.

We develop a novel metal contact approach using an antimony (Sb)-platinum (Pt) bilayer to mitigate Fermi-level pinning in 2D transition metal dichalcogenide channels. This strategy allows for control over the transport polarity in monolayer WSe2 devices. By adjustment of the Sb interfacial layer thickness from 10 to 30 nm, the effective work function of the contact/WSe2 interface can be tuned from 4.42 eV (p-type) to 4.19 eV (n-type), enabling selectable n-/p-FET operation in enhancement mode. The shift in effective work function is linked to Sb-Se bond formation and an emerging n-doping effect. This work demonstrates high-performance n- and p-FETs with a single WSe2 channel through Sb-Pt contact modulation. After oxide encapsulation, the maximum current density at |VD| = 1 V reaches 170 µA/µm for p-FET and 165 µA/µm for n-FET. This approach shows promise for cost-effective CMOS transistor applications using a single channel material and metal contact scheme.

Two glycosyl transferase 2 genes from the gram-positive bacterium Clostridium ventriculi encode (1,3;1,4)-ß-D-glucan synthases.

The exopolysaccharides of the Gram-positive bacterium Romboutsia ilealis have recently been shown to include (1,3;1,4)-ß-D-glucans. In the present study, we examined another Clostridia bacterium Clostridium ventriculi that has long been considered to contain abundant amounts of cellulose in its exopolysaccharides. We treated alcohol insoluble residues of C. ventriculi that include the exopolysaccharides with the enzyme lichenase that specifically hydrolyses (1,3;1,4)-ß-D-glucans, and examined the oligosaccharides released. This showed the presence of (1,3;1,4)-ß-D-glucans, which may have previously been mistaken for cellulose. Through genomic analysis, we identified the two family 2 glycosyltransferase genes CvGT2-1 and CvGT2-2 as possible genes encoding (1,3;1,4)-ß-D-glucan synthases. Gain-of-function experiments in the yeast Saccharomyces cerevisiae demonstrated that both of these genes do indeed encode (1,3;1,4)-ß-D-glucan synthases.

Mindsets of suicide trajectories: An Linguistic Inquiry and Word Count analysis of suicide hotline conversations.

OBJECTIVE: The aim of the study was to explore the psychological characteristics of the individuals with various suicide risks using computerized text analysis, in the hopes of a better understanding of suicide trajectories. METHODS: 627 first-time callers' records were randomly selected from Taiwan An-Shin Hotline database between 2013 and 2018. The voice records were evaluated by two psychologists to determine the levels of suicide risk (156 with uncertainty of risk, 177 with low suicidal ideation, 157 with high suicidal ideation, and 137 with suicide preparation/attempt) and transcribed into text. The Linguistic Inquiry and Word Count 2015 (LIWC2015) program combined with Chinese dictionary were then used to calculate the frequency of word categories. RESULTS: Exploratory factor analysis identified four mindsets of language characteristics, named "opposition and questioning", "active engagement", "negative rumination", and "focus on death". Psychological descriptions of the mindsets were also obtained through correlation analysis with the LIWC2015 categories and indicators. The four mindsets effectively distinguished the callers with different levels of suicide risk. CONCLUSION: The psychological characteristics of people with various suicide risks can be described and differentiated via the closed-word categories and composite indicators. These results provide useful information for practitioners and researchers.

Lipopolysaccharide-Induced Lysosomal Cell Death Through Reactive Oxygen Species in Rat Liver Cell Clone 9.

In sepsis, bacterial components, particularly lipopolysaccharide (LPS), trigger organ injuries such as liver dysfunction. Although sepsis induces hepatocyte damage, the mechanisms underlying sepsis-related hepatic failure remain unclear. In this study, we demonstrated that the LPS-treated rat hepatocyte cell line Clone 9 not only induced reactive oxygen species (ROS) generation and apoptosis but also increased the expression of the autophagy marker proteins LC3-II and p62, and decreased the expression of intact Lamp2A, a lysosomal membrane protein. Additionally, LPS increased lysosomal membrane permeability and galectin-3 puncta formation, and promoted lysosomal alkalization in Clone 9 cells. Pharmacological inhibition of caspase-8 and cathepsin D (CTSD) suppressed the activation of caspase-3 and rescued the viability of LPS-treated Clone 9 cells. Furthermore, LPS induced CTSD release associated with lysosomal leakage and contributed to caspase-8 activation. Pretreatment with the antioxidant N-acetylcysteine (NAC) not only diminished ROS generation and increased the cell survival rate, but also decreased the expression of activated caspase-8 and caspase-3 and increased the protein level of Lamp2A in LPS-treated Clone 9 cells. These results demonstrate that LPS-induced ROS causes lysosomal membrane permeabilization and lysosomal cell death, which may play a crucial role in hepatic failure in sepsis. Our results may facilitate the development of new strategies for sepsis management.