A G-quadruplex stabilizer, CX-5461 combined with two immune checkpoint inhibitors enhances in vivo therapeutic efficacy by increasing PD-L1 expression in colorectal cancer.

PURPOSE: Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy can improve the limited efficacy of colorectal cancer (CRC) immunotherapy. CX-5461 causes substantial DNA damage and genomic instability and can increase ICIs' therapeutic efficacies through tumor microenvironment alteration. RESULTS: We analyzed whether CX-5461 enhances ICIs' effects in CRC and discovered that CX-5461 causes severe DNA damage, including cytosolic dsDNA appearance, in various human and mouse CRC cells. Our bioinformatics analysis predicted CX-5461-based interferon (IFN) signaling pathway activation in these cells, which was verified by the finding that CX-5461 induces IFN-α and IFN-ß secretion in these cells. Next, cGAMP, phospho-IRF3, CCL5, and CXCL10 levels exhibited significant posttreatment increases in CRC cells, indicating that CX-5461 activates the cGAS-STING-IFN pathway. CX-5461 also enhanced PD-L1 expression through STAT1 activation. CX-5461 alone inhibited tumor growth and prolonged survival in mice. CX-5461+anti-PD-1 or anti-PD-L1 alone exhibited synergistic growth-suppressive effects against CRC and breast cancer. CX-5461 alone or CX-5461+anti-PD-1 increased cytotoxic T-cell numbers and reduced myeloid-derived suppressor cell numbers in mouse spleens. CONCLUSIONS: Therefore, clinically, CX-5461 combined with ICIs for CRC therapy warrants consideration because CX-5461 can turn cold tumors into hot ones.

The relationship between students' counseling center contact and long-term educational outcomes.

Numerous studies have demonstrated that counseling centers deliver a positive impact on the emotional and social development of college students who receive services. These healthy outcomes, in turn, can lead to increased academic success, such as improved performance, retention, and persistence. While these short-term academic outcomes have been widely investigated, very few studies have explored the relationship between counseling center services and longer-term educational outcomes, such as final grade point average (GPA), time spent at the university, and degree completion. In the current study, counseling center usage, including appointments that were attended, cancelled, and no showed, as well as distal educational variables were examined within 2 cohorts of first-time full-time students over a 6-year period. Findings revealed that both users and nonusers of counseling center services spent a similar amount of time to degree completion and achieved comparable final semester GPAs as well. However, students who utilized counseling services graduated at a significantly lower rate (79.8%) than those who did not use services (86.2%) across the 6-year time span. Post hoc analyses indicated that among students who used counseling services, those who did not graduate scheduled significantly more services than those who graduated, suggesting that students who use the counseling center, and have more chronic and severe mental health problems, may be graduating at a lower rate. Implications are discussed. (PsycINFO Database Record

Physical and chemical mechanisms in oxide-based resistance random access memory.

In this review, we provide an overview of our work in resistive switching mechanisms on oxide-based resistance random access memory (RRAM) devices. Based on the investigation of physical and chemical mechanisms, we focus on its materials, device structures, and treatment methods so as to provide an in-depth perspective of state-of-the-art oxide-based RRAM. The critical voltage and constant reaction energy properties were found, which can be used to prospectively modulate voltage and operation time to control RRAM device working performance and forecast material composition. The quantized switching phenomena in RRAM devices were demonstrated at ultra-cryogenic temperature (4K), which is attributed to the atomic-level reaction in metallic filament. In the aspect of chemical mechanisms, we use the Coulomb Faraday theorem to investigate the chemical reaction equations of RRAM for the first time. We can clearly observe that the first-order reaction series is the basis for chemical reaction during reset process in the study. Furthermore, the activation energy of chemical reactions can be extracted by changing temperature during the reset process, from which the oxygen ion reaction process can be found in the RRAM device. As for its materials, silicon oxide is compatible to semiconductor fabrication lines. It is especially promising for the silicon oxide-doped metal technology to be introduced into the industry. Based on that, double-ended graphene oxide-doped silicon oxide based via-structure RRAM with filament self-aligning formation, and self-current limiting operation ability is demonstrated. The outstanding device characteristics are attributed to the oxidation and reduction of graphene oxide flakes formed during the sputter process. Besides, we have also adopted a new concept of supercritical CO2 fluid treatment to efficiently reduce the operation current of RRAM devices for portable electronic applications.

Effects of a stability ball exercise programme on low back pain and daily life interference during pregnancy.

BACKGROUND: most pregnant women experience back pain during pregnancy, a serious issue that negatively impacts life quality during pregnancy. Research into an exercise intervention programme targeting low back pain and daily life interference is lacking. OBJECTIVE: this study evaluates how a stability ball exercise programme influences low back pain and daily life interference across the second and third pregnancy trimester. METHODS: the study was non-randomised and controlled, examining a target population of low-risk pregnancy women between 20 and 22 weeks of gestation located in a regional hospital in northern Taiwan. All participants had at least minimal low back pain, no prior history of chronic low back pain before pregnancy, and no indications of preterm labour. In total, 89 individuals participated: 45 in the control group and 44 in the experimental group (who attended an antenatal stability ball exercise programme). This programme lasted 12 weeks, composed of at least three sessions per week. Fitness workouts lasted from 25 to 30 minutes. The women completed their basic personal information, the Brief Pain Inventory-Short Form, and the Family Exercise Support Attitude Questionnaire. RESULTS: after adjusting for demographic data and antenatal exercise status by propensity scores, experimental-group women who participated in the antenatal stability ball exercise programme reported significantly less low back pain and daily life interferences than the control group at 36 weeks of gestation. DISCUSSION: the inclusion of stability ball exercises during pregnancy may reduce pregnancy low back pain and boost daily life functions. This stability ball exercise programme provides health-care professionals with an evidence-based intervention.

Effects of a prenatal yoga programme on the discomforts of pregnancy and maternal childbirth self-efficacy in Taiwan.

OBJECTIVE: to evaluate a yoga programme provided to primigravidas in the third trimester of pregnancy with the aim of decreasing the discomforts associated with pregnancy and increasing childbirth self-efficacy. DESIGN: non-randomised controlled experimental study. SETTING: a hospital in northern Taiwan. PARTICIPANTS: the target population was primigravidas at 26-28 weeks of gestation (no high-risk pregnancies) who had not engaged in regular exercise or yoga for at least one year. The study included 88 individuals; 43 in the control group and 45 in the experimental group who took part in the prenatal yoga programme. INTERVENTION: the duration of the prenatal yoga programme was 12-14 weeks, with at least three sessions per week. Each workout lasted for 30 minutes. MEASUREMENTS AND FINDINGS: women who took part in the prenatal yoga programme reported significantly fewer pregnancy discomforts than the control group (38.28 vs 43.26, z=-2.58, p=0.01) at 38-40 weeks of gestation. The subjects who participated in the yoga programme exhibited higher outcome and self-efficacy expectancies during the active stage of labour (104.13 vs 83.53, t=3.24, p=0.002; 99.26 vs 77.70, t=3.99, p ≤ 0.001) and the second stage of labour (113.33 vs 88.42, t=3.33, p=0.002; 102.19 vs 79.40, t=3.71, p ≤ 0.001) compared with the control group. KEY CONCLUSIONS: the provision of booklets and videos on yoga during pregnancy may contribute to a reduction in pregnancy discomforts and improved childbirth self-efficacy. IMPLICATIONS FOR PRACTICE: this yoga programme provides health-care professionals with an evidence-based intervention.