Awareness of HPV and HPV vaccine among college students in China.

Background: Cervical cancer is the fourth most common cancer among women, HPV vaccine can reduce the incidence of cervical cancer by approximately 70%. Sexual behavior is a direct risk factor for HPV infection, and sexually active college students, therefore, receive attention for HPV vaccination. This study aimed to investigate the awareness of HPV and its vaccine among college students in Zhengzhou, and to explore the factors influencing their awareness of HPV vaccine, to understand college students' willingness to receive the vaccine. The findings of this study will lay a foundation for cervical cancer prevention. Methods: Using a multistage random sampling method, 650 college students from four universities in Zhengzhou were selected. A self-administered questionnaire on the awareness of HPV and its vaccine, and willingness to receive HPV vaccination was carried out. Logistic regression was used to analyze the factors influencing students' awareness of the HPV vaccine. Results: 58.0% of college students had heard of HPV, and 72.8% of college students had heard of HPV vaccine. Logistic regression showed that gender, major, grade, mean monthly consumption level, sexual history, and mother cervical cancer screening participation significantly influenced the awareness of HPV vaccine (p < 0.05). Only 27(4.2%) college students had received the HPV vaccine. 63.2% of college students expressed their willingness to get vaccinated. Conclusion: The awareness of HPV and its vaccine among college students in Zhengzhou needs improvement. Although the vaccination rate is low, most college students are willing to be vaccinated. Diverse health education programs should be conducted for different groups to improve awareness of cervical cancer prevention and promote vaccination.

Electrochemically Driven Nickel-Catalyzed Enantioselective Hydro-Arylation/Alkenylation of Enones.

Herein, the study reports the first electrochemical nickel-catalyzed enantioselective hydro-arylation/alkenylation of enones in an undivided cell with low-cost electrodes in the absence of external reductants and supporting electrolytes. Aryl bromides/iodides/triflates or alkenyl bromides are employed as electrophiles for the efficient preparation of more than 56 valuable ß-arylated/alkenylated ketones in a simple manner (up to 97% yield, 97% ee). With the advantages of electrochemistry, excellent functional group tolerance and late-stage modification of complex natural products and pharmaceuticals made the established protocol greener and more economic. Mechanism investigation suggests that a NiI/NiIII cycle may be involved in this electro-reductive reaction rather than metal reductant driven Ni0/NiII cycle. Overall, the efficient electrochemical activation and turnover of the nickel catalyst avoid the drawbacks posed by the employment of stoichiometric amount of sensitive metal powder reductants.

Effect of vaccine hesitancy on female college students' willingness to receive the HPV vaccine in China: a multicenter cross-sectional study.

OBJECTIVE: To analyse the influencing factors of vaccine hesitancy on HPV vaccination willingness of female college students in order to promote the promotion of HPV vaccine in female college student population. METHODS: From September-October 2022, a convenience sampling method was used to conduct a questionnaire survey among freshman female students from four higher vocational colleges in Henan Province, China. The survey comprised a general information questionnaire, as well as inquiries regarding vaccine hesitancy and willingness to receive the human papillomavirus (HPV) vaccine. In PSM analyses, vaccine-hesitant students were matched with non-vaccine-hesitant students at a 1:1 ratio; subsequently, both univariate and multivariatble logistic regression analyses were applied to assess the impact of vaccine hesitancy on female university students' willingness to receive the HPV vaccine. RESULTS: The results revealed a vaccine hesitancy rate of 44.75% among female university students, with 82.9% expressing willingness to receive the HPV vaccine. The results of the multivariable ordinal logistic regression analysis indicated vaccine hesitancy is a risk factor for HPV vaccination intentions among female university students [OR = 4.38, 95% CI (2.74, 6.99), P < 0.001]. Furthermore, the field of study (P = 0.01) and independently seeking information about the HPV vaccine (P = 0.04) were identified as factors influencing female university students' willingness to receive the HPV vaccine. CONCLUSIONS: Non-vaccine-hesitant students were more likely to be willing to receive the HPV vaccine than vaccine-hesitant students. Healthcare providers and educators should focus on vaccine attitudes among female college students to reduce vaccine hesitancy and enhance community education on cervical cancer, HPV infection and prevention through multichannel campaigns.

Electrochemical Nickel-Catalyzed Cross-Electrophile Coupling of Alkenyl Triflates with α-Chloroamides.

Cross-electrophile coupling reactions of different electrophiles have been extensively studied but mainly limited to bromides and iodides. Here, we report an electrochemically induced nickel-catalyzed cross-electrophile coupling strategy between alkenyl triflates and α-chloroamides in an undivided cell under mild reaction conditions, affording the α-functionalized amide derivatives in good to excellent yields with broad substrate scopes and good functional group tolerance. The control experiments were conducted, and a plausible mechanism was proposed.

Factors influencing self-regulatory fatigue in patients undergoing chemotherapy for gynecologic cancer: a cross-sectional study.

Objective: To understand the current status of self-regulatory fatigue among gynecologic cancer chemotherapy patients and explore influencing factors. Methods: Using convenient sampling, a total of 232 gynecological cancer chemotherapy patients from two tertiary hospitals in Zhengzhou, Henan, China, were selected as study subjects from February 2023 to April 2023. General information questionnaire, Self-Regulatory Fatigue Scale (SRF-S), Strategies Used by People to Promote Health (SUPPH) Scale, Connor-Davidson resilience scale (CD-RISC) and Perceived Social Support Scale (PSSS) were employed for data collection. The data were analyzed using SPSS 26.0 software. Chi-square test and binary logistic regression were executed to explore the correlates of self-regulatory fatigue, the significance level (α) was set at 0.05. Results: The self-regulatory fatigue score of the 232 patients was 44 (36, 56). Binary logistic regression analyses revealed significant associations, demonstrating that residing in urban areas (OR=0.241, P=0.015), having no comorbidities (OR=0.158, P=0.015), increased perceived social support (OR=0.937, P=0.001), strong self-efficacy (OR=0.959, P=0.021), and heightened psychological resilience (OR=0.895, P<0.001) acted as protective factors against self-regulatory fatigue (P < 0.05). Conclusion: Patients residing in rural areas, having more than two comorbidities, lower self-efficacy and psychological resilience levels, and lower perceived social support are indicative of higher levels of self-regulatory fatigue. Identifying these influencing factors can provide references and support for developing individualized support and intervention measures to improve patients' physical and mental well-being.

Discovery of a doublecortin-like kinase 1 inhibitor to prevent inflammatory responses in acute lung injury.

Doublecortin-like kinase 1 (DCLK1) is a microtubule-associated protein kinase involved in neurogenesis and human cancer. Recent studies have revealed a novel functional role for DCLK1 in inflammatory signaling, thus positioning it as a novel target kinase for respiratory inflammatory disease treatment. In this study, we designed and synthesized a series of NVP-TAE684-based derivatives as novel anti-inflammatory agents targeting DCLK1. Bio-layer interferometry binding screening and kinase assays of the NVP-TAE684 derivatives led to the discovery of an effective DCLK1 inhibitor (a24), with an IC50 of 179.7 nM. Compound a24 effectively inhibited lipopolysaccharide (LPS)-induced inflammation in macrophages with higher potency than the lead compound. Mechanistically, compound a24 inhibited LPS-induced inflammation by inhibiting DCLK1-mediated IKKß phosphorylation. Furthermore, compound a24 showed in vivo anti-inflammatory activity in an LPS-challenged acute lung injury model. These findings suggest that compound a24 may serve as a novel candidate for the development of DCLK1 inhibitors and a potential therapeutic agent for the treatment of inflammatory diseases.

Analysis of the status and factors influencing physical activity in patients undergoing ovarian cancer chemotherapy.

Background: Ovarian cancer is a common gynecological malignancy, leading to approximately 200,000 deaths globally in 2020. Research has shown that regular physical activity can reduce the toxic side effects of cancer treatment, reduce morbidity and mortality, extend survival time, and improve quality of life. We aimed to evaluate physical activity regimens in patients undergoing chemotherapy for ovarian cancer and analyze the factors influencing physical activity levels. Methods: To facilitate the selection of patients with ovarian cancer hospitalized for chemotherapy in the Third Affiliated Hospital of Zhengzhou University and the First Affiliated Hospital of Zhengzhou University from August 2022 to February 2023, questionnaire surveys were conducted using the General Information Questionnaire, International Physical Activity Questionnaire, Hospital Anxiety and Depression Scale, and Revised Piper Fatigue Scale. Results: Data were collected from 167 patients with ovarian cancer. Overall, 96 (57.5%) patients had low physical activity levels, 53 (31.7%) had moderate physical activity levels, and 18 (10.8%) had high physical activity levels. Logistic regression analysis revealed that sleep status, social support, anxiety, depression, and cancer-related fatigue were the main factors influencing physical activity in patients undergoing chemotherapy for ovarian cancer. Conclusions: Physical activity levels of patients undergoing ovarian cancer chemotherapy were generally low. Therefore, healthcare professionals should pay greater attention to the physical activity in these patients. Targeted and individualized health guidance is recommended, and activity interventions should be implemented according to the influencing factors to promote disease understanding and increase physical activity levels.

Radical Crotylation of Aldehydes with 1,3-Butadiene by Photoredox Cobalt and Titanium Dual Catalysis.

Metal-hydride hydrogen atom transfer (MHAT) has been recognized as a powerful method for alkene functionalization; however, photochemical MAT-mediated chemoselective functionalization of dienes remains undeveloped. In this study, we report a radical strategy (1e-) through MHAT using photoredox cobalt and titanium dual catalysis for aldehyde crotylation with butadiene, achieving excellent regio- and diastereoselectivity.

Removal of tetracycline in aqueous solution by iron-loaded biochar derived from polymeric ferric sulfate and bagasse.

In this study, the tetracycline (TC) removal performance of iron-loaded biochar (BPFSB) derived from sugarcane bagasse and polymerized iron sulfate was investigated, and the mechanism of TC removal was also explored by study of isotherms, kinetics and thermodynamics and characterization of fresh and used BPFSB (XRD, FTIR, SEM and XPS). The results showed that under optimized conditions (initial pH 2; BPFSB dosage 0.8 g·L-1; TC initial concentration 100 mg·L-1; Contact time 24 h; temperature 298 K), the removal efficiency of TC was as high as 99.03%. The isothermal removal of TC followed well the Langmuir, Freundlich, and Temkin models, indicating that multilayer surface chemisorption dominated the TC removal. The maximum removal capacity of TC by BPFSB at different temperatures was 185.5 mg·g-1 (298 K), 192.7 mg·g-1 (308 K), and 230.9 mg·g-1 (318 K), respectively. The pseudo-second-kinetic model described the TC removal better, while its rate-controlling step was a combination of liquid film diffusion, intraparticle diffusion, and chemical reaction. Meanwhile, TC removal was also a spontaneous and endothermic process, during which the randomness and disorder between the solid-liquid interface was increased. According to the characterization of BPFSBs before and after TC removal, H-bonding and complexation were the major interactions for TC surface adsorption. Furthermore, BPFSB was efficiently regenerated by NaOH. In summary, BPFSB had the potential for practical application in TC removal.

Novel O-benzylcinnamic acid derivative L26 treats acute lung injury in mice by MD-2.

Acute lung injury (ALI) is an inflammation-mediated respiratory disease that is associated with a high mortality rate. In this study, a series of novel O-benzylcinnamic acid derivatives were designed and synthesized using cinnamic acid as the lead compound. We tested the preliminary anti-inflammatory activity of the compounds by evaluating their effect on inhibiting the activity of alkaline phosphatase (ALP) in Hek-Blue-TLR4 cells, in which compound L26 showed the best activity and 7-fold more active than CIN. ELISA, immunoprecipitation, and molecular docking indicated that L26 targeted MD-2 protein and competed with LPS to bind to MD-2, which resulted in the inhibition of inflammation. In the LPS-induced mouse model of ALI, L26 was found to decrease ALP activity and inflammatory cytokine TNF-α release to reduce lung injury by inhibiting the NF-κB signaling pathway. Acute toxicity experiments showed that high doses of L26 did not cause adverse reactions in mice, and it was safe in vivo. Also, the preliminary pharmacokinetic parameters of L26 were investigated in SD rats (T1/2 = 4.246 h). In summary, L26 exhibited optimal pharmacodynamic and pharmacokinetic characteristics, which suggested that L26 could serve as a potential agent for the development of ALI treatment.

Facile preparation of activated carbon supported nano zero-valent iron for Cd(â ¡) removal in aqueous environment.

Activated carbon-supported nano-zero-valent iron (nZVI@AC) is considered to be one of the most promising materials for in-situ remediation of pollutants in aqueous environment, while liquid phase reduction (LPR) is one of the most commonly used preparation methods for nZVI@AC. However, the complex operation and the requirement of various agents limit the practical application of the traditional liquid-phase reduction (TLPR). In this study, an improved liquid phase reduction method (ILPR) was proposed, which was characterized by solid-state dosing of reducing agents. Compared with TLPR, ILPR simplified the preparation process, while there was no requirement of polyethylene glycol and ethanol. When the Cd(II) removal efficiency was used as the evaluation index, the preferred parameters of ILPR were as follows: AC/FeSO4·7H2O mass ratio was 15:1; NaBH4 dosage was 8 g; ultrasonic time was 1 h; stirring time was 20 min. Moreover, the Cd(II) removal efficiency of nZVI@AC prepared by ILPR (nZVI@AC-I) was greater than 92.00%, which was superior to that of nZVI@AC prepared by TLPR (nZVI@AC-T). The characterization results showed that the pore parameters, surface functional groups and iron contents of nZVI@AC-I and nZVI@AC-T were basically the same. However, the distribution of iron-containing particles on the surface of nZVI@AC-I was more uniform. Furthermore, the Fe0 in nZVI@AC-I had a smaller particle size and a higher content. Overall, this study provided a promising approach for nZVI@AC preparation.

Knowledge of cervical cancer prevention and treatment, and willingness to receive HPV vaccination among college students in China.

BACKGROUND: Cervical cancer is the fourth most common cancer in women. Up to 99% of cervical cancer cases are associated with high-risk human papillomavirus (HPV). Sexual behavior is a direct risk factor for HPV infection, and sexually active college students, therefore, receive attention for HPV vaccination. At present, most Chinese studies lack of in-depth research on influencing factors, and are limited to cervical cancer, HPV, or HPV vaccine, without comprehensive consideration. This study investigated Chinese college students' cervical cancer prevention and treatment knowledge level, and explored the influencing factors, and understood their willingness to receive HPV vaccination. The findings of this study will lay a foundation for promoting the early screening of cervical cancer and vaccination process. METHODS: A total of 800 college students from four universities in Zhengzhou, China were selected by multistage random sampling method. A self-administered questionnaire on the knowledge of cervical cancer prevention and treatment, and willingness to receive HPV vaccination was carried out. A logistic regression model was conducted to analyze factors influencing knowledge of cervical cancer prevention and treatment among college students. RESULTS: Up to 87.9% of college students said they had heard of cervical cancer. The proportion of college students with good knowledge of cervical cancer prevention and treatment was 46.7%. Logistic regression showed that gender, major, grade, level of education, the father's level of education, premarital sex attitude, and mother cervical cancer screening participation had a significant influence on cervical cancer prevention and treatment knowledge level (P < 0.05). In addition, 589 (74.0%) of college students had heard of HPV vaccine, and 92.8% of college students said they were willing to get vaccinated or recommended that their relatives and friends get vaccinated. CONCLUSIONS: The knowledge level of cervical cancer prevention and treatment knowledge among college students in Zhengzhou is low. Many of them had poor knowledge about HPV vaccine, but their willingness to vaccination is high. Various health education modes should be carried out for people with different characteristics, to improve their knowledge of cervical cancer prevention and promote the vaccination process.

Iron/photoredox dual catalysis for acyl nitrene-based C-O bond formation towards phthalides.

This paper describes iron/photoredox dual-catalyzed acyl nitrene formation and the use of acyl nitrene in constructing various C-O bonds towards phthalides. The developed reaction starts from N-methoxyl-2-alkylbenzamides. Mechanism surveys suggest the reaction involves iron nitrene-based hydrogen atom abstraction (HAA), radical-polar crossover and O-nucleophilic SN1. Distinctively, the often-reported radical rebound in previous publications is not observed. The reaction represents the first example on acyl nitrene-based synthesis of phthalides. Moreover, it also serves as a supplement for the synthesis of marketed medicines such as 3-butylphthalides (NBP), thalidomide, Pomalyst and Otezia.

Transferrin improved the generation of cardiomyocyte from human pluripotent stem cells for myocardial infarction repair.

Human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) hold great promise for the repair of the injured heart, but optimal cell production in a fully chemically defined and cost-effective system is essential for the efficacy and safety of cell transplantation therapies. In this study, we provided a simple and efficient strategy for cardiac differentiation from hPSCs and performed functional evaluation in a rat model of myocardial infarction. Using a chemically defined medium including four components, recombinant human albumin, ascorbic acid, human transferrin, and RPMI 1640, we developed a manageable and cost-effective protocol for robust generation of CMs from hPSCs. Interestingly, the addition of transferrin helped hPSCs to transit from TeSR-E8 medium to the simple cardiac differentiation medium and successfully initiated mesoderm differentiation without significant cell death. The CM generation efficiency was up to 85% based on cTnT expression. We performed transcriptome profiling from differentiation day 0 to 35, and characterized interesting dynamic change of cardiac genes. CMs derived from transferrin-supplemented simple medium have similar transcriptome and the maturation level compared to those generated in B27 minus insulin medium as well as their in vivo counterparts. Importantly, after transplantation, hPSC-derived CMs survived in the infarcted rat heart, significantly improved the physiological function and reduced fibrosis. Our study offers an easy-to-use and cost-effective method for cardiac differentiation and facilitates the translational application of hPSC-derived CMs for heart repair.

Homozygous MESP1 knock-in reporter hESCs facilitated cardiovascular cell differentiation and myocardial infarction repair.

Different populations of cardiovascular progenitor cells have been shown to possess varying differentiation potentials. They have also been used to facilitate heart repair. However, sensitive reporter cell lines that mark the human cardiovascular progenitors are in short supply. Methods: MESP1 marks the earliest population of cardiovascular progenitor cells during embryo development. Here, we generated a homozygous MESP1 knock-in reporter hESC line where mTomato gene joined to the MESP1 coding region via a 2A peptide, in which both MESP1 alleles were preserved. We performed transcriptome and functional analysis of human MESP1+ cardiovascular progenitor cells and tested their therapeutic potential using a rat model of myocardial infarction. Results: MESP1-mTomato knock-in reporter faithfully recapitulated the endogenous level of MESP1. Transcriptome analysis revealed that MESP1+ cells highly expressed early cardiovascular genes and heart development genes. The activation of MESP1 relied on the strength of canonical Wnt signaling, peak MESP1-mTomato fluorescence correlated with the window of canonical Wnt inhibition during in vitro differentiation. We further showed that MESP1 bound to the promoter of the WNT5A gene and the up-regulation of WNT5A expression suppressed canonical Wnt/ß-CATENIN signaling. Moreover, induced MESP1 expression could substitute the canonical Wnt inhibition step and promote robust cardiomyocyte formation. We used a configurable, chemically defined, tri-lineage differentiation system to obtain cardiomyocytes, endothelial cells, and smooth muscle cells from MESP1+ cells at high efficiency. Finally, we showed that the engraftment of MESP1+ cells repaired rat myocardial infarction model. Conclusions: MESP1-mTomato reporter cells offered a useful platform to study cardiovascular differentiation from human pluripotent stem cells and explore their therapeutic potential in regenerative medicine.

Development of a Novel Cell-Permeable Protein-Protein Interaction Inhibitor for the Polo-box Domain of Polo-like Kinase 1.

Polo-like kinase 1 (PLK1) is a key regulator of mitosis and a recognized drug target for cancer therapy. Inhibiting the polo-box domain of PLK1 offers potential advantages of increased selectivity and subsequently reduced toxicity compared with targeting the kinase domain. However, many if not all existing polo-box domain inhibitors have been shown to be unsuitable for further development. In this paper, we describe a novel compound series, which inhibits the protein-protein interactions of PLK1 via the polo-box domain. We combine high throughput screening with molecular modeling and computer-aided design, synthetic chemistry, and cell biology to address some of the common problems with protein-protein interaction inhibitors, such as solubility and potency. We use molecular modeling to improve the solubility of a hit series with initially poor physicochemical properties, enabling biophysical and biochemical characterization. We isolate and characterize enantiomers to improve potency and demonstrate on-target activity in both cell-free and cell-based assays, entirely consistent with the proposed binding model. The resulting compound series represents a promising starting point for further progression along the drug discovery pipeline and a new tool compound to study kinase-independent PLK functions.

Highly branched poly(ß-amino ester) delivery of minicircle DNA for transfection of neurodegenerative disease related cells.

Current therapies for most neurodegenerative disorders are only symptomatic in nature and do not change the course of the disease. Gene therapy plays an important role in disease modifying therapeutic strategies. Herein, we have designed and optimized a series of highly branched poly(ß-amino ester)s (HPAEs) containing biodegradable disulfide units in the HPAE backbone (HPAESS) and guanidine moieties (HPAESG) at the extremities. The optimized polymers are used to deliver minicircle DNA to multipotent adipose derived stem cells (ADSCs) and astrocytes, and high transfection efficiency is achieved (77% in human ADSCs and 52% in primary astrocytes) whilst preserving over 90% cell viability. Furthermore, the top-performing candidate mediates high levels of nerve growth factor (NGF) secretion from astrocytes, causing neurite outgrowth from a model neuron cell line. This synergistic gene delivery system provides a viable method for highly efficient non-viral transfection of ADSCs and astrocytes.

Preliminary Effectiveness of Auricular Point Acupressure on Chemotherapy-Induced Neuropathy: Part 2 Laboratory-Assessed and Objective Outcomes.

PURPOSE: To manage chemotherapy-induced neuropathy (CIN), this paper explores reliable and valid objectives measures to evaluate the treatment effects of auricular point acupressure (APA). DESIGN/METHOD: This study was a repeated-measures one-group design. Participants received four weeks of APA to manage their CIN. The laboratory-assessed and objective outcomes included quantitative sensory testing, grip and pinch strength, and inflammatory biomarkers. Wilcoxon matched pairs signed-rank tests were conducted to determine change scores of outcomes at pre- vs. post- and pre- vs. 1-month follow-up. Spearman's rho correlation coefficient was used to examine the linear association of score changes of all objective study outcomes. RESULTS: Comparing pre-and-post APA, (1) the mean score of the monofilament for all lower extremity sites tested decreased after APA, indicating sensory improvement; (2) the suprathreshold pinprick stimuli mean scores on the upper extremities increased, except the scores from the index finger and thumb; (3) the pain tolerance of thumb and trapezius areas increased; (4) decreasing IL1ß (p = .05), IFNγ (p = .02), IL-2 (p = .03), IL-6 (p = .05), IL-10 (p = .05), and IP10/CXCL10 (p = .04) were observed pre-post APA. Conditional pain modulation was significantly (p< .05) associated with pain intensity (r = 0.55), tingling (r = 0.59); and IL1ß concentration (r = 0.53) pre-post APA. The sustained effects of 4-week APA were observed at the 1-month follow-up. CONCLUSIONS: Our study findings demonstrated the promising effectiveness of APA in the management of CIN, and these treatment effects can be assessed using reliable and valid objective measures. CLINICAL IMPLICATIONS: If the efficacy of APA to manage CIN is confirmed in a larger sample, APA has the potential to be a scalable treatment for CIN because it is a reproducible, standardized, and easy-to-perform intervention.

Preliminary Effectiveness of Auricular Point Acupressure on Chemotherapy-Induced Neuropathy: Part 1 Self-Reported Outcomes.

PURPOSE: To reduce chemotherapy-induced neuropathy (CIN)-a significant challenge among cancer patients following chemotherapy-we explored the effects of auricular point acupressure (APA), which involves needleless, acupuncture-like stimulation on specific ear points. DESIGN/METHOD: This pilot study examined the effects of a 4-week APA intervention in the management of CIN. Descriptive analysis was used to examine the changes in study outcomes. RESULTS: Fifteen participants were enrolled. Two participants dropped out because they developed new medical conditions. Thirteen participants completed the study (87% retention rate). Study participants had more severe symptoms in their lower extremities (i.e., toes, feet, soles) than in their upper extremities (i.e., fingers, wrists, elbows). After the 4-week APA intervention, the mean percentage change scores ranged from 38% (tingling) to 49% (numbness); compared to pre-intervention, the therapeutic effects of APA were sustained at the 1-month follow-up. Function in both upper and lower extremities improved after the APA intervention (≥28%) and continued to improve at the 1-month follow-up (≥36%). CONCLUSIONS: Preliminary results from this small sample provide initial evidence of the effectiveness of APA on CIN. Future studies should confirm these results using a larger sample, a comparative sham control, and an examination of the underlying physiological mechanisms of the anti-CIN effects of APA. CLINICAL IMPLICATIONS: APA may provide an inexpensive and effective complementary approach for the self-management of CIN. Once the seeds have been taped to the patient's ear by the provider, patients are empowered to self-manage their CIN in their own environment.

Anti-apoptotic Mutations Desensitize Human Pluripotent Stem Cells to Mitotic Stress and Enable Aneuploid Cell Survival.

Human pluripotent stem cells (hPSCs) are susceptible to numerical and structural chromosomal alterations during long-term culture. We show that mitotic errors occur frequently in hPSCs and that prometaphase arrest leads to very rapid apoptosis in undifferentiated but not in differentiated cells. hPSCs express high levels of proapoptotic protein NOXA in undifferentiated state. Knocking out NOXA by CRISPR or upregulation of the anti-apoptosis gene BCL-XL significantly reduced mitotic cell death, allowing the survival of aneuploid cells and the formation of teratomas significantly larger than their wild-type parental hPSCs. These results indicate that the normally low threshold of apoptosis in hPSCs can safeguard their genome integrity by clearing cells undergoing abnormal division. The amplification of BCL2L1 on chromosome 20q11.21, a frequent mutation in hPSCs, although not directly oncogenic, reduces the sensitivity of hPSCs to damage caused by erroneous mitosis and increases the risk of gaining aneuploidy.