After a year of the COVID-19 pandemic, countries have repeatedly imposed strict quarantine regimes as the virus mutates and becomes more contagious. Medical undergraduate education has been disrupted and transformed into prolonged home isolation and online learning. Although studies have reported that the COVID-19 pandemic tends to increase perceived stress (PS) and affect the mental health of medical students, the influencing factors are unclear. Therefore, based on the stress process model, this study will comprehensively evaluate the distribution of stressors of medical students and explore the personal and environmental predictors of PS during the epidemic. Participants and Methods: An online survey was conducted among medical students (n=369) from three medical universities in western China who engaged in online learning. A stress process conceptual framework was formed to explore the influencing factors of PS. The survey items contained four sections: (a) the potential stressors derived from academic, psychosocial and health-related demands; coping resources such as (b) online learning environment support and (c) personal resilience, including online learning behavior and individual characteristics; and (d) PS, perception of imbalanced demands and coping resources. Results: The mean PS score was 17.39 (SD=4.58), and over four-fifths (82.3%) of the students had moderate to high levels of stress. The average item scores of academic, psychosocial and health-related stressors were 2.72 (SD=0.55), 2.31 (SD=0.55) and 2.07 (SD=0.50), respectively. Gender, grade, psychosocial stressors, health-related stressors, specific online learning behavior (persistence, attitude and flexibility), and the online learning environment (teaching, social and cognitive presence) were predictors of PS. Conclusion:Our results specify that a reduction in psychological and health-related stressor stimulation, specific online learning behavior promotion, and well-established online learning environment support could be considered essential for alleviating the negative impacts of COVID-19 on the psychosocial health of medical undergraduates.

Dilated cardiomyopathy (DCM) is a major cause of sudden cardiac death and heart failure, and it is characterized by genetic and clinical heterogeneity, even for some patients with a very poor clinical prognosis; in the majority of cases, DCM necessitates a heart transplant. Genetic mutations have long been considered to be associated with this disease. At present, mutations in over 50 genes related to DCM have been documented. This study was carried out to elucidate the characteristics of gene mutations in patients with DCM. The candidate genes that may cause DCM include MYBPC3, MYH6, MYH7, LMNA, TNNT2, TNNI3, MYPN, MYL3, TPM1, SCN5A, DES, ACTC1 and RBM20. Using next-generation sequencing (NGS) and subsequent mutation confirmation with traditional capillary Sanger sequencing analysis, possible causative non-synonymous mutations were identified in ~57% (12/21) of patients with DCM. As a result, 7 novel mutations (MYPN, p.E630K; TNNT2, p.G180A; MYH6, p.R1047C; TNNC1, p.D3V; DES, p.R386H; MYBPC3, p.C1124F; and MYL3, p.D126G), 3 variants of uncertain significance (RBM20, p.R1182H; MYH6, p.T1253M; and VCL, p.M209L), and 2 known mutations (MYH7, p.A26V and MYBPC3, p.R160W) were revealed to be associated with DCM. The mutations were most frequently found in the sarcomere (MYH6, MYBPC3, MYH7, TNNC1, TNNT2 and MYL3) and cytoskeletal (MYPN, DES and VCL) genes. As genetic testing is a useful tool in the clinical management of disease, testing for pathogenic mutations is beneficial to the treatment of patients with DCM and may assist in predicting disease risk for their family members before the onset of symptoms.

Background Tumor chemo-resistance is a hallmark of malignant tumors as well as the major cause of poor survival rates in lung cancer. Transmembrane-4 L-six family member-1 (TM4SF1) , an antigen that serves as an oncogene, mainly affects tumor invasion and metastasis. We investigated the roles of TM4SF1 in non-small-cell lung cancer progression, particularly in the regulation of chemo-sensitivity. Methods TM4SF1 was silenced by small interfering RNA transfection. TM4SF1 expression in cell lines and tissues were determined by Quantitative Real-time PCR. MTS, clonogenic, Transwell assay, Flow cytometry verified cell function. By RT-PCR, Western blot, the mechanisms were studied. Results TM4SF1 was upregulated in both lung cancer cell lines and tissues, compared with 293 T epithelial cells. Analysis of online databases revealed that high expression of TM4SF1 is associated with the older patient age, smoking habits, and poor patient survival and outcome. Knockdown of TM4SF1 substantially inhibited tumor cell growth, migration, and invasion, and enhanced the chemo-sensitivity of the lung cancer cell lines A549 and H1299 to cisplatin and paclitaxel. Furthermore, the silencing of TM4SF1 induced lung cancer cell apoptosis and arrested cells at the G2/M phase. These results suggest that TM4SF1 is associated with lung cancer progression and appears to be required for tumor cell growth, maintenance of chemo-resistance and metastasis. We further found that TM4SF1 exerts these effects in part by regulating the expression of the discoidin domain receptor DDR1 and its downstream target, the Akt/ERK/mTOR pathway, and consequently alters cell sensitivity to chemo-reagents and contributes to invasion and metastasis. Conclusions These findings demonstrate that TM4SF1 may serve as a prognostic factor for lung cancer chemo-response and patient outcome.

Two kinds of ion-dependent DNAzymes and tailored substrates enable the design of the logic gates (OR, AND, INHIBIT) using Pb 2+ and Cu 2+ as inputs; then, a three-input AND logic gate is developed utilizing the unique feature that Hg 2+ ions interact with the thymine− thymine (T−T). At first, the substrates are blocked by ion-dependent DNAzymes that include the horseradish peroxidase (HRP)-mimicking DNAzyme sequence. The released product strands then self-assemble into the hemin/G-quadruplex-HRP-mimicking DNAzyme that biocatalyze the formation of a colored product and provide an output signal for the different logic gates. We are able to recognize the logic output signals effortlessly by our naked eyes. It is a simple, economic, and safe approach for the design of a complex multiple-input DNA logic molecular device.

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An electronic integrated circuit system is composed of elementary logic gates, which are capable of performing Boolean logic by receiving Boolean inputs representing true (1, high voltage) or false (0, low voltage) values and generating the appropriate Boolean output. [1] By analogy, molecular logic gates may enable the development of molecular-scale computers and "autonomously regulated" chemical systems, ideas that have recently attracted significant interest. [2][3] Because nucleic acids exhibit many advantages that would rival silicon-based computation in developing biologically relevant computation systems, such as structural simplicity, straight forward sequence-specific hybridization between complementary strands, as well as the ability to capture certain target molecules (e.g., metal ions, small molecules, and proteins in a highly specific manner [4][5] ), the design of addressable DNA logic gates is at the center of significant research efforts to construct DNA computation. [6] To date, considerable efforts have been dedicated to problems about the DNA logic gates primarily focused on identifying ideal candidates that satisfy logic operations. [2][3][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] For example, Zhang and co-workers have designed a system of colorimetric logic gates (OR, AND, and INHIBIT) utilizing Pb 2 + and Mg 2 + ions as the DNAzyme cofactors for the activation of the respective scission DNAzymes. [1] Famulok and co-workers have developed optical NOR, INHIBIT, and AND logic-gates operations employing K + -H + -triggered structural conversion of multiple nucleic-acid helices. [20] However, most of these logic gates employ colorimetric or fluorescent as outputs, which often suffer from relatively complex designs, complicated handling procedures, and a lack of portability. In addition, a potential limitation of these important proof-of-principle examples is that interfacing their optical outputs with nonmolecular-based technologies may prove to be cumbersome. Hence, the development of DNA electrochemical logic gates, which can be implemented with minimized reagents, working steps, and simplified optical setup would be more desirable.Herein, we report a series of new metal-ion-mediated DNA logic gates (AND, NAND, and NOR) based on electrochemical outputs. Utilizing the unique features of Ag + ions, which interact with the cytosine-cytosine (C-C) mismatch, and of Hg 2 + ions, which interact with the thyminethymine (T-T) mismatch in DNA duplexes, [23] an AND logic system is constructed based on the proximity-dependent surface hybridization between a thiolated T-/C-rich DNA on gold electrode surface and another T-/C-rich DNA labeled with ferrocenecarboxylic acid (Fc), in which the Hg 2 + and Ag + ions are employed as inputs and the current of the Fc as output. Subsequently, a NAND logic gate is constructed based on the strand dissociation, as well as the conformational switch of T-/C-rich DNA triggered by Ag + and Hg 2 + ions. In addition, we first found that the C-Ag + -C and T...

A horseradish peroxidase (HRP)-mimicking DNAzyme sequence is first blocked by the triplex-based molecular beacon (tMB). Upon hybridization with singlestranded DNA inputs, triplex−helix molecular switch occurs, and the released product strand self-assembles into the hemin/ G-quadruplex-HRP-mimicking DNAzyme that biocatalyzes the formation of a colored product and provides an output signal for the different logic gates. On the basis of this principle, a series of logic gates (OR, XOR, INHIBIT, and AND) have been developed. Moreover, a multilevel circuit (MC) that enforces an overall OR Boolean behavior is developed by connecting the AND and XOR logic gates. The logic output signals can be recognized by naked eyes, thus providing a flexible, secure, economic, and simple method for designing a complex DNA-based logic device.

Most antitumor ingredients found in nature have poor solubility. These ingredients are expected to have much better absorption and higher bioavailability than synthetic antitumor agents. Woody oil emulsive nanosystems carrying poorly soluble natural alkaloids were fabricated (evodiamine (EA) carried by fructus bruceae oil-based emulsive nanosystems, or EFEN). Fructus bruceae oil has two excipient-like properties (oil phase and stabilizer) that contribute to the formulation and one drug-like property (antitumor effects) that synergizes with the antitumor effect of EA. The properties of EFEN were compared with free EA, a blank nanoemulsion, an EA-loaded emulsive nanosystem, and a fructus bruceae oil-loaded emulsive nanosystem. For the first time, this suggests that increases in the sensitivity of lung cancer cells to poorly soluble natural alkaloids can be achieved by delivering drugs using woody oil-based emulsive nanosystems. In this study, woody oil-based emulsive nanosystems efficiently deliver poorly soluble natural alkaloids.