Recombinant Lactococcus lactis NZ9000 secretes a bioactive kisspeptin that inhibits proliferation and migration of human colon carcinoma HT-29 cells

BACKGROUND: Proteinaceous bioactive substances and pharmaceuticals are most conveniently administered orally. However, the facing problems are the side effects of proteolytic degradation and denaturation in the gastrointestinal tract. In recent years, lactic acid bacteria (LAB) have been verified to be a promising delivery vector for susceptible functional proteins and drugs. KiSS-1 peptide, a cancer suppressor, plays a critical role in inhibiting cancer metastasis and its activity has been confirmed by direct administration. However, whether this peptide can be functionally expressed in LAB and exert activity on cancer cells, thus providing a potential alternative administration manner in the future, has not been demonstrated. RESULTS: A recombinant Lactococcus lactis strain NZ9000-401-kiss1 harboring a plasmid containing the gene of the tumor metastasis-inhibiting peptide KiSS1 was constructed. After optimization of the nisin induction conditions, the recombinant strain efficiently secreted KiSS1 with a maximum detectable amount of 27.9 μg/ml in Dulbecco’s Modified Eagle medium. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide and would healing assays, respectively, indicated that the secreted KiSS1 peptide remarkably inhibited HT-29 cell proliferation and migration. Furthermore, the expressed KiSS1 was shown to induce HT-29 cell morphological changes, apoptosis and reduce the expression of matrix metalloproteinase 9 (MMP-9) at both mRNA and protein levels. CONCLUSIONS: A recombinant L. lactis NZ9000-401-kiss1 successfully expressing the human kiss1 was constructed. The secreted KiSS1 peptide inhibited human HT-29 cells’ proliferation and migration probably by invoking, or mediating the cell-apoptosis pathway and by down regulating MMP-9 expression, respectively. Our results suggest that L. lactis is an ideal cell factory for secretory expression of tumor metastasis-inhibiting peptide KiSS1, and the KiSS1-producing L. lactis strain may serve as a new tool for cancer therapy in the future

Z-OFDM: A New High-Performance Solution for Underwater Acoustic Communication

This paper presents Z-OFDM, a high-performance solution for underwater acoustic communication. Traditional underwater orthogonal frequency division multiplexing (OFDM) systems suffer from spectrum leakage and distortion due to the narrowband nature of underwater acoustic signals and the picket fence effect of the fast Fourier transform (FFT). Z-OFDM addresses these issues by integrating zoom-fast Fourier transform (ZoomFFT) with OFDM and redesigning the modulator and demodulator to replace the conventional FFT. This integration enhances spectral resolution, resulting in higher channel capacity, improved Signal to Interference plus Noise Ratio (SINR), and reduced Bit Error Rate (BER). Computer simulations using underwater acoustic channels from Fuxian Lake and Wuyuan Bay demonstrate that the Z-OFDM system achieves a 6 dB gain compared to conventional OFDM systems at a BER of 10−3. These results demonstrate the effectiveness of Z-OFDM in overcoming the limitations of traditional FFT-based OFDM systems in underwater environments

The Relationship between Family Doctor Contract Services Policy and Perceived Participation in Primary Health Care among Chronic Disease Patients in China: The Mediating Role of the Patient Trust

Participation by patients with chronic diseases under primary health care requires more attention to achieve effective disease management and better health outcomes. In 2016, China proposed accelerating the establishment of a system of family doctors (FDs) and strengthening doctor-patient communication to better meet residents’ health service needs. This study aimed to describe perceived participation in primary health care among patients with chronic diseases in northeastern China and explore the impact of FD contract services and patient’s trust on patients’ perceived participation. A cross-sectional survey of 847 patients with chronic diseases in 16 primary healthcare institutions was conducted in Jilin Province, China. Among all participants, 453 patients reported signing up for FD contract services (62.93%). The perceived participation of patients with chronic diseases was at a low level (mean = 6.71 and SD = 3.35). After controlling for sociodemographic variables and health-related variables, FD contract services directly and indirectly influenced patients’ perceived participation. The patient’s trust was a mediator in the relationship between FD contract services and perceived participation. This study confirmed the valuation of family doctor contract services and provided a theoretical basis for the formulation of primary health service policies. Health organizations should continue to enhance the capacity of primary health services and attract more chronic disease patients to contract with FD teams, thereby enhancing doctor-patient trust and increasing patient’s participation in primary health care.</jats:p

Academic Performance and Peer or Parental Tobacco Use among Non-Smoking Adolescents: Influence of Smoking Interactions on Intention to Smoke

Background: Intention to smoke is an important predictor of future smoking among adolescents. The purpose of our study was to examine the interaction between academic performance and parents/peer tobacco use on adolescents’ intention to smoke. Methods: A multi-stage stratified sampling was used to select participants, involving 9394 students aged between 9–16 years in Changchun city, northeastern China. Multiple logistic regression analyses were conducted to examine the individual effect of academic performance and peer/parental smoking behavior. Stratified logistic regressions were conducted to examine the protective effect of academic performance based on peer or parental smoking. Interaction effects of academic performance × peer/parental smoking on adolescents’ intention to smoke were tested. Results: Of all the non-smoking students sampled, 11.9% intended to smoke within the next five years. The individual effect of academic performance and peer/parental smoking was significant. The protective effect of academic performance on the intention to smoke was significant regardless of whether peers smoked or not. However, the protective effect was not significant among adolescents with only maternal smoking and both parental smoking. The current study found the significant interaction effects of academic performance × peer smoking and the academic performance × both parents’ smoking. Students with poor academic performance were more likely to intend to smoke if their peers or both parents smoked. Conclusion: These preliminary results suggest that peer smoking or smoking by both parents reinforces the association between low academic performance and the intention to smoke among adolescents. Enhancing school engagement, focusing on social interaction among adolescents with low academic performance, and building smoke-free families may reduce adolescents’ intention to smoke.</jats:p

Academic Performance and Peer or Parental Tobacco Use among Non-Smoking Adolescents: Influence of Smoking Interactions on Intention to Smoke

Background: Intention to smoke is an important predictor of future smoking among adolescents. The purpose of our study was to examine the interaction between academic performance and parents/peer tobacco use on adolescents’ intention to smoke. Methods: A multi-stage stratified sampling was used to select participants, involving 9394 students aged between 9–16 years in Changchun city, northeastern China. Multiple logistic regression analyses were conducted to examine the individual effect of academic performance and peer/parental smoking behavior. Stratified logistic regressions were conducted to examine the protective effect of academic performance based on peer or parental smoking. Interaction effects of academic performance × peer/parental smoking on adolescents’ intention to smoke were tested. Results: Of all the non-smoking students sampled, 11.9% intended to smoke within the next five years. The individual effect of academic performance and peer/parental smoking was significant. The protective effect of academic performance on the intention to smoke was significant regardless of whether peers smoked or not. However, the protective effect was not significant among adolescents with only maternal smoking and both parental smoking. The current study found the significant interaction effects of academic performance × peer smoking and the academic performance × both parents’ smoking. Students with poor academic performance were more likely to intend to smoke if their peers or both parents smoked. Conclusion: These preliminary results suggest that peer smoking or smoking by both parents reinforces the association between low academic performance and the intention to smoke among adolescents. Enhancing school engagement, focusing on social interaction among adolescents with low academic performance, and building smoke-free families may reduce adolescents’ intention to smoke

In situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography.

Actin mediates insulin secretion in pancreatic β-cells through remodeling. Hampered by limited resolution, previous studies have offered an ambiguous depiction as depolymerization and repolymerization. We report the in situ structure of actin remodeling in INS-1E β-cells during glucose-stimulated insulin secretion at nanoscale resolution. After remodeling, the actin filament network at the cell periphery exhibits three marked differences: 12% of actin filaments reorient quasi-orthogonally to the ventral membrane; the filament network mainly remains as cell-stabilizing bundles but partially reconfigures into a less compact arrangement; actin filaments anchored to the ventral membrane reorganize from a netlike to a blooming architecture. Furthermore, the density of actin filaments and microtubules around insulin secretory granules decreases, while actin filaments and microtubules become more densely packed. The actin filament network after remodeling potentially precedes the transport and release of insulin secretory granules. These findings advance our understanding of actin remodeling and its role in glucose-stimulated insulin secretion

Auto-segmentation and time-dependent systematic analysis of mesoscale cellular structure in β-cells during insulin secretion

The mesoscale description of the subcellular organization informs about cellular mechanisms in disease state. However, applications of soft X-ray tomography (SXT), an important approach for characterizing organelle organization, are limited by labor-intensive manual segmentation. Here we report a pipeline for automated segmentation and systematic analysis of SXT tomograms. Our approach combines semantic and first-applied instance segmentation to produce separate organelle masks with high Dice and Recall indexes, followed by analysis of organelle localization based on the radial distribution function. We demonstrated this technique by investigating the organization of INS-1E pancreatic β-cell organization under different treatments at multiple time points. Consistent with a previous analysis of a similar dataset, our results revealed the impact of glucose stimulation on the localization and molecular density of insulin vesicles and mitochondria. This pipeline can be extended to SXT tomograms of any cell type to shed light on the subcellular rearrangements under different drug treatments.</jats:p