Blocking Metallothionein-2 Expression by Copper-Doped Carbon Dots Induces Cellular Antioxidant System Collapse for Antitumor Therapy.

The insufficient antioxidant reserves in tumor cells play a critical role in reactive oxygen species (ROS)-mediated therapeutics. Metallothionein-2 (MT-2), an intracellular cysteine-rich protein renowned for its potent antioxidant properties, is intricately involved in tumor development and correlates with a poor prognosis. Consequently, MT-2 emerges as a promising target for tumor therapy. Herein, we present the development of copper-doped carbon dots (Cu-CDs) to target MT-2 to compromise the delicate antioxidant reserves in tumor cells. These Cu-CDs with high tumor accumulation and prolonged body retention can effectively suppress tumor growth by inducing oxidative stress. Transcriptome sequencing unveils a significant decrease in MT-2 expression within the in vivo tumor samples. Further mechanical investigations demonstrate that the antitumor effect of Cu-CDs is intricately linked to apolipoprotein E (ApoE)-mediated downregulation of MT-2 expression and the collapse of the antioxidant system. The robust antitumor efficacy of Cu-CDs provides invaluable insights into developing MT-2-targeted nanomedicine for cancer therapies.

Integrative analysis of the transcriptome and proteome reveals the molecular responses of tobacco to boron deficiency.

BACKGROUND: Boron (B) is an essential micronutrient for plants. Inappropriate B supply detrimentally affects the productivity of numerous crops. Understanding of the molecular responses of plants to different B supply levels would be of significance in crop improvement and cultivation practices to deal with the problem. RESULTS: We conducted a comprehensive analysis of the transcriptome and proteome of tobacco seedlings to investigate the expression changes of genes/proteins in response to different B supply levels, with a particular focus on B deficiency. The global gene and protein expression profiles revealed the potential mechanisms involved in the responses of tobacco to B deficiency, including up-regulation of the NIP5;1-BORs module, complex regulation of genes/proteins related to cell wall metabolism, and up-regulation of the antioxidant machinery. CONCLUSION: Our results demonstrated that B deficiency caused severe morphological and physiological disorders in tobacco seedlings, and revealed dynamic expression changes of tobacco genes/proteins in response to different B supply levels, especially to B deficiency, thus offering valuable insights into the molecular responses of tobacco to B deficiency.

Combined transcriptome and proteome analysis revealed the molecular regulation mechanisms of zinc homeostasis and antioxidant machinery in tobacco in response to different zinc supplies.

Zinc (Zn) is an essential micronutrient for plants. Adequate regulation of Zn uptake, transport and distribution, and adaptation to Zn-deficiency stress or Zn-excess toxicity are crucial for plant growth and development. However, little has been done to understand the molecular responses of plants toward different Zn supply levels. In the present study, we investigated the growth and physiological responses of tobacco seedlings grown under Zn-completely deficient, Zn-limiting, Zn-normal, and Zn-4-fold sufficient conditions, respectively, and demonstrated that Zn deficiency/limitation caused oxidative stress and impaired growth of tobacco plants. Combined transcriptome and proteome analysis revealed up-regulation of genes/proteins associated with Zn uptake and distribution, including ZIPs, NAS3s, and HMA1s, and up-regulation of genes/proteins involved in regulation of oxidative stress, including SODs, APX1s, GPX6, and GSTs in tobacco seedlings in response to Zn deficiency/limitation, suggesting that tobacco possessed mechanisms to regulate Zn homeostasis primarily through up-regulation of the ZIPs-NAS3s module, and to alleviate Zn deficiency/limitation-induced oxidative stress through activation of the antioxidant machinery. Our results provide novel insights into the adaptive mechanisms of tobacco in response to different Zn supplies, and would lay a theoretical foundation for development of varieties of tobacco or its relatives with high tolerance to Zn-deficiency.

Dezocine as a potent analgesic: overview of its pharmacological characterization.

Dezocine, a synthetic opioid, introduced in 1970s as an analgesic, was redeveloped for relieving moderate to severe pain by Yangtze River Pharmaceutical Group in China in 2009. To date, dezocine occupies 45% of China's opioid analgesic market. Along with dezocine being a dominated painkiller, a certain amount of research was conducted to elucidate dezocine's action. In this review we summarize the current knowledge on the receptor, preclinical and clinical pharmacology of dezocine. Briefly, preclinical data show that dezocine is effective under varying pain conditions, particularly chronic neuropathic pain and cancer pain, through activation of opioid receptors, and inhibition of norepinephrine reuptake. Clinical data establish the effectiveness of dezocine either as a primary analgesic for postoperative pain management or a supplement for balanced analgesia. The receptor profile of dezocine is different from known pure µ agonists, and allows it to be used in combination with other opioids for additivity in efficacy or lower incidence of adverse effects.

Association of cancer screening and residing in a coal-polluted East Asian region with overall survival of lung cancer patients: a retrospective cohort study.

Lung cancer is the leading cause of cancer death worldwide. The Xuanwei-Fuyuan (XF) region of Yunnan, China has a high incidence of lung cancer from coal-related pollution. Effort to raise public awareness screening for lung cancer has been ongoing. We retrospectively analyzed overall survival (OS) of lung cancer patients of a tertiary cancer center in Yunnan to investigate screening and regional residential status as predictive factors. Consecutive cases of newly diagnosed lung cancer were reviewed. The lung cancer cases diagnosed by screening were more likely to be early-staged and treated by surgery than those diagnosed not by screening. In patients diagnosed not by screening, XF residential status was a significant predictor of improved OS. Frailty model detected significant heterogeneity associated with region of residence in unscreened patients. Potential biases associated with screening were examined by Monte Carlo simulations and sensitivity analyses. Focused effort in cancer screening and increased public awareness of pollution-related lung cancer in XF might have led to early diagnosis and improved OS, and increased investment in health care resources in high risk areas may have produced additional unobserved factors that underlay the association of XF residential status with improved OS in patients diagnosed not by screening.