The effects of the predictability of acclimatory temperature on the growth and thermal tolerance of juvenile Spinibarbus sinensis.

Heated effluent injection, cold hypolimnetic water inputs from dams, and extreme weather events can lead to unpredictable temperature fluctuations in natural waters, impacting fish performance and fitness. We hypothesized that fish exposed to such unpredictable fluctuations would exhibit weaker growth and enhanced thermal tolerance compared to predictable conditions. Qingbo (Spinibarbus sinensis) was selected as the experimental subject in this study. The qingbo were divided into a constant temperature group (C, 22 ± 0.5 °C), a predictable temperature fluctuation group (PF, 22 ± 4 °C, first warming, then cooling within a day) and an unpredictable temperature fluctuation group (UF, 22 ± 4 °C, the order of warming or cooling is random). After 40 days of temperature acclimation, the growth, metabolic rate, spontaneous activity, thermal tolerance, plasma cortisol concentration and liver hsp70 level of the fish were measured. Unexpectedly, neither the PF nor the UF group showed decreased growth compared to the C group. This could be attributed to the fact that temperature variation did not lead to a substantial increase in basic energy expenditure. Furthermore, feeding rates increased due to temperature fluctuations, although the difference was not significant. Both the PF and UF groups exhibited increased upper thermal tolerance, but only the UF group exhibited improved lower thermal tolerance and higher liver hsp70 levels compared to the C group. The qingbo that experienced unpredictable temperature fluctuations had the best thermal tolerance among the 3 groups, which might have occurred because they had the highest level of hsp70 expression. This may safeguard fish against the potential lethal consequences of extreme temperatures in the future. These findings suggested that qingbo exhibited excellent adaptability to both predictable and unpredictable temperature fluctuations, which may be associated with frequent temperature fluctuations in its natural habitat.

Diverse and precision therapies open new horizons for patients with advanced pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a common cause of cancer-related death, and most patients are with advanced disease when diagnosed. At present, despite a variety of treatments have been developed for PDAC, few effective treatment options are available; on the other hand, PDAC shows significant resistance to chemoradiotherapy, targeted therapy, and immunotherapy due to its heterogeneous genetic profile, molecular signaling pathways, and complex tumor immune microenvironment. Nevertheless, over the past decades, there have been many new advances in the key theory and understanding of the intrinsic mechanisms and complexity of molecular biology and molecular immunology in pancreatic cancer, based on which more and more diverse new means and reasonable combination strategies for PDAC treatment have been developed and preliminary breakthroughs have been made. With the continuous exploration, from surgical local treatment to comprehensive medical management, the research-diagnosis-management system of pancreatic cancer is improving. This review focused on the variety of treatments for advanced PDAC, including traditional chemotherapy, targeted therapy, immunotherapy, microenvironment matrix regulation as well as the treatment targeting epigenetics, metabolism and cancer stem cells. We pointed out the current research bottlenecks and future exploration directions.

The promising role of antibody drug conjugate in cancer therapy: Combining targeting ability with cytotoxicity effectively.

INTRODUCTION: Traditional cancer therapy has many disadvantages such as low selectivity and high toxicity of chemotherapy, as well as insufficient efficacy of targeted therapy. To enhance the cytotoxic effect and targeting ability, while reducing the toxicity of antitumor drugs, an antibody drug conjugate (ADC) was developed to deliver small molecular cytotoxic payloads directly to tumor cells by binding to specific antibodies via linkers. METHOD: By reviewing published literature and the current progress of ADCs, we aimed to summarize the basic characteristics, clinical progress, and challenges of ADCs to provide a reference for clinical practice and further research. RESULTS: ADC is a conjugate composed of three fundamental components, including monoclonal antibodies, cytotoxic payloads, and stable linkers. The mechanisms of ADC including the classical internalization pathway, antitumor activity of antibodies, bystander effect, and non-internalizing mechanism. With the development of new drugs and advances in technology, various ADCs have achieved clinical efficacy. To date, nine ADCs have received US Food and Drug Administration (FDA) approval in the field of hematologic tumors and solid tumors, which have become routine clinical treatments. CONCLUSION: ADC has changed traditional treatment patterns for cancer patients, which enable the same treatment for pancreatic cancer patients and promote individualized precision treatment. Further exploration of indications could focus on early-stage cancer patients and combined therapy settings. Besides, the mechanisms of drug resistance, manufacturing techniques, optimized treatment regimens, and appropriate patient selection remain the major topics.

Distribution of polychlorinated biphenyls in soil around three typical industrial sites in Beijing, China.

We investigated three locations in Beijing, China, containing different industrial plants that may cause pollution of polychlorinated biphenyls (PCBs). The highest soil concentration of 1,000 pg g(-1) (dry wt) was found in the chemical plant. The concentrations of ΣPCBs tended to decrease with distance from each of the investigated sites. The principal component analysis demonstrated that there were not substantial differences in PCB homologue patterns among these industrial sites. Tri-CBs and tetra-CBs were the dominant congeners. Based on the data obtained in this investigation, further study of the emission of PCBs from these industrial sites in Beijing is warranted.