Neurotoxicological mechanisms of carbon quantum dots in a new animal model Dugesia japonica.

As luminescent nanomaterials, the carbon quantum dots (CQDs) research focused on emerging applications since their discovery. However, their toxicological effects on the natural environment are still unclear. The freshwater planarian Dugesia japonica is distributed extensively in aquatic ecosystems and can regenerate a new brain in 5 days after amputation. Therefore it can be used as a new model organism in the field of neuroregeneration toxicology. In our study, D. japonica was cut and incubated in medium treated with CQDs. The results showed that the injured planarian lost the neuronal ability of brain regeneration after treatment with CQDs. Its Hh signalling system was interfered with at Day 5, and all cultured pieces died on or before Day 10 due to head lysis. Our work reveals that CQDs might affect the nerve regeneration of freshwater planarians via the Hh signalling pathway. The results of this study improve our understanding of CQD neuronal development toxicology and can aid in the development of warning systems for aquatic ecosystem damage.

Clinical Characteristics of Elderly Patients with Diffuse Large B-cell Lymphoma and the Risk Factors Affecting Cardiotoxicity of Anthracycline.

Objective: The objective of this study was to describe the clinical characteristics of elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) and to identify the risk factors associated with anthracycline-related cardiotoxicity in this patient population. Methods: A retrospective analysis was conducted on a cohort of 170 elderly patients (≥65 years old) with DLBCL who were treated at our hospital between January 2015 and December 2020. Clinical characteristics and laboratory parameters were collected and analyzed. All patients were followed up until June 2021 to record survival, short-term efficacy, recurrence, and anthracycline-related cardiotoxicity in those who received chemotherapy. Results: Among the 170 elderly patients with DLBCL, the median progression-free survival (PFS) and median overall survival (OS) were 47 and 91 months, respectively. The 3-year PFS and OS rates were 54.1% and 70.1%, while the 5-year PFS and OS rates were 47.7% and 64.1%, respectively. The objective remission rate (ORR) was 78.83%, with a complete remission rate of 44.12% and a partial remission rate of 34.71%. Out of 143 patients who received anthracycline treatment, 46 patients experienced cardiotoxicity. Multivariate logistic regression analysis indicated that non-liposomal anthracycline use, no use of dextrexacin, and diabetes mellitus with complications were significant risk factors affecting cardiotoxicity (P < .05). Conclusions: The study showed that elderly patients with DLBCL had a high incidence of cardiotoxicity when treated with anthracycline. The results emphasize the importance of considering clinical characteristics and auxiliary examinations to prevent cardiotoxicity associated with anthracycline use.

Benefits of Dynamic Nomogram Models for Elderly Diffuse Large B-Cell Lymphoma Patients' Early Death Prediction and Clinical Application.

Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy, and about 60% of the patients are diagnosed in their elderly age (≥65 years old). However, little is known about the early mortality and risk factors related to elderly patients with DLBCL. Methodology. From 2000 to 2019, elderly patients diagnosed with DLBCL in the Surveillance, Epidemiology, and End Result (SEER) database were involved in this research and served as test cohort. Moreover, elderly DLBCL patients from Peking University Third Hospital were used for external validation cohort. Risk factors were identified by univariate and multivariate logistic regression analyses. Nomogram models were constructed based on significance risk factors to predict the overall and cancer-specific early death. Besides that, the predictive value of the models was validated by receiver operating characteristic (ROC) analysis. Calibration plots were used to evaluate the calibrating ability. Clinical benefits of nomogram were evaluated by decision curve analysis (DCA). Results: 15242 elderly DLBCL patients obtained from the SEER database and 152 patients from Peking University Third Hospital were enrolled in this research. In the SEER database, 36.6% (5584/15242) of the patients had early death and 30.7% (4680/15242) of them were cancer-specific early death. Marital status, Ann Arbor stage, surgical treatment, radiotherapy, and chemotherapy were significant risk factors for overall and cancer-specific early death of elderly DLBCL patients. Nomograms were constructed according to these risk factors. Then, ROC analysis showed that the AUC of OS was 0.764 (0.756~0.772), and CSS was 0.742 (0.733~0.751). In the validation group, the AUC of OS was 0.767 (0.689~0.846) and CSS was 0.742 (0.743~0.83). Conclusion: The calibration plots and DCA analysis revealed that the nomograms were good at early death prediction and clinical application. Predictive dynamic nomogram models for elderly DLBCL patients were established and validated, which might play an essential role in helping physicians enact better treatment strategies.

Emotional learning retroactively promotes memory integration through rapid neural reactivation and reorganization.

Neutral events preceding emotional experiences can be better remembered, likely by assigning them as significant to guide possible use in future. Yet, the neurobiological mechanisms of how emotional learning enhances memory for past mundane events remain unclear. By two behavioral studies and one functional magnetic resonance imaging study with an adapted sensory preconditioning paradigm, we show rapid neural reactivation and connectivity changes underlying emotion-charged retroactive memory enhancement. Behaviorally, emotional learning retroactively enhanced initial memory for neutral associations across the three studies. Neurally, emotional learning potentiated trial-specific reactivation of overlapping neural traces in the hippocampus and stimulus-relevant neocortex. It further induced rapid hippocampal-neocortical functional reorganization supporting such retroactive memory benefit, as characterized by enhanced hippocampal-neocortical coupling modulated by the amygdala during emotional learning, and a shift of hippocampal connectivity from stimulus-relevant neocortex to distributed transmodal prefrontal-parietal areas at post-learning rests. Together, emotional learning retroactively promotes memory integration for past neutral events through stimulating trial-specific reactivation of overlapping representations and reorganization of associated memories into an integrated network to foster its priority for future use.

Dual-Wavelength Laser Speckle Contrast Imaging (dwLSCI) Improves Chronic Measurement of Superficial Blood Flow in Hands.

Laser speckle contrast imaging (LSCI) has been widely used to determine blood flow and perfusion in biological tissues. The physical model of traditional LSCI ignores the effects of scattering property distribution in relation to speckle correlation time τc and blood flow v, which further results in biased estimation. In this study, we developed a dual-wavelength laser speckle contrast imaging (dwLSCI) method and a portable device for imaging the blood flow and tissue perfusion in human hands. Experimental data showed that dwLSCI could retrieve the vein vasculatures under the surface skin, and it further provided accurate measurements of vein blood flow signals, tissue perfusion signals, and fingertip perfusion signals, which assist with assessments of rehabilitation therapy for stroke patients. Fingertip perfusion signals demonstrated better performance in early assessments, while vein blood flow signals assisted the Fugl-Meyer Assessment Scale (FMA) and the Wolf Motor Function Test (WMFT) behavior assessments. As a general noninvasive imaging method, dwLSCI can be applied in clinical studies related to hand functions combined with behavior assessments.

Chronic wide-field imaging of brain hemodynamics in behaving animals.

Chronically monitoring cerebral activities in awake and freely moving status is very important in physiological and pathological studies. We present a novel standalone micro-imager for monitoring the cerebral blood flow (CBF) and total hemoglobin (HbT) activities in freely moving animals using the laser speckle contrast imaging (LSCI) and optical intrinsic signal (OIS) methods. A new cranial window method, using contact lens and wide field optics, is also proposed to achieve the chronic and wide-field imaging of rat's cerebral cortex. The hemodynamic activities of rats' cortex were measured for the first time without restriction of cables or fibers in awake and behaving animals. Chronic imaging showed the increase of CBF and HbT in motor cortex when the rats were climbing on the cage wall. Interestingly, the CBF activation of supplying vessel was smaller than that of parenchyma. Furthermore, after the climbing, CBF demonstrated fully return to the baseline while HbT showed a delayed recovery. The standalone micro-imager technology provides new possibilities of brain imaging in cognitive neuroscience studies.