Platelet-membrane-camouflaged bismuth sulfide nanorods for synergistic radio-photothermal therapy against cancer.

Bismuth-containing nanoparticles (BNPs) are potential enhancers for tumor radiotherapy. Improving the bioavailability and developing synergistic therapeutic regimens benefit the drug transformation of BNPs. In the present study, we prepare a mesoporous silica-coated bismuth nanorod (BMSNR) camouflaged by a platelet membrane (PM). This biomimetic material is termed BMSNR@PM. The PM camouflage enhances the immune escape of the BMSNRs by lowering endocytosis by macrophages in the reticuloendothelial system. Additionally, the PM camouflage strengthens the material tumor-targeting capacity and leads to better radiotherapeutic efficacy compared with bare BMSNRs. Owing to the photothermal effect, BMSNR@PMs alters the cell cycle of 4T1 cancer cells post-treatment with 808 nm near-infrared irradiation (NIR). The proportions of S phase and G2/M phase cells decrease and increase, respectively, which explains the synergistic effect of NIR on BMSNR@PM-based radiotherapy. BMSNR@PMs efficiently eradicates cancer cells by the combined action of photothermal therapy (PTT) and radiotherapy in vivo and markedly improves the survival of 4T1-tumor-bearing mice. The synergistic therapeutic effect is superior to the outcomes of PTT and radiotherapy performed alone. Our study demonstrates a versatile bismuth-containing nanoplatform with tumor-targeting, immune escape, and radiosensitizing functionalities using an autologous cell membrane biomimetic concept that may promote the development of radiotherapy enhancers.

Impacts of leachates from single-use polyethylene plastic bags on the early development of clam Meretrix meretrix (Bivalvia: Veneridae).

Plastic debris in the oceans is a major and growing problem in global environmental pollution. There are increasing concerns that plastic debris is a source of contaminant, either added during manufacturing or adsorbed from the environment. However, there is little information about the acute toxicity of leachates from plastic debris on marine organisms. In this study, we conducted experiments to evaluate the toxicity of leachates from two single-use polyethylene plastic bags (PB1 and PB2) with the embryo and larvae of the commercial clam Meretrix meretrix. Results showed that fertilization of the embryos was not affected by plastic leachates, but the developments of D-veliger larvae, including survival, deformity, and shell height, were significantly affected by plastic leachates from both PB1 and PB2 compared to the controls of filtered seawater. We speculate that compounds leaching from plastic bags are responsible for the observed toxicity. Therefore, leaching toxicity from plastic debris should be considered when assessing the risks of plastic pollution in the oceans.

Optogenetic inhibition of ventral hippocampal neurons alleviates associative motor learning dysfunction in a rodent model of schizophrenia.

Schizophrenia (SZ) is a serious and incurable mental disorder characterized by clinical manifestations of positive and negative symptoms and cognitive dysfunction. High-frequency deep brain stimulation (DBS) of the ventral hippocampus (VHP) has been recently applied as a therapeutic approach for SZ in both experimental and clinical studies. However, little is known about the precise mechanism of VHP-DBS treatment for SZ and the role of hippocampal cell activation in the pathogenesis of SZ. With optogenetic technology in this study, we tried to inhibit neuronal activity in the VHP which has dense projections to the prefrontal cortex, before measuring long stumulus-induced delay eyeblink conditioning (long-dEBC) in a rodent model of SZ. Rats were administrated with phencyclidine (PCP, 3 mg/kg, 1/d, ip) for successive 7 days before optogenetic intervention. The current data show that PCP administration causes significant impairment in the acquisition and timing of long-dEBC; the inhibition of bilateral VHP neurons alleviates the decreased acquisition and impaired timing of longd-dEBC in PCP-administered rats. The results provide direct evidence at the cellular level that the inhibition of VHP neuronal cells may be a prominent effect of hippocampal DBS intervention, and increased activity in the hippocampal network play a pivotal role in SZ.

Predictive nature of prefrontal theta oscillation on the performance of trace conditioned eyeblink responses in guinea pigs.

Stimulus-evoked theta oscillations are observed in the medial prefrontal cortex (mPFC) when executing a variety of learning tasks. Here, we aimed to further determine whether spontaneous theta-band (5.0-10.0 Hz) oscillations in the mPFC predicted the subsequent behavioral performance in trace eyeblink conditioning (TEBC), in which the conditioned stimulus (CS) was separated from the unconditioned stimulus (US) by 500 ms trace interval. By recording local field potentials (LFP) signals in the guinea pigs performing the TEBC task, we found that, a higher mPFC relative theta ratio [theta/(delta+beta)] during the baseline (850-ms period prior to the onset of the CS) was predictive of higher magnitude and more adaptive timing rather than faster acquisition of trace conditioned eyeblink responses (CR). However, the prediction of baseline mPFC theta activity was time-limited to the well-learning stage. Additionally, the relative power of mPFC theta activity did not correlate with the CR performance if the trace interval between the CS and the US was shortened to 100 ms. These results suggest that the brain state in which the baseline mPFC theta activity is present or absent is detrimental for the subsequent performance of trace CRs especially when the asymptotic learning state is achieved.

Genetic distribution and association analysis of DRD2 gene polymorphisms with major depressive disorder in the Chinese Han population.

Dopamine D2 receptor is involved in reward-mediating mesocorticolimbic pathways. It plays an important role in major depressive disorder (MDD). Three gene polymorphisms Taq1A, C957T and -141C ins/del, were identified in the DRD2 gene among the Western population. These variants in the DRD2 gene might be associated with the susceptibility of MDD patients through affecting the bioeffects of endogenous dopamine neurotransmission. However, little is known about their occurrence in Chinese population and their association with the susceptibility of patients with major depressive disorder. In this study, a total of 338 unrelated adult Chinese Han population, including 224 healthy volunteers and 114 patients with major depressive disorder, were recruited. DRD2 polymorphisms (Taq1A and -141C ins/del) were detected using restriction fragment length polymorphism (RFLP) analysis and the C957T were detected by sequencing directly. As a result, three polymorphisms were identified in Chinese Han population and all were common SNP. However, we could detect no evidence of genetic association between 3 markers in DRD2 and major depressive disorder in the Chinese Han population. To conclude, this result suggests that Taq1A, C957T and -141C ins/del of DRD2 gene may not be associated with major depressive disorder, also may be the sample sizes too small to allow a meaningful test.

Classical eyeblink conditioning using electrical stimulation of caudal mPFC as conditioned stimulus is dependent on cerebellar interpositus nucleus in guinea pigs.

AIM: To determine whether electrical stimulation of caudal medial prefrontal cortex (mPFC) as conditioned stimulus (CS) paired with airpuff unconditioned stimulus (US) was sufficient for establishing eyeblink conditioning in guinea pigs, and whether it was dependent on cerebellar interpositus nucleus. METHODS: Thirty adult guinea pigs were divided into 3 conditioned groups, and trained on the delay eyeblink conditioning, short-trace eyeblink conditioning, and long-trace eyeblink conditioning paradigms, respectively, in which electrical stimulation of the right caudal mPFC was used as CS and paired with corneal airpuff US. A pseudo conditioned group of another 10 adult guinea pigs was given unpaired caudal mPFC electrical stimulation and the US. Muscimol (1 µg in 1 µL saline) and saline (1 µL) were infused into the cerebellar interpositus nucleus of the animals through the infusion cannula on d 11 and 12, respectively. RESULTS: The 3 eyeblink conditioning paradigms have been successfully established in guinea pigs. The animals acquired the delay and short-trace conditioned responses more rapidly than long-trace conditioned responses. Muscimol infusion into the cerebellar interpositus nucleus markedly impaired the expression of the 3 eyeblink conditioned responses. CONCLUSION: Electrical stimulation of caudal mPFC is effective CS for establishing eyeblink conditioning in guinea pigs, and it is dependent on the cerebellar interpositus nucleus.

Reevaluating the role of the medial prefrontal cortex in delay eyeblink conditioning.

It has been proposed that the medial prefrontal cortex (mPFC) is not necessary for delay eyeblink conditioning (DEC). Here, we investigated the involvement of the mPFC in DEC with a soft or loud tone as the conditioned stimulus (CS) by using electrolytic lesions or muscimol inactivation of guinea pig mPFC. Interestingly, when a soft tone was used as a CS, electrolytic lesions of the mPFC significantly retarded acquisition of the conditioned response (CR), and muscimol infusions into mPFC distinctly inhibited the acquisition and expression of CR, but had no significant effect on consolidation of well-learned CR. In contrast, both electrolytic lesions and muscimol inactivation of mPFC produced no significant deficits in the CR when a loud tone was used as the CS, or in the unconditioned response (UR) when a soft or loud tone was used as the CS. These results demonstrate that the mPFC is essential for the DEC with the soft tone CS but not for the DEC with the loud tone CS.

WITHDRAWN: Anterior cingulate cortex substitutes for the impaired retrieval role of prelimbic cortex in trace eyeblink conditioning.

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Disrupted topography of the acquired trace-conditioned eyeblink responses in guinea pigs after suppression of cerebellar cortical inhibition to the interpositus nucleus.

Trace conditioning of the eyeblink reflex, a form of associative motor learning in which presentations of the conditioned stimulus (CS) and the unconditioned stimulus (US) are separated in time by a silent trace interval, requires intact forebrain structures such as the hippocampus and medial prefrontal cortex. Recently, increased learning-related activities have also been observed in specific cerebellar cortical area such as the lobule of HVI during this conditioning task. To date, however, it remains controversial how the cerebellar cortex contributes to trace eyeblink conditioning. In the present study, we addressed this issue by reversibly suppressing the cerebellar cortical inhibition via microinjections of the GABA(A) receptor antagonist bicuculline methiodide (BICM) into the interpositus nucleus of guinea pigs. We showed that, in the well-trained guinea pigs, the BICM administrations failed to abolish the acquired trace-conditioned eyeblink responses (CRs). Although the acquired trace CRs were mostly retained, their peak latencies were shortened and their peak amplitudes diminished as evidenced by only half of the spared trace CRs preserving the topography of adaptive peak latencies or middle-/high-peak amplitudes. In the same animals, the acquired trace CRs were abolished by microinjections of the GABA(A) receptor agonist muscimol and were unaffected by microinjections of the artificial cerebrospinal fluid. Furthermore, we demonstrated that with concurrent BICM-induced suppression of the cerebellar cortical inhibition and presentations of the tone CSs in the guinea pigs receiving unpaired conditioning training, CR-like eyeblink responses were not generated. Altogether, these results support the hypothesis that GABAergic neurotransmission from cerebellar cortex to the interpositus nucleus may participate in regulating the expression of acquired trace CRs.