Case Report: A neurolinguistic and neuroimaging study on a Chinese follow-up case with logopenic-variant of primary progressive aphasia.

Primary progressive aphasia (PPA), typically resulting from a neurodegenerative disease, is characterized by a progressive loss of specific language functions while other cognitive domains are relatively unaffected. The logopenic variant, characterized by impairments of word retrieval and sentence repetition along with preserved semantic, syntactic, and motor speech abilities, is the most recently described and remains less understood than other variants due to a comparatively small number of case studies and a lack of investigations with a thorough specification. In this article, we report a 2-year follow-up case study of a 74-year-old Chinese female patient with a logopenic variant of primary progressive aphasia, including its neurolinguistic study, magnetic resonance imaging (MRI), and 11C-Pittsburgh compound B-Positron emission tomography imaging analyses, as well as gene sequencing. This case confirms that, in addition to word-finding and sentence repetition difficulties, the logopenic variant may also present with mild auditory comprehension and naming deficits attributed to impaired access to lexical representations. The observation of clinical treatment suggests the efficacy of memantine hydrochloride tablet and rivastigmine transdermal patch in slowing down the cognitive deterioration of this patient. The description and exploration of this case may shed new insights into a better understanding of the Chinese logopenic variant of primary progressive aphasia.

Broaden sources and reduce expenditure: Tumor-specific transformable oxidative stress nanoamplifier enabling economized photodynamic therapy for reinforced oxidation therapy.

Cancer cells immersed in inherent oxidative stress are more vulnerable to exogenous oxidative damages than normal cells. Reactive oxygen species (ROS)-mediated oxidation therapy preferentially aggravating tumor oxidative stress to disrupt redox homeostasis, has emerged as an effective and specific anticancer treatment. Herein, following an ingenious strategy of "broaden sources and reduce expenditure", we designed a versatile tumor-specific oxidative stress nanoamplifier enabling economized photodynamic therapy (PDT), to achieve synergistic oxidative stress explosion for superior oxidation therapy. Methods: Cinnamaldehyde (CA) as a therapeutic ROS generator was first conjugated to hyaluronic acid (HA) through acid-labile hydrazone bond to synthesize tailored amphiphilic HA@CA conjugates, which could surprisingly self-assemble into uniform nanofibers in aqueous media. Photosensitizer protoporphyrin (PpIX) was efficiently encapsulated into HA@CA nanofibers and transformed HA@CA nanofibers to final spherical HA@CAP. Results: With beneficial pH-responsiveness and morphology transformation, improved bioavailability and selective tumor accumulation, HA@CAP combining ROS-based dual chemo/photodynamic treatment modalities could induce cytotoxic ROS generation in a two-pronged approach to amplify tumor oxidative stress, termed "broaden sources". Moreover, utilizing CA-induced H2O2 production and cascaded Fenton reaction in mitochondria to consume intracellular overloaded Fe(II), HA@CAP could skillfully block endogenic heme biosynthesis pathway on site to restrain undesired elimination of PpIX for economized PDT, termed "reduce expenditure". Both in vitro and in vivo results demonstrated the superior antitumor performance of HA@CAP. Conclusion: This study offered an inspiring strategy of "broaden sources and reduce expenditure" to specifically boost tumor oxidative stress for reinforced oxidation therapy.

The Role of Context in Processing Chinese Three-Character Verb-Object Metaphors: An Event-Related Potential Study.

Whether and how context plays a role in metaphor processing remains a controversial issue. One major theory on metaphor comprehension, the graded salience hypothesis (GSH) model, emphasizes salience as the key factor determining the precedence of semantic access. Using event-related potential technique, the present study examined Chinese metaphors to investigate whether the salient meaning is always processed first regardless of context. The experiment employed a Prime-Target-Probe paradigm. Three-character Chinese verb-object metaphors were used as the Target proceeded by one of the three contexts (the Prime): (1) metaphorical context priming the Target's metaphorical meaning, (2) literal context priming the Target's literal meaning, and (3) irrelevant context as the control condition. The Target was then followed by the Probe, which was always related to the Target (except in the filler condition). Forty participants were asked to judge whether the Target and the following Probe were semantically related. The N400 elicited by the Target showed no contextual effect. The N400 amplitude elicited by the Probe was smaller in the metaphorical priming condition compared with the literal priming condition, while the N400 in the irrelevant control condition was between the other two conditions, demonstrating a clear context effect. In addition, an unexpected P240 component also showed the similar graded pattern. Our results mostly support the GSH model, indicating that the salient meaning invariantly gets activated first before the activation of the nonsalient meaning at the lexical access stage. However, context does play a role in a parallel way either facilitating or suppressing this interpretation in the latter meaning integration stage.

Near infrared light triggered reactive oxygen species responsive nanoparticles for chemo-photodynamic combined therapy.

Currently, the strategy of combining photodynamic therapy (PDT) and chemotherapy for enhancing cancer therapeutic efficiency has aroused extensive interest. Nonetheless, weaknesses such as low local concentration, uncontrollable release of the drug, a non-suitable treatment light source, and a low response to the tumor site of PDT lead to the combined treatment effect not being ideal. Herein, we proposed simple and intelligent ROS-responsive zinc phthalocyanine sensitized TiO2 nanoparticles which conjugated with chlorambucil (CBL) (mTiO2-BCBL@ZnPC NPs) in an attempt to solve these issues. Not only were the nanoparticles triggered in near infrared radiation (NIR) for PDT with various reactive oxygen species (ROS) being generated, but the nanoparticles also realized the controllable release of CBL by H2O2, a major kind of ROS, through cleavage of the phenylboronic ester between CBL and the nanoparticle. Impressively, the controllable release of CBL under NIR irradiation showed an on-off characteristic and time dependency. In addition, the well-defined mTiO2-BCBL@ZnPC NPs with a 30 nm average diameter showed good stability and biocompatibility. The in vitro cytotoxicity studies demonstrated that the mTiO2-BCBL@ZnPC NPs were more cytotoxic under NIR irradiation than the mTiO2@ZnPC NPs and CBL, while the mTiO2-BCBL@ZnPC NPs were less cytotoxic under dark conditions. The above results implied that photo-controlled drug release is a promising choice for cancer therapy due to its high selectivity, good safety and low side-effects, and would be expected to be used in chemo-photodynamic combined therapy for improving the therapeutic efficiency.

Systemic toxicity induced by aggregated layered double hydroxide nanoparticles.

Layered double hydroxide (LDH) nanoparticles are emerging as one of the promising nanomaterials for biomedical applications, but their systemic toxicity in vivo has received little attention. In the present study, the effects of inorganic nanoparticle aggregation on their systemic toxicity were examined. Remarkably, aggregation was observed after the mixing of naked LDH nanoparticles with saline or erythrocytes. Significant accumulation of the naked LDH nanoparticles in the lungs of mice was detected 1 h after intravenous administration, and the survival rate of mice was 0% after 6 repeated injections. Furthermore, flocculent precipitates in the alveoli and congestion in the lung interstitium were observed in the dead mice. However, lipid membrane-coated LDH nanoparticles would not form aggregates and could be injected intravenously >6 times without causing death. These findings suggested that repeated injections of LDH were lethal even at low dose (30 mg/kg), and lipid membrane coating can be considered as an approach for reducing this risk.