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Background: Parkinson’s disease (PD) is one of the most common neurological disorders that can severely affect the ability to perform daily activities. The clinical presentation of PD includes motor and nonmotor symptoms. The motor symptoms generally involve movement conditions like tremors, rigidity, slowness, and impaired balance. In contrast, the nonmotor symptoms are often not apparent but can affect various organ systems, such as the urinary and gastrointestinal systems, and mental health. Gene mutations and toxic environmental factors have contributed significantly to PD; nevertheless, its cause and underlying mechanism remain unknown. Currently, treatments such as dopamine agonists, RNA molecules, and antioxidants can, to some extent, alleviate the motor symptoms triggered by PD. However, these medicines cannot effectively halt ongoing dopaminergic damage, mainly because the blood-brain barrier (BBB) lowers the efficiency of drug delivery. Recently, extracellular vesicles (EVs), a novel drug delivery platform, have been widely used in various neurological diseases, including stroke and brain tumors, because of their excellent biocompatibility, their ability to penetrate the BBB without toxicity, and their target specificity. EVs thus provide a promising therapeutic for treating PD. Objective: This review focuses on novel therapies based on EVs in practice. Herein, we briefly introduce the biogenesis, composition, isolation, and characterization of EVs, and we discuss strategies for loading therapeutic agents onto EVs and recent applications for PD treatment. Moreover, we discuss perspectives on the direction of preclinical and clinical studies regarding novel and effective therapies. Methods: A literature search regarding PD treatment based on extracellular vesicles was performed in PubMed (updated in June 2020). Treatment, therapy, drug delivery, extracellular vesicles, and their combinations were the search queries. Both systematic reviews and original publications were included. Searched results were selected and compared based on relevance. Articles published in the last five years were given top priority. Conclusion: PD is a heterogeneous disease that can be treated by using pharmacologic approaches (e.g. dopamine agonists and levodopa) and nonpharmacologic approaches (e.g. music), based on symptoms and progression level in patients. Even though current treatments have demonstrated effectiveness, clinical challenges remain because the BBB reduces the medication received and lowers the efficacy of drug delivery, which impairs the treatment’s effect. Therefore, EVs, as an emerging delivery platform, are highly promising for PD treatment since they can readily cross the BBB with high therapeutic efficiency through the loading or functionalization process. However, defining a safe source of EVs, reliably purifying and isolating EVs with high yield, and improving the efficacy of therapeutic loading in EVs remain challenging in this field. Therefore, future investigations should focus on generating large-scale exosomal carriers and designing new effective drugs encapsulated in EVs for better efficacy.

Purpose: To investigate the effect of miR-665 in neuropathic pain and the possible molecular mechanism involved.Methods: A neuropathic pain model was established using chronic constriction injury (CCI) methods in Sprague Dawley (SD) rats. Mechanical and thermal hyperalgesia were measured using paw withdrawal threshold (PWT) and paw withdrawal latency (PWL), respectively. The inflammation response was determined by assessing the production of inflammation factors. The target relationship of miR-665 and suppressor of cytokine signaling 1 (SOCS1) was verified by luciferase assay.Results: In the CCI rat model, PWT and PWL decreased following treatment with miR-665 (p < 0.01). MiR-665 was elevated in the spinal cord and microglia of CCI rats at different time points (p < 0.01). Down-regulation of miR-665 increased PWT and PWL and inhibited the production of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in CCI rats (p < 0.01). Luciferase assay results indicate that SOCS1 was the target of miR-665 (p < 0.01). SOCS1 decreased in CCI rats (p < 0.01) after treatment with miR-665. MiR-665 negatively regulated the expression of SOCS1 (p < 0.01). Down-regulation of SOCS1 reversed the alleviating effect of decreased miR-665 on pain sensitivity and inflammationresponse (p < 0.01).Conclusion: Down-regulation of miR-665 alleviates neuropathic pain by targeting SOCS1, and hence making miR-665 a promising therapeutic target for neuropathic pain. Keywords: MiR-665, SOCS1, Neuropathic pain, CCI, Spinal cord

It is a rapidly developed subject in expanding the fundamental properties and application of two‐dimensional (2D) materials. The weak van der Waals interaction in 2D materials inspired researchers to explore 2D heterostructures (2DHs) based broadband photodetectors in the far‐infrared (IR) and middle‐IR regions with high response and high detectivity. This review focuses on the strategy and motivation of designing 2DHs based high‐performance IR photodetectors, which provides a wide view of this field and new expectation for advanced photodetectors. First, the photocarriers' generation mechanism and frequently employed device structures are presented. Then, the 2DHs are divided into semimetal/semiconductor 2DHs, semiconductor/semiconductor 2DHs, and multidimensional semi‐2DHs; the advantages, motivation, mechanism, recent progress, and outlook are discussed. Finally, the challenges for next‐generation photodetectors are described for this rapidly developing field.

Biomarker discovery and its clinical use have attracted considerable attention since early cancer diagnosis can significantly decrease mortality. Cancer biomarkers include a wide range of biomolecules, such as nucleic acids, proteins, metabolites, sugars, and cytogenetic substances present in human biofluids. Except for free-circulating biomarkers, tumor-extracellular vesicles (tEVs) and circulating tumor cells (CTCs) can serve as biomarkers for the diagnosis and prognosis of various cancers. Considering the potential of tumor biomarkers in clinical settings, several bioinspired detection systems based on nanotechnologies are in the spotlight for detection. However, tremendous challenges remain in detection because of massive contamination, unstable signal-to-noise ratios due to heterogeneity, nonspecific bindings, or a lack of efficient amplification. To date, many approaches are under development to improve the sensitivity and specificity of tumor biomarker isolation and detection. Particularly, the exploration of natural materials in biological frames has encouraged researchers to develop new bioinspired and biomimetic nanostructures, which can mimic the natural processes to facilitate biomarker capture and detection in clinical settings. These platforms have substantial influence in biomedical applications, owing to their capture ability, significant contrast increase, high sensitivity, and specificity. In this review, we first describe the potential of tumor biomarkers in a liquid biopsy and then provide an overview of the progress of biomimetic nanostructure platforms to isolate and detect tumor biomarkers, including in vitro and in vivo studies. Capture efficiency, scale, amplification, sensitivity, and specificity are the criteria that will be further discussed for evaluating the capability of platforms. Bioinspired and biomimetic systems appear to have a bright future to settle obstacles encountered in tumor biomarker detection, thus enhancing effective cancer diagnosis.

Cerebral infarction is a common cerebrovascular disease in clinical medicine. Cerebral infarction in the anterior circulation accounts for about 90% of cerebral infarction. Its treatment and rehabilitation has always been a research hotspot in the medical field. Functional retraining can enhance the afferent impulses received by receptors, make the plasticity development of cerebral cortex function, and improve the loss of function. Based on the patient’s individual condition, exercise therapy carries out the corresponding comprehensive functional training plan, which also includes the training of patients’ daily living ability, turning over, bridge exercise, trunk rotation, etc., in order to improve the motor function of patients. The other is psychotherapy, which can cause emotional fluctuations, depression, anxiety, and other negative emotions due to the occurrence of diseases. In the rehabilitation treatment, relevant personnel can conduct psychological counseling for patients through timely and effective communication, so as to better establish patients’ confidence in rehabilitation and improve the effect of rehabilitation treatment. The third is acupuncture treatment. Acupuncture is a traditional rehabilitation treatment in China. The rehabilitation effect of stroke has been proved by a large number of clinical practice. Acupuncture at Hegu, Quchi, Zusanli, and Taichong points can dredge channels and improve blood circulation. This paper mainly studies and analyzes the effect of behavior rehabilitation of hemiplegic patients with cerebral anterior circulation infarction treated by cranial magnetic stimulation. The rehabilitation treatment status of hemiplegic patients with anterior circulation cerebral infarction in a hospital was selected, and 100 cases were studied. Among them, 50 cases were treated with conventional rehabilitation therapy, and the other 50 cases were treated with cranial magnetic stimulation. The motor function, activities of daily living, and language expression ability of the two groups were compared for statistical analysis. After transcranial magnetic stimulation treatment, the abilities of the study group were better than those of the control group, P < 0.05 , with statistical significance. Based on the reliable experimental data, we can draw a conclusion that the treatment of cranial magnetic stimulation has a significant effect on the rehabilitation of hemiplegic patients with cerebral anterior circulation infarction, which is higher than the conventional treatment and rehabilitation methods, and can be popularized in clinical application.

Power consumption is one of the most challenging bottlenecks for complementary metal-oxide-semiconductor integration. Negative-capacitance field-effect transistors (NC-FETs) offer a promising platform to break the thermionic limit defined by the Boltzmann tyranny and architect energy-efficient devices. However, it is a great challenge to achieving ultralow-subthreshold-swing (SS) (10 mV dec-1 ) and small-hysteresis NC-FETs simultaneously at room temperature, which has only been reported using the hafnium zirconium oxide system. Here, based on a ferroelectric LiNbO3 thin film with great spontaneous polarization, an ultralow-SS NC-FET with small hysteresis is designed. The LiNbO3 NC-FET platform exhibits a record-low SS of 4.97 mV dec-1 with great repeatability due to the superior capacitance matching characteristic as evidenced by the negative differential resistance phenomenon. By modulating the structure and operating parameters (such as channel length (Lch ), drain-sourse bias (Vds ), and gate bias (Vg )) of devices, an optimized SS from ≈40 to ≈10 mV dec-1 and hysteresis from ≈900 to ≈60 mV are achieved simultaneously. The results provide a new potential method for future highly integrated electronic and optical integrated energy-efficient devices.

The ultrabroadband spectrum detection from ultraviolet (UV) to long-wavelength infrared (LWIR) is promising for diversified optoelectronic applications of imaging, sensing, and communication. However, the current LWIR-detecting devices suffer from low photoresponsivity, high cost, and cryogenic environment. Herein, a high-performance ultrabroadband photodetector is demonstrated with detecting range from UV to LWIR based on air-stable nonlayered ultrathin Fe3 O4 nanosheets synthesized via a space-confined chemical vapor deposition (CVD) method. Ultrahigh photoresponsivity (R) of 561.2 A W-1 , external quantum efficiency (EQE) of 6.6 × 103 %, and detectivity (D*) of 7.42 × 108 Jones are achieved at the wavelength of 10.6 µm. The multimechanism synergistic effect of photoconductive effect and bolometric effect demonstrates the high sensitivity for light with any light intensities. The outstanding device performance and complementary mixing photoresponse mechanisms open up new potential applications of nonlayered 2D materials for future infrared optoelectronic devices.

MicroRNAs (miRs) have been proposed to be involved in the pathological processes of cerebral ischemia/reperfusion (CIR) injury. The present study aimed to investigate the potential role and molecular mechanisms of miR‑217 in the regulation of neuronal survival in CIR injury. To perform the investigation, an in vitro cellular model of CIR injury was established by treating neurons with oxygen‑glucose deprivation and reoxygenation (OGD/R). miR‑217 levels in neurons were detected using reverse transcription‑quantitative PCR. The association between miR‑217 and sirtuin 1 (SIRT1) was identified using TargetScan and validated in a dual‑luciferase reporter assay. Cell viability and apoptosis were measured using a Cell Counting Kit‑8 assay and flow cytometry, respectively. The release of lactate dehydrogenase, and the production of proinflammatory factors and oxidative stress biomarkers were analyzed by ELISAs and using specific assay kits. It was revealed that miR‑217 was significantly upregulated in OGD/R‑treated neurons. SIRT1 was a direct target of miR‑217, and was downregulated in neurons following OGD/R treatment. Downregulation of miR‑217 significantly ameliorated OGD/R‑induced neuronal injury, inflammatory responses and oxidative stress. The effects of miR‑217 inhibitor on OGD/R treated neurons were attenuated by SIRT1 knockdown. Additionally, western blotting revealed that the SIRT1/AMP‑activated protein kinase‑α/NF‑κB pathway was partially involved in the regulation of OGD/R‑induced neuronal injury by miR‑217. In conclusion, the data of the present study indicated that the downregulation of miR‑217 protected neurons against OGD/R‑induced injury by targeting SIRT1.

The disruption of blood–brain barrier (BBB) is a critical event in the formation of brain edema during early phases of ischemic brain injury. Poly(ADP-ribose) polymerase (PARP) activation, which contributes to BBB damage, has been reported in ischemia–reperfusion and traumatic brain injury. Here, we investigated the effect of 3-aminobenzamide (3-AB), a PARP-1 inhibitor, on the ultrastructure of BBB. Male Sprague Dawley rats were suffered from 90 minutes of middle cerebral artery occlusion, followed by 4.5 hours or 22.5 hours of reperfusion (R). The vehicle or 3-AB (10 mg/kg) was administered intraperitoneally (ip) 60 minutes after lacking of blood. Tissue Evans Blue (EB) levels, ultrastructures of astrocytes and microvessels, and areas of perivascular edema were examined in penumbra and core, at I 1.5 hours /R 4.5 hours and I 1.5 hours /R 22.5 hours, respectively. The severity of ultrastructural changes was graded with a scoring system in each group. We showed that 3-AB treatment significantly decreased tissue EB levels and ultrastructural scores, attenuated damages in astrocytes and microvessels, and reduced areas of perivascular edema. In conclusion, PARP inhibition may provide a novel therapeutic approach to ischemic brain injury.