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1.
Exp Neurol ; 339: 113612, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33453213

RESUMO

This paper is an interdisciplinary narrative review of efficacious non-invasive therapies that are increasingly used to restore function in people with chronic spinal cord injuries (SCI). First presented are the secondary injury cascade set in motion by the primary lesion and highlights in therapeutic development for mitigating the acute pathophysiologic process. Then summarized are current pharmacological strategies for modulation of noradrenergic, serotonergic, and dopaminergic neurotransmission to enhance recovery in bench and clinical studies of subacute and chronic SCI. Last examined is how neuromechanical devices (i.e., electrical stimulation, robotic assistance, brain-computer interface, and augmented sensory feedback) could be comprehensively engineered to engage efferent and afferent motosensory pathways to induce neuroplasticity-based neural pattern generation. Emerging evidence shows that computational models of the human neuromusculoskeletal system (i.e., human digital twins) can serve as functionalized anchors to integrate different neuromechanical and pharmacological interventions into a single multimodal prothesis. The system, if appropriately built, may cybernetically optimize treatment outcomes via coordination of heterogeneous biosensory, system output, and control signals. Overall, these rehabilitation protocols involved neuromodulation to evoke beneficial adaptive changes within spared supraspinal, intracord, and peripheral neuromuscular circuits to elicit neurological improvement. Therefore, qualitatively advancing the theoretical understanding of spinal cord neurobiology and neuromechanics is pivotal to designing new ways to reinstate locomotion after SCI. Future research efforts should concentrate on personalizing combination therapies consisting of pharmacological adjuncts, targeted neurobiological and neuromuscular repairs, and brain-computer interfaces, which follow multimodal neuromechanical principles.

2.
J Am Chem Soc ; 142(47): 20124-20133, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33170682

RESUMO

We designed and synthesized a series of fused-ring electron acceptors (FREAs) based on naphthalene-fused octacyclic cores end-capped by 3-(1,1-dicyanomethylene)-5,6-difluoro-1- indanone (NOICs) using a bottom-up approach. The NOIC series shares the same end groups and side chains, as well as similar fused-ring cores. The butterfly effects, arising from different methoxy positions in the starting materials, impact the design of the final FREAs, as well as their molecular packing, optical and electronic properties, charge transport, film morphology, and performance of organic solar cells. The binary-blend devices based on this NOIC series show power conversion efficiencies varying from 7.15% to 14.1%, due to the different intrinsic properties of the NOIC series, morphologies of blend films, and voltage losses of devices.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33058442

RESUMO

Regulating molecular structure to optimize the active layer morphology is of considerable significance for improving the power conversion efficiencies (PCEs) in organic solar cells (OSCs). Herein, we demonstrated a simple ternary copolymerization approach to develop a terpolymer donor PM6-Tz20 by incorporating the 5,5'-dithienyl-2,2'-bithiazole (DTBTz, 20 mol%) unit into the backbone of PM6 (PM6-Tz00). This method can effectively tailor the molecular orientation and aggregation of the polymer, and then optimize the active layer morphology and the corresponding physical processes of devices, ultimately boosting FF and then PCE. Hence, the PM6-Tz20: Y6-based OSCs achieved a PCE of up to 17.1% with a significantly enhanced FF of 0.77. Using Ag (220 nm) instead of Al (100 nm) as cathode, the champion PCE was further improved to 17.6%. This work provides a simple and effective molecular design strategy to optimize the active layer morphology of OSCs for improving photovoltaic performance.

4.
Nat Commun ; 11(1): 4612, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929082

RESUMO

Developing a high-performance donor polymer is critical for achieving efficient non-fullerene organic solar cells (OSCs). Currently, most high-efficiency OSCs are based on a donor polymer named PM6, unfortunately, whose performance is highly sensitive to its molecular weight and thus has significant batch-to-batch variations. Here we report a donor polymer (named PM1) based on a random ternary polymerization strategy that enables highly efficient non-fullerene OSCs with efficiencies reaching 17.6%. Importantly, the PM1 polymer exhibits excellent batch-to-batch reproducibility. By including 20% of a weak electron-withdrawing thiophene-thiazolothiazole (TTz) into the PM6 polymer backbone, the resulting polymer (PM1) can maintain the positive effects (such as downshifted energy level and reduced miscibility) while minimize the negative ones (including reduced temperature-dependent aggregation property). With higher performance and greater synthesis reproducibility, the PM1 polymer has the promise to become the work-horse material for the non-fullerene OSC community.

5.
J Am Chem Soc ; 142(34): 14725-14732, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32804498

RESUMO

Traditional pharmacotherapy suffers from multiple drawbacks that hamper patient treatment, such as the buildup of antibiotic resistances or low drug selectivity and toxicity during systemic application. To overcome these challenges, drug activity can be controlled by employing delivery, targeting, or release solutions that mostly rely on the response to external physicochemical stimuli. Due to various technical limitations, mechanical force as a stimulus in the context of polymer mechanochemistry has so far not been used for this purpose, yet it has been proven to be a convenient and robust method to site-selectively rearrange or cleave bonds with submolecular precision in the realm of materials chemistry. Here, we present an unprecedented mechanochemically responsive system capable of successively releasing small furan-containing molecules, including the furylated fluorophore dansyl and the drugs furosemide as well as furylated doxorubicin, by ultrasound-induced selective scission of disulfide-centered polymers in solution. We show that mechanochemically generated thiol-terminated polymers undergo a Michael-type addition to Diels-Alder (DA) adducts of furylated drugs and acetylenedicarboxylate derivatives, initiating the downstream release of the small molecule drug by a retro DA reaction. We believe that this method can serve as a blueprint for the activation of many other small molecules.

6.
Clin Neurol Neurosurg ; 184: 105416, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31319234

RESUMO

OBJECTIVES: A prospective, blinded, randomized trial was performed to evaluate the incidence rates of external ventricular drainage (EVD)-related infection (ERI) after tunneled EVD (T-EVD) and standard EVD (S-EVD). PATIENTS AND METHODS: From February 2018 to February 2019, all adult patients admitted to the Union Hospital Neurosurgery Center for EVD placement were eligible for inclusion. After the application of strict exclusion criteria, all enrolled patients were randomly divided into two groups. The patients in Group A received S-EVD, and the remaining patients in Group B received T-EVD. A linear incision was made for T-EVD. The distal end of the catheter was inserted approximately 5 cm until cerebrospinal fluid was readily obtained, and then the catheter was tunneled approximately 4-5 cm from the insertion point. Finally, an external CSF drainage system was connected to the catheter. For the S-EVD patients, we secured the catheter at the original incision site after insertion, and an external CSF drainage system was also connected to the catheter. The rates of ERI were compared between the two patient groups. The odds ratios and χ² test were used to analyze the results. RESULTS: One hundred twenty patients were randomly divided into two groups and underwent EVD placement. Among them, 60 patients in Group A received S-EVD, and 60 patients in Group B received T-EVD. Finally, 51 patients in Group A and 50 patients in Group B met all of the study inclusion/exclusion criteria and were thus eligible for inclusion in the evaluation of ERI rates. All clinical features of the two groups were similar. A total of 12 patients' (11.9%) CSF cultures were positive for infection. Ten (19.6%) patients who underwent S-EVD had CSF-positive cultures, while only 2 (4.0%) patients who underwent T-EVD had CSF-positive cultures (P = 0.034). Additionally, 8 patients in Group A and 1 patient in Group B were complicated with CSF leakage (P = 0.039). CONCLUSIONS: Compared to S-EVD, T-EVD, when performed according to a previously established perioperative management protocol, resulted in lower infection and CSF leakage rates. We recommend that T-EVD should be preferentially performed when surgeons determine whether a catheter can be removed within 10 days, and the catheter used for EVD should be removed as soon as permitted by the clinical circumstances.


Assuntos
Cateteres de Demora/efeitos adversos , Derivações do Líquido Cefalorraquidiano/efeitos adversos , Drenagem/efeitos adversos , Infecções/epidemiologia , Adulto , Idoso , Drenagem/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ventriculostomia/métodos
7.
J Pain Res ; 12: 1259-1268, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118749

RESUMO

Purpose: We determined whether electroacupuncture (EA) reduces Netrin-1-induced myelinated primary afferent nerve fiber sprouting in the spinal cord and pain hypersensitivity associated with postherpetic neuralgia (PHN) through activation of µ-opioid receptors. Methods: PHN was induced by systemic injection of resiniferatoxin (RTX) in rats. Thirty-six days after RTX injection, a µ-opioid receptor antagonist, beta-funaltrexamine (ß-FNA) or a κ-opioid receptor antagonist, nor Binaltorphimine (nor-BNI), was injected intrathecally 30 mins before EA, once every other day for 4 times. Mechanical allodynia was tested with von Frey filaments. The protein expression level of Netrin-1 and its receptors (DCC and UNC5H2) were quantified by using western blotting. The myelinated primary afferent nerve fiber sprouting was mapped with the transganglionic tracer cholera toxin B-subunit (CTB). Results: Treatment with 2 Hz EA at "Huantiao" (GB30) and "Yanglingquan" (GB34) decreased the mechanical allodynia at 22 days and the myelinated primary afferent nerve fiber preternatural sprouting into the lamina II of the spinal dorsal horn at 42 days after RTX injection. Also, treatment with 2 Hz EA reduced the protein levels of DCC and Netrin-1 and promoted the expression of UNC5H2 in the spinal dorsal horn 42 days after RTX injection. Furthermore, the µ-opioid receptor antagonist ß-FNA, but not the κ-opioid receptor antagonist nor-BNI, reversed the effect of EA on neuropathic pain caused by RTX. In addition, morphine inhibited the Netrin-1 protein level induced by RTX in SH-SY5Y cells. Conclusions: Through activation of µ-opioid receptors, treatment with EA reduces the expression level of DCC and Netrin-1 and changes a growth-permissive environment in spinal dorsal horn into an inhibitory environment by increasing UNC5H2, thus decreasing RTX-caused primary afferent nerve sprouting in the spinal dorsal horn and neuropathic pain.

8.
Phys Chem Chem Phys ; 21(20): 10660-10666, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31080967

RESUMO

As promising candidates for future applications in building-integrated photovoltaics, semitransparent organic solar cells (ST-OSCs) have made tremendous progress. However, power conversion efficiency (PCE) of the ST-OSCs is limited by intrinsic narrow absorption spectra concentrated in the near infrared region (NIR), weak extinction coefficient, and mismatched molecular energy levels of thin active layers. Here, an efficient ST-OSC based on a donor/acceptor electron pair of a trifluorinated polymer donor PBFTT and a tetrachlorinated acceptor IT-4Cl was fabricated. Due to halogenation, photovoltaic materials show stronger extinction coefficient, improved crystallinity and higher charge carrier mobility; PBFTT shows lower electronic energy levels, and IT-4Cl shows a red-shifted absorption spectrum. As a result, the PBFTT:IT-4Cl pair shows matched energy levels, complementary absorption spectra in the NIR region and a good blend morphology. Hence, as-cast OSCs based on PBFTT:IT-4Cl achieved a high PCE of 11.1% with a high short-circuit current density of 19.7 mA cm-2 and a high fill factor of 73.9%. Owing to the complementary absorption spectra in the NIR region, high EQE values between 600 and 830 nm and a favourable transparency window between 400 and 600 nm, while the human eye has the highest sensitivity in the yellow-green wavelength region (500-600 nm), ST-OSCs using an ultra-thin (10-20 nm) Au cathode showed high PCEs of 7.9-9.1% at a high average visible transmittance of 37.3-27.6% in the photopic region. The PCE of 9.1% is one of the highest values reported in the literature for ST-OSCs without any extra treatment and with an AVT of more than 25% in the photopic region so far.

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