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1.
J Craniofac Surg ; 2021 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-34855629

RESUMEN

ABSTRACT: Reconstruction of complete bilateral maxillary defects (CBMDs) can be challenging due to the extensive loss of bone and soft tissues. This is a retrospective case series of 46 consecutive patients with CBMDs that were reconstructed with different microvascular free flaps. The authors aimed to evaluate the surgical outcomes and discuss the different reconstruction options in this case series. Thirty-six patients underwent reconstruction following ablation surgery for malignant tumors, 6 for benign tumors, 3 patients were treated for osteomyelitis, and 1 patient underwent free flap reconstruction for posttraumatic defects. Free fibula flap (n = 26) is the most commonly used reconstruction method in this case series, which was used in all defect types. This is followed by anterolateral thigh flap (n = 10), 5 rectus abdominis myocutaneous free flap, 3 radial forearm free flaps, and 2 composite free flaps. In this series, 44 free flaps survived, whereas only 2 flaps were lost. All patients could resume a soft diet postoperatively. Reconstruction of CBMDs with vascularized free flaps is a safe and reliable procedure.

2.
Front Oncol ; 11: 679173, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34804913

RESUMEN

Castration-resistant prostate cancer (CRPC) continues to be a major clinical problem and its underlying mechanisms are still not fully understood. The epidermal growth factor receptor (EGFR) activation is an important event that regulates mitogenic signaling. EGFR signaling plays an important role in the transition from androgen dependence to castration-resistant state in prostate cancer (PCa). Kinesin family member 15 (KIF15) has been suggested to be overexpressed in multiple malignancies. Here, we demonstrate that KIF15 expression is elevated in CRPC. We show that KIF15 contributes to CRPC progression by enhancing the EGFR signaling pathway, which includes complex network intermediates such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. In CRPC tumors, increased expression of KIF15 is positively correlated with EGFR protein level. KIF15 binds to EGFR, and prevents EGFR proteins from degradation in a Cdc42-dependent manner. These findings highlight the key role of KIF15 in the development of CRPC and rationalize KIF15 as a potential therapeutic target.

3.
Pharm Biol ; 59(1): 1607-1618, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34818128

RESUMEN

CONTEXT: Qingre Huoxue (QRHX) decoction, a traditional Chinese medicine, has been widely used to prevent and treat myocardial infarction (MI). OBJECTIVE: This study elucidates the possible mechanisms of QRHX in preventing or treating MI in a rat model. MATERIALS AND METHODS: The chemical constituents of QRHX were identified by UPLC-MS. Sprague-Dawley rats were randomly divided into the Sham (normal saline), Model (normal saline), QRHX-L, QRHX-M and QRHX-H group (n = 10 per group). QRHX decoction was administered by gavage to the rats for 14 days (5, 10 and 20 g/kg/day). The left anterior descending ligation method was performed to develop MI in Model and QRHX groups, and the same surgical procedures excluding ligation sutures were performed for the sham group. Finally, we evaluated cardiac function, myocardial fibrosis degree, serum inflammatory factors, autophagy levels and verified the signalling pathways in vivo. RESULTS: A total of 68 active components of QRHX corresponding to 223 active targets were obtained and 2558 MI-related disease targets were collected. After integration, 123 QRHX anti-MI targets were obtained, and 70 signalling pathways, such as PI3K/Akt, were identified by enrichment analysis. In vivo experiments suggest that QRHX could reduce the degree of myocardial fibrosis, downregulate serum inflammatory factors, and promote autophagy in MI rats. DISCUSSION AND CONCLUSIONS: QRHX plays a protective role in the myocardium by mediating PI3K/Akt signalling pathway to activate autophagy and inhibiting inflammatory factor expression. These findings provide a scientific basis for further research and validation of QRHX as a potential therapeutic for MI.

4.
Nano Lett ; 21(21): 8979-8986, 2021 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-34644095

RESUMEN

Plexcitonic strong coupling between a plasmon-polariton and a quantum emitter empowers ultrafast quantum manipulations in the nanoscale under ambient conditions. The main body of previous studies deals with homogeneous quantum emitters. To enable multiqubit states for future quantum computing and network, the strong coupling involving two excitons of the same material but different resonant energies has been investigated and observed primarily at very low temperature. Here, we report a room-temperature diexcitonic strong coupling (DiSC) nanosystem in which the excitons of a transition metal dichalcogenide monolayer and dye molecules are both strongly coupled to a single Au nanocube. Coherent information exchange in this DiSC nanosystem could be observed even when exciton energy detuning is about five times larger than the respective line widths. The strong coupling behaviors in such a DiSC nanosystem can be manipulated by tuning the plasmon resonant energies and the coupling strengths, opening up a paradigm of controlling plasmon-assisted coherent energy transfer.

5.
Artículo en Inglés | MEDLINE | ID: mdl-34620538

RESUMEN

This retrospective case-series study aimed to elucidate the three-dimensional attachment morphometric features and to quantify the volumetric changes of the masticatory muscles following free fibular flap reconstruction of the mandibular condyle. Navigation software (iPlan, version 3.0; Brainlab) was used to perform delineation and volumetric measurement of the masticatory muscles using DICOM data. In total, 30 patients were included in this retrospective case series. In 25 cases (83.33%), the lateral pterygoid muscle achieved reattachment within 6 months postoperatively. The medial pterygoid muscles on the affected side achieved ectopic attachment in all cases. However, masseter reattachment on the affected side was achieved in only three cases. On the normal side, the volumes of lateral pterygoid muscle, medial pterygoid muscle, and masseter had recovered to almost preoperative levels at 1 year postoperatively. On the affected side, the volume of medial pterygoid muscle had decreased significantly (p = 2.4e-04) at 3 months postoperatively. The volumes of lateral pterygoid muscle and masseter showed mild decreases at 3 months postoperatively, but these were not significant (p = 0.52 and p = 0.05 for the pterygoid muscle and masseter, respectively). At 6 months after surgery, with the exception of the volume of the lateral pterygoid muscle (p = 0.06), the total volume of the masticatory muscles decreased significantly on the affected side. The volumes of lateral pterygoid muscle, medial pterygoid muscle, and masseter showed significant decreases at 1 year postoperatively (p = 0.03, p = 4.7e-08, and p = 1.1e-05, respectively) on the affected side. The postoperative volumes of the masseter, medial pterygoid, and lateral pterygoid muscles showed significant decreases due to the loss of reattachment. The results of this study may not help to ascertain whether reattachment of masticatory muscles will lead to better function. As a consequence, clinical trials of higher quality are needed.

6.
Opt Express ; 29(18): 28190-28201, 2021 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-34614956

RESUMEN

Polarization mode dispersion (PMD) is one of the fundamental properties of a standard single-mode fiber. It affects the propagating signals and degrades the performance of high-speed optical fiber communication systems. PMD also gives an effect on the nonlinear spectra or scattering data in nonlinear frequency division multiplexing (NFDM) systems. However, PMD is usually described in the linear frequency domain, and there are few investigations about the influence of PMD in the nonlinear frequency domain (NFD). An NFD-PMD model is needed to understand the impact of PMD in the NFD. In this work, using a linear approximation method, we first propose an NFD-PMD model and verify its effectiveness. With the guide of the NFD-PMD model, a blind NFD-PMD equalization scheme is designed. The simulation results indicate that the proposed NFD-PMD equalization scheme has better performance than the training sequence method based on linear frequency domain equalization.

7.
Ann Palliat Med ; 10(9): 9848-9858, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34628911

RESUMEN

BACKGROUND: Minimally invasive transforaminal interbody fusion (MI-TLIF) can minimize surgical incision, tissue damage, and intraoperative blood loss in the treatment of spondylolisthesis. However, there is a lack of evidence-based research to confirm its clinical efficacy. METHODS: Chinese and English databases were searched with "open", "minimally invasive transforaminal interbody fusion", "MIS-TLIF", "spondylolisthesis", and "open transforaminal interbody fusion" as search terms. Rev Man 5.3 provided by the Cochrane system was used to assess the quality of the literature. RESULTS: Of the 12 randomized controlled trials (RCTs), 7 references were level A (58.34%), 4 were B level (33.33%), and 1 reference was C level (8.33%). There was a statistically significant difference in intraoperative blood loss between MI-TLIF and open transforaminal interbody fusion (O-TLIF) in the treatment of spondylolisthesis [mean difference (MD) =-349.35, 95% confidence interval (CI): (-410.66, -288.03), P<0.00001]. There was also a statistically significant difference in visual analogue scale (VAS) scores before and after MI-TLIF at the last follow-up [MD =5.72, 95% CI: (4.83, 6.62), P<0.00001], and in the complication rate between MI-TLIF and O-TLIF [odds ratio (OR) =0.48, 95% CI: (0.30, 0.76), P<0.00001]. DISCUSSION: This meta-analysis confirmed that MI-TLIF could significantly reduce intraoperative blood loss, mitigate patient pain, and reduce the incidence of complications without increasing the operation time in the treatment of spondylolisthesis.


Asunto(s)
Fusión Vertebral , Espondilolistesis , Humanos , Vértebras Lumbares/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos , Espondilolistesis/cirugía , Resultado del Tratamiento
8.
Polymers (Basel) ; 13(19)2021 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-34641222

RESUMEN

Electrostatic interaction between polymers and nanofillers is of great importance for the properties and design of their composites. Polyacrylates with carboxyl, hydroxyl and acylamino groups were synthesized via emulsion polymerization and marked as P(MMA-BA-AA), P(MMA-BA-HEA) and P(MMA-BA-AM), respectively. Amino-functionalized graphene oxide (NGO) was prepared by Hoffman rearrangement using GO as the raw material. The polyacrylate composites were prepared by mixing NGO with each of the three kinds of polyacrylate. Effects of pH and NGO amounts on the properties of polyacrylate composites were studied. It was found that the surface charge of polyacrylate and NGO had the greatest effect on the composite properties. P(MMA-BA-AM)/NGO was not stable at any pH (2-8). With the same NGO amount of 0.1 wt%, the toughening effect of NGO on P(MMA-BA-AA) was larger than that on P(MMA-BA-HEA). The break strength of P(MMA-BA-AA)/NGO and P(MMA-BA-HEA)/NGO increased to 5.22 MPa by 47% and 3.08 MPa by 31%, respectively. NGO could increase the thermal stability of P(MMA-BA-AA) and P(MMA-BA-HEA) to different degrees. The polyacrylate film-forming processes were tested, and it showed that NGO influenced polyacrylate through the whole film-forming process. The results provide potential methods for the design of polymer-based nanocomposites.

9.
Shanghai Kou Qiang Yi Xue ; 30(4): 344-349, 2021 Aug.
Artículo en Chino | MEDLINE | ID: mdl-34693424

RESUMEN

PURPOSE: To investigate the osteogenic effect of nano-grade pearl powder(NPP)/chitosan-hyaluronic acid (C-HA)/recombinant human bone morphology protein-2 (rhBMP-2) artificial bone. METHODS: A bone defect model with a diameter of 7 mm and a height of 10 mm was made at the distal end of the femur. NPP/C-HA stent containing rhBMP-2 was prepared according to the shape of the defect. No material was implanted in the defect as blank group. NPP/C-HA was used as the control group, NPP/C-HA/rhBMP-2 was implanted into the experimental group. At 4 weeks, 8 weeks, and 12 weeks, the bone effects of each component were detected by cone-beam CT(CBCT), H-E and Masson staining. Serum ALP activity and OCN in tissues to determine the osteogenic differentiation and osteogenesis maturity were detected. SPSS 18.0 software package was used for statistical analysis. RESULTS: At 12 weeks, the defect was completely repaired in the experimental group. No immunological side effects such as inflammation and rejection were observed. At 8 and 12 weeks, CBCT showed that the experimental group had a higher CT value (Hounsfield units, HU) compared with the control group and the blank group(P<0.05). H-E and Masson staining showed that the experimental group had obvious new bone formation compared with the control group and the blank group at 8 weeks and 12 weeks, and ALP activity of the experimental group was significantly different from the control group and the blank group at 8 weeks. OCN immunohistochemical scoring of the experimental group was significantly different from the control group and the blank group(P<0.05). CONCLUSIONS: NPP/C-HA/rhBMP-2 has good tissue fusion, osteoinductivity, osteoconductivity and osteogenicity, which is expected to provide more effective treatment for bone repair.


Asunto(s)
Quitosano , Animales , Proteína Morfogenética Ósea 2 , Fémur/diagnóstico por imagen , Ácido Hialurónico , Osteogénesis , Conejos , Proteínas Recombinantes , Factor de Crecimiento Transformador beta
10.
Front Oncol ; 11: 724191, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34490121

RESUMEN

As a highly malignant tumor, the incidence and mortality of glioma are not optimistic. Predicting the survival time of patients with glioma by extracting the feature information from gliomas is beneficial for doctors to develop more targeted treatments. Magnetic resonance imaging (MRI) is a way to quickly and clearly capture the details of brain tissue. However, manually segmenting brain tumors from MRI will cost doctors a lot of energy, and doctors can only vaguely estimate the survival time of glioma patients, which are not conducive to the formulation of treatment plans. Therefore, automatically segmenting brain tumors and accurately predicting survival time has important significance. In this article, we first propose the NLSE-VNet model, which integrates the Non-Local module and the Squeeze-and-Excitation module into V-Net to segment three brain tumor sub-regions in multimodal MRI. Then extract the intensity, texture, wavelet, shape and other radiological features from the tumor area, and use the CNN network to extract the deep features. The factor analysis method is used to reduce the dimensionality of features, and finally the dimensionality-reduced features and clinical features such as age and tumor grade are combined into the random forest regression model to predict survival. We evaluate the effect on the BraTS 2019 and BraTS 2020 datasets. The average Dice of brain tumor segmentation tasks up to 79% and the average RMSE of the survival predictive task is as low as 311.5. The results indicate that the method in this paper has great advantages in segmentation and survival prediction of gliomas.

11.
Appl Environ Microbiol ; 87(23): e0160121, 2021 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-34550751

RESUMEN

Soybean root rot caused by the oomycete Phytophthora sojae is a serious soilborne disease threatening soybean production in China. Bacillus velezensis FZB42 is a model strain for Gram-positive plant growth-promoting rhizobacteria and is able to produce multiple antibiotics. In this study, we demonstrated that B. velezensis FZB42 can efficiently antagonize P. sojae. The underlying mechanism for the inhibition was then investigated. The FZB42 mutants deficient in the synthesis of lipopeptides (bacillomycin D and fengycin), known to have antifungal activities, and polyketides (bacillaene, difficidin, and macrolactin), known to have antibacterial activities, were not impaired in their antagonism toward P. sojae; in contrast, mutants deficient in bacilysin biosynthesis completely lost their antagonistic activities toward P. sojae, indicating that bacilysin was responsible for the activity. Isolated pure bacilysin confirmed this inference. Bacilysin was previously shown to be antagonistic mainly toward prokaryotic bacteria rather than eukaryotes. Here, we found that bacilysin could severely damage the hyphal structures of P. sojae and lead to the loss of its intracellular contents. A device was invented allowing interactions between P. sojae and B. velezensis FZB42 on nutrient agar. In this manner, the effect of FZB42 on P. sojae was studied by transcriptomics. FZB42 significantly inhibited the expression of P. sojae genes related to growth, macromolecule biosynthesis, pathogenicity, and ribosomes. Among them, the genes for pectate lyase were the most significantly downregulated. Additionally, we showed that bacilysin effectively prevents soybean sprouts from being infected by P. sojae and could antagonize diverse Phytophthora species, such as Phytophthora palmivora, P. melonis, P. capsici, P. litchi, and, most importantly, P. infestans. IMPORTANCE Phytophthora spp. are widespread eukaryotic phytopathogens and often extremely harmful. Phytophthora can infect many types of plants important to agriculture and forestry and thus cause large economic losses. Perhaps due to inappropriate recognition of Phytophthora as a common pathogen in history, research on the biological control of Phytophthora is limited. This study shows that B. velezensis FZB42 can antagonize various Phytophthora species and prevent the infection of soybean seedlings by P. sojae. The antibiotic produced by FZB42, bacilysin, which was already known to have antibacterial effectiveness, is responsible for the inhibitory action against Phytophthora. We further showed that some Phytophthora genes and pathways may be targeted in future biocontrol studies. Therefore, our data provide a basis for the development of new tools for the prevention and control of root and stem rot in soybean and other plant diseases caused by Phytophthora.

12.
Nature ; 597(7876): 360-365, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34526707

RESUMEN

Fish and other aquatic foods (blue foods) present an opportunity for more sustainable diets1,2. Yet comprehensive comparison has been limited due to sparse inclusion of blue foods in environmental impact studies3,4 relative to the vast diversity of production5. Here we provide standardized estimates of greenhouse gas, nitrogen, phosphorus, freshwater and land stressors for species groups covering nearly three quarters of global production. We find that across all blue foods, farmed bivalves and seaweeds generate the lowest stressors. Capture fisheries predominantly generate greenhouse gas emissions, with small pelagic fishes generating lower emissions than all fed aquaculture, but flatfish and crustaceans generating the highest. Among farmed finfish and crustaceans, silver and bighead carps have the lowest greenhouse gas, nitrogen and phosphorus emissions, but highest water use, while farmed salmon and trout use the least land and water. Finally, we model intervention scenarios and find improving feed conversion ratios reduces stressors across all fed groups, increasing fish yield reduces land and water use by up to half, and optimizing gears reduces capture fishery emissions by more than half for some groups. Collectively, our analysis identifies high-performing blue foods, highlights opportunities to improve environmental performance, advances data-poor environmental assessments, and informs sustainable diets.


Asunto(s)
Acuicultura , Ecosistema , Monitoreo del Ambiente , Alimentos Marinos , Desarrollo Sostenible , Animales , Acuicultura/tendencias , Cambio Climático , Dieta , Ecología , Política Ambiental , Explotaciones Pesqueras , Abastecimiento de Alimentos/métodos , Gases de Efecto Invernadero , Humanos , Moluscos , Nitrógeno , Fósforo , Alimentos Marinos/provisión & distribución , Algas Marinas , Desarrollo Sostenible/tendencias
13.
Cell Death Discov ; 7(1): 255, 2021 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-34545072

RESUMEN

The long noncoding RNA (lncRNA) DLGAP1-AS2 has recently been characterized as an oncogenic lncRNA in several cancers. However, its biological roles and clinical significance in gastric cancer (GC) remains barely understood. In this study, we performed a systematic analysis of DLGAP1-AS2 expression with data from the TCGA and GEO database as well as our clinic GC samples. In agreement with previous studies, our findings demonstrated that DLGAP1-AS2 was significantly up-regulated in GC and its high expression was associated with poor prognosis, suggesting that DLGAP1-AS2 might be a putative oncogenic lncRNA of GC. Loss of DLGAP1-AS2 restricted cell proliferation, migration, and invasion in GC cell lines. Mechanically, Wnt1 was identified as the downstream target of DLGAP1-AS2 by using bioinformatics analysis coupled with qPCR and Western blot assays. Furthermore, DLGAP1-AS2 was found to directly interact with the transcriptional repressor Six3, and this interaction hampered Six3 binding to the promoter regions of the Wnt1 gene, thereby leading to transcriptional activation of Wnt1. Consequently, GC cells lacking DLGAP1-AS2 showed a decreased Wnt1 expression and weakened Wnt/ß-catenin signaling. Further, Six3 silencing could reverse the above effects, highlighting a pivotal role of Six3 in the DLGAP1-AS2-mediated activation of Wnt/ß-catenin signaling. Either genetic (Wnt1 knockdown) or pharmacological (LF3) inhibition of Wnt/ß-catenin signaling could effectively abolish the activation of Wnt/ß-catenin signaling by Six3 depletion, thereby preventing GC cell malignant transformation. Taken together, our results suggest that DLGAP1-AS2 functions as an oncogenic factor by directly interacting with Six3 to relieve its suppression on Wnt1 expression, thereby driving the malignancy of GC. DLGAP1-AS2/Six3/Wnt1/ß-catenin signaling axis might serve as a promising diagnostic and therapeutic target for GC.

14.
Acta Pharm Sin B ; 11(8): 2114-2135, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34522580

RESUMEN

Natural extracellular vesicles (EVs) play important roles in many life processes such as in the intermolecular transfer of substances and genetic information exchanges. Investigating the origins and working mechanisms of natural EVs may provide an understanding of life activities, especially regarding the occurrence and development of diseases. Additionally, due to their vesicular structure, EVs (in small molecules, nucleic acids, proteins, etc.) could act as efficient drug-delivery carriers. Herein, we describe the sources and biological functions of various EVs, summarize the roles of EVs in disease diagnosis and treatment, and review the application of EVs as drug-delivery carriers. We also assess the challenges and perspectives of EVs in biomedical applications.

15.
Oral Dis ; 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34479400

RESUMEN

BACKGROUND: Oral squamous cell carcinoma (OSCC), a main type of squamous cell cancer, is associated with considerable morbidity and mortality. Recent reports suggested methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) modification to be an essential regulator in the fate determination of stem cells. However, the functional significance of METTL3 in OSCC remains largely unknown. METHODS: METTL3 expression was examined in OSCC patient samples, followed by correlation analysis against clinical tumor features. Functional assays, such as assessment of surface marker expression, colony forming, BrdU incorporation, tumor xenograft assay, and m6A dot blot, were conducted to study the impact of METTL3 knockdown (KD) in OSCC cells. RESULTS: High METTL3 expression was positively correlated with more severe clinical features of OSCC tumors. METTL3 KD caused impairment of stem-like capacities in OSCC cells, such as tumorigenicity in vivo and colony-forming ability in vitro. Furthermore, METTL3-KD and cycloleucine, a methylation inhibitor, decreased m6A levels and down-regulated p38 expression in OSCC cells. On the contrary, the impaired cell proliferation capacity of OSCC cells after METTL3-KD was restored by exogenous expression of p38. CONCLUSION: Our findings identified m6A methyltransferase METTL3 as a key element in the regulation of tumorigenesis in OSCC.

16.
Glob Food Sec ; 28: 100494, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34513582

RESUMEN

The COVID-19 pandemic and subsequent lockdowns are creating health and economic crises that threaten food and nutrition security. The seafood sector provides important sources of nutrition and employment, especially in low-income countries, and is highly globalized allowing shocks to propagate. We studied COVID-19-related disruptions, impacts, and responses to the seafood sector from January through May 2020, using a food system resilience 'action cycle' framework as a guide. We find that some supply chains, market segments, companies, small-scale actors and civil society have shown initial signs of greater resilience than others. COVID-19 has also highlighted the vulnerability of certain groups working in- or dependent on the seafood sector. We discuss early coping and adaptive responses combined with lessons from past shocks that could be considered when building resilience in the sector. We end with strategic research needs to support learning from COVID-19 impacts and responses.

17.
Front Chem ; 9: 752630, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34540811

RESUMEN

The interplay between the hydrophobic interactions generated by the nonpolar region and the proximal functional groups within nanometers of the nonpolar region offers a promising strategy to manipulate the intermolecular hydrophobic attractions in an artificial molecule system, but the outcomes of such modulations in the building of a native protein architecture remain unclear. Here we focus on the intermediate filament (IF) coiled-coil superfamily to assess the conservation of positively charged residue identity via a biostatistical approach. By screening the disease-correlated mutations throughout the IF superfamily, 10 distinct hotspots where a cation-to-cation substitution is associated with a pathogenic syndrome have been identified. The analysis of the local chemical context surrounding the hotspots revealed that the cationic diversity depends on their separation distance to the hydrophobic domain. The nearby cationic residues flanking the hydrophobic domain of a helix (separation <1 nm) are relatively conserved in evolution. In contrast, the cationic residues that are not adjacent to the hydrophobic domain (separation >1 nm) tolerate higher levels of variation and replaceability. We attribute this bias in the conservation degree of the cationic residue identity to reflect the interplay between the proximal cations and the hydrophobic interactions.

18.
JAMA Neurol ; 78(11): 1345-1354, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34570177

RESUMEN

Importance: Network hyperexcitability may contribute to cognitive dysfunction in patients with Alzheimer disease (AD). Objective: To determine the ability of the antiseizure drug levetiracetam to improve cognition in persons with AD. Design, Setting, and Participants: The Levetiracetam for Alzheimer's Disease-Associated Network Hyperexcitability (LEV-AD) study was a phase 2a randomized double-blinded placebo-controlled crossover clinical trial of 34 adults with AD that was conducted at the University of California, San Francisco, and the University of Minnesota, Twin Cities, between October 16, 2014, and July 21, 2020. Participants were adults 80 years and younger who had a Mini-Mental State Examination score of 18 points or higher and/or a Clinical Dementia Rating score of less than 2 points. Screening included overnight video electroencephalography and a 1-hour resting magnetoencephalography examination. Interventions: Group A received placebo twice daily for 4 weeks followed by a 4-week washout period, then oral levetiracetam, 125 mg, twice daily for 4 weeks. Group B received treatment using the reverse sequence. Main Outcomes and Measures: The primary outcome was the ability of levetiracetam treatment to improve executive function (measured by the National Institutes of Health Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research [NIH-EXAMINER] composite score). Secondary outcomes were cognition (measured by the Stroop Color and Word Test [Stroop] interference naming subscale and the Alzheimer's Disease Assessment Scale-Cognitive Subscale) and disability. Exploratory outcomes included performance on a virtual route learning test and scores on cognitive and functional tests among participants with epileptiform activity. Results: Of 54 adults assessed for eligibility, 11 did not meet study criteria, and 9 declined to participate. A total of 34 adults (21 women [61.8%]; mean [SD] age, 62.3 [7.7] years) with AD were enrolled and randomized (17 participants to group A and 17 participants to group B). Thirteen participants (38.2%) were categorized as having epileptiform activity. In total, 28 participants (82.4%) completed the study, 10 of whom (35.7%) had epileptiform activity. Overall, treatment with levetiracetam did not change NIH-EXAMINER composite scores (mean difference vs placebo, 0.07 points; 95% CI, -0.18 to 0.32 points; P = .55) or secondary measures. However, among participants with epileptiform activity, levetiracetam treatment improved performance on the Stroop interference naming subscale (net improvement vs placebo, 7.4 points; 95% CI, 0.2-14.7 points; P = .046) and the virtual route learning test (t = 2.36; Cohen f2 = 0.11; P = .02). There were no treatment discontinuations because of adverse events. Conclusions and Relevance: In this randomized clinical trial, levetiracetam was well tolerated and, although it did not improve the primary outcome, in prespecified analysis, levetiracetam improved performance on spatial memory and executive function tasks in patients with AD and epileptiform activity. These exploratory findings warrant further assessment of antiseizure approaches in AD. Trial Registration: ClinicalTrials.gov Identifier: NCT02002819.

19.
Plant Cell Physiol ; 2021 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-34428298

RESUMEN

Abscisic acid (ABA) regulates plant development mainly through its signaling in which ABA binds to receptors to inhibit type 2C protein phosphatases (PP2Cs). The exact roles of PP2Cs in fruit development are still unclear. In this work, we verify that tomato SlPP2C5 works as a negative regulator in ABA signaling during fruit development. SlPP2C5 was inhibited by both monomeric and dimer ABA receptors SlPYLs through ABA dose-dependent way and it interacted physically with SlPYLs and SlSnRK2s. SlPP2C5 was highly expressed in fruits induced by exogenous ABA. Plants with over-expressed SlPP2C5 had lower sensitivity to ABA which showed faster seed germination and primary root growth compared to WT, while SlPP2C5-suppressed plants were more sensitive to ABA. SlPP2C5-OE delayed fruit ripening onset while SlPP2C5-RNAi advanced fruit ripening. Alteration of SlPP2C5 expression impacts fruit quality parameters as well, including pericarp thickness, fruit shape index, seed number and weight, and the soluble solid content. RNA-seq analysis revealed that there were significant expression differences of genes related to ethylene release and lycopene synthesis between WT and both SlPP2C5-OE and SlPP2C5-RNAi lines with an inversed variation. Taken together, our findings demonstrate that SlPP2C5 plays an important role in the regulation of fruit development, ripening and quality.

20.
Opt Lett ; 46(15): 3697-3700, 2021 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-34329259

RESUMEN

A joint scheme introducing probabilistic shaping (PS) at the transmitter and utilizing a neural network (NN) equalizer at the receiver is proposed to improve the performance of the b-modulated nonlinear frequency division multiplexing (NFDM) system. Through a numerical simulation, we demonstrate that PS plays a leading role for low launch power case, which improves the performance of the system effectively, while the NN equalizer's superiority appears in a high launch power region, whose main role is to weaken the correlation among subcarriers for improving system performance. The proposed scheme would enlighten the optimum modulation and detection schemes of the NFDM system.

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