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1.
J Craniofac Surg ; 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980838

RESUMO

ABSTRACT: Maxillary sinusitis is 1 of the postoperative complications of the Le Fort I osteotomy, this study investigated the related factors of maxillary sinusitis after Le Fort I osteotomy. A total of 23 cases, 92 controls, and 11 related factors were included in this case-control study with a 1:4 case-control ratio. The risk factors for maxillary sinusitis after Le Fort I were examined by least absolute shrinkage and selection operator multivariate conditional logistic regression and least absolute shrinkage and selection operator multivariate linear regression. The patency of maxillary sinus ostium at 6 months after surgery was significantly associated with maxillary sinusitis after Le Fort I osteotomy. Compared with the obstructed maxillary sinus ostium, the percentage of the volume of the healthy air cavity in the complete sinus cavity increased 70.7% when the maxillary sinus ostium was unobstructed, and 95% confidence interval was 0.610 to 0.805. Similarly, when the maxillary sinus ostium was wide, the percentage increased 6.0% compared with the narrow 1, and 95% confidence interval was 0.013 to 0.107. This study indicated that the patency of maxillary sinus ostium has an important impact on maxillary sinusitis after Le Fort I osteotomy. Close attention should be paid to maintain the maxillary sinus ostium and the drainage of maxillary sinuses unobstructed in a clinical setting.

2.
J Cell Mol Med ; 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35040253

RESUMO

Ventricular arrhythmias (VAs) triggers by sympathetic nerve hyperactivity contribute to sudden cardiac death in myocardial infarction (MI) patients. Microglia-mediated inflammation in the paraventricular nucleus (PVN) is involved in sympathetic hyperactivity after MI. N6-methyladenosine (m6 A), the most prevalent mRNA and epigenetic modification, is critical for mediating cell inflammation. We aimed to explore whether METTL3-mediated m6 A modification is involved in microglia-mediated sympathetic hyperactivity after MI in the PVN. MI model was established by left coronary artery ligation. METTL3-mediated m6 A modification was markedly increased in the PVN at 3 days after MI, and METTL3 was primarily located in microglia by immunofluorescence. RNA-seq, MeRIP-seq, MeRIP-qPCR, immunohistochemistry, ELISA, heart rate variability measurements, renal sympathetic nerve activity recording and programmed electrical stimulation confirmed that the elevated toll-like receptor 4 (TLR4) expression by m6 A modification on TLR4 mRNA 3'-UTR region combined with activated NF-κB signalling led to the overwhelming production of pro-inflammatory cytokines IL-1ß and TNF-α in the PVN, thus inducing the sympathetic hyperactivity and increasing the incidence of VAs post-MI. Targeting METTL3 attenuated the inflammatory response and sympathetic hyperactivity and reduced the incidence of VAs post-MI.

3.
J Pain Res ; 15: 13-22, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35023967

RESUMO

Background: Sciatica-related spinal imbalance could be observed in lumbar disc herniation (LDH) patients. However, their characteristics and recovery process remained unclear. The purpose was to analyze the radiological characteristics of spinal imbalance related to sciatica and recovery following endoscopic discectomy. Methods: The records of LDH patients with sciatica and spinal imbalance receiving endoscopic discectomy were retrospectively reviewed. The patients were divided to Group A (sagittal imbalance), Group B (coronal imbalance) and Group C (sagittal and coronal imbalance). The whole-spine x-ray was performed at pre-operation, immediately post-operation, 3-month and 6-month follow-up and related radiological parameters were measured. Results: A total of 110 LDH patients (18.3%) presented with spinal imbalance were included and there were 31 patients in Group A, 38 patients in Group B and 41 patients in Group C. In this study, 77.2% of the coronal imbalance patients present with trunk shifted to contralateral side of disc herniation and 65.3% of the sagittal imbalance patients present with forward trunk. Most patients present mild and moderate sagittal and coronal imbalance. The magnitude of sagittal and coronal imbalance in Group C was significantly more severe than that of Group A and Group B. Most patients (≥75%) acquired spinal balance immediately after surgery. The sagittal imbalance improved better than coronal imbalance and single plane imbalance improved better than biplane imbalance. At the postoperative 6-month follow-up, all patients recovered to normal sagittal and coronal balance. Conclusion: Sciatica-related spinal imbalance occurs in 18.3% of the LDH patients receiving endoscopic discectomy. Different subgroups of spinal imbalance present different characteristics. Spontaneous correction of the spinal imbalance could be achieved when sciatica was relieved immediately after surgery and well maintained during follow-up.

4.
J Cell Sci ; 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34897465

RESUMO

Integrin α6ß4 binds plectin to associate with vimentin; however, the biological function remains unclear. Here, we utilized various integrin ß4 mutants and CRISPR-Cas9 editing to investigate this association. Upon laminin binding, integrin α6ß4 distinctly distributed peripherally, and centrally proximal to the nucleus. Upon fibronectin addition, integrin α6ß4 was centrally recruited to large focal adhesions (FAs) and enhanced Fak phosphorylation. Integrin ß4 plectin-binding mutants or genetic deletion of plectin inhibited ß4 recruitment to FAs and integrin α6ß4-enhanced cell spreading, migration and three-dimensional invasive growth. Loss of the ß4 signaling domain (but retains plectin binding) blocked migration and invasiveness but not cell spreading, recruitment to FAs or colony growth. Immunostaining revealed that integrin α6ß4 redistributed vimentin perinuclearly where it colocalized with plectin and FAs. Depletion of vimentin completely blocked integrin ß4-enhanced invasive growth, Fak phosphorylation and proliferation in three-dimensions but not two-dimensions. In summary, we demonstrate the essential roles of plectin and vimentin in promoting an invasive phenotype downstream of integrin α6ß4.

5.
Patient Prefer Adherence ; 15: 2725-2730, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34916782

RESUMO

Objective: This study determined the reference interval of pepsinogen (PG) of healthy people in the local region to provide a basis for early screening of gastric cancer. Methods: Among the healthy people who underwent a physical examination in our hospital from January 2020 to December 2020, 2568 subjects were selected based on the relevant screening criteria. Their serum PG I and II levels and PG I:PG II ratio were determined by chemiluminescent microparticle immunoassay (CIMA), and the results were statistically analyzed. Finally, according to document CLSI-C28-A3, the PG reference interval of the local region was determined. Results: The PG I and II levels of the males in all age groups were higher than those of the females in the corresponding age groups, and the differences were statistically significant (P < 0.05). However, the differences in the PG I:PG II ratio between the genders in the different age groups were not statistically significant (P > 0.05). The PG I and II levels increased with age in both men and women, while the PG I:PG II ratio was not correlated with age in either gender. Conclusion: The PG reference interval of the local region was initially determined as providing a reliable reference basis for clinical treatment.

6.
Micromachines (Basel) ; 12(12)2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34945383

RESUMO

In this paper, to address the problems of large blood draws, long testing times, and the inability to achieve dynamic detection of invasive testing for diabetes, stemming from the principle that type 1 diabetic patients exhale significantly higher levels of acetone than normal people, a FAIMS-MEMS gas sensor was designed to detect acetone, which utilizes the characteristics of high sensitivity, fast response, and non-invasive operation. It is prepared by MEMS processes, such as photolithography, etching, and sputtering, its specific dimensions are 4000 µm in length, 3000 µm in width and 800 µm in height and the related test system was built to detect acetone gas. The test results show that when acetone below 0.8 ppm is introduced, the voltage value detected by the sensor basically does not change, while when acetone gas exceeds 1.8 ppm, the voltage value detected by the sensor increases significantly. The detection accuracy of the sensor prepared by this method is about 0.02 ppm/mV, and the voltage change can reach 1 V with a response time of 3 s and a recovery time of 4 s when tested under 20 ppm acetone environment; this has good repeatability and stability, and has great prospects in the field of non-invasive detection of type 1 diabetes.

7.
World J Clin Cases ; 9(30): 9023-9037, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34786385

RESUMO

BACKGROUND: Multiple myeloma is an incurable malignant plasma cell disorder that represents the most common primary malignant bone tumor. It commonly involves bone metastasis in multiple vertebral bodies, and the Spinal Instability Neoplastic Score scoring system may not be fully applicable to multiple myeloma (MM) patients. AIM: To evaluate the spinal stability of patients with MM spinal involvement to guide their clinical treatment. METHODS: By using the Delphi method, we collected and extracted information through a series of questionnaires and improved it via feedback. We also preliminarily established a spinal stability scoring system for multiple myeloma. RESULTS: Fifteen clinicians completed a second round of questionnaires and compared their answers with those of the first round of questionnaires to identify significant comments or changes that required group discussions. As a result, no further feedback was used to improve the scoring system. After integrating the information from the expert consultation questionnaire, we established the initial scoring system for MM spine stability and used the scoring system to assess a series of representative clinical cases. The MM spinal stability scoring system was created by calculating the scores of the six separate components: location, pain, number of segments, physiological curvature, comorbidities, and neurological function. The minimum value was "0", and the maximum value was "24". A score of "0-10" indicated "spine stability", a score of "11-17" indicated "potential instability", and a score of "18-24" indicated "spine instability". Patients with a score of "11-24" need an intervention such as surgery. CONCLUSION: The initial establishment of the MM spine stability scoring system provides a vital theoretical basis for the evaluation of spine stability in individuals with MM.

8.
World J Pediatr ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34822129

RESUMO

BACKGROUND: Prenatal diagnosis and planned peripartum care is an unexplored concept in China. This study aimed to evaluate the effects of the "prenatal diagnosis and postnatal treatment integrated model" for newborns with critical congenital heart disease. METHODS: The medical records of neonates (≤ 28 days) admitted to Fuwai Hospital were reviewed retrospectively from January 2019 to December 2020. The patients were divided into "prenatal diagnosis and postnatal treatment integrated group" (n = 47) and "non-integrated group" (n = 69). RESULTS: The age of admission to the hospital and the age at surgery were earlier in the integrated group than in the non-integrated group (5.2 ± 7.2 days vs. 11.8 ± 8.0 days, P < 0.001; 11.9 ± 7.0 days vs. 16.5 ± 7.7 days, P = 0.001, respectively). The weight at surgery also was lower in the integrated group than in the non-integrated group (3.3 ± 0.4 kg vs. 3.6 ± 0.6 kg, P = 0.010). Longer postoperative recovery time was needed in the integrated group, with a median mechanical ventilation time of 97 h (interquartile range 51-259 h) vs. 69 h (29-168 h) (P = 0.030) and with intensive care unit time of 13.0 days (8.0-21.0 days) vs. 9.0 days (4.5-16.0 days) (P = 0.048). No significant difference was observed in the all-cause mortality (2.1 vs. 8.7%, P = 0.238), but it was significantly lower in the integrated group for transposition of the great arteries (0 vs. 18.8%, log rank P = 0.032). CONCLUSIONS: The prenatal diagnosis and postnatal treatment integrated model could significantly shorten the diagnosis and hospitalization interval of newborns, and surgical intervention could be performed with a lower risk of death, especially for transposition of the great arteries.

9.
Ann Transl Med ; 9(20): 1519, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790725

RESUMO

Background: Sepsis is a systemic disease characterized by extensive inflammatory responses and impaired organ function, which are characteristics that make it easily missed and complex to treat. A large number of laboratory and clinical studies on the diagnosis and treatment of sepsis have been continuously carried out, confirming the importance of mitochondrial function during the development of sepsis. STEAP4 is an important metalloreductase in mitochondria, which is involved in the biogenesis and respiratory chain of mitochondria. The role of STEAP4 in inflammation remains controversial. Research in this field may contribute to the development of new diagnostic and treatment options for sepsis. Methods: The expression of STEAP4 was measured in the peripheral blood of patients with severe sepsis and compared with healthy controls. Cell and mouse inflammatory models were established to detect the expression of STEAP4 and other inflammatory cytokines. Results: (I) The expression of STEAP4 in the peripheral blood of patients with severe sepsis is higher than that of healthy volunteers (P<0.01), which is related to the SOFA score and transaminase. (II) STEAP4 has a certain predictive effect on the outcome of patients [area under curve (AUC) =0.696, P<0.05, 95% CI: 0.528 to 0.833]. (III) Inflammation led to increased expression of STEAP4 gene in RAW264.7 cells and mouse liver tissue. Conclusions: The expression of STEAP4 is elevated in the early stage of sepsis and the degree of its elevation can be used to predict the clinical outcome of sepsis patients.

10.
J Transl Med ; 19(1): 459, 2021 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-34743703

RESUMO

BACKGROUND: Adoptive transfer of chimeric antigen receptor (CAR)-engineered T cells combined with checkpoint inhibition may prevent T cell exhaustion and improve clinical outcomes. However, the approach is limited by cumulative costs and toxicities. METHODS: To overcome this drawback, we created a CAR-T (RB-340-1) that unites in one product the two modalities: a CRISPR interference-(CRISPRi) circuit prevents programmed cell death protein 1 (PD-1) expression upon antigen-encounter. RB-340-1 is engineered to express an anti-human epidermal growth factor receptor 2 (HER2) CAR single chain variable fragment (scFv), with CD28 and CD3ζ co-stimulatory domains linked to the tobacco etch virus (TEV) protease and a single guide RNA (sgRNA) targeting the PD-1 transcription start site (TSS). A second constructs includes linker for activation of T cells (LAT) fused to nuclease-deactivated spCas9 (dCas9)-Kruppel-associated box (KRAB) via a TEV-cleavable sequence (TCS). Upon antigen encounter, the LAT-dCas9-KRAB (LdCK) complex is cleaved by TEV allowing targeting of dCas9-KRAB to the PD-1 gene TSS. RESULTS: Here, we show that RB-340-1 consistently demonstrated higher production of homeostatic cytokines, enhanced expansion of CAR-T cells in vitro, prolonged in vivo persistence and more efficient suppression of HER2+ FaDu oropharyngeal cancer growth compared to the respective conventional CAR-T cell product. CONCLUSIONS: As the first application of CRISPRi toward a clinically relevant product, RB-340-1 with the conditional, non-gene editing and reversible suppression promotes CAR-T cells resilience to checkpoint inhibition, and their persistence and effectiveness against HER2-expressing cancer xenografts.

11.
BMC Oral Health ; 21(1): 604, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34814921

RESUMO

BACKGROUND: Earlier studies have not given clear results of concentrated growth factor (CGF) on gingival thickness (GT) in periodontal accelerated osteogenic orthodontics (PAOO). This randomized controlled trial aimed to evaluate the effects of CGF on GT in patients with thin gingival phenotype undergoing PAOO. METHODS: Forty four patients presenting 264 anterior mandibular teeth were recruited and randomly allocated to one of the groups: test-positioning of autologous CGF after PAOO or control-positioning of a collagen membrane after PAOO. GT, gingival height (GH), buccal alveolar bone thickness (BT), and buccal alveolar bone height (BH) were evaluated depending on cross-sectional CBCT images at t0 (before surgery) and t1(6 months after surgery). RESULTS: GT were increased in both groups at t1 compared to t0. Yet, higher values were observed in the test group (from 0.94 ± 0.23 to 1.31 ± 0.33 mm) compared to the control group (from 0.94 ± 0.19 to 1.02 ± 0.16 mm) (p < 0.05). Moreover, in the intergroup comparison, GT at t1 in the test group was significantly higher compared to the control group (p < 0.01). Furthermore, the GT of central incisors, lateral incisors and canine teeth all showed significantly changes compared with baseline and the test group showed higher increase (p < 0.01). No statistically significant difference were found in GH, BT, BH and all clinical parameters between two groups at t1 (p > 0.05). CONCLUSIONS: Within the limitation of this study, gingival thickness could be increased by using CGF in PAOO for the patients with thin gingival phenotype. Trial registration The study was registered in Chinese Clinical Trial Registry ( http://www.chictr.org.cn/index.aspx ) under the number ChiCTRINR17013346, Registered 11 November 2017.

12.
J Cardiol ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34750029

RESUMO

BACKGROUND: Cardiac sympathetic hyperinnervation after myocardial infarction (MI) is associated with a high incidence of lethal arrhythmia. Erythropoietin-producing hepatoma interactor B2 (EphrinB2), a diffusible axonal chemorepellent that can induce growth cone collapse and axon repulsion of several neuronal populations, is crucial in neurodevelopment during disease development and progression. However, whether EphrinB2 could inhibit cardiac sympathetic hyperinnervation after MI remains unclear. METHODS AND RESULTS: A rat model of MI was developed by left anterior descending coronary artery ligation. EphrinB2 expression was markedly increased in the infarcted border at 3 days after MI. Downregulation of EphrinB2 by intramyocardial injection of lentivirus carrying EphrinB2-shRNA significantly increased sympathetic hyperinnervation along with downregulated RhoA expression. In contrast, injection of EphrinB2-overexpressing lentivirus markedly upregulated EphrinB2, concomitant with inhibition of sympathetic sprouting and upregulated RhoA expression, accompanied by decreased incidence of ventricular arrhythmias (VAs). However, co-administering EphrinB2-overexpressing lentivirus and Fasudil (Rho kinase inhibitor) nearly abolished the inhibition of nerve sprouting effect. Additionally, EphrinB2 expression did not affect nerve growth factor level in the infarcted heart. CONCLUSIONS: Overexpression of EphrinB2 may ameliorate MI-induced sympathetic hyperinnervation and further reduce the incidence of VAs, at least in part by activating RhoA-mediated axonal retraction.

13.
IEEE Trans Med Imaging ; PP2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606452

RESUMO

In semi-supervised medical image segmentation, most previous works draw on the common assumption that higher entropy means higher uncertainty. In this paper, we investigate a novel method of estimating uncertainty. We observe that, when assigned different misclassification costs in a certain degree, if the segmentation result of a pixel becomes inconsistent, this pixel shows a relative uncertainty in its segmentation. Therefore, we present a new semi-supervised segmentation model, namely, conservative-radical network (CoraNet in short) based on our uncertainty estimation and separate self-training strategy. In particular, our CoraNet model consists of three major components: a conservative-radical module (CRM), a certain region segmentation network (C-SN), and an uncertain region segmentation network (UC-SN) that could be alternatively trained in an end-to-end manner. We have extensively evaluated our method on various segmentation tasks with publicly available benchmark datasets, including CT pancreas, MR endocardium, and MR multi-structures segmentation on the ACDC dataset. Compared with the current state of the art, our CoraNet has demonstrated superior performance. In addition, we have also analyzed its connection with and difference from conventional methods of uncertainty estimation in semi-supervised medical image segmentation.

14.
Ann Thorac Surg ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34624264

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) is a perioperative management protocol that aims to accelerate patient recovery. This study aimed to evaluate its benefits in patients with resectable esophageal cancer. METHODS: This retrospective study compared patients before (January 2013 to December 2016) and after (June 2018 to December 2020) ERAS protocol implementation in our hospital. A propensity score-matched (PSM) analysis was used to compare short-term surgical outcomes between ERAS and non-ERAS groups. After PSM, each group included 243 patients. RESULTS: There were significant differences in hospital length of stay after surgery (7.40 vs. 11.17 days, P<.001) and hospitalization cost (¥69380 vs. ¥78075, P<.001) between the ERAS and non-ERAS groups. The time to chest tube removal (4.91 vs. 7.16 days, P<.001) and first bowel movement (2.87 vs. 3.97 days, P<.001) was significantly shorter in the ERAS group. However, there was no significant difference in total postoperative complication morbidity (20.2% vs. 25.1%, P=0.193). The complication of postoperative atelectasis or pneumonia was significantly lower in the ERAS group (P=0.003), but there was no significant difference in occurrence of ≥Grade III complications between the two groups (12.3% vs. 11.5%, P=0.889). CONCLUSIONS: We demonstrated that ERAS could reduce the hospital stay, numerical pain scores, and hospitalization costs without increasing postoperative complication and readmission. Furthermore, subgroup analyses revealed that ERAS was safe for older people (>70 years old).

15.
Rev Sci Instrum ; 92(9): 094902, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598524

RESUMO

Vacuum leakage is extremely harmful to aircraft and needs to be discovered as soon as possible. Aiming at the problem of vacuum leakage location, this paper proposes a cross-correlation wavenumber domain imaging method. This method obtains the time-space domain information of the leakage elastic wave through the array sensor and transforms it into the frequency-wavenumber domain through the three-dimensional Fourier transform. The direction of the maximum value of the wavenumber vector represents the direction of the leakage source. In the algorithm, the cross-correlation operation is added, and the synchronous acquisition of multiple array elements is replaced by the polling scan method, which greatly improves the possibility of the realization of the algorithm. A 64-element ultrasonic sensor was fabricated and the method was verified. The results show that the method proposed in this paper can realize the continuous leakage signal direction of the planar structure and is applicable to the leakage holes of different apertures, and it has the potential for application on orbiting spacecraft and aircraft.

16.
Front Aging Neurosci ; 13: 717263, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504419

RESUMO

Shank3 is a postsynaptic scaffolding protein of excitatory synapses. Mutations or variations of SHANK3 are associated with various psychiatric and neurological disorders. We set to determine its normal expression pattern in the human brain, and its change, if any, with age and Alzheimer's disease (AD)-type ß-amyloid (Aß) and Tau pathogenesis. In general, Shank3 immunoreactivity (IR) exhibited largely a neuropil pattern with differential laminar/regional distribution across brain regions. In youth and adults, subsets of pyramidal/multipolar neurons in the cerebrum, striatum, and thalamus showed moderate IR, while some large-sized neurons in the brainstem and the granule cells in the cerebellar cortex exhibited light IR. In double immunofluorescence, Shank3 IR occurred at the sublemmal regions in neuronal somata and large dendrites, apposing to synaptophysin-labeled presynaptic terminals. In aged cases, immunolabeled neuronal somata were reduced, with disrupted neuropil labeling seen in the molecular layer of the dentate gyrus in AD cases. In immunoblot, levels of Shank3 protein were positively correlated with that of the postsynaptic density protein 95 (PSD95) among different brain regions. Levels of Shank3, PSD95, and synaptophysin immunoblotted in the prefrontal, precentral, and cerebellar cortical lysates were reduced in the aged and AD relative to youth and adult groups. Taken together, the differential Shank3 expression among brain structures/regions indicates the varied local density of the excitatory synapses. The enriched Shank3 expression in the forebrain subregions appears inconsistent with a role of this protein in the modulation of high cognitive functions. The decline of its expression in aged and AD brains may relate to the degeneration of excitatory synapses.

17.
J Neurosci Res ; 99(11): 3035-3046, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34498762

RESUMO

Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy, presenting both structural and metabolic abnormalities in the ipsilateral mesial temporal lobe. While it has been demonstrated that the metabolic abnormalities in MTLE actually extend beyond the epileptogenic zone, how such multidimensional information is associated with the diagnosis of MTLE remains to be tested. Here, we explore the whole-brain metabolic patterns in 23 patients with MTLE and 24 healthy controls using [18 F]fluorodeoxyglucose PET imaging. Based on a multivariate machine learning approach, we demonstrate that the brain metabolic patterns can discriminate patients with MTLE from controls with a superior accuracy (>95%). Importantly, voxels showing the most extreme contributing weights to the classification (i.e., the most important regional predictors) distribute across both hemispheres, involving both ipsilateral negative weights over the anterior part of lateral and medial temporal lobe, posterior insula, and lateral orbital frontal gyrus, and contralateral positive weights over the anterior frontal lobe, temporal lobe, and lingual gyrus. Through region-of-interest analyses, we verify that in patients with MTLE, the negatively weighted regions are hypometabolic, and the positively weighted regions are hypermetabolic, compared to controls. Interestingly, despite that both hypo- and hypermetabolism have mutually contributed to our model, they may reflect different pathological and/or compensative responses. For instance, patients with earlier age at epilepsy onset present greater hypometabolism in the ipsilateral inferior temporal gyrus, while we find no evidence of such association with hypermetabolism. In summary, quantitative models utilizing multidimensional brain metabolic information may provide additional assistance to presurgical workups in TLE.

18.
Elife ; 102021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499031

RESUMO

The type V-A Cas12a protein can process its CRISPR array, a feature useful for multiplexed gene editing and regulation. However, CRISPR arrays often exhibit unpredictable performance due to interference between multiple guide RNA (gRNAs). Here, we report that Cas12a array performance is hypersensitive to the GC content of gRNA spacers, as high-GC spacers can impair activity of the downstream gRNA. We analyze naturally occurring CRISPR arrays and observe that natural repeats always contain an AT-rich fragment that separates gRNAs, which we term a CRISPR separator. Inspired by this observation, we design short, AT-rich synthetic separators (synSeparators) that successfully remove the disruptive effects between gRNAs. We further demonstrate enhanced simultaneous activation of seven endogenous genes in human cells using an array containing the synSeparator. These results elucidate a previously underexplored feature of natural CRISPR arrays and demonstrate how nature-inspired engineering solutions can improve multi-gene control in mammalian cells.


Assuntos
Proteínas de Bactérias/genética , Proteínas Associadas a CRISPR/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Endodesoxirribonucleases/genética , Regulação da Expressão Gênica , Proteínas de Fluorescência Verde/genética , Células HEK293 , Humanos , Óperon , RNA Guia/genética
19.
Micromachines (Basel) ; 12(9)2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34577777

RESUMO

In this paper, we design and optimize a low-cost, closed-film structure of a microelectromechanical systems (MEMS) thermopile infrared detector. By optimizing the circular arrangement of thermocouple strips and the thermal isolation design of the cold end to pursue a higher temperature difference, in addition to eliminating the absorption region, silicon nitride is deposited on the whole device surface as a passivated absorption layer. This reduces the cost while maintaining the voltage response and is suitable for mass production. The optimized detector had a 22.6% improvement in the response rate to 34.2 V/W, a detection rate of 1.02 × 108 cm·Hz1/2/W, and a response time of 26.9 ms. The design optimization of this detector provides a reference for further development of IR detectors.

20.
Mol Cell ; 81(20): 4333-4345.e4, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34480847

RESUMO

Compact and versatile CRISPR-Cas systems will enable genome engineering applications through high-efficiency delivery in a wide variety of contexts. Here, we create an efficient miniature Cas system (CasMINI) engineered from the type V-F Cas12f (Cas14) system by guide RNA and protein engineering, which is less than half the size of currently used CRISPR systems (Cas9 or Cas12a). We demonstrate that CasMINI can drive high levels of gene activation (up to thousands-fold increases), while the natural Cas12f system fails to function in mammalian cells. We show that the CasMINI system has comparable activities to Cas12a for gene activation, is highly specific, and allows robust base editing and gene editing. We expect that CasMINI can be broadly useful for cell engineering and gene therapy applications ex vivo and in vivo.

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