Mnemonic But Not Contextual Feedback Signals Defy Dedifferentiation in the Aging Early Visual Cortex.

Perception is an intricate interplay between feedforward visual input and internally generated feedback signals that comprise concurrent contextual and time-distant mnemonic (episodic and semantic) information. Yet, an unresolved question is how the composition of feedback signals changes across the lifespan and to what extent feedback signals undergo age-related dedifferentiation, that is, a decline in neural specificity. Previous research on this topic has focused on feedforward perceptual representation and episodic memory reinstatement, suggesting reduced fidelity of neural representations at the item and category levels. In this fMRI study, we combined an occlusion paradigm that filters feedforward input to the visual cortex and multivariate analysis techniques to investigate the information content in cortical feedback, focusing on age-related differences in its composition. We further asked to what extent differentiation in feedback signals (in the occluded region) is correlated to differentiation in feedforward signals. Comparing younger (18-30 years) and older female and male adults (65-75 years), we found that contextual but not mnemonic feedback was prone to age-related dedifferentiation. Semantic feedback signals were even better differentiated in older adults, highlighting the growing importance of generalized knowledge across ages. We also found that differentiation in feedforward signals was correlated with differentiation in episodic but not semantic feedback signals. Our results provide evidence for age-related adjustments in the composition of feedback signals and underscore the importance of examining dedifferentiation in aging for both feedforward and feedback processing.

Performance of ChatGPT on the Taiwan urology board examination: insights into current strengths and shortcomings.

PURPOSE: To compare ChatGPT-4 and ChatGPT-3.5's performance on Taiwan urology board examination (TUBE), focusing on answer accuracy, explanation consistency, and uncertainty management tactics to minimize score penalties from incorrect responses across 12 urology domains. METHODS: 450 multiple-choice questions from TUBE(2020-2022) were presented to two models. Three urologists assessed correctness and consistency of each response. Accuracy quantifies correct answers; consistency assesses logic and coherence in explanations out of total responses, alongside a penalty reduction experiment with prompt variations. Univariate logistic regression was applied for subgroup comparison. RESULTS: ChatGPT-4 showed strengths in urology, achieved an overall accuracy of 57.8%, with annual accuracies of 64.7% (2020), 58.0% (2021), and 50.7% (2022), significantly surpassing ChatGPT-3.5 (33.8%, OR = 2.68, 95% CI [2.05-3.52]). It could have passed the TUBE written exams if solely based on accuracy but failed in the final score due to penalties. ChatGPT-4 displayed a declining accuracy trend over time. Variability in accuracy across 12 urological domains was noted, with more frequently updated knowledge domains showing lower accuracy (53.2% vs. 62.2%, OR = 0.69, p = 0.05). A high consistency rate of 91.6% in explanations across all domains indicates reliable delivery of coherent and logical information. The simple prompt outperformed strategy-based prompts in accuracy (60% vs. 40%, p = 0.016), highlighting ChatGPT's limitations in its inability to accurately self-assess uncertainty and a tendency towards overconfidence, which may hinder medical decision-making. CONCLUSIONS: ChatGPT-4's high accuracy and consistent explanations in urology board examination demonstrate its potential in medical information processing. However, its limitations in self-assessment and overconfidence necessitate caution in its application, especially for inexperienced users. These insights call for ongoing advancements of urology-specific AI tools.

Focal ischemic myocardial fibrosis assessed by late gadolinium enhancement cardiovascular magnetic resonance in patients with hypertrophic cardiomyopathy.

BACKGROUND: In patients with hypertrophic cardiomyopathy (HCM), ischemic myocardial fibrosis assessed by late gadolinium enhancement (I-LGE) using cardiovascular magnetic resonance (CMR) have been reported. However, the clinical significance of I-LGE has not been completely understood. We aim to evaluate the I-LGE differ phenotypically from HCM without LGE or nonischemic myocardial fibrosis assessed by late gadolinium enhancement (NI-LGE) in the left ventricle (LV). METHODS: The patients with HCM whom was underwent CMR were enrolled, using cine cardiac magnetic resonance to evaluate LV function and LGE to detect the myocardial fibrosis. Three groups were assorted: 1) HCM without LGE; 2) HCM with LGE involved the subendocardial layer was defined as I-LGE; 3) HCM with LGE not involved the subendocardial layer was defined as NI-LGE. RESULTS: We enrolled 122 patients with HCM in the present study. LGE was detected in 58 of 122 (48%) patients with HCM, and 22 (18%) of patients reported I-LGE. HCM with I-LGE had increased higher left ventricular mass index (LVMI) (P < 0.0001) than HCM with NI-LGE or without LGE. In addition, HCM with I-LGE had a larger LV end- systolic volume (P = 0.045), lower LV ejection fraction (LVEF) (P = 0.026), higher LV myocardial mass (P < 0.001) and thicker LV wall (P < 0.001) more than HCM without LGE alone. The I-LGE were significantly associated with LVEF (OR: 0.961; P = 0.016), LV mass (OR: 1.028; P < 0.001), and maximal end-diastolic LVWT (OR: 1.567; P < 0.001). On multivariate analysis, LVEF (OR: 0.948; P = 0.013) and maximal end-diastolic LVWT (OR: 1.548; P = 0.001) were associated with higher risk for I-LGE compared to HCM without LGE. Noticeably, the maximal end-diastolic LVWT (OR: 1.316; P = 0.011) was the only associated with NI-LGE compared to HCM without LGE. CONCLUSIONS: I-LGE is not uncommon in patients with HCM. HCM with I-LGE was associated with significant LV hypertrophy, extensive LGE and poor LV ejection fraction. We should consider focal ischemic myocardial fibrosis when applying LGE to risk stratification for HCM.

Discovery of Oxidized p-Terphenyls as Phosphodiesterase 4 Inhibitors from Marine-Derived Fungi.

Four new p-terphenyl derivatives, talaroterphenyls A-D (1-4), together with three biosynthetically related known ones (5-7), were obtained from the mangrove sediment-derived Talaromyces sp. SCSIO 41412. Compounds 1-3 are rare p-terphenyls, which are completely substituted on the central benzene ring by oxygen atoms; this is the first report of their isolation from natural sources. Their structures were elucidated through NMR spectroscopy, HRESIMS, and X-ray diffraction. Genome sequence analysis revealed that 1-7 were biosynthesized from tyrosine and phenylalanine, involving four key biosynthetic genes (ttpB-ttpE). These p-terphenyls (1-7) and 36 marine-derived terphenyl analogues (8-43) were screened for phosphodiesterase 4 (PDE4) inhibitory activities, and 1-5, 14, 17, 23, and 26 showed notable activities with IC50 values of 0.40-16 µM. The binding pattern of p-terphenyl inhibitors 1-3 with PDE4 were explored by molecular docking analysis. Talaroterphenyl A (1), with a low cytotoxicity, showed obvious anti-inflammatory activity in LPS-stimulated RAW264.7 cells. Furthermore, in the TGF-ß1-induced medical research council cell strain-5 (MRC-5) pulmonary fibrosis model, 1 could down-regulate the expression levels of FN1, COL1, and α-SMA significantly at concentrations of 5-20 µM. This study suggests that the oxidized p-terphenyl 1, as a marine-derived PDE4 inhibitor, could be used as a promising antifibrotic agent.

Structural optimization of Moracin M as novel selective phosphodiesterase 4 inhibitors for the treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and high mortality lung disease. Although the antifibrotic drugs pirfenidone and nintedanib could slow the rate of lung function decline, the usual course of the condition is inexorably to respiratory failure and death. Therefore, new approaches and novel therapeutic drugs for the treatment of IPF are urgently needed. And the selective PDE4 inhibitor has in vivo and in vitro anti-fibrotic effects in IPF models. But the clinical application of most PDE4 inhibitors are limited by their unexpected and severe side effects such as nausea, vomiting, and diarrhea. Herein, structure-based optimizations of the natural product Moracin M resulted in a novel a novel series of 2-arylbenzofurans as potent PDE4 inhibitors. The most potent inhibitor L13 has an IC50 of 36 ± 7 nM with remarkable selectivity across the PDE families and administration of L13·citrate (10.0 mg/kg) exhibited comparable anti-pulmonary fibrosis effects to pirfenidone (300 mg/kg) in a bleomycin-induced IPF mice model, indicate that L13 is a potential lead for the treatment of IPF.

[Construction of the Whole Process Management Model of Hospice and Palliative Care Outpatient Clinic].

Objective To construct a scientific and practical management model of the hospice and palliative care outpatient clinic and provide a reference for the operation and development of the outpatient clinic. Methods The basic framework of the whole process management model of hospice and palliative care outpatient clinic was determined preliminarily by literature analysis,qualitative interviews and experts group meetings.Two rounds of consultation were conducted among 18 experts in hospice and palliative care and medical-nursing combined outpatient service by the Delphi method. Results The questionnaire response rates of the two rounds of expert consultation were both 100% and the authority coefficients of the two rounds of expert consultation were 0.88 and 0.91,respectively.Finally,the whole process management model of hospice and palliative care outpatient clinic was constructed,which was composed of three first-level indicators including staff composition,work structure and effect evaluation,5 second-level indicators and 62 third-level indicators. Conclusion The constructed whole process management model is scientific,innovative and continuous,which can provide a reference for the operation and development of the hospice and palliative care outpatient clinic.

Correlation between ARID1B gene mutation (p.A460, p.V215G) and prognosis of high-risk refractory neuroblastoma.

In a few reports, ARID1B/A mutation was found in neuroblastoma. We analyzed the clinical characteristics, clinical efficacy, and prognosis of three children with high-risk refractory neuroblastoma (NB) with somatic ARID1B gene mutation. The whole exon sequencing results showed that there were involved in transcription, DNA synthesis, and repair of ARID1B gene mutations. All mutation sites were located in the promoter region of the exon: ARID1B (p.A460) mutation was found in cases 1 and 2, and ARID1B (p.V215G) mutation was found in cases 1 and 3. The nucleic acid site of ARID1B (p.A460) mutation was c.1379 (exon1) C > G, and the nucleic acid site of ARID1B (p.V215G) mutation was c.644 (exon1) T > G. The meningeal metastasis in case 1 turned negative after 4 cycles of intrathecal injection combined with chemotherapy. However, the child died of agranulocytosis combined with sepsis during the 5th cycle of chemotherapy. Case 2 achieved complete remission (CR). Case 3 achieved CR after chemotherapy, surgery, metaiodobenzylguanidine, and 3F-8 (Naxitamab) immunotherapy after the initial diagnosis. The mediastinum and lymph node metastasis occurred during the 6-month observation period after stopping treatment. He achieved very good partial remission after individualized chemotherapy and surgical treatment. ARID1B is a component protein of the SWI/SNF chromatin-remodeling complex that participates in the occurrence of a variety of tumors by regulating DNA repair and synthesis. ARID1B nucleic acid mutation (p.A460, p.V215G) in the promoter region of three children may contribute to the poor prognosis of NB children.

Bioactive Polyketides and Benzene Derivatives from Two Mangrove Sediment-Derived Fungi in the Beibu Gulf.

To discover bioactive natural products from mangrove sediment-derived microbes, a chemical investigation of the two Beibu Gulf-derived fungi strains, Talaromyces sp. SCSIO 41050 and Penicillium sp. SCSIO 41411, led to the isolation of 23 natural products. Five of them were identified as new ones, including two polyketide derivatives with unusual acid anhydride moieties named cordyanhydride A ethyl ester (1) and maleicanhydridane (4), and three hydroxyphenylacetic acid derivatives named stachylines H-J (10-12). Their structures were determined by detailed nuclear magnetic resonance (NMR) and mass spectroscopic (MS) analyses, while the absolute configurations were established by theoretical electronic circular dichroism (ECD) calculation. A variety of bioactive screens revealed three polyketide derivatives (1-3) with obvious antifungal activities, and 4 displayed moderate cytotoxicity against cell lines A549 and WPMY-1. Compounds 1 and 6 at 10 µM exhibited obvious inhibition against phosphodiesterase 4 (PDE4) with inhibitory ratios of 49.7% and 39.6%, respectively, while 5, 10, and 11 showed the potential of inhibiting acetylcholinesterase (AChE) by an enzyme activity test, as well as in silico docking analysis.

Identify potent SARS-CoV-2 main protease inhibitors via accelerated free energy perturbation-based virtual screening of existing drugs.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global crisis. There is no therapeutic treatment specific for COVID-19. It is highly desirable to identify potential antiviral agents against SARS-CoV-2 from existing drugs available for other diseases and thus repurpose them for treatment of COVID-19. In general, a drug repurposing effort for treatment of a new disease, such as COVID-19, usually starts from a virtual screening of existing drugs, followed by experimental validation, but the actual hit rate is generally rather low with traditional computational methods. Here we report a virtual screening approach with accelerated free energy perturbation-based absolute binding free energy (FEP-ABFE) predictions and its use in identifying drugs targeting SARS-CoV-2 main protease (Mpro). The accurate FEP-ABFE predictions were based on the use of a restraint energy distribution (RED) function, making the practical FEP-ABFE-based virtual screening of the existing drug library possible. As a result, out of 25 drugs predicted, 15 were confirmed as potent inhibitors of SARS-CoV-2 Mpro The most potent one is dipyridamole (inhibitory constant Ki = 0.04 µM) which has shown promising therapeutic effects in subsequently conducted clinical studies for treatment of patients with COVID-19. Additionally, hydroxychloroquine (Ki = 0.36 µM) and chloroquine (Ki = 0.56 µM) were also found to potently inhibit SARS-CoV-2 Mpro We anticipate that the FEP-ABFE prediction-based virtual screening approach will be useful in many other drug repurposing or discovery efforts.

Comparison of Trends in the Incidence of Traumatic Spinal Cord Injury in Daily Life, Automobile Accidents, and Industrial Accidents: A National Multi-Insurance Study in Korea.

BACKGROUND: To examine the incidence of traumatic spinal cord injury (TSCI) from all etiologies, we measured and compared the incidence of TSCI from three national or quasi-national databases in South Korea, namely, the National Health Insurance Service (NHIS), automobile insurance (AUI), and Industrial Accident Compensation Insurance (IACI). METHODS: We reviewed patients with TSCI reported in the NHIS database between 2009 and 2018, and in the AUI and IACI databases between 2014 and 2018. TSCI patients were defined as those first admitted to the hospital with a diagnosis of TSCI according to the International Classification of Diseases (10th revision) criteria. Age-adjusted incidence was calculated using direct standardization using the 2005 South Korean population or the 2000 US population as the standard population. The annual percentage changes (APC) of TSCI incidence were calculated. The Cochrane-Armitage trend test was performed according to the injured body region. RESULTS: In the NHIS database, age-adjusted TSCI incidence using the Korean standard population increased significantly from 2009 to 2018 (from 33.73 per million in 2009 to 38.14 per million in 2018, APC = 1.2%, P = 0.014). Contrarily, age-adjusted incidence in the AUI database significantly decreased from 13.88 per million in 2014 to 11.57 per million in 2018 (APC = - 5.1%, P = 0.009). In the IACI database, the age-adjusted incidence showed no significant difference, while crude incidence showed a significant increase (from 22.02 per million in 2014 to 28.92 per million in 2018, APC = 6.1%, P = 0.038). According to the age group, all the three databases showed high incidences of TSCI in those in their 60s and 70s or older. Among those in their 70s or older, the incidence of TSCI increased dramatically in the NHIS and IACI databases, while no significant trend was found in AUI database. In 2018, the number of TSCI patients was the highest among those over 70 years of age in the NHIS, whereas among those in their 50s were the highest in both AUI and IACI. The proportion of patients with cervical spinal cord injury was the most common in all these databases. CONCLUSIONS: The differences in trends in the incidence of TSCI may be due to the different etiologies and different characteristics of subjects depending on insurance type. These results imply the need for tailored medical strategies for the different injury mechanisms represented by three national insurance services in South Korea.

METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis.

BACKGROUND: N6-methyladenosine (m6A) RNA methylation and circular RNAs (circRNAs) have been shown to act vital roles in multiple malignancies including gastric cancer (GC). However, there is little knowledge about how m6A modification of circRNAs contributes to GC progression. METHODS: The association of METTL14 expression with the clinicopathological characteristics and prognosis in patients with GC was assessed by Western blot, Immunohistochemistry and public datasets. In vitro and vivo function experiments were conducted to investigate the role of METTL14 in GC. Furthermore, m6A-circRNA epitranscriptomic microarray was utilized to identify METTL14-mediated m6A modification of circRNAs, which were validated by methylated RNA immunoprecipitation (Me-RIP), RT-qPCR and rescue experiments in GC cells. The sponge of circORC5 with miR-30c-2-3p was confirmed by luciferase gene report and RNA immunoprecipitation assays. The expression, localization and prognosis of circORC5 in GC were evaluated by fluorescence in situ hybridization. The effects of METTL14 and (or) circORC5 on miR-30c-2-3p-mediated AKT1S1 and EIF4B were estimated by RT-qPCR and Western blot analyses. RESULTS: We found that METTL14 was downregulated in GC tissue samples and its low expression acted as a prognostic factor of poor survival in patients with GC. Ectopic expression of METTL14 markedly repressed growth and invasion of GC cells in vitro and in vivo, whereas knockdown of METTL14 harbored the opposite effects. Mechanically, m6A-circRNA epitranscriptomic microarray and Me-RIP identified circORC5 as the downstream target of METTL14. Silencing of METTL14 reduced the m6A level of circORC5, but increased circORC5 expression. Moreover, circORC5 could sponge miR-30c-2-3p, and reverse METTL14-caused upregulation of miR-30c-2-3p and downregulation of AKT1S1 and EIF4B. In addition, circORC5 possessed a negative correlation with miR-30c-2-3p and indicated a poor survival in GC. CONCLUSION: Our findings demonstrate that METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis.

Alterations in the saliva microbiome in patients with gastritis and small bowel inflammation.

The oral microbiome is an important part of the human microbiome. Accumulating data have shown that oral microbiome alterations are closely related to multiple human diseases. However, salivary microbiota distributions remain unclear in patients with gastritis and small bowel inflammation. Magnetically guided capsule endoscopy (MGCE) is a noninvasive diagnostic tool for patients with gastritis and small bowel inflammation. Herein, we analysed the alterations in saliva microbiota in the normal, small intestinal inflammation and chronic gastritis groups through 16S rRNA gene amplicon sequencing. We found that the abundance of Lactobacillaceae was dramatically higher in chronic gastritis group than healthy individuals (p = 0.001). The levels of Porphyromonas and Faecalibaculum in gastritis samples were increased (p = 0.028; p = 0.006), and the enrichments of Faecalibaculum and Kosakonia in small intestine inflammation samples were elevated (p < 0.001; p = 0.002) compared to those in normal individuals. Our findings clarify the saliva microbiota components and their importance of specific bacteria in gastritis and small bowel inflammation.

Finite element analysis after rod fracture of the spinal hybrid elastic rod system.

BACKGROUND: The spinal hybrid elastic (SHE) rod dynamic stabilization system can provide sufficient spine support and less adjacent segment stress. This study aimed to investigate the biomechanical effects after the internal fracture of SHE rods using finite element analysis. METHODS: A three-dimensional nonlinear finite element model was developed. The SHE rod comprises an inner nitinol stick (NS) and an outer polycarbonate urethane (PCU) shell (PS). The fracture was set at the caudal third portion of the NS, where the maximum stress occurred. The resultant intervertebral range of motion (ROM), intervertebral disc stress, facet joint contact force, screw stress, NS stress, and PCU stress were analyzed. RESULTS: When compared with the intact spine model, the overall trend was that the ROM, intervertebral disc stress, and facet joint force decreased in the implanted level and increased in the adjacent level. When compared with the Ns-I, the trend in the Ns-F decreased and remained nearly half effect. Except for torsion, the PS stress of the Ns-F increased because of the sharing of NS stress after the NS fracture. CONCLUSIONS: The study concluded the biomechanical effects still afford nearly sufficient spine support and gentle adjacent segment stress after rod fracture in a worst-case scenario of the thinnest PS of the SHE rod system.

Varifocal Metalens for Optical Sectioning Fluorescence Microscopy.

Fluorescence microscopy with optical sectioning capabilities is extensively utilized in biological research to obtain three-dimensional structural images of volumetric samples. Tunable lenses have been applied in microscopy for axial scanning to acquire multiplane images. However, images acquired by conventional tunable lenses suffer from spherical aberration and distortions. Here, we design, fabricate, and implement a dielectric Moiré metalens for fluorescence imaging. The Moiré metalens consists of two complementary phase metasurfaces, with variable focal length, ranging from ∼10 to ∼125 mm at 532 nm by tuning mutual angles. In addition, a telecentric configuration using the Moiré metalens is designed for high-contrast multiplane fluorescence imaging. The performance of our system is evaluated by optically sectioned images obtained from HiLo illumination of fluorescently labeled beads, as well as ex vivo mice intestine tissue samples. The compact design of the varifocal metalens may find important applications in fluorescence microscopy and endoscopy for clinical purposes.

Therapeutic targets and potential agents for the treatment of COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a global crisis. As of November 9, COVID-19 has already spread to more than 190 countries with 50,000,000 infections and 1,250,000 deaths. Effective therapeutics and drugs are in high demand. The structure of SARS-CoV-2 is highly conserved with those of SARS-CoV and Middle East respiratory syndrome-CoV. Enzymes, including RdRp, Mpro /3CLpro , and PLpro , which play important roles in viral transcription and replication, have been regarded as key targets for therapies against coronaviruses, including SARS-CoV-2. The identification of readily available drugs for repositioning in COVID-19 therapy is a relatively rapid approach for clinical treatment, and a series of approved or candidate drugs have been proven to be efficient against COVID-19 in preclinical or clinical studies. This review summarizes recent progress in the development of drugs against SARS-CoV-2 and the targets involved.

Clinical features and imaging manifestations of retinoblastoma with hepatic metastasis.

Clinical data of five patients with hepatic metastases of retinoblastoma were analyzed retrospectively (two had bilateral tumors three had unilateral intraocular tumors). On computed tomography, multiple and single low-density foci were observed. Four patients had tumor remission, and one showed no response after chemotherapy. Three patients who underwent enucleation were at high risk for extensive choroidal invasion. Central nervous system and bone metastases occurred in all five patients. Neuron-specific enolase and lactate dehydrogenase levels were significantly elevated in all patients. Two patients died (not from hepatic metastasis). Three patients (one with tumor progression and two with shorter courses) are continuing treatment.

Reliability and Validity of the Eating and Drinking Ability Classification System in Adults with Cerebral Palsy.

The Eating and Drinking Ability Classification System (EDACS) was developed to evaluate dysphagia in children with cerebral palsy (CP). This study aimed to investigate the interrater reliability and validity of the EDACS in adults with CP. This cross-sectional study included 117 community-dwelling adults (mean age, 37.9 ± 12.5 years) with a confirmed CP diagnosis. A swallowing occupational therapist (SwOT) conducted detailed interviews with participants and/or caregivers to classify the EDACS. Another SwOT and participants/caregivers evaluated the EDACS. Correlations were evaluated between the EDACS and Functional Oral Intake Scale (FOIS), Swallowing Quality of Life (SWAL-QOL), Gross Motor Function Classification System (GMFCS), and Manual Ability Classification System (MACS). Interrater reliabilities between SwOTs (κ = 0.866, intraclass correlation coefficient (ICC) = 0.867), and between SwOT and participant/caregiver (κ = 0.884, ICC = 0.717) were reported. The EDACS correlated with the FOIS, SWAL-QOL, and MACS, although no significant correlation was found with the GMFCS. The EDACS of spastic-type showed better correlation than that of dyskinetic-type with the FOIS, MACS, and GMFCS. There was a significant correlation between the EDACS and the GMFCS in those aged ≤ 30 years, whereas there was no correlation in those aged ≥ 30 years. The EDACS is a reliable and valid tool for classifying eating and drinking ability in adults with CP. The correlation between the EDACS with gait or hand function was more prominent in individuals with spastic CP and in younger individuals. The EDACS is a valuable adjunct to comprehensive functional classification in adults with CP.

Novel insights into the interplay between m6A modification and noncoding RNAs in cancer.

N6-methyladenosine (m6A) is one of the most common RNA modifications in eukaryotes, mainly in messenger RNA (mRNA). Increasing evidence shows that m6A methylation modification acts an essential role in various physiological and pathological bioprocesses. Noncoding RNAs (ncRNAs), including miRNAs, lncRNAs and circRNAs, are known to participate in regulating cell differentiation, angiogenesis, immune response, inflammatory response and carcinogenesis. m6A regulators, such as METTL3, ALKBH5 and IGF2BP1 have been reported to execute a m6A-dependent modification of ncRNAs involved in carcinogenesis. Meanwhile, ncRNAs can target or modulate m6A regulators to influence cancer development. In this review, we provide an insight into the interplay between m6A modification and ncRNAs in cancer.

Simultaneous multi-color optical sectioning fluorescence microscopy with wavelength-coded volume holographic gratings.

Optical sectioning fluorescence microscopy provides high contrast images of volumetric samples and has been widely used for many biological applications. However, simultaneously acquiring multi-color fluorescence images require additional optical elements and devices, which are bulky, wavelength specific, and not cost-effective. In this paper, wavelength-coded volume holographic gratings (WC-VHGs) based optical sectioning fluorescence microscopy is proposed to simultaneously offer multi-color fluorescence images with fine out-of-focus background rejection. Due to wavelength degeneracy, multiplexed WC-VHGs are capable of acquiring multi-wavelength fluorescence images in a single shot, and displaying the laterally separated multi-wavelength images onto CCD. In our system optical sectioning capability is achieved through speckle illumination and HiLo imaging method. To demonstrate imaging characteristics of our system, dual-wavelength fluorescence images of both standard fluorescent microspheres and ex vivo mT/mG mice cardiac tissue are presented. Current results may find important applications in hyperspectral imaging for biomedical research.

The use of micro-needle arrays to deliver cells for cellular therapies.

Cell therapy is used to treat various diseases and to repair injuries. Cell delivery is a crucial process that delivers cells to target sites. Cells must be precisely delivered to a target site and the cells that are delivered must be localized to the target site to repair damaged tissue. For stem cell therapy, the most convenient method of cell delivery involves directly injecting cells into damaged tissue. Other strategies use carriers to transplant stem cells into damaged tissue. These are termed, stem cell delivery systems (SCDSs). Micro-needle arrays are minimally invasive transdermal delivery systems. The devices can pass through the stratum corneum barrier and deliver macromolecules into the skin. They can also access the microcirculation system in the skin. This study fabricates PMMA micro-needle using a two-stage micro-molding method. Cells are seeded on the micro-needle arrays and then transferred into the target tissue. Collagen hydrogel is used as a model biomimetic tissue. Cells are efficiently delivered to regions of interest, collagen hydrogel, by using this system. The delivery rate is about 83.2%. This demonstrates that micro-needle arrays allow very efficient delivery of cells.