Analysis of Factors and T-Lymphocyte Subset Changes in Pediatric Recurrent Respiratory Infections Post-Pidotimod Treatment.

Objective: This study aims to analyze factors contributing to recurrent respiratory tract infections (RRTIs) in pediatric patients and evaluate the efficacy of pidotimod (PI) treatment. Methods: This study utilized a retrospective cohort design, enrolling a total of 85 children diagnosed with RRTIs between September 2020 and September 2022, alongside 54 healthy children. Logistic regression analysis was employed to identify factors contributing to RRTI occurrence. Among the participants, 40 children underwent conventional treatment (control group), while 45 received PI treatment (research group). Comparative analyses were conducted to assess clinical efficacy and adverse effects between the two treatment groups. Results: The history of family members' smoking and parental allergy emerged as independent risk factors for RRTIs (P < .05, OR>1), whereas parental education level, outdoor activity, and micronutrient intake were identified as independent protective factors for RRTIs (P < .05, OR<1). Symptoms such as cough, fever, rhonchi, moist rales, and tonsillar enlargement resolved significantly faster in the research group compared to the control group (P < .05). Additionally, the research group exhibited reduced infection duration and fewer recurrent infections (P < .05). Following treatment, the overall treatment efficacy was superior in the research group compared to the control group (P < .05), with no significant difference in the incidence of adverse effects (P > .05). Post-treatment, levels of CD3+, CD4+, and CD4+/CD8+ were elevated in the research group compared to the control group, while CD8+ levels were lower (P < .05). Conclusions: Daily outdoor activity among children, family members' history of smoking, parental allergy history, education level, and micronutrient intake emerged as independent factors influencing pediatric RRTIs. Furthermore, PI was identified as a significant treatment option for RRTIs.

Excessive iron deposition in root apoplast is involved in growth arrest of roots in response to proton stress.

The rhizotoxicity of protons (H+) in acidic soils is a fundamental constraint that results in serious yield losses. However, the mechanisms underlying H+-mediated inhibition of root growth are poorly understood. In this study, we revealed that H+-induced root growth inhibition depends considerably on excessive iron deposition in root apoplasts. Reducing such aberrant iron deposition by decreasing the iron supply or disrupting the ferroxidases LOW PHOSPHATE ROOT 1 (LPR1) and LOW PHOSPHATE ROOT 2 (LPR2) attenuates the inhibitory effect of H+ on primary root growth efficiently. Further analysis showed that excessive iron deposition triggers a burst of highly reactive oxygen species, consequently impairing normal root development. Our study uncovered a valuable strategy for improving the ability of plants to tolerate H+ toxicity by manipulating iron availability.

In vitro and in vivo Biological Evaluation of Newly Tacrine-Selegiline Hybrids as Multi-Target Inhibitors of Cholinesterases and Monoamine Oxidases for Alzheimer's Disease.

Purpose: Alzheimer's disease (AD) is the most common neurodegenerative disease, and its multifactorial nature increases the difficulty of medical research. To explore an effective treatment for AD, a series of novel tacrine-selegiline hybrids with ChEs and MAOs inhibitory activities were designed and synthesized as multifunctional drugs. Methods: All designed compounds were evaluated in vitro for their inhibition of cholinesterases (AChE/BuChE) and monoamine oxidases (MAO-A/B) along with their blood-brain barrier permeability. Then, further biological activities of the optimizing compound 7d were determined, including molecular model analysis, in vitro cytotoxicity, acute toxicity studies in vivo, and pharmacokinetic and pharmacodynamic property studies in vivo. Results: Most synthesized compounds demonstrated potent inhibitory activity against ChEs/MAOs. Particularly, compound 7d exhibited good and well-balanced activity against ChEs (hAChE: IC50 = 1.57 µM, hBuChE: IC50 = 0.43 µM) and MAOs (hMAO-A: IC50 = 2.30 µM, hMAO-B: IC50 = 4.75 µM). Molecular modeling analysis demonstrated that 7d could interact simultaneously with both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE in a mixed-type manner and also exhibits binding affinity towards BuChE and MAO-B. Additionally, 7d displayed excellent permeability of the blood-brain barrier, and under the experimental conditions, it elicited low or no toxicity toward PC12 and BV-2 cells. Furthermore, 7d was not acutely toxic in mice at doses up to 2500 mg/kg and could improve the cognitive function of mice with scopolamine-induced memory impairment. Lastly, 7d possessed well pharmacokinetic characteristics. Conclusion: In light of these results, it is clear that 7d could potentially serve as a promising multi-functional drug for the treatment of AD.

Nanotrap Grafted Anionic MOF for Superior Uranium Extraction from Seawater.

On-demand uranium extraction from seawater (UES) can mitigate growing sustainable energy needs, while high salinity and low concentration hinder its recovery. A novel anionic metal-organic framework (iMOF-1A) is demonstrated adorned with rare Lewis basic pyrazinic sites as uranyl-specific nanotrap serving as robust ion exchange material for selective uranium extraction, rendering its intrinsic ionic characteristics to minimize leaching. Ionic adsorbents sequestrate 99.8% of the uranium in 120 mins (from 20,000 ppb to 24 ppb) and adsorb large amounts of 1336.8 mg g-1 and 625.6 mg g-1 from uranium-spiked deionized water and artificial seawater, respectively, with high distribution coefficient, Kd U ≥ 0.97 × 106  mL g-1 . The material offers a very high enrichment index of ≈5754 and it achieves the UES standard of 6.0 mg g-1 in 16 days, and harvests 9.42 mg g-1 in 30 days from natural seawater. Isothermal titration calorimetry (ITC) studies quantify thermodynamic parameters, previously uncharted in uranium sorption experiments. Infrared nearfield nanospectroscopy (nano-FTIR) and tip-force microscopy (TFM) enable chemical and mechanical elucidation of host-guest interaction at atomic level in sub-micron crystals revealing extant capture events throughout the crystal rather than surface solely. Comprehensive experimentally guided computational studies reveal ultrahigh-selectivity for uranium from seawater, marking mechanistic insight.

Unlocking Diabetic Acetone Vapor Detection by A Portable Metal-Organic Framework-Based Turn-On Optical Sensor Device.

Despite exhaled human breath having enabled noninvasive diabetes diagnosis, selective acetone vapor detection by fluorescence approach in the diabetic range (1.8-3.5 ppm) remains a long-standing challenge. A set of water-resistant luminescent metal-organic framework (MOF)-based composites have been reported for detecting acetone vapor in the diabetic range with a limit of detection of 200 ppb. The luminescent materials possess the ability to selectively detect acetone vapor from a mixture comprising nitrogen, oxygen, carbon dioxide, water vapor, and alcohol vapor, which are prevalent in exhaled breath. It is noteworthy that this is the first luminescent MOF material capable of selectively detecting acetone vapor in the diabetic range via a turn-on mechanism. The material can be reused within a matter of minutes under ambient conditions. Industrially pertinent electrospun luminescent fibers are likewise fabricated alongside various luminescent films for selective detection of ultratrace quantities of acetone vapor present in the air. Ab initio theoretical calculations combined with in situ synchrotron-based dosing studies uncovered the material's remarkable hypersensitivity toward acetone vapor. Finally, a freshly designed prototype fluorescence-based portable optical sensor is utilized as a proof-of-concept for the rapid detection of acetone vapor within the diabetic range.

Fifty-year pollution history of microplastics and influencing factors in offshore sediments: A case study of Ningbo, China.

Sediment cores are optimal mediums for investigating the historical presence of offshore microplastics (MPs). In this study, two sediment cores were collected at varying water depths, i.e., XS2 (10 m) and XS3 (20 m), from the Xiangshan offshore (XSO) in Ningbo. We focused on the spatiotemporal distribution characteristics of MPs within two sediment cores and explored the response differences of MPs abundance to natural factors and human activities. The results showed that the MPs abundance in sediments has gradually increased since the late 1960s, but with interannual fluctuations. MPs abundance in XS2 and XS3 were 1133-8700 and 633-11433 items/kg dry weight, respectively. The predominant polymers were PA, PU, PET and ACR, with fragmented particles being the most prevalent shape of MPs. The MPs abundance in XS2 and XS3 had a similar response to natural factors, mainly including (i) MPs abundance significantly correlated with the sediment load of the Qiantang River (p < 0.01), indicating that sediment load might be an important factor affecting the MPs abundance and that MPs transported by rivers had characteristics of near-source sedimentation; (ii) typhoons had the effect of weakening the MPs abundance; and (iii) geological activities might be potential contributing factors to variations in MPs' abundance in deep sediments. Correlation analyses demonstrated that MPs in XSO was the result of multiple sources, stemming from plastic production, sewage discharge, marine fisheries and shipping activities. Notably, XS3 exhibited higher sensitivity to human activities compared to XS2, owing to differences in sampling locations. This study underscores the significance of employing two sediment cores, rather than a single core, as it provides a more comprehensive insight into the overarching trends and disparities in the historical pollution of MPs. Our findings contribute to a deeper understanding of the history of offshore MPs pollution, shedding new light on this critical environmental issue.

Microwave-activated Cu-doped zirconium metal-organic framework for a highly effective combination of microwave dynamic and thermal therapy.

Percutaneous microwave ablation (PMA) is a thermoablative method used as a minimally invasive treatment for liver cancer. However, the application of PMA is limited by its insufficient ROS generation efficiency and thermal effects. Herein, a new microwave-activated Cu-doped zirconium metal-organic framework (MOF) (CuZr MOF) used for enhanced PMA has a significantly improved microwave sensitizing effect. Owing to the strong inelastic collisions between ions confined in numerous micropores, CuZr MOF has strong microwave sensitivity and high thermal conversion efficiency, which can significantly improve microwave thermal therapy (MTT). Moreover, because of the existence of Cu2+ ions, a further benefit of CuZr MOF is their Fenton-like activity, in particular, microwaves used as an excitation source for microwave dynamic therapy (MDT) can improve the Fenton-like reaction to maximize the synergistic effectiveness of cancer therapy. Importantly, CuZr MOF can inhibit the production of heat shock proteins (HSPs) by producing abundant ROS to enhance tumor destruction. Mechanistically, we found that CuZr MOF + MW treatment modulates ferroptosis-mediated tumor cell death by targeting the HMOX1/GPX4 axis. In summary, this study develops a novel CuZr MOF microwave sensitizer with great potential for synergistic treatment of liver cancer by MTT and MDT.

Liquids with High Compressibility.

Compressibility is a fundamental property of all materials. For fluids, that is, gases and liquids, compressibility forms the basis of technologies such as pneumatics and hydraulics and determines basic phenomena such as the propagation of sound and shock waves. In contrast to gases, liquids are almost incompressible. If the compressibility of liquids could be increased and controlled, new applications in hydraulics and shock absorption could result. Here, it is shown that dispersing hydrophobic porous particles into water gives aqueous suspensions with much greater compressibilities than any normal liquids such as water (specifically, up to 20 times greater over certain pressure ranges). The increased compressibility results from water molecules being forced into the hydrophobic pores of the particles under applied pressure. The degree of compression can be controlled by varying the amount of porous particles added. Also, the pressure range of compression can be reduced by adding methanol or increased by adding salt. In all cases, the liquids expand back to their original volume when the applied pressure is released. The approach shown here is simple and economical and could potentially be scaled up to give large amounts of highly compressible liquids.

Sub-Cluster Identification through Semi-Supervised Optimization of Rare-Cell Silhouettes (SCISSORS) in single-cell RNA-sequencing.

MOTIVATION: Single-cell RNA-sequencing (scRNA-seq) has enabled the molecular profiling of thousands to millions of cells simultaneously in biologically heterogenous samples. Currently, the common practice in scRNA-seq is to determine cell type labels through unsupervised clustering and the examination of cluster-specific genes. However, even small differences in analysis and parameter choosing can greatly alter clustering results and thus impose great influence on which cell types are identified. Existing methods largely focus on determining the optimal number of robust clusters, which can be problematic for identifying cells of extremely low abundance due to their subtle contributions toward overall patterns of gene expression. RESULTS: Here, we present a carefully designed framework, SCISSORS, which accurately profiles subclusters within broad cluster(s) for the identification of rare cell types in scRNA-seq data. SCISSORS employs silhouette scoring for the estimation of heterogeneity of clusters and reveals rare cells in heterogenous clusters by a multi-step semi-supervised reclustering process. Additionally, SCISSORS provides a method for the identification of marker genes of high specificity to the cell type. SCISSORS is wrapped around the popular Seurat R package and can be easily integrated into existing Seurat pipelines. AVAILABILITY AND IMPLEMENTATION: SCISSORS, including source code and vignettes, are freely available at https://github.com/jr-leary7/SCISSORS.

The multikinase inhibitor axitinib in the treatment of advanced hepatocellular carcinoma: the current clinical applications and the molecular mechanisms.

Advanced hepatocellular carcinoma (HCC) is a formidable public health problem with limited curable treatment options. Axitinib, an oral tyrosine kinase inhibitor, is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptor (VEGFR) 1, 2, and 3. This anti-angiogenic drug was found to have promising activity in various solid tumors, including advanced HCC. At present, however, there is no relevant review article that summarizes the exact roles of axitinib in advanced HCC. In this review, 24 eligible studies (seven studies in the ClinicalTrials, eight experimental studies, and nine clinical trials) were included for further evaluation. The included randomized or single-arm phase II trials indicated that axitinib could not prolong the overall survival compared to the placebo for the treatment of advanced HCC, but improvements in progression free survival and time to tumor progression were observed. Experimental studies showed that the biochemical effects of axitinib in HCC might be regulated by its associated genes and affected signaling cascades (e.g. VEGFR2/PAK1, CYP1A2, CaMKII/ERK, Akt/mTor, and miR-509-3p/PDGFRA). FDA approved sorafenib combined with nivolumab (an inhibitor of PD-1/PD-L1) as the first line regimen for the treatment of advanced HCC. Since both axitinib and sorafenib are tyrosine kinase inhibitors as well as the VEGFR inhibitors, axitinib combined with anti-PDL-1/PD-1 antibodies may also exhibit tremendous potential in anti-tumoral effects for advanced HCC. The present review highlights the current clinical applications and the molecular mechanisms of axitinib in advanced HCC. To move toward clinical applications by combining axitinib and other treatments in advanced HCC, more studies are still warranted in the near future.

Manganese catalysed dehydrogenative synthesis of polyureas from diformamide and diamines.

We report here the synthesis of polyureas from the dehydrogenative coupling of diamines and diformamides. The reaction is catalysed by a manganese pincer complex and releases H2 gas as the only by-product making the process atom-economic and sustainable. The reported method is greener in comparison to the current state-of-the-art production routes that involve diisocyanate and phosgene feedstock. We also report here the physical, morphological, and mechanical properties of synthesized polyureas. Based on our mechanistic studies, we suggest that the reaction proceeds via isocyanate intermediates formed by the manganese catalysed dehydrogenation of formamides.

PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDKN1C and SMC1A.

BACKGROUND: Liver cancer is a highly malignant disease and the third leading cause of cancer death worldwide. Abnormal activation of PI3K/Akt signaling is common in cancer, but whether phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) plays a role in liver cancer is largely unexplored. METHODS: We determined the expression of PIK3R3 in liver cancer by using TCGA data and our clinical samples and knocked it down by siRNA or overexpressing it by the lentivirus vector system. We also investigated the function of PIK3R3 by colony formation, 5-Ethynyl-2-Deoxyuridine, flow cytometry assay, and subcutaneous xenograft model. The downstream of PIK3R3 was explored by RNA sequence and rescue assays. RESULTS: We found that PIK3R3 was significantly upregulated in liver cancer and correlated with prognosis. PIK3R3 promoted liver cancer growth in vitro and in vivo by controlling cell proliferation and cell cycle. RNA sequence revealed that hundreds of genes were dysregulated upon PIK3R3 knockdown in liver cancer cells. CDKN1C, a cyclin-dependent kinase inhibitor, was significantly upregulated by PIK3R3 knockdown, and CDKN1C siRNA rescued the impaired tumor cell growth. SMC1A was partially responsible for PIK3R3 regulated function, and SMC1A overexpression rescued the impaired tumor cell growth in liver cancer cells. Immunoprecipitation demonstrated there is indirect interaction between PIK3R3 and CNKN1C or SMC1A. Importantly, we verified that PIK3R3-activated Akt signaling determined the expression of CDKN1C and SMC1A, two downstream of PIK3R3 in liver cancer cells. CONCLUSION: PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDNK1C and SMC1A. Targeting PIK3R3 could be a promising treatment strategy for liver cancer that deserves further investigation.

In situ micropillar compression of an anisotropic metal-organic framework single crystal.

Understanding of the complex mechanical behavior of metal-organic frameworks (MOF) beyond their elastic limit will allow the design of real-world applications in chemical engineering, optoelectronics, energy conversion apparatus, and sensing devices. Through in situ compression of micropillars, the uniaxial stress-strain curves of a copper paddlewheel MOF (HKUST-1) were determined along two unique crystallographic directions, namely the (100) and (111) facets. We show strongly anisotropic elastic response where the ratio of the Young's moduli are E(111) ≈ 3.6 × E(100), followed by extensive plastic flows. Likewise, the yield strengths are considerably different, in which Y(111) ≈ 2 × Y(100) because of the underlying framework anisotropy. We measure the fracture toughness using micropillar splitting. While in situ tests revealed differential cracking behavior, the resultant toughness values of the two facets are comparable, yielding Kc ~ 0.5 MPa[Formula: see text]. This work provides insights of porous framework ductility at the micron scale under compression and failure by bonds breakage.

Beyond iron-storage pool: functions of plant apoplastic iron during stress.

Iron (Fe) is an essential micronutrient for plants, and its storage in the apoplast represents an important Fe pool. Plants have developed various strategies to reutilize this apoplastic Fe pool to adapt to Fe deficiency. In addition, growing evidence indicates that the dynamic changes in apoplastic Fe are critical for plant adaptation to other stresses, including ammonium stress, phosphate deficiency, and pathogen attack. In this review, we discuss and scrutinize the relevance of apoplastic Fe for plant behavior changes in response to stress cues. We mainly focus on the relevant components that modulate the actions and downstream events of apoplastic Fe in stress signaling networks.

The mechanism of flavonoids from Cyclocarya paliurus on inhibiting liver cancer based on in vitro experiments and network pharmacology.

Introduction: Cyclocarya paliurus (Batal.) Iljinsk., a subtropical tree belonging to the family Juglandaceae, is rich in polysaccharides, flavonoids, and terpenoids. It has important pharmacological effects such as lowering blood lipids, blood sugar, and blood pressure. However, little has been discerned regarding anti tumor effects and their potential mechanisms. Method: In vitro cell culture experiments were used to test the effect of C. paliurus total flavonoids (CTFs) extract on apoptosis mechanisms in HepG2 cells. Network pharmacology was applied to further explore the effects of CTFs on liver cancer as well as the mechanisms through which these effects might be achieved. Both 3 hydroxyflavone and luteolin were randomly selected to verify the effect on inducing apoptosis and inhibiting the proliferation of HepG2 cells. Results and Discussion: Network pharmacological analysis was applied to these 62 compounds and their targets, and 13 flavonoids were further screened for their potential anti liver cancer activity. These 13 flavonoids included: tangeretin, baicalein, 7,3'-dihydroxyflavone, velutin, 3-hydroxyflavone, chrysin, kumatakenin, tricin, luteolin, chrysoeriol, apigenin, pinocembrin, and butin. Together, these flavonoids were predicted to interact with AKT1, MAPK3, PIK3CA, EGFR, MAP2K1, SRC, IGF1R, IKBKB, MET, and MAPK14. It was predicted that the inhibitory effect on hepatocellular carcinoma would be accomplished by regulation of core proteins relating to such KEGG pathways as cancer, PI3K-Akt, proteoglycans in cancer, microRNAs in cancer, and endocrine resistance via core target proteins. Both 3-hydroxyflavone and luteolin were demonstrated to induce apoptosis and inhibit the proliferation of HepG2 cells. Our study provides scientific evidence supporting the use of CTFs for the treatment of liver cancer.

Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies.

Hepatocellular carcinoma (HCC) is one of the most common digestive malignancies. HCC It ranges as the fifth most common cause of cancer mortality worldwide. While The prognosis of metastatic or advanced HCC is still quite poor. Recently, locoregional treatment, especially local ablation therapies, plays an important role in the treatment of HCC. Radiofrequency ablation (RFA) and high-intensity focused ultrasound (HIFU) ablation are the most common-used methods effective and feasible for treating HCC. However, the molecular mechanisms underlying the actions of ablation in the treatments for HCC and the HCC recurrence after ablation still are poorly understood. Hypoxia-inducible factor (HIF), the key gene switch for adaptive responses to hypoxia, has been found to play an essential role in the rapid aggressive recurrence of HCC after ablation treatment. In this review, we summarized the current evidence of the roles of HIF in the treatment of HCC with ablation. Fifteen relevant studies were included and further analyzed. Among them, three clinical studies suggested that HIF-1α might serve as a crucial role in the RAF treatment of HCC or the local recurrence of HCC after RFA. The remainder included experimental studies demonstrated that HIF-1, 2α might target the different molecules (e.g., BNIP3, CA-IX, and arginase-1) and signaling cascades (e.g., VEGFA/EphA2 pathway), constituting a complex network that promoted HCC invasion and metastasis after ablation. Currently, the inhibitors of HIF have been developed, providing important proof of targeting HIF for the prevention of HCC recurrence after IRFA and HIFU ablation. Further confirmation by prospective clinical and in-depth experimental studies is still warranted to illustrate the effects of HIF in HCC recurrence followed ablation treatment in the future.

A systematic scoping review of reflective writing in medical education.

BACKGROUND: Reflective writing (RW) allows physicians to step back, review their thoughts, goals and actions and recognise how their perspectives, motives and emotions impact their conduct. RW also helps physicians consolidate their learning and boosts their professional and personal development. In the absence of a consistent approach and amidst growing threats to RW's place in medical training, a review of theories of RW in medical education and a review to map regnant practices, programs and assessment methods are proposed. METHODS: A Systematic Evidence-Based Approach guided Systematic Scoping Review (SSR in SEBA) was adopted to guide and structure the two concurrent reviews. Independent searches were carried out on publications featured between 1st January 2000 and 30th June 2022 in PubMed, Embase, PsychINFO, CINAHL, ERIC, ASSIA, Scopus, Google Scholar, OpenGrey, GreyLit and ProQuest. The Split Approach saw the included articles analysed separately using thematic and content analysis. Like pieces of a jigsaw puzzle, the Jigsaw Perspective combined the themes and categories identified from both reviews. The Funnelling Process saw the themes/categories created compared with the tabulated summaries. The final domains which emerged structured the discussion that followed. RESULTS: A total of 33,076 abstracts were reviewed, 1826 full-text articles were appraised and 199 articles were included and analysed. The domains identified were theories and models, current methods, benefits and shortcomings, and recommendations. CONCLUSIONS: This SSR in SEBA suggests that a structured approach to RW shapes the physician's belief system, guides their practice and nurtures their professional identity formation. In advancing a theoretical concept of RW, this SSR in SEBA proffers new insight into the process of RW, and the need for longitudinal, personalised feedback and support.

Stimuli-Responsive Electrospun Fluorescent Fibers Augmented with Aggregation-Induced Emission (AIE) for Smart Applications.

This review addresses the latest advancements in the integration of aggregation-induced emission (AIE) materials with polymer electrospinning, to accomplish fine-scale electrospun fibers with tunable photophysical and photochemical properties. Micro- and nanoscale fibers augmented with AIE dyes (termed AIEgens) are bespoke composite systems that can overcome the limitation posed by aggregation-caused quenching, a critical deficiency of conventional luminescent materials. This review comprises three parts. First, the reader is exposed to the basic concepts of AIE and the fundamental mechanisms underpinning the restriction of intermolecular motions. This is followed by an introduction to electrospinning techniques pertinent to AIE-based fibers, and the core parameters for controlling fiber architecture and resultant properties. Second, exemplars are drawn from latest research to demonstrate how electrospun nanofibers and porous films incorporating modified AIEgens (especially tetraphenylethylene and triphenylamine derivatives) can yield enhanced photostability, photothermal properties, photoefficiency (quantum yield), and improved device sensitivity. Advanced applications are drawn from several promising sectors, encompassing optoelectronics, drug delivery and biology, chemosensors and mechanochromic sensors, and innovative photothermal devices, among others. Finally, the outstanding challenges together with potential opportunities in the nascent field of electrospun AIE-active fibers are presented, for stimulating frontier research and explorations in this exciting field.

The roles of RNA N6-methyladenosine in esophageal cancer.

Esophageal cancer is a malignant tumour with a high degree of malignancy and high mortality. Its pathogenesis and treatment strategy remain unclear. N6-methyladenosine (m6A) is important for various biological functions in RNA modification and is currently being investigated extensively. It plays an essential role in RNA modification. m6A modification is a dynamic process that reversibly regulates the target RNA through its regulatory factors and plays an important role in several diseases, especially cancer. However, the role of m6A in esophageal cancer remains elusive. RNA modification and splicing are regulated by RNA methylation regulators called 'writers' (methyltransferases), 'erasers' (demethylases) and 'readers' (modified RNA-binding proteins). These regulatory factors recognise and bind to RNA methylation sites, regulate biological functions such as RNA splicing and translation and influence the occurrence, development, invasion and metastasis of tumours. Considering the importance of m6A modification, we reviewed the regulatory mechanisms, biological functions and therapeutic prospects of m6A RNA methylation regulators in esophageal cancer.

Association of Concurrent Olfactory Dysfunction and Probable Rapid Eye Movement Sleep Behavior Disorder with Early Parkinson's Disease Progression.

Background: Parkinson's disease (PD), with either rapid eye movement sleep behavior disorder (RBD) or olfactory dysfunction (OD), has been associated with disease progression. However, there is currently heterogeneity in predicting prognosis. Objectives: To identify whether the concurrent presence of OD and probable RBD (pRBD) in PD (Dual hit in PD, PD-DH) is associated with disease progression. Methods: We included 420 patients with de novo PD from the Parkinson's Progression Markers Initiative: 180 PD only (PD), 82 PD with OD (PD-OD), 94 PD with pRBD (PD-pRBD), and 64 PD with both OD and pRBD (PD-DH). Participants underwent motor and nonmotor evaluations, dopamine transporter imaging, and cerebrospinal fluid (CSF) assessment. Data were analyzed with generalized estimating equations and Cox proportional hazards analysis. Results: The PD-DH subtype was associated with higher scores and faster progression rates in Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) Parts II and III. Also, patients in PD-DH group had faster deterioration in nonmotor symptoms, including MDS-UPDRS Part I score, Montreal Cognitive Assessment, Hopkins Verbal Learning Test-Revised, Wechsler Memory Scale-Third edition (WMS-III) Letter Number Sequencing score, Symbol Digit Modalities Test, and Scales for Outcomes in PD-Autonomic scores, with all P values <0.002. Moreover, the PD-DH subtype had a higher mild cognitive impairment risk (hazard ratio = 1.756, 95% confidence interval [CI] = 1.132-2.722; P = 0.012), faster decline in caudate standard uptake values (ß = -0.03, 95% CI = -0.06 to -0.008, P = 0.012), and CSF α-synuclein levels (ß = -77, 95% CI = -149 to -5, P = 0.034) than the PD group. Conclusion: Coexisting pRBD and OD in patients with PD may be associated with faster progressions in motor measurements and in cognitive and autonomic symptoms, indicating PD-DH as a more aggressive subtype for PD.