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Background: Considering that changes in the choroidal thickness are closely related to ocular growth, we studied the choroidal thickness (CT) and the blood flow features in children with unilateral myopic anisometropia (UMA) as well as investigating the relationship between choroidal changes and myopia., Methods: Subjective refractive, axial length (AL), and biometric parameters were measured in 98 UMA children (age: 8-15 years). CT and choroidal blood-flow features, including the choroidal vessel volume (CVV), choroidal vascularity index (CVI), and choriocapillaris perfusion area (CCPA), were measured through swept-source optical coherence tomography angiography. The macular region was categorized into four concentric circles of diameters 0-1 mm (central fovea), 1-3 mm (parafovea), 3-6 mm (perifovea), and 6-9 mm (extended), and further categorized into superior (S), inferior (I), temporal (T), and nasal (N) quadrants., Results: The aforementioned four regions of myopic eyes displayed significantly lower CT, CVV, and CVI than those of non-myopic eyes. CCPA changes differed across different regions of both the eyes (parts of N and T quadrants). There was an inverse association between CT and the interocular AL difference (central and other regions S, T quadrant). No correlation was noted between CVV and CVI with interocular AL difference. CT and CVV were positively correlated in the 0-6-mm macular region of myopic eyes (Spearman correlation coefficient = 0.763, P < 0.001)., Conclusions: In UMA children, CCT and blood flow may be related to myopia progression. A robust correlation between CT and CVV in the 0-6-mm macular region and reduced CT and diminished blood flow indicated an association with myopia., (© 2024. The Author(s).)

Background: Exposure to light at night (LAN) has been associated with multiple adverse health outcomes. However, evidence is limited regarding the impacts of LAN exposure on human inflammation., Objectives: To examine the association between real-ambient bedroom LAN exposure with systemic inflammation and circadian rhythm of inflammatory markers., Methods: Using data from a prospective cohort study of Chinese young adults. At baseline, bedroom LAN exposure was measured with a portable illuminance meter; fasting blood sample for high-sensitivity C-reactive protein (hs-CRP) assay was collected. At 3-year follow-up, 20 healthy young adults (10 LAN avg < 5 lx, 10 LAN avg ≥ 5 lx) were recruited from the same cohort; time-series venous blood samples were sampled every 4 h over a 24 h-cycle for the detection of 8 inflammatory markers. Circadian rhythm of inflammatory markers was assessed using cosinor analysis., Results: At baseline, the average age of the 276 participants was 18.7 years, and 33.3 % were male. Higher levels of bedroom LAN exposure were significantly associated with increased hs-CRP levels. The association between bedroom LAN exposure and systemic inflammation was only significant in the inactive group (MVPA < 2 h/d) but not in the physically active group (MVPA ≥ 2 h/d). In addition, exposure to higher levels of nighttime light (LAN avg ≥ 5 lx) disrupted circadian rhythms (including rhythmic expression, circadian amplitude and circadian phase) of some inflammatory cytokines and inflammatory balance indicators., Conclusion: Exposure to bedroom nighttime light increases systemic inflammation and disrupts circadian rhythm of inflammatory markers. Keep bedroom darkness at night may represent important strategies for the prevention of chronic inflammation. Additionally, for people living a community with higher nighttime light pollution, regular physical activity may be a viable option to counteract the negative impacts of LAN exposure on chronic inflammation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

β-Alanine is the only β-amino acid in nature and one of the most important three-carbon chemicals. This work was aimed to construct a non-inducible β-alanine producer with enhanced metabolic flux towards β-alanine biosynthesis in Escherichia coli. First of all, the assembled E. coli endogenous promoters and 5'-untranslated regions (PUTR) were screened to finely regulate the combinatorial expression of genes panD BS and aspB CG for an optimal flux match between two key pathways. Subsequently, additional copies of key genes (panD BS K104S and ppc) were chromosomally introduced into the host A1. On these bases, dynamical regulation of the gene thrA was performed to reduce the carbon flux directed in the competitive pathway. Finally, the β-alanine titer reached 10.25 g/L by strain A14-R15, 361.7% higher than that of the original strain. Under fed-batch fermentation in a 5-L fermentor, a titer of 57.13 g/L β-alanine was achieved at 80 h. This is the highest titer of β-alanine production ever reported using non-inducible engineered E. coli. This metabolic modification strategy for optimal carbon flux distribution developed in this work could also be used for the production of various metabolic products., (© 2024 Wiley Periodicals LLC.)

Background: Conjoined twins are a rare twin malformation commonly presenting as single amniotic sac twinning, with double amniotic sac twinning being extremely rare and poorly reported. Most conjoined twins are females., Case Summary: A woman of childbearing age conceived naturally, and at 8 wk of gestation, transvaginal ultrasonography showed an embryo and cardiac tube pulsation in both amniotic sacs. On dynamic observation, the two embryos were connected in the lower abdomen, with restricted movement. A repeat transvaginal ultrasound at 11 wk showed that the intestinal tubes of both fetuses were connected in the lower abdomen. The pregnancy was terminated and labor was induced., Conclusion: Transvaginal ultrasound may detect conjoined twin malformations in an early stage. Our case provides diagnostic insights for ultrasonographers and can help develop early therapeutic interventions., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Quantum heat engines and refrigerators are open quantum systems, whose dynamics can be well understood using a non-Hermitian formalism. A prominent feature of non-Hermiticity is the existence of exceptional points (EPs), which has no counterpart in closed quantum systems. It has been shown in classical systems that dynamical encirclement in the vicinity of an EP, whether the loop includes the EP or not, could lead to chiral mode conversion. Here, we show that this is valid also for quantum systems when dynamical encircling is performed in the vicinity of their Liouvillian EPs (LEPs), which include the effects of quantum jumps and associated noise-an important quantum feature not present in previous works. We demonstrate, using a Paul-trapped ultracold ion, the first chiral quantum heating and refrigeration by dynamically encircling a closed loop in the vicinity of an LEP. We witness the cycling direction to be associated with the chirality and heat release (absorption) of the quantum heat engine (quantum refrigerator). Our experiments have revealed that not only the adiabaticity breakdown but also the Landau-Zener-Stückelberg process play an essential role during dynamic encircling, resulting in chiral thermodynamic cycles. Our observations contribute to further understanding of chiral and topological features in non-Hermitian systems and pave a way to exploring the relation between chirality and quantum thermodynamics., (© 2024. The Author(s).)

Background: Light at night (LAN) have attracted increased research attention on account of its widespread health hazards. However, the underlying mechanism remains unknown. The objective of this study was to investigate the effects of real-ambient bedroom LAN exposure on circadian rhythm among young adults and potential sex differences., Methods: Bedroom LAN exposure was measured at 60-s intervals for 2 consecutive days using a portable illuminance meter. Circadian phase was determined by the dim light melatonin onset (DLMO) time in 7 time-series saliva samples., Results: The mean age of the 142 participants was 20.7 ± 0.8 years, and 59.9% were women. The average DLMO time was 21:00 ± 1:11 h, with men (21:19 ± 1:12 h) later than women (20:48 ± 1:07 h). Higher level of LAN intensity (LAN avg ≥ 3lx vs. LAN avg < 3lx) was associated with an 81.0-min later in DLMO time (95% CI: 0.99, 1.72), and longer duration of nighttime light intensity ≥ 5lx (LAN5; LAN5 ≥ 45 min vs. LAN5 < 45 min) was associated with a 51.6-min later in DLMO time (95% CI: 0.46, 1.26). In addition, the delayed effect of LAN exposure on circadian phase was more pronounced in men than in women (all P-values <0.05)., Conclusions: Overall, bedroom LAN exposure was significantly associated with delayed circadian rhythm. Additionally, the delayed effect is more significant in men. Keeping bedroom dark at night may be a practicable option to prevent circadian disruption and associated health implications. Future studies with more advanced light measurement instrument and consensus methodology for DLMO assessment are warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Endogenous opioid antinociception is a self-regulatory mechanism that reduces chronic pain, but its underlying circuit mechanism remains largely unknown. Here, we showed that endogenous opioid antinociception required the activation of mu-opioid receptors (MORs) in GABAergic neurons of the central amygdala nucleus (CEA) in a persistent-hyperalgesia mouse model. Pharmacogenetic suppression of these CEA MOR neurons, which mimics the effect of MOR activation, alleviated the persistent hyperalgesia. Furthermore, single-neuron projection analysis revealed multiple projectome-based subtypes of CEA MOR neurons, each innervating distinct target brain regions. We found that the suppression of axon branches projecting to the parabrachial nucleus (PB) of one subtype of CEA MOR neurons alleviated persistent hyperalgesia, indicating a subtype- and axonal-branch-specific mechanism of action. Further electrophysiological analysis revealed that suppression of a distinct CEA-PB disinhibitory circuit controlled endogenous opioid antinociception. Thus, this study identified the central neural circuit that underlies endogenous opioid antinociception, providing new insight into the endogenous pain modulatory mechanisms., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

The approach of shortcuts to adiabaticity enables the effective execution of adiabatic dynamics in quantum information processing with enhanced speed. Owing to the inherent trade-off between dynamical speed and the cost associated with the transitionless driving field, executing arbitrarily fast operations becomes impractical. To understand the accurate interplay between speed and energetic cost in this process, we propose theoretically and verify experimentally a new trade-off, which is characterized by a tightly optimized bound within s-parametrized phase spaces. Our experiment is carried out in a single ultracold ^{40}Ca^{+} ion trapped in a harmonic potential. By exactly operating the quantum states of the ion, we execute the Landau-Zener model as an example, where the quantum speed limit as well as the cost are governed by the spectral gap. We witness that our proposed trade-off is indeed tight in scenarios involving both initially eigenstates and initially thermal equilibrium states. Our work helps understanding the fundamental constraints in shortcuts to adiabaticity and illuminates the potential of underutilized phase spaces that have been traditionally overlooked.

Although entanglement is considered as an essential resource for quantum information processing, whether entanglement helps for energy conversion or output in the quantum regime is still lack of experimental witness. Here, we report on an energy-conversion device operating as a quantum engine with the working medium acted by two entangled ions confined in a harmonic potential. The two ions are entangled by virtually coupling to one of the vibrational modes shared by the two ions, and the quantum engine couples to a quantum load, which is another shared vibrational mode. We explore the energy conversion efficiency of the quantum engine and investigate the useful energy (i.e., the maximum extractable work) stored in the quantum load by tuning the two ions in different degrees of entanglement as well as detecting the change of the phonons in the load. Our observation provides, for the first time, quantitative evidence that entanglement fuels the useful energy produced by the quantum engine, but not helpful for the energy conversion efficiency. We consider that our results may be useful to the study of quantum batteries for which one of the most indexes is the maximum extractable energy.

Genotoxic therapy triggers reactive oxygen species (ROS) production and oxidative tissue injury. S-nitrosylation is a selective and reversible posttranslational modification of protein thiols by nitric oxide (NO), and 5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor for NO synthesis. However, the mechanism by which BH4 affects protein S-nitrosylation and ROS generation has not been determined. Here, we showed that ionizing radiation disrupted the structural integrity of BH4 and downregulated GTP cyclohydrolase I (GCH1), which is the rate-limiting enzyme in BH4 biosynthesis, resulting in deficiency in overall protein S-nitrosylation. GCH1-mediated BH4 synthesis significantly reduced radiation-induced ROS production and fueled the global protein S-nitrosylation that was disrupted by radiation. Likewise, GCH1 overexpression or the administration of exogenous BH4 protected against radiation-induced oxidative injury in vitro and in vivo. Conditional pulmonary Gch1 knockout in mice (Gch1 fl/fl ; Sftpa1-Cre +/- mice) aggravated lung injury following irradiation, whereas Gch1 knock-in mice (Gch1 lsl/lsl ; Sftpa1-Cre +/- mice) exhibited attenuated radiation-induced pulmonary toxicity. Mechanistically, lactate dehydrogenase (LDHA) mediated ROS generation downstream of the BH4/NO axis, as determined by iodoacetyl tandem mass tag (iodoTMT)-based protein quantification. Notably, S-nitrosylation of LDHA at Cys163 and Cys293 was regulated by BH4 availability and could restrict ROS generation. The loss of S-nitrosylation in LDHA after irradiation increased radiosensitivity. Overall, the results of the present study showed that GCH1-mediated BH4 biosynthesis played a key role in the ROS cascade and radiosensitivity through LDHA S-nitrosylation, identifying novel therapeutic strategies for the treatment of radiation-induced lung injury., (© 2024. The Author(s).)

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignant disease with a low 5-year overall survival rate. It is the third-leading cause of cancer-related deaths in the United States. The lack of robust therapeutics, absence of effective biomarkers for early detection, and aggressive nature of the tumor contribute to the high mortality rate of PDAC. Notably, the outcomes of recent immunotherapy and targeted therapy against PDAC remain unsatisfactory, indicating the need for novel therapeutic strategies. One of the newly described molecular features of PDAC is the altered expression of protein arginine methyltransferases (PRMTs). PRMTs are a group of enzymes known to methylate arginine residues in both histone and non-histone proteins, thereby mediating cellular homeostasis in biological systems. Some of the PRMT enzymes are known to be overexpressed in PDAC that promotes tumor progression and chemo-resistance via regulating gene transcription, cellular metabolic processes, RNA metabolism, and epithelial mesenchymal transition (EMT). Small-molecule inhibitors of PRMTs are currently under clinical trials and can potentially become a new generation of anti-cancer drugs. This review aims to provide an overview of the current understanding of PRMTs in PDAC, focusing on their pathological roles and their potential as new therapeutic targets.

Small extracellular vesicles (sEVs) contain lipids, proteins and nucleic acids, which often resemble their cells of origin. Therefore, plasma sEVs are considered valuable resources for cancer biomarker development. However, previous efforts have been largely focused on the level of proteins and miRNAs in plasma sEVs, and the post-translational modifications of sEV proteins, such as arginine methylation, have not been explored. Protein arginine methylation, a relatively stable post-translational modification, is a newly described molecular feature of PDAC. The present study examined arginine methylation patterns in plasma sEVs derived from patients with early-stage PDAC ( n = 23) and matched controls. By utilizing the arginine methylation-specific antibodies for western blotting, we found that protein arginine methylation patterns in plasma sEVs are altered in patients with early-stage PDAC. Specifically, we observed a reduction in the level of symmetric dimethyl arginine (SDMA) in plasma sEV proteins derived from patients with early- and late-stage PDAC. Importantly, immunoprecipitation followed by proteomics analysis identified a number of arginine-methylated proteins exclusively present in plasma sEVs derived from patients with early-stage PDAC. These results indicate that arginine methylation patterns in plasma sEVs are potential indicators of PDAC, a new concept meriting further investigation.

Light at night (LAN) is a significant but underappreciated risk factor contributing to cardiometabolic disease (CMD). We therefore conducted the review examining the relationship of LAN exposure with CMD in order to investigate the effects of LAN exposure on CMD. We searched PubMed, Web of Science, Embase, and Scopus for eligible studies published from database inception to August 17, 2023. The pooled effect size was calculated using random-effects models. Heterogeneity among the studies was quantified by Cochran's Q test and I 2 statistic. A total of 1,019,739 participants from 14 studies (5 cohort studies and 9 cross-sectional) were included. Among the 14 eligible studies, 9 on obesity, 4 on diabetes, 2 on hypertension, 1 on dyslipidemia, and 1 on coronary heart disease. Exposure to higher levels of LAN were associated with 21% higher risk of CMD (Summary risk ratio, SRR: 1.21, 95% CI = 1.16-1.27), accompanied by substantial heterogeneity (I 2  = 61%; tau 2  = 0.004; Cochran's Q = 41.02). Specifically, individuals in the highest category of LAN exposure exhibited 23% higher risk of obesity (SRR: 1.23, 95% CI = 1.14-1.32), 46% higher risk of diabetes (SRR: 1.46, 95% CI = 1.05-2.03) and 21% higher risk of other CMDs (SRR: 1.21, 95% CI = 1.10-1.34). Subgroup analyses revealed that the pooled-effect size of LAN and CMD was higher for indoor LAN than outdoor LAN (indoor LAN: SRR = 1.36; outdoor LAN: SRR = 1.17, P = 0.03). The overall quality was rated as moderate using GRADE guideline. Our study strengthens the evidence on the increase in CMD risk due to LAN exposure. Findings from this study have important implications for identifying modifiable risk factor of CMD, future prevention strategy development, and resource allocation for high-risk group., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: To explore the relationship of triglyceride-glucose index (TyG), triglyceride-glucose-body mass index (TyG-BMI), and triglyceride-glucose-waist circumference index (TyG-WC) with blood pressure abnormalities in adolescents, providing theoretical basis for the prevention and control of hypertension in adolescents., Methods: A stratified cluster sampling method was used to select 1 572 adolescents aged 12 to 18 years in Yinchuan City for questionnaire surveys, physical measurements, and laboratory tests. Logistic regression analysis and restricted cubic spline analysis were employed to examine the relationship of TyG, TyG-BMI, and TyG-WC with blood pressure abnormalities in adolescents., Results: Multivariable logistic regression analysis revealed that after adjusting for confounding factors, the groups with the highest quartile of TyG, TyG-BMI, and TyG-WC had 1.48 times (95% CI : 1.07-2.04), 3.71 times (95% CI : 2.67-5.15), and 4.07 times (95% CI : 2.89-5.73) higher risks of blood pressure abnormalities compared to the groups with the lowest quartile, respectively. Moreover, as the levels of TyG, TyG-BMI, and TyG-WC increased, the risk of blood pressure abnormalities gradually increased ( P <0.05). A non-linear dose-response relationship was observed between TyG-BMI and the risk of blood pressure abnormalities ( P overall trend <0.001, P non-linearity =0.002). Linear dose-response relationships were found between TyG and the risk of blood pressure abnormalities ( P overall trend <0.001, P non-linearit =0.232), and between TyG-WC and the risk of blood pressure abnormalities ( P overall trend <0.001, P non-linearity =0.224)., Conclusions: Higher levels of TyG and its derivatives are associated with an increased risk of blood pressure abnormalities in adolescents, with linear or non-linear dose-response relationships.

The itch-scratching cycle is mediated by neural dynamics in the brain. However, our understanding of the neural dynamics during this cycle remains limited. In this study, we examine the neural dynamics of 126 mouse brain areas by measuring the calcium signal using fiber photometry. We present numerous response patterns in the mouse brain during the itch-scratching cycle. Interestingly, we find that a group of brain areas exhibit activation only at the end of histamine-induced scratching behavior. Additionally, several brain areas exhibit transient activation at the onset of scratching induced by chloroquine. Both histamine- and chloroquine-induced itch evoke diverse response patterns across the mouse brain. In summary, our study provides a comprehensive dataset for the diverse activity pattern of mouse brain during the itch-scratching cycle, paving the way for further exploration into the neural mechanisms underlying the itch-scratching cycle., Competing Interests: Declaration of interests The authors have no competing financial interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Metal-organic frameworks (MOFs) are emerging as advanced nanoporous materials to remove phenylarsenic acid, p -arsanilic acid ( p -ASA), and roxarsone (ROX) in the aqueous solution, while MOFs are often present as powder state and encounter difficulties in recovery after adsorption, which greatly limit their practical application in the aqueous environments. Herein, MIL-101 (Fe), a typical MOF, was mixed with sodium alginate and gelatin to prepare MIL-101@CAGE by three-dimensional (3D) printing technology, which was then used as a separatable adsorbent to remove phenylarsenic acid in the aqueous solution. The structure of 3D-printed MIL-101@CAGE was first characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and thermogravimetry and differential thermogravimetry (TG-DTG). The octahedral morphology of MIL-101 (Fe) was found unchanged during the 3D printing process. Then, the adsorption process of MIL-101@CAGE on phenylarsenic acids was systematically investigated by adsorption kinetics, adsorption isotherms, adsorption thermodynamics, condition experiments, and cyclic regeneration experiments. Finally, the adsorption mechanism between MIL-101@CAGE and phenylarsenic acid was further investigated. The results showed that the Langmuir, Freundlich, and Temkin isotherms were well fit, and according to the Langmuir fitting results, the maximum adsorption amounts of MIL-101@CAGE on p -ASA and ROX at 25 °C were 106.98 and 120.28 mg/g, respectively. The removal of p -ASA and ROX by MIL-101@CAGE remained stable over a wide pH range and in the presence of various coexisting ions. The regeneration experiments showed that the 3D-printed MIL-101@CAGE could still maintain a more than 90% removal rate after five cycles. The adsorption mechanism of this system might include π-π stacking interactions between the benzene ring on the phenylarsenic acids and the organic ligands in MIL-101@CAGE, hydrogen-bonding, and ligand-bonding interactions (Fe-O-As). This study provides a new idea for the scale preparation of a separatable and recyclable adsorbent based on MOF material for the efficient removal of phenylarsenic acid in the aqueous solution.

Arsenic (As) is a highly toxic heavy metal and has been widely concerned for its hazardous environmental impact. Aromatic organic arsenic (AOCs) has been frequently used as an animal supplement to enhance feed utilization and prevent dysentery. The majority of organic arsenic could be discharged from the body and evolve as highly toxic inorganic arsenic that is hazardous to the environment and human health via biological conversion, photodegradation, and photo-oxidation. Current environmental issues necessitate the development and application of multifunctional porous materials in environmental remediation. Compared to the conventional adsorbent, such as activated carbon and zeolite, metal-organic frameworks (MOFs) exhibit a number of advantages, including simple synthesis, wide variety, simple modulation of pore size, large specific surface area, excellent chemical stability, and easy modification. In recent years, numerous scientists have investigated MOFs related materials involved with organic arsenic. These studies can be divided into three categories: detection of organic arsenic by MOFs, adsorption to remove organic arsenic by MOFs, and catalytic removal of organic arsenic by MOFs. Here, we conduct a critical analysis of current research findings and knowledge pertaining to the structural characteristics, application methods, removal properties, interaction mechanisms, and spectral analysis of MOFs. We summarized the application of MOFs in organic arsenic detection, adsorption, and catalytic degradation. Other arsenic removal technologies and conventional substances are also being investigated. This review will provide relevant scientific researchers with references., Competing Interests: Declaration of competing interest The authors declared that they have no known conflict of interest or personal relationships that could have appeared to influence the work submitted., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Radiotherapy resistance is an important and urgent challenge in the clinical management of esophageal squamous carcinoma (ESCC). However, the factors mediating the ESCC resistance to radiotherapy and its underlying molecular mechanisms are not fully clarified. Our previous studies have demonstrated the critical role of DNA polymerase iota (POLI) in ESCC development and progression, here, we aimed to investigate the involvement of POLI in ESCC radiotherapy resistance and elucidate the underlying molecular mechanism. We found that highly expressed POLI was correlated with shorter overall survival of ESCC patients received radiotherapy. Down-regulation of POLI sensitized ESCC to IR, prolonged γH2AX foci in nuclei and comet tails after IR. HR but not NHEJ repair is inhibited in POLI-deficient ESCC cells. POLI stabilizes RAD51 protein via competitively binding with and blocking the interaction between RAD51 and E3 ligase XIAP and XIAP-mediated ubiquitination. Furthermore, loss of POLI leads to the activation of GAS signaling. Our findings provide novel insight into the role of POLI in the development of radioresistance mediated by stabilizing RAD51 protein in ESCC., (© 2023. Cell Death Differentiation Association (ADMC).)

Introduction: Both cigarette smoking and gut microbiota play important roles in colorectal carcinogenesis. We explored whether the association between smoking and colorectal cancer (CRC) risk varies by gut microbial enterotypes and how smoking-related enterotypes promote colorectal carcinogenesis., Methods: A case-control study was conducted. Fecal microbiota was determined by 16S rDNA sequencing. The cases with CRC or adenoma were subclassified by gut microbiota enterotypes. Multivariate analyses were used to test associations between smoking and the odds of colorectal neoplasm subtypes. Mann-Whitney U tests were used to find differential genera, genes, and pathways between the subtypes., Results: Included in the study were 130 CRC patients (type I: n=77; type II: n=53), 120 adenoma patients (type I: n=66; type II: n=54), and 130 healthy participants. Smoking increased the odds for type II tumors significantly (all p for trend <0.05) but not for type I tumors. The associations of smoking with increased odds of colorectal neoplasm significantly differed by gut microbiota enterotypes (p<0.05 for heterogeneity). An increase in carcinogenic bacteria (genus Escherichia shigella ) and a decrease in probiotics (family Lachnospiraceae and Ruminococcaceae ) in type II tumors may drive disease progression by upregulating oncogenic signaling pathways and inflammatory/oxidative stress response pathways, as well as protein phospholipase D1/2, cytochrome C, and prostaglandin-endoperoxide synthase 2 expression., Conclusions: Smoking was associated with a higher odds of type II colorectal neoplasms but not type I tumors, supporting a potential role for the gut microbiota in mediating the association between smoking and colorectal neoplasms., Competing Interests: The authors have each completed and submitted an ICMJE form for disclosure of potential conflicts of interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. J.A. Cai reports that since the initial planning of the work, Xiyuan Program from Fudan University's Undergraduate Research Opportunities Program (FDUROP) (in 2020) was supported by the Undergraduate Innovation and Entrepreneurship Program (Qingfeng Scholars Program) of Shanghai Medical College, Fudan University (QF2006) and by Shanghai Undergraduate Innovation Training Program (S202110246209). Y.Z. Zhang reports that since the initial planning of the work, this study was supported from Youth Foundation Project of Hainan Natural Science Foundation of China (SQ2020QNJJ0433). Q.C. Cai reports that since the initial planning of the work, this study was supported from the National Natural Science Foundation of China (81473045)., (© 2023 Cai J.A. et al.)

Colorectal cancer (CRC) risk is influenced by dietary patterns and gut microbiota enterotypes. However, the interaction between these factors remains unclear. This study examines this relationship, hypothesizing that different diets may affect colorectal tumor risk in individuals with varied gut microbiota enterotypes. We conducted a case-control study involving 410 Han Chinese individuals, using exploratory structural equation modeling to identify two dietary patterns, and a Dirichlet multinomial mixture model to classify 250 colorectal neoplasm cases into three gut microbiota enterotypes. We assessed the association between dietary patterns and the risk of each tumor subtype using logistic regression analysis. We found that a healthy diet, rich in vegetables, fruits, milk, and yogurt, lowers CRC risk, particularly in individuals with type I (dominated by Bacteroides and Lachnoclostridium ) and type II (dominated by Bacteroides and Faecalibacterium ) gut microbiota enterotypes, with adjusted odds ratios (ORs) of 0.66 (95% confidence interval [CI] = 0.48-0.89) and 0.42 (95% CI = 0.29-0.62), respectively. Fruit consumption was the main contributor to this protective effect. No association was found between a healthy dietary pattern and colorectal adenoma risk or between a high-fat diet and colorectal neoplasm risk. Different CRC subtypes associated with gut microbiota enterotypes displayed unique microbial compositions and functions. Our study suggests that specific gut microbiota enterotypes can modulate the effects of diet on CRC risk, offering new perspectives on the relationship between diet, gut microbiota, and colorectal neoplasm risk.

Objectives: To study the relationship between skeletal muscle mass index (SMI) and metabolic phenotypes of obesity in adolescents, and to provide a basis for the prevention and control of adolescent obesity and related metabolic diseases., Methods: A total of 1 352 adolescents aged 12 to 18 years were randomly selected by stratified cluster sampling in Yinchuan City from October 2017 to September 2020, and they were surveyed using questionnaires, physical measurements, body composition measurements, and laboratory tests. According to the diagnostic criteria for metabolic abnormalities and the definition of obesity based on the body mass index, the subjects were divided into four metabolic phenotypes: metabolically healthy normal weight, metabolically healthy obesity, metabolically unhealthy normal weight, and metabolically unhealthy obesity. The association between SMI and the metabolic phenotypes was analyzed using multivariate logistic regression., Results: The SMI level in the metabolically unhealthy normal weight, metabolically healthy obesity, and metabolically unhealthy obesity groups was lower than that in the metabolically healthy normal weight group ( P <0.001). Multivariate logistic regression analysis showed that after adjusting for gender and age, a higher SMI level was a protective factors for adolescents to develop metabolic unhealthy normal weight, metabolically healthy obesity, and metabolically unhealthy obesity phenotypes ( OR =0.74, 0.60, and 0.54, respectively; P <0.001)., Conclusions: Increasing SMI can reduce the risk of the development of metabolic unhealthy/obesity.

Pancreatic cancer is the third leading cause of cancer-related death in the United States. Pancreatic ductal adenocarcinoma (PDAC) is the major form of pancreatic cancer with the worst outcomes. Early detection is key to improving the overall survival rate of PDAC patients. Recent studies have demonstrated that microRNA (miRNA) signatures in plasma small extracellular vesicles (EVs) are potential biomarkers for the early detection of PDAC. However, published results are inconsistent due to the heterogeneity of plasma small EVs and the methods used for small EV isolation. We have recently refined the process of plasma small EV isolation using double filtration and ultracentrifugation. In the present study, we applied this protocol and analyzed plasma small EV miRNA signatures by small RNA sequencing and quantitative RT-PCR in a pilot cohort, consisting of patients with early-stage PDAC, and age- and gender-matched healthy subjects (n = 20). We found, via small RNA sequencing, that there are several miRNAs enriched in plasma small EVs of PDAC patients, and the levels of miR-18a and miR-106a were confirmed by quantitative RT-PCR to be significantly elevated in patients with early-stage PDAC compared with age- and gender-matched healthy subjects. Furthermore, using an immunoaffinity-based plasma small EV isolation approach, we confirmed that the levels of miR-18a and miR-106a in plasma small EVs were significantly higher in PDAC patients versus the healthy subjects. We thus conclude that the levels of miR-18a and miR-106a in plasma small EVs are promising biomarkers for the early detection of PDAC.

Quantum heat engines are expected to outperform the classical counterparts due to quantum coherences involved. Here we experimentally execute a single-ion quantum heat engine and demonstrate, for the first time, the dynamics and the enhanced performance of the heat engine originating from the Liouvillian exceptional points (LEPs). In addition to the topological effects related to LEPs, we focus on thermodynamic effects, which can be understood by the Landau-Zener-Stückelberg process under decoherence. We witness a positive net work from the quantum heat engine if the heat engine cycle dynamically encircles a LEP. Further investigation reveals that a larger net work is done when the system is operated closer to the LEP. We attribute the enhanced performance of the quantum heat engine to the Landau-Zener-Stückelberg process, enabled by the eigenenergy landscape in the vicinity of the LEP, and the exceptional point-induced topological transition. Therefore, our results open new possibilities toward LEP-enabled control of quantum heat engines and of thermodynamic processes in open quantum systems.

With the development and generalization of endoscopic technology and screening, clinical application of magnetically controlled capsule gastroscopy (MCCG) has been increasing. In recent years, various types of MCCG are used globally. Therefore, establishing relevant guidelines on MCCG is of great significance. The current guidelines containing 23 statements were established based on clinical evidence and expert opinions, mainly focus on aspects including definition and diagnostic accuracy, application population, technical optimization, inspection process, and quality control of MCCG. The level of evidence and strength of recommendations were evaluated. The guidelines are expected to guide the standardized application and scientific innovation of MCCG for the reference of clinicians., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

The somatosensory system processes diverse types of information including mechanical, thermal, and chemical signals. It has an essential role in sensory perception and body movement and, thus, is crucial for organism survival. The neural network for processing somatosensory information comprises multiple key nodes. Spinal projection neurons represent the key node for transmitting somatosensory information from the periphery to the brain. Although the anatomy of spinal ascending pathways has been characterized, the mechanisms underlying somatosensory information processing by spinal ascending pathways are incompletely understood. Recent studies have begun to reveal the diversity of spinal ascending pathways and their functional roles in somatosensory information processing. Here, we review the anatomic, molecular, and functional characteristics of spinal ascending pathways., Competing Interests: Declaration of interests The authors declare no competing interests in relation to this work., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Chemo-resistance challenges the clinical management of pancreatic ductal adenocarcinoma (PDAC). A limited admittance of chemotherapeutics to PDAC tissues is a key obstacle in chemotherapy of the malignancy. An enhanced uptake of drugs into PDAC cells is required for a more effective treatment. Extracellular vesicles (EVs), especially small EVs (sEVs), have emerged as drug carriers for delivering chemotherapeutics due to their low immunogenicity and propensity for homing toward tumor cells. The present study evaluated sEVs derived from six different human cell lines as carriers for paclitaxel (PTX). The encapsulation of the chemotherapeutics was achieved using incubation, sonication and electroporation. The cytotoxicity of the EV drugs was evaluated by MTS assay. While sonication led to a higher efficiency of drug loading than incubation and electroporation, PTX loaded through incubation with HPNE-derived sEVs (HI-PTX) was the most efficacious in killing PDAC cells. Furthermore, HI-PTX was taken up by PDAC cells more efficiently than other EV drugs, implying that the efficacy of HI-PTX is associated with its efficient uptake. This was supported by the observation that the cytotoxicity and uptake of HI-PTX is mediated via the clathrin-dependent endocytosis. Our results indicate that the hTERT-HPNE cell-derived EVs are effective drug carriers to enhance paclitaxel's efficacy in PDAC cells.

A patient with chief complaint of bilateral progressive visual impairment was diagnosed with Fuchs corneal dystrophy (FECD) in both eyes, macular hole in the left eye, and intraocular lens eye in the right eye. After communication with the patient and his family, they agreed to receive Descemet's stripping without endothelial keratoplasty (DWEK) in the left eye. One year after the operation, the cornea of the left eye was transparent, and the central posterior elastic layer was missing about 4.0 mm diameter. The naked vision of left eye was 0.1, and the correction was not improved. It can be seen that DWEK surgery has a good therapeutic effect on patients with mild FECD.

Three new erythrina alkaloids, eryalkals A ( 1 ), B ( 2 ), and C ( 3 ), were isolated from the roots of Erythrina corallodendron L. Their structures, including their absolute configurations, were elucidated based on analyses of HR-ESI-MS, 1D/2D NMR and single-crystal X-ray diffraction techniques. The isolated erythrina alkaloids were screened for the antioxidant and cytotoxic activities. All the compounds showed no antioxidant activity and cytotoxic activities.

β-Alanine is the only naturally occurring β-amino acid, widely used in the fine chemical and pharmaceutical fields. In this study, metabolic design strategies were attempted in Escherichia coli W3110 for enhancing β-alanine biosynthesis. Specifically, heterologous L-aspartate-α-decarboxylase was used, the aspartate kinase I and III involved in competitive pathways were down-regulated, the β-alanine uptake system was disrupted, the phosphoenolpyruvate carboxylase was overexpressed, and the isocitrate lyase repressor repressing glyoxylate cycle shunt was delete, the glucose uptake system was modified, and the regeneration of amino donor was up-regulated. On this basis, a plasmid harboring the heterologous panD and aspB was constructed. The resultant strain ALA17/pTrc99a-panD BS -aspB CG could yield 4.20 g/L β-alanine in shake flask and 43.94 g/L β-alanine (a yield of 0.20 g/g glucose) in 5-L bioreactor via fed-batch cultivation. These modification strategies were proved effective and the constructed β-alanine producer was a promising microbial cell factory for industrial production of β-alanine., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

microRNAs (miRNA) in extracellular vesicles (EVs) have been investigated as potential biomarkers for pancreatic ductal adenocarcinoma (PDAC). However, a mixed population of EVs is often obtained using conventional exosome isolation methods for biomarker development. EVs are derived from different cellular processes and present in various sizes, therefore miRNA expression among them is undoubtedly different. We developed a simple protocol utilizing sequential filtration and ultracentrifugation to separate PDAC EVs into three groups, one with an average diameter of more than 220 nm, named operational 3 (OP3); one with average diameters between 100-220 nm, named operational 2 (OP2); and another with average diameters around 100 nm, named operational 1 (OP1)). EVs were isolated from conditioned cell culture media and plasma of human PDAC xenograft mice and early stage PDAC patients, and verified by nanoparticle tracking, western blot, and electronic microscopy. We demonstrate that exosome specific markers are only enriched in the OP1 group. qRT-PCR analysis of miRNA expression in EVs from PDAC cells revealed that expression of miR-196a and miR-1246, two previously identified miRNAs highly enriched in PDAC cell-derived exosomes, is significantly elevated in the OP1 group relative to the other EV groups. This was confirmed using plasma EVs from PDAC xenograft mice and patients with localized PDAC. Our results indicate that OP1 can be utilized for the identification of circulating EV miRNA signatures as potential biomarkers for PDAC., Competing Interests: The authors have declared that no competing interests exist.

Biological invasion is a hot topic in ecological research. Most studies on the physiological mechanisms of plants focus on leaves, but few studies focus on stems. To study the tolerance of invasive plant (Sphagneticola trilobata L.) to low temperature, relevant physiological indicators (including anthocyanin and chlorophyll) in different organs (leaves and stems) were analyzed, using a native species (Sphagneticola calendulacea L.) as the control. The results showed that, upon exposure to low temperature for 15 days, the stems of two Sphagneticola species were markedly reddened, their anthocyanin content increased, chlorophyll and chlorophyll fluorescence parameters decreased, and the accumulation of reactive oxygen species in the stem increased. The percentage increases of antioxidants and total antioxidant capacities in stems were significantly higher in S. trilobata than in S. calendulacea. This showed that S. trilobata had higher cold tolerance in stems while leaves were opposite. To further verify the higher cold tolerance of the stem of S. trilobata, a defoliation experiment was designed. We found that the defoliated stem of S. trilobata reduced anthocyanin accumulation and increased chlorophyll content, while alleviating membrane lipid damage and electrical conductivity, and the defoliated stem still showed an increase in stem diameter and biomass under low temperature. The discovery of the physiological and adaptive mechanisms of the stem of S. trilobata to low temperature will provide a theoretical basis for explaining how S. trilobata maintains its annual growth in South China. This is of great significance for predicting the future spread of cloned and propagated invasive plants., (© 2020. Springer Nature B.V.)

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers with rapid progression and a high mortality rate. Our previous study demonstrated that DNA polymerase iota (Pol ι) is overexpressed in ESCC tumors and correlates with poor prognosis. However, its role in ESCC proliferation remains obscure. We report here that Pol ι promotes ESCC proliferation and progression through Erk- O-GlcNAc transferase (OGT) regulated Glucose-6-phosphate dehydrogenase (G6PD) overactivation. Cell clonogenic ability was assessed by colony formation assay. Cell proliferation was assessed by EdU incorporation assay. Our transcriptome data was reanalyzed by GSEA and validated by analysis of cellular metabolism, G6PD activity, and cellular NADPH concentration. The level of Pol ι, OGT, G6PD and O-GlcNAcylation in ESCC cells and patient samples were analyzed. The MEK inhibitor PD98059 was applied to confirm OGT expression regulation by the Erk signaling. The G6PD inhibitor polydatin was used to examine the role of G6PD activation in Pol ι promoted proliferation. We found that Pol ι promotes ESCC proliferation. It shunted the glucose flux towards the pentose phosphate pathway (PPP) by activating G6PD through OGT-promoted O-GlcNAcylation. The expression of OGT was positively correlated with Pol ι expression and O-GlcNAcylation. Notably, elevated O-GlcNAcylation was correlated with poor prognosis in ESCC patients. Pol ι was shown to stimulate Erk signaling to enhance OGT expression, and the G6PD inhibitor polydatin attenuated Pol ι induced tumor growth in vitro and in vivo . In conclusion, Pol ι activates G6PD through Erk-OGT-induced O-GlcNAcylation to promote the proliferation and progression of ESCC, supporting the notion that Pol ι is a potential biomarker and therapeutic target of ESCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Su, Gao, Li, Zou, He, Wu, Ding and Zhou.)

Recently, smart nanomaterials from peptide self-assembly have received extensive attention in the field of biological and medical applications. Through rationally designing the molecular structure, we constructed a borono-peptide that self-assembled into well-defined nanofibers. Relying on the specific recognition between the vicinal diol compound and boronic acid, a novel alizarin red S (ARS)-borono-peptide (BP) spherical nanoindicator was fabricated, accompanying with the emission of strong fluorescent signal. The fluorescent nanoindicator displayed an intense response to copper(II) ions and underwent the fluorescent "turn-off" due to the strong binding-induced displacement. Originating from the high selectivity toward copper(II) ions, good biocompatibility and cancer cell targeting, the nanoindicator offered the opportunity to image copper(II) ions in cancer cells via fluorescent change.

Background: Radiotherapy is one of the main strategies for the treatment of esophageal squamous cell carcinoma (ESCC). However, treatment failure often occurs due to the emergence of radioresistance. In this study, we report a key regulator of radiation sensitivity, termed TAB182 that may become an ideal biomarker and therapeutic target to overcome radioresistance., Materials and Methods: By applying qRT-PCR and immunohistochemical staining, the expression of TAB182 was detected in patient tissues. We next assessed the influence of TAB182 downregulation to radiosensitivity using clonogenic survival assay and γ-H2A.X foci analysis in TE-1, TE-10, and radioresistant TE-1R cell lines after ionizing radiation. To unveil the mechanism underlying, TAB182 interacting proteins were identified by mass spectrometry following co-immunoprecipitation. Furthermore, flow cytometry and western blot assay were applied to validate the identified proteins., Results: Our results demonstrated that the expression of TAB182 is higher in cancer tissues than normal tissues and elevated expression of TAB182 correlates with poor outcomes of postoperative radiotherapy. Downregulation of TAB182 sensitized cancer cells to ionizing radiation, particularly in radioresistant TE-1R cells that spontaneously overexpress TAB182. Mechanically, TAB182 interacts with FHL2 to induce G2-M arrest through wiring the CHK2/CDC25C/CDC2 signaling pathway. Finally, overexpression of shRNA-resistant TAB182 restored the checkpoint and radioresistance., Conclusion: TAB182 potentiates the radioresistance of ESCC cells by modulating the G2-M checkpoint through its interaction with FHL2. Thus, TAB182 may become an ideal biomarker and therapeutic target of ESCC radiotherapy., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Despite the rapid progress in peptide liquid crystals (LCs) due to their prominent properties, our investigation on flexible peptide-based LCs is incomplete, mainly resulted from their unclear formation mechanisms and unexploited applications in organic solvents. Here, we develop a lyotropic LC based on a flexible oligopeptide amphiphile, which aggregates into aligned cylinder-like nanostructures in dimethyl sulfoxide (DMSO). The formation mechanism of lyotropic LC in DMSO was probed by the experimental investigation and molecular dynamics simulation, indicating that the hydrogen bonding and hydrophobic and electrostatic interactions contribute to the formation of ordered nanostructures in the organic solvent. Arising from the orientational order and suitable fluidity, we exploit the application of lyotropic LC as an aligned medium to measure the residual dipolar couplings of bioactive molecules. This study not only offers the understanding of the mechanism to create LC systems without rigid aromatic groups but also expands the applications of ordered bottom-up nanomaterials in organic solvents.

Sphagneticola trilobata (L.) Pruski is one of the fast-growing malignant weeds in South China. It has severely influenced local biodiversity and native plant habitat. Photosynthesis is the material basis of plant growth and development. However, there are few reports on the photosynthetic transcriptome of S. trilobata. In this study, S. trilobata had a relatively large leaf area and biomass. The gas exchange parameters per unit area of leaves, including net photosynthetic capacity (P n ), intercellular CO 2 (C i ), stomatal conductance (G s ), transpiration rate (T r ), water use efficiency (WUE), photosynthetic pigment and Rubisco protein content were higher than those of the native plant Sphagneticola calendulacea (L.) Pruski. On this basis, the differences in photosynthesis pathways between the two Sphagneticola species were analyzed by using the Illumina HiSeq platform. The sequencing results for S. trilobata and S. calendulacea revealed 159,366 and 177,069 unigenes, respectively. Functional annotation revealed 119,350 and 150,846 non-redundant protein database annotations (Nr), 96,637 and 115,711 Swiss-Prot annotations, 49,159 and 60,116 Kyoto Encyclopedia of Genes and Genomes annotations (KEGG), and 83,712 and 97,957 Gene Ontology annotations (GO) in S. trilobata and S. calendulacea, respectively. Additionally, our analysis showed that the expression of key protease genes involved in the photosynthesis pathway, particularly CP43, CP47, PsbA and PetC, had high expression levels in leaves of S. trilobata in comparison to native species. Physiological and transcriptomic analyses suggest the high expression of photosynthetic genes ensures the high photosynthetic capacity of leaves, which is one of the inherent advantages underlying the successful invasion by S. trilobata.

Extracellular vesicles (EVs) are small lipid bilayer-delimited nanoparticles released from all types of cells examined thus far. Several groups of EVs, including exosomes, microvesicles, and apoptotic bodies, have been identified according to their size and biogenesis. With extensive investigations on EVs over the last decade, it is now recognized that EVs play a pleiotropic role in various physiological processes as well as pathological conditions through mediating intercellular communication. Most notably, EVs have been shown to be involved in cancer initiation and progression and EV signaling in cancer are viewed as potential therapeutic targets. Furthermore, as membrane nanoparticles, EVs are natural products with some of them, such as tumor exosomes, possessing tumor homing propensity, thus leading to strategies utilizing EVs as drug carriers to effectively deliver cancer therapeutics. In this review, we summarize recent reports on exploring EVs signaling as potential therapeutic targets in cancer as well as on developing EVs as therapeutic delivery carriers for cancer therapy. Findings from preclinical studies are primarily discussed, with early phase clinical trials reviewed. We hope to provide readers updated information on the development of EVs as cancer therapeutic targets or therapeutic carriers.

Background: Exosomes are extracellular vesicles containing a variety of biological molecules including microRNAs (miRNAs). We have recently demonstrated that certain miRNA species are selectively and highly enriched in pancreatic cancer exosomes with miR-1246 being the most abundant. Exosome miRNAs have been shown to mediate intercellular communication in the tumor microenvironment and promote cancer progression. Therefore, understanding how exosomes selectively enrich specific miRNAs to initiate exosome miRNA signaling in cancer cells is critical to advancing cancer exosome biology., Results: The aim of this study was to identify RNA binding proteins responsible for selective enrichment of exosome miRNAs in cancer cells. A biotin-labeled miR-1246 probe was used to capture RNA binding proteins (RBPs) from PANC-1 cells. Among the RBPs identified through proteomic analysis, SRSF1, EIF3B and TIA1 were highly associated with the miR-1246 probe. RNA immunoprecipitation (RIP) and electrophoretic mobility shift assay (EMSA) confirmed the binding of SRSF1 to miR-1246. Lentivirus shRNA knockdown of SRSF1 in pancreatic cancer cells selectively reduced exosome miRNA enrichment whereas GFP-SRSF1 overexpression enhanced the enrichment as analyzed by next generation small RNA sequencing and qRT-PCR. miRNA sequence motif analysis identified a common motif shared by 36/45 of SRSF1-associated exosome miRNAs. EMSA confirmed that shared motif decoys inhibit the binding of SRSF1 to the miR-1246 sequence., Conclusions: We conclude that SRSF1 mediates selective exosome miRNA enrichment in pancreatic cancer cells by binding to a commonly shared miRNA sequence motif. Video Abstract.

The retinal pigment epithelium (RPE), the outermost layer of the retina, provides essential support to both the neural retina and choroid. Additionally, the RPE is highly active in modulating functions of immune cells such as microglia, which migrate to the subretinal compartment during aging and age-related degeneration. Recently, studies have highlighted the important roles of microRNA (miRNA) in the coordination of general tissue maintenance as well as in chronic inflammatory conditions. In this study, we analyzed the miRNA profiles in extracellular vesicles (EVs) released by the RPE, and identified and validated miRNA species whose expression levels showed age-dependent changes in the EVs. Using co-culture of RPE and retinal microglia, we further demonstrated that miR-21 was transferred between the two types of cells, and the increased miR-21 in microglia influenced the expression of genes downstream of the p53 pathway. These findings suggest that exosome-mediated miRNA transfer is a signaling mechanism that contributes to the regulation of microglia function in the aging retina.

Background and Aim: Clear visualization of the small bowel is a requirement for satisfactory video capsule endoscopy (VCE). The aim of this study was to identify the optimal dose and timing of polyethylene glycol (PEG) for small bowel preparation before VCE., Methods: A total of 410 patients were enrolled in this prospective randomized trial. All patients fasted for 12 h and ingested 320 mg simethicone 30 min before swallowing the capsule. Patients were randomized into five groups: Group A (no PEG), Group B (1-L PEG, 12 h before VCE), Group C (2-L PEG, 12 h before VCE), Group D (1-L PEG, 4 h before VCE), and Group E (2-L PEG, 4 h before VCE). The primary endpoint was small bowel visualization quality (SBVQ), and the secondary endpoints were patient acceptability and diagnosis rate of VCE., Results: Excellent SBVQ was achieved in 27 (32.5%) of Group A, 38 (46.3%) of Group B, 40 (48.2%) of Group C, 55 (66.3%) of Group D, and 43 (54.4%) of Group E. The percentage of excellent SBVQ in Group D was significantly more than in Group A (66.3% vs 32.5%, P < 0.001), and diagnostic rate in the distal segment was higher (28.9% vs 10.8%, P = 0.0035). Patient acceptance of 1-L PEG was better than of 2-L PEG (P < 0.005)., Conclusion: Small bowel cleansing with 1-L PEG given 4 h before VCE was the optimal preparation for visualization of the bowel and patient acceptance (ClinicalTrials.gov, ID: NCT02486536)., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Esophageal squamous cell carcinoma (ESCC) is an aggressive type of cancer with high mortality rate in China, largely due to its high invasive and metastatic potential. The purposes of this study are to investigate the potential molecular mechanisms behind the aggressive nature of ESCC and search for new prognostic biomarkers. By employing the quantitative proteomic based strategy, we compared the proteomic profile between three ESCC samples and paired adjacent tissues. After bioinformatics analysis, four candidate proteins were validated in thirteen paired patient samples. Further validation of the key candidate, integrin-linked kinase (ILK), was carried out in one hundred patient samples. The specific inhibitor compound 22 (cpd22) was used to assess the influence of ILK to ESCC cell motility and invasiveness by applying wound-healing and transwell assay. Western blot analysis was performed to elucidate the signaling pathways involved in ILK-mediated ESCC invasion. Total 236 proteins were identified by proteomic analysis. Bioinformatics analysis suggested a key role of the collagen/integrin/ILK signaling pathway during ESCC progression. Further validation indicated that ILK is overexpressed in ESCC tissues and is correlated with poor patient prognosis. Inhibition of ILK kinase activity suppresses proliferation and blocks invasion and migration of ESCC cells. Signaling pathway analysis revealed that ILK regulates AKT phosphorylation on Ser473 but not GSK-3β on Ser9 to promote proliferation and motility of ESCC cells. In conclusion, our results indicated that ILK may play a crucial role in ESCC invasion and metastasis and may serve as a prognostic biomarker and therapeutic target for ESCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

This project is to investigate chemical compositions from the roots of Erythrina corallodendron. Through the methods of silica gel,ODS,Sephadex LH-20 column chromatography and preparative HPLC,15 compounds were isolated from the 95% ethanol extract of the roots of E. corallodendron. Based on spectroscopic techniques,the structures of these compounds were identified as 10,11-dioxoerythraline( 1),erythrinine( 2),erythraline( 3),11-methoxyerythraline( 4),cristanines B( 5),erythratine( 6),erysotrine( 7),medioresinol( 8),( ±)-ficusesquilignan A( 9),( +)-pinoresinol( 10),nicotinic acid( 11),dibutyl phthalate( 12),vanillic acid( 13),3-hydroxy-1-( 4-hydroxy-3-methoxyphenyl)-1-propanone( 14),and syringic acid( 15). Compounds 8-10 are isolated from genus Erythrina for the first time and all compounds are isolated from E. corallodendron for the first time. Furthermore,this paper screened the antioxidant and cytotoxic activities of the compounds using models of liver microsomal oxidation inhibition and MTT.

Background: Altered expression of microRNAs (miRNAs) is known to contribute to cancer progression. miR-23b and miR-27b, encoded within the same miRNA cluster, are reported to have both tumor suppressive and oncogenic activity across human cancers, including breast cancer., Methods: To clarify this dichotomous role in breast cancer, miR-23b and miR-27b were knocked out using CRISPR/Cas9 gene knockout technology, and the role of endogenous miR-23b and miR-27b was examined in a breast cancer model system in vitro and in vivo., Results: Characterization of the knockout cells in vitro demonstrated that miR-23b and miR-27b are indeed oncogenic miRNAs in MCF7 breast cancer cells. miR-23b and miR-27b knockout reduced tumor growth in xenograft nude mice fed a standard diet, supporting their oncogenic role in vivo. However, when xenograft mice were provided a fish-oil diet, miR-27b depletion, but not miR-23b depletion, compromised fish-oil-induced suppression of xenograft growth, indicating a context-dependent nature of miR-27b oncogenic activity., Conclusions: Our results demonstrate that miR-23b and miR-27b are primarily oncogenic in MCF7 breast cancer cells and that miR-27b may have tumor suppressive activity under certain circumstances.

Neoadjuvant chemoradiotherapy (nCRT) has been widely applied to improve the local control rate and survival rate in patients with locally advanced rectal cancer (LARC), yet only part of LARC patients would benefit from nCRT. Therefore, it is imperative to predict the therapeutic outcome of nCRT. Here, we showed that RAD18, an E3 ubiquitin-linked enzyme, played a fundamental role in predicting the response of LARC patients to nCRT. According to clinical data, patients with low RAD18 expression level in their pre-nCRT biopsies had a superior response to nCRT compared to those with high RAD18 expression. Inhibition of RAD18 expression in rectal cancer cells pronouncedly attenuated the proliferation and promoted apoptosis after exposing to irradiation or/and 5-fluorouracil (5-Fu). Downregulated RAD18 levels increased cell apoptosis by activating caspase-9-caspase-3-mediated apoptotic pathway, thus resulting in the enhancement of cell radiosensitivity and 5-Fu susceptibility. Furthermore, a xenograft nude mouse model showed that silencing RAD18 significantly slowed tumor growth after irradiation or/and 5-Fu in vivo. Collectively, these results implied that RAD18 could be a new biomarker to predict LARC patients who might benefit from nCRT and provide new strategies for clinical treatment of LARC., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Competing Interests: None

miR-1246 is considered an oncomiR in various cancer types. However, the origin and biogenesis of miR-1246 remain controversial which often leads to misinterpretation of its detection and biological function, and inevitably masking its mechanisms of action. Using next generation small RNA sequencing, CRISPR-Cas9 knockout, siRNA knockdown and the poly-A tailing SYBR qRT-PCR, we examined the biogenesis of exosomal miR-1246 in human cancer cell model systems. We found that miR-1246 is highly enriched in exosomes derived from human cancer cells and that it originates from RNU2-1, a small nuclear RNA and essential component of the U2 complex of the spliceosome. Knockdown of Drosha and Dicer did not reduce exosomal miR-1246 levels, indicating that exosomal miR-1246 is generated in a Drosha- and Dicer-independent manner. Direct digestion of cellular lysate by RNase A and knockdown of the RNU2-1 binding protein SmB/B' demonstrated that exosomal miR-1246 is a RNU2-1 degradation product. Furthermore, the GCAG motif present in the RUN2-1 transcript was shown to mediate miR-1246 enrichment in cancer exosomes. We conclude that exosome miR-1246 is derived from RNU2-1 degradation through a non-canonical microRNA biogenesis process. These findings reveal the origin of an oncomiR in human cancer cells, providing guidance in understanding miR-1246 detection and biological function. Abbreviations: CRISPR, Clustered Regularly Interspaced Short Palindromic Repeats; miRNA, microRNA; PDAC, pancreatic ductal adenocarcinoma; RNU2-1, U2 small nuclear RNA; RT-PCR, Reverse transcription polymerase chain reaction; sgRNA, single-guide RNA.

miRNAs are small RNAs that influence gene expression by targeting mRNAs. Depending on the function of their target genes, miRNAs may regulate the expression of oncogenes and tumor suppressors, thereby contributing to the promotion or inhibition of tumor progression. Ductal carcinoma in situ (DCIS), although often diagnosed as breast cancer, is a potential precursor to invasive ductal carcinoma. Many of the genetic events required for the invasive progression of DCIS occur at the preinvasive stage, and these events include changes in the expression of miRNAs. Aberrant expression of miRNAs can influence specific oncogenic or tumor-suppressive pathways required for breast cancer progression. miRNAs in DCIS have been shown to influence hormone signaling, cell-cell adhesion, epithelial-to-mesenchymal transition, transforming growth factor β signaling, maintenance of cancer stem cells, and modulation of the extracellular matrix. Additionally, extracellular DCIS miRNAs, such as those found in exosomes, may promote invasive progression by modifying the tumor microenvironment. Here, we review the miRNAs that have been identified in DCIS and how they may contribute to the progression to invasive disease. We also touch on the current state of miRNA therapy development, including the current challenges, and discuss the key future perspectives for research into miRNA function for the purpose of miRNA therapy development for DCIS., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Chronic active Esptein-Barr virus (CAEBV) enteritis if rarely observed in immunocompetent patients and can be often misdiagnosed as inflammatory bowel disease., Case: We hereby present a case of CAEBV enteritis diagnosed with double-balloon enteroscopy and EBER in-situ hybridization., Conclusion: This case demonstrates the clinical presentation and diagnosis of CAEBV enteritis and highlights the importance of early recognition of the disease., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Exosomes are small membrane-bound vesicles that contribute to tumor progression and metastasis by mediating cell-to-cell communication and modifying the tumor microenvironment at both local and distant sites. However, little is known about the predominant factors in exosomes that contribute to breast cancer (BC) progression. MTA1 is a transcriptional co-regulator that can act as both a co-activator and co-repressor to regulate pathways that contribute to cancer development. MTA1 is also one of the most up-regulated proteins in cancer, whose expression correlates with cancer progression, poor prognosis and increased metastatic potential., Methods: We identified MTA1 in BC exosomes by antibody array and confirmed expression of exosome-MTA1 across five breast cancer cells lines. Ectopic expression of tdTomato-tagged MTA1 and exosome transfer were examined by fluorescent microscopy. CRISPR/Cas9 genetic engineering was implemented to knockout MTA1 in MCF7 and MDA-MB-231 breast cancer cells. Reporter assays were used to monitor hypoxia and estrogen receptor signaling regulation by exosome-MTA1 transfer., Results: Ectopic overexpression of tdTomato-MTA1 in BC cell lines demonstrated exosome transfer of MTA1 to BC and vascular endothelial cells. MTA1 knockout in BC cells reduced cell proliferation and attenuated the hypoxic response in these cells, presumably through its co-repressor function, which could be rescued by the addition of exosomes containing MTA1. On the other hand, consistent with its co-activator function, estrogen receptor signaling was enhanced in MTA1 knockout cells and could be reversed by addition of MTA1-exosomes. Importantly, MTA1 knockout sensitized hormone receptor negative cells to 4-hydroxy tamoxifen treatment, which could be reversed by the addition of MTA1-exosomes., Conclusions: This is the first report showing that BC exosomes contain MTA1 and can transfer it to other cells resulting in changes to hypoxia and estrogen receptor signaling in the tumor microenvironment. These results, collectively, provide evidence suggesting that exosome-mediated transfer of MTA1 contributes to BC progression by modifying cellular responses to important signaling pathways and that exosome-MTA1 may be developed as a biomarker and therapeutic target for BC.