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Azo switches are widely employed as essential components in light-responsive systems. Here, we develop an azo-fluorescent switch that is visible light-responsive and its light-responsive processes can be monitored using fluorescence imaging. Visible light irradiation promotes isomerization, accompanied by changes in fluorescence that enable the process to be monitored through fluorescence imaging. Furthermore, we document that the nanocavity size of liposome encapsulated nanoparticles containing azo changes in the isomerization process and show that this change enables construction of a light-responsive nanoplatform for optically controlled release of antimycotics. Also, natural light activation of nanoparticles of the switch loaded with an antimycotic agent causes death of Rhizoctonia solani. The results show that these nanoparticles can double the holding period in comparison to small molecule antimycotics. The strategy used to design the imaging-guided light-controlled nano-antimycotic release system can be applicable to protocols for controlled delivery of a wide variety of drugs., (© 2024. The Author(s).)

Introduction: Brain organoids are believed to be able to regenerate impaired neural circuits and reinstate brain functionality. The neuronal activity of organoids is considered a crucial factor for restoring host function after implantation. However, the optimal stage of brain organoid post-transplantation has not yet been established. External electrical signal plays a crucial role in the physiology and development of a majority of human tissues. However, whether electrical input modulates the development of brain organoids, making them ideal transplant donors, is elusive., Methods: Bioelectricity was input into cortical organoids by electrical stimulation (ES) with a multi-electrode array (MEA) to obtain a better-transplanted candidate with better viability and maturity, realizing structural-functional integration with the host brain., Results: We found that electrical stimulation facilitated the differentiation and maturation of organoids, displaying well-defined cortical plates and robust functional electrophysiology, which was probably mediated via the pathway of calcium-calmodulin (CaM) dependent protein kinase II (CAMK II)-protein kinase A (PKA)-cyclic-AMP response binding protein (pCREB). The ES-pretreated D40 organoids displayed superior cell viability and higher cell maturity, and were selected to transplant into the damaged primary sensory cortex (S1) of host. The enhanced maturation was exhibited within grafts after transplantation, including synapses and complex functional activities. Moreover, structural-functional integration between grafts and host was observed, conducive to strengthening functional connectivity and restoring the function of the host injury., Conclusion: Our findings supported that electrical stimulation could promote the development of cortical organoids. ES-pretreated organoids were better-transplanted donors for strengthening connectivity between grafts and host. Our work presented a new physical approach to regulating organoids, potentially providing a novel translational strategy for functional recovery after brain injury. In the future, the development of 3D flexible electrodes is anticipated to overcome the drawbacks of 2D planar MEA, promisingly achieving multimodal stimulation and long-term recordings of brain organoids., 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. Production and hosting by Elsevier B.V.)

Objective: To explore the clinical efficacy and safety of transarterial chemoembolization (TACE) combined with targeted therapy for primary hepatocellular carcinoma (PHC)., Methods: This was a retrospective study. Retrospective selection of 150 PHC patients admitted to the Renmin Hospital, Hubei University of Medicine January 2019 and June 2021 were included. The patients were divided into the control group and the experimental group according to their treatment regimens. The control group received TACE treatment, while the experimental group received TACE combined with targeted therapy. We analyze the relevant data of two groups of patients and evaluate the clinical efficacy and safety of TACE combined with targeted therapy., Results: The tumor remission rate and control rate in the control group were 41.89% and 75.68%, respectively, while those in the experimental group were 77.63% and 90.79%, with statistically significant differences (p<0.05). The 1-year and 3-year recurrence rates in the control group were 52.71% and 98.65%, respectively, while those in the experimental group were 39.47% and 61.84%, with statistically significant differences (p<0.05). After treatment, the AFP, VEGF, ALT, and AST in the experimental group were significantly reduced compared to the control group (p<0.05). During the treatment period, the incidence and severity of nausea, vomiting, and fever in the experimental group were significantly lower than those in the control group (p<0.05)., Conclusion: The clinical efficacy of TACE combined with targeted therapy for PHC is superior to that of TACE alone, with improved disease control rate, improved long-term survival rate, and good safety., Competing Interests: Conflicts of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Phenylketonuria (PKU), hereditary tyrosinemia type 1 (HT1), and mucopolysaccharidosis type 1 (MPSI) are autosomal recessive disorders linked to the phenylalanine hydroxylase ( PAH ) gene, fumarylacetoacetate hydrolase ( FAH ) gene, and alpha-L-iduronidase ( IDUA ) gene, respectively. Potential therapeutic strategies to ameliorate disease include corrective editing of pathogenic variants in the PAH and IDUA genes and, as a variant-agnostic approach, inactivation of the 4-hydroxyphenylpyruvate dioxygenase ( HPD ) gene, a modifier of HT1, via adenine base editing. Here we evaluated the off-target editing profiles of therapeutic lead guide RNAs (gRNAs) that, when combined with adenine base editors correct the recurrent PAH P281L variant, PAH R408W variant, or IDUA W402X variant or disrupt the HPD gene in human hepatocytes. To mitigate off-target mutagenesis, we systematically screened hybrid gRNAs with DNA nucleotide substitutions. Comprehensive and variant-aware specificity profiling of these hybrid gRNAs reveal dramatically reduced off-target editing and reduced bystander editing. Lastly, in a humanized PAH P281L mouse model, we showed that when formulated in lipid nanoparticles (LNPs) with adenine base editor mRNA, selected hybrid gRNAs revert the PKU phenotype, substantially enhance on-target editing, and reduce bystander editing in vivo . These studies highlight the utility of hybrid gRNAs to improve the safety and efficacy of base-editing therapies., Competing Interests: M.N.W. is a fellow with Artis Ventures. J.Z.W. is an employee of Agilent Technologies. R.C.A.-N. is an advisor to Latus Bio. K.M. is an advisor to and holds equity in Verve Therapeutics and Variant Bio, is an advisor to LEXEO Therapeutics, and receives research funding from Nava Therapeutics and Beam Therapeutics. M.-G.A. is an advisor to Afrigen Biologics. The University of Pennsylvania and Children’s Hospital of Philadelphia have filed patent applications related to the use of base editing for the treatment of phenylketonuria and tyrosinemia (inventors include M.N.W., D.L.B., R.C.A.-N., K.M., W.H.P., and X.W.).The remaining authors declare no competing interests.

The exploitation of carbon dioxide (CO 2 ) as a sustainable, plentiful, and harmless C1 source for the catalytic synthesis of enantioenriched carboxylic acids has long been acknowledged as a pivotal task in synthetic chemistry. Herein, we present a current-driven nickel-catalyzed reductive carboxylation reaction with CO 2 fixation, facilitating the formation of C(sp 3 )-C(sp 2 ) bonds by circumventing the handling of moisture-sensitive organometallic reagents. This electroreductive protocol serves as a practical platform, paving the way for the synthesis of enantioenriched propargylic carboxylic acids (up to 98% enantiomeric excess) from racemic propargylic carbonates and CO 2 . The efficacy of this transformation is exemplified by its successful utilization in the asymmetric total synthesis of ( S )-arundic acid, ( R )-PIA, ( S )-chizhine D, ( S )-cochlearin G, and ( S , S )-alexidine, thereby underscoring the potential of asymmetric electrosynthesis to achieve complex molecular architectures sustainably.

The reconstruction of neural function and recovery of chronic damage following traumatic brain injury (TBI) remain significant clinical challenges. Exosomes derived from neural stem cells (NSCs) offer various benefits in TBI treatment. Numerous studies confirmed that appropriate preconditioning methods enhanced the targeted efficacy of exosome therapy. Interferon-gamma (IFN-γ) possesses immunomodulatory capabilities and is widely involved in neurological disorders. In this study, IFN-γ was employed for preconditioning NSCs to enhance the efficacy of exosome (IFN-Exo, IE) for TBI. miRNA sequencing revealed the potential of IFN-Exo in promoting neural differentiation and modulating inflammatory responses. Through low-temperature 3D printing, IFN-Exo was combined with collagen/chitosan (3D-CC-IE) to preserve the biological activity of the exosome. The delivery of exosomes via biomaterial scaffolds benefited the retention and therapeutic potential of exosomes, ensuring that they could exert long-term effects at the injury site. The 3D-CC-IE scaffold exhibited excellent biocompatibility and mechanical properties. Subsequently, 3D-CC-IE scaffold significantly improved impaired motor and cognitive functions after TBI in rat. Histological results showed that 3D-CC-IE scaffold markedly facilitated the reconstruction of damaged neural tissue and promoted endogenous neurogenesis. Further mechanistic validation suggested that IFN-Exo alleviated neuroinflammation by modulating the MAPK/mTOR signaling pathway. In summary, the results of this study indicated that 3D-CC-IE scaffold engaged in long-term pathophysiological processes, fostering neural function recovery after TBI, offering a promising regenerative therapy avenue., Competing Interests: The authors report no competing interests., (© 2024 The Authors.)

Upgrading CO 2 to value-added chiral molecules via catalytic asymmetric C-C bond formation is a highly important yet challenging task. Although great progress on the formation of centrally chiral carboxylic acids has been achieved, catalytic construction of axially chiral carboxylic acids with CO 2 has never been reported to date. Herein, we report the first catalytic asymmetric synthesis of axially chiral carboxylic acids with CO 2 , which is enabled by nickel-catalyzed dynamic kinetic asymmetric reductive carboxylation of racemic aza-biaryl triflates. A variety of important axially chiral carboxylic acids, which are valuable but difficult to obtain via catalysis, are generated in an enantioconvergent version. This new methodology features good functional group tolerance, easy to scale-up, facile transformation and avoids cumbersome steps, handling organometallic reagents and using stoichiometric chiral materials. Mechanistic investigations indicate a dynamic kinetic asymmetric transformation process induced by chiral nickel catalysis., (© 2024 Wiley-VCH GmbH.)

Human brain organoids represent a remarkable platform for modeling neurological disorders and a promising brain repair approach. However, the effects of physical stimulation on their development and integration remain unclear. Here, we report that low-intensity ultrasound significantly increases neural progenitor cell proliferation and neuronal maturation in cortical organoids. Histological assays and single-cell gene expression analyses reveal that low-intensity ultrasound improves the neural development in cortical organoids. Following organoid grafts transplantation into the injured somatosensory cortices of adult mice, longitudinal electrophysiological recordings and histological assays reveal that ultrasound-treated organoid grafts undergo advanced maturation. They also exhibit enhanced pain-related gamma-band activity and more disseminated projections into the host brain than the untreated groups. Finally, low-intensity ultrasound ameliorates neuropathological deficits in a microcephaly brain organoid model. Hence, low-intensity ultrasound stimulation advances the development and integration of brain organoids, providing a strategy for treating neurodevelopmental disorders and repairing cortical damage., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes have been reported to be effective in the treatment of cancer. The miR-214-3p is a suppressor miRNA that has been extensively studied and has been proposed as a diagnostic and prognostic biomarker in some cancers., Objectives: The aim of this study was to investigate whether the regulatory mechanism of hucMSC-derived exosomal miR-214-3p with GLUT1 and ACLY affects the proliferation and apoptosis of gallbladder cancer (GBC) cells., Material and Methods: We found that the target genes of miR-214-3p on the TargetScan website contain GLUT1 and ACLY, and the targeting relationship was verified using luciferases. The GBC-SD cells overexpressing GLUT1 and ACLY were constructed to determine proliferation, apoptosis, migration, and other cellular activities., Results: We identified hucMSCs and exosomes, and found that the exosomes contained miR-214-3p. Furthermore, TargetScan predicted that miR-214-3p had base interactions with ACLY. Dual luciferase assays showed that miR-214-3p could inhibit ACLY (p < 0.05). The results of quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot showed that exosomal miR-214-3p could inhibit the expression of ACLY and GLUT1 (p < 0.05). Exosomal miR-214-3p can inhibit the proliferation, cloning and migration of GBC-SD cells (p < 0.05). The apoptosis of GBC-SD cells was increased (p < 0.05). The GBC-SD cells overexpressing ACLY and GLUT1 could reverse the efficacy of miR-214-3p., Conclusions: Exosomal miR-214-3p can inhibit the downstream expression of ACLY and GLUT1. The ACLY and GLUT1 could affect the proliferation and apoptosis of GBC-SD cells.

Background: Breast cancer (BC) continues to pose a substantial challenge to global health, necessitating an enhanced understanding of its fundamental mechanisms. Among its various pathological classifications, breast invasive carcinoma (BRCA) is the most prevalent. The role of the transcription factor forkhead box P3 ( FOXP3 ), associated with regulatory T cells, in BRCA's diagnosis and prognosis remains insufficiently explored, despite its recognized importance., Methods: We examined the mRNA expression profile of FOXP3 in BRCA patients, assessing its correlation with disease detection, patient survival, immune checkpoint alterations, and response to anticancer drugs., Results: Our analysis revealed significantly elevated FOXP3 mRNA levels in BRCA patients, with a 95.7% accuracy for BRCA detection based on the area under the curve. High FOXP3 mRNA levels were positively correlated with overall survival and showed significant associations with CTLA4, CD274, PDCD1 , TMB, and immune cell infiltration status. Furthermore, FOXP3 mRNA expression was linked to the efficacy of anticancer drugs and the tumor inflammation signature., Discussion: These findings suggest that FOXP3 serves as a promising biomarker for BRCA, offering valuable insights into its diagnosis and prognosis. The correlation between FOXP3 expression and immune checkpoint alterations, along with its predictive value for treatment response, underscores its potential in guiding therapeutic strategies., Conclusion: FOXP3 stands out as an influential factor in BRCA, highlighting its diagnostic accuracy and prognostic value. Its association with immune responses and treatment efficacy opens new avenues for research and clinical applications, positioning FOXP3 as a vital target for further investigation in BRCA management., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Liu et al.)

Detecting early warning indicators for abrupt dynamical transitions in complex systems or high-dimensional observation data are essential in many real-world applications, such as brain diseases, natural disasters, and engineering reliability. To this end, we develop a novel approach: the directed anisotropic diffusion map that captures the latent evolutionary dynamics in the low-dimensional manifold. Then three effective warning signals (Onsager-Machlup indicator, sample entropy indicator, and transition probability indicator) are derived through the latent coordinates and the latent stochastic dynamical systems. To validate our framework, we apply this methodology to authentic electroencephalogram data. We find that our early warning indicators are capable of detecting the tipping point during state transition. This framework not only bridges the latent dynamics with real-world data but also shows the potential ability for automatic labeling on complex high-dimensional time series., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Competing Interests: Conflict of interest statement. The authors have no conflict of interest to declared.

Dicarboxylic acids and derivatives are important building blocks in organic synthesis, biochemistry, and the polymer industry. Although catalytic dicarboxylation with CO 2 represents a straightforward and sustainable route to dicarboxylic acids, it is still highly challenging and limited to generation of achiral or racemic dicarboxylic acids. To date, catalytic asymmetric dicarboxylation with CO 2 to give chiral dicarboxylic acids has not been reported. Herein, we report the first asymmetric dicarboxylation of 1,3-dienes with CO 2 via Cu catalysis. This strategy provides an efficient and environmentally benign route to chiral dicarboxylic acids with high regio-, chemo-, and enantioselectivities. The copper self-relay catalysis, that is, Cu-catalyzed boracarboxylation of 1,3-dienes to give carboxylated allyl boronic ester intermediates and subsequent carboxylation of C-B bonds to give dicarboxylates, is key to the success of this dicarboxylation. Moreover, this protocol exhibits broad substrate scope, good functional group tolerance, easy product derivatizations, and facile synthesis of chiral liquid crystalline polyester and drug-like scaffolds.

Migraine without aura is a multidimensional neurological disorder characterized by sensory, emotional, and cognitive symptoms linked to structural and functional abnormalities in the anterior cingulate cortex. Anterior cingulate cortex subregions play differential roles in the clinical symptoms of migraine without aura; however, the specific patterns and mechanisms remain unclear. In this study, voxel-based morphometry and seed-based functional connectivity were used to investigate structural and functional alterations in the anterior cingulate cortex subdivisions in 50 patients with migraine without aura and 50 matched healthy controls. Compared with healthy controls, patients exhibited (1) decreased gray matter volume in the subgenual anterior cingulate cortex, (2) increased functional connectivity between the bilateral subgenual anterior cingulate cortex and right middle frontal gyrus, and between the posterior part of anterior cingulate cortex and right middle frontal gyrus, orbital part, and (3) decreased functional connectivity between the anterior cingulate cortex and left anterior cingulate and paracingulate gyri. Notably, left subgenual anterior cingulate cortex was correlated with the duration of each attack, whereas the right subgenual anterior cingulate cortex was associated with migraine-specific quality-of-life questionnaire (emotion) and self-rating anxiety scale scores. Our findings provide new evidence supporting the hypothesis of abnormal anterior cingulate cortex subcircuitry, revealing structural and functional abnormalities in its subregions and emphasizing the potential involvement of the left subgenual anterior cingulate cortex-related pain sensation subcircuit and right subgenual anterior cingulate cortex -related pain emotion subcircuit in migraine., (© The Author(s) 2024. Published by Oxford University Press.)

Ethnopharmacological Relevance: Anxiety disorders leads to a decline in quality of life and increased risk of morbidity and mortality. The Baihe Dihuang decoction (BDD) is a classic Chinese medical formula that has been widely used to treat anxiety disorders for thousands of years in China. However, the pharmacodynamic material that is responsible for the antianxiety of BDD remains unclear., Aim of the Study: To screen the main ingredients of anti-anxiety in BDD based on the establishment of spectrum-effect relationship and verified experiment., Methods: The UPLC-Q-TOF/MS technique was utilized to establish fingerprints of various fractions of BDD and identify the main compounds. The anti-anxiety effects of BDD were comprehensively evaluated through multiple assessments, including the open field test, elevated plus maze test, and neurotransmitters tests. Then, the spectrum-effect relationship was established through Pearson correlation analysis, gray correlation analysis, orthogonal partial least squares regression analysis. The spectrum-effect relationship results were confirmed through various measures on an anxiety condition cell model, induced by a corticosterone and lipopolysaccharide intervention. These measures included assessing neuronal cell viability, morphology, apoptosis, synaptic damage, and the expression of neurotransmitters and inflammatory factors., Results: In the UPLC-Q-TOF-MS fingerprint, 46 common peaks were identified. The pharmacological results indicated that different fractions of BDD have strong effects on improving anxiety-like behavior and regulating neurotransmitters. Among them, butanol fraction has the highest comprehensive evaluation score of anti-anxiety efficacy, which is main active fraction of BDD for anti-anxiety. The analysis of the spectrum-effect relationship revealed that the 46 peaks exhibited varying degrees of correlation with the anti-anxiety efficacy indicators of BDD. Among them, 14 components have a high correlation with the anti-anxiety efficacy indicators, which may be the potential anti-anxiety efficacy components of BDD. The in vitro activity verification of active components verified our prediction, regaloside A, B, C, D, H, acteoside, and isoacteoside improved neuronal cell viability, cell morphology, apoptosis, and synaptic damage. Additionally, regaloside A, B, C, D, H and acteoside regulated the neurotransmitter levels, while regaloside A, B, C, D, acteoside and isoacteoside inhibited the levels of inflammatory cytokines., Conclusion: The butanol fraction was found to be the main active fraction of BDD, and 14 compounds were the major anxiolytic active components. The results of verifying the major active components were consistent with the predicted results of the spectrum-effect analysis. The developed spectrum-effect analysis in this study demonstrates high accuracy and reliability for screening active components in TCMs., 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 B.V. All rights reserved.)

Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is rarely expressed in normal tissues but highly abundant in pathological diseases, including fibrosis, arthritis, and cancer. Ever since its discovery, we have deciphered its structure and biological properties and continue to investigate its roles in various diseases while attempting to utilize it for targeted therapy. To date, no significant breakthroughs have been made in terms of efficacy. However, in recent years, several practical applications in the realm of imaging diagnosis have been discovered. Given its unique expression in a diverse array of pathological tissues, the fundamental biological characteristics of FAP render it a crucial target for disease diagnosis and immunotherapy. To obtain a more comprehensive understanding of the research progress of FAP, its biological characteristics, involvement in diseases, and recent targeted application research have been reviewed. Moreover, we explored its development trend in the direction of clinical diagnoses and treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Fibroblast growth factor 21 ( FGF21 ), primarily secreted by the pancreas, liver, and adipose tissues, plays a pivotal role in regulating glucose and lipid metabolism. Acute pancreatitis (AP) is a common inflammatory disease with specific clinical manifestations. Many patients with diabetes present with concurrent inflammatory symptoms. Diabetes exacerbates intestinal permeability and intestinal inflammation, thus leading to the progression to AP. Our previous study indicated that FGF21 significantly attenuated susceptibility to AP in mice., Aim: To investigate the potential protective role of FGF21 against AP in diabetic mice., Methods: In the present study, a mouse model of AP was established in diabetic (db)/db diabetic mice through ceruletide injections. Thereafter, the protective effects of recombinant FGF21 protein against AP were evaluated, with an emphasis on examining serum amylase (AMS) levels and pancreatic and intestinal inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor-alpha (TNF-), and intestinal IL-1β]. Additionally, the impact of this treatment on the histopathologic changes of the pancreas and small intestinal was examined to elucidate the role of FGF21 in diabetic mice with AP. An antibiotic (Abx) cocktail was administered in combination with FGF21 therapy to investigate whether the effect of FGF21 on AP in diabetic mice with AP was mediated through the modulation of the gut microbiota. Subsequently, the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), a bioinformatics software package, was used to predict different pathways between the groups and to explore the potential mechanisms by which the gut microbiota influenced the protective effect of FGF21 ., Results: The results indicated that FGF21 notably diminished the levels of serum AMS (944.5 ± 15.9 vs 1732 ± 83.9, P < 0.01) and inflammatory factors including IL-6 (0.2400 ± 0.55 vs 1.233 ± 0.053, P < 0.01), TNF- (0.7067 ± 0.22 vs 1.433 ± 0.051, P < 0.01), and IL-1β (1.377 ± 0.069 vs 0.3328 ± 0.02542, P < 0.01) in diabetic mice with AP. Moreover, notable signs of recovery were observed in the pancreatic structure of the mice. The histologic evidence of inflammation in the small intestine, including edema and villous damage, was significantly alleviated. FGF21 also significantly altered the composition of the gut microbiota, reestablishing the Bacteroidetes/Firmicutes ratio. Upon treatment with an Abx cocktail to deplete the gut microbiota, the FGF21 + Abx group showed lower levels of serum AMS (0.9328 ± 0.075 vs 0.2249 ± 0.023, P < 0.01) and inflammatory factors (1.083 ± 0.12 vs 0.2799 ± 0.032, p < 0.01) than the FGF21 group. Furthermore, the FGF21 + Abx group exhibited diminished injury to the pancreatic and small intestinal tissues, accompanied by a significant decrease in blood glucose levels (17.50 ± 1.1 vs 9.817 ± 0.69 mmol/L, P < 0.001). These findings underscored the superior protective effects of the combination therapy involving an Abx cocktail with FGF21 over the FGF21 treatment alone in diabetic mice with AP. The gut microbiota composition across different groups was further characterized, and a differential expression analysis of gene functions was undertaken using the PICRUSt2 prediction method. These findings suggested that FGF21 could potentially confer therapeutic effects on diabetic mice with AP by modulating the sulfate reduction I pathway and the superpathway of n-acetylceramide degradation in the gut microbiota., Conclusion: This study reveals the potential of FGF21 in improving pancreatic and intestinal damage recovery, reducing blood glucose levels, and reshaping gut microbiota composition in diabetic mice with AP. Notably, the protective effects of FGF21 are augmented when combined with the Abx cocktail., Competing Interests: Conflict-of-interest statement: The author declare that there is no conflict of interest regarding the publication of this manuscript., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

We report herein an organic charge transfer cocrystal complex, consisting of a stable radical TPVr and an electron acceptor TCNQF 4 , as a rare sort of all-organic-based magnetic bistable materials with a thermally activated magnetic hysteresis loop over the temperature range from 170 to 260 K. Detailed X-ray crystallographic studies and theoretical calculations revealed that while a π-associated radical anion dimer was formed upon an integer charge transfer process from TPVr to the TCNQF 4 molecules within the cocrystal lattice, the resulting TCNQF 4 ·- π-dimers were found to exhibit varied intradimer π-stacking distances and singly occupied molecular orbital overlaps at different temperatures, thus yielding two different singlet states with distinct singlet-triplet gaps above and below the loop, which eventually contributed to the thermally excited molecular magnetic bistability.

Background: Early recurrent intussusception (ERI) in children is common and seriously affects the physical and mental health of the children. There are few reports discussing risk factors for ERI in children, and this study aims to identify risk factors for ERI in children and build predictive models., Methods: We conducted a retrospective study of 787 children with no relapse intussusception (NRI) and 82 children with ERI between January 2011 and December 2021. Univariate and multifactorial stepwise logistic regression analysis was used to analyze the correlation between 11 factors and ERI, to determine the independent risk factors for ERI in children. The prediction model was established by independent risk factors and then verified., Results: Age, vomiting, bloody stools, and monocyte ratios were independently correlated with the composite endpoint (P<0.05). A nomogram was constructed and a calibration curve was plotted, using independent risk factors. Based on the disease's diagnostic score, the predictive model's performance was validated by using logistic regression receiver operating characteristic (ROC) curve detection, with area under the curve (AUC) value of 0.883 [95% confidence interval (CI): 0.846-0.920], and the calibration curve was close to the ideal diagonal line. In addition, the decision curve analysis (DCA) showed that the model had significant net benefits., Conclusions: Independent risk factors for ERI in children are age, vomiting, bloody stool, and monocyte ratio. Children older than 1 year in age, who lacked vomiting and bloody stool symptoms, and who exhibited an elevated ratio of monocytes were more likely to relapse early. The predictive model constructed herein can predict the early recurrence of children with ERI, providing a reference for clinicians' individualized judgments., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-269/coif). All authors report that receiving funding from the National Natural Science Foundation of China (No. 81801432), the Natural Science Foundation of Guangdong Province of China (Nos. 2022A1515010407, 2020A1515010135, and 2018A030307045), the Guangdong Provincial Science and Technology Fund for High-Level Hospital Construction (No. STKJ2021119), the “Dengfeng Project” for the Construction of High-Level Hospitals in Guangdong Province-the First Affiliated Hospital of Shantou University Medical College Supporting Funding (No. [2019]70), and the Major Science and Technology Project of Nanshan District of Shenzhen City (No. NSZD2023022). The authors have no other conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)

Light absorption and scattering exist in the underwater environment, which can lead to blurring, reduced brightness, and color distortion in underwater images. Polarized images have the advantages of eliminating underwater scattering interference, enhancing contrast, and detecting material information of the object in underwater detection. In this paper, from the perspective of polarization imaging, different concentrations (0.15 g/ml, 0.30 g/ml, and 0.50 g/ml), different wave bands (red, green, and blue), different materials (copper, wood, high-density PVC, aluminum, cloth, foam, cloth sheet, low-density PVC, rubber, and porcelain tile), and different depths (10 cm, 20 cm, 30 cm, and 40 cm) are set up in a chamber for the experimental environment. By combining the degradation mechanism of underwater images and the analysis of polarization detection results, it is proved that the degree of polarization images have greater advantages than degree of linear polarization images, degree of circular polarization images, S1, S2, and S3 images, and visible images underwater. Finally, a fusion algorithm of underwater visible images and polarization images based on compressed sensing is proposed to enhance underwater degraded images. To improve the quality of fused images, we introduce orthogonal matching pursuit (OMP) in the high-frequency part to improve image sparsity and consistency detection in the low-frequency part to improve the image mutation phenomenon. The fusion results show that the peak SNR values of the fusion result maps using OMP in this paper are improved by 32.19% and 22.14% on average over those using backpropagation and subspace pursuit methods. With different materials and concentrations, the underwater image enhancement algorithm proposed in this paper improves information entropy, average gradient, and standard deviation by 7.76%, 18.12%, and 40.8%, respectively, on average over previous algorithms. The image NIQE value shows that the image quality obtained by this paper's algorithm is improved by about 69.26% over the original S0 image.

Background : Brain imaging results in sleep deprived patients showed structural changes in the cerebral cortex; however, the reasons for this phenomenon need to be further explored. Methods : This MR study evaluated causal associations between morningness, ease of getting up, insomnia, long sleep, short sleep, and the cortex structure. Results : At the functional level, morningness increased the surface area (SA) of cuneus with global weighted (beta(b) (95% CI): 32.63 (10.35, 54.90), p = 0.004). Short sleep increased SA of the lateral occipital with global weighted (b (95% CI): 394.37(107.89, 680.85), p = 0.007. Short sleep reduced cortical thickness (TH) of paracentral with global weighted (OR (95% CI): -0.11 (-0.19, -0.03), p = 0.006). Short sleep reduced TH of parahippocampal with global weighted (b (95% CI): -0.25 (-0.42, -0.07), p = 0.006). No pleiotropy was detected. However, none of the Bonferroni-corrected p values of the causal relationship between cortical structure and the five types of sleep traits met the threshold. Conclusions : Our results potentially show evidence of a higher risk association between neuropsychiatric disorders and not only paracentral and parahippocampal brain areas atrophy, but also an increase in the middle temporal zone. Our findings shed light on the associations of cortical structure with the occurrence of five types of sleep traits.

The construction of sensors with specific recognition functions can easily, sensitively and efficiently detect heavy metal ions, which is a demand in the field of electrochemical sensing and an important topic in the detection of environmental pollutants. An electrochemical sensor based on MOFs composites was developed for sensing of multiplex metal ions. The large surface area, adjustable porosities and channels in MOFs facilitate successful loading of sufficient quantities highly active units. The active units and pore structures of MOFs are regulated and synergetic with each other to enhance the electrochemical activity of MOFs composites. Thus, the selectivity, sensitivity and reproducibility of MOFs composites have been improved. Fortunately, after characterization, Fe@YAU-101/GCE sensor with strong signal was successfully constructed. In the presence of target metal ions in solution, the Fe@YAU-101/GCE can efficiently and synchronously identify Hg 2+ , Pb 2+ , and Cd 2+ . The detection limits (LOD) are 6.67 × 10 -10  M(Cd 2+ ), 3.33 × 10 -10  M(Pb 2+ ) and 1.33 × 10 -8  M (Hg 2+ ), and are superior to the permissible limits set by the National Environmental Protection Agency. The electrochemical sensor is simple without sophisticated instrumentation and testing processes, hence promising for practical applications., 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 B.V. All rights reserved.)

Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

Introduction: Immunity is involved in a variety of bone metabolic processes, especially osteoporosis. The aim of this study is to explore new bone immune-related markers by bioinformatics method and evaluate their ability to predict osteoporosis., Methods: The mRNA expression profiles were obtained from GSE7158 in Gene expression Omnibus (GEO), and immune-related genes were obtained from ImmPort database (https://www.immport.org/shared/). immune genes related to bone mineral density(BMD) were screened out for differential analysis. protein-protein interaction (PPIs) networks were used to analyze the interrelationships between different immune-related genes (DIRGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of DIRGs function were performed. A least absolute shrinkage and selection operation (LASSO) regression model and multiple Support Vector Machine-Recursive Feature Elimination (mSVM-RFE) model were constructed to identify the candidate genes for osteoporosis prediction The receiver operator characteristic (ROC) curves were used to validate the performances of predictive models and candidate genes in GEO database (GSE7158,GSE13850).Through the RT - qPCR verify the key genes differentially expressed in peripheral blood mononuclear cells Finally, we constructed a nomogram model for predicting osteoporosis based on five immune-related genes. CIBERSORT algorithm was used to calculate the relative proportion of 22 immune cells., Results: A total of 1158 DEGs and 66 DIRGs were identified between high-BMD and low-BMD women. These DIRGs were mainly enriched in cytokine-mediated signaling pathway, positive regulation of response to external stimulus and the cellular components of genes are mostly localized to external side of plasma membrane. And the KEGG enrichment analysis were mainly involved in Cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, Neuroactive ligand-receptor interaction,Natural killer cell mediated cytotoxicity. Then five key genes (CCR5, IAPP, IFNA4, IGHV3-73 and PTGER1) were identified and used as features to construct a predictive prognostic model for osteoporosis using the GSE7158 dataset., Conclusion: Immunity plays an important role in the development of osteoporosis.CCR5, IAPP, IFNA4, IGHV3-73 and PTGER1were play an important role in the occurrences and diagnosis of OP., 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 © 2023 Hao, Xinqi, Weicheng, Shiwei, Lumin, Xiao, Dong and Jun.)

We designed and synthesized a new tripyridine dipyrrolide pincer ligand, which could be doubly deprotonated to provide five-nitrogen-donor sites and then utilized to prepare a subnanometric chiral silver cluster. The cluster belongs to an S 4 point group and shows a double-stranded helicate. DFT calculations were performed to analyze the electronic structure of the cluster. Interestingly, through hierarchical intercluster interactions, the cluster helicates evolve into complex secondary structures including a right-handed helix and a folded sheet, both of which are reminiscent of secondary structures of proteins, i.e. , an α-helix and an antiparallel β-sheet.

Liver fibrosis is a repair response to injury caused by various chronic stimuli that continually act on the liver. Among them, the activation of hepatic stellate cells (HSCs) and their transformation into a myofibroblast phenotype is a key event leading to liver fibrosis, however the mechanism has not yet been elucidated. The molecular basis of HSC activation involves changes in the regulation of gene expression without changes in the genome sequence, namely, via epigenetic regulation. DNA methylation is a key focus of epigenetic research, as it affects the expression of fibrosis-related, metabolism-related, and tumor suppressor genes. Increasing studies have shown that DNA methylation is closely related to several physiological and pathological processes including HSC activation and liver fibrosis. This review aimed to discuss the mechanism of DNA methylation in the pathogenesis of liver fibrosis, explore DNA methylation inhibitors as potential therapies for liver fibrosis, and provide new insights on the prevention and clinical treatment of liver fibrosis., 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 © 2023 Lyu, Xiao, Cui, Yu, Liu, Lyu, Kuang, Xiao and Luo.)

We report here a novel family of boraolympicenes, structurally featuring boron-doping at the concave 11a-position of their π-skeletons and synthetically prepared via a facile one-pot triply borylation-based double-fold borocyclization reaction. Despite having no bulky protecting groups, these boraolympicenes exhibit excellent chemical stability against air and moisture, ascribed to the significant π-electron delocalization over the vacant p z orbitals of boron atoms as evidenced by both single-crystallographic and theoretical analyses. More importantly, the modular synthesis of these boraolympicenes allows the fine-tuning of their physicochemical properties, endowing them with intriguing electronic features, such as intense visible-to-NIR absorption and low-lying LUMO energy levels (∼-3.8 eV) as well as tunable molecular stacking characteristics in the crystalline state. As a model compound, a radical-anion salt of 6-phenyl-11a-boraolympicene was further generated through chemical reduction and well characterized by UV- vis -NIR absorption, ESR, and IR spectroscopy. This radical anion salt is sensitive to air and moisture but shows persistent stability under inert conditions benefiting from its stable borataalkene-containing resonant form., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We study the wrinkling dynamics of three-dimensional vesicles in a time-dependent elongation flow by utilizing an immersed boundary method. For a quasispherical vesicle, our numerical results well match the predictions of perturbation analysis, where similar exponential relationships between wrinkles' characteristic wavelength and the flow strength are observed. Using the same parameters as in the experiments by Kantsler et al. [V. Kantsler et al., Phys. Rev. Lett. 99, 178102 (2007)0031-900710.1103/PhysRevLett.99.178102], our simulations of an elongated vesicle are in good agreement with their results. In addition, we get rich three-dimensional morphological details, which are favorable to comprehend the two-dimensional snapshots. This morphological information helps identify wrinkle patterns. We analyze the morphological evolution of wrinkles using spherical harmonics. We find discrepancies in elongated vesicle dynamics between simulations and perturbation analysis, highlighting the importance of the nonlinear effects. Finally, we investigate the unevenly distributed local surface tension, which largely determines the position of wrinkles excited on the vesicle membrane.

Background: Mismatch repair-proficient (pMMR) microsatellite stability (MSS) in colorectal cancer (CRC) indicates an unfavorable therapeutic response to immunotherapy with immune checkpoint inhibitors (ICIs). However, the molecular characteristics of CRC patients with pMMR MSS remain largely unknown. Methods: Heterogeneities between mismatch repair-deficient (dMMR) microsatellite instability (MSI) and pMMR MSS CRC patients were investigated at the single-cell level. Next, an MSS-related risk score was constructed by single-sample gene set enrichment analysis (ssGSEA). The differences in immune and functional characteristics between the high- and low-score groups were systematically analyzed. Results: Based on the single-cell RNA (scRNA) atlas, an MSS-specific cancer cell subpopulation was identified. By taking the intersection of the significant differentially expressed genes (DEGs) between different cancer cell subtypes of the single-cell training and validation cohorts, 29 MSS-specific cancer cell marker genes were screened out for the construction of the MSS-related risk score. This risk score signature could efficiently separate pMMR MSS CRC patients into two subtypes with significantly different immune characteristics. The interactions among the different cell types were stronger in the MSS group than in the MSI group, especially for the outgoing signals of the cancer cells. In addition, functional differences between the high- and low-score groups were preliminarily investigated. Conclusion: In this study, we constructed an effective risk model to classify pMMR MSS CRC patients into two completely different groups based on the specific genes identified by single-cell analysis to identify potential CRC patients sensitive to immunotherapy and screen effective synergistic targets., 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 © 2023 Fu, Jin, Chen, Chen, Wu, Xiao, Liu and Deng.)

The dried roots of Scutellaria baicalensis are important traditional Chinese medicine used to treat liver and lung inflammation. An anomalous structure, hollowed root, was discovered in perennial cultivated Scutellaria baicalensis . The presence of the hollow may change the contents of bioactive metabolites, such as baicalein, and other 4'-hydroxyflavones in Scutellaria baicalensis roots, but the relationship between the hollowed root and bioactive metabolite contents is poorly understood. In this study, we identified the anatomical structure of the hollowed root and detected differentially accumulating flavonoid metabolites and enzymes related to 4'-hydroxyflavone biosynthesis in 3-year-old roots with a hollow. We confirmed that methyl jasmonate (MeJA) induced the accumulation of 4'-hydroxyflavones and the expression of enzymes related to 4'-hydroxyflavone biosynthesis in hydroponically cultured Scutellaria baicalensis roots. The development of the hollowed root were divided into 4 stages. The 4'-hydroxyflavone contents and expression of enzymes related to 4'-hydroxyflavone biosynthesis increased synchronously with the content of MeJA during the development of hollowed root. Pathogen and programed-cell-death related genes were induced during hollowed root development. Taken together, our results provide novel insight into the importance of MeJA in the development of hollowed root and the accumulation of 4'-hydroxyflavones in Scutellaria baicalensis roots. Our results suggest that a pathogen and senescence are the two major causes for the development of hollowed root in Scutellaria baicalensis roots., 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 © 2023 Geng, Jiang, Dong, Wang, Lu, Liu, Guo, Huang and Xiao.)

Background: Due to the lack of effective drug treatment, triple-negative breast cancer (TNBC) is prone to recurrence and metastasis after an operation. As a glycolytic inhibitor, 3-bromopyruvic acid (3-BrPA) can inhibit the proliferation and induce apoptosis of TNBC cells. However, whether it has similar effects in animal models remains unclear., Objective: To observe the effect of 3-BrPA on the growth and glucose metabolism of human TNBC transplanted tumors in nude mice and to investigate the mechanism., Methods: We constructed subcutaneous xenografts of human TNBC in nude mice and treated them with low, medium and high concentrations of 3-BrPA. After 15 days, nude mice were sacrificed to detect hexokinase (HK) activity and adenosine triphosphate (ATP) content in tumor tissues. Hematoxylin-eosin (HE) staining was used to detect the damage of transplanted tumors and liver and kidney in nude mice, which 3-BrPA caused. The expression of c-Myc in tumor tissues was detected by Immunohistochemistry (IHC). Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used to detect the apoptosis of tumor tissues. Besides, the expressions of Cytc, Bax, Bcl-2 and Caspase-9 were detected by Western blotting., Results: Compared with the control group, intraperitoneal injection of 3-BrPA inhibited the growth of human TNBC transplant tumors, decreased HK activity and ATP production in tumor tissues, disrupted the tissue structure of transplant tumors, and did not significantly damage liver and kidney tissues. IHC staining and Western blotting showed that 3-BrPA could decrease the expression of c-Myc and Bcl-2, increase the expression of Cyt -c, Bax and Caspase-9 expression and promote apoptosis in tumor tissues., Conclusion: The above data indicate that 3-BrPA inhibits the growth of human TNBC transplanted tumors and promotes their apoptosis. Its anti-cancer mechanism might reduce HK activity by down-regulating c-Myc expression, eventually leading to decreased glycolytic pathway energy production and promoting apoptosis of transplanted tumors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The involvement of the 2-phosphaethynolate anion species with ambident nucleophilic properties serves as an essential protocol for synthesizing oxygen-bound or phosphorus-bound complexes. This work mainly describes the synthesis and characterization of U, Th, and Ti phosphaethynolate complexes featuring a preferential O-coordination fashion. Among these complexes, the first examples of a Ti(IV)-OCP complex 3A, Th(IV)-OCP complex 3B, and U(IV)-OCP complex 3C were assembled by a salt metathesis reaction between M(Trapen TMS )(Cl) (M = Ti, Th, U) and NaOCP(dioxane) 2.5 and were all crystallographically characterized. The structural similarity of this series of phosphaethynolate complexes allows us to compare the bonding properties of d- and f-block elements in the corresponding compounds. The well-established density functional theory (DFT) computational method was employed to explore the electronic structures and covalency in M-O bonding, and the results showed a consistent pattern. The calculation result showed that 2-phosphaethynolate complexes exhibited the covalency trend of U-O > Th-O > Ti-O due to the involvement of 5f orbitals.

Background: Lamin family members play crucial roles in promoting oncogenesis and cancer development. The values of lamin family in predicting prognosis and immunotherapy response remain largely unclarified. Our research is aimed at comprehensively estimating the clinical significance of lamin family in hepatocellular carcinoma and constructing a novel lamin family-based signature to predict prognosis and guide the precise immunotherapy., Methods: The expression features and prognostic value of LMNA, LMNB1, and LMNB2 were explored in the TCGA and GEO databases. The biological functions of LMNB1 and LMNB2 were validated by in vitro assays. A lamin family-based signature was built using the TCGA training set. The TCGA test set, entire TCGA set, and GSE14520 set were used to validate its predictive power. Univariate and multivariate analyses were performed to evaluate the independence of the lamin family-based signature from other clinicopathological characteristics. A nomogram was constructed using the lamin family-based signature and TNM stage. The associations of this signature with molecular pathways, clinical characteristics, immune cell infiltration, and immunotherapy response were analyzed., Results: Lamin family members were upregulated in HCC. Upregulation of LMNB1 and LMNB2 promoted HCC proliferation, migration, and invasion. The predictive signature was initially established based on LMNB1 and LMNB2 which could effectively identify differences in overall survival, immune cell infiltration, and clinicopathological characteristics of high- and low-risk patients. The nomogram showed high prognostic predictive accuracy. Importantly, the lamin family-based signature was correlated with immune suppression and expression of immune checkpoint molecules., Conclusions: The lamin family-based signature is a robust biomarker to predict overall survival and immunotherapy response in HCC. High-risk score patients have a poorer overall survival and might be more sensitive to immunotherapy. This signature may contribute to improving individualized prognosis prediction and precision immunotherapy for HCC patients., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2022 Yongyu Yang et al.)

Noninflammatory clearance of dying cells by professional phagocytes, termed efferocytosis, is fundamental in both homeostasis and inflammatory fibrosis disease but has not been confirmed to occur in chronic pancreatitis (CP). Here, we investigated whether efferocytosis constitutes a novel regulatory target in CP and its mechanisms. PRSS1 transgenic (PRSS1 Tg ) mice were treated with caerulein to mimic CP development. Phospholipid metabolite profiling and epigenetic assays were performed with PRSS1 Tg CP models. The potential functions of Atp8b1 in CP model were clarified using Atp8b1-overexpressing adeno-associated virus, immunofluorescence, enzyme-linked immunosorbent assay(ELISA), and lipid metabolomic approaches. ATAC-seq combined with RNA-seq was then used to identify transcription factors binding to the Atp8b1 promoter, and ChIP-qPCR and luciferase assays were used to confirm that the identified transcription factor bound to the Atp8b1 promoter, and to identify the specific binding site. Flow cytometry was performed to analyze the proportion of pancreatic macrophages. Decreased efferocytosis with aggravated inflammation was identified in CP. The lysophosphatidylcholine (LPC) pathway was the most obviously dysregulated phospholipid pathway, and LPC and Atp8b1 expression gradually decreased during CP development. H3K27me3 ChIP-seq showed that increased Atp8b1 promoter methylation led to transcriptional inhibition. Atp8b1 complementation substantially increased the LPC concentration and improved CP outcomes. Bhlha15 was identified as a transcription factor that binds to the Atp8b1 promoter and regulates phospholipid metabolism. Our study indicates that the acinar Atp8b1/LPC pathway acts as an important "find-me" signal for macrophages and plays a protective role in CP, with Atp8b1 transcription promoted by the acinar cell-specific transcription factor Bhlha15. Bhlha15, Atp8b1, and LPC could be clinically translated into valuable therapeutic targets to overcome the limitations of current CP therapies., (© 2022. The Author(s).)

Background: Portulaca oleracea is a known medicinal plant with antioxidant, anti-inflammatory, and anticancer activities, and it may also function an important role in colorectal cancer (CRC)., Purpose: We probed into study the critical function of Portulaca oleracea extract (POE) in CRC and the related downstream factors., Methods: Azoxymethane (AOM) and dextransodiumsulfate (DSS) were used to induce mouse models of CRC, which were then administered different doses of POE to evaluate the therapeutic effects of POE on CRC. Diversity, abundance, and function of gut microbiota were analyzed. Moreover, the potential molecular targets of POE inhibiting CRC development were determined. Expression of c-Myc and cyclin D1 as well as CRC cell proliferation and apoptosis was detected., Results: POE treatment inhibited AOM/DSS-induced CRC development in mice and ameliorated gut microbial imbalance. Bioinformatic analysis revealed marked differences in the gut microbiota between CRC samples and normal samples and that 20 differential microbiota may be involved in CRC development through the Wnt signaling pathway. Additionally, c-Myc and cyclin D1 were identified to be the key downstream target genes of the Wnt/β-catenin signaling pathway. In vitro data revealed that POE played a suppressive role in the proliferation of CRC cells by reducing the expression of c-Myc and cyclin D1 and inactivating the Wnt/β-catenin signaling pathway., Conclusion: This study underlines that POE reduces gut microbiota imbalance and inhibits CRC development and progression via inactivation of the Wnt/β-catenin signaling pathway and downregulation of c-Myc and cyclin D1 expression, which is expected to be a potential biomarker for CRC., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Use of α-androgenic receptor blockers remains a mainstay therapeutic approach for the treatment of urological diseases. Silodosin is recommended over other α-blockers for the treatment of lower urinary tract symptoms (LUTS) and benign prostate hyperplasia (BPH), due to its high α 1A uroselectivity. Current research data suggest that silodosin is efficacious in the management of various urological diseases. Thus, we herein review the current evidence of silodosin related to its efficacy and tolerability and appraise the available literature that might ultimately aid in management of various urological conditions at routine clinical practice. Literature reveals that silodosin is beneficial in improving nocturia events related to LUTS/BPH. Silodosin exerts effect on relaxing muscles involved in detrusor obstruction, therefore prolonging the need for patients undergoing invasive surgery. Silodosin treatment, either as a monotherapy or combination, significantly improves International Prostate Symptom Score (IPSS) including both storage and voiding symptoms in patients with BPH/LUTS. Patients on other treatment therapies such as phosphodiesterase 5 inhibitors or other α-blockers are well managed with this drug. Steadily, silodosin has proved beneficial in the treatment of other urological disorders such as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), overactive bladder/acute urinary retention (AUR), premature ejaculation (PE), and prostate cancer post brachytherapy-induced progression. In patients with distal ureteral stones, silodosin treatment is beneficial in decreasing stone expulsion time without affecting stone expulsion rate or analgesic need. Moreover, there were significant improvements in intravaginal ejaculation latency time, quality of life scores, and decrease in PE profile among patients with PE. Silodosin has also demonstrated promising results in increasing the likelihood of successful trial without catheter in patients with AUR and those taking antihypertensive drugs. Reports from Phase II studies have shown promising role of silodosin in the treatment of CP/CPPS as well as facilitating ureteral stone passage. From the robust data in this review, further silodosin treatment strategies in the management of different urological conditions need to be focused on., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Jindan et al.)

The ongoing debate on whether non-alcoholic fatty liver disease (NAFLD) is an active contributor or an innocent bystander in the development of cardiovascular disease (CVD) has sparked interests in understanding the common mediators between the two biologically distinct entities. This comprehensive review identifies and curates genetic studies of NAFLD overlapping with CVD, and describes the colinear as well as opposing correlations between genetic associations for the two diseases. Here, CVD described in relation to NAFLD are coronary artery disease, cardiomyopathy and atrial fibrillation. Unique findings of this review included certain NAFLD susceptibility genes that possessed cardioprotective properties. Moreover, the complex interactions of genetic and environmental risk factors shed light on the disparity in genetic influence on NAFLD and its incident CVD. This serves to unravel NAFLD-mediated pathways in order to reduce CVD events, and helps identify targeted treatment strategies, develop polygenic risk scores to improve risk prediction and personalise disease prevention., 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 © 2022 Chew, Chong, Ng, Kong, Chin, Xiao, Lee, Dan, Muthiah and Foo.)

Background: Many aspects of steady-state responses of the brain remain unclear in bipolar disorder (BD) due to the small number of auditory steady-state response (ASSR) studies and the lack of steady-state visual evoked potential (SSVEP) studies on this complex disorder. Therefore, we assessed the patterns of SSVEP and ASSR in adolescents with BD during an active task to detect possible deficits in these important brain responses compared to normal subjects., Methods: 27 adolescents with BD and 30 healthy adolescents were assessed in this study. The blinking background of the monitor presented at 15 Hz and the tone signal stimulation at 40 Hz evoked SSVEPs and ASSRs, respectively. The phase and amplitude of the steady-state responses were calculated in the auditory and visual conditions., Results: Patients exhibited a substantially worse performance in the motor control inhibition task during both auditory and visual modalities. Patients showed increased SSVEP amplitude and phase in the frontal region compared to control adolescents. Also, patients exhibited decreased ASSR amplitude in the prefrontal and increased ASSR amplitude in the right-frontal and centro-parietal areas compared to healthy adolescents., Conclusions: impairments in the production and preservation of SSVEP and ASSR are evident in BD, implicating abnormalities in visual and auditory pathways. Neurophysiological deficits and worse performance in BD adolescents may imply that visual and auditory pathways cannot well transfer the pertinent information from arriving sensory data to the visual and auditory cortices, and the frontal cortex cannot well integrate incoming signals into a unified and coherent perceptual action., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP., Methods: Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1 Tg ) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1 Tg model mice. The potential functions of St13 were investigated by crossing PRSS1 Tg mice with St13 -/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model., Results: The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68 Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling., Conclusion: St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68 Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP., (© 2022. The Author(s).)

Hepatocellular carcinoma (HCC) is an aggressive malignancy. Previous studies have found that lamin B1 (LMNB1) contributes to the development of human cancers. However, the biological functions and prognostic values of LMNB1 in HCC have not been adequately elucidated. In our present research, the expression pattern of LMNB1 was analyzed. The prognostic values of LMNB1 were evaluated by Kaplan-Meier survival analysis and Cox proportional hazards regression analysis. The effects of LMNB1 on HCC progression were assessed by Cell Counting Kit-8 (CCK-8), colony formation, wound healing, Transwell and in vivo xenograft assays. The mechanisms of LMNB1 in HCC progression were elucidated by gene set enrichment analysis (GSEA) and loss-of-function assays. Besides, a nomogram for predicting overall survival (OS) was constructed. The results demonstrated that LMNB1 was overexpressed in HCC and that increased LMNB1 expression predicted a dismal prognosis. Further experiments showed that LMNB1 facilitated cell proliferation and metastasis in HCC. Functional enrichment analysis revealed that LMNB1 modulated metastasis-associated biological functions such as focal adhesion, extracellular matrix, cell junctions and cell adhesion. Mechanistically, we revealed that LMNB1 promoted HCC progression by regulating the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Moreover, incorporating LMNB1, Ki67 and Barcelona Clinic Liver Cancer (BCLC) stage into a nomogram showed better predictive accuracy than the Tumor-Node-Metastasis (TNM) stage and BCLC stage. In conclusion, LMNB1 may serve as an effective therapeutic target as well as a reliable prognostic biomarker for HCC.

The propensity of uranyl for hydrolysis in aqueous environments prevents precise control of uranyl species in the scenarios of on-demand separation and tailored synthesis. Herein, using cucurbit[7]uril (CB[7]) as the macrocyclic molecule and 4,4'-bipyridine-N,N'-dioxide (DPO) as the string molecule, we propose a new kind of multidentate pseudorotaxane ligand, DPO@CB[7] for capturing uranyl species at different pH's. With the aprotic nature of DPO for metal coordination, the coordination ability of the DPO@CB[7] ligand is less affected by pH and can work in a wide range of pH's. Furthermore, by adaptive uranyl coordination, this aprotic pseudorotaxane ligand achieves effective recognition for different uranyl species ranging from monomeric to tetrameric originating from hydrolysis at varying pH's, and four novel uranyl-rotaxane compounds (URC1-4) are successfully obtained. Single-crystal X-ray diffraction analysis reveals that the DPO@CB[7] ligand coordinates with uranyl centers from monomeric to tetrameric in four different modes, as a result of structural flexibility of the DPO@CB[7] pseudorotaxane ligand. A detailed discussion for conformation flexibility of the DPO@CB[7] ligand has been conducted on the position changes of the DPO ligand trapped in the CB[7], which thus reveals good adaptivity of DPO@CB[7] that is noncovalently bonded as a supramolecular motif. In addition, characterization of the physicochemical properties of URC1 and URC2 with high phase purity, including powder X-ray diffraction (PXRD), infrared spectroscopy (IR), thermogravimetric analysis (TGA), and luminescence properties, are also provided. This work provides a good case of an adaptive pseudorotaxane ligand for the recognition and capture of different uranyl species and will bring valuable hints to the design of multifunctional supramolecular ligands for actinide separation in the future.

Background: Pancreatic cancer (PC) is prevalent among malignant tumors with poor prognosis and lacks efficient therapeutic strategies. Endoplasmic reticulum (ER) stress and apoptosis are associated with chronic inflammation and cancer progression. However, the prognostic value of ER stress-related, and apoptosis-related genes in PC remains to be further elucidated. Our study aimed at confirming the prognostic values of the ER stress-related genes, ATF6, EMC6, XBP1, and CHOP, and the apoptosis-related gene, APAF1, in PC patients. Methods: Gene Expression Profiling Interactive Analysis 2 (GEPIA2) was used to evaluate prognosis value of ATF6, EMC6, XBP1, CHOP, and APAF1 in PC. Clinical data from 69 PC patients were retrospectively analyzed. Immunohistochemistry, Western blotting, and qRT-PCR were used for the assessment of gene or protein expression. The cell counting kit-8 (CCK-8) and the Transwell invasion assays were, respectively, used for the assessment of the proliferative and invasive abilities of PC cells. The prognostic values of ATF6, XBP1, CHOP, EMC6, and APAF1 in PC patients were evaluated using Kaplan-Meier and Cox regression analyses. Results: XBP1 and CHOP expressions were not associated with PC recurrence-free survival (RFS), overall survival (OS) and disease-specific survival (DSS). ATF6 upregulation and EMC6 and APAF1 downregulations significantly correlated with the poor RFS, OS, and DSS of PC patients. ATF6 promoted PC cell proliferation and invasion, while EMC6 and APAF1 inhibited these events. Conclusion: ATF6 upregulation and EMC6 and APAF1 downregulations may be valid indicators of poor prognosis of PC patients. Moreover, ATF6, EMC6, and APAF1 may constitute potential therapeutic targets in PC patients., 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 © 2022 Xiao, Cao, Yang, Tan, Liu, Kan, Zhou, Zhang, Chen, Chen, Xu, Zhang and Shen.)

A hydrodynamic model is developed for rainfall-runoff on asphalt pavement using two-dimensional shallow water equations. A simple yet precise expression is presented to compute flow velocity in order to alleviate the problems associated with numerical instabilities due to small water depths of thin sheet flow. The developed model performed well against measured data and numerical results in two segments. Then, the model was applied to study the influence of highway horizontal alignment, drainage manner, rainfall pattern, surface roughness and geometric parameters on pavement runoff. The results demonstrate that: (i) the influence of highway horizontal alignment on pavement runoff is nonsignificant, while that of drainage manner and the pavement surface roughness is significant. Great differences are observed in flow depth under concentrated drainage and overflow drainage conditions, especially in the area beyond 6 m away from the highway center axis; (ii) remarkable differences in maximum flow depth and peak runoff are presented under uneven and even rainfall conditions, while no great differences are found under three uneven rainfall conditions (front type, center front type and back front type); (iii) the sensitivity of the geometric parameters to the maximum flow depth from strong to weak is cross slope, width, slope length, and longitudinal slope under overflow drainage condition; while that is width, slope length, longitudinal slope and cross slope under concentrated drainage condition.

Bioleaching is a biological conditioning technology for sludge, which not only improves sludge dewatering performance but also removes heavy metals from sludge. As the bioleaching process is a comprehensive biological and chemical process, it is necessary to explore the effects of dissolved oxygen (DO) concentrations on bioleaching efficiency. Three bioleaching experiments with different DO concentrations (T1: 0.8-3.1 mg/L, T2: 3.1-5.5 mg/L, T3: 5.5-7.5 mg/L) were conducted for five days. The sludge dewatering efficiency was evaluated using capillary suction time (CST) and specific resistance to filtration (SRF). The relationship between sludge dewaterability and extracellular polymeric substance (EPS) fraction distribution was investigated. In the treatment with the highest DO concentration, the minimum values of SRF and CST were 4.31 × 10 11  m/kg and 13.5 s, which occurred earlier than the treatment with the lower DO concentrations by approximately 24-48 h. A significant decrease (83.4-93.2%) in tightly bound EPS (TB-EPS) protein (PN) was observed in all treatments, while a positive correlation (r = 0.924, P < 0.01) was observed between SRF and PN content in TB-EPS. A relatively higher abundance of Acidithiobacillus was found with the increase in DO concentration. Additionally, other genera including Metallibacterium, Alicyclobacillus, Acidibacter, Acidocella, and Luteococcus also played important roles in EPS biodegradation. These results revealed that increasing the DO concentration could improve sludge dewatering performance and heavy metal removal by enhancing bioleaching microbial activity, the degradation of PN in TB-EPS, and sludge floc fragmentation, but only if sufficient energy sources were provided., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Obesity induces inflammation and oxidative stress, and ultimately leads to vasodilatory dysfunction in which Transient receptor potential vanilloid type 4 (TRPV4) and Nicotinamide Adenine Dinucleotide Phosphate Oxidase (Nox2) have been reported to be involved. However, little attention has been paid to the role of the TRPV4-Nox2 complex in these problems. The purpose of this study was to figure out the role of the TRPV4-Nox2 complex in obesity-induced inflammation, oxidative stress, and vasodilatory dysfunction. Using fluorescence resonance energy transfer and immunoprecipitation assays, we found enhanced TRPV4 and Nox2 interactions in obese mice. Using q-PCR, fluorescent dye dihydroethidium staining, and myotonic techniques, we found that obesity caused inflammation, oxidative stress, and vasodilatory dysfunction. Using adeno-associated viruses, we found that enhancement or attenuation of TRPV4-Nox2 interaction altered the vaso-function. Based on these findings, we found a small-molecule drug, M12, that interrupted the TRPV4-Nox2 interaction, thereby reducing inflammatory factors and reactive oxygen species production and helping to restore the vasodilatory function. In summary, our results revealed a new mechanism by which obesity-induced inflammation, oxidative stress, and vasodilatory dysfunction is caused by enhanced TRPV4-Nox2 interactions. Using M12 to interrupt the TRPV4-Nox2 interaction may have anti-inflammatory and anti-oxidative stress effects and help restore vasodilatory function and thus provide a new therapeutic approach to obesity., (Copyright © 2021 Elsevier Ltd. All rights reserved.)