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Esophageal epithelium is one of the most proliferative and regenerative epithelia in our body, indicating robust stem cell activity. However, the underlying mechanisms regulating the self-renewal and differentiation of esophageal stem cells need to be more elucidated. Here, we identify the role of YAP1 in esophageal stem cells. YAP1 is differentially expressed in the nuclei of esophageal basal cells. Furthermore, the treatment of verteporfin, a YAP1 inhibitor, interfered with esophageal organoid formation. Consistently, YAP1 deletion decreased esophageal organoid formation and the expression of basal genes while increasing the expression of suprabasal genes. Finally, global transcriptomic analysis revealed that YAP1 inhibition induced a significant enrichment of gene sets related to keratinization and cornification, while depleting gene sets related to DNA repair and chromosome maintenance. Our data uncover a novel regulatory mechanism for esophageal stem cells, which could provide a potential strategy for esophageal regenerative medicine., Competing Interests: Declaration of competing interest The authors declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Macrophages have been recognized as pivotal players in the progression of MASLD/MASH. However, the molecular mechanisms underlying their multifaceted functions in the disease remain to be further clarified. In the current study, we developed a new mouse model with YAP activation in macrophages to delineate the effect and mechanism of YAP signaling in the pathogenesis of MASLD/MASH. Genetically modified mice, featuring specific depletion of both Mst1 and Mst2 in macrophages/monocytes, were generated and exposed to a high-fat diet for 12 weeks to induce MASLD. Following this period, livers were collected for histopathological examination, and liver non-parenchymal cells were isolated and subjected to various analyses, including single-cell RNA-sequencing, immunofluorescence and immunoblotting and qRT-PCR to investigate the impact of YAP signaling on the progression of MASLD. Our data revealed that Mst1/2 depletion in liver macrophages enhanced liver inflammation and fibrosis in MASLD. Using single-cell RNA-sequencing, we showed that YAP activation via Mst1/2 depletion upregulated the expressions of both pro-inflammatory genes and genes associated with resolution/tissue repair. We observed that YAP activation increases Kupffer cell populations (i.e., Kupffer-2 and Kupffer-3) which are importantly implicated in the pathogenesis of MASLD/MASH. Our data indicate that YAP activation via Mst1/2 deletion enhances both the pro-inflammatory and tissue repairing functions of Kupffer-1 and -2 cells at least in part through C1q. These YAP-regulatory mechanisms control the plasticity of liver macrophages in the context of MASLD/MASH. Our findings provide important evidence supporting the critical regulatory role of YAP signaling in liver macrophage plasticity and the progression of MASLD. Therefore, targeting the Hippo-YAP pathway may present a promising therapeutic strategy for the treatment of MASH., (© 2024 Federation of American Societies for Experimental Biology.)

Background: Depression and suicidal ideation often co-occur in children and adolescents, yet they possess distinct characteristics. This study sought to identify the different related factors associated with depression and suicidal ideation., Methods: A nationwide cross-sectional survey collected data from Chinese children and adolescents aged 8 to 18 (N = 160,962; 48.91 % girls). The survey included inquiries about demographics, depression, suicidal ideation, anxiety, perceived stress, academic burnout, internet addiction, non-suicidal self-injury, bullying, and being bullied. Fifteen machine learning algorithms were conducted to identify the different related factors associated with depression and suicidal ideation. Additionally, we conducted external validation on an independent sample of 1,812,889 children and adolescents., Results: Our findings revealed seven related factors linked to depression and six associated with suicidal ideation, with average accuracy rates of 86.86 % and 85.82 %, respectively. For depression, the most influential factors were anxiety, perceived stress, academic burnout, internet addiction, non-suicidal self-injury, experience of bullying, and age. Similarly, anxiety, non-suicidal self-injury, perceived stress, internet addiction, academic burnout, and age emerged as paramount factors for suicidal ideation. Moreover, these related factors showed notable variations in their predictive capacities for depression and suicidal ideation across different subgroups., Conclusion: Anxiety emerged as the predominant shared factor for both depression and suicidal ideation, whereas the other related factors displayed distinct predictive patterns for each condition. These findings highlight the critical need for tailored strategies from public mental health service providers and policymakers to address the pressing concerns of depression and suicidal ideation., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Collapsing and degradation of active materials caused by the electrode/electrolyte interface instability in aqueous batteries are one of the main obstacles that mitigate the capacity. Herein by reversing the notorious side reactions include the loss and dissolution of electrode materials: as we applied Ostwald ripening (OR) in the electrochemical cycling of a copper hexacyanoferrate electrode in a hydronium-ion batteries, the dissolved Cu and Fe ions undergo a crystallization process that creates a stable interface layer of cross-linked cubes on the electrode surface. The layer exposed the low-index crystal planes (100) and (110) through OR-induced electrode particle growth, supplemented by vacancy-ordered (100) superlattices that facilitated ion migration. Our design stabilized the electrode-electrolyte interface considerably, achieving a cycle life of one million cycles with capacity retention of 91.6%, and a capacity retention of 91.7% after 3000 cycles for a full battery., (© 2024 Wiley‐VCH GmbH.)

To enhance the mechanical properties of polylactic acid (PLA) material, the PLA-based composite films are prepared by using Pueraria lobata (Willd.) Ohwi root microcrystalline cellulose (PRMCC) treated with 3-aminopropyl triethoxysilane (KH550) silane coupling agent as the dispersed phase through solvent casting method. The effects of the concentrations of PRMCC and KH550 as well as the KH550 pretreating condition (ethanol concentration) on the tensile properties of PLA-based composite films are investigated. The PLA-based composite film treated with 5 wt% PRMCC and 18 wt% KH550 (pretreated by 90 % EtOH) exhibits the greatest performance. Its elongation at break value is detected to be 4.0 %, 1.6 times as large as that of pure PLA film. The water absorption of the as-prepared PLA-based composite film is reduced from 0.49 % of the unmodified PLA/PRMCC film to 0.12 %. Moreover, the modified PLA-based composite film has a hydrophobic surface and exhibits good thermal stability. Compared with pure PLA film, the modified PLA-based composite film exhibits improved UV shielding performance with acceptable transparency. Furthermore, after adding poly(butylene adipate-co-terephthalate) (PBAT) to the composite system, the elongation at break of the PLA-based composite film is up to 7.2 %. This research can provide theoretical guidance for enhancing the performance of PLA products., 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. Published by Elsevier B.V.)

Autophagy is a membrane trafficking pathway through which eukaryotic cells target their own cytoplasmic constituents for degradation in the lytic compartment. Proper biogenesis of autophagic organelles requires a conserved set of autophagy-related (ATG) proteins and their interacting factors, such as signalling phospholipid phosphatidylinositol 3-phosphate (PI3P) and coat complex II (COPII). The COPII machinery, which was originally identified as a membrane coat involved in the formation of vesicles budding from the endoplasmic reticulum, contributes to the initiation of autophagic membrane formation in yeast, metazoan, and plant cells; however, the exact mechanisms remain elusive. Recent studies using the plant model species Arabidopsis thaliana have revealed that plant-specific PI3P effectors are involved in autophagy. The PI3P effector FYVE2 interacts with the conserved PI3P effector ATG18 and with COPII components, indicating an additional role for the COPII machinery in the later stages of autophagosome biogenesis. In this Update, we examined recent research on plant autophagosome biogenesis and proposed working models on the functions of the COPII machinery in autophagy, including its potential roles in stabilizing membrane curvature and sealing the phagophore., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. 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.)

Fluoroquinolones are a widely used class of antibiotics, with a large variety, which are frequently monitored in the aqueous environment, threatening ecological and human health. To date, effective degradation of fluoroquinolone antibiotics remains a major challenge. Focused on the broad-spectrum degradation of fluoroquinolone antibiotics, a novel biomimetic peroxidase nanozyme named Hemin-His-Fe (HHF)-peroxidase nanozyme was synthesized through a green and rapid "one-pot" method involving hemin, Fmoc-L-His and Fe 2+ as precursors. After systematic optimization of the reaction conditions, fluoroquinolone antibiotics can be degraded by the HHF-peroxidase nanozyme when supplemented with H 2 O 2 in acidic environments. Through validation and analysis, it was proved that the generated strong oxidative hydroxyl radicals are the main active species in the degradation process. In addition, it was verified that this method shows great universal applicability in real water samples.

Background: The global spread of the plasmid-mediated mcr (mobilized colistin resistance) gene family presents a significant threat to the efficacy of colistin, a last-line defense against numerous Gram-negative pathogens. The mcr-9 is the second most prevalent variant after mcr-1., Methods: A dataset of 698 mcr-9-positive isolates from 44 countries is compiled. The historical trajectory of the mcr-9 gene is reconstructed using Bayesian analysis. The effective reproduction number is used innovatively to study the transmission dynamics of this mobile-drug-resistant gene., Findings: Our investigation traces the origins of mcr-9 back to the 1960s, revealing a subsequent expansion from Western Europe to the America and East Asia in the late 20th century. Currently, its transmissibility remains high in Western Europe. Intriguingly, mcr-9 likely emerged from human-associated Salmonella and exhibits a unique propensity for transmission within the Enterobacter. Our research provides a new perspective that this host preference may be driven by codon usage biases in plasmids. Specifically, mcr-9-carrying plasmids prefer the nucleotide C over T compared to mcr-1-carrying plasmids among synonymous codons. The same bias is seen in Enterobacter compared to Escherichia (respectively as their most dominant genus). Furthermore, we uncovered fascinating patterns of coexistence between different mcr-9 subtypes and other resistance genes. Characterized by its low colistin resistance, mcr-9 has used this seemingly benign feature to silently circumnavigate the globe, evading conventional detection methods. However, colistin-resistant Enterobacter strains with high mcr-9 expression have emerged clinically, implying a strong risk of mcr-9 evolving into a global "true-resistance-gene"., Interpretation: This study explores the mcr-9 gene, emphasizing its origin, adaptability, and dissemination potential. Given the high mcr-9 expression colistin-resistant strains was observed in clinically the prevalence of mcr-9 poses a significant challenge to drug resistance prevention and control within the One Health framework., Funding: This work was partially supported by the National Natural Science Foundation of China (Grant No. 32141001 and 81991533)., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The transplantation of islet beta cells offers an alternative to heterotopic islet transplantation for treating type 1 diabetes mellitus (T1DM). However, the use of systemic immunosuppressive drugs in islet transplantation poses significant risks to the body. To address this issue, we constructed an encapsulated hybrid scaffold loaded with islet beta cells. This article focuses on the preparation of the encapsulated structure using 3D printing, which incorporates porcine pancreas decellularized extracellular matrix (dECM) to the core scaffold. The improved decellularization method successfully preserved a substantial proportion of protein (such as Collagen I and Laminins) architecture and glycosaminoglycans in the dECM hydrogel, while effectively removing most of the DNA. The inclusion of dECM enhanced the physical and chemical properties of the scaffold, resulting in a porosity of 83.62±1.09% and a tensile stress of 1.85±0.16 MPa. In teams of biological activity, dECM demonstrated enhanced proliferation, differentiation, and expression of transcription factors such as Ki67, PDX1, and NKX6.1, leading to improved insulin secretion function in MIN-6 pancreatic beta cells. In the glucose-stimulated insulin secretion (GSIS) experiment on day 21, the maximum insulin secretion from the encapsulated structure reached 1.96±0.08 mIU/mL, representing a 44% increase compared to the control group. Furthermore, conventional capsule scaffolds leaverage the compatibility of natural biomaterials with macrophages to mitigate immune rejection. Here, incorporating curcumin into the capsule scaffold significantly reduced the secretion of pro-inflammatory cytokine (IL-1β, IL-6, TNF-α, IFN-γ) secretion by RAW264.7 macrophages and T cells in T1DM mice. This approach protected pancreatic islet cells against immune cell infiltration mediated by inflammatory factors and prevented insulitis. Overall, the encapsulated scaffold developed in this study shows promise as a natural platform for clinical treatment of T1DM., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Methods: We conducted a retrospective study to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation., Results: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs. 38.0 days, Z = 2.095, P = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs. 84.5% vs. 80.6%, P <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs. 73.9%, P = 0.003)., Conclusion: In summary, compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT)., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Fine-tuning of microstructures enables the modulation of optical properties at multiple scales from metasurfaces to geometric optics. However, a dynamic system with a significant deformation range and topology transformation remains challenging. Owing to its magnetic controllability, ferrofluid has proven to be fertile ground for a wide range of engineering and technological applications. Here, we demonstrate a series of intelligent optical surfaces based on ferrofluid, through which multiple optical functions inspired by nature can be realized. The tunability is based on the topological transition of the ferrofluid between the flat state and cone array upon magnetic actuation. In the visible band, a tunable visual appearance is realized. In the mid-infrared band, active manipulation of reflection is realized based on the gradient-index (GRIN) effect. This system also features low latency response and straightforward manufacturability, and it may open opportunities for novel technologies such as smart windows, color displays, infrared camouflage, and other infrared-related technologies.

Motivated by the success of 9,9'-spirobifluorene ( SBF ) in optoelectronic materials, we synthesized a novel spiro compound, spirophenanthrene ( SP ). Incorporating a phenanthrene unit as the core, we aimed to leverage the π-conjugation of SPs to surpass the limitations of SBF . Experimental and theoretical studies revealed significant advantages over SBF , including red-shifted wavelengths, tunable LUMO energy levels, and enhanced thermal stability. These advantages suggest the potential of SPs as versatile building blocks for diverse optoelectronic devices.

Soybean meal (SM) serves as a primary alternative to fish meal in aquafeeds. However, a high-SM diet may result in intestinal injury. Our previous study demonstrated the probiotic effects of heat-inactivated Bacillus subtilis (LCBS1) on bullfrogs (Aquarana catesbeianus) fed a high-SM diet, probably attributed to the bioactive constituent of cell wall. Therefore, in this study, the main constituents of cell wall from LCBS1, including peptidoglycan (PGN), lipoteichoic acid (LTA), cell wall protein (CWP), and whole cell wall (WCW), were extracted and added to a high-SM (~55 %) diet to investigate their probiotic effects on bullfrogs and reveal the possible mechanisms. The results indicated that bullfrogs fed the LTA of LCBS1 showed the highest weight gain, feed efficiency, and protein efficiency ratio. Additionally, the LTA of LCBS1 could activate the humoral immunity and modulate intestinal microbiota. It might activate JAK2-STAT3 and MAPK-ERK pathways, as well as up-regulate tlr5 gene to promote intestinal cell proliferation, thereby alleviating jejunal injury. The WCW of LCBS1 effectively increased the growth performance of bullfrogs by improving the humoral immunity, enhancing intestinal barrier function, and alleviating intestinal inflammatory response. The PGN and CWP of LCBS1 could stimulate the humoral immunity and enhance intestinal barrier function, but had no significant effect on the growth performance of bullfrogs. In conclusion, the LTA might be the primary bioactive constituent of heat-inactivated LCBS1, with the beneficial effects of promoting intestinal cell proliferation and enhancing intestinal barrier function, therefore alleviating the intestinal injury induced by SM on bullfrogs. This study establishes a theoretical basis for the efficient utilization of plant proteins by the application of postbiotics additive in aquafeed, which further saves the feed costs and promotes development of economically sustainable aquaculture., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Perfluorooctanoic acid (PFOA) as emerging pollutants was largely produced and stable in nature environment. Its fate and effect to the wasted sludge digestion process and corresponding microbial mechanism was rarely reported. This study investigated the different dose of PFOA to the wasted sludge digestion process, where the methane yield and microbial mechanism was illustrated. The PFOA added before digestion were 0-10000 μg/L, no significant variation in daily and accumulated methane production between each group. The 9th day methane yield was significantly higher than other days (p < 0.05). The soluble protein was significantly decreased after 76 days digestion (p < 0.001). The total PFOA in sludge (R 2  = 0.8817) and liquid (R 2  = 0.9083) phase after digestion was exponentially correlated with PFOA dosed. The PFOA in liquid phase was occupied 54.10 ± 18.38% of the total PFOA in all reactors. The dewatering rate was keep decreasing with the increase of PFOA added (R 2  = 0.7748, p < 0.001). The mcrA abundance was significantly correlated with the pH value and organic matter concentration in the reactors. Chloroflexi was the predominant phyla, Aminicenantales, Bellilinea and Candidatus&#95;Cloacimonas were predominant genera in all reactors. Candidatus&#95;Methanofastidiosum and Methanolinea were predominant archaea in all reactors. The function prediction by FAPROTAX and Tax4fun implied that various PFOA dosage resulted in significant function variation. The fermentation and anaerobic chemoheterotrophy function were improved with the PFOA dose. Co-occurrence network implied the potent cooperation among the organic matter degradation and methanogenic microbe in the digestion system. PFOA has little impact to the methane generation while affect the microbe function significantly, its remaining in the digested sludge should be concerned to reduce its potential environmental risks., 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 Ltd. All rights reserved.)

As the first identified multidrug efflux pump in Mycobacterium tuberculosis (Mtb), EfpA is an essential protein and promising drug target. However, the functional and inhibitory mechanisms of EfpA are poorly understood. Here we report cryo-EM structures of EfpA in outward-open conformation, either bound to three endogenous lipids or the inhibitor BRD-8000.3. Three lipids inside EfpA span from the inner leaflet to the outer leaflet of the membrane. BRD-8000.3 occupies one lipid site at the level of inner membrane leaflet, competitively inhibiting lipid binding. EfpA resembles the related lysophospholipid transporter MFSD2A in both overall structure and lipid binding sites and may function as a lipid flippase. Combining AlphaFold-predicted EfpA structure, which is inward-open, we propose a complete conformational transition cycle for EfpA. Together, our results provide a structural and mechanistic foundation to comprehend EfpA function and develop EfpA-targeting anti-TB drugs., (© 2024. The Author(s).)

CT and MR tools are commonly used to diagnose lumbar fractures (LF). However, numerous limitations have been found in practice. The aims of this study were to innovate and develop a spinal disease-specific neural network and to evaluate whether synthetic MRI of the LF affected clinical diagnosis and treatment strategies. A total of 675 LF patients who met the inclusion and exclusion criteria were included in the study. For each participant, two mid-sagittal CT and T2-weighted MR images were selected; 1350 pairs of LF images were also included. A new Self-pix based on Pix2pix and Self-Attention was constructed. A total of 1350 pairs of CT and MR images, which were randomly divided into a training group (1147 pairs) and a test group (203 pairs), were fed into Pix2pix and Self-pix. The quantitative evaluation included PSNR and SSIM (PSNR1 and SSIM1: real MR images and Pix2pix-generated MR images; PSNR2 and SSIM2: real MR images and Self-pix-generated MR images). The qualitative evaluation, including accurate diagnosis of acute fractures and accurate selection of treatment strategies based on Self-pix-generated MRI, was performed by three spine surgeons. In the LF group, PSNR1 and PSNR2 were 10.884 and 11.021 (p < 0.001), and SSIM1 and SSIM2 were 0.766 and 0.771 (p < 0.001), respectively. In the ROI group, PSNR1 and PSNR2 were 12.350 and 12.670 (p = 0.004), and SSIM1 and SSIM2 were 0.816 and 0.832 (p = 0.005), respectively. According to the qualitative evaluation, Self-pix-generated MRI showed no significant difference from real MRI in identifying acute fractures (p = 0.689), with a good sensitivity of 84.36% and specificity of 96.65%. No difference in treatment strategy was found between the Self-pix-generated MRI group and the real MRI group (p = 0.135). In this study, a disease-specific GAN named Self-pix was developed, which demonstrated better image generation performance compared to traditional GAN. The spine surgeon could accurately diagnose LF and select treatment strategies based on Self-pix-generated T2 MR images., (© 2024. The Author(s).)

Background: Intestinal dysfunction plays an important role in the clinical progress and prognosis of severe acute pancreatitis (SAP). Qingyi decoction (QYD) has shown beneficial effects on intestinal function recovery, but the prevention actions of the QYD on intestinal paralysis and its mechanism have not been fully explored., Methods: The possible molecular mechanism was unraveled by network pharmacology, including active ingredients and potential target prediction, as well as GO, KEGG, and REATCOME pathway enrichment analyses. The potential interactions between the main active ingredients of the QYD and core genes were explored by molecular docking. A retrospective cohort study on 137 patients with SAP from Tianjin Nankai Hospital was conducted to evaluate the preventive effect of QYD on intestinal paralysis., Results: A total of 110 active ingredients in QYD were screened out, and 37 key targets were predicted by network pharmacology. GO, KEGG, and REATCOME enrichment analyses showed that bioinformatics annotation of the hub genes was mainly involved in intestinal epithelial functions and inflammatory response pathways. The main components of QYD possessed good affinity with IL-6, TNF, CASP3, CXCL8, and CRP by molecular docking. Patients who used QYD plus usual care seemed to have fewer intestinal paralysis rates, lower risk of renal insufficiency, ARDS and blood purification therapy, and shorter hospital and ICU stays. The multivariable regression analyses indicated that the mode of nasogastric and enemas administration of QYD (P = 0.010) and timely intervention with QYD (P = 0.045) were the independent protective factors for intestinal paralysis prevention in patients with SAP., Conclusion: In conclusion, QYD can be used as an effective adjuvant procedure to prevent the occurrence and development of intestinal paralysis in patients with SAP. The mechanisms may be involved in the anti-inflammatory response and maintenance of intestinal epithelial function., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Membrane materials that resist nonspecific or specific adsorption are urgently required in widespread practical applications, such as water purification, food processing, and life sciences. In water purification, inevitable membrane fouling not only limits membrane separation performance, leading to a decline in both permeance and selectivity, but also remarkably increases operation requirements, and augments extra maintenance costs and higher energy consumption. In this work, we report a freestanding interfacial polymerization (IP) fabrication strategy for in situ creation of asymmetric block copolymer (BCP) nanofilms with antifouling properties, greatly outperforming the conventional surface post-modification approaches. The resultant free-standing asymmetric BCP nanofilms with highly-dense, highly-hydrophilic polyethylene glycol (PEG) brushes on one side, can be readily formed via a typical IP process of a well-defined double-hydrophilic BCP composed of a highly-efficient antifouling PEG block and a membrane-forming multiamine block. The asymmetric BCP nanofilms have been applied for efficient and sustainable natural water purification, demonstrating extraordinary antifouling capabilities accompanied with superior separation performance far beyond commercial polyamide nanofiltration membranes. The antifouling behaviors of asymmetric BCP nanofilms derived from the combined effect of the hydration layer, electrostatic repulsion and steric hindrance were further elucidated by water flux and fouling resistance in combination with all-atom molecular dynamics (MD) simulation. This work opens up a new avenue for the large-scale and low-cost creation of broad-spectrum, asymmetric membrane materials with diverse functional "defect-free" surfaces in real-world applications., (© 2024 Wiley-VCH GmbH.)

Bifidobacterium animalis subsp. lactis BLa80 is a new probiotic strain with extensive applications in food products both domestically and internationally. Given the rising consumption of this probiotic, its safety assessment is increasingly crucial in the food industry. This study evaluates the safety of strain BLa80 using a combination of in vitro and in vivo assays along with genomic analysis. Methods included exposing the strain to artificial gastric and intestinal fluids, as well as a medium containing bile salts, to stimulate human digestive conditions. The strain showed high tolerance to gastric fluid at pH of 2.5 and to 0.3 % bile salts. It maintained a 99.92 % survival rate in intestinal fluid. Additional tests assessed hemolytic activity, antibiotic susceptibility (revealing sensitivity to 7 antibiotics), and biogenic amine production using HPLC-ELSD, confirming the absence of histamine, and other harmful amines. Bile salt hydrolase activity was demonstrated qualitatively, and metabolic byproducts were quantitatively analyzed using a D-/l-lactic acid assay kit, showing that BLa80 produces 1.48 mg/mL of l-lactic acid and no harmful d-lactic acid. Genomic analysis confirmed the absence of virulence or pathogenicity genes, and a 90-day oral toxicity study in rats confirmed no toxic effects at various doses. Overall, these findings support the safety classification of the strain BLa80., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest in relation to the topics or materials covered in this manuscript., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In patients with multiple myeloma (MM), the presence of high-risk cytogenetic abnormalities is associated with worse disease control and survival. Autologous stem cell transplant (ASCT) does benefit these patients. Tandem transplantation has been explored as a means to deepen responses and further improve survival however, its role remains controversial. This is particularly true in the era of novel agent induction and post-transplant maintenance therapy. The aim of this study was to use the Canadian Myeloma Research Group database and examine a large cohort of real-world patients comparing the outcomes of tandem versus single ASCT specifically in high-risk patients receiving novel agent-based induction and post-transplant maintenance. The data for this study was derived retrospectively from a comprehensive national-level database of Canadian patients with MM. High-risk cytogenetics was defined as presence of del17p, t(4;14), or t(14;16). Those receiving allogeneic transplant were excluded. Tandem transplantation was defined as a second ASCT performed consecutively without interim relapse or progression after first ASCT. Those with relapse or progressive disease within 3 months of completing a first transplant were excluded. We compared response depth, progression-free, and overall survival (OS) based on single or tandem transplantation procedures. The impact of covariates of interest was also assessed. A total of 381 patients with high-risk cytogenetics were identified. A total of 242 received single and 139 patients received tandem transplants. All received post-transplant maintenance. The most common induction regimen for these patients was cyclophosphamide, bortezomib, and steroids (CyBorD, 87%). Forty-one patients (10.8%) required reinduction prior to first ASCT. The best overall responses at any time were 98.3% (90.5% ≥ very good partial response [VGPR]) and 98.6% (89.9% ≥ VGPR) in the single and tandem ASCT groups, respectively. Survival outcomes were similar with the median progression-free survival for single or tandem ASCT of 35.2 and 35.3 months (P = .88) and the median OS were 92.6 and 88.9 months, respectively (P = .72). No statistically significant differences were seen based on type of cytogenetic abnormality or type of maintenance. This was confirmed on multivariate analysis. In the real-world setting, tandem ASCT does not improve outcomes for MM patients with high-risk cytogenetics. This may be driven by the use of effective pre- and post-ASCT therapies. The development of more potent induction and consolidation along with current nearly ubiquitous continuous maintenance therapies until disease progression does not support the use of a second high-dose procedure., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation. We aimed to evaluate the effectiveness and safety of ruxolitinib plus basiliximab for treating SR-aGVHD after unrelated cord blood transplantation (UCBT). Among the 1154 patients with hematological malignancies who underwent UCBT between February 2014 and May 2022, 198 patients with grade II to IV SR-aGVHD were enrolled, 112 of whom were treated with basiliximab alone (basiliximab group) and 86 of whom received basiliximab plus ruxolitinib (combined therapy group). The combined therapy group demonstrated a significantly higher complete response rate (CRR) on day 28 (36.0%) than did the basiliximab group (12.5%, P < .001). SR-aGVHD patients were further stratified into standard-risk and high-risk groups using the refined Minnesota aGVHD risk score. For standard-risk patients, combined therapy significantly improved the CRR (51.1% versus 13.6%, P < .001) and 3-year overall survival (74.5% versus 52.4%, P = .033). However, high-risk patients did not exhibit the same benefits. Compared with basiliximab monotherapy, ruxolitinib plus basiliximab therapy was an effective therapy for patients with standard-risk SR-aGVHD following UCBT. The effectiveness of combined therapy in high-risk patients was not apparent, indicating the need for other treatments., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Hirschsprung's disease (HSCR) is a complex congenital neurodevelopmental disorder affecting colons caused by both genetic and environmental factors. Although several genes have been identified as contributing factors in HSCR, the pathogenesis is still largely unclear, especially for the low prevalent long-segment HSCR (L-HSCR). Gap junction protein alpha 8 ( GJA8 ) is involved in several physiological processes and has been implicated in several diseases. However, the relationship between GJA8 single nucleotide polymorphism (SNP) rs17160783 and HSCR in the southern Chinese population remains unknown. The study aimed to explore the association of genetic variants in GJA8 and HSCR susceptibility in southern Chinese., Methods: SNP rs17160783 A>G in GJA8 was genotyped by TaqMan SNP Genotyping Assay in all samples, which included 1,329 HSCR children (cases) and 1,473 healthy children (controls). Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association of GJA8 polymorphisms with HSCR susceptibility. The GTEx database and transcription factor binding site (TFBS) prediction were used to analyze the potential regulatory function of rs17160783., Results: Genetic association analysis illustrated that rs17160783 could increase the risk of L-HSCR (P adj =0.04, OR adj =1.48, 95% CI: 1.02-2.14). We also found that GJA8 expression was increased in HSCR and neurodevelopmentally impaired animal models. External epigenetic data revealed that GJA8 rs17160783 may have the potential to regulate the expression of the GJA8 , possibly by altering the binding of transcription factors for GJA8 , and consequently impacting the PI3K-Akt signaling pathway during the enteric nervous system (ENS) development., Conclusions: Our results suggested that rs17160783 might play a regulatory role in GJA8 expression and increase the susceptibility of L-HSCR in children from southern China., 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-24-153/coif). Y.W. reports support from the grant of the Research Foundation of Guangzhou Women and Children’s Medical Center for Clinical Doctor (No. 2023BS013). C.L. reports support from the Guangdong Basic and Applied Basic Research Foundation (No. 2024A1515013190), National Natural Science Foundation of China (No. 82301955), Science and Technology Project of Guangzhou (No. 2024A03J1238), and the China Postdoctor Science Foundation (No. 2023M730791). W.Z. reports support from the Guangdong Basic and Applied Basic Research Foundation (No. 202201010833) and the National Natural Science Foundation of China (No. 82370526). The other authors have no conflicts of interest to declare., (2024 Translational Pediatrics. All rights reserved.)

The COVID-19 pandemic brought forth an urgent need for widespread genomic surveillance for rapid detection and monitoring of emerging SARS-CoV-2 variants. It necessitated design, development, and deployment of a nationwide infrastructure designed for sequestration, consolidation, and characterization of patient samples that disseminates de-identified information to public authorities in tight turnaround times. Here, we describe our development of such an infrastructure, which sequenced 594,832 high coverage SARS-CoV-2 genomes from isolates we collected in the United States (U.S.) from March 13th 2020 to July 3rd 2023. Our sequencing protocol ('Virseq') utilizes wet and dry lab procedures to generate mutation-resistant sequencing of the entire SARS-CoV-2 genome, capturing all major lineages. We also characterize 379 clinically relevant SARS-CoV-2 multi-strain co-infections and ensure robust detection of emerging lineages via simulation. The modular infrastructure, sequencing, and analysis capabilities we describe support the U.S. Centers for Disease Control and Prevention national surveillance program and serve as a model for rapid response to emerging pandemics at a national scale., (© 2024. The Author(s).)

Metal halide perovskites (MHPs) have undergone rapid development in the fields of solar cells, light diodes, lasing, photodetectors, etc. However, the MHPs still face significant challenges, such as poor stability and heterocompositing with other functional materials at the single nanoparticle level. Herein, the successful synthesis of well-dispersed CsPbBr 3 @TiO 2 heterostructure nanocrystals (NCs) is reported, in which each heterostructure NC has only one CsPbBr 3 with a precise anatase TiO 2 coating ranging from asymmetric to symmetric. Due to the protection of anatase TiO 2 , CsPbBr 3 shows dramatically improved chemical stability and photostability. More significantly, the synthesized CsPbBr 3 @TiO 2 heterostructure NCs form a type II heterojunction, which strongly promoted efficient photogenerated carrier separation between anatase TiO 2 and CsPbBr 3 , hence leading to improved optoelectronic activity. This study provides a robust avenue for synthesizing stable and highly efficient MHPs@metal oxide heterostructure NCs, paving the way for the practical application of all inorganic perovskites., (© 2024 Wiley‐VCH GmbH.)

Objective: The purpose of this study is to evaluate the effectiveness of hospital appraisals, specifically the Performance Appraisal for Tertiary Public Hospitals (PATPH), and to examine its impact on the job satisfaction of healthcare professionals in tertiary public hospitals in China., Design: A cross-sectional study using a multistage sampling method. Improvements induced by PATPH in the working environment, job satisfaction and other covariates were measured. A series of weighted linear regressions with weights from the inverse probability-of-treatment weighting method were used to examine the effect of PATPH on job satisfaction., Setting: Nine tertiary public hospitals across three economic and geographic regions in China., Participants: In August 2020, a total of 13 211 hospital employees were surveyed, and 8417 doctors and nurses fully completed questionnaires forming the primary dataset for analysis. Of these respondents, males comprised 18.64% and doctors constituted 28.15%., Results: This study revealed that PATPH had a positive impact on the job satisfaction of healthcare professionals. A 'more effective' PATPH working environment resulted in an improvement of 9.57 points (95% CI 8.99 to 10.16) in job satisfaction scores, controlling for all other variables. The finding persisted consistently through a series of sensitivity analyses., Conclusion: The findings offered insights and inspiration for improving the job satisfaction of healthcare professionals, especially in the development of macrolevel policies targeted towards organisational enhancement., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Mitochondria are known to synthesize adenosine triphosphate (ATP) through oxidative phosphorylation. Understanding and accurately measuring mitochondrial ATP synthesis rate can provide insights into the functional status of mitochondria and how it contributes to overall cellular energy homeostasis. Traditional methods only estimate mitochondrial function by measuring ATP levels at a single point in time or through oxygen consumption rates. This study introduced the relative mitochondrial ATP synthesis response against inhibiting and stimulating substrates (MitoRAISE), designed to detect real-time changes in ATP levels as the cells respond to substrates., Methods: The sensitivity and specificity of the MitoRAISE assay were verified under various conditions, including the isolation of mitochondria, variations in cell numbers, cells exhibiting mitochondrial damage, and heterogeneous mixtures. Using peripheral blood mononuclear cells (PBMCs), we analyzed MitoRAISE data from 19 patients with breast cancer and 23 healthy women., Results: The parameters observed in the MitoRAISE data increased depending on the quantity of isolated mitochondria and cell count, whereas it remained unmeasured in mitochondrial-damaged cell lines. Basal ATP, rotenone response, malonate response, and mitochondrial DNA copy numbers were lower in PBMCs from patients with breast cancer than in those from healthy women., Conclusions: The MitoRAISE assay has demonstrated its sensitivity and specificity by measuring relative ATP synthesis rates under various conditions. We propose MitoRAISE assay as a potential tool for monitoring changes in the mitochondrial metabolic status associated with various diseases., (© 2024. The Author(s).)

The nanoconfinement effect plays an important role in chemical reactions. Inspired by enzymes, this work presents a new way to conduct the rapid flow synthesis of benzothiazoles in the two-dimensional (2D) nanoconfined space created by a graphene oxide membrane. The conversion reaches 96.7% in a short reaction time of less than 23 s at 22 °C.

Introduction: Anti-thymocyte globulin (ATG) has been demonstrated to reduce the incidence of graft-versus-host disease (GVHD); however, it remains controversial whether these gains are offset by an increase in relapse., Methods: We conducted a retrospective historical control study consisting patients (n=210) who underwent myeloablative allogeneic hematopoietic stem-cell transplantation (HSCT) from 2014 to 2020., Results: The incidence of acute GVHD was lower in the ATG group (51.4%) than the non-ATG group (control) (70.0%, p=0.010). The incidence of chronic GVHD was also lower in the ATG group at 1-year (36.4% vs. 62.9%, p &lt;0.001) and 2-year (40.0% vs. 65.7%, p &lt;0.001) post-HSCT. The mortality due to GVHD was higher in the control (18.5%) than the ATG group (4.3%; p= 0.024). The severe GVHD-relapse-free survival was higher in the ATG group (36.4%) than the control (12.9%; p &lt;0.001). Nevertheless, the 2-year overall survival was similar., Conclusion: Our results confirm the effectiveness of ATG in prevention of GVHD in the real-world setting and enhanced GVHD-free survival. An important result is the equalization of overall survival between the ATG and control groups at 1- and 2-year post-HSCT and implies that earlier GVHD-associated mortality may be offset by later relapse mortality producing similar overall survival over time., (S. Karger AG, Basel.)

Background: Multiple cell death modalities are implicated in sepsis pathobiology. However, the clinical relevance of NINJ1, a key mediator of plasma membrane rupture during lytic cell death, in sepsis progression and outcomes has remained poorly explored., Methods: Circulating NINJ1 levels were measured in 116 septic ICU patients, 16 non-septic ICU controls, and 16 healthy controls. Comparative analysis of serum NINJ1 across these groups was performed. Correlations between NINJ1 and clinical disease severity scores (SOFA, APACHE II) as well as laboratory parameters were examined in the sepsis cohort. Furthermore, we assessed the prognostic performance of NINJ1 for predicting 28-day mortality in septic patients using receiver operating characteristic (ROC) analyses., Results: Circulating NINJ1 levels were elevated in septic patients and positively correlated with sepsis severity scores. NINJ1 also showed positive correlations with liver injury markers (AST/ALT) and coagulation parameters (D-dimer, APTT, PT, TT) in sepsis. Further analysis using the ISTH overt DIC scoring system revealed an association between NINJ1 and sepsis-induced coagulopathy.ROC analysis demonstrated NINJ1 outperformed traditional inflammatory biomarkers PCT and CRP in predicting 28-day sepsis mortality, although its prognostic accuracy was lower than SOFA and APACHE II scores. Combining NINJ1 with SOFA improved mortality prediction from an AUC of 0.6843 to 0.773., Conclusions: Circulating NINJ1 serves as a novel sepsis biomarker indicative of disease severity, coagulopathy and mortality risk, and its integration with SOFA and APACHE II scores substantially enhances prognostic risk stratification. These findings highlight the prospective clinical utility of NINJ1 for sepsis prognostication and monitoring, warranting further validation studies to facilitate implementation., (Copyright © 2024 by the Shock Society.)

Deciphering the fine structure has always been a crucial approach to unlocking the distinct advantages of high activity, selectivity, and stability in single-atom catalysts (SACs). However, the complex system and unclear catalytic mechanism have obscured the significance of exploring the fine structure. Therefore, we endeavored to develop a three-component strategy to enhance oxygen reduction reaction (ORR), delving deep into the profound implications of the fine structure, focusing on central atoms, coordinating atoms, and environmental atoms. Firstly, the mechanism by which the chemical state and element type of central atoms influence catalytic performance is discussed. Secondly, the significance of coordinating atoms in SACs is analyzed, considering both the number and type. Lastly, the impact of environmental atoms in SACs is reviewed, encompassing existence state and atomic structure. Thorough analysis and summarization of how the fine structure of SACs influences the ORR have the potential to offer valuable insights for the accurate design and construction of SACs., (© 2024 Wiley‐VCH GmbH.)

So-called strength-ductility trade-off is usually an inevitable scenario in precipitation-strengthened alloys. To address this challenge, high-density coherent nanoprecipitates (CNPs) as a microstructure effectively promote ductility though multiple interactions between CNPs and dislocations (i.e., coherency, order, or Orowan mechanism). Although some strain hardening theories have been reported for individual strengthening, how to increase, artificially and quantitatively, the ductility arising from cooperative strengthening due to the multiple interactions has not been realized. Accordingly, a dislocation-based theoretical framework for strain hardening is constructed in terms of irreversible thermodynamics, where nucleation, gliding, and annihilation arising from dislocations have been integrated, so that the cooperative strengthening can be treated through thermodynamic driving force ∆G and the kinetic energy barrier. Further combined with synchrotron high-energy X-ray diffraction, the current model is verified. Following the modeling, the yield stress σy is proved to be correlated with the modified strengthening mechanism, whereas the necking strain εn is shown to depend on the evolving dislocation density and, essentially, the enhanced activation volume. A criterion of high ∆G-high generalized stability is proposed to guarantee the volume fraction of CNPs improving σy and the radius of CNPs accelerating εn. This strategy of breaking the strength-ductility trade-off phenomena by controlling the cooperative strengthening can be generalized to designing metallic structured materials.

Freshwater rivers are hotspots of N 2 O greenhouse gas emissions. Dissolved organic carbon (DOC) is the dominant electron donor for microbial N 2 O reduction, which can reduce N 2 O emission through enriching high N 2 O affinity denitrifiers or enriching non-denitrifying N 2 O-reducing bacteria (N 2 ORB), but the primary regulatory pathway remains unclear. Here, field study indicated that high DOC concentration in rivers enhanced denitrification rate but reduced N 2 O flux by improving nosZ gene abundance. Then, four N 2 O-fed membrane aeration biofilm reactors inoculated with river sediments from river channel, estuary, adjacent lake, and a mixture were continuously performed for 360 days, including low, high, and mixed DOC stages. During enrichment stages, the (nirS+nirK)/nosZ ratio showed no significant difference, but the community structure of denitrifiers and N 2 ORB changed significantly (p < 0.05). In addition, N 2 ORB strains isolated from different enrichment stages positioned in different branches of the phylogenetic tree. N 2 ORB strains isolated during high DOC stage showed significant higher maximum N 2 O-reducing capability (V max : 0.6 ± 0.4 ×10 -4 pmol h -1 cell -1 ) and N 2 O affinity (a 0 : 7.8 ± 7.7 ×1 0 -12 L cell -1 h -1 ) than strains isolated during low (V max : 0.1 ± 0.1 ×10 -4 pmol h -1 cell -1 , a 0 : 0.7 ± 0.4 ×1 0 -12 L cell -1 h -1 ) and mixed DOC stages (V max : 0.1 ± 0.1 ×10 -4 pmol h -1 cell -1 , a 0 : 0.9 ± 0.9 ×1 0 -12 L cell -1 h -1 ) (p < 0.05). Hence, under high DOC concentration conditions, the primary factor in reducing N 2 O emissions in rivers is the enrichment of complete denitrifiers with high N 2 O affinity, rather than non-denitrifying N 2 ORB., 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 B.V. All rights reserved.)

The short-video application TikTok shows great potential for disseminating health information. We assessed the content, sources, and quality of information in videos related to nonalcoholic fatty liver disease (NAFLD) on TikTok. Our study aims to identify upload sources, content, and characteristic information for NAFLD videos on TikTok and further evaluate factors related to video quality. We investigated the top 100 videos related to NAFLD on TikTok and analyzed the upload sources, content, and characteristics of these videos. Evaluate video quality using the DISCERN tool and Global Quality Score (GQS). In addition, the correlation between video quality and video characteristics is further studied. In terms of video sources, the majority of NAFLD videos on TikTok (85/100, 85%) were posted by doctors, ensuring the professionalism of the content, and among the video content, disease knowledge was the most dominant video content, accounting for 57% (57/100) of all videos, and the average DISCERN and GQS scores of all 100 videos were 39.59 (SD 3.31) and 2.99 (SD 0.95), respectively. DISCERN and GQS data show that videos related to NAFLD do not have high-quality scores on TikTok, mainly fair (68/100, 68%) and moderate (49/100, 49%). In general, the quality of NAFLD video information from professional content and professional sources was higher than that of nonprofessional sources and nonprofessional content, the video quality of general surgeons was better than that of other department physicians, and the video quality of junior physicians was better than that of senior physicians. In terms of video correlation, durations, the number of fans, and the total number of works were negatively correlated with DISCERN scores (R < 0, P < .05), while likes, comments, collections, shares, and days since upload were not significantly correlated with DISCERN and GQS scores (P > .05). The medical information on TikTok is not rigorous enough to guide patients to make accurate judgments, platforms should monitor and guide publishers to help promote and disseminate quality content., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

PFOA has garnered heightened scrutiny for its impact on denitrification, especially given its frequent detection in secondary effluent discharged from wastewater treatment plants. However, it is still unclear what potential risk PFOA release poses to a typical advanced treatment process, especially the sulfur-based autotrophic denitrification (SAD) process. In this study, different PFOA concentration were tested to explore their impact on denitrification kinetics and microbial dynamic responses of the SAD process. The results showed that an increase PFOA concentration from 0 to 1000 μg/L resulted in a decrease in nitrate removal rate from 9.52 to 7.73 mg-N/L·h. At the same time, it increased nitrite accumulation and N 2 O emission by 6.11 and 2.03 times, respectively. The inhibitory effect of PFOA on nitrate and nitrite reductase activity in the SAD process was linked to the observed fluctuations in nitrate and nitrite levels. It is noteworthy that nitrite reductase was more vulnerable to the influence of PFOA than nitrate reductase. Furthermore, PFOA showed a significant impact on gene expression and microbial community. Metabolic function prediction revealed a notable decrease in nitrogen metabolism and an increase in sulfur metabolism under PFOA exposure. This study highlights that PFOA has a considerable inhibitory effect on SAD performance., 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. Published by Elsevier B.V.)

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined., Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months., Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Background: Insulin resistance (IR) can predict the prognosis of patients suffering from cerebrovascular disorders. The triglyceride-glucose (TyG) index and triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio have been confirmed to be easy and reliable indicators of IR. However, the relationships between the TyG index or TG/HDL-C ratio and early neurological deterioration (END) after thrombolysis in patients with acute ischemic stroke (AIS) are uncertain., Methods: A retrospective analysis of 1,187 patients diagnosed with AIS who underwent intravenous thrombolysis between January 2018 and February 2024 was performed. Post-thrombolysis END was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score of ≥4 within 24 h after thrombolysis. Logistic regression analysis was performed to explore the relationships of the TyG index and TG/HDL-C ratio with post-thrombolysis END. Receiver operating characteristic (ROC) analysis was used to assess the ability of the TyG index and TG/HDL-C ratio to discriminate post-thrombolysis END., Results: Among the 1,187 recruited patients, 179 (15.08%) were diagnosed with post-thrombolysis END, and 1,008 (84.92%) were diagnosed with non-END. A binary logistic regression model indicated that the TyG index (odds ratio [OR], 2.015; 95% confidence interval [CI] 1.964-2.414, p  = 0.015) and TG/HDL-C ratio (OR, 1.542; 95% CI, 1.160-2.049, p  = 0.004) were independent factors for post-thrombolysis END. The area under the curve (AUC) values for the TyG index, TG/HDL-C ratio, and TyG index combined with the TG/HDL-C ratio for post-thrombolysis END were 0.704, 0.674, and 0.755, respectively., Conclusion: This study indicates that the TyG index and TG/HDL-C ratio can be used as prognostic factors to predict post-thrombolysis END., 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 © 2024 Deng, Song, Xu, He, Hu, Xiao, Zhou, Chen, Xu, Tong, Zhang, Wang and Li.)

Hyperuricemia is closely linked to obesity. As lifestyles and dietary patterns evolve, the prevalence of hyperuricemia has been on the rise. Bariatric surgery, an efficacious intervention for morbid obesity and its associated metabolic disorders, not only manages the weight of patients with severe obesity but also exerts beneficial therapeutic effects on hyperuricemia and gout. Moreover, it demonstrates substantial efficacy against other obesity-related metabolic conditions. However, the dramatic fluctuations in serum uric acid levels and acute gouty attacks in the immediate postoperative period are issues that should not be overlooked, and effective preventative strategies for some related adverse complications are still underexplored. This review discusses and reviews the advancements in the treatment of obese patients with hyperuricemia through bariatric surgery. By reviewing pertinent literature, it summarizes the short-term and long-term therapeutic outcomes of bariatric surgery for hyperuricemia, as well as common adverse reactions. Furthermore, by discussing preoperative and postoperative interventional measures and influential factors, this review aims to provide novel perspectives for the clinical management of hyperuricemia and offer insights for the prevention of related complications., (© 2024. The Author(s).)

Self-propelled nanomotors possess strong propulsion and penetration abilities, which can increase the efficiency of cellular uptake of nanoparticles and enhance their cytotoxicity against tumor cells, opening a new path for treating major diseases. In this study, the concept of driving nanomotors by alternately stretching and contracting a temperature-sensitive polymer (TS-P) chain is proposed. The TS-Ps are successfully linked to one side of Cu 2-x Se@Au (CS@Au) nanoparticles to form a Janus structure, which is designated as Cu 2-x Se@Au-polymer (CS@Au-P) nanomotors. Under near-infrared (NIR) light irradiation, Cu 2-x Se nanoparticles generate photothermal effects that change the system temperature, triggering the alternation of the TS-P structure to generate a mechanical force that propels the motion of CS@Au-P nanomotors. The nanomotor significantly improved the cellular uptake of nanoparticles and enhanced their penetration and accumulation in tumor. Furthermore, the exceptional photothermal conversion efficiency of CS@Au-P nanomotors suggests their potential as nanomaterials for photothermal therapy (PTT). The prepared material exhibited good biocompatibility and anti-tumor effects both in vivo and in vitro, providing new research insights into the design and application of nanomotors in tumor therapy., (© 2024 Wiley‐VCH GmbH.)

Background: Digestive system cancers constitute a significant number of cancer cases, but their burden is not uniform. As Global Cancer Observatory (GLOBOCAN) 2022 has recently updated its estimates of cancer burden, we aimed to investigate the burden of six major digestive system cancers both worldwide and in China, along with geographical and temporal variations in cancer-specific incidence and mortality., Methods: We extracted data on primary cancers of the esophagus, stomach, colorectum, liver, pancreas, and gallbladder from the GLOBOCAN database for 2022. Age-standardized incidence and mortality rates were calculated and stratified by sex, country, region, and human development index (HDI). We used the 2022 revision of the World Population Prospects (United Nations) to obtain demographic data for various age groups in China from 1988 to 2012 and used the joinpoint model and the average annual percentage change (AAPC) to analyze cancer incidence trends in China., Results: In 2022, the estimated global incidence of digestive system cancers reached 4,905,882, with an estimated 3,324,774 cancer-related deaths. Colorectal cancer was most prevalent in terms of incidence and mortality. There was a significant correlation between the burden of gastrointestinal cancers and country HDI. From 1988 to 2012, the incidence of esophageal, gastric, and liver cancers declined in China, whereas colorectal and pancreatic cancer incidences continued to increase. By 2050, colorectal and liver cancers are projected to remain the leading cancer types in China in terms of incidence and mortality, respectively., Conclusions: Digestive system cancers remain a significant public health challenge globally and in China. Although progress has been made in the prevention and control of some cancers, the burden of digestive system cancers persists. The implementation of tertiary prevention strategies must be intensified to reduce the incidence and mortality of digestive system cancers, mitigating their impact on public health., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

The development of ultrasensitive and visual methods is of great significance for molecular diagnosis at the point-of-care. In this study, we have integrated recombinase polymerase amplification (RPA) with the CRISPR-Cas12a system to design an ultrasensitive strategy for visual nucleic acid testing. RPA is utilized to amplify the target nucleic acid, producing amplicons that activate the single-stranded DNase property of CRISPR-Cas12a. The activated CRISPR-Cas12a then degrades the single-stranded DNA on magnetic nanoparticles (MNPs), releasing immobilized GOx from the MNPs which catalyses the chromogenic substrate. The developed method exhibits remarkable sensitivity, successfully detecting as low as 10 aM (∼6 copies per μL) of the target nucleic acid by visual colour changes in solution. The instrumental limit of detection is calculated to be 2.86 aM (∼2 copies per μL), comparable to the sensitivity of polymerase chain reaction (PCR). Importantly, this approach only requires isothermal incubation operation and does not involve costly instruments. The method has been validated by visually detecting the SARS-CoV-2 RNA gene fragment within 50 minutes. With its ultrasensitivity, simplicity of operation, and potential for integration into a point-of-care detection kit, this strategy holds great promise for nucleic acid testing in various settings.

The accumulation of amyloid fibrils has been identified in tissues outside the brain, yet little is understood about the formation of extracerebral amyloidosis and its impact on the aging process of these organs. Here, we demonstrate that both transgenic mice modeling Alzheimer's disease (AD) and naturally aging mice exhibit accumulated senescent bone marrow adipocytes (BMAds), accompanied by amyloid deposits surrounding the BMAds. Senescent BMAds acquire a secretory phenotype, resulting in a marked increase in the secretion of serum amyloid P component (SAP), also known as pentraxin 2 (PTX2). SAP/PTX2 colocalizes with amyloid deposits around senescent BMAds in vivo and is sufficient to promote the formation of insoluble amyloid deposits from soluble Aβ peptides in in vitro and ex vivo 3D BMAd-based culture experiments. Additionally, Combined treatment with SAP/PTX2 and Aβ peptides promotes osteoclastogenesis but inhibits osteoblastogenesis of the precursor cells. Transplantation of senescent BMAds into the bone marrow cavity of healthy young mice is sufficient to induce bone loss. Finally, pharmacological depletion of SAP/PTX2 from aged mice abolishes bone marrow amyloid deposition and effectively rescues the low bone mass phenotype. Thus, senescent BMAds, through the secretion of SAP/PTX2, contribute to the age-associated development of skeletal amyloidosis and resultant bone deficits.

Background: Minute gastric cancers (MGCs) have a favorable prognosis, but they are too small to be detected by endoscopy, with a maximum diameter ≤ 5 mm., Aim: To explore endoscopic detection and diagnostic strategies for MGCs., Methods: This was a real-world observational study. The endoscopic and clinicopathological parameters of 191 MGCs between January 2015 and December 2022 were retrospectively analyzed. Endoscopic discoverable opportunity and typical neoplastic features were emphatically reviewed., Results: All MGCs in our study were of a single pathological type, 97.38% (186/191) of which were differentiated-type tumors. White light endoscopy (WLE) detected 84.29% (161/191) of MGCs, and the most common morphology of MGCs found by WLE was protruding. Narrow-band imaging (NBI) secondary observation detected 14.14% (27/191) of MGCs, and the most common morphology of MGCs found by NBI was flat. Another three MGCs were detected by indigo carmine third observation. If a well-demarcated border lesion exhibited a typical neoplastic color, such as yellowish-red or whitish under WLE and brownish under NBI, MGCs should be diagnosed. The proportion with high diagnostic confidence by magnifying endoscopy with NBI (ME-NBI) was significantly higher than the proportion with low diagnostic confidence and the only visible groups (94.19% > 56.92% > 32.50%, P < 0.001)., Conclusion: WLE combined with NBI and indigo carmine are helpful for detection of MGCs. A clear demarcation line combined with a typical neoplastic color using nonmagnifying observation is sufficient for diagnosis of MGCs. ME-NBI improves the endoscopic diagnostic confidence of MGCs., Competing Interests: Conflict-of-interest statement: The manuscript has been approved by all of the authors and there are no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The hydrogen abstraction reaction of OH + CH 3 OH plays a great role in combustion and atmospheric and interstellar chemistry and has been extensively studied theoretically and experimentally. Theoretically, the numerical gradients with respect to the Cartesian coordinates of atoms in molecular simulations on our recent potential energy surface (PES) for the title reaction trained using the permutationally invariant polynomial neural network (PIP-NN) approach hinder the extensive calculation because of the unaffordable computation cost. To address this issue, we in this work report a new full-dimensional accurate analytical PES for the title reaction using the fundamental invariant neural network (FI-NN) approach based on 140,192 points of the quality UCCSD(T)-F12a/AVTZ. Besides, the spin-orbit (SO) corrections of OH in the entrance channel were determined at the level of complete active space self-consistent field with the AVTZ basis set. As a compromise between computational cost and efficiency, the Δ-machine learning approach was employed to construct the SO-corrected PES. Based on this new FI-NN PES with analytical forces, thermal rate coefficients and various dynamic properties, including the integral cross sections, the differential cross sections, and the product energy partitioning, were determined by running a total of 5.5 million trajectories. The use of analytical gradients of the FI-NN PES accelerated simulations and about 99% of computation cost was saved, compared to that for the PIP-NN PES with numerical gradients. Such a significant acceleration is achieved mainly by replacing PIPs with FIs.

Landscape changes resulting from anthropogenic activities and climate changes severely impact surface water quality. A global perspective on understanding their relationship is a prerequisite for pursuing equity in water security and sustainable development. A sequent meta-analysis synthesizing 625 regional studies from 63 countries worldwide was conducted to analyze the impacts on water quality from changing landscape compositions in the catchment and explore the moderating factors and temporal evolution. Results exhibit that total nitrogen (TN), total phosphorus (TP), and chemical oxygen demand (COD) in water are mostly concerned and highly responsive to landscape changes. Expansion of urban lands fundamentally degraded worldwide water quality over the past 20 years, of which the arid areas tended to suffer more harsh deterioration. Increasing forest cover, particularly low-latitude forests, significantly decreased the risk of water pollution, especially biological and heavy metal contamination, suggesting the importance of forest restoration in global urbanization. The effect size of agricultural land changes on water quality was spatially scale-dependent, decreasing and then increasing with the buffer radius expanding. Wetland coverage positively correlated with organic matter in water typified by COD, and the correlation coefficient peaked in the boreal areas (r=0.82, p<0.01). Overall, the global impacts of landscape changes on water quality have been intensifying since the 1990s. Nevertheless, knowledge gaps still exist in developing areas, especially in Africa and South America, where the water quality is sensitive to landscape changes and is expected to experience dramatic shifts in foreseeable future development. Our study revealed the worldwide consistency and heterogeneity between regions, thus serving as a research roadmap to address the quality-induced global water scarcity under landscape changes and to direct the management of land and water., 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 Ltd. All rights reserved.)

Gastric cancer (GC) remains a significant global health challenge, particularly prevalent in East Asia. Despite advancements in various treatment modalities, the prognosis for patients, especially those in advanced stages, remains poor, highlighting the need for innovative therapeutic approaches. This review explores the promising potential of diterpenes, naturally occurring compounds with robust anticancer properties, derived from diverse sources such as plants, marine organisms, and fungi. Diterpenes have shown the ability to influence reactive oxygen species (ROS) generation, ferroptosis, and autophagy, positioning them as attractive candidates for novel cancer therapies. This review explores the mechanisms of action of diterpenes and their clinical implications for the treatment of GC. Additionally, it addresses the challenges in translating these compounds from preclinical studies to clinical applications, emphasizing the need for further research to enhance their therapeutic profiles and minimize potential side effects. The discussion underscores the importance of diterpenes in future anticancer strategies, particularly in the fight against gastric cancer.

Objective: To compare the effectiveness of spinal robot-assisted pedicle screw placement through different surgical approaches and to guide the clinical selection of appropriate robot-assisted surgical approaches., Methods: The clinical data of 14 patients with thoracolumbar vertebral diseases who met the selection criteria between January 2023 and August 2023 were retrospectively analyzed, and all of them underwent pedicle screw placement under assistant of the Mazor X spinal surgery robot through different surgical approaches. The patients were divided into posterior median approach (PMA) group ( n =6) and intermuscular approach (IMA) group ( n =8) according to the surgical approaches, and there was no significant difference in age, gender, body mass index, disease type, and fixed segment between the two groups ( P >0.05). The operation time, intraoperative blood loss, screw-related complications, and reoperation rate were recorded and compared between the two groups; the inclination angle of the screw, the distance between the screw and the midline, and the caudal inclination angle of the screw were measured based on X-ray films at immediate after operation., Results: There was no significant difference in operation time and intraoperative blood loss between the two groups ( P >0.05). There was no screw-related complication such as nerve injury in both groups, and no patients underwent secondary surgery. At immediate after operation, the inclination angle of the screw, the distance between the screw and the midline, and the caudal inclination angle of the screw in the IMA group were significantly greater than those in the PMA group ( P <0.05)., Conclusion: There are differences in the position and inclination angle of screws placed with robot-assisted surgery through different surgical approaches, which may be due to the obstruction of the screw path by soft tissues such as skin and muscles. When using spinal robot-assisted surgery, selecting the appropriate surgical approach for different diseases can make the treatment more reasonable and effective.