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Two examples of human decision-making biases are reexamined from an evolutionary perspective. The framing effect and ambiguity avoidance effect both violate core assumptions of normative models of rational decision making. These violations were often used to showcase that the human mind is predisposed against optimal decision making. The authors argue that the human mind is fine-tuned to solve complex decision tasks that had been recurrent in hominid evolution. By studying the biases within the framework of risk-sensitivity theory, they demonstrate that humans take into account the mean outcome of an option, the variability of the outcome, and their current goal to arrive at a decision that is most likely to guarantee survival. Thus, an evolutionary approach helps us reveal important features of human choice behavior and provides insights into the nature of human decision rationality.

Over the past decade, the field of urological and male reproductive system pathology has experienced rapid development. Numerous accomplishments were achieved in clinical diagnosis and molecular research in this area in China, gradually gaining international recognition. As the most influential academic journal in the field of pathology in China, the Chinese Journal of Pathology has witnessed the vigorous growth and innovation in this domain. On the occasion of the journal's 70th anniversary, a summary on the developments in this field have been provided, along with an outlook for the future.

Objective: To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of MED15-TFE3 gene fusion renal cell carcinoma (MED15-TFE3 RCC). Methods: A total of 12 MED15-TFE3 RCCs, diagnosed from 2016 to 2023, were collected from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China for clinicopathologic, immunohistochemical, fluorescence in situ hybridization (FISH) and RNA sequencing (RNA-seq) analyses and follow-up. In addition, its diagnosis and differential diagnosis were also explored. Results: There were five males and seven females. The patients' ages ranged from 16 to 60 years, with an average age of 40.4 years. The follow-up time ranged from 15 to 92 months, and no recurrence or metastasis was observed. Histologically, 6 cases exhibited extensive cystic structures with almost no solid sheet components, while the remaining 6 cases displayed a cysto-solid growth pattern. The cytoplasm of the tumor cells appeared flocculent, with a clear or faintly eosinophilic appearance, and nucleoli were inconspicuous. Psammoma bodies were observed in 12 cases. There was deposition of basement membrane-like material in 5 cases. All cases showed strong expression of TFE3, GPNMB, Cathepsin K, Melan A, and PAX8, while no expression of CAⅨ or CK7. FISH analyses showed that all 12 cases were positive for the MED15-TFE3 fusion, while the MED15-TFE3 fusion gene and specific fusion sites were detected in 2 cases using RNA-seq. Conclusions: MED15-TFE3 RCC is a type of TFE3-rearranged renal cell carcinoma that exhibits both identifiable diagnostic characteristics and highly deceptive morphology. Its distinct extensive cystic structure can be easily confused with multilocular cystic renal neoplasm of low malignant potential, necessitating careful differentiation in routine practice.

Adeno-associated virus (AAV)-associated gene therapy has been increasingly promising, in light of the drugs progressed to clinical trials or approved for medications internationally. Therefore, scalable and efficient production of recombinant AAV is pivotal for advancing gene therapy. Traditional methods, such as the triple-plasmid transfection of human embryonic kidney 293 cells in suspension culture, have been widely employed but often hampered by low unit yield. In this study, we optimized the cell culture process with high cell density up to 2 × 10 7 cells/mL by employing a perfusion culture system with centrifugation and medium exchange in shake flasks and perfusion device in bioreactor. Furthermore, we utilized a design of experiments strategy to systematically modulate a series of transfection-related variables including the quantity of plasmid DNA, the DNA-to-polyethylenimine ratio, incubation duration, and the impact of post-transfection feeding strategies on the yield of recombinant AAV (rAAV). Our comprehensive analysis and subsequent optimizations actualized a remarkable unit yield reaching nearly 2 × 10 12 vector genomes (vg)/mL. Importantly, the resulting single-cell yield and biological activity were found to be comparable with those obtained from fed-batch cultures, underscoring the efficacy of our approach. Based on these findings, we investigated rAAV yield via high-density suspend culture in bioreactor, particularly focusing on cell aggregation and the use of perfusion technology. Intriguingly, we attempted to elevate the yield of an oversized recombinant coagulation factor VIII AAV843 vector by 3.5-fold, reaching a yield of 1 × 10 12 vg/mL. Concurrently, the medium usage rate was only double that of batch feeding, thereby significantly shrinking the upstream cost of rAAV manufacture. In summary, this strategy significantly benefits large-scale AAV production for both commercial and clinical applications.

Hot spots can generate intense local electromagnetic (EM) fields, thereby boosting diverse innovative applications. However, these applications may face challenges due to their subtle structural changes that can significantly impact their EM field strength. Herein, we report a large-scale synthesis of monodisperse, highly spherical, single crystalline (SC) Au nanospheres (Au NSs) with tunable sizes ranging from 38 to 92 nm for constructing uniform and reproducible hot spots with a nanosphere-on-mirror (NSoM) configuration. Surface-enhanced Raman scattering tests reveal that single NSoM hot spots generate homogeneous EM fields with intensity variation of <4.0% due to their identical "point-to-mirror" configuration. Moreover, the SC nature of the Au NSs can further increase the EM field by 9% because of their higher quality factor, resulting in less energy dissipation in the plasmon. Therefore, these Au NSs may serve as ideal building blocks for the construction of hot spots with homogeneous EM fields.

Background: Many studies have shown that the COVID-19 pandemic has increased the risk of suicidal tendencies among the public. However, there is limited research reporting on the changing trends in suicidal ideation after 2020 in the context of the long-term normalization of COVID-19 prevention and control measures in China., Methods: The self-administered online questionnaire was adopted to collect 12-month suicidal ideation, depressive symptoms, anxiety symptoms, stress, and some demographic information from university students by convenient cluster sampling in Shandong, Shaanxi, and Jilin Provinces, China. Multivariate logistic regressions were performed to assess the association between different factors and suicidal ideation., Results: The prevalence of 12-month suicidal ideation from 2021 to 2023 among university students was 3.89 %, 5.81 %, and 4.33 %, respectively, showing a trend of first increasing and then decreasing. The trends presented a similar tendency in the subgroups according to gender, majors, and grades, except among urban freshman-year students. The associated factors of suicidal ideation were different among university students in different surveys. However, female gender, poor mental health, and depressive symptoms were linked to a higher risk of suicidal ideation., Limitations: More representative large-scale longitudinal studies should be used to monitor the suicidal behavior of university students., Conclusions: The prevalence of 12-month suicidal ideation among Chinese university students exhibited a pattern of initial increase followed by a subsequent decrease from 2021 to 2023. Despite the complete lifting of COVID-19 prevention and control measures in China, the prolonged three-year epidemic may have enduring adverse effects on university students, underscoring the ongoing importance of providing continuous mental health services to this population., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Acute Kidney Injury (AKI) is a multifaceted condition characterised by rapid deterioration of renal function, often precipitated by diverse etiologies. A comprehensive understanding of the molecular underpinnings of AKI is pivotal for identifying potential diagnostic markers and therapeutic targets. This study utilised bioinformatics to elucidate gene expression and immune infiltration in AKI. Publicly available mRNA and miRNA datasets were harnessed to discern differentially expressed genes (DEGs) and miRNAs in AKI. The CIBERSORT algorithm was employed to quantify immune cell infiltration in AKI samples. Functional enrichment analyses were conducted to unravel the implicated biological processes. Furthermore, the expression of identified genes and miRNAs was validated by quantitative real-time PCR in an AKI model. Our study revealed significant dysregulation of three genes (Aspn, Clec2h, Tmigd1) and two miRNAs (mmu-miR-21a-3p, mmu-miR-223-3p) in AKI, each with p < 0.0001. These molecular markers are implicated in immune responses, tissue remodelling, and inflammation. We observed notable disturbances in specific immune cells, including activated and immature dendritic cells, M1 macrophages, and subsets of T cells (Treg, Th1, Th17). These alterations correlated significantly with AKI pathology, with dendritic cells and M1 macrophages showing p < 0.01, and T cell subsets demonstrating p < 0.05. These results highlight the intricate involvement of the immune system in AKI and indicate significant enrichment of pathways related to immune response, inflammation, and tissue remodelling, pointing to their pivotal roles in AKI pathophysiology. Our study underscored the significance of immune cell infiltration and dysregulated gene and miRNA expression in AKI. The identified genes (Clec2h, Aspn, and Tmigd1) and miRNAs (mmu-miR-21a-3p and mmu-miR-223-3p) offer potential diagnostic markers and therapeutic avenues for AKI. Subsequent investigations targeting these genes and miRNAs, along with the elucidated pathways, may augment the clinical management and outcomes for AKI patients., Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of interest. Ethics Approval and Consent to Participate: The Ethics Committee of the First Affiliated Hospital of Harbin Medical University reviewed and approved the study (Ethics Committee Approval Number: 2022064). Consent for Publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Increasing evidence suggests that immune cell clearance is closely linked to cellular metabolism. Neurosyphilis, a severe neurological disorder caused by Treponema pallidum (T. pallidum) infection, significantly impacts the brain. Microglia, the innate immune cells of the central nervous system, play a critical role in neuroinflammation and immune surveillance. However, the inability of the nervous system to fully eliminate T. pallidum points to a compromised clearance function of microglia. This study investigates how T. pallidum alters the immune clearance ability of microglia and explores the underlying metabolic mechanisms. RNA sequencing (RNA seq), LC-MS metabolomics, and XFe96 Seahorse assays were employed to assess metabolic activity in microglial cells. Western blotting, qPCR, and immunofluorescence imaging were utilized to evaluate autophagy flux and extent of T. pallidum infections. Transcriptomic analysis revealed that T. pallidum alters the transcription expression of key glycolytic enzymes, including hexokinase 1 (HK1), hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA), leading to significant metabolic dysregulation. Specifically, metabolomic analysis showed reduced levels of phosphoenolpyruvate and citrate, while lactate production was notably increased. Functional assays confirmed that T. pallidum impairs glycolytic activity in microglial, as evidenced by decreased glycolytic flux, glycolytic reserve capacity, and maximum glycolytic capacity. Moreover, our results indicate that HK2, a crucial glycolytic enzyme, is closely associated with the autophagy. T. pallidum infection inhibits HK2 expression, which in turn suppresses autophagic flux by reducing the formation of lysosome-associated membrane protein 2 (LAMP2) and disrupting autophagosome-lysosome fusion. These findings suggest that T. pallidum hijacks microglial metabolic pathways, specifically glycolysis, to evade immune clearance. By inhibiting the glycolytic enzyme HK2, T. pallidum modulates autophagy and enhances immune evasion, providing a novel insight into the pathogenesis of neurosyphilis. This study paves the way for further investigations into the role of metabolic reprogramming in the immune escape mechanisms of T. pallidum., 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.)

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare subtype of RCC characterized by the presence of a germline mutation in one of the four subunits of the SDH enzyme complex (SDHA, SDHB, SDHC and SDHD). Together with a somatic second hit, these variants lead to the loss of function of the SDH complex. SDH-deficient RCC associated with SDHA mutation is a rare condition; to the best of our knowledge, there have been only four patients reported in the literature. The present study describes the case of a 22-year-old female patient with RCC associated with SDHA gene mutation. Next-generation sequencing and Sanger sequencing identified a novel heterozygous frameshift variant (NM&#95;004168.4: c.992&#95;999dup) in the SDHA gene. In the literature, this mutation has not previously been reported to be associated with RCC. The present description of a patient with a heterozygous SDHA frameshift variant expands the phenotypic spectrum of the SDHA gene, and provides further clinical, morphological and molecular data of SDHA-deficient RCC., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Hu et al.)

Background: Risk factors associated with infection and traumatic lacerations affecting the face are still not fully understood. This study investigated risk factors for poor outcomes in adult patients with through-and-through lip wounds who underwent debridement and suturing., Methods: Patients with through-and-through lip wounds who underwent debridement in our emergency department between January 1, 2017, and December 31, 2021, were included. The effects of gender, age, wound age (time from injury to wound closure), antibiotic application, injury mechanism, diabetes, wound length, wound cleanliness, peripheral tissue damage, and postoperative wound blood scab on the poor outcome rate were assessed for all patients. Poor outcome was analyzed based on atraumatic wound dehiscence before suture removal, pus in the wound, and unhealed oral wounds with a length >1 cm or deeper than the muscle layer 5-6 days after surgery., Results: A total of 728 cases were included, with a poor outcome rate of 20.88 %. The univariable analysis showed that the proportion of poor outcomes was significantly associated with male gender, age (65-79 years old), bicycle/electric bicyble, antibiotic use, wound length of 4-8 cm, wound contamination, peripheral tissue damage, and scabs. Binary logistic analysis showed that the proportion of poor outcomes was significantly associated with older age (65-79 years old), wound length of 4-8 cm, peripheral tissue damage and wounds covered by scabs. In the binary logistic regression analysis, poor outcomes were not associated with gender, injury mechanism, wound contamination or the use of antibiotics., Conclusion: Our findings provide valuable information on the risk factors for poor outcomes in adult patients with lip through-and-through wounds who underwent debridement and suturing., 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 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

The cerebellum is heavily connected with other brain regions, sub-serving not only motor but also nonmotor functions. Genetic mutations leading to cerebellar dysfunction are associated with mental diseases, but cerebellar outputs have not been systematically studied in this context. Here, we present three dimensional distributions of 50,168 target neurons of cerebellar nuclei (CN) from wild-type mice and Nlgn3R451C mutant mice, a mouse model for autism. Our results derived from 36 target nuclei show that the projections from CN to thalamus, midbrain and brainstem are differentially affected by Nlgn3R451C mutation. Importantly, Nlgn3R451C mutation altered the innervation power of CN→zona incerta (ZI) pathway, and chemogenetic inhibition of a neuronal subpopulation in the ZI that receives inputs from the CN rescues social defects in Nlgn3R451C mice. Our study highlights potential role of cerebellar outputs in the pathogenesis of autism and provides potential new therapeutic strategy for this disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of Higher Education Press.)

Objectives: To evaluate the effectiveness of computer-aided design (CAD)/computer-aided manufacturing (CAM) in designing and manufacturing 3D-printed dental models used to make thermoplastic removable splints for children with traumatized anterior permanent teeth., Methods: A total of 28 patients with dental trauma (subluxation, extrusive luxation, and lateral luxation) were divided into experimental (14 patients) and control groups (14 patients). The experimental group was treated with the removable splint made using a new 3D printed dental model designed with CAD/CAM technology, while the control group received a wire-composite splint. Follow-up was performed at week 2 and 1, 2, 3, 6, 12, 18, and 24 months post-treatment, and every year after that. The traumatized teeth were evaluated according to clinical symptoms, tooth color, mobility, position, percussion pain, abnormal percussion sounds indicating ankylosis or other pathosis, swelling, fistula of gums, vitality test, and radiographic examination., Results: No significant difference was found in gender and age between the two groups. The experimental group had 23 traumatic teeth, and the control group had 24 traumatic teeth. Traumatic teeth in the two groups most commonly involved open apex teeth (>90 %). The average follow-up time for the experimental and control group was 35.47±14.23 and 32.92±14.79 months (P > 0.05), respectively. The pulp survival rate and periodontal healing rate in the experimental group (86.96 %, 91.30 %) were higher compared to the control group (62.50 %, 75.00 %) (all P > 0.05)., Conclusion: A removable splint made by a 3D printed dental model designed with CAD/CAM technology achieved an equivalent treatment effect to a wire-composite splint., Clinical Significance: A 3D-printed dental model designed with CAD/CAM technology can be used to fabricate removable splints, which in turn can decrease iatrogenic injuries frequently encountered during the traditional model production process. For example, taking the impression directly from the patient's mouth can cause displacement of a traumatized tooth or even exfoliation. The removable splints produced using a new 3D-printed dental model can meet clinical treatment requirements of traumatized teeth, especially for children and adolescents with occlusal trauma in mixed dentition., 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.)

Objective To explore the application value of multi-model adaptive statistical iterative reconstruction-Veo (ASiR-V) in ultra-low dose chest CT examination of children in the plateau area. Methods The children who underwent chest CT examination in Xizang Autonomous Region People's Hospital were enrolled in this study and assigned into two groups according to the scanning conditions.Group A underwent scanning at a tube voltage of 100 kV and ASiR-V 50% reconstruction,and group B underwent scanning at a tube voltage of 80 kV and ASiR-V 0 (Group B1) and ASiR-V 50% (Group B2) reconstruction.The image quality of each group was evaluated objectively and subjectively.The radiation dose and image quality were compared between groups. Results Groups A and B showed the volume CT dose indexes of (2.33±0.62) mGy and (0.86±0.01) mGy and the dose length products of (65.01±25.12) mGy·cm and (23.55±3.38) mGy·cm,respectively,which presented differences between groups (both P<0.001).The image noise in the bilateral upper and middle lung areas in group B2 was lower than that in group B1 but higher than that in group A (all P<0.001).There was no significant difference in image quality score of the lung window among groups (all P>0.05).Groups A,B1,and B2 had no significant differences in ascending aorta (P=0.538) or liver CT value (P=0.175) in the mediastinal window.The signal-to-noise ratios and contrast-to-noise ratios of ascending aorta and liver in group B2 were higher than those in group B1 (all P<0.001) and lower than those in group A (all P<0.05).The image quality score of the mediastinal window followed a descending order of group A>group B2>group B1 (all P<0.001). Conclusion ASiR-V combined with low tube voltage can effectively reduce the radiation dose and guarantee the image quality of chest CT of children in the plateau area.

The imperative advance towards achieving "carbon neutrality" necessitates the development of porous structures possessing dual acoustic and mechanical properties in order to mitigate energy consumption. Nevertheless, enhancing various functionalities often leads to an increase in the structural weight, which limits the feasibility of using such structures in weight-sensitive applications. In accordance with the outlined specifications, a novel structural design incorporating carbon fiber reinforced polymer (CFRP) composites alongside mechanical and acoustic metamaterials has been introduced for the first time. This innovative construction exhibits a lightweight composition with excellent mechanical and acoustic characteristics. Experimental findings demonstrate that with meticulous planning and fabrication, CFRP composite structures can achieve a balance of lightweight construction, high strength, exceptional energy absorption, and remarkable resilience. By introducing membrane and reasonable cavity design, the structure can produce low broadband noise reduction performance by a local resonance effect and impedance matching mechanism of metamaterials. The structural sound insulation capability breaks traditional mass law, resulting in an exceptionally broadband sound insulation peak (bandwidth of nearly 1000 Hz). Furthermore, the sound absorption characteristic of the structure surpasses that of the melamine sponge at frequencies below 300 Hz, demonstrating superior low-frequency sound absorption properties. The proposed structure provides new approaches for the design of multifunctional lightweight superstructures.

1-Hexadecene has been detected at a level of mg/L in both influent and effluent of wastewater treatment plants situated in chemical/pharmaceutical industrial parks, which poses a potential threat to the environment. However, few reports are available on aerobic metabolic pathways and microorganisms involved in 1-Hexadecene degradation. In this study, a new strain of 1-Hexadecene-degrading bacteria, Bacillus sp. Hex-HIT36 (HIT36), was isolated from the activated sludge of a wastewater treatment plants located in an industrial park. The physicochemical properties and degradation efficacy of HIT36 were investigated. HIT36 was cultured on a medium containing 1-Hexadecene as a sole carbon source; it was found to remove ∼67% of total organic carbon as confirmed by mass spectrometric analysis of intermediate metabolites. Metabolomic and genomic analysis showed that HIT36 possesses various enzymes, namely, pyruvate dehydrogenase, dihydropolyhydroxyl dehydrogenase, and 2-oxoglutarate-2-oxoiron oxidoreductase (subunit alpha), which assist in the metabolization of readily available carbon source or long chain hydrocarbons present in the growth medium/vicinity. This suggests that HIT36 has efficient long-chain alkane degradation efficacy, and understanding the alkane degradation mechanism of this strain can help in developing technologies for the degradation of long-chain alkanes present in wastewater, thereby assisting in the bioremediation of environment., 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 Inc.)

Applied voltage is a crucial parameter in hybrid microbial electrolysis cells-anaerobic digestion (MEC-AD) systems for enhancing methane production from waste activated sludge (WAS). This study explored the impact of applied voltage on the initial biofilm formation on electrodes during the MEC-AD startup using raw WAS (Rr) and heat-pretreated WAS (Rh). The findings indicated that the maximum methane productivity for Rr and Rh were 3.4 ± 0.5 and 3.4 ± 0.2 mL/gVSS/d, respectively, increasing 1.5 times and 2.6 times over the productivity at 0 V. The biomass on electrode biofilms for Rr and Rh at 0.8 V increased by 70 % and 100 % compared to 0 V. The core functional microorganisms in the cathode biofilm were Methanobacterium and Syntrophomonas, and Geobacter in the anode biofilm, enhancing methane production through syntrophism and direct interspecies electron transfer, respectively. These results offer academic insights into optimizing AD functional electrode biofilms by applying voltage., 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 Ltd.)

Metalloproteinases are ubiquitous in organisms. Most metalloproteinases secreted by pathogenic microorganisms are also called virulence factors, because they degrade proteins in the external tissues of the host, thereby reducing the host's immunity and increasing its susceptibility to disease. Zinc metalloproteinase is one of the most common metalloproteinases. In our report, we studied the biological function of zinc metalloprotease FgM35 in Fusarium graminearum and the pathogen-host interaction during infection. We found that the asexual and sexual reproduction of the deletion mutant ΔFgM35 were affected, as well as the tolerance of F. graminearum to metal stress. In addition, deletion of FgM35 reduced the virulence of F. graminearum. The wheat target TaZnBP was screened using a wheat yeast cDNA library, and the interaction between FgM35 and TaZnBP was verified by HADDOCK molecular docking, yeast two-hybrid, Bi-FC, Luc, and Co-IP assays. The contribution of TaZnBP to plant immunity was also demonstrated. In summary, our work revealed the indispensable role of FgM35 in the reproductive process and the pathogenicity of F. graminearum, and it identified the interaction between FgM35 and TaZnBP as well as the function of TaZnBP. This provides a theoretical basis for further study of the function of metalloproteinases in pathogen-host interactions., (© 2024. The Author(s).)

The ocean has experienced substantial oxygen loss over recent decades, affecting marine ecosystems and fisheries. Investigating ocean deoxygenation during hyperthermal events, such as the Paleocene-Eocene Thermal Maximum (PETM), offers insights into its future dynamics. Here, sediment cores from the South Atlantic reveal a pronounced decline in foraminifera-bound δ 15 N, concurrent with an increase in marine barite δ 34 S and enhanced ocean productivity during the PETM. These findings suggest an expansion of oxygen-deficient zones (ODZs) from suboxia to anoxia in the thermocline, with ammonium and sulfide accumulation. Model simulations indicate "ammonium-type" ODZs were driven by Southern Ocean warming and elevated productivity. Intense fixed nitrogen loss at the upper boundary of these ODZs, along with increased oceanic phosphorus inventory, likely spurred a compensatory rise in N 2 fixation. While the Pacific might experience different oxygenation conditions during the PETM, parts of the Atlantic thermocline became anoxic, highlighting potential spatial variabilities of ocean deoxygenation under global warming., (© 2024. The Author(s).)

A widespread concern had been there regarding soil ecological and environmental problems caused by microplastic pollution in agricultural soils. A controlled laboratory incubation experiment was performed to examine the effects of different types of microplastics on soil properties, N 2 O emissions, and nitrogen （N） transformations in tropical arable soils from a pepper-corn cropping system in Hainan Province. Three treatments were done： soil without microplastics （CK） and soil amended with 5% of polyethylene （PE） or with 5% of polybutylene adipate co-terephthalate （PBAT）. The results showed that both types of microplastic addition increased soil pH, soil organic carbon （SOC）, and dissolved organic carbon （DOC） contents, with stronger treatment effects observed for PBAT than those for the PE treatment. In addition, the PE and PBAT treatments increased soil ammonium nitrogen （NH 4 + -N） contents by 66.07% and 119.65% and decreased nitrate nitrogen （NO 3 - -N） contents by 8.56% and 29.68%, respectively. Compared to those in the CK treatment, the addition of PBAT significantly increased soil N 2 O emissions by 254.92% （ P < 0.05）, whereas that of PE produced no significant effects. Furthermore, both the PE and PBAT treatments increased soil net nitrogen mineralization rate （NMR） and decreased soil net nitrification rate （NNR）, with more obvious treatment effects observed in PBAT than in the PE treatment. PBAT addition increased the abundance of ureC , while PE had no significant effects. Microplastic addition reduced the abundance of nitrifying gene abundances （AOA- amoA , AOB- amoA , and nxrA ）, with more obvious treatment effects found in the PBAT treatment. Further, PBAT addition significantly increased the gene abundances of nirK , nirS , nosZ , and fungal nirK （ P < 0.05）, whereas the addition of PE had no significant effect on those gene abundances. Soil N 2 O emissions had positive relationships with NH 4 + -N intensity, pH, DOC, SOC, and nirS abundance. In conclusion, biodegradable microplastics addition produced stronger influences on soil properties and N transformations than the non-biodegradable one in tropical arable soils and aggravated soil N 2 O emissions mainly by promoting denitrification.

This study employed network pharmacology, molecular docking, and animal experiments to investigate the mechanism of ginger-processed Anemarrhenae Rhizoma in treating cough due to cold and dampness in lung, aiming to provide a modern pharmacological basis for this therapy. The active ingredients of ginger-processed Anemarrhenae Rhizoma were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) with the oral bioavailability(OB≥30%) and drug likeness(DL≥0.18) as the screening conditions and from the relevant literature. A library of the active ingredients of ginger-processed Anemarrhenae Rhizoma was established, and SwissTargetPrediction was used to predict the potential targets of the active ingredients. The western medical symptom corresponding to cough due to cold and dampness in lung was identified as acute bronchitis based on SymMap, and the targets related to acute bronchitis were obtained from GeneCards, and the Online Mendelian Inheritance in Man(OMIM). Venny was utilized to obtain the common targets between the active ingredients and the disease, and STRING and Cytoscape were used to establish the protein-protein interaction(PPI) network for the common targets. The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of potential therapeutic targets were performed with DAVID. AutoDock was used to simulate the molecular docking between the active ingredients with potential targets. Finally, a mouse model of acute bronchitis was prepared with the smoke plus cold stimulation method for validation. In this study, a total of 557 potential targets of the active ingredients of ginger-processed Anemarrhenae Rhizoma were retrieved, including 157 common targets shared with acute bronchitis. The enrichment analysis yielded 1 072 GO terms and 169 KEGG pathways. The results of molecular docking showed that the active ingredients had good binding affinity with MAPK14 and MMP3, and timosaponin AⅢ showcased the strongest binding affinity among the active ingredients. In the animal experiments, other treatment groups except the low-and high-dose raw Anemarrhenae Rhizoma and the ginger decoction groups showed reduced pathological changes in the lung tissue, attenuated inflammatory cell infiltration, lowered levels of interleukin(IL)-1β, IL-18, and tumor necrosis factor(TNF)-α in the bronchoalveolar lavage fluid(BALF), and down-regulated mRNA and protein levels of MAPK14 and MMP3 in the lung tissue. Moreover, ginger-processed Anemarrhenae Rhizoma outperformed raw Anemarrhenae Rhizoma. This study preliminarily revealed that ginger-processed Anemarrhenae Rhizoma can inhibit inflammation by regulating the IL-17, TNF, and other signaling pathways to treat cough due to cold and dampness in lung, verifying the rationality of this therapy. The findings provide a basis for the inheritance and application of the characteristic ginger processing of Anemarrhenae Rhizoma.

A series of TADF-active compounds: 0D chiral Ln-Ag(I) clusters L-/D-Ln 2 Ag 28 -0D (Ln=Eu/Gd) and 2D chiral Ln-Ag(I) cluster-based frameworks L-/D-Ln 2 Ag 28 -2D (Ln=Gd) has been synthesized. Atomic-level structural analysis showed that the chiral Ag(I) cluster units {Ag 14 S 12 } in L-/D-Ln 2 Ag 28 -0D and L-/D-Ln 2 Ag 28 -2D exhibited similar configurations, linked by varying numbers of [Ln(H 2 O) x ] 3+ (x=6 for 0D, x=3 for 2D) to form the final target compounds. Temperature-dependent emission spectra and decay lifetimes measurement demonstrated the presence of TADF in L-Ln 2 Ag 28 -0D (Ln=Eu/Gd) and L-Gd 2 Ag 28 -2D. Experimentally, the remarkable TADF properties primarily originated from {Ag 14 S 12 } moieties in these compounds. Notably, {Ag 14 S 12 } in L-Eu 2 Ag 28 -0D and L-Gd 2 Ag 28 -2D displayed higher promote fluorescence rate and shorter TADF decay times than L-Gd 2 Ag 28 -0D. Combined with theoretical calculations, it was determined that the TADF behaviors of {Ag 14 S 12 } cluster units were induced by 4 f perturbation of Ln 3+ ions. Specially, while maintaining ΔE(S 1 -T 1 ) small enough, it can significantly increase k(S 1 →S 0 ) and reduce TADF decay time by adjusting the type or number of Ln 3+ ions, thus achieving the purpose of improving TADF for cluster-based luminescent materials., (© 2024 Wiley-VCH GmbH.)

The U.S. Food and Drug Administration (FDA) has broadly supported quality by design initiatives for clinical trials - including monitoring and data validation - by releasing two related guidance documents (FDA 2013 and 2019). Centralized statistical monitoring (CSM) can be a component of a quality by design process. In this article, we describe our experience with a CSM platform as part of a Cooperative Research and Development Agreement between CluePoints and FDA. This agreement's approach to CSM is based on many statistical tests performed on all relevant subject-level data submitted to identify outlying sites. An overall data inconsistency score is calculated to assess the inconsistency of data from one site compared to data from all sites. Sites are ranked by the data inconsistency score ( - log 10 p , where p is an aggregated p -value). Results from a deidentified trial demonstrate the typical data anomaly findings through Statistical Monitoring Applied to Research Trials analyses. Sensitivity analyses were performed after excluding laboratory data and questionnaire data. Graphics from deidentified subject-level trial data illustrate abnormal data patterns. The analyses were performed by site, country/region, and patient separately. Key risk indicator analyses were conducted for the selected endpoints. Potential data anomalies and their possible causes are discussed. This data-driven approach can be effective and efficient in selecting sites that exhibit data anomalies and provides insights to statistical reviewers for conducting sensitivity analyses, subgroup analyses, and site by treatment effect explorations. Messy data, data failing to conform to standards, and other disruptions (e.g. the COVID-19 pandemic) can pose challenges.

The growing utilization of critical care echocardiography (CCE) by clinicians necessitates a meticulous review of clinical conditions in critically ill patients, both before and during the examination. The reviewing process of clinical conditions minimizes the risk of overlooking or misinterpreting crucial findings. This article proposes a comprehensive strategy, namely BILL strategy, to integrate into the CCE protocol, where "B" represents baseline respiratory and hemodynamic support, "I" signifies information gleaned from invasive monitoring, including central venous pressure and thermodilution-derived cardiac output, the first "L" denotes laboratory results such as central venous oxygen saturation, troponin, and brain natriuretic peptide, and the second "L" refers to lung ultrasound data. Combining the BILL strategy with CCE can enhance comprehensive understanding of critical conditions, potentially leading to improved diagnostic accuracy and patient outcomes.

The indolylfulgide systems have been extensively investigated due to their potential applications as photochromic materials. In this work, the photoinduced ring-closure/opening and isomerization reactions of a photochromic indolylfulgide in vacuum and acetonitrile solvent have been investigated by means of MS-CASPT2//CASSCF and QM(MS-CASPT2)//CASSCF/MM. The deactivation mechanisms of indolylfulgide have been proposed based on the optimized structures in the S 0 and S 1 states, S 1 /S 0 conical intersections, and the calculated minimum-energy paths. After excitation into the first singlet excited-state, which is spectroscopically bright in the Franck-Condon point of the E, the photoprocesses proceed toward a nearby S 1 minimum. Then, two possible nonadiabatic relaxation paths exist to repopulate the ground state. In the ring closure reaction, the S 1 E isomer evolves directly into one S 1 /S 0 conical intersection and decays to the ground state with bifurcation toward C or E. In the E → Z tautomerization pathway, the excited system can deactivate to the S 0 state via a distinct conical intersection. The minimum-energy paths of the indolylfulgide revealed that the ring closure reaction in the solvent is more facile to take place than the E → Z isomerization after irradiation of the same E. Furthermore, for the ring opening reaction from the C side, there exists an energy barrier (11.1 kcal/mol) in the S 1 state before arriving at the conical intersection. The computational results showed that the solvent has some influence on the system compared with that in the gas phase. The present work could contribute to comprehending the photoreactions of indolylfulgide and its derivatives in solution.

Objective: To summarize and analyze the clinical characteristics and prognosis of thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Methods: A retrospective analysis was conducted on the clinical data of 51 patients with SMARCA4-UT who were diagnosed in the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2023, and 52 patients with SMARCA4-intact non-small cell lung cancer (SMARCA4-iNSCLC) expression admitted during the same period were used as controls. The Kaplan-Meier survival analysis and log-rank test were used to analyze the survival difference between the two groups of patients, and the Cox regression model was used to explore the factors influencing the prognosis of the two groups of patients. Results: In the SMARCA4-UT group, there were 50 males and 1 female, with the age of (63.8±9.7) years. Compared to the SMARCA4-iNSCLC group, the SMARCA4-UT group exhibited a higher proportion of male patients and smokers, as well as a higher Ki-67 level (all P <0.05). SMARCA4-UT is mainly characterized by solid lesions with poor adhesion, and some of them exhibit rhabdomyoid morphology. Immunohistochemistry revealed negative results for BRG1, thyroid transcription factor-1, P40, NapsinA, and others were mostly negative, while some patients were positive for spalt-like transcription factor 4. There were a relatively large number of cases with Ki-67≥30% (47/51, 92%). Among the 10 patients in the SMARCA4-UT group who underwent next-generation sequencing genetic testing, 6 patients were found to have SMARCA4 mutations, often accompanied by TP53 (8/10, 80%), STK 11(3/10, 30%), KRAS(2/10, 20%), with fewer common driver gene mutations. The average tumor mutation burden was 16.12 mutations/Mb. Compared with SMARCA4-iNSCLC patients, the median overall survival of SMARCA4-UT patients was significantly shorter (12 months vs 45 months, P <0.001), and the median overall survival of patients with stage Ⅲ-Ⅳ SMARCA4-UT treated with immunotherapy was longer than that of patients without immunotherapy (23 months vs 7 months, P =0.027). The results of the multivariate Cox regression model analysis indicated that SMARCA4 deficiency is a risk factor for prognosis in patients with SMARCA4-UT and SMARCA4-iNSCLC [ HR =7.954(95% CI： 2.764-22.890), P <0.001]. Conclusions: SMARCA4-UT is a rare undifferentiated tumour distinct from SMARCA4-iNSCLC, which is prevalent among elderly male smokers. It possesses high invasiveness and poor prognosis. The typical pathological characteristic is negative BRG1. Immunotherapy demonstrates a certain effect.

The aim of this study was to investigate whether the protective effect of 2-deoxyglucose (2-DG) on lung ischemia/reperfusion (I/R) injury is mediated by inhibiting nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated pyroptosis in rats. Male Sprague-Dawley rats were randomly divided into control group, 2-DG group, lung I/R injury group (I/R group) and 2-DG+I/R group. 2-DG (0.7 g/kg) was intraperitoneally injected 1 h prior to lung ischemia. The tissue structure was measured under light microscope. Lung injury parameters were detected. The contents of malondialdehyde (MDA), myeloperoxidase (MPO) and lactate were determined by commercially available kits. ELISA was used to detect the levels of IL-1β and IL-18. Western blot, qRT-PCR and immunofluorescence staining were used to measure the expression changes of glycolysis and pyroptosis related indicators. The results showed that there was no significant difference in the parameters between the control group and the 2-DG group. However, the lung injury parameters, oxidative stress response, lactic acid content, IL-1β, and IL-18 levels were significantly increased in the I/R group. The protein expression levels of glycolysis and pyroptosis related indicators including hexokinase 2 (HK2), pyruvate kinase 2 (PKM2), NLRP3, Gasdermin superfamily member GSDMD-N, cleaved-Caspase1, cleaved-IL-1β and cleaved-IL-18, and the gene expression levels of HK2, PKM2 and NLRP3 were markedly up-regulated in the I/R group compared with those in the control group. The expression of HK2 and NLRP3 was also increased detected by immunofluorescence staining. Compared with the I/R group, the 2-DG+I/R group exhibited significantly improved alveolar structure and inflammatory infiltration, reduced lung injury parameters, and decreased expression of glycolysis and pyroptosis related indicators. These results suggest that 2-DG protects against lung I/R injury possibly by inhibiting NLRP3-mediated pyroptosis in rats.

Due to the rapid increase in the number of spent lithium-ion batteries, there has been a growing interest in the recovery of degraded graphite. In this work, a rapid thermal shock (RTS) strategy is proposed to regenerate spent graphite for use in lithium-ion batteries. The results of structural and morphological characterization demonstrate that the graphite is well regenerated by the RTS process. Additionally, an amorphous carbon layer forms and coats onto the surface of the graphite, contributing to excellent rate performance. The regenerated graphite (RG-1000) displays excellent rate performance, with capacities of 413 mAh g -1 at 50 mA g -1 and 102.1 mAh g -1 at 1000 mA g -1 , respectively. Furthermore, it demonstrates long-term cycle stability, maintaining a capacity of 80 mAh g -1 at 1000 mA g -1 with a capacity retention of 78.4 % after 600 cycles. This RTS method enables rapid and efficient regeneration of spent graphite anodes for lithium-ion batteries, providing a facile and environmentally friendly strategy for their direct regeneration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Heart failure (HF) has emerged as the most pressing health concerns globally, and extant clinical therapies are accompanied by side effects and patients have a high burden of financial. The protein products of nuclear factor erythroid 2-related factor 2 (Nrf2) target genes have a variety of cardioprotective effects, including antioxidant, metabolic functions and anti-inflammatory. By evaluating established preclinical and clinical research in HF to date, we explored the potential of Nrf2 to exert unique cardioprotective functions as a novel therapeutic receptor for HF. In this review, we generalize the progression, structure, and function of Nrf2 research in the cardiovascular system. The mechanism of action of Nrf2 involved in HF as well as agonists of Nrf2 in natural compounds are summarized. Additionally, we discuss the challenges and implications for future clinical translation and application of pharmacology targeting Nrf2. It's critical to developing new drugs for HF., Competing Interests: Declaration of Competing Interest This manuscript has not been published previously and is not currently under consideration by any other journals. All authors have read and approved the submission of this manuscript to Pharmacological Research. And all authors declare no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus. The progressive damage to glomeruli, tubules, and interstitium in the kidneys can lead to the development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Most of the energy we need comes from mitochondria. Mitochondria are best known as the sites for production of respiratory ATP and are essential for eukaryotic life. The pathogenesis of DN involves a variety of factors, such as altered haemodynamics, oxidative stress, and inflammation, and studies from animal models suggest that mitochondrial dysfunction plays an important role in the development of DN. Traditional Chinese medicine (TCM) has a history of more than 2,500 years and has rich experience and remarkable efficacy in the treatment of DN. Recent studies have found that TCM may have great potential in regulating mitochondrial dysfunction in the treatment of DN. This review will elucidate the main causes of mitochondrial dysfunction and the relationship with DN, and explore in depth the potential mechanisms of TCM to protect the kidney by improving mitochondrial dysfunction. Current pharmacological treatments for patients with DN do not prevent the inevitable progression to ESRD. With the rich variety of Chinese herbs, TCM is expected to be the most promising candidate for the treatment of DN as we continue to learn more about the mechanisms of DN and incorporate the current advances in extraction techniques., 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 Zhao, Zhong, Wang and Yan.)

2D compounds exfoliated from weakly bonded bulk materials with van der Waals (vdW) interaction are easily accessible. However, the strong internal ionic/covalent bonding of most inorganic crystal frameworks greatly hinders 2D material exfoliation. Herein, we first proposed a radical/strain-synergistic strategy to exfoliate non-vdW interacting pseudo-layered phosphate framework. Specifically, hydroxyl radicals (⋅OH) distort the covalent bond irreversibly, meanwhile, H 2 O molecules as solvents, further accelerating interlayered ionic bond breakage but mechanical expansion. The innovative 2D laminar NASICON-type Na 3 V 2 (PO 4 ) 2 O 2 F crystal, exfoliated by ⋅OH/H 2 O synergistic strategy, exhibits enhanced sodium-ion storage capacity, high-rate performance (85.7 mAh g -1 at 20 C), cyclic life (2300 cycles), and ion migration rates, compared with the bulk framework. Importantly, this chemical/physical dual driving technique realized the effective exfoliation for strongly coupled pseudo-layered frameworks, which accelerates 2D functional material development., (© 2024 Wiley-VCH GmbH.)

Background: Enterocutaneous fistula (ECF) is an abnormal connection between the gastrointestinal tract and the skin. ECF can lead to massive body fluid loss, hypercatabolism, and malnutrition. Therefore, nutritional support plays a crucial role in managing ECFs and promoting the healing of fistulas. For nutritional support, enteral nutrition (EN) is the preferred method when gastrointestinal function is recovering. Currently, various EN approaches have been applied for different anatomical positions of the ECF. However, the effectiveness of administering EN support for treating lower ECFs still needs further exploration and improvement., Case Summary: We present the case of a 46-year-old male who underwent gastrointestinal stromal tumour resection. Six days after the surgery, the patient presented with fever, fatigue, severe upper abdominal pain, and septic shock. Subsequently, lower ECFs were diagnosed through laboratory and imaging examinations. In addition to symptomatic treatment for homeostasis, total parenteral nutrition support was administered in the first 72 h due to dysfunction of the intestine. After that, we gradually provided EN support through the intestinal obstruction catheter in consideration of the specific anatomic position of the fistula instead of using the nasal jejunal tube. Ultimately, the patient could receive optimal EN support via the catheter, and no complications were found during the treatment., Conclusion: Nutritional support is a crucial element in ECF management, and intestinal obstruction catheters could be used for early EN administration., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The unique electronic and crystal structures of rare earth metals (RE) offer promising opportunities for enhancing the hydrogen evolution reaction (HER) properties of materials. In this work, a series of RE (Sm, Nd, Pr and Ho)-doped Rh@NSPC (NSPC stands for N, S co-doped porous carbon nanosheets) with sizes less than 2 nm are prepared, utilizing a simple, rapid and solvent-free joule-heat pyrolysis method for the first time. The optimized Sm-Rh@NSPC achieves HER performance. The high-catalytic performance and stability of Sm-Rh@NSPC are attributed to the synergistic electronic interactions between Sm and Rh clusters, leading to an increase in the electron cloud density of Rh, which promotes the adsorption of H + , the dissociation of Rh-H bonds and the release of H 2 . Notably, the overpotential of the Sm-Rh@NSPC catalyst is a mere 18.1 mV at current density of 10 mAcm -2 , with a Tafel slope of only 15.2 mV dec -1 . Furthermore, it exhibits stable operation in a 1.0 M KOH electrolyte at 10 mA cm -2 for more than 100 h. This study provides new insights into the synthesis of composite RE hybrid cluster nanocatalysts and their RE-enhanced electrocatalytic performance. It also introduces fresh perspectives for the development of efficient electrocatalysts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The AT-hook motif nuclear-localized ( AHL ) family is pivotal for the abiotic stress response in plants. However, the function of the cassava AHL genes has not been elucidated. Promoters, as important regulatory elements of gene expression, play a crucial role in stress resistance. In this study, the promoter of the cassava MeAHL31 gene was cloned. The MeAHL31 protein was localized to the cytoplasm and the nucleus. qRT-PCR analysis revealed that the MeAHL31 gene was expressed in almost all tissues tested, and the expression in tuber roots was 321.3 times higher than that in petioles. Promoter analysis showed that the MeAHL31 promoter contains drought, methyl jasmonate (MeJA), abscisic acid (ABA), and gibberellin (GA) cis -acting elements. Expression analysis indicated that the MeAHL31 gene is dramatically affected by treatments with salt, drought, MeJA, ABA, and GA3. Histochemical staining in the proMeAHL31-GUS transgenic Arabidopsis corroborated that the GUS staining was found in most tissues and organs, excluding seeds. Beta-glucuronidase (GUS) activity assays showed that the activities in the proMeAHL31-GUS transgenic Arabidopsis were enhanced by different concentrations of NaCl, mannitol (for simulating drought), and MeJA treatments. The integrated findings suggest that the MeAHL31 promoter responds to the abiotic stresses of salt and drought, and its activity is regulated by the MeJA hormone signal.

To overcome the trade-off challenge encountered in the engineering of alginate lyase AlyG2 from Seonamhaeicola algicola Gy8 T and to expand its potential industrial applications, we devised a two-step strategy encompassing activity enhancement followed by thermal stability engineering. To enhance the specific activity of efficient AlyG2, we strategically substituted residues with bulky steric hindrance proximal to the active pocket with glycine or alanine. This led to the generation of three promising positive mutants, with particular emphasis on the T91S mutant, exhibiting a 1.91-fold specific activity compared to the wild type. To mitigate the poor thermal stability of T91S, mutants with negative ΔΔG values in the thermal flexibility region were screened out. Notably, the S72Y a mutant not only displayed 17.96 % further increase in specific activity but also exhibited improved stability compared to T91S, manifesting as a remarkable 30.97 % increase in relative activity following a 1-hour incubation at 42 °C. Furthermore, enhanced kinetic stability was observed. To gain deeper insights into the mechanism underlying the enhanced thermostability of the S72Y a mutant, we conducted molecular dynamics simulations, principal component analysis (PCA), dynamic cross-correlation map (DCCM), and free energy landscape (FEL) analysis. The results unveiled a reduction in the flexibility of the surface loop, a stronger correlation dynamic and a narrower motion subspace in S72Y a system, along with the formation of more stable hydrogen bonds. Collectively, our findings suggest amino acids substitutions resulting in smaller side chains proximate to the active site can positively impact enzyme activity, while reducing the flexibility of surface loops emerges as a pivotal factor in conferring thermal stability. These insights offer valuable guidance and a framework for the engineering of other enzyme types., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Abstract: Renal hemangioblastoma (HB) is a rare subset of HBs arising outside of the central nervous system (CNS), with its molecular drivers remaining entirely unknown. There were no significant alterations detected in previous studies, including von Hippel-Lindau gene alterations, which are commonly associated with CNS-HB. This study aimed to determine the real molecular identity of renal HB and better understand its relationship with CNS-HB. A cohort of 10 renal HBs was submitted for next-generation sequencing technology. As a control, 5 classic CNS-HBs were similarly analyzed. Based on the molecular results, glycoprotein nonmetastatic B (GPNMB) immunohistochemistry was further performed in the cases of renal HB and CNS-HB. Mutational analysis demonstrated that all 10 renal HBs harbored somatic mutations in tuberous sclerosis complex 1 ( TSC1 , 5 cases), TSC2 (3 cases), and mammalian target of rapamycin (2 cases), with the majority classified as pathogenic or likely pathogenic. The CNS-HB cohort uniformly demonstrated somatic mutations in the von Hippel-Lindau gene. GPNMB was strong and diffuse in all 10 renal HBs and completely negative in CNS-HBs, reinforcing the molecular findings. Our study reveals a specific molecular hallmark in renal HB, characterized by recurrent TSC/mammalian target of rapamycin mutations, which defines it as a unique entity distinct from CNS-HB. This molecular finding potentially expands the therapeutic options for patients with renal HB. GPNMB can be considered for inclusion in immunohistochemical panels to improve renal HB identification., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Two new monoterpenoid indole alkaloids, named taberibogines E and F ( 1 and 2 ), together with three known ones ( 3 - 5 ) were isolated from the stems of Tabernaemontana bovina Lour (Apocynaceae). Their structures including absolute configurations were elucidated from a combination of NMR and HRESIMS data and NMR calculations as well as DP4+ probability analyses. Compounds 1 and 2 exhibited inhibitory effects on LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages.