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With the rapid development of genetic technology, the application of genetically modified crops has brought revolutionary changes to the global agricultural production and agricultural trade patterns, and has played an important role in ensuring human health, environmental safety and sustainable agricultural development. In order to strengthen genetically modified organisms (GMO) safety management, countries around the world have formulated GMO safety management policies adapted to their own national conditions with reference to internationally accepted practices. In this study, we carried out comparative studies among the United States, the European Union, Japan and other developed countries or regions and China from the aspects of regulations and management institutions, safety evaluation systems, and label management, so as to provide references for the improvement of China's GMO safety management policies. [ABSTRACT FROM AUTHOR]

Background and Purpose: Accumulated evidence suggests that oxidative stress is involved in amyloid beta (Abeta)-induced cognitive dysfunction. Silibinin (silybin), a flavonoid derived from the herb milk thistle (Silybum marianum), has been shown to have antioxidative properties; however, it remains unclear whether silibinin improves Abeta-induced neurotoxicity. In the present study, we examined the effect of silibinin on the memory impairment and accumulation of oxidative stress induced by Abeta(25-35) in mice.Experimental Approach: Aggregated Abeta(25-35) (3 nmol) was intracerebroventricularly administered to mice. Treatment with silibinin (2, 20 and 200 mg.kg(-1), once a day, p.o.) was started immediately after the injection of Abeta(25-35). Locomotor activity was evaluated 6 days after the Abeta(25-35) treatment, and cognitive function was evaluated in a Y-maze and novel object recognition tests 6-11 days after the Abeta(25-35) treatment. The levels of lipid peroxidation (malondialdehyde) and antioxidant (glutathione) in the hippocampus were measured 7 days after the Abeta(25-35) injection.Key Results: Silibinin prevented the memory impairment induced by Abeta(25-35) in the Y-maze and novel object recognition tests. Repeated treatment with silibinin attenuated the Abeta(25-35)-induced accumulation of malondialdehyde and depletion of glutathione in the hippocampus.Conclusions and Implications: Silibinin prevents memory impairment and oxidative damage induced by Abeta(25-35) and may be a potential therapeutic agent for Alzheimer's disease. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study examines the relationship between birth-place and mortality from circulatory diseases among American Blacks. METHODS: All Black deaths from circulatory diseases (International Classification of Diseases, 9th Revision. codes 390 through 459) were extracted from the National Center for Health Statistics mortality detail files for 1979 through 1991. Age-specific and age-adjusted mortality rates with 95% confidence intervals were calculated for males and females for combinations of five regions of residence at birth and four regions of residence at death. RESULTS: Males had higher mortality rates from circulatory diseases than females in every regional combination of birthplace and residence at death. For both genders, the highest rates were for those who were born in the South but died in the Midwest; the lowest rates were for those who were born in the West but died in the South. Excess mortality for both Southern-born males and females begins at ages 25 through 44. CONCLUSIONS: There is a region-of-birth component that affects mortality risk from circulatory diseases regardless of gender or residence at time of death. We must examine how early life experiences affect the development of circulatory disorders. [ABSTRACT FROM AUTHOR]

Mine fires caused by spontaneous coal combustion are major disasters in coal mines. The staged oxidation kinetic parameters of various coal samples at oxygen concentrations of 21 %, 15 %, 10 %, 5 %, and 3 % were analyzed using a programmed temperature testing system. Herein, the temperature increase rate of coal, the temperature difference between the furnace and coal, and the oxygen consumption characteristics were obtained. Based on the amount of CO produced and the temperature sensitivity coefficient, three characteristic temperatures and four stages of low-temperature oxidation (LTO) were identified. The results showed that at a critical temperature (T C ), the amount of CO gas released from the coal samples increased with increasing oxygen concentration, and the difference in the oxygen consumption rate increased. After the limit temperature (T u ), the amount of CO gas increased steadily, and the increase in the oxygen consumption rate stagnated. CO production, the maximum heating rate, and the maximum heat release rate were positively correlated with the oxygen concentration. As the oxygen concentration increased, the activation energy during the oxygen absorption stage gradually decreased. The average reaction enthalpy (ΔH) of pre-oxidized water-immersed coal was 19.37 kJ/kg greater than that of raw coal. The equation for the conservation of energy of the coal oxidation warming process was normalized. The theoretical values of the awakening stage and the stable stage were τν and τν (1-B), respectively. When B was >1, pre-oxidized water-immersed coal at a low oxygen concentration was prone to crossover points during the oxygen absorption stage, which increased the risk of coal spontaneous combustion (CSC). The research results could provide a theoretical basis for the staged control of the spontaneous combustion of water-immersed coal in goaf areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationship that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

A recent study has introduced a recombinant fusion protein, consisting of the extracellular domain (ECD) of p75 and the Fc fragment of human immunoglobulin IgG1 (p75ECD-Fc), as a multifaceted agent within the nervous system. This research aimed to assess the effects of p75ECD-Fc on neuronal growth and the restoration of neurological functions in rats afflicted with neonatal hypoxic-ischemic encephalopathy (NHIE). In vitro analyses revealed that 1 μM p75ECD-Fc treatment markedly increased cell viability and facilitated neurite outgrowth in neurons exposed to oxygen-glucose deprivation (OGD). Subsequent in vivo studies determined that a dose of 78.6 μg/3 μl of p75ECD-Fc significantly mitigated brain damage and both acute and long-term neurological impairments, outperforming the therapeutic efficacy of hypothermia, as evidenced through behavioral assessments. Additionally, in vivo immunostaining showed that p75ECD-Fc administration enhanced neuronal survival and regeneration, and reduced astrocytosis and microglia activation in the cortex and hippocampus of NHIE rats. A noteworthy shift from A1 to A2 astrocyte phenotypes and from M1 to M2 microglia phenotypes was observed after p75ECD-Fc treatment. Furthermore, a co-expression of the p75 neurotrophin receptor (p75NTR) and Nestin was identified, with an overexpression of Nestin alleviating the neurological dysfunction induced by NHIE. Mechanistically, the neuroprotective effects of p75ECD-Fc, particularly its inhibition of neuronal apoptosis post-OGD, may be attributed to Nestin. Taken together, these results highlight the neuroprotective and anti-inflammatory effects of p75ECD-Fc treatment through the modulation of glial cell phenotypes and the Nestin-mediated inhibition of neuronal apoptosis, positioning it as a viable therapeutic approach for NHIE., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Coccidiosis is an important parasitic disease that has serious adverse effects on the global poultry industry. The mechanism by which the pathogenic factors of Eimeria tenella damage host cells is unknown. Some kinases from the rhoptry compartment can regulate apoptosis of host cells. This study focused on revealing the role and critical nodes of E. tenella rhoptry protein (EtROP) 38 in controlling the apoptosis of host cells via the P38 mitogen-activated protein kinase (MAPK) signaling pathway. The cells were treated with EtROP38 protein, siRNA p38MAPK, or both. The rate of infection, apoptosis, and the dynamic changes in the expression and activation of key factor genes of the P38MAPK signaling pathway in host cells infected with E. tenella were measured. The results showed that the addition of EtROP38 and/or knockdown of the host cells p38 gene reduced the apoptosis rate of cecal epithelial cells (CECS), decreased the mRNA expressions of p38, p53, c-myc, c-fos, and c-jun and increased the expression of p65, decreased the protein expressions of c-myc, c-fos, and c-jun, decreased the p38 protein phosphorylation level, and increased the p65 protein phosphorylation level in CECS. When E. tenella was inoculated for 4-96 h, the addition of Et ROP38 and/or host cell p38 knockdown both increased the infection rate of host cells, and this effect was more pronounced with the addition of EtROP38 with the host cell p38 knockdown. These observations indicate that E. tenella can inhibits the activation of the p38MAPK signaling pathway in host cells via EtROP38, which suppresses apoptosis in host cells., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Strong evidence indicates that environmental stressors are the risk factors for male testosterone deficiency (TD). However, the mechanisms of environmental stress-induced TD remain unclear. Based on our all-cause male reproductive cohort, we found that serum ferrous iron (Fe 2 ⁺) levels were elevated in TD donors. Then, we explored the role and mechanism of ferroptosis in environmental stress-reduced testosterone levels through in vivo and in vitro models. Data demonstrated that ferroptosis and lipid droplet deposition were observed in environmental stress-exposed testicular Leydig cells. Pretreatment with ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, markedly mitigated environmental stress-reduced testosterone levels. Through screening of core genes involved in lipid droplets formation, it was found that environmental stress significantly increased the levels of perilipins 4 (PLIN4) protein and mRNA in testicular Leydig cells. Further experiments showed that Plin4 siRNA reversed environmental stress-induced lipid droplet deposition and ferroptosis in Leydig cells. Additionally, environmental stress increased the levels of METTL3, METTL14, and total RNA m6A in testicular Leydig cells. Mechanistically, S-adenosylhomocysteine, an inhibitor of METTL3 and METTL14 heterodimer activity, restored the abnormal levels of Plin4, Fe 2 ⁺ and testosterone in environmental stress-treated Leydig cells. Collectively, these results suggest that Plin4 exacerbates environmental stress-decreased testosterone level via inducing ferroptosis in testicular Leydig cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Diminished testosterone levels have been documented as a key factor in numerous male health disorders. Both human and animal studies have consistently demonstrated that cadmium (Cd), a pervasive environmental heavy metal, results in decreased testosterone levels. However, the exact mechanism through which Cd interferes with testosterone synthesis remains incompletely elucidated. This research sought to examine the impact of cellular senescence on Cd-suppressed testosterone synthesis. We also investigated the related m6A modification mechanism. The results demonstrated that Cd (100 mg/L) led to a decrease in testosterone levels, along with downregulated expression of testosterone synthase in C57BL/6 N male mice. Furthermore, Cd significantly increased β-galactosidase staining intensity, senescence-related proteins, and senescence-related secretory phenotypes in mouse testicular Leydig cells. Subsequent investigations revealed that Cd decreased the mRNA and protein levels of NAD-dependent deacetylase Sirtuin-1 (SIRT1) in Leydig cells. Mechanistically, mice treated with resveratrol (50 mg/kg), a specific SIRT1 activator, mitigated Leydig cell senescence and reversed Cd-reduced testosterone levels in mouse testes. These effects were also restored by SIRT1 overexpression in Leydig cells. Additionally, we found that Cd increased the level of methyltransferase enzyme METTL3 and Sirt1 m6A modification in Leydig cells. Mettl3 siRNA effectively restored Cd-enhanced Sirt1 m6A level and reversed Cd-downregulated Sirt1 mRNA expression in Leydig cells. Overall, our findings suggest that Cd exposure inhibits testosterone synthesis via Sirt1 m6A modification-mediated senescence in mouse testes. These results offer an experimental basis for investigating the causes and potential treatments of hypotestosteronemia induced by environmental factors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Prenylated indole alkaloids, which are mainly produced by genera Aspergillus and Penicillium, are a class of structurally intriguing specialized metabolites with remarkable biomedical interests. In this study, chemically guided isolation of the Nicotiana tabacum-derived endophytic fungus Aspergillus japonicus TE-739D yielded eight structurally diverse prenylated indole alkaloids, including an undescribed compound, namely aspertaichamide B (ATB, 1), together with seven previously discovered derivatives (compounds 2 - 8). Their chemical structures as well as the stereochemical features were determined by integrated spectroscopic analyses, including HRESIMS, NMR, NMR calculations with DP4 + probability analysis, and a comparison of the experimental ECD data with computed DFT-based quantum chemical calculations. In vitro cytotoxic effects against the gastric cancer MFC cells revealed that the new compound ATB demonstrated considerable activity. Further studies found that ATB suppressed the viability, colony formation, and migration ability of MFC cells, and induced MFC cells apoptosis in a concentration-dependent way. Moreover, ATB stimulated ROS production in MFC cells and inhibited the tumor growth in the MFC-sourced subcutaneous tumor model while not significantly reducing the weight of mice. The pharmacological results suggested that the newly discovered ATB may be a promising anti-tumor lead compound. KEY POINTS: • Eight structurally diverse prenylated indole alkaloids including a new aspertaichamide B (ATB) were isolated from the fungus Aspergillus japonicus TE-739D. • The structure of ATB was elucidated by HRESIMS, NMR, NMR calculations with DP4 + probability analysis, and ECD calculations. • ATB inhibited cell proliferation, promoted apoptosis, and increased ROS production in gastric cancer cells, and exhibited inhibitory effects on tumor growth in vivo., (© 2024. The Author(s).)

Clostridioides difficile infection (CDI) is a common healthcare-associated infection and the leading cause of gastroenteritis-related deaths worldwide. To investigate the effects of peptide composition of different protein products on CDI, we analyzed and compared the peptide sequences and compositions from Engraulis japonicus and Glycine max using Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). An animal model of CDI was also established to investigate the potential therapeutic effects of these peptides in vivo. The peptide compositions of E. japonicus and G. max differed, with only 11% of the peptide sequences being identical. Oral administration of the tested peptides could reduce intestinal inflammation, repair the intestinal barrier, increase the proportion of beneficial bacteria, and reduce the proportion of harmful bacteria, providing a therapeutic effect against CDI. However, the peptides may differ considerably in some aspects. E. japonicus peptides were superior to G. max peptides in promoting colon epithelial cell proliferation and repairing tight intestinal cell junctions. Interestingly, the two sources of peptides have different effects on the cecal microbiome. E. japonicus peptides can effectively restore the diversity and richness of intestinal microbiota, while G. max peptides have poor regulatory effects on the intestinal microbiota structure. Overall, E. japonicus peptides showed better results than G. max peptides in treating CDI. This study supports the potential treatment of CDI with natural peptides and promotes the development of specialty foods for CDI enteritis. Clostridioides difficile infection (CDI) is a common healthcare-associated infection and the leading cause of gastroenteritis-related deaths worldwide. To investigate the effects of peptide composition of different protein products on CDI, we analyzed and compared the peptide sequences and compositions from Engraulis japonicus and Glycine max using Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). An animal model of CDI was also established to investigate the potential therapeutic effects of these peptides in vivo. The peptide compositions of E. japonicus and G. max differed, with only 11% of the peptide sequences being identical. Oral administration of the tested peptides could reduce intestinal inflammation, repair the intestinal barrier, increase the proportion of beneficial bacteria, and reduce the proportion of harmful bacteria, providing a therapeutic effect against CDI. However, the peptides may differ considerably in some aspects. E. japonicus peptides were superior to G. max peptides in promoting colon epithelial cell proliferation and repairing tight intestinal cell junctions. Interestingly, the two sources of peptides have different effects on the cecal microbiome. E. japonicus peptides can effectively restore the diversity and richness of intestinal microbiota, while G. max peptides have poor regulatory effects on the intestinal microbiota structure., (© 2024. The Author(s).)

Organic linker-based luminescent metal-organic frameworks (LMOFs) have received extensive studies due to the unlimited species of emissive organic linkers and tunable structure of MOFs. However, the multiple-step organic synthesis is always a great challenge for the development of LMOFs. As an alternative strategy, in situ "one-pot" strategy, in which the generation of emissive organic linkers and sequential construction of LMOFs happen in one reaction condition, can avoid time-consuming pre-synthesis of organic linkers. In the present work, we demonstrate the successful utilization of in situ "one-pot" strategy to construct a series of LMOFs via the single-site modification between the reaction of aldehydes and o-phenylenediamine-based tetratopic carboxylic acid. The resultant MOFs possess csq topology with emission covering blue to near-infrared. The nanosized LMOFs exhibit excellent sensitivity and selectivity for tryptophan detection. In addition, two component-based LMOFs can also be prepared via the in situ "one-pot" strategy and used to study energy transfer. This work not only reports the construction of LMOFs with full-color emissions, which can be utilized for various applications, but also indicates that in situ "one-pot" strategy indeed is a useful and powerful method to complement the traditional MOFs construction method for preparing porous materials with tunable functionalities and properties., (© 2024 Wiley‐VCH GmbH.)

This study explored the mechanism by which the m6A demethylase ALKBH5 mediates epithelial-mesenchymal transition (EMT) in sepsis-associated acute kidney injury (SA-AKI) and AKI-chronic kidney disease (CKD) transition. HK-2 cells were stimulated with lipopolysaccharide (LPS) to establish an in vitro model of SA-AKI. ALKBH5 expression was reduced through the transfection of si-ALKBH5. Cell viability, apoptosis, and migration were detected by CCK-8 assay, TUNEL staining, and Transwell. The levels of TNF-α, IL-1β, and IL-6 were measured by enzyme-linked immunosorbent assay. Quantitative real-time polymerase chain reaction or Western blotting was performed to determine the expressions of ALKBH5, miR-205-5p, DDX5, E-cadherin, and α-SMA. The m6A level was quantitatively analyzed. The expression of pri-miR-205 bound to DGCR8 and m6A-modified pri-miR-205 after intervention with ALKBH5 expression was detected by RNA immunoprecipitation. A dual-luciferase assay confirmed the binding between miR-205-5p and DDX5. ALKBH5 was highly expressed in LPS-induced HK-2 cells. Inhibition of ALKBH5 increased cell viability, repressed apoptosis, and reduced EMT. Inhibition of ALKBH5 increased the m6A modification level, thereby promoting DGCR8 binding to pri-miR-205 to increase miR-205-5p expression and eventually targeting DDX5 expression. Low expression of miR-205-5p or overexpression of DDX5 partially abolished the inhibitory effect of ALKBH5 silencing on EMT. In conclusion, ALKBH5 represses miR-205-5p expression by removing m6A modification to upregulate DDX5 expression, thereby promoting EMT and AKI-CKD transition after SA-AKI., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Hexavalent chromium (Cr(VI)) is an environmental pollutant and recognized as a human carcinogen. Therefore, it is necessary to develop a simple and sensitive detection technique for Cr(VI). Herein, it is found that Cu 2+ interacts with guanosine 5'-monophosphate (GMP) to form a homogeneous Cu(II)-GMP complex (Cu 2+ ·GMP) that efficiently displays the oxidoreductase-like catalytic activity. Cu 2+ ·GMP can catalyze the oxidation between Cr(VI) and substrate 3,3',5,5'- tetramethylbenzidine (TMB), resulting in color change recognized by the naked eyes. Base on this, a convenient colorimetric assay for Cr(VI) detection was developed. The detection limit (3σ/s) of this sensor for Cr(VI) was 23 nM with a linear range of 0.1-25 μM. Moreover, the proposed assay was successfully applied to detect Cr(VI) in different environmental water samples with satisfactory recoveries. Our method is simple, efficient, rapid and cost-effective for Cr(VI) detection without the need for complicated material preparation or special separation, which shows great potential in environmental monitoring., 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.)

Aqueous rechargeable lithium-ion batteries (ARLIBs) are extensively researched due to their inherent safety, typical affordability, and potential high energy density. However, fabricating ARLIBs with both high energy density and power performance remains challenging. Herein, based on cyanoethyl-modified bacterial cellulose nanofibers (CBCNs), a multifunctional fast ion transport framework is developed to construct the flexible free-standing ARLIBs with high areal loading and excellent rate performance. Benefiting from the unique merits of CBCNs, such as ultra-high aspect ratio, excellent toughness, superior adhesion, good lithiophilicity and ideal stability, the flexible free-standing and highly robust electrodes are fabricated and exhibit a long-term stable cycling of 1200 cycles with a high specific capacity of 117 mAh∙g -1 at 15 C. Remarkably, the corresponding full cell with the free-standing high mass loading (45.5 mg∙cm -2 ) electrodes under the condition of ultra-low addition of battery binder demonstrates a cycle lifespan of over 1000 cycles with a specific capacity of 120 mAh∙g -1 and a capacity decay as low as 0.03% per cycle, which is far superior to those of almost all previous reports. This work provides a strategy for constructing ARLIBs with high energy density and power performance by introducing a unique fast ion transport nanofiber framework., (© 2024 Wiley‐VCH GmbH.)

A novel water-soluble polysaccharide, named PF90-1, with a molecular weight of 1.8 kDa, was isolated and purified from the fibrous root of Pseudostellaria heterophylla . PF90-1 is composed of Gal, Glc and Man in a molar ratio of 73.61: 19.11: 7.28. Methylation analysis revealed that PF90-1 comprises of T-Gal p , 1,4-Gal p , 1,3,4-Gal p , 1,2,3,4-Gal p , T-Glc p and 1,3-Man p in a molar ratio of 37.89: 9.37: 17.01: 12.01: 15.88: 7.83. Bioactivity experiments showed that PF90-1 significantly improved lipopolysaccharide (LPS)-induced inflammatory damage in RAW264.7 cells by inhibiting nitric oxide (NO) production and reducing the levels of pro-inflammatory factors (IL-1β and TNF-α). In addition, PF90-1 exhibited strong antioxidant effects, protecting PC12 cells from H 2 O 2 -induced oxidative damage. This findings suggest that PF90-1 holds potential therapeutic value for the treatment of inflammatory and oxidative injuries.

Purpose: This study aims to assess the diagnostic efficacy of Korean Thyroid imaging reporting and data system (K-TIRADS), S-Detect software and contrast-enhanced ultrasound (CEUS) when employed individually, as well as their combined application, for the evaluation of thyroid nodules, with the objective of identifying the optimal method for diagnosing thyroid nodules., Methods: Two hundred and sixty eight cases pathologically proven of thyroid nodules were retrospectively enrolled. Each nodule was classified according to K-TIRADS. S-Detect software was utilized for intelligent analysis. CEUS was employed to acquire contrast-enhanced features., Results: The area under curve (AUC) values for diagnosing benign and malignant thyroid nodules using K-TIRADS alone, S-Detect software alone, CEUS alone, the combined application of K-TIRADS and CEUS, the combined application of S-Detect software and CEUS were 0.668, 0.668, 0.719, 0.741, and 0.759, respectively (p < 0.001). The sensitivity rate of S-Detect software was 89.9% (p < 0.001). It was the highest of the five diagnostic methods above., Conclusion: The utilization of S-Detect software can be served as a powerful tool for early screening. Notably, the combined utilization of S-Detect software with CEUS demonstrates superior diagnostic performance compared to employing K-TIRADS, S-Detect software, CEUS used individually, as well as the combined application of K-TIRADS with CEUS., (© 2024 Wiley Periodicals LLC.)

Because of its high specific capacity and superior rate performance, porous carbon is regarded as a potential anode material for lithium-ion batteries (LIBs). However, porous carbon materials with wide pore diameter distributions suffer from low structural stability and low electrical conductivity during the application process. During this study, the calcium carbonate nanoparticle template method is used to prepare coal tar pitch-derived porous carbon (CTP-X). The coal tar pitch-derived porous carbon has a well-developed macroporous-mesoporous-microporous hierarchical porous network structure, which provides abundant active sites for Li + storage, significantly reduces polarization and charge transfer resistance, shortens the diffusion path and promotes the rapid transport of Li + . More specifically, the CTP-2 anode shows high charge capacity (496.9 mAh g -1 at 50 mA g -1 ), excellent rate performance (413.6 mAh g -1 even at 500 mA g -1 ), and high cycling stability (capacity retention rate of about 100 % after 1,000 cycles at 2 A g -1 ). The clean and eco-friendly large-scale utilization of coal tar pitch will facilitate the development of high-performance anodes in the field of LIBs., (© 2024 Wiley-VCH GmbH.)

The effects and underlying mechanisms of adolescent exposure to combined environmental hazards on cognitive function remain unclear. Here, using a combined exposure model, we found significant cognitive decline, hippocampal neuronal damage, and neuronal senescence in mice exposed to cadmium (Cd) and high-fat diet (HFD) during adolescence. Furthermore, we observed a significant downregulation of Sirtuin 6 (SIRT6) expression in the hippocampi of co-exposed mice. UBCS039, a specific SIRT6 activator, markedly reversed the above adverse effects. Further investigation revealed that co-exposure obviously reduced the levels of La ribonucleoprotein 7 (LARP7), disrupted the interaction between LARP7 and SIRT6, ultimately decreasing SIRT6 expression in mouse hippocampal neuronal cells. Overexpression of Larp7 reversed the combined exposure-induced SIRT6 decrease and senescence in mouse hippocampal neuronal cells. Additionally, the results showed notably elevated levels of Larp7 m6A and YTH domain family protein 2 (YTHDF2) in mouse hippocampal neuronal cells treated with the combined hazards. Ythdf2 short interfering RNA, RNA immunoprecipitation, and RNA stability assays further demonstrated that YTHDF2 mediated the degradation of Larp7 mRNA under combined exposure. Collectively, adolescent co-exposure to Cd and HFD causes hippocampal senescence and cognitive decline in mice by inhibiting LARP7-mediated SIRT6 expression in an m6A-dependent manner., 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.)

A novel colorimetric-fluorescent dual-mode chemosensor (JT5) based on rhodamine B has been produced for monitoring Sn 4+ in the DMSO/H 2 O (4:1, v/v) medium. It has high sensitivity, a low detection limit, a short response time (1 s) and high stability, and can still be maintained after two weeks with the red dual fluorescence/ colorimetric response. Enhancement of red fluorescence (591 nm) and red colorimetric (567 nm) response of JT5 by Sn 4+ addition. The electrostatic potential of the sensor JT5 molecule was simulated to speculate on the sensing mechanism, and the IR, mass spectrometry and 1 H NMR titration were utilized to further demonstrate that JT5 was coordinated to Sn 4+ with a 1:1 type, the rhodamine spironolactam ring of JT5 opens up to form a penta-membered ring with Sn 4+ , meanwhile, its system may have chelation enhanced fluorescence (CHEF) effect. In addition, theoretical calculations were carried out to give the energy gaps of JT5 and [JT5 + Sn 4+ ] as well as to simulate the electronic properties of the maximal absorption peaks. Notably, the sensor JT5 was successfully applied to monitoring Sn 4+ in zebrafish, and the JT5-loaded filter paper provided a solid-state platform for detecting Sn 4+ by both naked eye and fluorescent methods. In summary, this work contributes to monitoring Sn 4+ in organisms and solid-state materials and promotes understanding of Sn 4+ functions in biological systems, environments, and solid-state materials., 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.)

Cognitive dysfunction is an important comorbidity of type 2 diabetes mellitus (T2DM). Sodium butyrate (NaB) is a short-chain fatty acid and has an effect improving T2DM-associated cognitive dysfunction. Using a high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM mouse model, the present study investigated the mechanism involved in the beneficial effect of butyrate on diabetic cognitive dysfunction, with a focus on ameliorating mitochondrial damage through regulating the adenosine monophosphate-activated protein kinase/peroxisome proliferator- activated receptor gamma coactivator 1α (AMPK/PGC-1α) pathway considering the important role of mitochondrial impairments in the occurrence of T2DM-associated cognitive dysfunction. We found, based on reconfirmation of the improvement of NaB on cognitive impairment, that NaB treatment improved damaged synaptic structural plasticity including the decrease in dendritic spine density and downregulation in the expression of postsynaptic density protein 95 and synaptophysin in the hippocampus in the model mice. NaB treatment also ameliorated mitochondrial ultrastructural damage, increased mitochondrial membrane potential and adenosine 5'-triphosphate content, and improved mitochondrial biogenesis and dynamics in the model mice. Furthermore, the expression of phosphorylated AMPK and PGC-1α was upregulated after NaB treatment in the model mice. In particular, the above beneficial effects of NaB were blocked by the inhibition of either AMPK or PGC-1α. In conclusion, NaB treatment improved cognitive impairment and damaged synaptic structural plasticity in the hippocampus by ameliorating damage to mitochondrial morphology and function through regulating the AMPK/PGC-1α pathway in HFD/STZ-induced T2DM mice., Competing Interests: Declaration of Competing Interest We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. All authors have approved the manuscript and agree with submission to Neuropharmacology. The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Alzheimer's disease (AD) is the most prevalent type of dementia, and its causes are currently diverse and not fully understood. In a previous study, we discovered that short-term treatment with miracle fruit seed (MFS) had a therapeutic effect on AD model mice, however, the precise mechanism behind the effect remains unclear. In this research, we aimed to establish the efficacy and safety of long-term use of MFS in AD model mice. A variety of cytokines and chemokines have been implicated in the development of AD. Previous studies have validated a correlation between the expression levels of C-X-C chemokine receptor type 4 (CXCR4) and disease severity in AD. In this research, we observed an upregulation of CXCR4 expression in hippocampal tissues in the AD model group, which was then reversed after MFS treatment. Moreover, CXCR4 knockout led to improving cognitive function in AD model mice, and MFS showed the ability to regulate CXCR4 expression. Finally, our findings indicate that CXCR4 knockout and long-term MFS treatment produce comparable effects in treating AD model mice. In conclusion, this research demonstrates that therapeutic efficacy and safety of long-term use of MFS in AD model mice. MFS treatment and the subsequent reduction of CXCR4 expression exhibit a neuroprotective role in the brain, highlighting their potential as therapeutic targets for AD., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists with respect to the current research., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Cardiopulmonary bypass (CPB) leads to severe inflammation and lung injury. Our previous study showed that Ac2-26 (an active n-terminal peptide of Annexin A1) can reduce acute lung injury. The aim of this study was to evaluate the effect of Ac2-26 on lung injury in CPB rats., Methods: Forty rats were randomly divided into the sham, CPB, Ac, Ac/serine/threonine kinase 1 (AKT1), and Ac/ glycogen synthase kinase (GSK)-3β groups. The rats in the sham group only received anesthesia, intubation, and cannulation. The rats in the other 4 groups received the standard CPB procedure. The rats in the CPB, Ac, Ac/AKT1, and Ac/GSK3β groups were immediately injected with saline, Ac2-26 (1 mg/kg), Ac2-26 combined with short hairpin RNA (AKT1), or Ac2-26 combined with a GSK3β inhibitor after CPB. At 12 h after the end of CPB, the PaO 2 / fraction of inspired oxygen ratio, wet/dry weight ratio and protein content in the bronchoalveolar lavage fluid (BALF) were recorded. The numbers of macrophages and neutrophils in the BALF and blood were determined. Cytokine levels in the blood and BALF were investigated. Lung tissue histology and apoptosis were estimated. The expression of nuclear factor kappa- B, AKT1, GSK3β, endothelial nitric oxide synthase and apoptosis-related proteins was analyzed. The survival of all the rats was recorded., Results: Compared with the rats in the sham group, all the parameters examined worsened in the rats that received CPB. Compared with those in the CPB group, Ac2-26 significantly improved pulmonary capillary permeability, reduced cytokine levels, and decreased histological scores and apoptosis. The protective effect of Ac2-26 on lung injury was significantly reversed by AKT1 short hairpin RNA or a GSK3β inhibitor., Conclusions: Ac2-26 significantly reduced lung injury and inflammation after CPB. The protective effect of Ac2-26 mainly depended on the AKT1/GSK3β/endothelial nitric oxide synthase pathway., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The study characterized the transcriptionally regulatory mechanism and functions of three zinc (Zn) transporters (znt4, znt5 and znt10) in Zn 2+ metabolism in yellow catfish (Pelteobagrus fulvidraco), commonly freshwater fish in China and other countries. We cloned the sequences of znt4 promoter, spanning from -1217 bp to +80 bp relative to TSS (1297 bp); znt5, spanning from -1783 bp to +49 bp relative to TSS (1832 bp) and znt10, spanning from -1923 bp to +190 bp relative to TSS (2113 bp). In addition, after conducting the experiments of sequential deletion of promoter region and mutation of potential binding site, we found that the Nrf2 binding site (-607/-621 bp) and Klf4 binding site (-5/-14 bp) were required on znt4 promoter, the Mtf-1 binding site (-1674/-1687 bp) and Atf4 binding site (-444/-456 bp) were required on znt5 promoter and the Atf4 binding site (-905/-918 bp) was required on znt10 promoter. Then, according to EMSA and ChIP, we found that Zn 2+ incubation increased DNA affinity of Atf4 to znt5 or znt10 promoter, but decreased DNA affinity of Nrf2 to znt4 promoter, Klf4 to znt4 promoter and Mtf-1 to znt5 promoter. Using fluorescent microscopy, it was revealed that Znt4 and Znt10 were located in the lysosome and Golgi, and Znt5 was located in the Golgi. Finally, we found that znt4 knockdown reduced the zinc content of lysosome and Golgi in the control and zinc-treated group; znt5 knockdown reduced the zinc content of Golgi in the control and zinc-treated group and znt10 knockdown reduced the zinc content of Golgi in the zinc-treated group. High dietary zinc supplement up-regulated Znt4 and Znt5 protein expression. Above all, for the first time, we revealed that Klf4 and Nrf2 transcriptionally regulated the activities of znt4 promoter; Mtf-1 and Atf4 transcriptionally regulated the activities of znt5 promoter and Atf4 transcriptionally regulated the activities of znt10 promoter, which provided innovative regulatory mechanism of zinc transporting in yellow catfish. Our study also elucidated their subcellular location, and regulatory role of zinc homeostasis in yellow catfish., Competing Interests: Declaration of competing interest The authors declared 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.)

Opium poppy, coca and cannabis are raw materials for three notorious illicit drugs. For a long time, drug lords have been growing and smuggling these drugs in a variety of ways and channels and are continually finding new ways of trafficking their wares, which has led to the increasing difficulty of global drug enforcement. In the present paper, we propose an innovative pollen identification system for these important drug plants, which provides a tool for screening and detection of the drugs to aid in drug enforcement. By utilizing the characteristics of these fine particles, their abundant production, and high resistance to decay, we believe this tool could be applied in the following scenarios: detecting and dynamically monitoring drug cultivation activities; determining whether a suspect has been to fields of drug plants and determining whether the site has ever been planted with a drug plant and/or was involved in drug production. In the future, combined with microscope automatic image acquisition technology and intelligent image recognition technology, this pollen identification system is expected to be used to screen three notorious illicit drug plants, thus enhancing the efficiency of drug related crime investigations., (© 2024 American Academy of Forensic Sciences.)

Oxidative stress contributes greatly to doxorubicin (DOX)-induced cardiotoxicity. Down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) is a key factor in DOX-induced myocardial oxidative injury. Recently, we found that mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1)-dependent k48-linked ubiquitination was responsible for down-regulation of myocardial Nrf2 in DOX-treated mice. Micafungin, an antifungal drug, was identified as a potential MALT1 inhibitor. This study aims to explore whether micafungin can reduce DOX-induced myocardial oxidative injury and if its anti-oxidative effect involves a suppression of MALT1-dependent k48-linked ubiquitination of Nrf2. To establish the cardiotoxicity models in vivo and in vitro, mice were treated with a single dose of DOX (15 mg/kg, i.p.) and cardiomyocytes were incubated with DOX (1 μM) for 24 h, respectively. Using mouse model of DOX-induced cardiotoxicity, micafungin (10 or 20 mg/kg) was shown to improve cardiac function, concomitant with suppression of oxidative stress, mitochondrial dysfunction, and cell death in a dose-dependent manner. Similar protective roles of micafungin (1 or 5 μM) were observed in DOX-treated cardiomyocytes. Mechanistically, micafungin weakened the interaction between MALT1 and Nrf2, decreased the k48-linked ubiquitination of Nrf2 while elevated the protein levels of Nrf2 in both DOX-treated mice and cardiomyocytes. Furthermore, MALT1 overexpression counteracted the cardioprotective effects of micafungin. In conclusion, micafungin reduces DOX-induced myocardial oxidative injury via suppression of MALT1, which decreases the k48-linked ubiquitination of Nrf2 and elevates Nrf2 protein levels. Thus, micafungin may be repurposed for treating DOX-induced cardiotoxicity., 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.)

To reveal the protective effect on the nephrotoxicity of Quercus salicina Blume(QS), a traditional medicine for the treatment of urolithiasis, the 50 % ethanol extract from the branches and leaves of QS was chemically studied by systematic solvent extraction and HPLC chromatography. Two phenolic acids and three flavonoids were identified by nuclear magnetic resonance spectroscopy, namely Ferulic acid (1), p-Hydroxycinnamic acid (2), Hesperidin (3), Formononetin (4), and Quercetin (5). At the same time, the gentamicin-induced nephrotoxicity of zebrafish was used as a model for the first time. The antioxidant activity of these derivatives with good antioxidant activity screened from free radical scavenging experiments in vitro (DPPH and ABTS) was evaluated in vivo, including protein levels (LPO, NO, GSH, and SOD), kidney injury factor (KIM-1), zebrafish kidney pathology and real-time PCR. The results showed that metabolites 1, 3, and 5 had strong antioxidant activity, and oxidative stress in renal tissue was significantly reduced; KIM-1, TNF-α, and IL-6 mRNA expression in a dose-dependent manner, which preliminarily revealed the protective effect of the secondary metabolites of QS on nephrotoxicity, and preliminarily discussed the structure-activity relationship. This study provides an experimental basis for further exploring the mechanism of QS in the kidney., 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.)

Cow milk consumption (CMC) and downstream alterations of serum metabolites are commonly considered important factors regulating human health status. Foods may lead to metabolic changes directly or indirectly through remodelling gut microbiota (GM). We sought to identify the metabolic alterations in Chinese Peri-/Postmenopausal women with habitual CMC and explore if the GM mediates the CMC-metabolite associations. 346 Chinese Peri-/Postmenopausal women participants were recruited in this study. Fixed effects regression and partial least squares discriminant analysis (PLS-DA) were applied to reveal alterations of serum metabolic features in different CMC groups. Spearman correlation coefficient was computed to detect metabolome-metagenome association. 36 CMC-associated metabolites including palmitic acid (FA(16:0)), 7alpha-hydroxy-4-cholesterin-3-one (7alphaC4), citrulline were identified by both fixed effects regression (FDR < 0.05) and PLS-DA (VIP score > 2). Some significant metabolite-GM associations were observed, including FA(16:0) with gut species Bacteroides ovatus, Bacteroides sp.D2. These findings would further prompt our understanding of the effect of cow milk on human health.

Background: Resting energy expenditure (REE) refers to the energy consumption of the body in a resting state without skeletal muscle activity. This study aimed to examine the REE among children hospitalized with varying nutritional status., Methods: This was a retrospective study. We enrolled 109 pediatric cases that underwent indirect calorimetry (IC) and divided into four groups: mild malnutrition group (15 cases), moderate malnutrition group (30 cases), severe malnutrition group (32 cases), and obesity group (32 cases). We compared and analyzed the measured REE (mREE) using IC with the predicted REE (pREE) using five energy equations. The paired t-test was used to compare the results of two samples. Pearson analysis was used to assess the correlation between two values. The agreement analysis was performed using the Bland-Altman method., Results: There was no significant difference in mREE between the mild, moderate, and severe malnutrition groups, but each differed significantly from the obesity group. All populations exhibited significant correlation between the mREEs and all five energy equations, and the equation with the highest predictive accuracy was the Schofield equation, which achieved an accuracy of 47.7%. In subgroup analysis, there was no significant difference between mREE and pREE for each of the five equations in the mild, moderate malnutrition groups. Only the prediction result of the Liu equation was not significantly different from the mREE in the severe malnutrition group. The prediction accuracy of the Liu equation was relatively the highest (34.4%). However, in the obese group, there were significant differences in pREE and mREE between the Liu equation and Mifflin equation. Under different nutritional statuses, the results of the Bland-Altman analysis suggested that deviation values between REEs predicted by each equation and mREE were greater than ±10%., Conclusions: There were differences in REE among children with different nutritional status. The results obtained from the five predictive energy equations deviated from the IC results. When REE cannot be measured by IC, it is essential to choose an appropriate predictive energy equation based on the nutritional status of the individual., 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-24-168/coif). The authors have no conflicts of interest to declare., (2024 Translational Pediatrics. All rights reserved.)

The establishment of reticular chemistry has significantly facilitated the development of porous materials, especially for metal-organic frameworks (MOFs). On the other hand, as an alternative approach, in situ "one-pot" strategy has been explored as a promising approach to constructing MOFs, in which the synthesis of organic linkers and the sequential construction of MOFs are integrated into one solvothermal condition. This strategy can efficiently avoid the limitations faced in the traditional construction method, such as time-consuming organic synthesis and multiple separation and purification. Herein, inspired by the reaction of aldehydes and o-phenylenediamine and deep structural analysis of UiO-68, a series of tetra-, hexa-, and octa-topic carboxylic acids are synthesized using 2',3'-diamino-[1,1':4',1'"-terphenyl]-4,4'"-dicarboxylic acid and di-, tri-, and tetra-topic aldehydes as precursor. Then nine multicarboxylate-based zirconium MOFs (Zr-MOFs) are successfully constructed via the combination of reticular chemistry and in situ "one-pot" strategy. The resultant Zr-MOFs can be regarded as the partial face decoration of UiO-68. More importantly, the emission properties of resultant Zr-MOFs can be well controlled using aldehydes with tunable electronic structures. This work provides a new path to rational design and construction of porous materials with specific structures guided by reticular chemistry and conducted using in situ "one-pot" strategy., (© 2024 Wiley‐VCH GmbH.)

Cervical mucus not only provides energy for sperm but also forms a barrier to block sperm. This paper aims to study the microstructure of cervical mucus in dairy cows during the proestrus, estrus, and metestrus and its effect on sperm permeability. The experiment collected cervical mucus from 60 Holstein cows during these phases, then observed the different shapes of the mucus after crystallization, classified the mucus, and analyzed its proportions. Scanning electron microscopy was used to observe the ultrastructure of the cervical mucus and measure the micro-pore sizes, followed by sperm permeability tests using mucus from different estrous stages and counting the number of permeated sperm. The results indicate that cervical mucus from cows in different estrous phases includes four types (L, S, P, G), with each type constituting a different proportion. During the proestrus, the L type was significantly more prevalent than the other types ( p < 0.05); during estrus, the S type was significantly more prevalent than the other types ( p < 0.05); and during the metestrus, the p type was significantly more prevalent than the other types ( p < 0.05). The micro-pore sizes of the same type of cervical mucus did not show significant differences across different estrous phases ( p > 0.05). However, within the same estrous phase, there were significant differences in the micro-pore sizes among the four types ( p < 0.05). The number of sperm that permeated the cervical mucus during estrus and metestrus was significantly higher than during the proestrus ( p < 0.05). This study provides data support for the research on cervical mucus in dairy cows.

Quantum communication networks are crucial for both secure communication and cryptographic networked tasks. Building quantum communication networks in a scalable and cost-effective way is essential for their widespread adoption. Here, we establish a complete polarization entanglement-based fully connected network, which features an ultrabright integrated Bragg reflection waveguide quantum source, managed by an untrusted service provider, and a streamlined polarization analysis module, which requires only one single-photon detector for each user. We perform a continuously working quantum entanglement distribution and create correlated bit strings between users. Within the framework of one-time universal hashing, we provide the experimental implementation of source-independent quantum digital signatures using imperfect keys circumventing the necessity for private amplification. We further beat the 1/3 fault tolerance bound in the Byzantine agreement, achieving unconditional security without relying on sophisticated techniques. Our results offer an affordable and practical route for addressing consensus challenges within the emerging quantum network landscape.

A new Cyrtodactylus species, C. laevis sp. nov. , from the dry-hot valleys near the Yarlung Zangbo River in Re Village, Jindong Countryside, Lang County, Linzhi City, Xizang Autonomous Region, China, is described herein based upon the integrative taxonomic results combining molecular phylogenetic systematics and morphological characteristic comparisons. Our molecular phylogeny was inferred by combining three mitochondrial gene fragments ( 16S / CO1 / ND2 ), and it indicated a distinct differentiation between the new species and C. tibetanus species complex, with obvious genetic distances ( 16S 9.9-11.8%/ CO1 16.5-18.2%/ ND2 16.6-18.5%) detected, supporting its validity. Morphologically, the new species can be easily distinguished from its congers by the following characters: (1) medium size (SVL 48.58-50.92 mm), (2) tubercles on dorsum sparse, (3) tail segments absent and tubercles on tails absent, (4) supralabials 10-12 and infralabials 8-10, (5) interorbital scales between anterior corners of the eyes 28-32, (6) scale rows at midbody 96-98, (7) ventral scales between mental and cloacal slit 145-153, (8) ventral scale rows 41-45, and (9) 4 to 5 white-yellow transverse bands with brown dots and black merges between the nape and sacrum. The description of C. laevis sp. nov. increased the total species number of C. tibetanus group to three, and the total Cyrtodactylus species number in Xizang to six and in China to eleven. The new species is currently only known from the type locality with its extremely small populations and needs future surveys to reveal its distribution range, population status, natural history, and mechanisms so that the new species can coexist with Altiphylax medogense .

Diquat (DQ) is a typical bipyridine herbicide widely used to control weeds in fields and orchards. The severe toxicity of diquat poses a serious threat to the environment and human health. Metal-organic frameworks (MOFs) have received widespread attention due to their unique physical and chemical properties and applications in the detection of toxic and harmful substances. In this work, a two-dimensional (2D) Tb(III) functionalized MOF Tb(III)@1 (1 = [Cd(HTATB)(bimb)] n ·H 2 O (Cd-MOF), H 3 TATB = 4,4',4″-triazine-2,4,6-tribenzoicacid, bimb = 1,4-bis((1H-imidazol-1-yl)methyl)benzene) has been prepared and characterized. Tb(III)@1 has excellent optical properties and high water and chemical stability. After the Tb(III) is fixed by the uncoordinated -COO- in the 1 framework, Tb(III)@1 emits the typical green fluorescence of the lanthanide ion Tb(III) through the "antenna effect". It is worth noting that Tb(III)@1 can be used as a dual emission fluorescence chemical sensor for the ratio fluorescence detection of pesticide DQ, exhibiting a relatively low detection limit of 0.06 nM and a wide detection range of 0-50 nM. After the addition of DQ, a rapid color change of Tb(III)@1 fluorescence from green to blue was observed due to the combined effects of IFE, FRET and dynamic quenching. Therefore, a simple test paper box has been designed for direct on-site determination of pesticide DQ. In addition, the developed sensor has been successfully applied to the detection of DQ in real samples (fruits a Yin-Xia Sun and Bo-Tao Ji contributed equally to this work and should be considered co-first authors.nd vegetables) with satisfactory results. The results indicate that the probe developed in this study has broad application prospects in both real sample detection and actual on-site testing., Competing Interests: Declaration of competing interest All of the authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients., Methods: This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded., Results: Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217)., Conclusions: Sirolimus's long-term administration is not associated with adverse effects on children's physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration., Trial Registration: Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892., (© 2024. The Author(s).)

Developing a Surface-enhanced Raman spectroscopy (SERS) method with excellent detecting ability, good recyclability and analyzing multiple pollutants rapidly are critical for evaluation of water quality in emergency pollution affairs. While constructing a multifunctional substrate with these characteristics to realize the application of SERS in water quality monitoring remains a challenge. In this work, a reusable Au@R-Fe 3 O 4 /g-C 3 N 4 SERS substrate is prepared by loading Au nanoparticles (Au NPs) on Fe 3 O 4 nanorings (R-Fe 3 O 4 ) and the formed Au@R-Fe 3 O 4 is further combined with g-C 3 N 4 nanosheets through a simple electrostatic assembly method. The Au@R-Fe 3 O 4 /g-C 3 N 4 nanocomposite presents multifunction of magnetic enrichment, SERS signal enhancement, multiple pollutants analyzing, and photocatalytic activity, which achieves quantitative detection of rhodamine B (RhB), tetracycline hydrochloride (TC), and 4-chlorophenol (4-CP), with detection limits of 5.30 × 10 -9 , 7.50 × 10 -8 , 7.69 × 10 -8  mol/L, respectively. Furthermore, the recyclable detection capability of Au@R-Fe 3 O 4 /g-C 3 N 4 for multi components is demonstrated by the strong SERS signal after 9 cycles of "detection-degradation" processes. Combined with good uniformity and stability, this SERS method based on Au@R-Fe 3 O 4 /g-C 3 N 4 substrate provides a new strategy for the multi-pollutants detection and degradation in water 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 Elsevier B.V. All rights reserved.)

Pyroptosis is a type of programmed cell death mediated by gasdermines (GSDMs). The N-terminal domain of GSDMs forms pores in the plasma membrane, causing cell membrane rupture and the release of cell contents, leading to an inflammatory response and mediating pyrodeath. Pyroptosis plays an important role in inflammatory diseases and malignant tumors. With the further study of pyroptosis, an increasing number of studies have shown that the pyroptosis pathway can regulate the tumor microenvironment and antitumor immunity of colorectal cancer and is closely related to the occurrence, development, treatment and prognosis of colorectal cancer. This review aimed to explore the molecular mechanism of pyroptosis and the role of pyroptosis in the occurrence, development, treatment and prognosis of colorectal cancer (CRC) and to provide ideas for the clinical diagnosis and treatment of CRC., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The threats to the safety of humans and the environment and the resistance of agricultural chemicals to plant pathogenic fungi and bacteria highlight an urgent need to find safe and efficient alternatives to chemical fungicides and bactericides. In this study, a series of Berberine (BBR) derivatives were designed, synthesized and evaluated for in vitro and in vivo antimicrobial activity against plant pathogenic fungi and bacteria., Results: Bioassay results indicated that compounds A11, A14, A20, A21, A22, A25, A26, E1, E2, E3, Z1 and Z2 showed high inhibitory activity against Sclerotinia sclerotiorum and Botrytis cinerea. Especially, A25 showed a broad spectrum and the highest antifungal activity among these compounds. Its EC 50 value against Botrytis cinerea was 1.34 μg mL -1 . Compound E6 possessed high inhibitory activity against Xanthomonas oryzae and Xanthomonas Campestris, with MIC 90 values of 3.12 μg mL -1 and 1.56 μg mL -1 . A Topomer CoMFA model was generated for 3D-QSAR studies based on anti-B. cinerea effects, with high predictive accuracy, showed that the addition of an appropriate substituent group at the para-position of benzyl of BBR derivatives could effectively improve the anti-B. cinerea activity. In addition, compound A25 could significantly inhibit the spore germination of Botrytis cinerea at low concentration, and compound F4 exhibited remarkable curative and protective efficiencies on rice bacterial leaf blight., Conclusion: This study indicates that the BBR derivatives are hopeful for further exploration as the lead compound with novel antimicrobial agents. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: We aimed to explore the impact of adherence to Life's Simple 7 (LS7) metrics on risk of obstructive sleep apnea (OSA), and the impact of inflammation on the association, in adults in the United States., Methods: Data from 13,825 community-dwelling adults aged ≥ 20 years recruited in the National Health and Nutrition Examination Surveys (NHANES) 2005-2008, 2015-2018 was analyzed. The LS7 score was calculated based on the AHA definition of LS7 metrics. The diagnosis of OSA was based on self-reported symptoms of sleep disturbance using a standard questionnaire. The Multivariable Apnea Prediction (MAP) Index score was also calculated to assess the risk of OSA. Log-binominal regression and negative binomial regression were performed to estimate the associations between LS7 and OSA and MAP index, with odds ratios (ORs) and prevalence ratios (PRs) and their 95% confidence intervals (CIs) calculated. Mediation analysis was performed to estimate the mediating effects of inflammatory indicators on the associations., Results: A total of 4473 participants (32.4%) had OSA, and the mean MAP index was 0.39. In fully adjusted log-binominal regression models, with total score < 6 as the reference, the ORs (95% CIs) for risk of OSA were 0.90 (0.73, 1.10), 0.76 (0.65, 0.89), 0.78 (0.64, 0.95), and 0.45 (0.38, 0.54) for total score = 6, total score = 7, total score = 8, and total score > 8, respectively (P for trend < 0.001). When LS7 score was analyzed as a continuous variable, each 1-point increase in LS7 score was associated with a 15% decrease in OSA risk (P < 0.001). In negative binominal regression models, the adjusted PRs (95% CIs) for the MAP index were 0.93 (0.90, 0.97), 0.87 (0.84, 0.91), 0.80 (0.77, 0.84), and 0.55 (0.53, 0.57) for total score = 6, total score = 7, total score = 8, and total score > 8, respectively (P for trend < 0.001). For each 1-point increase in LS7 score, the risk of OSA decreased by 13% (P < 0.001). Consistent results were observed in subgroup analysis. Mediation analysis indicated that inflammatory factors, including blood cell count, neutrophil count, and C-reactive protein, positively mediated the association of LS7 with OSA, with a mediation proportion of 0.022 (P = 0.04), 0.02 (P = 0.04), and 0.02 (P = 0.02), respectively., Conclusions: In a nationally representative sample of US adults, adherence to LS7 metrics was independently associated with reduced OSA risk. Inflammation plays a mediating role in the association between LS7 and OSA., (© 2024. The Author(s).)

Recurrence risks of cancer patient can change during treatment as a result of treatment-related tumor evolution. However, biomarkers that can monitor these changes are lacking. Here, we investigated whether tracking circulating tumor DNA (ctDNA) dynamics through liquid biopsy can inform real-time recurrence risk. Nasopharyngeal carcinoma (NPC) provides an ideal model where cell-free Epstein-Barr virus (EBV) DNA (cfEBV DNA), a ctDNA, can be sensitively detected. We conducted the EP-SEASON study (NCT03855020) and prospectively recruited 1,000 NPC patients undergoing per-protocol cfEBV DNA assessments at 11 time points and receiving sequential chemo-radiotherapy. Longitudinal cfEBV DNA displayed distinct patterns during neoadjuvant chemotherapy and radiotherapy. Despite the prognostic significance of cfEBV DNA at each time point, real-time recurrence risks changed in sync with cfEBV DNA dynamics. Furthermore, we identified phenotypes of whole-course ctDNA changing dynamics associated with different survival outcomes. In conclusion, tracking longitudinal on-treatment ctDNA can forecast real-time recurrence risk, facilitating risk-adapted, individualized patient management., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Microbial communities play an important role in water quality regulation and biogeochemical cycles in lakes, and their community structure and function are affected by environmental factors. Therein, antibiotics affect the abundance, diversity, composition, and function of microbial communities. In this study, Baiyangdian Lake was selected as the study area. Sediment samples of 16 sites were collected in August 2018 and April 2019, respectively. Ultra-high performance liquid chromatography-mass spectrometry （HPLC-MS/MS） was used to determine the content of typical antibiotics-quinolones （QNs） in sediment. Through high-throughput sequencing technology, the structure and function of microbial communities was analyzed in the sediments to explore the spatiotemporal variation. Thereinto, redundancy analysis （RDA） was used to identify the key influencing factors of spatiotemporal variation of microbial communities. The results showed that： ① From August to April, the average ω （QNs） showed an increasing trend, and its mean value changed from 3.91 ng·g -1 to 6.34 ng·g -1 , with significant seasonal differences in oxolinic acid （OXO） and total QNs content （ P &lt; 0.05）. ② In terms of temporal variation, the dominant bacteria were Proteobacteria and Chloroflexi. The relative abundance of Proteobacteria showed a decreasing trend, whereas Chloroflexi showed an increasing trend； at the genus level, the dominant bacteria genera in August were norank&#95; f&#95;&#95;Anaerolineaceae and Thiobacilus , and the dominant bacteria genera in April were Acinetobacter and norank&#95; f&#95;Anaerolineaceae, and the dominant bacteria genera had significant seasonal differences （ P &lt; 0.05）. ③ In terms of temporal variation, the index of Simpson, Chao, Ace, and OTU number all showed an increasing trend, and the seasonal differences were significant （ P &lt; 0.05）. ④ In terms of spatial variation, there were no significant spatial differences among functional genes of COG. In terms of temporal variation, there were significant seasonal differences in functional genes of energy production and conversion, carbohydrate transport and metabolism, transcription, cell wall/membrane/envelope biogenesis, and signal transduction mechanisms （ P &lt; 0.01 and P &lt; 0.05）. ⑤ Microbial community structure and functional genes were significantly correlated with QNs （ P &lt; 0.01 and P &lt; 0.05）, and QNs were the main influencing factors. Therefore, QNs were the main factor affecting the changes in microbial community structure and functional genes in sediments of Baiyangdian Lake. Thus, comprehensive control of antibiotic pollution in sediments should be further strengthened.

Habitual daytime napping is a common behavioral and lifestyle practice in particular countries and is often considered part of a normal daily routine. However, recent evidence suggests that the health effects of habitual daytime napping are controversial. We systematically searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to March 9, 2024, to synthesize cohort studies of napping and health outcome risk. A total of 44 cohort studies with 1,864,274 subjects aged 20-86 years (mean age 56.4 years) were included. Overall, habitual napping increased the risk of several adverse health outcomes, including all-cause mortality, cardiovascular disease, metabolic disease, and cancer, and decreased the risk of cognitive impairment and sarcopenia. Individuals with a napping duration of 30 min or longer exhibited a higher risk of all-cause mortality, cardiovascular disease, and metabolic disease, whereas those with napping durations less than 30 min had no significant risks. No significant differences in napping and health risks were observed for napping frequency, percentage of nappers, sample size, sex, age, body mass index, follow-up years, or comorbidity status. These findings indicate that individuals with a long napping duration should consider shortening their daily nap duration to 30 min or less., Competing Interests: Declaration of competing interest The authors do not have any conflicts of interest to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A biocompatible metal-organic framework (MOF), named HSTC-4, constructed using the flexible 4,4'-oxybis(benzoic acid) (OBA), was developed to enable efficient loading and controlled release of vitamin C (VC) through a combination of strategies involving ligand length, structure design, and metal selection. The kinetic product HSTC-4 demonstrates a propensity for transforming into the thermodynamically stable HSTC-5 under external stimuli, such as photoillumination and vacuum heating, as witnessed by single-crystal to single-crystal transformation. Density functional theory (DFT) calculations reveal that the VC guest molecules exhibit stronger binding affinity with HSTC-5 due to its narrower pores compared to HSTC-4, resulting in a slower release of VC from VC@HSTC-5. Furthermore, precise control over VC release can be achieved by introducing surface modifications involving SiO 2 onto the structure of VC@HSCT-5, while simultaneously adjusting environmental factors such as pH and temperature conditions. Preliminary cell culture experiments and cytotoxicity assays highlight the biocompatibility of HSTC-5, suggesting that it is a promising platform for sustained drug delivery and diverse biomedical applications.

Chronic cerebral hypoperfusion (CCH), a disease afflicting numerous individuals worldwide, is a primary cause of cognitive deficits, the pathogenesis of which remains poorly understood. Bruton's tyrosine kinase inhibition (BTKi) is considered a promising strategy to regulate inflammatory responses within the brain, a crucial process that is assumed to drive ischemic demyelination progression. However, the potential role of BTKi in CCH has not been investigated so far. In the present study, we elucidated potential therapeutic roles of BTK in both in vitro hypoxia and in vivo ischemic demyelination model. We found that cerebral hypoperfusion induced white matter injury, cognitive impairments, microglial BTK activation, along with a series of microglia responses associated with inflammation, oxidative stress, mitochondrial dysfunction, and ferroptosis. Tolebrutinib treatment suppressed both the activation of microglia and microglial BTK expression. Meanwhile, microglia-related inflammation and ferroptosis processes were attenuated evidently, contributing to lower levels of disease severity. Taken together, BTKi ameliorated white matter injury and cognitive impairments induced by CCH, possibly via skewing microglia polarization towards anti-inflammatory and homeostatic phenotypes, as well as decreasing microglial oxidative stress damage and ferroptosis, which exhibits promising therapeutic potential in chronic cerebral hypoperfusion-induced demyelination., (© 2024. The Author(s).)