High Young's Modulus LixTiO2 Layer Suppressing the Pulverization and Deactivation of Lithiophilic Ag Nanoparticles.

Anode-free Lithium metal batteries, with their high energy density (>500 Wh/kg), are emerging as a promising solution for high-energy-density rechargeable batteries. However, the Coulombic Efficiency and capacity often decline due to interface side reactions. To address this, a lithiophilic layer is introduced, promoting stable and uniform Li deposition. Despite its effectiveness, this layer often undergoes electrochemical deactivation over time. This work investigates lithiophilic silver (Ag), prepared via magnetron sputtering on a copper (Cu) current collector. Finite element simulations identify stress changes from alloying reactions as a key cause of Ag particle pulverization and deactivation. A high Young's modulus coating layer is proposed to mitigate this. The Ag2TiO3@Ag@TiO2@Cu composite electrode, designed with multi-layer structures, demonstrates a slower deactivation process through galvanostatic electrochemical cycling. Characterization methods such as SEM, AFM, and TEM confirm the suppression of Ag particle pulverization, while uncoated Ag fractures and deactivates. This work uncovers a potential failure mechanism of lithiophilic metallic nanoparticles and proposes a strategy for deactivation suppression using an artificial coating layer.

Bidirectional wavelength-division-multiplexing fibre-free-space optical communications using polarisation multiplexing technique and tunable optical vestigial sideband filter.

To address the growing demand from emerging applications, high transmission capacity is essential for both fibre backbones and last-mile communications. This can be achieved by integrating optical fibre with optical wireless technologies, facilitating the development of fibre-free-space optical communications. Here we report a bidirectional wavelength-division-multiplexing fibre-free-space optical communication employing polarisation multiplexing technique and tunable optical vestigial sideband filter. The transmission capacity is considerably increased by integrating the polarisation multiplexing technique with the wavelength-division-multiplexing scheme. The transmission performance is extensively enhanced by using a tunable optical vestigial sideband filter and vestigial sideband-four-level pulse amplitude modulation. Moreover, the optical wireless link is substantially extended through the operation of triplet lenses. Low bit error rates and clear vestigial sideband-four-level pulse amplitude modulation eye diagrams are attained with a high aggregate transmission capacity of 480 Gb/s for downstream/upstream transmission. This capability of bidirectional fibre-free-space optical communications holds substantial potential for enhancing advanced wired-wireless communications.

Maternal folic acid over-supplementation impairs cardiac function in mice offspring by inhibiting SOD1 expression.

BACKGROUND: Folic acid (FA) supplementation during pregnancy aims to protect foetal development. However, maternal over-supplementation of FA has been demonstrated to cause metabolic dysfunction and increase the risk of autism, retinoblastoma, and respiratory illness in the offspring. Moreover, FA supplementation reduces the risk of congenital heart disease. However, little is known about its possible adverse effects on cardiac health resulting from maternal over-supplementation. In this study, we assessed the detrimental effects of maternal FA over-supplementation on the cardiac health of the offspring. METHODS AND RESULTS: Eight-week-old C57BL/6J pregnant mice were randomly divided into control and over-supplemented groups. The offspring cardiac function was assessed using echocardiography. Cardiac fibrosis was assessed in the left ventricular myocardium by histological analysis. Proteomic, protein, RNA, and DNA methylation analyses were performed by liquid chromatography-tandem mass spectrometry, western blotting, real-time quantitative PCR, and bisulfite sequencing, respectively. We found that maternal periconceptional FA over-supplementation impaired cardiac function with the decreased left ventricular ejection fraction in the offspring. Biochemical indices and tissue staining further confirmed impaired cardiac function in offspring caused by maternal FA over-supplementation. The combined proteomic, RNA expression, and DNA methylation analyses suggested that key genes involved in cardiac function were inhibited at the transcriptional level possibly due to increased DNA methylation. Among these, superoxide dismutase 1 was downregulated, and reactive oxygen species (ROS) levels increased in the mouse heart. Inhibition of ROS generation using the antioxidant N-acetylcysteine rescued the impaired cardiac function resulting from maternal FA over-supplementation. CONCLUSIONS: Our study revealed that over-supplementation with FA during mouse pregnancy is detrimental to cardiac function with the decreased left ventricular ejection fraction in the offspring and provides insights into the mechanisms underlying the association between maternal FA status and health outcomes in the offspring.

Energy Landscape Reveals the Underlying Mechanism of Cancer-Adipose Conversion in Gene Network Models.

Cancer is a systemic heterogeneous disease involving complex molecular networks. Tumor formation involves an epithelial-mesenchymal transition (EMT), which promotes both metastasis and plasticity of cancer cells. Recent experiments have proposed that cancer cells can be transformed into adipocytes via a combination of drugs. However, the underlying mechanisms for how these drugs work, from a molecular network perspective, remain elusive. To reveal the mechanism of cancer-adipose conversion (CAC), this study adopts a systems biology approach by combing mathematical modeling and molecular experiments, based on underlying molecular regulatory networks. Four types of attractors are identified, corresponding to epithelial (E), mesenchymal (M), adipose (A) and partial/intermediate EMT (P) cell states on the CAC landscape. Landscape and transition path results illustrate that intermediate states play critical roles in the cancer to adipose transition. Through a landscape control approach, two new therapeutic strategies for drug combinations are identified, that promote CAC. These predictions are verified by molecular experiments in different cell lines. The combined computational and experimental approach provides a powerful tool to explore molecular mechanisms for cell fate transitions in cancer networks. The results reveal underlying mechanisms of intermediate cell states that govern the CAC, and identified new potential drug combinations to induce cancer adipogenesis.

Divergent syntheses of complex Veratrum alkaloids.

The Veratrum alkaloids are a class of highly intricate natural products renowned for their complex structural and stereochemical characteristics, which underlie a diverse array of pharmacological activities ranging from anti-hypertensive properties to antimicrobial effects. These properties have generated substantial interest among both synthetic chemists and biologists. While numerous advancements have been made in the synthesis of jervanine and veratramine subtypes over the past 50 years, the total synthesis of highly oxidized cevanine subtypes has remained relatively scarce. Building on the efficiency of our previously developed strategy for constructing the hexacyclic carbon skeleton of the Veratrum alkaloid family via a stereoselective intramolecular Diels-Alder reaction and radical cyclization, here we show the development of a unified synthetic approach to access highly oxidized Veratrum alkaloids. This includes the total synthesis of (-)-zygadenine, (-)-germine, (-)-protoverine and the alkamine of veramadine A, by capitalizing on a meticulously designed sequence of redox manipulations and a late-stage neighboring-group participation strategy.

Substrate specificity of a branch of aromatic dioxygenases determined by three distinct motifs.

The inversion of substrate size specificity is an evolutionary roadblock for proteins. The Duf4243 dioxygenases GedK and BTG13 are known to catalyze the aromatic cleavage of bulky tricyclic hydroquinone. In this study, we discover a Duf4243 dioxygenase PaD that favors small monocyclic hydroquinones from the penicillic-acid biosynthetic pathway. Sequence alignments between PaD and GedK and BTG13 suggest PaD has three additional motifs, namely motifs 1-3, distributed at different positions in the protein sequence. X-ray crystal structures of PaD with the substrate at high resolution show motifs 1-3 determine three loops (loops 1-3). Most intriguing, loops 1-3 stack together at the top of the pocket, creating a lid-like tertiary structure with a narrow channel and a clearly constricted opening. This drastically changes the substrate specificity by determining the entry and binding of much smaller substrates. Further genome mining suggests Duf4243 dioxygenases with motifs 1-3 belong to an evolutionary branch that is extensively involved in the biosynthesis of natural products and has the ability to degrade diverse monocyclic hydroquinone pollutants. This study showcases how natural enzymes alter the substrate specificity fundamentally by incorporating new small motifs, with a fixed overall scaffold-architecture. It will also offer a theoretical foundation for the engineering of substrate specificity in enzymes and act as a guide for the identification of aromatic dioxygenases with distinct substrate specificities.

Toward High-Energy-Density Initial-Anode-Free Lithium-Metal Batteries via Ultra-Thin Protective Ion-Transport-Promoting Interface Modification and Surface Prelithiation.

Anode-free lithium-metal batteries (AFLMBs) are desirable candidates for achieving high-energy-density batteries, while severe active Li+ loss and uneven Li plating/stripping behavior impede their practical application. Herein, a trilaminar LS-Cu (LiCPON + Si/C-Cu) current collector is fabricated by radio frequency magnetron sputtering, including a Si/C hybrid lithiophilic layer and a supernatant carbon-incorporated lithium phosphorus oxynitride (LiCPON) solid-state electrolyte layer. Joint experimental and computational characterizations and simulations reveal that the LiCPON solid-state electrolyte layer can decompose into an in situ stout ion-transport-promoting protective layer, which can not only regulate homogeneous Li plating/stripping behavior but also inhibit the pulverization and deactivation of Si/C hybrid lithiophilic layer. When combined with surface prelithiated Li1.2Ni0.13Co0.13Mn0.54O2 (Preli-LRM) cathode, the Preli-LRM||LS-Cu full cell delivers 896.1 Wh kg-1 initially and retains 354.1 Wh kg-1 after 50 cycles. This strategy offers an innovative design of compensating for active Li+ loss and inducing uniform Li plating/stripping behavior simultaneously for the development of AFLMBs.

Short-peptide-based enteral nutrition affects rats MDP translocation and protects against gut-lung injury via the PepT1-NOD2-beclin-1 pathway in vivo.

BACKGROUND: Peptide transporter 1 (PepT1) transports bacterial oligopeptide products and induces inflammation of the bowel. Nutritional peptides compete for the binding of intestinal bacterial products to PepT1. We investigated the mechanism of short-peptide-based enteral nutrition (SPEN) on the damage to the gut caused by the bacterial oligopeptide product muramyl dipeptide (MDP), which is transported by PepT1. The gut-lung axis is a shared mucosal immune system, and immune responses and disorders can affect the gut-respiratory relationship. METHODS AND RESULTS: Sprague-Dawley rats were gavaged with solutions containing MDP, MDP + SPEN, MDP + intact-protein-based enteral nutrition (IPEN), glucose as a control, or glucose with GSK669 (a NOD2 antagonist). Inflammation, mitochondrial damage, autophagy, and apoptosis were explored to determine the role of the PepT1-nucleotide-binding oligomerization domain-containing protein 2 (NOD2)-beclin-1 signaling pathway in the small intestinal mucosa. MDP and proinflammatory factors of lung tissue were explored to determine that MDP can migrate to lung tissue and cause inflammation. Induction of proinflammatory cell accumulation and intestinal damage in MDP gavage rats was associated with increased NOD2 and Beclin-1 mRNA expression. IL-6 and TNF-α expression and apoptosis were increased, and mitochondrial damage was severe, as indicated by increased mtDNA in the MDP group compared with controls. MDP levels and expression of proinflammatory factors in lung tissue increased in the MDP group compared with the control group. SPEN, but not IPEN, eliminated these impacts. CONCLUSIONS: Gavage of MDP to rats resulted in damage to the gut-lung axis. SPEN reverses the adverse effects of MDP. The PepT1-NOD2-beclin-1 pathway plays a role in small intestinal inflammation, mitochondrial damage, autophagy, and apoptosis.

Heterotopic mesenteric ossification caused by trauma: A case report.

BACKGROUND: Heterotopic mesenteric ossification (HMO) is a clinically rare condition characterized by the formation of bone tissue in the mesentery. The worldwide reporting of such cases is limited to just over 70 instances in the medical literature. The etiology of HMO remains unclear, but the disease is possibly induced by mechanical trauma, ischemia, or intra-left lower quadrant abdominal infection, leading to the differentiation of mesenchymal stem cells into osteoblasts. Here, we present a rare case of HMO that occurred in a 34-year-old male, who presented with left lower quadrant abdominal pain. CASE SUMMARY: We report the case of a 34-year-old male patient who presented with left lower abdominal pain following trauma to the left lower abdomen. He subsequently underwent surgical treatment, and the postoperative pathological diagnosis was HMO. CONCLUSION: We believe that although there is limited literature and research on HMO, when patients with a history of trauma or surgery to the left lower abdomen present with corresponding imaging findings, clinicians should be vigilant in distinguishing this condition and promptly selecting appropriate diagnostic and therapeutic interventions.

A diagnostic model for differentiating tuberculous spondylodiscitis from pyogenic spondylodiscitis based on pathogen-confirmed patients.

OBJECTIVE: This study aimed to distinguish tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) based on laboratory, magnetic resonance imaging (MRI) and computed tomography (CT) findings. Further, a novel diagnostic model for differential diagnosis was developed. METHODS: We obtained MRI, CT and laboratory data from TS and PS patients. Predictive models were built using binary logistic regression analysis. The receiver operating characteristic curve was analyzed. Both internal and external validation was performed. RESULTS: A total of 81 patients with PS (n = 46) or TS (n = 35) were enrolled. All patients had etiological evidence from the focal lesion. Disc signal or height preservation, skip lesion or multi segment (involved segments ≥ 3) involvement, paravertebral calcification, massive sequestra formation, subligamentous bone destruction, bone erosion with osteosclerotic margin, higher White Blood Cell Count (WBC) and positive result of tuberculosis infection T cell spot test (T-SPOT.TB) were more prevalent in the TS group. A diagnostic model was developed and included four predictors: WBC<7.265 * (10^9/L), skip lesion or involved segments ≥ 3, massive sequestra formation and subligamentous bone destruction. The model showed good sensitivity, specificity, and total accuracy (91.4%, 95.7%, and 93.8%, respectively); the area under the receiver operating characteristic curve (AUC) was 0.981, similar to the results of internal validation using bootstrap resampling (1000 replicates) and external validation set, indicating good clinical predictive ability. CONCLUSIONS: This study develop a good diagnostic model based on both CT and MRI, as well as laboratory findings, which may help clinicians distinguish between TS and PS.

Superconductivity under pressure in a chromium-based kagome metal.

Superconductivity in a highly correlated kagome system has been theoretically proposed for years (refs. 1-5), yet the experimental realization is hard to achieve6,7. The recently discovered vanadium-based kagome materials8, which exhibit both superconductivity9-11 and charge-density-wave orders12-14, are nonmagnetic8,9 and weakly correlated15,16. Thus these materials are unlikely to host the exotic superconductivity theoretically proposed. Here we report the discovery of a chromium-based kagome metal, CsCr3Sb5, which is contrastingly featured with strong electron correlations, frustrated magnetism and characteristic flat bands close to the Fermi level. Under ambient pressure, this kagome metal undergoes a concurrent structural and magnetic phase transition at 55 K, with a stripe-like 4a0 structural modulation. At high pressure, the phase transition evolves into two transitions, possibly associated with charge-density-wave and antiferromagnetic spin-density-wave orderings. These density-wave-like orders are gradually suppressed with pressure and, remarkably, a superconducting dome emerges at 3.65-8.0 GPa. The maximum of the superconducting transition temperature, Tcmax = 6.4 K, appears when the density-wave-like orders are completely suppressed at 4.2 GPa, and the normal state exhibits a non-Fermi-liquid behaviour, reminiscent of unconventional superconductivity and quantum criticality in iron-based superconductors17,18. Our work offers an unprecedented platform for investigating superconductivity in correlated kagome systems.

Prognostic Value of Coronary Angiography-Derived Index of Microcirculatory Resistance in Non-ST-Segment Elevation Myocardial Infarction Patients.

BACKGROUND: The index of microcirculatory resistance is a reliable measure for evaluating coronary microvasculature, but its prognostic value in patients with non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear. OBJECTIVES: This study aimed to evaluate the prognostic impact of postpercutaneous coronary intervention (PCI) angiography-derived index of microcirculatory resistance (angio-IMR) in patients with NSTEMI. METHODS: The culprit vessel's angio-IMR was measured after PCI in 2,212 NSTEMI patients at 3 sites. The primary endpoint was 2-year major adverse cardiac events (MACEs), defined as a composite of cardiac death, readmission for heart failure, myocardial reinfarction, and target vessel revascularization. RESULTS: The mean post-PCI angio-IMR was 20.63 ± 4.17 in NSTEMI patients. A total of 206 patients were categorized as the high post-PCI angio-IMR group according to maximally selected log-rank statistics. Patients with angio-IMR >25 showed a higher rate of MACEs than those with angio-IMR ≤25 (32.52% vs 9.37%; P < 0.001). Post-PCI angio-IMR >25 was an independent predictor of MACEs (HR: 4.230; 95% CI: 3.151-5.679; P < 0.001) and showed incremental prognostic value compared with conventional risk factors (AUC: 0.774 vs 0.716; P < 0.001; net reclassification index: 0.317; P < 0.001; integrated discrimination improvement: 0.075; P < 0.001). CONCLUSIONS: In patients undergoing PCI for NSTEMI, an increased post-PCI angio-IMR is associated with a higher risk of MACEs. The addition of post-PCI angio-IMR into conventional risk factors significantly improves the ability to reclassify patients and estimate the risk of MACEs. (Angiograph-Derived Index of Microcirculatory Resistance in Patients With Acute Myocardial Infarction; NCT05696379).

Structural Basis of Bifunctional CTP/dCTP Synthase.

The final step in the de novo synthesis of cytidine 5'-triphosphate (CTP) is catalyzed by CTP synthase (CTPS), which can form cytoophidia in all three domains of life. Recently, we have discovered that CTPS binds to ribonucleotides (NTPs) to form filaments, and have successfully resolved the structures of Drosophila melanogaster CTPS bound with NTPs. Previous biochemical studies have shown that CTPS can bind to deoxyribonucleotides (dNTPs) to produce 2'-deoxycytidine-5'-triphosphate (dCTP). However, the structural basis of CTPS binding to dNTPs is still unclear. In this study, we find that Drosophila CTPS can also form filaments with dNTPs. Using cryo-electron microscopy, we are able to resolve the structure of Drosophila melanogaster CTPS bound to dNTPs with a resolution of up to 2.7 Å. By combining these structural findings with biochemical analysis, we compare the binding and reaction characteristics of NTPs and dNTPs with CTPS. Our results indicate that the same enzyme can act bifunctionally as CTP/dCTP synthase in vitro, and provide a structural basis for these activities.

Single-cell sequencing analysis revealed that WDR72 was a novel cancer stem cells related gene in gastric cancer.

Background: Cancer stem cells (CSCs) are pivotal in tumor resistance to chemotherapy and gastric cancer's rapid proliferation and metastasis. We aimed to explore the CSCs-related genes in gastric cancer epithelial cells. Methods: The mRNA expression profile and single-cell sequencing data of gastric cancer were downloaded from the public database. Results: We identified WDR72 as a CSCs-related gene in gastric cancer epithelial cells. WDR72 was highly expressed in gastric cancer tissues, and high expression of WDR72 was associated with inferior prognosis of patients. WDR72 expression had a significant negative correlation with the infiltration of CD8 + T cells and activated memory CD4 + T cells. PD-L1 expression was significantly reduced in gastric cancer patients with high WDR72 expression. WDR72 was correlated with IC50 of multiple small-molecule drugs. Conclusion: We identified a novel CSCs-related gene in gastric cancer epithelial cells, WDR72, which was highly expressed in patients with high stemness scores.

Endogenous nege-like viral elements in arthropod genomes reveal virus-host coevolution and ancient history of two plant virus families.

Negevirus is a recently proposed taxon of arthropod-infecting virus, which is associated with plant viruses of two families (Virgaviridae and Kitaviridae). Nevertheless, the evolutionary history of negevirus-host and its relationship with plant viruses remain poorly understood. Endogenous nege-like viral elements (ENVEs) are ancient nege-like viral sequences integrated into the arthropod genomes, which can serve as the molecular fossil records of previous viral infection. In this study, 292 ENVEs were identified in 150 published arthropod genomes, revealing the evolutionary history of nege-like viruses and two related plant virus families. We discovered three novel and eight strains of nege-like viruses in 11 aphid species. Further analysis indicated that 10 ENVEs were detected in six aphid genomes, and they were divided into four types (ENVE1-ENVE4). Orthologous integration and phylogenetic analyses revealed that nege-like viruses had a history of infection of over 60 My and coexisted with aphid ancestors throughout the Cenozoic Era. Moreover, two nege-like viral proteins (CP and SP24) were highly homologous to those of plant viruses in the families Virgaviridae and Kitaviridae. CP- and SP24-derived ENVEs were widely integrated into numerous arthropod genomes. These results demonstrate that nege-like viruses have a long-term coexistence with arthropod hosts and plant viruses of the two families, Virgaviridae and Kitaviridae, which may have evolved from the nege-like virus ancestor through horizontal virus transfer events. These findings broaden our perspective on the history of viral infection in arthropods and the origins of plant viruses. IMPORTANCE: Although negevirus is phylogenetically related to plant virus, the evolutionary history of negevirus-host and its relationship with plant virus remain largely unknown. In this study, we used endogenous nege-like viral elements (ENVEs) as the molecular fossil records to investigate the history of nege-like viral infection in arthropod hosts and the evolution of two related plant virus families (Virgaviridae and Kitaviridae). Our results showed the infection of nege-like viruses for over 60 My during the arthropod evolution. ENVEs highly homologous to viral sequences in Virgaviridae and Kitaviridae were present in a wide range of arthropod genomes but were absent in plant genomes, indicating that plant viruses in these two families possibly evolved from the nege-like virus ancestor through cross-species horizontal virus transmission. Our findings provide a new perspective on the virus-host coevolution and the origins of plant viruses.

Active Heme Metabolism Suppresses Macrophage Phagocytosis via the TLR4/Type I IFN Signaling/CD36 in Uterine Endometrial Cancer.

BACKGROUND: Uterine endometrial cancer (UEC) is a common gynecological estrogen-dependent carcinoma, usually accompanied by intermenstrual bleeding. Active heme metabolism frequently plays an increasingly important role in many diseases, especially in cancers. Tumor-associated macrophages (TAMs) are the major population in the immune microenvironment of UEC. However, the roles of heme metabolisms in the crosstalk between UEC cells (UECCs) and macrophages are unclear. MATERIALS AND METHODS: In our study, by using TCGA database analysis, integration analysis of the protein-protein interaction (PPI) network and sample RNA transcriptome sequencing were done. The expression level of both heme-associated molecules and iron metabolism-related molecules were measured by quantitative real-time polymerase chain reaction. Heme level detection was done through dehydrohorseradish peroxidase assay. In addition to immunohistochemistry, phagocytosis assay of macrophages, immunofluorescence staining, intracellular ferrous iron staining, as well as enzyme-linked immune sorbent assay were performed. RESULTS: In the study, we verified that heme accumulation in UECCs is apparently higher than in endometrial epithelium cells. Low expression of succinate dehydrogenase B under the regulation of estrogen contributes to over-production of succinate and heme accumulation in UECC. More importantly, excessive heme in UECCs impaired macrophage phagocytosis by regulation of CD36. Mechanistically, this process is dependent on toll-like receptor (TLR4)/type I interferons alpha (IFN Iα) regulatory axis in macrophage. CONCLUSION: Collectively, these findings elucidate that active heme metabolism of UECCs directly decreases phagocytosis by controlling the secretion of TLR4-mediated IFN Iα and the expression of CD36, and further contributing to the immune escape of UEC.

The Protective Efficacy of a SARS-CoV-2 Vaccine Candidate B.1.351V against Several Variant Challenges in K18-hACE2 Mice.

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.1.351 variant inactivated vaccine candidate (B.1.351V) generated strong binding and neutralizing antibody responses in BALB/c mice against the B.1.351 virus and other SARS-CoV-2 variants after two doses within 28 days. Immunized K18-hACE2 mice also exhibited elevated levels of live virus-neutralizing antibodies against various SARS-CoV-2 viruses. Following infection with these viruses, K18-hACE2 mice displayed a stable body weight, a high survival rate, minimal virus copies in lung tissue, and no lung damage compared to the control group. These findings indicate that B.1.351V offered protection against infection with multiple SARS-CoV-2 variants in mice, providing insights for the development of a vaccine targeting SARS-CoV-2 VOCs for human use.

Alleviating effect of chlorogenic acid on oxidative damage caused by hydrogen peroxide in bovine intestinal epithelial cells.

Chlorogenic acid (CGA) is a polyphenol substance contained in many plants, which has good antioxidant activity. This experiment aimed to explore the protective effects of CGA on hydrogen peroxide(H2O2)-induced inflammatory response, apoptosis, and antioxidant capacity of bovine intestinal epithelial cells (BIECs-21) under oxidative stress and its mechanism. The results showed that compared with cells treated with H2O2 alone, CGA pretreatment could improve the viability of BIECs-21. Importantly, Chlorogenic acid pretreatment significantly reduced the formation of malondialdehyde (MDA), lowered reactive oxygen species (ROS) levels, and enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) (P<0.05). In addition, CGA can also improve the intestinal barrier by increasing the abundance of tight junction proteins claudin-1 and occuludin. Meanwhile, CGA can reduce the gene expression levels of pro-inflammatory factors Interleukin-6 (IL-6) and Interleukin-8 (IL-8), increase the expression of anti-inflammatory factor Interleukin-10 (IL-10), promote the expression of the nuclear factor-related factor 2 (Nrf2) signaling pathway, enhance cell antioxidant capacity, and inhibit Nuclear Factor Kappa B (NF-κB) the activation of the signaling pathway reducing the inflammatory response, thereby alleviating inflammation and oxidative stress damage.

Sonographic Cortical Development and Anomalies in the Fetus: A Systematic Review and Meta-Analysis.

The aim of this systematic review is to report the normal cortical development of different fetal cerebral fissures on ultrasound, describe associated anomalies in fetuses with cortical malformations, and evaluate the quality of published charts of cortical fissures. The inclusion criteria were studies reporting development, anomalies, and reference charts of fetal cortical structures on ultrasound. The outcomes observed were the timing of the appearance of different cortical fissures according to different gestational age windows, associated central nervous system (CNS) and extra-CNS anomalies detected at ultrasound in fetuses with cortical malformation, and rate of fetuses with isolated anomaly. Furthermore, we performed a critical evaluation of the published reference charts for cortical development on ultrasound. Random-effect meta-analyses of proportions were used to combine the data. Twenty-seven studies (6875 fetuses) were included. Sylvian fissure was visualized on ultrasound in 97.69% (95% CI 92.0-100) of cases at 18-19, 98.17% (95% CI 94.8-99.8) at 20-21, 98.94% (95% CI 97.0-99.9) at 22-23, and in all cases from 24 weeks of gestation. Parieto-occipital fissure was visualized in 81.56% (95% CI 48.4-99.3) of cases at 18-19, 96.59% (95% CI 83.2-99.8) at 20-21, 96.85% (95% CI 88.8-100) at 22-23, and in all cases from 24 weeks of gestation, while the corresponding figures for calcarine fissure were 37.27% (95% CI 0.5-89.6), 80.42% (95% CI 50.2-98.2), 89.18% (95% CI 74.0-98.2), and 96.02% (95% CI 96.9-100). Malformations of cortical development were diagnosed as an isolated finding at ultrasound in 6.21% (95% CI 2.9-10.9) of cases, while they were associated with additional CNS anomalies in 93.79% (95% CI 89.1-97.2) of cases. These findings highlight the need for large studies specifically looking at the timing of the appearance of the different brain sulci. Standardized algorithms for prenatal assessment of fetuses at high risk of malformations of cortical development are also warranted.

Reversible ON- and OFF-switch receptors Clec4G and Rab1A reveal the hormetic effects of a pectin polysaccharide in Aralia elata (Miq.) Seem.

BACKGROUND: Numerous studies indicate that natural polysaccharides have immune-enhancing effects as a host defense potentiator. Few reports are available on hormetic effects of natural polysaccharides, and the underlying mechanisms remain unclear. PURPOSE: AELP-B6 (arabinose- and galactose-rich pectin polysaccharide) from Aralia elata (Miq.) Seem was taken as a case study to clarify the potential mechanism of hormetic effects of natural polysaccharides. METHODS: The pharmacodynamic effect of AELP-B6 was verified by constructing the CTX-immunosuppressive mouse model. The hormetic effects were explored by TMT-labeled proteomics, energy metabolism analysis, flow cytometry and western blot. The core-affinity target of AELP-B6 was determined by pull down, nanoLC-nanoESI+-MS, CETSA, immunoblot and SPR assay. The RAW264.7Clec4G-RFP and RAW264.7Rab1A-RFP cell lines were simultaneously constructed to determine the affinity difference between AELP-B6 and targets by confocal laser scanning live-cell imaging. Antibody blocking assays were further used to verify the mechanism of hormetic effects. RESULTS: AELP-B6 at low and medium doses may maintain the structural integrity of thymus and spleen, increase the concentrations of TNF-α, IFN-γ, IL-3 and IL-8, and alleviate CTX-induced reduction of immune cell viability in vivo. Proteomics and energy metabolism analysis revealed that AELP-B6 regulate HIF-1α-mediated metabolic programming, causing Warburg effects in macrophages. AELP-B6 at low and medium doses promoted the release of intracellular immune factors, and driving M1-like polarization of macrophages. As a contrast, AELP-B6 at high dose enhanced the expression levels of apoptosis related proteins, indicating activation of the intrinsic apoptotic cascade. Two highly expressed transmembrane proteins in macrophages, Clec4G and Rab1A, were identified as the primary binding targets of AELP-B6 which co-localized with the cell membrane and directly impacted with immune cell activation and apoptosis. AELP-B6 exhibits affinity differences with Clec4G and Rab1A, which is the key to the hormetic effects. CONCLUSION: We observed hormesis of natural polysaccharide (AELP-B6) for the first time, and AELP-B6 mediates the hormetic effects through two dose-related targets. Low dose of AELP-B6 targets Clec4G, thereby driving the M1-like polarization via regulating NF-κB signaling pathway and HIF-1α-mediated metabolic programming, whereas high dose of AELP-B6 targets Rab1A, leading to mitochondria-dependent apoptosis.