Exploiting breakdown in nonhost effector-target interactions to boost host disease resistance.

Plants are resistant to most microbial species due to nonhost resistance (NHR), providing broad-spectrum and durable immunity. However, the molecular components contributing to NHR are poorly characterised. We address the question of whether failure of pathogen effectors to manipulate nonhost plants plays a critical role in NHR. RxLR (Arg-any amino acid-Leu-Arg) effectors from two oomycete pathogens, Phytophthora infestans and Hyaloperonospora arabidopsidis, enhanced pathogen infection when expressed in host plants (Nicotiana benthamiana and Arabidopsis, respectively) but the same effectors performed poorly in distantly related nonhost pathosystems. Putative target proteins in the host plant potato were identified for 64 P. infestans RxLR effectors using yeast 2-hybrid (Y2H) screens. Candidate orthologues of these target proteins in the distantly related non-host plant Arabidopsis were identified and screened using matrix Y2H for interaction with RxLR effectors from both P. infestans and H. arabidopsidis. Few P. infestans effector-target protein interactions were conserved from potato to candidate Arabidopsis target orthologues (cAtOrths). However, there was an enrichment of H. arabidopsidis RxLR effectors interacting with cAtOrths. We expressed the cAtOrth AtPUB33, which unlike its potato orthologue did not interact with P. infestans effector PiSFI3, in potato and Nicotiana benthamiana. Expression of AtPUB33 significantly reduced P. infestans colonization in both host plants. Our results provide evidence that failure of pathogen effectors to interact with and/or correctly manipulate target proteins in distantly related non-host plants contributes to NHR. Moreover, exploiting this breakdown in effector-nonhost target interaction, transferring effector target orthologues from non-host to host plants is a strategy to reduce disease.

A Bioinspired Copper-Pair Catalyst in Metal-Organic Frameworks for Molecular Dioxygen Activation and Aerobic Oxidative C-N Coupling.

Open Cu sites were loaded to the UiO-67 metal-organic framework (MOF) skeleton by introduction of flexible Cu-binding pyridylmethylamine (pyma) side chains to the biphenyldicarboxylate linkers. Distance between Cu centers in the MOF pores was tuned by controlling the density of metal-binding side chains. "Interacted" Cu-pair or "isolated" monomeric Cu sites were achieved with high and low (pyma)Cu side chain loading, respectively. Spectroscopic and theoretical studies indicate that "interacted" Cu pairs can effectively bind and activate molecular dioxygen to form Cu2O2 clusters, which showed high catalytic activity for aerobic oxidative C-N coupling. On the contrary, MOF catalyst bearing isolated monomeric Cu sites only showed modest catalytic activity. Enhancement in catalytic performance for the Cu-pair catalyst is attributed to the remote synergistic effect of the paired Cu site, which binds molecular dioxygen and cleaves the O═O bond in a collaborative manner. This work demonstrates that noncovalently interacted metal-pair sites can effectively activate inert small molecules and promote heterogeneous catalytic processes.

Steering CO2 Electroreduction Selectivity U-Turn to Ethylene by Cu-Si Bonded Interface.

Copper (Cu), with the advantage of producing a deep reduction product, is a unique catalyst for the electrochemical reduction of CO2 (CO2RR). Designing a Cu-based catalyst to trigger CO2RR to a multicarbon product and understanding the accurate structure-activity relationship for elucidating reaction mechanisms still remain a challenge. Herein, we demonstrate a rational design of a core-shell structured silica-copper catalyst (p-Cu@m-SiO2) through Cu-Si direct bonding for efficient and selective CO2RR. The Cu-Si interface fulfills the inversion in CO2RR product selectivity. The product ratio of C2H4/CH4 changes from 0.6 to 14.4 after silica modification, and the current density reaches a high of up to 450 mA cm-2. The kinetic isotopic effect, in situ attenuated total reflection Fourier-transform infrared spectra, and density functional theory were applied to elucidate the reaction mechanism. The SiO2 shell stabilizes the *H intermediate by forming Si-O-H and inhibits the hydrogen evolution reaction effectively. Moreover, the direct-bonded Cu-Si interface makes bare Cu sites with larger charge density. Such bare Cu sites and Si-O-H sites stabilized the *CHO and activated the *CO, promoting the coupling of *CHO and *CO intermediates to form C2H4. This work provides a promising strategy for designing Cu-based catalysts with high C2H4 catalytic activity.

Suppression of frequency-mixing effect for pm-level heterodyne interferometers based on "zero coupling" optical path length control.

Optical path length (OPL) noise resulting from stray light significantly constrains interferometry displacement measurements in the low-frequency band. This paper presents an analytical model considering the presence of stray light in heterodyne laser interferometers. Due to the cyclic nonlinear coupling effect, there will be some special OPLs of stray light, minimizing the frequency-mixing impact to zero. Consequently, we propose a noise suppression scheme that locks the OPL of stray light at the zero coupling point. Therefore, we significantly enhanced the interference displacement measurement noise within the low-frequency band. Experimental results show that the interferometer achieves a displacement noise level lower than 6 pm/Hz1/2 covering 1 mHz.

Efficacy and safety of potassium-competitive acid inhibitors in the treatment of gastroesophageal reflux: a systematic review and meta-analysis.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton-pump inhibitors (PPIs) are recommended as a first-line therapy to treat GERD. Recently, the potassium-competitive acid inhibitors have been increasingly in use in clinical practice. We aimed to evaluate the efficacy and safety of P-CABs in GERD. METHODS: We searched PubMed, the Cochrane Library, EMBASE and Web Of Science for publications regarding randomized controlled trials comparing potassium-competitive acid inhibitors to PPI monotherapy or Placebo with respect to efficacy and safety in GERD (until April 2023). The primary outcome was an absence or global symptom improvement and the incidence of adverse events in GERD. The quality of the included literature was assessed using the bias assessment tool recommended in the Cochrane Systematic Assessor's Handbook 5.1.0. We use RevMan 5.3 software for Meta-analysis, sensitivity analysis and publication bias analysis. RESULTS: Of the 991 screened studies, 14 studies including 4868 participants were analyzed. The ORs for the healing rates of GERD with P-CABs versus PPI/Placebo were 2.10 (95% confidence interval [CI] 1.53-2.88), additionally, 1.09 (95% CI 1.05-1.14), 1.03 (95% CI 1.00-1.06) and 1.03 (95% CI 0.99-1.06) in Weeks 2, 4, and 8, respectively. The effectiveness rate of the experimental group was significantly higher than that of the control group (RR 1.73; 95% CI 1.27-2.36). The overall OR of Incidence of adverse events with P-CABs versus PPI/Placebo was 1.08 (95% CI 0.88-1.12). Overall, the risk of bias was low to some concerns. Furthermore, sensitivity analyses confirmed the robustness of the study's conclusion. CONCLUSIONS: Our findings suggest that potassium-competitive acid inhibitors is non-inferior to PPIs as therapy for patients with GERD. The safety outcomes for potassium-competitive acid inhibitors are similar to those for PPIs.

Diagnostic and prognostic potential of long non-coding RNA NORAD in patients with acute deep vein thrombosis and its role in endothelial cell function.

BACKGROUND: Deep venous thrombosis (DVT) is the common clinical cardiovascular disease, and easily develops into post-thrombotic syndrome (PTS). The study aimed to examine the clinical value of long non-coding RNA NORAD gene in the development of DVT and PTS. In vitro, the underlying mechanism was explored. METHODS: Serum levels of lncRNA NORAD gene in 85 DVT cases and 85 healthy individuals were tested. The role of lncRNA NORAD gene in human umbilical vein endothelial cells (HUVECs) proliferation, migration and inflammation was examined. The candidate downstream target gene was predicted via bioinformatic analysis. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were done for the function annotation and pathway enrichment. RESULTS: LncRNA NORAD gene was at high expression in the serum of DVT patients, it can distinguish DVT patients from healthy controls with the area under the curve of 0.919. Elevated expression of lncRNA NORAD gene in PTS patients was detected, DVT cases with high expression of lncRNA NORAD gene were more susceptible to PTS. LncRNA NORAD gene knockdown promoted HUVECs' proliferation, migration while suppressing cell apoptosis and inflammation. MiR-93-5p served as a target of lncRNA NORAD gene, and its overexpression reversed the role of lncRNA NORAD gene in the biological function of HUVECs. The target genes of miR-93-5p were enriched in HIF-1 signaling, TGF-beta signaling and PI3K-Akt signaling, protein-protein interaction (PPI) network indicated STAT3, MAPK1 to be the key targets. CONCLUSIONS: Upregulation of expression of lncRNA NORAD gene was a potential diagnostic biomarker for DVT and related to the development of PTS. LncRNA NORAD/miR-93-5p axis was involved in the progress of DVT through regulating endothelial cell function.

Multielectron Redox-Bipolar Tetranitroporphyrin Macrocycle Cathode for High-Performance Zinc-Organic Batteries.

Bipolar organics fuse the merits of n/p-type redox reactions for better Zn-organic batteries (ZOBs), but face the capacity plafond due to low density of active units and single-electron reactions. Here we report multielectron redox-bipolar tetranitroporphyrin (TNP) with quadruple two-electron-accepting n-type nitro motifs and dual-electron-donating p-type amine moieties towards high-capacity-voltage ZOBs. TNP cathode initiates high-kinetics, hybrid anion-cation 10e- charge storage involving four nitro sites coordinating with Zn2+ ions at low potential and two amine species coupling with SO4 2- ions at high potential. Consequently, Zn||TNP battery harvests high capacity (338 mAh g-1), boosted average voltage (1.08 V), and outstanding energy density (365 Wh kg-1 TNP). Moreover, the extended π-conjugated TNP macrocycle achieves anti-dissolution in electrolytes, prolonging the battery life to 50,000 cycles at 10 A g-1 with 71.6 % capacity retention. This work expands the chemical landscape of multielectron redox-bipolar organics for state-of-the-art ZOBs.

A Dual Anion Chemistry-Based Superionic Glass Enabling Long-Cycling All-Solid-State Sodium-Ion Batteries.

Glassy Na-ion solid-state electrolytes (GNSSEs) are an important group of amorphous SSEs. However, the insufficient ionic conductivity of state-of-the-art GNSSEs at room temperature lessens their promise in the development of all-solid-state Na-ion batteries (ASSNIBs) with high energy density and improved safety. Here we report the discovery of a new sodium superionic glass, 0.5Na2 O2 -TaCl5 (NTOC), based on dual-anion sublattice of oxychlorides. The unique local structures with abundant bridging and non-bridging oxygen atoms contributes to a highly disordered Na-ion distribution as well as low Na+ migration barrier within NTOC, enabling an ultrahigh ionic conductivity of 4.62 mS cm-1 at 25 °C (more than 20 times higher than those of previously reported GNSSEs). Moreover, the excellent formability of glassy NTOC electrolyte and its high electrochemical oxidative stability ensure a favourable electrolyte-electrode interface, contributing to superior cycling stability of ASSNIBs for over 500 cycles at room temperature. The discovery of glassy NTOC electrolyte would reignite research enthusiasm in superionic glassy SSEs based on multi-anion chemistry.

A Universal Self-Propagating Synthesis of Aluminum-Based Oxyhalide Solid-State Electrolytes.

Inorganic solid-state electrolytes (SSEs) play a vital role in high-energy all-solid-state batteries (ASSBs). However, the current method of SSE preparation usually involves high-energy mechanical ball milling and/or a high-temperature annealing process, which is not suitable for practical application. Here, a facile strategy is developed to realize the scalable synthesis of cost-effective aluminum-based oxyhalide SSEs, which involves a self-propagating method by the exothermic reaction of the raw materials. This strategy enables the synthesis of various aluminum-based oxyhalide SSEs with tunable components and high ionic conductivities (over 10-3 S cm-1 at 25 °C) for different cations (Li+, Na+, Ag+). It is elucidated that the amorphous matrix, which mainly consists of various oxidized chloroaluminate species that provide numerous sites for smooth ion migration, is actually the key factor for the achieved high conductivities. Benefit from their easy synthesis, low cost, and low weight, the aluminum-based oxyhalide SSEs synthesized by our approach could further promote practical application of high-energy-density ASSBs.

Boosting CO2 Electroreduction over a Covalent Organic Framework in the Presence of Oxygen.

Herein, we propose an oxygen-containing species coordination strategy to boost CO2 electroreduction in the presence of O2. A two-dimensional (2D) conjugated metal-covalent organic framework (MCOF), denoted as NiPc-Salen(Co)2-COF that is composed of the Ni-phthalocyanine (NiPc) unit with well-defined Ni-N4-O sites and the salen(Co)2 moiety with binuclear Co-N2O2 sites, is developed and synthesized for enhancing the CO2RR under aerobic condition. In the presence of O2, one of the Co sites in the NiPc-Salen(Co)2-COF that coordinated with the intermediate of *OOH from ORR could decrease the energy barrier of the activation of CO2 molecules and stabilize the key intermediate *COOH of the CO2RR over the adjacent Co center. Besides, the oxygen species axially coordinated Ni-N4-O sites can favor in reducing the energy barrier of the intermediate *COOH formation for the CO2RR. Thus, NiPc-Salen(Co)2-COF exhibits high oxygen-tolerant CO2RR performance and achieves outstanding CO Faradaic efficiency (FECO) of 97.2 % at -1.0 V vs. the reversible hydrogen electrode (RHE) and a high CO partial current density of 40.3 mA cm-2 at -1.1 V in the presence of 0.5 % O2, which is superior to that in pure CO2 feed gas (FECO=94.8 %, jCO=19.9 mA cm-2). Notably, the NiPc-Salen(Co)2-COF achieves an industrial-level current density of 128.3 mA cm-2 in the flow-cell reactor with 0.5 % O2 at -0.8 V, which is higher than that in pure CO2 atmosphere (jCO=104.8 mA cm-2). It is worth noting that an excellent FECO of 86.8 % is still achieved in the presence of 5 % O2 at -1.0 V. This work provides an effective strategy to enable the CO2RR under O2 atmosphere by utilizing the *OOH intermediates of ORR to boost CO2 electroreduction.

Photocoupled Electroreduction of CO2 over Photosensitizer-Decorated Covalent Organic Frameworks.

Introducing an external visible-light field would be a promising strategy to improve the activity of the electrocatalytic CO2 reduction reaction (CO2RR), but it still remains a challenge due to the short excited-state lifetime of active sites. Herein, Ru(bpy)3Cl2 struts as powerful photosensitive donors were immobilized into the backbones of Co-porphyrin-based covalent organic frameworks (named Co-Bpy-COF-Rux, x is the molar ratio of Ru and Co species, x = 1/2 and 2/3) via coordination bonds, for the photo-coupled CO2RR to produce CO. The optimal Co-Bpy-COF-Ru1/2 displays a high CO Faradaic efficiency of 96.7% at -0.7 V vs reversible hydrogen electrode (RHE) and a CO partial current density of 16.27 mA cm-2 at -1.1 V vs RHE under the assistance of light, both of which were far surpassing the values observed in the dark. The significantly enhanced activity is mainly attributed to the incorporation of a Ru(bpy)3Cl2 donor with long excited-state lifetime and concomitantly giant built-in electric field in Co-Bpy-COF-Ru1/2, which efficiently accelerate the photo-induced electron transfer from Ru(bpy)3Cl2 to the cobalt-porphyrin under the external light. Thus, the cobalt-porphyrin active sites have a longer excited-state lifetime to lower the rate-determining steps' energy occurring during the actual photo-coupled electrocatalytic CO2RR process. This is the first work of porphyrin-based COFs for photo-coupled CO2RR, opening a new frontier for the construction of efficient photo-coupled electrocatalysts.

Tandem Photocatalysis of CO2 to C2H4 via a Synergistic Rhenium-(I) Bipyridine/Copper-Porphyrinic Triazine Framework.

The photocatalytic conversion of CO2 into C2+ products such as ethylene is a promising path toward the carbon neutral goal but remains a big challenge due to the high activation barrier for CO2 and similar reduction potentials of many possible multi-electron-transfer products. Herein, an effective tandem photocatalysis strategy has been developed to support conversion of CO2 to ethylene by construction of the synergistic dual sites in rhenium-(I) bipyridine fac-[ReI(bpy)(CO)3Cl] (Re-bpy) and copper-porphyrinic triazine framework [PTF(Cu)]. With these two catalysts, a large amount of ethylene can be produced at a rate of 73.2 µmol g-1 h-1 under visible light irradiation. However, ethylene cannot be obtained from CO2 by use of either component of the Re-bpy or PTF(Cu) catalysts alone; with a single catalyst, only monocarbon product CO is produced under similar conditions. In the tandem photocatalytic system, the CO generated at the Re-bpy sites is adsorbed by the nearby Cu single sites in PTF(Cu), and this is followed by a synergistic C-C coupling process which ultimately produces ethylene. Density functional theory calculations demonstrate that the coupling process between PTF(Cu)-*CO and Re-bpy-*CO to form the key intermediate Re-bpy-*CO-*CO-PTF(Cu) is vital to the C2H4 production. This work provides a new pathway for the design of efficient photocatalysts for photoconversion of CO2 to C2 products via a tandem process driven by visible light under mild conditions.

Superionic Conducting Halide Frameworks Enabled by Interface-Bonded Halides.

The revival of ternary halides Li-M-X (M = Y, In, Zr, etc.; X = F, Cl, Br) as solid-state electrolytes (SSEs) shows promise in realizing practical solid-state batteries due to their direct compatibility toward high-voltage cathodes and favorable room-temperature ionic conductivities. Most of the reported superionic halide SSEs have a structural pattern of [MCl6]x- octahedra and generate a tetrahedron-assisted Li+ ion diffusion pathway. Here, we report a new class of zeolite-like halide frameworks, SmCl3, for example, in which 1-dimensional channels are enclosed by [SmCl9]6- tricapped trigonal prisms to provide a short jumping distance of 2.08 Å between two octahedra for Li+ ion hopping. The fast Li+ diffusion along the channels is verified through ab initio molecular dynamics simulations. Similar to zeolites, the SmCl3 framework can be grafted with halide species to obtain mobile ions without altering the base structure, achieving an ionic conductivity over 10-4 S cm-1 at 30 °C with LiCl as the adsorbent. Moreover, the universality of the interface-bonding behavior and ionic diffusion in a class of framework materials is demonstrated. It is suggested that the ionic conductivity of the MCl3/halide composite (M = La-Gd) is likely in correlation with the ionic conductivity of the grafted halide species, interfacial bonding, and framework composition/dimensions. This work reveals a potential class of halide structures for superionic conductors and opens up a new frontier for constructing zeolite-like frameworks in halide-based materials, which will promote the innovation of superionic conductor design and contribute to a broader selection of halide SSEs.

PoDPBT, a BAHD acyltransferase, catalyses the benzoylation in paeoniflorin biosynthesis in Paeonia ostii.

PoDPBT, an O-benzoyltransferase belonging to the BAHD family, can catalyze the benzoylation of 8-debenzoylpaeoniflorin to paeoniflorin. PoDPBT is the first enzyme demonstrated to be involved in the modification stage of paeoniflorin biosynthesis. DFGGG, a new DFGWG-like motif, was revealed in the BAHD family. The transcriptome database provides a resource for further investigation of other enzyme genes involved in paeoniflorin biosynthesis.

Aberration-compensated supercritical lens for sub-diffractive focusing within 20° field of view.

The supercritical lens has shown a remarkable capability of achieving far-field sub-diffraction limited focusing through elaborating a modulated interference effect. Benefiting from the relative high energy utilization efficiency and weak sidelobe properties, the supercritical lens holds significant advantage in a series of application scenarios. However, all of the demonstrated supercritical lenses mainly work in the on-axis illumination condition, so the off-axis aberration effect will severely deteriorate its sub-diffraction limit focusing capability for the illuminating beam with an oblique angle. In this work, an aberration-compensated supercritical lens with single-layer configuration is proposed and experimentally demonstrated. Such a single-layer supercritical lens consists of multilevel phase configurations patterned with the two-photon polymerization lithography technique. The simulation and experimental recorded results show that the aberration-compensated supercritical lens with a numerical aperture value of 0.63 could achieve a far-field sub-diffraction limited focusing property within 20° field of view at a wavelength of λ = 633 nm. This monochromatic aberration-compensated supercritical lens with single-layer configuration indicates excellent potential in the development of laser scanning ultrahigh optical storage and label free super-resolution imaging.

Tumor lesion detection in patients with cervical cancer by indocyanine green near-infrared imaging.

PURPOSE: To investigate the feasibility and accuracy of near-infrared fluorescence (NIRF) imaging for detecting the extent of tumor invasion in cervical cancer using indocyanine green (ICG). METHODS: We enrolled 51 patients who were diagnosed with cervical cancer with FIGO stage IB1-IIA2 disease. Patients were administered indocyanine green (ICG) at a dose of 5 mg/kg 24 h prior to surgery. A customized near-infrared fluorescence (NIRF) imaging system was used to identify the extent of tumor invasion when radical hysterectomy specimens were harvested. The relationship between tumor fluorescence intensity and clinicopathological characteristics was analyzed. RESULTS: Of the 51 enrolled patients, 3 patients did not have residual tumors after cervical conization, and tumor lesions were identified by NIRF imaging in all the remaining 48 patients. The results of NIRF imaging were in agreement with the postoperative pathological findings in 95.8% of the patients with stromal invasion, 100% of those with surgical margin invasion, 100% of those with parametrial tumor involvement, and 100% of patients with uterine corpus invasion. The mean signal-to-background ratio (SBR) of the cervical tumors was 2.91 ± 1.64, and the SBR was independent of clinicopathological characteristics. Fluorescence microscopy confirmed that ICG fluorescence was present in the tumor nests. CONCLUSIONS: NIRF imaging enables objective, accurate, and safe identification of tumor invasion during cervical cancer surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04224467.

Characterization of host-effector transcription dynamics during pathogen infection in engineered late blight resistant potato.

Phytophthora infestans, the etiologic agent of late blight, is a threat to potato production in areas with high humidity during the growing season. The oomycete pathogen is hemi-biotrophic, it establishes infection on living plant cells and then spreads, kills, and feeds off the necrotized plant tissue material. The interaction between host and pathogen is complex with dynamic pathogen RXLR effectors and potato NB-LRR resistance proteins actively competing for dominance and survival. Late blight protection was brought to several cultivars of potato through insertion of the wild potato (Solanum venturii) NB-LRR resistance gene Rpi-vnt1.1. We have established that the late blight protection trait, mediated by Rpi-vnt1.1, is effective despite low expression of RNA. The RNA expression dynamics of Rpi-vnt1.1 and the cognate pathogen RXLR effector, Avr-vnt1, were evaluated following spray inoculation with up to five different contemporary late blight isolates from North America and South America. Following inoculations, RXLR effector transcript profiles provided insight into interaction compatibility in relation to markers of the late blight hemi-biotrophic lifecycle.

Interaction of beta-glucans with gut microbiota: Dietary origins, structures, degradation, metabolism, and beneficial function.

Beta-glucan (BG), a polysaccharide comprised of interfacing glucose monomers joined via beta-glycosidic linkages, can be defined as a type of dietary fiber with high specificity based on its interaction with the gut microbiota. It can induce similar interindividual microbiota responses, thereby having beneficial effects on the human body. In this paper, we review the four main sources of BG (cereals, fungi, algae, and bacteria) and their differences in structure and content. The interaction of BG with gut microbiota and the resulting health effects have been highlighted, including immune enhancement, regulation of serum cholesterol and insulin levels, alleviation of obesity and improvement of cognitive disorders. Finally, the application of BG in food products and its beneficial effects on the gut microbiota of consumers were discussed. Although some of the mechanisms of action remain unclear, revealing the beneficial functions of BG from the perspective of gut microbiota can help provide theoretical support for the development of diets that target the regulation of microbiota.

Gut microbiota and anti-aging: Focusing on spermidine.

The human gut microbiota plays numerous roles in regulating host growth, the immune system, and metabolism. Age-related changes in the gut environment lead to chronic inflammation, metabolic dysfunction, and illness, which in turn affect aging and increase the risk of neurodegenerative disorders. Local immunity is also affected by changes in the gut environment. Polyamines are crucial for cell development, proliferation, and tissue regeneration. They regulate enzyme activity, bind to and stabilize DNA and RNA, have antioxidative properties, and are necessary for the control of translation. All living organisms contain the natural polyamine spermidine, which has anti-inflammatory and antioxidant properties. It can regulate protein expression, prolong life, and improve mitochondrial metabolic activity and respiration. Spermidine levels experience an age-related decrease, and the development of age-related diseases is correlated with decreased endogenous spermidine concentrations. As more than just a consequence, this review explores the connection between polyamine metabolism and aging and identifies advantageous bacteria for anti-aging and metabolites they produce. Further research is being conducted on probiotics and prebiotics that support the uptake and ingestion of spermidine from food extracts or stimulate the production of polyamines by gut microbiota. This provides a successful strategy to increase spermidine levels.

Rationality of FIGO 2018 IIIC restaging of cervical cancer according to local tumor size: A cohort study.

INTRODUCTION: FIGO 2018 IIIC remains controversial for the heterogeneity of its prognoses. To ensure a better management of cervical cancer patients in Stage IIIC, a revision of the FIGO IIIC version classification is required according to local tumor size. MATERIAL AND METHODS: We retrospectively enrolled cervical cancer patients of FIGO 2018 Stages I-IIIC who had undergone radical surgery or chemoradiotherapy. Based on the tumor factors from the Tumor Node Metastasis staging system, IIIC cases were divided into IIIC-T1, IIIC-T2a, IIIC-T2b, and IIIC-(T3a+T3b). Oncologcial outcomes of all stages were compared. RESULTS: A total of 63 926 cervical cancer cases were identified, among which 9452 fulfilled the inclusion criteria and were included in this study. Kaplan-Meier pairwise analysis showed that: the oncology outcomes of I and IIA were significantly better than of IIB, IIIA+IIIB, and IIIC; the oncology outcome of IIIC-(T1-T2b) was significantly better than of IIIA+IIIB and IIIC-(T3a+T3b); no significant difference was noted between IIB and IIIC-(T1-T2b), or IIIC-(T3a+T3b) and IIIA+IIIB. Multivariate analysis indicated that, compared with IIIC-T1, Stages T2a, T2b, IIIA+IIIB and IIIC-(T3a+T3b) were associated with a higher risk of death and recurrence/death. There was no significant difference in the risk of death or recurrence/death between patients with IIIC-(T1-T2b) and IIB. Also, compared with IIB, IIIC-(T3a+T3b) was associated with a higher risk of death and recurrence/death. No significant differences in the risk of death and recurrence/death were noted between IIIC-(T3a+T3b) and IIIA+IIIB. CONCLUSIONS: In terms of oncology outcomes of the study, FIGO 2018 Stage IIIC of cervical cancer is unreasonable. Stages IIIC-T1, T2a, and T2b may be integrated as IIC, and it might be unnecessary for T3a/T3b cases to be subdivided by lymph node status.