The Natural Product Secoemestrin C Inhibits Colorectal Cancer Stem Cells via p38-S100A8 Feed-Forward Regulatory Loop.

Cancer stem cells (CSCs) are closely associated with tumor initiation, metastasis, chemoresistance, and recurrence, which represent some of the primary obstacles to cancer treatment. Targeting CSCs has become an important therapeutic approach to cancer care. Secoemestrin C (Sec C) is a natural compound with strong anti-tumor activity and low toxicity. Here, we report that Sec C effectively inhibited colorectal CSCs and non-CSCs concurrently, mainly by inhibiting proliferation, self-renewal, metastasis, and drug resistance. Mechanistically, RNA-seq analysis showed that the pro-inflammation pathway of the IL17 axis was enriched, and its effector S100A8 was dramatically decreased in Sec C-treated cells, whose roles in the stemness of CSCs have not been fully clarified. We found that the overexpression of S100A8 hindered the anti-CSCs effect of Sec C, and S100A8 deficiency attenuated the stemness traits of CSCs to enhance the Sec C killing activity on them. Meanwhile, the p38 signal pathway, belonging to the IL17 downstream axis, can also mediate CSCs and counter with Sec C. Notably, we found that S100A8 upregulation increased the p38 protein level, and p38, in turn, promoted S100A8 expression. This indicated that p38 may have a mutual feedback loop with S100A8. Our study discovered that Sec C was a powerful anti-colorectal CSC agent, and that the positive feedback loop of p38-S100A8 mediated Sec C activity. This showed that Sec C could act as a promising clinical candidate in colorectal cancer treatment, and S100A8 could be a prospective drug target.

Neofunctionalization of an OMT cluster dominates polymethoxyflavone biosynthesis associated with the domestication of citrus.

Polymethoxyflavones (PMFs) are a class of abundant specialized metabolites with remarkable anticancer properties in citrus. Multiple methoxy groups in PMFs are derived from methylation modification catalyzed by a series of hydroxylases and O-methyltransferases (OMTs). However, the specific OMTs that catalyze the systematic O-methylation of hydroxyflavones remain largely unknown. Here, we report that PMFs are highly accumulated in wild mandarins and mandarin-derived accessions, while undetectable in early-diverging citrus species and related species. Our results demonstrated that three homologous genes, CreOMT3, CreOMT4, and CreOMT5, are crucial for PMF biosynthesis in citrus, and their encoded methyltransferases exhibit multisite O-methylation activities for hydroxyflavones, producing seven PMFs in vitro and in vivo. Comparative genomic and syntenic analyses indicated that the tandem CreOMT3, CreOMT4, and CreOMT5 may be duplicated from CreOMT6 and contributes to the genetic basis of PMF biosynthesis in the mandarin group through neofunctionalization. We also demonstrated that N17 in CreOMT4 is an essential amino acid residue for C3-, C5-, C6-, and C3'-O-methylation activity and provided a rationale for the functional deficiency of OMT6 to produce PMFs in early-diverging citrus and some domesticated citrus species. A 1,041-bp deletion in the CreOMT4 promoter, which is found in most modern cultivated mandarins, has reduced the PMF content relative to that in wild and early-admixture mandarins. This study provides a framework for reconstructing PMF biosynthetic pathways, which may facilitate the breeding of citrus fruits with enhanced health benefits.

Juice Vesicles Bioreactors Technology for Constructing Advanced Carbon-Based Energy Storage.

The construction of high-quality carbon-based energy materials through biotechnology has always been an eager goal of the scientific community. Herein, juice vesicles bioreactors (JVBs) bio-technology based on hesperidium (e.g., pomelo, waxberry, oranges) is first reported for preparation of carbon-based composites with controllable components, adjustable morphologies, and sizes. JVBs serve as miniature reaction vessels that enable sophisticated confined chemical reactions to take place, ultimately resulting in the formations of complex carbon composites. The newly developed approach is highly versatile and can be compatible with a wide range of materials including metals, alloys, and metal compounds. The growth and self-assembly mechanisms of carbon composites via JVBs are explained. For illustration, NiCo alloy nanoparticles are successfully in situ implanted into pomelo vesicles crosslinked carbon (PCC) by JVBs, and their applications as sulfur/carbon cathodes for lithium-sulfur batteries are explored. The well-designed PCC/NiCo-S electrode exhibits superior high-rate properties and enhanced long-term stability. Synergistic reinforcement mechanisms on transportation of ions/electrons of interface reactions and catalytic conversion of lithium polysulfides arising from metal alloy and carbon architecture are proposed with the aid of DFT calculations. The research provides a novel biosynthetic route to rational design and fabrication of carbon composites for advanced energy storage.

Multiomics integrated with sensory evaluations to identify characteristic aromas and key genes in a novel brown navel orange (Citrus sinensis).

'Zong Cheng' navel orange (ZC) is a brown mutant of Lane Late navel orange (LL) and emits a more pleasant odor than that of LL. However, the key volatile compound of this aroma and underlying mechanism remains unclear. In this study, sensory evaluations and volatile profiling were performed throughout fruit development to identify significant differences in sensory perception and metabolites between LL and ZC. It revealed that the sesquiterpene content varied significantly between ZC and LL. Based on aroma extract dilution and gas chromatography-olfactometry analyses, the volatile compound leading to the background aroma of LL and ZC is d-limonene, the orange note in LL was mainly attributed to octanal, whilst valencene, ß-myrcene, and (E)-ß-ocimene presented balsamic, sweet, and herb notes in ZC. Furthermore, Cs5g12900 and six potential transcription factors were identified as responsible for valencene accumulation in ZC, which is important for enhancing the aroma of ZC.

Plasma Technology for Advanced Electrochemical Energy Storage.

"Carbon Peak and Carbon Neutrality" is an important strategic goal for the sustainable development of human society. Typically, a key means to achieve these goals is through electrochemical energy storage technologies and materials. In this context, the rational synthesis and modification of battery materials through new technologies play critical roles. Plasma technology, based on the principles of free radical chemistry, is considered a promising alternative for the construction of advanced battery materials due to its inherent advantages such as superior versatility, high reactivity, excellent conformal properties, low consumption and environmental friendliness. In this perspective paper, we discuss the working principle of plasma and its applied research on battery materials based on plasma conversion, deposition, etching, doping, etc. Furthermore, the new application directions of multiphase plasma associated with solid, liquid and gas sources are proposed and their application examples for batteries (e. g. lithium-ion batteries, lithium-sulfur batteries, zinc-air batteries) are given. Finally, the current challenges and future development trends of plasma technology are briefly summarized to provide guidance for the next generation of energy technologies.

Low-Dose Versus Standard-Dose Alteplase in Bridging Therapy for Large Vessel Stroke: A Systematic Review and Meta-Analysis.

INTRODUCTION The efficacy and safety of low- and standard-dose alteplase for acute ischemic stroke (AIS) have not been consistently compared in previous studies. Nevertheless, the distinctions in the effects of low- and standard-dose alteplase, particularly within the context of bridging therapy (BT) for large vessel occlusion (LVO), warrant further exploration. This study compared clinical outcomes between BT with low- and standard-dose alteplase in patients with LVO-related AIS. METHODS We performed a search for randomized controlled trials and prospective or retrospective cohort studies investigating the clinical outcomes of BT in AIS in the PubMed, Embase, and Cochrane Library databases from inception to November 2022. The outcomes of interest were 90-day functional independence, successful recanalization, symptomatic intracerebral hemorrhage (sICH) and mortality; these outcomes were compared between patients who received BT with low- (primarily 0.6 mg/kg) and standard-dose alteplase (0.9 mg/kg). We used the standard-dose group as the reference and calculated the odds ratio (OR) and its 95% confidence interval (CI) from the raw numbers. Meta-analysis and ethnicity-based subgroup analysis (Asian and non-Asian) were performed. RESULTS Five observational studies, published after 2017 and including 408 patients, were included. The meta-analysis results demonstrated that compared with BT with standard-dose alteplase, BT with low-dose alteplase did not improve 90-day functional independence (odds ratio, [OR] 1.02; 95% confidence interval [CI], 0.58-1.80). Nevertheless, BT with low-dose alteplase was associated with a comparable successful recanalization rate (OR, 1.35; 95% CI, 0.68-2.67) and similar sICH incidence (OR 0.36; 95% CI, 0.10-1.36), and mortality (OR, 0.64; 95% CI, 0.27-1.54) compared with BT with standard-dose alteplase; however, the above three results were nonsignificant. In the ethnicity-based subgroup analyses, no differences were noted between Asian and non-Asian participants. CONCLUSIONS In patients with LVO-related AIS, BT with low- or standard-dose alteplase may provide similar efficacy, with no significant differences in sICH incidence and mortality. Additional well-designed prospective studies are required to confirm this result.

Unexpected Noremestrin with a Sulfur-Bearing 15-Membered Macrocyclic Lactone from Emericella sp. 1454.

Two previous unreported epipolythiodioxopiperazines of the emestrin family, namely, noremestrin A (1) and secoemestrin E (2), were successfully isolated from the fungal source Emericella sp. 1454. Employing comprehensive spectroscopic techniques, such as high-resolution electrospray ionization mass spectrometry, infrared, and nuclear magnetic resonance (NMR), along with NMR and electronic circular dichroism calculations, the chemical structures of compounds 1 and 2 were elucidated. Particularly noteworthy is the distinctive nature of noremestrin A, representing the inaugural instance of a noremestrin variant incorporating a sulfur-bearing 15-membered macrocyclic lactone moiety. Compounds 1 and 2 exhibited weak cytotoxic activities against the human chronic myelocytic leukemia cell lines MEG-01 and K562.

A prospective reappraisal of motor outcome prediction in patients with acute stroke by using atlas-based diffusion tensor imaging biomarkers.

BACKGROUND: Diffusion tensor imaging (DTI) biomarkers can be used to quantify microstructural changes in the cerebral white matter (WM) following injury. OBJECTIVES: This prospective single-center study aimed to evaluate whether atlas-based DTI-derived metrics obtained within 1 week after stroke can predict the motor outcome at 3 months. METHODS: Forty patients with small acute stroke (2-7 days after onset) involving the corticospinal tract were included. Each patient underwent magnetic resonance imaging (MRI) within 1 week and at 3 months after stroke, and the changes based on DTI-derived metrics were compared by performing WM tract atlas-based quantitative analysis. RESULTS: A total of 40 patients were included, with median age 63.5 years and a majority of males (72.5%). Patients were classified into good-prognosis group (mRS 0-2, n = 27) and poor-prognosis group (mRS 3-5, n = 13) by outcome. The median (25th-75th percentile) of MD (0.7 (0.6-0.7) vs. 0.7 (0.7-0.8); p = 0.049) and AD (0.6 (0.5, 0.7) vs. 0.7 (0.6, 0.8); p = 0.023) ratios within 1 week were significantly lower in the poor-prognosis group compared to the good-prognosis group. The ROC curve of the combined DTI-derived metrics model showed comparable Youden index (65.5% vs. 58.4%-65.4%) and higher specificity (96.3% vs. 69.2%-88.5%) compared to clinical indexes. The area under the ROC curve of the combined DTI-derived metrics model is comparable to those of the clinical indexes (all p > 0.1) and higher than those of the individual DTI-derived metrics parameters. CONCLUSIONS: Atlas-based DTI-derived metrics at acute stage provide objective information for prognosis prediction of patients with ischemic or lacunar stroke.

Hyphae Carbon Coupled with Gel Composite Assembly for Construction of Advanced Carbon/Sulfur Cathodes for Lithium-Sulfur Batteries.

The design and fabrication of novel carbon hosts with high conductivity, accelerated electrochemical catalytic activities, and superior physical/chemical confinement on sulfur and its reaction intermediates polysulfides are essential for the construction of high-performance C/S cathodes for lithium-sulfur batteries (LSBs). In this work, a novel biofermentation coupled gel composite assembly technology is developed to prepare cross-linked carbon composite hosts consisting of conductive Rhizopus hyphae carbon fiber (RHCF) skeleton and lamellar sodium alginate carbon (SAC) uniformly implanted with polarized nanoparticles (V2 O3 , Ag, Co, etc.) with diameters of several nanometers. Impressively, the RHCF/SAC/V2 O3 composites exhibit enhanced physical/chemical adsorption of polysulfides due to the synergistic effect between hierarchical pore structures, heteroatoms (N, P) doping, and polar V2 O3 generation. Additionally, the catalytic conversion kinetics of cathodes are effectively improved by regulating the 3D carbon structure and optimizing the V2 O3 catalyst. Consequently, the LSBs assembled with RHCF/SAC/V2 O3 -S cathode show exceptional cycle stability (capacity retention rate of 94.0% after 200 cycles at 0.1 C) and excellent rate performance (specific capacity of 578 mA h g-1 at 5 C). This work opens a new door for the fabrication of hyphae carbon composites via fermentation for electrochemical energy storage.

Dual-level clustering ensemble algorithm with three consensus strategies.

Clustering ensemble (CE), renowned for its robust and potent consensus capability, has garnered significant attention from scholars in recent years and has achieved numerous noteworthy breakthroughs. Nevertheless, three key issues persist: (1) the majority of CE selection strategies rely on preset parameters or empirical knowledge as a premise, lacking adaptive selectivity; (2) the construction of co-association matrix is excessively one-sided; (3) the CE method lacks a more macro perspective to reconcile the conflicts among different consensus results. To address these aforementioned problems, a dual-level clustering ensemble algorithm with three consensus strategies is proposed. Firstly, a backward clustering ensemble selection framework is devised, and its built-in selection strategy can adaptively eliminate redundant members. Then, at the base clustering consensus level, taking into account the interplay between actual spatial location information and the co-occurrence frequency, two modified relation matrices are reconstructed, resulting in the development of two consensus methods with different modes. Additionally, at the CE consensus level with a broader perspective, an adjustable Dempster-Shafer evidence theory is developed as the third consensus method in present algorithm to dynamically fuse multiple ensemble results. Experimental results demonstrate that compared to seven other state-of-the-art and typical CE algorithms, the proposed algorithm exhibits exceptional consensus ability and robustness.

An Advanced Gel Polymer Electrolyte for Solid-State Lithium Metal Batteries.

All-solid-state lithium metal batteries (LMBs) are regarded as one of the most viable energy storage devices and their comprehensive properties are mainly controlled by solid electrolytes and interface compatibility. This work proposes an advanced poly(vinylidene fluoride-hexafluoropropylene) based gel polymer electrolyte (AP-GPEs) via functional superposition strategy, which involves incorporating butyl acrylate and polyethylene glycol diacrylate as elastic optimization framework, triethyl phosphate and fluoroethylene carbonate as flameproof liquid plasticizers, and Li7 La3 Zr2 O12 nanowires (LLZO-w) as ion-conductive fillers, endowing the designed AP-GPEs/LLZO-w membrane with high mechanical strength, excellent flexibility, low flammability, low activation energy (0.137 eV), and improved ionic conductivity (0.42 × 10-3 S cm-1 at 20 °C) due to continuous ionic transport pathways. Additionally, the AP-GPEs/LLZO-w membrane shows good safety and chemical/electrochemical compatibility with the lithium anode, owing to the synergistic effect of LLZO-w filler, flexible frameworks, and flame retardants. Consequently, the LiFePO4 /Li batteries assembled with AP-GPEs/LLZO-w electrolyte exhibit enhanced cycling performance (87.3% capacity retention after 600 cycles at 1 C) and notable high-rate capacity (93.3 mAh g-1 at 5 C). This work proposes a novel functional superposition strategy for the synthesis of high-performance comprehensive GPEs for LMBs.

Three new isocoumarin analogues from an endolichenic fungus Aspergillus flavus CPCC 400810.

Five isocoumarin derivatives including three new compounds, aspermarolides A-C (1-3), and two known analogues, 8-methoxyldiaporthin (4) and diaporthin (5) were obtained from the culture extract of Aspergillus flavus CPCC 400810. The structures of these compounds were elucidated by spectroscopic methods. The double bond geometry of 1 and 2 were assigned by the coupling constants. The absolute configuration of 3 was determined by electronic circular dichroism experiment. All compounds showed no cytotoxic activities against the two human cancer cells HepG2 and Hela.

PVDF-HFP/PAN/PDA@LLZTO Composite Solid Electrolyte Enabling Reinforced Safety and Outstanding Low-Temperature Performance for Quasi-Solid-State Lithium Metal Batteries.

Lithium-ion batteries (LIBs) have achieved a triumph in the market of portable electronic devices since their commercialization in the 1990s due to their high energy density. However, safety issue originating from the flammable, volatile, and toxic organic liquid electrolytes remains a long-standing problem to be solved. Alternatively, composite solid electrolytes (CSEs) have gradually become one of the most promising candidates due to their higher safety and stable electrochemical performance. However, the uniform dispersity of ceramic filler within the polymer matrix remains to be addressed. Generally, all-solid-state lithium metal batteries without any liquid components suffer from poor interfacial contact and low ionic conductivity, which seriously affect the electrochemical performance. Here we report a CSE consisting of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), polydopamine (PDA) coated Li6.4La3Zr1.4Ta0.6O12 (LLZTO) (denoted as PDA@LLZTO) microfiller, polyacrylonitrile (PAN), and poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP). Introducing only 4 µL of liquid electrolyte at the electrode|electrolyte interface, the CSE-based cells exhibit high ionic conductivity (0.4 × 10-3 S cm-1 at 25 °C), superior cycle stability, and excellent thermal stability. Even under low temperatures, the impressive electrochemical performance (78.8% of capacity retention after 400 cycles at 1 C, 0 °C, and decent capacities delivered even at low temperature of -20 °C) highlights the potential of such quasi-solid-state lithium metal batteries as a viable solution for the next-generation high-performance lithium metal batteries.

Correlation between perioperative dexmedetomidine administration and postoperative acute kidney injury in hypertensive patients undergoing non-cardiac surgery.

Background: Previous studies have suggested that dexmedetomidine may have a protective effect on renal function. However, it is currently unclear whether perioperative dexmedetomidine administration is associated with postoperative acute kidney injury (AKI) incidence risk in hypertensive patients undergoing non-cardiac surgery. Methods: This investigation was a retrospective cohort study. Hypertensive patients undergoing non-cardiac surgery in Third Xiangya Hospital of Central South University from June 2018 to December 2019 were included. The relevant data were extracted through electronic cases. The univariable analysis identified demographic, preoperative laboratory, and intraoperative factors associated with acute kidney injury. Multivariable stepwise logistic regression was used to assess the association between perioperative dexmedetomidine administration and postoperative acute kidney injury after adjusting for interference factors. In addition, we further performed sensitivity analyses in four subgroups to further validate the robustness of the results. Results: A total of 5769 patients were included in this study, with a 7.66% incidence of postoperative acute kidney injury. The incidence of postoperative acute kidney injury was lower in the dexmedetomidine-administered group than in the control group (4.12% vs. 8.06%, p < 0.001). In the multivariable stepwise logistic regression analysis, perioperative dexmedetomidine administration significantly reduced the risk of postoperative acute kidney injury after adjusting for interference factors [odds ratio (OR) = 0.56, 95% confidence interval (CI): 0.36-0.87, p = 0.010]. In addition, sensitivity analysis in four subgroups indicated parallel findings: i) eGRF <90 mL/min·1.73/m2 subgroup (OR = 0.40, 95% CI: 0.19-0.84, p = 0.016), ii) intraoperative blood loss <1000 mL subgroup (OR = 0.58, 95% CI: 0.36-0.94, p = 0.025), iii) non-diabetes subgroup (OR = 0.51, 95% CI: 0.29-0.89, p = 0.018), and iv) older subgroup (OR = 0.55, 95% CI: 0.32-0.93, p = 0.027). Conclusion: In conclusion, our study suggests that perioperative dexmedetomidine administration is associated with lower risk and less severity of postoperative acute kidney injury in hypertensive individuals undergoing non-cardiac surgery. Therefore, future large-scale RCT studies are necessary to validate this benefit.

Solid-State Electrolytes in Lithium-Sulfur Batteries: Latest Progresses and Prospects.

Solid-state lithium-sulfur batteries (SSLSBs) have attracted tremendous research interest due to their large theoretical energy density and high safety, which are highly important indicators for the development of next-generation energy storage devices. Particularly, safety and "shuttle effect" issues originating from volatile and flammable liquid organic electrolytes can be fully mitigated by switching to a solid-state configuration. However, their road to thecommercial application is still plagued with numerous challenges, most notably the intrinsic electrochemical instability of solid-state electrolytes (SSEs) materials and their interfacial compatibility with electrodes and electrolytes. In this review, a critical discussion on the key issues and problems of different types of SSEs as well as the corresponding optimization strategies are first highlighted. Then, the state-of-the-art preparation methods and properties of different kinds of SSE materials, and their manufacture, characterization and performance in SSLSBs are summarized in detail. Finally, a scientific outlook for the future development of SSEs and the avenue to commercial application of SSLSBs is also proposed.

Identification of Fcl-29 as an Effective Antifungal Natural Product against Fusarium graminearum and Combinatorial Engineering Strategy for Improving Its Yield.

Fusarium head blight (FHB), caused by Fusarium graminearum, whose occurrence and prevalence causes 10-70% wheat production loss, is one of the most destructive diseases influencing the production of wheat globally. To identify the potential natural products (NPs) against F. graminearum, we screened 59 Xenorhabdus strains and discovered that the cell-free supernatant (CFS) of X. budapestensis 14 (XBD14) displays the highest bioactivity. Multiple genetic methods coupled with HRMS/MS analysis determined the major antifungal NP to be Fcl-29, a fabclavine derivative. Fcl-29 was found to effectively control FHB of wheat in the field test and demonstrated broad-spectrum antifungal activity against important pathogenic fungi. The production of Fcl-29 was dramatically improved by 33.82-fold with the combinatorial strategy of genetic engineering (1.66-fold) and fermentation engineering (20.39-fold). The exploration of a new biofungicide in global plant protection is now possible.

Large-scale genetic surveys for main extant population of wild giant panda (Ailuropoda melanoleuca) reveals an urgent need of human management.

There are only six isolated living giant panda populations, and a comprehensive understanding of their genetic health status is crucial for the conservation of this vulnerable species. Liangshan Mountains is one of the main distribution areas of living giant pandas and is outside the newly established Giant panda national park. In this study, 971 giant panda fecal samples were collected in the heartland of Liangshan Mountains (Mabian Dafengding Nature Reserve: MB; Meigu Dafengding Nature Reserve: MG; and Heizhugou Nature Reserve: HZG). Microsatellite markers and mitochondrial D-loop sequences were used to estimate population size and genetic diversity. We identified 92 individuals (MB: 27, MG: 22, HZG: 43) from the three reserves. Our results showed that: (1) genetic diversity of three giant panda populations was moderate; (2) several loci deviated significantly from the Hardy-Weinberg equilibrium and almost all these deviated loci showed significant heterozygote deficiencies and inbreeding; (3) three giant panda populations have substantial genetic differentiation with the most differentiation between MB and the two other populations; and (4) a large amount of giant panda feces outside the three reserves were found, implying the existence of protection gap. These results indicated that under stochastic events, the giant panda populations in Liangshan Mountains are at risk of genetic decline or extinction and urgent need of human management. This study revealed that high attention should be paid to the protection of these giant panda populations outside the Giant panda national park, to ensure their survival in their distribution areas.