The PLOD2/succinate axis regulates the epithelial-mesenchymal plasticity and cancer cell stemness.

Aberrant accumulation of succinate has been detected in many cancers. However, the cellular function and regulation of succinate in cancer progression is not completely understood. Using stable isotope-resolved metabolomics analysis, we showed that the epithelial mesenchymal transition (EMT) was associated with profound changes in metabolites, including elevation of cytoplasmic succinate levels. The treatment with cell-permeable succinate induced mesenchymal phenotypes in mammary epithelial cells and enhanced cancer cell stemness. Chromatin immunoprecipitation and sequence analysis showed that elevated cytoplasmic succinate levels were sufficient to reduce global 5-hydroxymethylcytosinene (5hmC) accumulation and induce transcriptional repression of EMT-related genes. We showed that expression of procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) was associated with elevation of cytoplasmic succinate during the EMT process. Silencing of PLOD2 expression in breast cancer cells reduced succinate levels and inhibited cancer cell mesenchymal phenotypes and stemness, which was accompanied by elevated 5hmC levels in chromatin. Importantly, exogenous succinate rescued cancer cell stemness and 5hmC levels in PLOD2-silenced cells, suggesting that PLOD2 promotes cancer progression at least partially through succinate. These results reveal the previously unidentified function of succinate in enhancing cancer cell plasticity and stemness.

The influence of first desaturase subfamily genes on fatty acid synthesis, desiccation tolerance and inter-caste nutrient transfer in the termite Coptotermes formosanus.

Desaturase enzymes play an essential role in the biosynthesis of unsaturated fatty acids (UFAs). In this study, we identified seven "first desaturase" subfamily genes (Cfor-desatA1, Cfor-desatA2-a, Cfor-desatA2-b, Cfor-desatB-a, Cfor-desatB-b, Cfor-desatD and Cfor-desatE) from the Formosan subterranean termite Coptotermes formosanus. These desaturases were highly expressed in the cuticle and fat body of C. formosanus. Inhibition of either the Cfor-desatA2-a or Cfor-desatA2-b gene resulted in a significant decrease in the contents of fatty acids (C16:0, C18:0, C18:1 and C18:2) in worker castes. Moreover, we observed that inhibition of most of desaturase genes identified in this study had a negative impact on the survival rate and desiccation tolerance of workers. Interestingly, when normal soldiers were reared together with dsCfor-desatA2-b-treated workers, they exhibited higher mortality, suggesting that desaturase had an impact on trophallaxis among C. formosanus castes. Our findings shed light on the novel roles of desaturase family genes in the eusocial termite C. formosanus.

Therapeutic progress in relapsed/refractory multiple myeloma.

Improvement in the therapeutics for multiple myeloma (MM) has been continuously developed owing to the application of novel drugs and technologies in the last 20 years. The standard first-line therapy for MM consists of a three-drug induction regimen based on immunomodulatory drugs and proteasome inhibitors combined with autologous stem cell transplantation. However, MM remains incurable; therefore, therapies for relapsed/refractory MM (RRMM) are emerging and evolving rapidly. This study aimed to summarize and review the results of RRMM trials over the past 5 years to provide a holistic overview and insights for practitioners in related fields and to provide additional ideas for clinical trialists. This study shows that daratumumab and isatuximab continue to significantly advance as treatment options. Additionally, novel antibody drugs, such as elotuzumab and selinexor, as well as bispecific antibodies, teclistamab and talquetamab, are currently undergoing clinical research with promising outcomes. However, chimeric antigen receptor-T cell therapy targeting B-cell maturation antigen remains the optimal approach for MM treatment.

Neuroinflammation changes with periodontal inflammation status during periodontitis in wild-type mice.

OBJECTIVE: To investigate neuroinflammation under different periodontal status. MATERIALS AND METHODS: Experimental periodontitis was induced by molar ligation (Lig group) or periodontal injection of lipopolysaccharide (LPS, Lps group). Periodontal status was assessed by alveolar bone resorption and periodontal inflammation. Micro-computed tomography and haematoxylin-eosin staining were performed to assess alveolar bone resorption and periodontal inflammation, respectively. Neuroinflammation was assessed by glial cell proliferation and proinflammatory factor expression. Microgliosis was determined by immunofluorescence. Astrogliosis was determined by immunohistochemistry. Expressions of tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-1ß were assessed by enzyme-linked immunosorbent assay. RESULTS: Microgliosis and astrogliosis in the Lig group were notable with molar ligation for 2 weeks and 4 weeks (p < .05), but were only slightly different similar from the control group by week 12. Microgliosis and astrogliosis in the Lps group were significant with LPS injection for 4 and 8 weeks (p < .05). The groups displayed a positive correlation between the degree of periodontal inflammation and the number of glial cells (p < .05). Expressions of IL-1ß and TNF-α in the Lps group were significantly increased with LPS injection for 8 weeks (p < .05). In the Lig group, only TNF-α was highly expressed with molar ligation for 12 weeks (p < .05). CONCLUSION: Both models demonstrated that the inflammatory response in the hippocampus of mice can change during periodontitis depending on the periodontal inflammation status.

Importing food damages domestic environment: Evidence from global soybean trade.

Protecting the environment and enhancing food security are among the world's Sustainable Development Goals and greatest challenges. International food trade is an important mechanism to enhance food security worldwide. Nonetheless, it is widely concluded that in international food trade importing countries gain environmental benefits, while exporting countries suffer environmental problems by using land and other resources to produce food for exports. Our study shows that international food trade can also lead to environmental pollution in importing countries. At the global level, our metaanalysis indicates that there was increased nitrogen (N) pollution after much farmland for domestically cultivated N-fixing soybeans in importing countries was converted to grow high N-demanding crops (wheat, corn, rice, and vegetables). The findings were further verified by an intensive study at the regional level in China, the largest soybean-importing country, where the conversion of soybean lands to corn fields and rice paddies has also led to N pollution. Our study provides a sharp contrast to the conventional wisdom that only exports contribute substantially to environmental woes. Our results suggest the need to evaluate environmental consequences of international trade of all other major goods and products in all importing countries, which have significant implications for fundamental rethinking in global policy-making and debates on environmental responsibilities among consumers, producers, and traders across the world.

Insights into Lithium and Sodium Storage in Porous Carbon.

The lithium and sodium storage behavior of porous carbon remains controversial, though it shows excellent cycling stability and rate performances. This Letter discloses the insertion, adsorption, and filling properties of porous carbon. 7Li nuclear magnetic resonance (NMR) spectroscopy recognized inserted and adsorbed lithium in this porous carbon but did not observe any other forms of lithium above 0.0 V vs. Li+/Li. In addition, although lithium insertion mainly takes place at low potentials, adsorption was found to be the main form of lithium storage throughout the investigated potential range. Such a storage feature is responsible for the excellent rate performance and high specific capacity of porous carbon. Raman spectroscopy further demonstrated the structural reversibility of the carbon in different potential ranges, verifying the necessity to optimize the potential range for a better cycling performance. These findings provide insights for the design and application of porous carbon.

Joint Cationic and Anionic Redox Chemistry for Advanced Mg Batteries.

Lack of appropriate cathodes severely restrains the development of high-energy Mg batteries. In this work, we proposed joint cationic and anionic redox chemistry of transition-metal (TM) sulfides as the most promising way out. A series of solid-solution pyrite FexCo1-xS2 (0 ≤ x ≤ 1) was specially designed, in which S 3p electrons pour into the d bands of Fe and Co, generating redox-active dimerized (S2)2-. The Fe0.5Co0.5S2 sample is highlighted to deliver a high specific energy of 240 Wh/kg at room temperature involving both cationic (Fe and Co) and anionic (S) redox. The highly delocalized electronic clouds in pyrite structures comfortably accommodate the charge of Mg2+, contributing to the fast kinetics and the superior cycling stability of the Fe0.5Co0.5S2. It is anticipated that the joint cationic and anionic redox chemistry proposed in this work would be the ultimate answer for designing high-energy cathodes for advanced Mg batteries.

Lithium Plating and Stripping on Carbon Nanotube Sponge.

Lithium metal is an ideal anode material due to its high specific capacity and low redox potential. However, issues such as dendritic growth and low Coulombic efficiency prevent its application in secondary lithium batteries. The use of three-dimensional (3D) porous current collector is an effective strategy to solve these problems. Herein, commercial carbon nanotube (CNT) sponge is used as a 3D current collector for dendrite-free lithium metal deposition to improve the Coulombic efficiency and the cycle stability of the lithium metal batteries. The high specific surface area of the CNT increases the density of the lithium nucleation sites and ensures the uniform lithium deposition while the "pre-lithiation" behavior of the porous CNT enhances its affinity with the deposited lithium. Meanwhile, the lithium plating/stripping on the sponge maintains high Coulombic efficiency and high cycling stability due to the robust structure of graphitic-amorphous carbon composite in the ether-based electrolyte. Our findings exhibit the feasibility of using CNT sponge as a 3D porous current collector for lithium deposition. They shed light on designing and developing advanced current collectors for the lithium metal electrode and will promote the commercialization of the secondary lithium batteries.

Carbon-Supported Divacancy-Anchored Platinum Single-Atom Electrocatalysts with Superhigh Pt Utilization for the Oxygen Reduction Reaction.

Maximizing the platinum utilization in electrocatalysts toward oxygen reduction reaction (ORR) is very desirable for large-scale sustainable application of Pt in energy systems. A cost-effective carbon-supported carbon-defect-anchored platinum single-atom electrocatalysts (Pt1 /C) with remarkable ORR performance is reported. An acidic H2 /O2 single cell with Pt1 /C as cathode delivers a maximum power density of 520 mW cm-2 at 80 °C, corresponding to a superhigh platinum utilization of 0.09 gPt kW-1 . Further physical characterization and density functional theory computations reveal that single Pt atoms anchored stably by four carbon atoms in carbon divacancies (Pt-C4 ) are the main active centers for the observed high ORR performance.

A Pyrazine-Based Polymer for Fast-Charge Batteries.

The lack of high-power and stable cathodes prohibits the development of rechargeable metal (Na, Mg, Al) batteries. Herein, poly(hexaazatrinaphthalene) (PHATN), an environmentally benign, abundant and sustainable polymer, is employed as a universal cathode material for these batteries. In Na-ion batteries (NIBs), PHATN delivers a reversible capacity of 220 mAh g-1 at 50 mA g-1 , corresponding to the energy density of 440 Wh kg-1 , and still retains 100 mAh g-1 at 10 Ag-1 after 50 000 cycles, which is among the best performances in NIBs. Such an exceptional performance is also observed in more challenging Mg and Al batteries. PHATN retains reversible capacities of 110 mAh g-1 after 200 cycles in Mg batteries and 92 mAh g-1 after 100 cycles in Al batteries. DFT calculations, X-ray photoelectron spectroscopy, Raman, and FTIR show that the electron-deficient pyrazine sites in PHATN are the redox centers to reversibly react with metal ions.

HSF1, in association with MORC2, downregulates ArgBP2 via the PRC2 family in gastric cancer cells.

Arg Kinase-binding protein 2 (ArgBP2) is considered to be a scaffold protein that coordinates multiple signaling pathways converging on cell adhesion and actin cytoskeletal organization. It also plays an important role in blocking cancer metastasis as a potential tumor suppressor. However, its regulation mechanisms in tumor migration, especially in gastric cancer, are not fully understood. Here, we identified an ArgBP2 enhancer and showed that heat shock factor 1 (HSF1) directly interacted with microrchidia CW-type zinc finger 2 (MORC2) and bound to the enhancer of ArgBP2. HSF1 was found to promote proliferation, migration and invasion of gastric cancer cells. HSF1 or/and MORC2 increased recruitment of the polycomb repressive complex 2 (PRC2), particularly enhancer of zeste homolog 2 (EZH2), to the ArgBP2 enhancer and catalyzed tri-methylation of lysine 27 on histone H3 (H3K27me3), leading to transcriptional repression of ArgBP2. In addition, HSF1 and MORC2-induced migration and invasion in gastric cancer cells was dependent on ArgBP2 or EZH2. Clinical data exhibited a negative correlation of ArgBP2 with MORC2, HSF1, and EZH2. Our results thus contribute to the knowledge of the regulatory mechanism of HSF1 in down-regulating ArgBP2, providing new insight into the HSF1&MORC2-PRC2-ArgBP2 signaling pathway and a better understanding of their functions in gastric cancer cells.

Microchidia protein 2, MORC2, downregulates the cytoskeleton adapter protein, ArgBP2, via histone methylation in gastric cancer cells.

ArgBP2 is an adapter protein that plays an important role in actin-dependent processes such as cell adhesion and migration. However, its function and regulation mechanisms in gastric cancer have not yet been investigated. Here, we showed the low expression of ArgBP2 mRNA level in gastric tumor samples and its repressive function in the proliferation, migration, and invasion of gastric cancer cells. Then, we cloned and identified ArgBP2 promoter and verified that MORC2 bound to the promoter. Moreover, we demonstrated that MORC2 enhanced the recruitment of EZH2, which promoted the tri-methylation of H3K27, leading to the transcriptional repression of ArgBP2. Our results might thus contribute to understanding the molecular mechanisms of ArgBP2 regulation and suggesting ArgBP2 as a potential therapeutic target for gastric cancer.

Different Preharvest Diseases in Garlic and Their Eco-Friendly Management Strategies.

BACKGROUND: garlic reproduces mainly through clove planting, as sexual reproduction via seeds is uncommon. Growers encounter challenges with pathogens due to the larger size and vegetative nature of seed cloves, as well as the storage conditions conducive to fungal growth. Some Phyto-pathogenic fungi, previously unrecognized as garlic infections, can remain latent within bulb tissues long after harvest. Although outwardly healthy, these infected bulbs may develop rot under specific conditions. AIM OF REVIEW: planting diseased seed cloves can contaminate field soil, with some fungal and bacterial infections persisting for extended periods. The substantial size of seed cloves makes complete eradication of deeply ingrained infections difficult, despite the use of systemic fungicides during the preplanting and postharvest phases. Additionally, viruses, resistant to fungicides, persist in vegetative material. They are prevalent in much of the garlic used for planting, and their host vectors are difficult to eliminate. To address these challenges, tissue-culture techniques are increasingly employed to produce disease-free planting stock. Key scientific concepts of the review: garlic faces a concealed spectrum of diseases that pose a global challenge, encompassing fungal threats like Fusarium's vascular wilt and Alternaria's moldy rot, bacterial blights, and the elusive garlic yellow stripe virus. The struggle to eliminate deeply ingrained infections is exacerbated by the substantial size of seed cloves. Moreover, viruses persist in garlic seeds, spreading through carrier vectors, and remain unaffected by fungicides. This review emphasizes eco-friendly strategies to address these challenges, focusing on preventive measures, biocontrol agents, and plant extracts. Tissue-culture techniques emerge as a promising solution for generating disease-free garlic planting material. The review advocates for ongoing research to ensure sustainable garlic cultivation, recognizing the imperative of safeguarding this culinary staple from an array of fungal and viral threats.

Intentional replantation for a Class 4/Stage C cemental tear: Etiology, choice and outcomes of treatment.

Cemental tears, root cracks, and associated periapical-periodontal lesions may occur simultaneously in one tooth, and can be effectively managed by intentional replantation and etiological control. A durable splint, along with occlusal and periodontal monitoring, is required as healing progresses slowly and may be insufficient.

Regulation of anthocyanin synthesis in red lettuce in plant factory conditions: A review.

Anthocyanins, natural pigments known for their vibrant hues and beneficial properties, undergo intricate genetic control. However, red vegetables grown in plant factories frequently exhibit reduced anthocyanin synthesis compared to those in open fields due to factors like inadequate light, temperature, humidity, and nutrient availability. Comprehending these factors is essential for optimizing plant factory environments to enhance anthocyanin synthesis. This review insights the impact of physiological and genetic factors on the production of anthocyanins in red lettuce grown under controlled conditions. Further, we aim to gain a better understanding of the mechanisms involved in both synthesis and degradation of anthocyanins. Moreover, this review summarizes the identified regulators of anthocyanin synthesis in lettuce, addressing the gap in knowledge on controlling anthocyanin production in plant factories, with potential implications for various crops beyond red lettuce.

Mechano-activated connexin hemichannels and glutathione transport protect lens fiber cells against oxidative insults.

Long-lived lens fiber cells require a robust cellular protective function against oxidative insults to maintain their hemostasis and viability; however, the underlying mechanism is largely obscure. In this study, we unveiled a new mechanism that protects lens fiber cells against oxidative stress-induced cell death. We found that mechano-activated connexin (Cx) hemichannels (HCs) mediate the transport of glutathione (GSH) into chick embryonic fibroblasts (CEF) and primary lens fiber cells, resulting in a decrease in the accumulation of intracellular reactive oxygen species induced by both H2O2 and ultraviolet B, providing protection to lens fiber cells against cell apoptosis and necrosis. Furthermore, HCs formed by both homomeric Cx50 or Cx46 and heteromeric Cx50/Cx46 were mechanosensitive and could transport GSH into CEF cells. Notably, mechano-activated Cx50 HCs exhibited a greater capacity to transport GSH than Cx46 HCs. Consistently, the deficiency of Cx50 in single lens fiber cells led to a higher level of oxidative stress. Additionally, outer cortical short lens fiber cells expressing full length Cxs demonstrated greater resistance to oxidative injury compared to central core long lens fibers. Taken together, our results suggest that the activation of Cx HCs by interstitial fluid flow in cultured epithelial cells and isolated fiber cells shows that HCs can serve as a pathway for moving GSH across the cell membrane to offer protection against oxidative stress.

Nucleo-cytoplasmic shuttling of PAK4 modulates ß-catenin intracellular translocation and signaling.

The canonical Wnt/ß-catenin signaling pathway plays a central role in development and cancer. The p21-activated kinase 4 (PAK4) involves in a wide range of cellular processes, including cytoskeletal reorganization, cell proliferation, gene transcription and oncogenic transformation. However, the cross talk between the Wnt and PAK4 signaling pathways is poorly understood. Here, we show that PAK4 is a nucleo-cytoplasmic shuttling protein, containing three nuclear export signals (NESs) and two nuclear localization signals (NLSs). PAK4 is exported by the chromosome region maintenance-1 (CRM-1)-dependent pathway and is imported into the nucleus in an importin α5-dependent manner. PAK4 interacts with and phosphorylates ß-catenin on Ser675, which promotes the TCF/LEF transcriptional activity and stabilizes ß-catenin through inhibition of its degradation. Moreover, nuclear import of PAK4 accompanies with the nuclear import of ß-catenin and increased TCF/LEF transcriptional activity. We further demonstrated that PAK4 associates with the TCF/LEF transcriptional complex by ChIP assays. These findings uncover a novel role for PAK4 in modulating intracellular translocation and signaling of ß-catenin.

Protein kinase A activation alleviates cataract formation via increased gap junction intercellular communication.

Cataract is the leading cause of blindness worldwide. Here, we reported a potential, effective therapeutic mean for cataract prevention and treatment. Gap junction communication, an important mechanism in maintaining lens transparency, is increased by protein kinase A (PKA). We found that PKA activation reduced cataracts induced by oxidative stress, increased gap junctions/hemichannels in connexin (Cx) 50, Cx46 or Cx50 and Cx46 co-expressing cells, and decreased reactive oxygen species (ROS) levels. However, ROS reduction was shown in wild-type, Cx46 and Cx50 knockout, but not in Cx46/Cx50 double KO lens. In addition, PKA activation protects lens fiber cell death induced by oxidative stress via hemichannel-mediated glutathione transport. Connexin deletion increased lens opacity induced by oxidative stress associated with reduction of anti-oxidative stress gene expression. Together, our results suggest that PKA activation through increased connexin channels in lens fiber cell decreases ROS levels and cell death, leading to alleviated cataracts.

Effects of hydrolyzed gallotannin on intestinal physical barrier, immune function, and microbiota structure of yellow-feather broilers.

The present study was performed to explore the effects of dietary supplementation of hydrolyzed gallotannin (HGT) on intestinal physical barrier, immune function and microbiota structure in yellow-feather broilers. A total of 288 male yellow-feather broilers were randomly allocated to 4 diet treatments: the basal diet (CON) and 3 diets supplemented with 150, 300, and 450 mg/kg HGT for 63 d, respectively, with 6 replicates per treatment and 12 birds per replicate. The findings demonstrated that 300 or 450 mg/kg HGT addition enhanced the expression of duodenal occludin (OCLN) and tight junction protein1 (TJP-1) genes of birds at 21 d of age, and the expression of duodenal and ileal OCLN gene in 63-day-old broilers was upregulated due to 450 mg/kg HGT treatment (P < 0.05). The dietary supplementation of 150 mg/kg HGT strengthened the expression of duodenal IL-6 and IL-4 genes and ileal IL-4 gene of 21-day-old broilers, whereas the expression of jejunal IL1B and IL-6 genes in birds at 63 d of age weakened because of 300 or 450 mg/kg HGT addition (P < 0.05). As for microbial community, the HGT addition altered the cecal microbiota structure of birds at 21 d of age based on analysis of similarities (ANOSIM) test and 450 mg/kg HGT treatment increased the relative abundance of norank Eubacterium coprostanoligenes group at 21 d of age and unclassified Lachnospiraceae at 63 d of age (P < 0.05). In short, diet supplemented with 300 to 450 mg/kg HGT may be the optimal for yellow-feather broilers to enhance intestinal barrier function. Altogether, our study clarified the regulatory role of HGT in broiler intestinal health in earnest, but the underlying mechanism is still unclear. Hence, more research is needed to carry out until the application of HGT as a new functional additive in broiler production.