Insights into the Impact of Trans-Zeatin Overproduction-Engineered Sinorhizobium meliloti on Alfalfa (Medicago sativa L.) Tolerance to Drought Stress.

Plant growth-promoting rhizobacteria have been shown to enhance plant tolerance to drought stress through various mechanisms. However, there is limited research on improving drought resistance in alfalfa by genetically modifying PGPR to produce increased levels of cytokinins. Herein, we employed synthetic biology approaches to engineer two novel strains of Sinorhizobium meliloti capable of overproducing trans-Zeatin and investigated their potential in enhancing drought tolerance in alfalfa. Our results demonstrate that alfalfa plants inoculated with these engineered S. meliloti strains exhibited reduced wilting and yellowing while maintaining higher relative water content under drought conditions. The engineered S. meliloti-induced tZ activated the activity of antioxidant enzymes and the accumulation of osmolytes. Additionally, the increased endogenous tZ content in plants alleviated the impact of drought stress on the alfalfa photosynthetic rate. However, under nondrought conditions, inoculation with the engineered S. meliloti strains had no significant effect on alfalfa biomass and nodule formation.

Carbon reduction and corporate sustainability: Evidence from low-carbon city pilot policy.

The enhancement of corporate environmental, social, and governance (ESG) performance represents a crucial aspect of the broader green transformation agenda. Using a DID design, this paper examines the impact of China's low-carbon city pilot (LCCP) policy on the corporate ESG performance. Our findings demonstrate that the construction of LCCP exerts a positive influence on corporate ESG performance in pilot regions, particularly in industries and areas with high carbon emission intensity. Channel analyses reveal that LCCP policy heightens the environmental concerns of local governments and the public. Furthermore, LCCP policy has a crowding out effect with firms located in the surrounding cities. This paper responds to the calls for the determinants of ESG and enriches the understanding of policy impacts on corporate sustainability practices.

Identification of desoxyrhapontigenin as a novel antiviral agent against congenital Zika virus infection.

Zika virus (ZIKV) infection arises as a global health threat owing to its association with Guillain-Barre syndrome and microcephaly in adults and fetuses since the most recent epidemics. Although extraordinary efforts have been underway globally to identify safe and effective treatments for ZIKV, therapeutic progressions seem to remain stagnant, especially for treating congenital ZIKV infection. Bio-compounds from medicinal plants evolutionarily optimized as drug-like molecules offer eligible sources of pharmaceuticals and lead drugs to fight against viral infections. Here, we identified desoxyrhapontigenin (DES), a naturally occurring bioactive product, as the strongest inhibitory compound against ZIKV infection among six conventional polyphenols in vitro. We also leveraged the trophoblast cell line, human trophoblast stem cells, and complex placental organoid models to provide solid evidence to support the anti-ZIKV bioactivity of DES. Notably, DES treatment effectively reduced the ZIKV burden in serum and target tissues, and correspondingly improved ZIKV-induced pathologic changes including weight loss, tissue inflammation, cell apoptosis, and adverse pregnancy outcomes, while it did not lead to obvious toxicity in both adult and pregnant mice. Furthermore, mechanistic studies revealed that DES could suppress ZIKV entry via dual mechanisms of direct targeting ZIKV E proteins and downregulating putative ZIKV receptors. These findings elucidate a previously unappreciated protective role of desoxyrhapontigenin against ZIKV infection both in vitro and in vivo, which shed light on the development of a novel and potent treatment for congenital ZIKV infection.

Distinctive effects of different types of advanced glycation end-products (AGEs) on liver glucose metabolism.

Increasing evidence has shown that AGEs can impair insulin sensitivity and affect glucose homeostasis. Owing to the heterogeneity of AGEs, it is still unclear which one has the strongest potential to disrupt glucose metabolism. Our study explored the effects of different types of AGEs on hepatic glucose metabolism. Three typical AGEs representing different formation pathways, namely AGEs from a glucose and lysine reaction mixture, methylglyoxal-modified BSA (MGO-BSA) and carboxymethyl lysine (CML), were chosen to treat HepG2 cells. The results indicate that only CML and MGO-BSA could disturb glucose metabolism, and MGO-BSA was the most active in promoting insulin resistance, as manifested by the inactivation of insulin receptor substrate-1 and decreased phosphorylation of AKT. Moreover, mice fed with an MGO-BSA-enriched diet showed increased blood glucose as well as impaired glucose tolerance. The present study revealed the distinctive effects of various AGEs on glucose metabolism and suggested that AGEs with high molecular weight might exert a higher pathogenic effect than small AGEs.

The mystery of the life tree: the placentas†.

The placenta is the interface between the fetal and maternal environments during mammalian gestation, critically safeguarding the health of the developing fetus and the mother. Placental trophoblasts origin from embryonic trophectoderm that differentiates into various trophoblastic subtypes through villous and extravillous pathways. The trophoblasts actively interact with multiple decidual cells and immune cells at the maternal-fetal interface and thus construct fundamental functional units, which are responsible for blood perfusion, maternal-fetal material exchange, placental endocrine, immune tolerance, and adequate defense barrier against pathogen infection. Various pregnant complications are tightly associated with the defects in placental development and function maintenance. In this review, we summarize the current views and our recent progress on the mechanisms underlying the formation of placental functional units, the interactions among trophoblasts and various uterine cells, as well as the placental barrier against pathogen infections during pregnancy. The involvement of placental dysregulation in adverse pregnancy outcomes is discussed.

Cellular and molecular atlas of the placenta from a COVID-19 pregnant woman infected at midgestation highlights the defective impacts on foetal health.

OBJECTIVES: The impacts of the current COVID-19 pandemic on maternal and foetal health are enormous and of serious concern. However, the influence of SARS-CoV-2 infection at early-to-mid gestation on maternal and foetal health remains unclear. MATERIALS AND METHODS: Here, we report the follow-up study of a pregnant woman of her whole infective course of SARS-CoV-2, from asymptomatic infection at gestational week 20 to mild and then severe illness state, and finally cured at Week 24. Following caesarean section due to incomplete uterine rupture at Week 28, histological examinations on the placenta and foetal tissues as well as single-cell RNA sequencing (scRNA-seq) for the placenta were performed. RESULTS: Compared with the gestational age-matched control placentas, the placenta from this COVID-19 case exhibited more syncytial knots and lowered expression of syncytiotrophoblast-related genes. The scRNA-seq analysis demonstrated impaired trophoblast differentiation, activation of antiviral and inflammatory CD8 T cells, as well as the tight association of increased inflammatory responses in the placenta with complement over-activation in macrophages. In addition, levels of several inflammatory factors increased in the placenta and foetal blood. CONCLUSION: These findings illustrate a systematic cellular and molecular signature of placental insufficiency and immune activation at the maternal-foetal interface that may be attributed to SARS-CoV-2 infection at the midgestation stage, which highly suggests the extensive care for maternal and foetal outcomes in pregnant women suffering from COVID-19.

Viral Infections During Pregnancy: The Big Challenge Threatening Maternal and Fetal Health.

Viral infections during pregnancy are associated with adverse pregnancy outcomes, including maternal and fetal mortality, pregnancy loss, premature labor, and congenital anomalies. Mammalian gestation encounters an immunological paradox wherein the placenta balances the tolerance of an allogeneic fetus with protection against pathogens. Viruses cannot easily transmit from mother to fetus due to physical and immunological barriers at the maternal-fetal interface posing a restricted threat to the fetus and newborns. Despite this, the unknown strategies utilized by certain viruses could weaken the placental barrier to trigger severe maternal and fetal health issues especially through vertical transmission, which was not fully understood until now. In this review, we summarize diverse aspects of the major viral infections relevant to pregnancy, including the characteristics of pathogenesis, related maternal-fetal complications, and the underlying molecular and cellular mechanisms of vertical transmission. We highlight the fundamental signatures of complex placental defense mechanisms, which will prepare us to fight the next emerging and re-emerging infectious disease in the pregnancy population.

Whole-Genome Duplication and Purifying Selection Contributes to the Functional Redundancy of Auxin Response Factor (ARF) Genes in Foxtail Millet (Setaria italica L.).

Auxin response factors (ARFs) play crucial roles in auxin-mediated response, whereas molecular genetics of ARF genes was seldom investigated in Setaria italica, an important crop and C4 model plant. In the present study, genome-wide evolutionary analysis of ARFs was performed in S. italica. Twenty-four SiARF genes were identified and unevenly distributed on eight of the nine chromosomes in S. italica. Duplication mode exploration implied that 13 SiARF proteins were originated from whole-genome duplication and suffered purifying selection. Phylogeny reconstruction of SiARFs by maximum likelihood and neighbor-joining trees revealed SiARFs could be divided into four clades. SiARFs clustered within the same clade shared similar gene structure and protein domain composition, implying functional redundancy. Moreover, amino acid composition of the middle regions was conserved in SiARFs belonged to the same clade. SiARFs were categorized into either activators or repressors according to the enrichment of specific amino acids. Intrinsic disorder was featured in the middle regions of ARF activators. Finally, expression profiles of SiARFs under hormone and abiotic stress treatment not only revealed their potential function in stress response but also indicate their functional redundancy. Overall, our results provide insights into evolutionary aspects of SiARFs and benefit for further functional characterization.

Pterostilbene Improves Insulin Resistance Caused by Advanced Glycation End Products (AGEs) in Hepatocytes and Mice.

SCOPE: Increased consumption of modern processed foods rich in AGEs is drawing worldwide concerns because they are related with rising diabetes prevalence. This study aimed to investigate if pterostilbene (PTE) regulates glucose metabolism and insulin signaling, as well as its potential mechanism in the context of AGEs exposure. METHODS AND RESULTS: In vitro, Lo2 and HepG2 cells are treated with vehicle, AGEs with or without PTE. AGEs exposure directly impair insulin action as evidenced by assays of insulin-stimulated glucose uptake, consumption, and output. However, PTE efficiently rescue the AGE-induced phenotypes in both cell lines, and enhance IRS-1/PI3K/AKT insulin signaling in a dose-dependent manner. In vivo, C57BL6 mice are fed with regular, high AGEs diet and high AGEs plus PTE. PTE administration effectively improves hyperglycemia, glucose tolerance, and impaired hepatic insulin signaling induced by AGEs, consistent with the in vitro experiments. Moreover, PTE reduce AGEs accumulation in liver and serum. RNA-seq data indicate that PTE counteracts several AGEs-induced dysfunctions including diabetes related process, glucose metabolic process, immune response, and so on. CONCLUSION: PTE treatment prominently reduced AGEs accumulation and alleviated AGEs-associated diabetes symptoms. PTE could be used as a promising glucose-sensitizing agent for nutritional intervention.

Anti-Inflammatory Effect of an Apigenin-Maillard Reaction Product in Macrophages and Macrophage-Endothelial Cocultures.

Chronic inflammation is involved in the progression of various diseases, while dietary flavonoids are reported to possess antioxidative and anti-inflammatory properties against age-related diseases. Previously, an apigenin-Maillard reaction product, dimethylglyoxal apigenin (DMA), was identified by us and demonstrated to be antioxidative. In this study, we investigated the inhibitory effect of DMA on advanced glycation end product- (AGE-) induced inflammation in macrophages and macrophage-endothelial cocultures. Results showed that DMA remarkably inhibited the mRNA and protein expression of receptor for AGEs (RAGE), thereby inhibiting the production of ROS and proinflammatory cytokines, including tumor necrosis factor- (TNF-) α, interleukin (IL) 1, IL 6, and monocyte chemoattractant protein- (MCP-) 1 in RAW 264.7 cells. In the coculture system which was performed in the Boyden chamber, macrophage infiltration and adhesion to endothelial cells were significantly suppressed by DMA. Further study indicated that DMA decreased AGE-evoked IL 6 and MCP-1 secretion, which might be achieved through RAGE and its downstream-regulated transforming growth factor- (TGF-) ß1 and intercellular adhesion molecule (ICAM) 1 expression in the coculture system. In conclusion, our study demonstrates that DMA, a thermally induced compound, has anti-inflammatory activity in both macrophages and macrophage-endothelial cocultures, offering a promising approach for slowing down the development of chronic diseases.

Naringenin, a common flavanone, inhibits the formation of AGEs in bread and attenuates AGEs-induced oxidative stress and inflammation in RAW264.7 cells.

Dietary flavonoids as popular food additives have attracted a wide range of research interests. Naringenin, a common flavanone, was evaluated of its impact on the formation of advanced glycation endproducts (AGEs) in bread crust. It was found that with the increase of naringenin content in bread (0.25-1% w/w), the formation of CML and total fluorescent AGEs were significantly inhibited (9.67-54.27% and 11.79-35.19%, respectively). In addition, the fortification with naringenin could also significantly inhibit the formation of acrylamide in bread crust, while enhancing the antioxidant and antibacterial activity of bread crumb without bringing undesirable changes to the bread quality attributes. Moreover, in RAW264.7 cells, naringenin significantly reduced of AGEs-induced ROS production as well as the contents of some inflammatory mediators. Altogether, our finding indicated naringenin can have dual inhibitory effects on both AGEs' formation in foods and AGEs-induced cellular oxidative stress and inflammation.

4'-Methoxyresveratrol Alleviated AGE-Induced Inflammation via RAGE-Mediated NF-κB and NLRP3 Inflammasome Pathway.

Advanced glycation end products (AGEs) could interact with the receptor for AGE (RAGE) as a sterile danger signal to induce inflammation. 4'-methoxyresveratrol (4'MR), a polyphenol derived from Dipterocarpaceae, has not been studied for its anti-inflammation effects. In the present study, we sought to explore the protective role of 4'MR in AGEs-induced inflammatory model using RAW264.7 macrophages. 4'MR significantly inhibited gene expression of pro-inflammatory cytokines and chemokines, such as interleukin 1ß (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), as well as two typical pro-inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Besides, 4'MR significantly decreased oxidative stress, demonstrated by levels of ROS production, protein carbonyl and advanced oxidation protein product via down-regulation of NADPH oxidase. Further analysis showed that 4'MR attenuated the RAGE overexpression induced by MGO-BSA. It also blocked the downstream signal of AGE-RAGE, particularly, MAPKs including p38 and JNK, and subsequently reduced NF-κB activation. Additionally, 4'MR significantly abated the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome including NLRP3 and cleaved caspase-1 and reduced the secretion of mature IL-1ß. Taken together, our results suggest that the anti-inflammatory effect of 4'MR is mainly through suppressing RAGE-mediated MAPK/NF-κB signaling pathway and NLRP3 inflammasome activation. 4'MR could be a novel therapeutic agent for inflammation-related diseases.

Band Gap Characters and Ferromagnetic/Antiferromagnetic Coupling in Group-IV Monolayers Tuned by Chemical Species and Hydrogen Adsorption Configurations.

One-side semihydrogenated monolayers of carbon, silicon, germanium, and their binary compounds with different configurations of hydrogen atoms are investigated by density functional theory. Among three considered configurations, zigzag, other than the most studied chair configuration, is energetically the most favorable structure of one-side semihydrogenation. Upon semihydrogenation, the semimetallic silicene, germanene, and SiGe become semiconductors, while the band gap in semiconducting SiC and GeC is reduced. Semihydrogenated silicene, germanene, SiGe, and GeC with chair configuration are found to be ferromagnetic semiconductors. For semihydrogenated SiC, it is ferromagnetic when all hydrogen atoms bond with silicon atoms, while an antiferromagnetic coupling is predicted when all hydrogen atoms bond with carbon atoms. The effect of interatomic distance between two neighboring magnetic atoms to the ferromagnetic or antiferromagnetic coupling is studied. For comparison, properties of one-side and both-side fully hydrogenated group-IV monolayers are also calculated. All fully hydrogenated group-IV monolayers are nonmagnetic semiconductors with band gaps larger than those of their semihydrogenated counterparts.