Establishment of RNAi-Mediated Pest Control Method for Red Imported Fire Ant, Solenopsis invicta.

RNAi plays a crucial role in insect gene function research and pest control field. Nonetheless, the variable efficiency of RNAi across diverse insects and off-target effects also limited its further application. In this study, we cloned six essential housekeeping genes from Solenopsis invicta and conducted RNAi experiments by orally administering dsRNA. Then, we found that mixing with liposomes significantly enhanced the RNAi efficiency by targeting for SiV-ATPaseE. Additionally, we observed a certain lethal effect of this dsRNA on queens by our established RNAi system. Furthermore, no strict sequence-related off-target effects were detected. Finally, the RNAi effect of large-scale bacteria expressing dsRNA was successfully confirmed for controlling S. invicta. In summary, this study established an RNAi system for S. invicta and provided a research template for the future development of nucleic acid drugs based on RNAi.

Synergistic Effects of TiO2 and Carbon Black for Water Evaporation-Induced Electricity Generation.

Water evaporation-induced electricity generators (WEGs) have drawn widespread attention in the field of hydrovoltaic technology, which can convert atmospheric thermal energy into sustainable electric power. However, it is restricted in the wide application of WEGs due to the low power output, complex fabrication process, and high cost. Herein, we present a simple and effective approach to fabricate TiO2-carbon black film-based WEGs (TC-WEGs). A single TC-WEG device can sustainably output an open-circuit voltage of 1.9 V and a maximum power density of 40.9 µW/cm2. Moreover, it has been shown that TC-WEGs exhibit stable electrical energy output when operating in seawater, which can yield a short-circuit current of 1.2 µA. The superior electricity generation performance can be attributed to the intrinsic characteristics of the TC-WEGs, including hydrophilicity, porous structure, and electrical conductivity. This work provides an important reference for the constant harvesting of clean energy.

Metabolomics reveals high fructose-1,6-bisphosphate from fluoride-resistant Streptococcus mutans.

BACKGROUND: Fluoride-resistant Streptococcus mutans (S. mutans) strains have developed due to the wide use of fluoride in dental caries prevention. However, the metabolomics of fluoride-resistant S. mutans remains unclear. OBJECTIVE: This study aimed to identify metabolites that discriminate fluoride-resistant from wild-type S. mutans. MATERIALS AND METHODS: Cell supernatants from fluoride-resistant and wild-type S. mutans were collected and analyzed by liquid chromatography-mass spectrometry. Principal components analysis and partial least-squares discriminant analysis were performed for the statistical analysis by variable influence on projection (VIP > 2.0) and p value (Mann-Whitney test, p < 0.05). Metabolites were assessed qualitatively using the Human Metabolome Database version 2.0 ( http://www.hmdb.ca ), or Kyoto Encyclopedia of Genes and Genomes ( http://www.kegg.jp ), and Metaboanalyst 6.0 ( https://www.metaboanalyst.ca ). RESULTS: Fourteen metabolites differed significantly between fluoride-resistant and wild-type strains in the early log phase. Among these metabolites, 5 were identified. There were 32 differential metabolites between the two strains in the stationary phase, 13 of which were identified. The pyrimidine metabolism for S. mutans FR was matched with the metabolic pathway. CONCLUSIONS: The fructose-1,6-bisphosphate concentration increased in fluoride-resistant strains under acidic conditions, suggesting enhanced acidogenicity and acid tolerance. This metabolite may be a promising target for elucidating the cariogenic and fluoride resistant mechanisms of S. mutans.

Application of fluidized bed homogeneous crystallization for simultaneous recovery of Fe(II) and Cu(II) as particles from wastewater.

The mixture of copper and iron often results in materials with favorable properties. The material production processes involving these metals including electroplating produce hazardous wastewater. In this study, the Fluidized Bed Homogeneous Crystallization (FBHC) process was applied to treat iron and copper-containing wastewater. The initial iron copper particles were successfully recovered from synthetic wastewater with [Fe]0:[Cu]0 of 2:1, the total metal concentration of 3 mM, at effluent pH = 7.75 ± 0.75, with the upflow velocity (U) of 1.76 m/h. The agglomerates hardening process is a crucial step for initial particle synthesis. The SEM analysis reveals the spherical particle's densified crust and porous core. The particle formation mechanism which includes the formation of the nucleus, attachment of precipitate flakes, and densification of particles was proposed after microscopic observation. The initial particles synthesized were used to initiate the treatment of synthetic wastewater at the operating condition pH = 7.75 ± 0.5, [Fe]0:[Cu]0 of 2:1, the total metal concentration of 3 mM, [CO32-]0:[M]0 = 1.2:1, and U of 28.66 m/h which results in the total metal removal of 99% and crystallization ratio of 90% and 88% for iron and copper respectively. The conditions were then applied to treat electroplating wastewater and resulted in the total metal removal of 99% for both iron and copper and a crystallization ratio of 83% and 79% for iron and copper, respectively. The treatment provided advantages in terms of treating larger amounts of sludge while eliminating the need to provide seed thus yielding a higher purity of product.

Loss of LPAR6 and CAB39L dysregulates the basal-to-luminal urothelial differentiation program, contributing to bladder carcinogenesis.

We describe a strategy that combines histologic and molecular mapping that permits interrogation of the chronology of changes associated with cancer development on a whole-organ scale. Using this approach, we present the sequence of alterations around RB1 in the development of bladder cancer. We show that RB1 is not involved in initial expansion of the preneoplastic clone. Instead, we found a set of contiguous genes that we term "forerunner" genes whose silencing is associated with the development of plaque-like field effects initiating carcinogenesis. Specifically, we identified five candidate forerunner genes (ITM2B, LPAR6, MLNR, CAB39L, and ARL11) mapping near RB1. Two of these genes, LPAR6 and CAB39L, are preferentially downregulated in the luminal and basal subtypes of bladder cancer, respectively. Their loss of function dysregulates urothelial differentiation, sensitizing the urothelium to N-butyl-N-(4-hydroxybutyl)nitrosamine-induced cancers, which recapitulate the luminal and basal subtypes of human bladder cancer.

CARM1 hypermethylates the NuRD chromatin remodeling complex to promote cell cycle gene expression and breast cancer development.

Protein arginine methyltransferase CARM1 has been shown to methylate a large number of non-histone proteins, and play important roles in gene transcriptional activation, cell cycle progress, and tumorigenesis. However, the critical substrates through which CARM1 exerts its functions remain to be fully characterized. Here, we reported that CARM1 directly interacts with the GATAD2A/2B subunit in the nucleosome remodeling and deacetylase (NuRD) complex, expanding the activities of NuRD to include protein arginine methylation. CARM1 and NuRD bind and activate a large cohort of genes with implications in cell cycle control to facilitate the G1 to S phase transition. This gene activation process requires CARM1 to hypermethylate GATAD2A/2B at a cluster of arginines, which is critical for the recruitment of the NuRD complex. The clinical significance of this gene activation mechanism is underscored by the high expression of CARM1 and NuRD in breast cancers, and the fact that knockdown CARM1 and NuRD inhibits cancer cell growth in vitro and tumorigenesis in vivo. Targeting CARM1-mediated GATAD2A/2B methylation with CARM1 specific inhibitors potently inhibit breast cancer cell growth in vitro and tumorigenesis in vivo. These findings reveal a gene activation program that requires arginine methylation established by CARM1 on a key chromatin remodeler, and targeting such methylation might represent a promising therapeutic avenue in the clinic.

Dysregulated Ribosome Biogenesis Is a Targetable Vulnerability in Triple-Negative Breast Cancer: MRPS27 as a Key Mediator of the Stemness-inhibitory Effect of Lovastatin.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with limited effective therapeutic options readily available. We have previously demonstrated that lovastatin, an FDA-approved lipid-lowering drug, selectively inhibits the stemness properties of TNBC. However, the intracellular targets of lovastatin in TNBC remain largely unknown. Here, we unexpectedly uncovered ribosome biogenesis as the predominant pathway targeted by lovastatin in TNBC. Lovastatin induced the translocation of ribosome biogenesis-related proteins including nucleophosmin (NPM), nucleolar and coiled-body phosphoprotein 1 (NOLC1), and the ribosomal protein RPL3. Lovastatin also suppressed the transcript levels of rRNAs and increased the nuclear protein level and transcriptional activity of p53, a master mediator of nucleolar stress. A prognostic model generated from 10 ribosome biogenesis-related genes showed outstanding performance in predicting the survival of TNBC patients. Mitochondrial ribosomal protein S27 (MRPS27), the top-ranked risky model gene, was highly expressed and correlated with tumor stage and lymph node involvement in TNBC. Mechanistically, MRPS27 knockdown inhibited the stemness properties and the malignant phenotypes of TNBC. Overexpression of MRPS27 attenuated the stemness-inhibitory effect of lovastatin in TNBC cells. Our findings reveal that dysregulated ribosome biogenesis is a targetable vulnerability and targeting MRPS27 could be a novel therapeutic strategy for TNBC patients.

Severe Venous Calcifications in Phlebosclerotic Colitis and Significantly Decreased Expression in Betaine.

Phlebosclerotic colitis (PC) is a rare type of chronic ischemic colitis. Its etiology is still unknown, and PC is also known as idiopathic mesenteric phlebosclerosis colitis. Currently, many studies have reported that long-term use of Chinese herbal medicine and drinking history are related to its pathogenesis. In the early stage of the lesion, due to insufficient understanding of PC, it is difficult to distinguish it from inflammatory bowel disease and other nonneoplastic intestinal diseases. We reported a case of severe diffuse total colon calcification with multiple misdiagnosis, summarizing and analyzing the clinical pathological characteristics to increase clinical and pathological physicians' understanding of the disease and reduce misdiagnosis. Moreover, for the first time, we conducted metabolomics sequencing on fresh intestinal specimens of PC, in order to explore the possible mechanism of severe calcification in the patient. We found that betaine was significantly decreased in the intestinal specimens of the patient, which is an amino acid that has been shown to improve vascular risk factors, and may be one of the mechanisms underlying severe calcification in the patient.

Crocus genome reveals the evolutionary origin of crocin biosynthesis.

Crocus sativus (saffron) is a globally autumn-flowering plant, and its stigmas are the most expensive spice and valuable herb medicine. Crocus specialized metabolites, crocins, are biosynthesized in distant species, Gardenia (eudicot) and Crocus (monocot), and the evolution of crocin biosynthesis remains poorly understood. With the chromosome-level Crocus genome assembly, we revealed that two rounds of lineage-specific whole genome triplication occurred, contributing important roles in the production of carotenoids and apocarotenoids. According to the kingdom-wide identification, phylogenetic analysis, and functional assays of carotenoid cleavage dioxygenases (CCDs), we deduced that the duplication, site positive selection, and neofunctionalization of Crocus-specific CCD2 from CCD1 members are responsible for the crocin biosynthesis. In addition, site mutation of CsCCD2 revealed the key amino acids, including I143, L146, R161, E181, T259, and S292 related to the catalytic activity of zeaxanthin cleavage. Our study provides important insights into the origin and evolution of plant specialized metabolites, which are derived by duplication events of biosynthetic genes.

Biosynthesis of Enfumafungin-type Antibiotic Reveals an Unusual Enzymatic Fusion Pattern and Unprecedented C-C Bond Cleavage.

Enfumafungin-type antibiotics, represented by enfumafungin and fuscoatroside, belong to a distinct group of triterpenoids derived from fungi. These compounds exhibit significant antifungal properties with ibrexafungerp, a semisynthetic derivative of enfumafungin, recently gaining FDA's approval as the first oral antifungal drug for treating invasive vulvar candidiasis. Enfumafungin-type antibiotics possess a cleaved E-ring with an oxidized carboxyl group and a reduced methyl group at the break site, suggesting unprecedented C-C bond cleavage chemistry involved in their biosynthesis. Here, we show that a 4-gene (fsoA, fsoD, fsoE, fsoF) biosynthetic gene cluster is sufficient to yield fuscoatroside by heterologous expression in Aspergillus oryzae. Notably, FsoA is an unheard-of terpene cyclase-glycosyltransferase fusion enzyme, affording a triterpene glycoside product that relies on enzymatic fusion. FsoE is a P450 enzyme that catalyzes successive oxidation reactions at C19 to facilitate a C-C bond cleavage, producing an oxidized carboxyl group and a reduced methyl group that have never been observed in known P450 enzymes. Our study thus sets the important foundation for the manufacture of enfumafungin-type antibiotics using biosynthetic approaches.

In Situ Probing the Structure Change and Interaction of Interfacial Water and Hydroxyl Intermediates on Ni(OH)2 Surface over Water Splitting.

There is growing acknowledgment that the properties of the electrochemical interfaces play an increasingly pivotal role in improving the performance of the hydrogen evolution reaction (HER). Here, we present, for the first time, direct dynamic spectral evidence illustrating the impact of the interaction between interfacial water molecules and adsorbed hydroxyl species (OHad) on the HER properties of Ni(OH)2 using Au/core-Ni(OH)2/shell nanoparticle-enhanced Raman spectroscopy. Notably, our findings highlight that the interaction between OHad and interfacial water molecules promotes the formation of weakly hydrogen-bonded water, fostering an environment conducive to improving the HER performance. Furthermore, the participation of OHad in the reaction is substantiated by the observed deprotonation step of Au@2 nm Ni(OH)2 during the HER process. This phenomenon is corroborated by the phase transition of Ni(OH)2 to NiO, as verified through Raman and X-ray photoelectron spectroscopy. The significant redshift in the OH-stretching frequency of water molecules during the phase transition confirms that surface OHad disrupts the hydrogen-bond network of interfacial water molecules. Through manipulation of the shell thickness of Au@Ni(OH)2, we additionally validate the interaction between OHad and interfacial water molecules. In summary, our insights emphasize the potential of electrochemical interfacial engineering as a potent approach to enhance electrocatalytic performance.

Single-incision plus one-port laparoscopy surgery versus conventional multi-port laparoscopy surgery for colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: The efficacy of single-incision plus one-port laparoscopic surgery (SILS + 1) versus conventional laparoscopic surgery (CLS) for colorectal cancer treatment remains unclear. This study compares the short-term and long-term outcomes of SILS + 1 and CLS using a high-quality systematic review and meta-analysis. METHOD: Literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, drawing from PubMed, Embase, Web of Science, and the Cochrane Library until December 10, 2023. Statistical analysis was conducted using RevMan and Stata. RESULT: The review and meta-analysis included seven studies with 1740 colorectal cancer patients. Compared to CLS, SILS + 1 showed significant improvements in operation time (WMD = - 18.33, P < 0.00001), blood loss (WMD = - 21.31, P < 0.00001), incision length (WMD = - 2.07, P < 0.00001), time to first defecation (WMD = - 14.91, P = 0.009), time to oral intake (WMD = - 11.46, P = 0.04), and time to ambulation (WMD = - 11.52, P = 0.01). There were no significant differences in lymph node harvest, resection margins, complications, anastomotic leakage, hospital stay, disease-free survival, overall survival, and postoperative recurrence. CONCLUSIONS: Compared to CLS, SILS + 1 demonstrates superiority in shortening the surgical incision and promoting postoperative recovery. SILS + 1 can provide a safe and feasible alternative to CLS.

Comparative genomics and phylogenomics of the genus Glycyrrhiza (Fabaceae) based on chloroplast genomes.

Glycyrrhiza (Fabaceae) species are rich in metabolites and widely used in medicine. Research on the chloroplast genome of Glycyrrhiza is important for understanding its phylogenetics, biogeography, genetic diversity, species identification, and medicinal properties. In this study, comparative genomics and phylogenomics of Glycyrrhiza were analyzed based on the chloroplast genome. The chloroplast genomes of six Glycyrrhiza species were obtained using various assembly and annotation tools. The final assembled chloroplast genome sizes for the six Glycyrrhiza species ranged from 126,380 bp to 129,115 bp, with a total of 109-110 genes annotated. Comparative genomics results showed that the chloroplast genomes of Glycyrrhiza showed typically lacking inverted repeat regions, and the genome length, structure, GC content, codon usage, and gene distribution were highly similar. Bioinformatics analysis revealed the presence of 69-96 simple sequence repeats and 61-138 long repeats in the chloroplast genomes. Combining the results of mVISTA and nucleotide diversity, four highly variable regions were screened for species identification and relationship studies. Selection pressure analysis indicated overall purifying selection in the chloroplast genomes of Glycyrrhiza, with a few positively selected genes potentially linked to environmental adaptation. Phylogenetic analyses involving all tribes of Fabaceae with published chloroplast genomes elucidated the evolutionary relationships, and divergence time estimation estimated the chronological order of species differentiations within the Fabaceae family. The results of phylogenetic analysis indicated that species from the six subfamilies formed distinct clusters, consistent with the classification scheme of the six subfamilies. In addition, the inverted repeat-lacking clade in the subfamily Papilionoideae clustered together, and it was the last to differentiate. Co-linear analysis confirmed the conserved nature of Glycyrrhiza chloroplast genomes, and instances of gene rearrangements and inversions were observed in the subfamily Papilionoideae.

Optimizing the robustness of higher-low order coupled networks.

Enhancing the robustness of complex networks is of great practical significance as it ensures the stable operation of infrastructure systems. We measure its robustness by examining the size of the largest connected component of the network after initial attacks. However, traditional research on network robustness enhancement has mainly focused on low-order networks, with little attention given to higher-order networks, particularly higher-low order coupling networks(the largest connected component of the network must exist in both higher-order and low-order networks). To address this issue, this paper proposes robust optimization methods for higher-low order coupled networks based on the greedy algorithm and the simulated annealing algorithm. By comparison, we found that the simulated annealing algorithm performs better. The proposed method optimizes the topology of the low-order network and the higher-order network by randomly reconnecting the edges, thereby enhancing the robustness of the higher-order and low-order coupled network. The experiments were conducted on multiple real networks to evaluate the change in the robustness coefficient before and after network optimization. The results demonstrate that the proposed method can effectively improve the robustness of both low-order and higher-order networks, ultimately enhancing the robustness of higher-low order coupled networks.

Dual-functional ionic liquids additive enables dendrite-free Zn anode with ultra-long cycle life over one year.

Zn anodes suffer from the formation of uncontrolled dendrites aggravated by the uneven electric field and the insulating by-product accumulation in aqueous zinc-ion batteries (AZIBs). Here, an effective strategy implemented by 1-butyl-3-methylimidazolium hydrogen sulfate (BMIHSO4) additive is proposed to synergistically tune the crystallographic orientation of zinc deposition and suppress the formation of zinc hydroxide sulfate for enhancing the reversibility on Zn anode surface. As a competing cation, BMI+ is proved to preferably adsorb on Zn-electrode compared with H2O molecules, which shields the "tip effect" and inhibits the Zn-deposition agglomerations to inducing the horizontal growth along Zn (002) crystallographic texture. Simultaneously, the protonated BMIHSO4 additives could remove the detrimental OH- in real-time to fundamentally eliminate the accumulation of 6Zn(OH)2·ZnSO4·4H2O and Zn4SO4(OH)6·H2O on Zn anode surface. Consequently, Zn anode exhibits an ultra-long cycling stability of one year (8762 h) at 0.2 mA cm-2/0.2 mAh cm-2, 3600 h at 2 mA cm-2/2 mAh cm-2 with a high plating cumulative capacity of 3.6 Ah cm-2, and a high average Coulombic efficiency of 99.6 % throughout 1000 cycles. This work of regulating Zn deposition texture combined with eliminating notorious by-products could offer a desirable way for stabilizing the Zn-anode/electrolyte interface in AZIBs.

Lineage-Specific CYP80 Expansion and Benzylisoquinoline Alkaloid Diversity in Early-Diverging Eudicots.

Menispermaceae species, as early-diverging eudicots, can synthesize valuable benzylisoquinoline alkaloids (BIAs) like bisbenzylisoquinoline alkaloids (bisBIAs) and sinomenines with a wide range of structural diversity. However, the evolutionary mechanisms responsible for their chemo-diversity are not well understood. Here, a chromosome-level genome assembly of Menispermum dauricum is presented and demonstrated the occurrence of two whole genome duplication (WGD) events that are shared by Ranunculales and specific to Menispermum, providing a model for understanding chromosomal evolution in early-diverging eudicots. The biosynthetic pathway for diverse BIAs in M. dauricum is reconstructed by analyzing the transcriptome and metabolome. Additionally, five catalytic enzymes - one norcoclaurine synthase (NCS) and four cytochrome P450 monooxygenases (CYP450s) - from M. dauricum are responsible for the formation of the skeleton, hydroxylated modification, and C-O/C-C phenol coupling of BIAs. Notably, a novel leaf-specific MdCYP80G10 enzyme that catalyzes C2'-C4a phenol coupling of (S)-reticuline into sinoacutine, the enantiomer of morphinan compounds, with predictable stereospecificity is discovered. Moreover, it is found that Menispermum-specific CYP80 gene expansion, as well as tissue-specific expression, has driven BIA diversity in Menispermaceae as compared to other Ranunculales species. This study sheds light on WGD occurrences in early-diverging eudicots and the evolution of diverse BIA biosynthesis.

Inhibition of MST1 ameliorates neuronal apoptosis via GSK3ß/ß-TrCP/NRF2 pathway in spinal cord injury accompanied by diabetes.

AIMS: Spinal cord injury (SCI) is a devastating neurological disease that often results in tremendous loss of motor function. Increasing evidence demonstrates that diabetes worsens outcomes for patients with SCI due to the higher levels of neuronal oxidative stress. Mammalian sterile 20-like kinase (MST1) is a key mediator of oxidative stress in the central nervous system; however, the mechanism of its action in SCI is still not clear. Here, we investigated the role of MST1 activation in induced neuronal oxidative stress in patients with both SCI and diabetes. METHODS: Diabetes was established in mice by diet induction combined with intraperitoneal injection of streptozotocin (STZ). SCI was performed at T10 level through weight dropping. Advanced glycation end products (AGEs) were applied to mimic diabetic conditions in PC12 cell line in vitro. We employed HE, Nissl staining, footprint assessment and Basso mouse scale to evaluate functional recovery after SCI. Moreover, immunoblotting, qPCR, immunofluorescence and protein-protein docking analysis were used to detect the mechanism. RESULTS: Regarding in vivo experiments, diabetes resulted in up-regulation of MST1, excessive neuronal apoptosis and weakened motor function in SCI mice. Furthermore, diabetes impeded NRF2-mediated antioxidant defense of neurons in the damaged spinal cord. Treatment with AAV-siMST1 could restore antioxidant properties of neurons to facilitate reactive oxygen species (ROS) clearance, which subsequently promoted neuronal survival to improve locomotor function recovery. In vitro model found that AGEs worsened mitochondrial dysfunction and increased cellular oxidative stress. While MST1 inhibition through the chemical inhibitor XMU-MP-1 or MST1-shRNA infection restored NRF2 nuclear accumulation and its transcription of downstream antioxidant enzymes, therefore preventing ROS generation. However, these antioxidant effects were reversed by NRF2 knockdown. Our in-depth studies showed that over-activation of MST1 in diabetes directly hindered the neuroprotective AKT1, and subsequently fostered NRF2 ubiquitination and degradation via the GSK3ß/ß-TrCP pathway. CONCLUSION: MST1 inhibition significantly restores neurological function in SCI mice with preexisting diabetes, which is largely attributed to the activation of antioxidant properties via the GSK3ß(Ser 9)/ß-TrCP/NRF2 pathway. MST1 may be a promising pharmacological target for the effective treatment of spinal cord injury patients with diabetes.

Disulfidptosis: Six Riddles Necessitating Solutions.

Disulfidptosis occurs as a result of the accumulation of intracellular cystine followed by disulfide stress in actin cytoskeleton proteins due to a reduction of NADPH produced through the pentose phosphate pathway in cells with high expression of SLC7A11. It is a cell death caused by the redox imbalance resulting from the disruption of amino acid metabolism and glucose metabolism. The discovery of disulfidptosis has sparked immense enthusiasm, but there are numerous unresolved issues that need to be addressed. Solutions to these riddles will provide insights into the detailed mechanisms and the pathophysiological relevance of disulfidptosis and utilizing disulfidptosis as an actionable therapeutic target.