Central-cell-produced attractants control fertilization recovery.

Animal fertilization relies on hundreds of sperm racing toward the egg, whereas, in angiosperms, only two sperm cells are delivered by a pollen tube to the female gametes (egg cell and central cell) for double fertilization. However, unsuccessful fertilization under this one-pollen-tube design can be detrimental to seed production and plant survival. To mitigate this risk, unfertilized-gamete-controlled extra pollen tube entry has been evolved to bring more sperm cells and salvage fertilization. Despite its importance, the underlying molecular mechanism of this phenomenon remains unclear. In this study, we report that, in Arabidopsis, the central cell secretes peptides SALVAGER1 and SALVAGER2 in a directional manner to attract pollen tubes when the synergid-dependent attraction fails or is terminated by pollen tubes carrying infertile sperm cells. Moreover, loss of SALs impairs the fertilization recovery capacity of the ovules. Therefore, this research uncovers a female gamete-attraction system that salvages seed production for reproductive assurance.

DT-13 inhibits the proliferation of pancreatic cancer by inducing apoptosis via AMPK-mTOR signaling.

BACKGROUND/OBJECTIVE: DT-13, the principal active component of Mysidium shortscapes from the Liliaceae family, has garnered substantial interest in cancer therapy owing to its potential anticancer properties. This study investigated the effects of DT-13 on the proliferation and apoptosis of human pancreatic cancer cell lines and aimed to elucidate the underlying mechanisms. METHODS: PANC1 and CFPAC1 cells were exposed to DT-13 and their proliferation was assessed using RTCA and clone formation assays. Apoptotic protein expression was analyzed by western blotting, and apoptotic cells were identified by flow cytometry. RNA was extracted from DT-13 treated and untreated PANC1 cells for RNA sequencing. Differentially expressed genes were identified and subjected to GO bioprocess, KEGG pathway analysis, and western blotting. Finally, to evaluate tumor growth, CFPAC1 cells were subcutaneously injected into BALB/c nude mice. RESULTS: DT-13 inhibited proliferation and induced apoptosis of PANC1 and CFPAC1 cells by activating the AMPK/mTOR pathway and suppressing p70 S6K. Moreover, DT-13 hindered the growth of CFPAC1 xenograft tumors in nude mice. CONCLUSIONS: DT-13 effectively inhibited the growth of human pancreatic cancer cells.

Plastid genome and its phylogenetic implications of Asiatic Spiraea (Rosaceae).

BACKGROUND: Spiraea L. is a genus comprising approximately 90 species that are distributed throughout the northern temperate regions. China is recognized as the center of species diversity for this genus, hosting more than 70 species, including 47 endemic species. While Spiraea is well-known for its ornamental value, its taxonomic and phylogenetic studies have been insufficient. RESULTS: In this study, we conducted sequencing and assembly of the plastid genomes (plastomes) of 34 Asiatic Spiraea accessions (representing 27 Asiatic Spiraea species) from China and neighboring regions. The Spiraea plastid genome exhibits typical quadripartite structures and encodes 113-114 genes, including 78-79 protein-coding genes (PCGs), 30 tRNA genes, and 4 rRNA genes. Linear regression analysis revealed a significant correlation between genome size and the length of the SC region. By the sliding windows method, we identified several hypervariable hotspots within the Spiraea plastome, all of which were localized in the SC regions. Our phylogenomic analysis successfully established a robust phylogenetic framework for Spiraea, but it did not support the current defined section boundaries. Additionally, we discovered that the genus underwent diversification after the Early Oligocene (~ 30 Ma), followed by a rapid speciation process during the Pliocene and Pleistocene periods. CONCLUSIONS: The plastomes of Spiraea provided us invaluable insights into its phylogenetic relationships and evolutionary history. In conjunction with plastome data, further investigations utilizing other genomes, such as the nuclear genome, are urgently needed to enhance our understanding of the evolutionary history of this genus.

The essential role of clathrin-mediated endocytosis and early endosomes in the trafficking of begomoviruses through the primary salivary glands of their whitefly vectors.

IMPORTANCE: Many plant viruses are transmitted by insect vectors in a circulative manner. For efficient transmission, the entry of the virus from vector hemolymph into the primary salivary gland (PSG) is a step of paramount importance. Yet, vector components mediating virus entry into PSG remain barely characterized. Here, we demonstrate the role of clathrin-mediated endocytosis and early endosomes in begomovirus entry into whitefly PSG. Our findings unravel the key components involved in begomovirus transport within the whitefly body and transmission by their whitefly vectors and provide novel clues for blocking begomovirus transmission.

Fibrotic Matrix Induces Mesenchymal Transformation of Epithelial Cells in Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant transformation of epithelial cells remains unknown. Herein, oral mucosa tissue from patients with OSF, OSF rat models, and their controls were used to observe the extracellular matrix changes and epithelial-mesenchymal transformation (EMT) in fibrotic lesions. Compared with controls, oral mucous tissues from patients with OSF showed an increased number of myofibroblasts, a decreased number of blood vessels, and increased type I and type III collagen levels. In addition, the oral mucous tissues from humans and OSF rats showed increased stiffness, accompanied by increased EMT activities of epithelial cells. The EMT activities of stiff construct-cultured epithelial cells were increased significantly by exogenous piezo-type mechanosensitive ion channel component 1 (Piezo1) activation, and decreased by yes-associated protein (YAP) inhibition. During ex vivo implantation, oral mucosal epithelial cells of the stiff group showed increased EMT activities and increased levels of Piezo1 and YAP compared with those in the sham and soft groups. These results indicate that increased stiffness of the fibrotic matrix in OSF led to increased proliferation and EMT of mucosal epithelial cells, in which the Piezo1-YAP signal transduction is important.

Association of RASGRP1 polymorphism with vascular complications in Chinese diabetic patients with glycemic control and antihypertensive treatment.

BACKGROUND: Studies have shown that RASGRP1 was potently associated with the onset of type 2 diabetes mellitus (T2DM), and RASGRP1 rs7403531 was significantly correlated with islet function in T2DM patients. However, the effect of RASGRP1 polymorphism on blood glucose and blood pressure in T2DM patients after continuous treatment has yet to be fully elucidated. OBJECTIVE: This study aimed to explore the association between RASGRP1 genetic polymorphism and cardiovascular complications in T2DM patients, so as to provide more evidence for the individualized treatment of T2DM patients. METHODS: We retrospectively analyzed a large-scale multicenter drug clinical study cohort that based on a 2 × 2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled design, with follow-up for 5 years. The major vascular endpoint events included cardiovascular death, non-fatal stroke, coronary heart disease, new-onset or worsening renal disease, and diabetic retinopathy. RASGRP1 rs12593201, rs56254815 and rs7403531 were finally selected as candidate single nucleotide polymorphisms. Mixed linear model and Cox hazard ratio (HR) model were used for data analysis with IBM SPSS (version 20.0 for windows; Chicago, IL). RESULTS: Our study enrolled 1357 patients with high-risk diabetes, with a mean follow-up duration of 4.8 years. RASGRP1 rs7403531 was associated with vascular events in hypoglycemic and antihypertensive therapy. Specifically, compared with CC carriers, patients with CT/TT genotype had fewer major microvascular events (HR = 0.41, 95% confidence interval (CI) 0.21-0.80, P = 0.009), and reduced the risk of major eye disease events (HR = 0.44, 95% CI 0.20-0.94, P = 0.03). For glucose lowering axis, CT/TT carriers had a lower risk of secondary nephropathy (HR = 0.48, 95% CI 0.25-0.92, P = 0.03) in patients with standard glycemic control. For blood pressure lowering axis, all cerebrovascular events (HR = 2.24, 95% CI 1.11-4.51, P = 0.025) and stroke events (HR = 2.07, 95% CI 1.03-4.15, P = 0.04) were increased in patients with CC genotype compared to those with CT/TT genotype in the placebo group, respectively. Furthermore, patients with CC genotype showed a reduced risk of major cerebrovascular events in antihypertensive group (HR = 0.36, 95% CI 0.15-0.86, P = 0.021). For RASGRP1 rs56254815, compared with the AA genotype carriers, the systolic blood pressure of AG/GG carriers in the antihypertensive group decreased by 1.5mmhg on average (P = 0.04). In the placebo group, the blood pressure of AG/GG carriers was 1.7mmHg higher than that of AA carriers (P = 0.02). CONCLUSION: We found that patients with G allele of RASGRP1 (rs56254815) showed a better antihypertensive therapy efficacy in T2DM patients. The rs7403531 T allele could reduce the risk of major microvascular events and major eye diseases in T2DM patients receiving either hypoglycemic or antihypertensive therapy. Our findings suggest that RASGRP1 genetic polymorphism might predict the cardiovascular complications in T2DM patients.

Exploiting urine-derived induced pluripotent stem cells for advancing precision medicine in cell therapy, disease modeling, and drug testing.

The field of regenerative medicine has witnessed remarkable advancements with the emergence of induced pluripotent stem cells (iPSCs) derived from a variety of sources. Among these, urine-derived induced pluripotent stem cells (u-iPSCs) have garnered substantial attention due to their non-invasive and patient-friendly acquisition method. This review manuscript delves into the potential and application of u-iPSCs in advancing precision medicine, particularly in the realms of drug testing, disease modeling, and cell therapy. U-iPSCs are generated through the reprogramming of somatic cells found in urine samples, offering a unique and renewable source of patient-specific pluripotent cells. Their utility in drug testing has revolutionized the pharmaceutical industry by providing personalized platforms for drug screening, toxicity assessment, and efficacy evaluation. The availability of u-iPSCs with diverse genetic backgrounds facilitates the development of tailored therapeutic approaches, minimizing adverse effects and optimizing treatment outcomes. Furthermore, u-iPSCs have demonstrated remarkable efficacy in disease modeling, allowing researchers to recapitulate patient-specific pathologies in vitro. This not only enhances our understanding of disease mechanisms but also serves as a valuable tool for drug discovery and development. In addition, u-iPSC-based disease models offer a platform for studying rare and genetically complex diseases, often underserved by traditional research methods. The versatility of u-iPSCs extends to cell therapy applications, where they hold immense promise for regenerative medicine. Their potential to differentiate into various cell types, including neurons, cardiomyocytes, and hepatocytes, enables the development of patient-specific cell replacement therapies. This personalized approach can revolutionize the treatment of degenerative diseases, organ failure, and tissue damage by minimizing immune rejection and optimizing therapeutic outcomes. However, several challenges and considerations, such as standardization of reprogramming protocols, genomic stability, and scalability, must be addressed to fully exploit u-iPSCs' potential in precision medicine. In conclusion, this review underscores the transformative impact of u-iPSCs on advancing precision medicine and highlights the future prospects and challenges in harnessing this innovative technology for improved healthcare outcomes.

Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days.

BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

USP16-mediated histone H2A lysine-119 deubiquitination during oocyte maturation is a prerequisite for zygotic genome activation.

Maternal-to-zygotic transition (MZT) is the first and key step in the control of animal development and intimately related to changes in chromatin structure and histone modifications. H2AK119ub1, an important epigenetic modification in regulating chromatin configuration and function, is primarily catalyzed by PRC1 and contributes to resistance to transcriptional reprogramming in mouse embryos. In this study, the genome-wide dynamic distribution of H2AK119ub1 during MZT in mice was investigated using chromosome immunoprecipitation and sequencing. The results indicated that H2AK119ub1 accumulated in fully grown oocytes and was enriched at the TSSs of maternal genes, but was promptly declined after meiotic resumption at genome-wide including the TSSs of early zygotic genes, by a previously unidentified mechanism. Genetic evidences indicated that ubiquitin-specific peptidase 16 (USP16) is the major deubiquitinase for H2AK119ub1 in mouse oocytes. Conditional knockout of Usp16 in oocytes did not impair their survival, growth, or meiotic maturation. However, oocytes lacking USP16 have defects when undergoing zygotic genome activation or gaining developmental competence after fertilization, potentially associated with high levels of maternal H2AK119ub1 deposition on the zygotic genomes. Taken together, H2AK119ub1 level is declined during oocyte maturation by an USP16-dependent mechanism, which ensures zygotic genome reprogramming and transcriptional activation of essential early zygotic genes.

Effect of Comfort Care on Perioperative Outcomes and Postoperative Recovery of Breast Cancer Patients.

Objective: The objective of this study was to evaluate the effects of comfort care on perioperative outcomes and postoperative recovery of breast cancer patients. Evaluating comfort care is important in the context of breast cancer surgery because it can potentially alleviate pain, improve patient comfort, enhance postoperative recovery, and reduce complications, ultimately leading to better patient outcomes. Methods: Between March 2020 and December 2021, 78 patients undergoing breast cancer surgery at our hospital were randomly assigned to receive either routine nursing (routine group) or comfort care (experimental group). The comfort care intervention included various components such as health education, preoperative care, intraoperative care, postoperative care, pain care, and psychological care. The routine group received standard nursing care following medical advice. Results: The patient characteristics between the two groups were comparable. Comfort care resulted in significantly higher visual analog scale (VAS) scores, indicating reduced pain, and better improvement in functional recovery of the upper limb compared to routine nursing. Comfort care was also associated with better postoperative recovery, as evidenced by lower self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores. The experimental group had a significantly lower incidence of complications compared to the routine group. Additionally, the experimental group reported better 24-hour comfort and higher nursing satisfaction. Conclusion: In conclusion, comfort care effectively reduces postoperative pain, promotes postoperative recovery, improves patient emotions, lowers the incidence of complications, and enhances comfort and care satisfaction in breast cancer patients undergoing radical surgery. These findings highlight the importance of incorporating comfort care interventions in the perioperative management of breast cancer patients. Further research and implementation of comfort care strategies may have implications for improving clinical practice and patient outcomes in the future.

CircTAOK1 regulates high glucose induced inflammation, oxidative stress, ECM accumulation, and apoptosis in diabetic nephropathy via targeting miR-142-3p/SOX6 axis.

BACKGROUND: Diabetic nephropathy (DN) is a complication caused by diabetes. Circular RNAs (circRNAs) are a kind of RNA with a closed circular structure, which has high stability and is involved in many disease-related processes. The mechanism of circRNA TAO kinase 1 (circTAOK1) in the pathogenesis and development of DN is unclear. METHODS: CircTAOK1, microRNA (miR)-142-3p, and sex-determining region Y-box transcription factor 6 (SOX6) mRNA levels were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Cell counting kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to analyze cell proliferation. Cell cycle distribution was detected by flow cytometry. Western blot assay was performed to test B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X (Bax), cleaved-caspase 3, and fibronectin (FN), collagen I (Col I), and collagen IV (Col IV) protein levels. ELISA assay was used to measure interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor (TNF-α) levels. The reactive oxygen species (ROS) and malondialdehyde (MDA) levels and the superoxide dismutase (SOD) activity were assessed by the corresponding kits. And the correlation between miR-142-3p and circTAOK1 or SOX6 was confirmed by dual luciferase reporter assay, RNA immunoprecipitation assay and RNA pull down assay. RESULTS: CircTAOK1 and SOX6 expression levels were up-regulated, while miR-142-3p expression was down-regulated in DN serum and HG-treated HK-2 cells. Knockdown of circTAOK1 could inhibit cell injury of HG-induced HK-2 cells. The inhibitory effect of circTAOK1 knockdown on HG-induced HK-2 cell injury was restored by miR-142-3p downregulation. CircTAOK1 acted as a sponge for miR-142-3p, and SOX6 was targeted by miR-142-3p. The overexpression of SOX6 could recover the effect of miR-142-3p overexpression on HG-induced HK-2 cell injury. CircTAOK1 regulated the expression of SOX6 by targeting miR-142-3p. CONCLUSION: CircTAOK1 knockdown inhibited HG-induced HK-2 cell damage in DN by the miR-142-3p/SOX6 axis.

Effects of positive psychological interventions on positive and negative emotions in depressed individuals: a systematic review and meta-analysis.

BACKGROUND: Positive psychological interventions (PPIs) are known to be effective in alleviating depression. However, the effect of PPIs on positive and negative emotions in depressed participants is not unclear. AIMS: To systematically investigate the effects of PPIs on positive and negative emotions in depressed individuals. METHODS: 6 databases were searched for randomized controlled trials of PPIs in individuals with depressive disorders or depressive symptoms. Hedges' g value was computed using a random-effects model to determine effect sizes. RESULTS: 14 trials from 13 studies were included. Our meta-analysis showed that PPIs had significant but small effects on improving positive affect (g = 0.33, p = .02), life satisfaction (g = 0.26, p = .03), happiness (g = 0.62, p = .03) and depression (g = -0.32, p = .001), and negligible effects on improving well-being (g = 0.13, p = .24) and negative affect (g = -0.15, p = .31). Subgroup analyses of depression showed that PPIs have experienced benefits in improving depression in most subgroups. In addition, none of the subgroup analyses performed for outcomes other than depression found PPIs to be more effective than controls. CONCLUSION: PPIs can improve positive affect, life satisfaction, happiness and depression in depressed individuals, but further studies are needed to validate their effects on well-being, and negative affect.

The impact of ulinastatin on wound infection and healing in patients with burn wounds: A meta-analysis.

Burn injuries result in localised tissue damage and precipitate systemic responses; routine clinical treatments, which typically include metabolic nutritional support and anti-infection therapies, do not yield optimal outcomes. Therefore, we aimed to systematically evaluate the effects of ulinastatin on wound infection and healing in patients with burns to provide reliable evidence-based recommendations for burn treatment. An electronic search of the Web of Science, PubMed, Cochrane Library, Embase, Wanfang, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure databases, supplemented by manual searches, was conducted from database inception to October 2023 to collect randomised controlled trials (RCTs) assessing the efficacy of ulinastatin for the treatment of burns. Two researchers screened all retrieved articles according to the inclusion and exclusion criteria; the included studies were evaluated for quality, and the relevant data were extracted. Stata 17.0 software was employed for data analysis. Overall, 8 RCTs with 803 patients were included, with 404 and 399 in the ulinastatin and conventional treatment groups, respectively. The analysis revealed that wound infections (odds ratio [OR] = 0.08, 95% CI: 0.02-0.35, p = 0.001) and complications (OR = 0.21, 95% CI: 0.10-0.42, p < 0.001) were significantly lower, and wound healing time (standardised mean differences [SMD] = -1.31, 95% CI: -2.05 to -0.57, p = 0.001) was significantly shorter, in the ulinastatin groups than in the control group. This meta-analysis revealed that ulinastatin can effectively reduce the incidence of wound infections and complications and significantly shorten the duration of wound healing in patients with burns, thereby promoting early recovery in these patients.

AGEs promote atherosclerosis by increasing LDL transcytosis across endothelial cells via RAGE/NF-κB/Caveolin-1 pathway.

OBJECTIVE: To elucidate the mechanism whereby advanced glycation end products (AGEs) accelerate atherosclerosis (AS) and to explore novel therapeutic strategies for atherosclerotic cardiovascular disease. METHODS AND RESULTS: The effect of AGEs on low-density lipoprotein (LDL) transcytosis across endothelial cells (ECs) was assessed using an in vitro model of LDL transcytosis. We observed that AGEs activated the receptor for advanced glycation end products (RAGE) on the surface of ECs and consequently upregulated Caveolin-1, which in turn increased caveolae-mediated LDL transcytosis and accelerated AS progression. Our molecular assessment revealed that AGEs activate the RAGE-NF-κB signaling, which then recruits the NF-κB subunit p65 to the RAGE promoter and consequently enhances RAGE transcription, thereby forming a positive feedback loop between the NF-κB signaling and RAGE expression. Increased NF-κB signaling ultimately upregulated Caveolin-1, promoting LDL transcytosis, and inhibition of RAGE suppressed AGE-induced LDL transcytosis. In ApoE-/- mice on a high-fat diet, atherosclerotic plaque formation was accelerated by AGEs but suppressed by EC-specific knockdown of RAGE. CONCLUSION: AGEs accelerate the development of diabetes-related AS by increasing the LDL transcytosis in ECs through the activation of the RAGE/NF-κB/Caveolin-1 axis, which may be targeted to prevent or treat diabetic macrovascular complications.

A new dimethylsulfoniopropionate lyase of the cupin superfamily in marine bacteria.

Dimethylsulfoniopropionate (DMSP) is a marine organosulfur compound with important roles in stress protection, marine biogeochemical cycling, chemical signalling and atmospheric chemistry. Diverse marine microorganisms catabolize DMSP via DMSP lyases to generate the climate-cooling gas and info-chemical dimethyl sulphide. Abundant marine heterotrophs of the Roseobacter group (MRG) are well known for their ability to catabolize DMSP via diverse DMSP lyases. Here, a new DMSP lyase DddU within the MRG strain Amylibacter cionae H-12 and other related bacteria was identified. DddU is a cupin superfamily DMSP lyase like DddL, DddQ, DddW, DddK and DddY, but shares <15% amino acid sequence identity with these enzymes. Moreover, DddU proteins forms a distinct clade from these other cupin-containing DMSP lyases. Structural prediction and mutational analyses suggested that a conserved tyrosine residue is the key catalytic amino acid residue in DddU. Bioinformatic analysis indicated that the dddU gene, mainly from Alphaproteobacteria, is widely distributed in the Atlantic, Pacific, Indian and polar oceans. For reference, dddU is less abundant than dddP, dddQ and dddK, but much more frequent than dddW, dddY and dddL in marine environments. This study broadens our knowledge on the diversity of DMSP lyases, and enhances our understanding of marine DMSP biotransformation.

Plastome evolution and phylogenomic insights into the evolution of Lysimachia (Primulaceae: Myrsinoideae).

BACKGROUND: Lysimachia L., the second largest genus within the subfamily Myrsinoideae of Primulaceae, comprises approximately 250 species worldwide. China is the species diversity center of Lysimachia, containing approximately 150 species. Despite advances in the backbone phylogeny of Lysimachia, species-level relationships remain poorly understood due to limited genomic information. This study analyzed 50 complete plastomes for 46 Lysimachia species. We aimed to identify the plastome structure features and hypervariable loci of Lysimachia. Additionally, the phylogenetic relationships and phylogenetic conflict signals in Lysimachia were examined. RESULTS: These fifty plastomes within Lysimachia had the typical quadripartite structure, with lengths varying from 152,691 to 155,784 bp. Plastome size was positively correlated with IR and intron length. Thirteen highly variable regions in Lysimachia plastomes were identified. Additionally, ndhB, petB and ycf2 were found to be under positive selection. Plastid ML trees and species tree strongly supported that L. maritima as sister to subg. Palladia + subg. Lysimachia (Christinae clade), while the nrDNA ML tree clearly placed L. maritima and subg. Palladia as a sister group. CONCLUSIONS: The structures of these plastomes of Lysimachia were generally conserved, but potential plastid markers and signatures of positive selection were detected. These genomic data provided new insights into the interspecific relationships of Lysimachia, including the cytonuclear discordance of the position of L. maritima, which may be the result of ghost introgression in the past. Our findings have established a basis for further exploration of the taxonomy, phylogeny and evolutionary history within Lysimachia.

Utilizing Topological Insulator Two-Dimensional Bismuth for Ultrasensitive Acoustic Detection.

Topological insulators (TIs) are characterized by a full insulating gap in the bulk and gapless edge or surface states, which have attracted tremendous attention. 2D Bi (110), as a typical TI, is of particular interest due to its low symmetry structure and topologically protected and spin-momentum-locked Dirac surface states. However, the material's potential applications are hindered by difficulties in fabrication, due to its strong semi-metallic bonding and poor stability. In this study, a novel electrochemical intercalation method for the fabrication of ultrathin Bi (110) nanosheets with the highest yield ever reported is presented. These nanosheets are stabilized through cathodic exfoliation in a reductive environment and further modification with polymer ionic liquids. The versatility of these nanosheets is demonstrated by fabricating flexible acoustic sensors with ultrahigh sensitivity. These sensors can even detect sounds as quiet as 45 dB. Furthermore, these sensors are utilized for acoustic-to-electric energy conversion and information transfer. This work offers a promising approach for scalable fabrication and preservation of ultrathin 2D TI Bi (110) nanosheets and paves the way for their integration into smart devices.

Base editing for reprogramming cyanobacterium Synechococcus elongatus.

Cyanobacteria can directly convert carbon dioxide (CO2) at the atmospheric level to biofuels, value-added chemicals and food products, making them ideal candidates to alleviate global climate change. Despite decades-long pioneering successes, the development of genome-editing tools, especially the CRISPR-Cas-based approaches, seems to lag behind other microbial chassis, slowing down the innovations of cyanobacteria. Here, we adapted and tailored base editing for cyanobacteria based on the CRISPR-Cas system and deamination. We achieved precise and efficient genome editing at a single-nucleotide resolution and demonstrated multiplex base editing in the model cyanobacterium Synechococcus elongatus. By using the base-editing tool, we successfully manipulated the glycogen metabolic pathway via the introduction of premature STOP codons in the relevant genes, building engineered strains with elevated potentials to produce chemicals and food from CO2. We present here the first report of base editing in the phylum of cyanobacteria, and a paradigm for applying CRISPR-Cas systems in bacteria. We believe that our work will accelerate the metabolic engineering and synthetic biology of cyanobacteria and drive more innovations to alleviate global climate change.

UDP-Galactopyranose Mutase Mediates Cell Wall Integrity, Polarity Growth, and Virulence in Fusarium graminearum.

CHY1 is a zinc finger protein unique to microorganisms that was found to regulate polarized tip growth in Fusarium graminearum, an important pathogen of wheat and barley. To further characterize its functions, in this study we identified CHY1-interacting proteins by affinity purification and selected UDP-galactofuranose (Galf) mutase (UGMA) for detailed characterization, because UGMA and UDP-Galf are unique to fungi and bacteria and absent in plants and animals. The interaction between CHY1 and UGMA was confirmed by yeast two-hybrid assays. Deletion of UGMA in F. graminearum resulted in significant defects in vegetative growth, reproduction, cell wall integrity, and pathogenicity. Infection with the ΔugmA mutant was restricted to the inoculated floret, and no vomitoxin was detected in kernels inoculated with the ΔugmA strain. Compared to the wild type, the ΔugmA mutant produced wide, highly branched hyphae with thick walls, as visualized by transmission electron microscopy. UGMA tagged with green fluorescent protein (GFP) mainly localized to the cytoplasm, consistent with the synthesis of Galf in the cytoplasm. The Δchy1 mutant was more sensitive, while the ΔugmA mutant was more tolerant, to cell wall-degrading enzymes. The growth of the ΔugmA mutant nearly ceased upon caspofungin treatment. More interestingly, nocodazole treatment of the ΔugmA strain attenuated its highly branched morphology, while caspofungin inhibited the degree of the twisted Δchy1 mycelia, indicating that CHY1 and UGMA probably have opposite effects on cell wall architecture. In conclusion, UGMA is an important pathogenic factor that is specific to fungi and bacteria and required for cell wall architecture, radial growth, and caspofungin tolerance, and it appears to be a promising target for antifungal agent development. IMPORTANCE The long-term use of chemical pesticides has had increasingly negative impacts on the ecological environment and human health. Low-toxicity, high-efficiency and environmentally friendly alternative pesticides are of great significance for maintaining the sustainable development of agriculture and human and environmental health. Using fungus- or microbe-specific genes as candidate targets provides a good foundation for the development of low-toxicity, environmentally friendly pesticides. In this study, we characterized a fungus- and bacterium-specific UDP-galactopyranose mutase gene, ugmA, that contributes to the synthesis of the cell wall component Galf and is required for vegetative growth, cell wall integrity, deoxynivalenol (DON) production, and pathogenicity in F. graminearum. The ugmA deletion mutant exhibited increased sensitivity to caspofungin. These results demonstrate the functional importance of UGMA in F. graminearum, and its absence from mammals and higher plants constitutes a considerable advantage as a low-toxicity target for the development of new anti-Fusarium agents.

Novel Tu translation elongation factor, mitochondrial (TUFM) homozygous variant in a consanguineous family with premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by cessation of menstruation occurring before the age of 40 years. The genetic causes of idiopathic POI remain unclear. Here we recruited a POI patient from a consanguineous family to screen for potential pathogenic variants associated with POI. Genetic variants of the pedigree were screened using whole-exome sequencing analysis and validated through direct Sanger sequencing. A homozygous variant in TUFM (c.524G>C: p.Gly175Ala) was identified in this family. TUFM (Tu translation elongation factor, mitochondrial) is a nuclear-encoded mitochondrial protein translation elongation factor that plays a critical role in maintaining normal mitochondrial function. The variant position was highly conserved among species and predicted to be disease causing. Our in vitro functional studies demonstrated that this variant causes decreased TUFM protein expression, leading to mitochondrial dysfunction and impaired autophagy activation. Moreover, we found that mice with targeted Tufm variant recapitulated the phenotypes of human POI. Thus, this is the first report of a homozygous pathogenic TUFM variant in POI. Our findings highlighted the essential role of mitochondrial genes in folliculogenesis and ovarian function maintenance.