An Integrated Nanoplatform via Dual Channel Excitation for Both Precise Fluorescence Imaging and Photodynamic Therapy of Orthotopic Breast Tumor in NIR-II Region.

Although research on photodynamic therapy (PDT) of malignant tumor has made considerable progress in recent years, it is a remaining challenge to extend PDT to the second near-infrared window (NIR-II) along with real-time and accurate NIR-II fluorescence imaging to determine drug enrichment status and achieve high treatment efficacy. In this work, lanthanide nanoparticles (Ln NPs)-based nanoplatform (LCR) equipped with photosensitizer Chlorin e6 (Ce6) and targeting molecular NH2-PEG1000-cRGDfK are developed, which can achieve NIR-II photodynamic therapy (PDT) and NIR-II fluorescence imaging by dual channel excitation. Under 808 nm excitation, Nd3+ in the outer layer can absorb the energy and transfer inward to emit strong NIR-II emissions (1064 and 1525 nm). Due to the low background noise of NIR-II light and the targeting effect of NH2-PEG1000-cRGDfK, LCR can recognize tiny tumor tissue (≈3 mm) and monitor drug distribution in vivo. Under 1530 nm excitation, internal Er3+ can be self-sensitized, generating intense upconversion emission (662 nm) that can effectively activate Ce6 for in vivo PDT due to the deep tissue penetration of NIR-II light. This study provides a paradigm of theranostic nanoplatform for both real-time fluorescence imaging and PDT of orthotopic breast tumor in NIR-II window.

Daylength variation affects growth, photosynthesis, leaf metabolism, partitioning, and metabolic fluxes.

Daylength, a seasonal and latitudinal variable, exerts a substantial impact on plant growth. However, the relationship between daylength and growth is nonproportional, suggesting the existence of adaptive mechanisms. Thus, our study aimed to comprehensively investigate the adaptive strategies employed by plants in response to daylength variation. We grew false flax (Camelina sativa) plants, a model oilseed crop, under long-day (LD) and short-day (SD) conditions and used growth measurements, gas exchange measurements, and isotopic labeling techniques, including 13C, 14C, and 2H2O, to determine responses to different daylengths. Our findings revealed that daylength influences various growth parameters, photosynthetic physiology, carbon partitioning, metabolic fluxes, and metabolite levels. SD plants employed diverse mechanisms to compensate for reduced CO2 fixation in the shorter photoperiod. These mechanisms included enhanced photosynthetic rates and reduced respiration in the light (RL), leading to increased shoot investment. Additionally, SD plants exhibited reduced rates of the glucose 6-phosphate (G6P) shunt and greater partitioning of sugars into starch, thereby sustaining carbon availability during the longer night. Isotopic labeling results further demonstrated substantial alterations in the partitioning of amino acids and TCA cycle intermediates between rapidly and slowly turning over pools. Overall, the results point to multiple developmental, physiological, and metabolic ways in which plants adapt to different daylengths to maintain growth.

Exploring factors impacting haplotype-based noninvasive prenatal diagnosis for single-gene recessive disorders.

Haplotype-based noninvasive prenatal diagnosis (NIPD) is applicable for various recessive single-gene disorders in proband families. However, a comprehensive exploration of critical factors influencing the assay performance, such as fetal fraction, informative single nucleotide polymorphism (SNP) count, and recombination events, has yet to be performed. It is critical to identify key factors affecting NIPD performance, including its accuracy and success rate, and their impact on clinical diagnostics to guide clinical practice. We conducted a prospective study, recruiting 219 proband families with singleton pregnancies at risk for eight recessive single-gene disorders (Duchenne muscular dystrophy, spinal muscular atrophy, phenylketonuria, methylmalonic acidemia, hemophilia A, hemophilia B, non-syndromic hearing loss, and congenital adrenal hyperplasia) at 7-14 weeks of gestation. Haplotype-based NIPD was performed by evaluating the relative haplotype dosage (RHDO) in maternal circulation, and the results were validated via invasive prenatal diagnosis or newborn follow-ups. Among the 219 families, the median gestational age at first blood draw was 8+5 weeks. Initial testing succeeded for 190 families and failed for 29 due to low fetal fraction (16), insufficient informative SNPs (9), and homologous recombination near pathogenic variation (4). Among low fetal fraction families, successful testing was achieved for 11 cases after a redraw, while 5 remained inconclusive. Test failures linked to insufficient informative SNPs correlated with linkage disequilibrium near the genes, with F8 and MMUT exhibiting the highest associated failure rates (14.3% and 25%, respectively). Homologous recombination was relatively frequent around the DMD and SMN1 genes (8.8% and 4.8%, respectively) but led to detection failure in only 44.4% (4/9) of such cases. All NIPD results from the 201 successful families were consistent with invasive diagnostic findings or newborn follow-up. Fetal fraction, informative SNPs count, and homologous recombination are pivotal to NIPD performance. Redrawing blood effectively improves the success rate for low fetal fraction samples. However, informative SNPs count and homologous recombination rates vary significantly across genes, necessitating careful consideration in clinical practice. We have designed an in silico method based on linkage disequilibrium data to predict the number of informative SNPs. This can identify genomic regions where there might be an insufficient number of SNPs, thereby guiding panel design. With these factors properly accounted for, NIPD is highly accurate and reliable.

First-trimester noninvasive prenatal diagnosis of seven facioscapulohumeral muscular dystrophy type 1 families using SNP-based amplicon sequencing: An earlier, rapid and safer way.

The study is to explore the feasibility and value of SNP-based noninvasive prenatal diagnosis (NIPD) for facioscapulohumeral muscular dystrophy type 1 (FSHD1) in early pregnancy weeks. We prospectively collected seven FSHD1 families, with an average gestational age of 8+6. Among these seven couples, there were three affected FSHD1 mothers and four affected fathers. A multiplex-PCR panel comprising 402 amplicons was designed to selective enrich for highly heterozygous SNPs upstream of the DUX4 gene. Risk haplotype was constructed based on familial linkage analysis. Fetal genotypes were accurately inferred through relative haplotype dosage analysis using Bayes Factor. All tests were successfully completed in a single attempt, and no recombination events were detected. NIPD results were provided within a week, which is 4 weeks earlier than karyomapping and 7 weeks earlier than Bionano single-molecule optical mapping (BOM). Ultimately, five FSHD1 fetuses and two normal fetuses were successfully identified, with a 100% concordance rate with karyomapping and BOM. Therefore, SNP-based NIPD for FSHD1 was demonstrated to be feasible and accurate in early weeks of gestation, although the risk of recombination events cannot be completely eliminated. In the future, testing of more cases is still necessary to fully determine the clinical utility.

Developing a Prognostic Model for Primary Biliary Cholangitis Based on a Random Survival Forest Model.

Background: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease with few effective treatments and a poor prognosis, and its incidence is on the rise. There is an urgent need for more targeted treatment strategies to accurately identify high-risk patients. The use of stochastic survival forest models in machine learning is an innovative approach to constructing a prognostic model for PBC that can improve the prognosis by identifying high-risk patients for targeted treatment. Method: Based on the inclusion and exclusion criteria, the clinical data and follow-up data of patients diagnosed with PBC-associated cirrhosis between January 2011 and December 2021 at Taizhou Hospital of Zhejiang Province were retrospectively collected and analyzed. Data analyses and random survival forest model construction were based on the R language. Result: Through a Cox univariate regression analysis of 90 included samples and 46 variables, 17 variables with p-values <0.1 were selected for initial model construction. The out-of-bag (OOB) performance error was 0.2094, and K-fold cross-validation yielded an internal validation C-index of 0.8182. Through model selection, cholinesterase, bile acid, the white blood cell count, total bilirubin, and albumin were chosen for the final predictive model, with a final OOB performance error of 0.2002 and C-index of 0.7805. Using the final model, patients were stratified into high- and low-risk groups, which showed significant differences with a P value <0.0001. The area under the curve was used to evaluate the predictive ability for patients in the first, third, and fifth years, with respective results of 0.9595, 0.8898, and 0.9088. Conclusion: The present study constructed a prognostic model for PBC-associated cirrhosis patients using a random survival forest model, which accurately stratified patients into low- and high-risk groups. Treatment strategies can thus be more targeted, leading to improved outcomes for high-risk patients.

Noninvasive twin genotyping for recessive monogenic disorders by relative haplotype dosage.

OBJECTIVE: To establish a haplotype-based noninvasive prenatal testing (NIPT) workflow for single-gene recessive disorders that adapt to dizygotic (DZ) twin pregnancies. METHOD: Twin pregnancies at risk of Duchenne muscular dystrophy, Becker muscular dystrophy, hemophilia B, spinal muscular atrophy, phenylketonuria, and nonsyndromic hearing loss were recruited. For subsequent analysis, capture sequencing targeting highly heterozygotic single nucleotide polymorphism sites was conducted. Paternal-specific alleles were used to calculate the total and individual fetal fractions and determine zygosity. A two-step Bayes Factor model was applied to clarify the complex genomic landscape in the maternal plasma: the first step involved determining whether the twins inherited the same haplotype, and the second step involved estimating their individual genotypes. NIPT results were subsequently confirmed by invasive diagnosis. RESULTS: Nine twin pregnancies were recruited, including five DZ and four monozygotic (MZ) twins. The earliest gestational age was 8+0 weeks, and the minimum fetal fraction was 4.6%. Three twin pregnancies were reported with one affected fetus, while the remaining six were reported without affected fetuses. Two dichorionic diamniotic twin pregnancies were confirmed to be MZ twins. The NIPT results were 100% consistent with those of invasive procedures or diagnostic genetic testing after birth. CONCLUSION: This study is the first to perform NIPT for single-gene disorders in twin pregnancies and preliminarily confirm its clinical feasibility. Acknowledging the twins' genotypes in the first trimester is valuable as it empowers obstetric care providers and parents to have adequate time for pregnancy management and decision-making.

High-Resolution Haplotyping of the PAH Gene Enables Early Gestation Noninvasive Prenatal Diagnosis of Phenylketonuria and Evolution Analysis of Recurrent Pathogenic Variations.

BACKGROUND: The clinical performance of RHDO-based NIPD for PKU during early gestation remains under-evaluated. Furthermore, studies focused on SNP loci obtained by next-generation sequencing to analyze the genetic evolution of pathogenic variations in PKU is limited. METHODS: Maternal peripheral blood, along with proband and paternal samples, was collected between 7 and 12 weeks of gestation. The PAH gene and surrounding high heterozygosity SNPs were targeted for enrichment and sequencing. Fetal genotypes were inferred using RHDO-based NIPD. High-resolution PAH haplotypes were used for the analysis of two common pathogenic variants in the Chinese population: c.728G>A and c.1238G>C. RESULTS: Sixty one PKU families participated with an average fetal fraction of 6.08%. The median gestational age was 8+6 weeks. RHDO-based NIPD successfully identified fetal genotypes in 59 cases (96.72%, 59/62). Two cases failed because of insufficient informative SNPs. In addition, a recombination event was assessed in one fetus of 59 cases. Six, and three haplotypes were identified for c.728G>A(p.Arg243Gln) and c.1238G>C(p.Arg413Pro), respectively. Hap_3 and hap_8 were identified as the ancestral haplotypes for these pathogenic variants, with other haplotypes arising from mutations or recombination based on these ancestral haplotypes. CONCLUSIONS: This study validates the feasibility of an RHDO-based assay for NIPD of PKU in early pregnancy and introduces its application in the demonstration of founder effects in recurrent pathogenic variations, offering new insights into the evolutionary analysis of PAH variations.

Mechanistic insights into aniline-induced liver injury: Role of the mmu_circ_26984/Myh9/NLRP3 axis and modulation by N-acetylcysteine.

Aniline is a widely used chemical. Chronic or high-dose exposure to aniline can lead to hepatocellular damage. Although the hepatic pathogenicity of aniline has been established in previous studies, studies involving pathogenic genes during aniline-induced liver injury are limited. Our study first discovered and identified the role and mechanism underlying a new circRNA mmu_circ_26984 in aniline-induced chemical liver injury. Further, we discuss the protective effect of N-acetylcysteine (NAC) in this pathway. After constructing in vitro and in vivo models of aniline treatment, we screened the circRNA with significant differences in expression in AML12 cells from control and aniline-treated groups by circRNA microarray analysis. Next, using RNA pulldown, liquid chromatography-mass spectrometry (LC-MS), and RNA immunoprecipitation, we analyzed the relationship between mmu_circ_26984 and myosin heavy chain 9 (Myh9). Subsequently, we determined the specific mechanism of action of mmu_circ_26984 and Myh9 in aniline-induced liver injury and the protective effect of NAC against aniline-induced liver injury process using Cell Counting Kit-8, Western blot, RNA extraction, a reverse transcription quantitative polymerase chain reaction (RT-qPCR), fluorescence in situ hybridization, immunohistochemistry, and immunofluorescence. The expression of mmu_circ_26984 was significantly increased in liver tissues and AML12 cells of aniline-treated mice compared with the control group. This high expression of mmu_circ_26984 increased the expression of injury-related inflammatory factors, such as NLRP3, Caspase-1, IL-18, and IL-1ß in vivo and ex vivo, which exacerbated the level of liver injury. The interaction of mmu_circ_26984 with Myh9 also affected the course of liver injury. Mmu_circ_26984 overexpression and reduced treatment affected the levels of Myh9 expression in AML12 cells, as well as downstream inflammatory factors associated with injury, such as NLRP3. In addition, NAC reduced the process of liver injury mediated by the mmu_circ_26984/Myh9/NLRP3 axis. In conclusion, mmu_circ_26984 is a potential molecular marker and therapeutic target in the process of aniline-induced liver injury that can mediate aniline-exposure-induced liver injury via modulation of the mmu_circ_26984/Myh9/NLRP3 axis, and NAC can effectively attenuate the effect of this liver injury.

Qualitative study on the perception of good death in patients with end-stage cancer in oncology nurses.

OBJECTIVE: To explore the perception of good death of patients with end-stage cancer by nurses in the oncology department. METHOD: In the study we used a phenomenological approach and semi-structured interviews. A total of 11 nurses from the oncology department of a Grade A hospital in Taizhou were interviewed on the cognition of good death from July 1 to September 30, 2022. Colaizzi's analysis method was used to analyse the interview data. This study followed the consolidated criteria for reporting qualitative research (COREQ). RESULT: Four themes were identified: a strong sense of responsibility and mission; To sustain hope and faith; The important role of family members; Improve patients' quality of life. CONCLUSION: The nurses in the department of oncology have a low level of knowledge about the "good death", and the correct understanding and view of the "good death" is the premise of the realization of " good death". The ability of nursing staff to improve the "good death", attention, and meet the needs and wishes of individuals and families, is the guarantee of the realization of "good death".

SOCS1 as a Biomarker Candidate for HPV Infection and Prognosis of Head and Neck Squamous Cell Carcinomas.

The pathogenesis of head and neck squamous cell carcinoma (HNSCC) is associated with human papillomavirus (HPV) infection. However, the molecular mechanisms underlying the interactions between HNSCC and HPV remain unclear. Bioinformatics was used to analyze the gene expression dataset of HPV-associated HNSCC based on the Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) in HPV-positive and HPV-negative HNSCC were screened. Gene function enrichment, protein-protein interactions (PPI), survival analysis, and immune cell infiltration of DEGs were performed. Furthermore, the clinical data of HNSCC tissue samples were analyzed using immunohistochemistry. In total, 194 DEGs were identified. A PPI network was constructed and 10 hub genes (EREG, PLCG1, ERBB4, HBEGF, ZFP42, CBX6, NFKBIA, SOCS1, ATP2B2, and CEND1) were identified. Survival analysis indicated that low expression of SOCS1 was associated with worse overall survival. Immunohistochemistry demonstrated that SOCS1 expression was higher in HPV-negative HNSCC than in HPV-positive HNSCC, and there was a positive correlation between SOCS1 expression and patient survival. This study provides new information on biological targets that may be relevant to the molecular mechanisms underpinning the occurrence and development of HNSCC. SOCS1 may play an important role in the interaction between HPV and HNSCC and serve as a potential biomarker for future therapeutic targets.

Dynamic response of photorespiration in fluctuating light environments.

Photorespiration is a dynamic process that is intimately linked to photosynthetic carbon assimilation. There is a growing interest in understanding carbon assimilation during dynamic conditions, but the role of photorespiration under such conditions is unclear. In this review, we discuss recent work relevant to the function of photorespiration under dynamic conditions, with a special focus on light transients. This work reveals that photorespiration is a fundamental component of the light induction of assimilation where variable diffusive processes limit CO2 exchange with the atmosphere. Additionally, metabolic interactions between photorespiration and the C3 cycle may help balance fluxes under dynamic light conditions. We further discuss how the energy demands of photorespiration present special challenges to energy balancing during dynamic conditions. We finish the review with an overview of why regulation of photorespiration may be important under dynamic conditions to maintain appropriate fluxes through metabolic pathways related to photorespiration such as nitrogen and one-carbon metabolism.

Development and validation of LightGBM algorithm for optimizing of Helicobacter pylori antibody during the minimum living guarantee crowd based gastric cancer screening program in Taizhou, China.

Gastric cancer continues to be a significant health concern in China, with a high incidence rate. To mitigate its impact, early detection and treatment is key. However, conducting large-scale endoscopic gastric cancer screening is not feasible in China. Instead, a more appropriate approach would be to initially screen high-risk groups and follow up with endoscopic testing as needed. We conducted a study on 25,622 asymptomatic participants aged 45-70 years from a free gastric cancer screening program in the Taizhou city government's Minimum Living Guarantee Crowd (MLGC) initiative. Participants completed questionnaires, blood tests, and underwent gastrin-17 (G-17), pepsinogen I and II (PGI and PGII), and H. pylori IgG antibody (IgG) assessments. Using the light gradient boosting machine (lightGBM) algorithm, we developed a predictive model for gastric cancer risk. In the full model, F1 score was 2.66%, precision was 1.36%, and recall was 58.14%. In the high-risk model, F1 score was 2.51%, precision was 1.27%, and recall was 94.55%. Excluding IgG, the F1 score was 2.73%, precision was 1.40%, and recall was 68.62%. We conclude that H. pylori IgG appears to be able to be excluded from the prediction model without significantly affecting its performance, which is important from a health economic point of view. It suggests that screening indicators can be optimized, and expenditures reduced. These findings can have important implications for policymakers, as we can focus resources on other important aspects of gastric cancer prevention and control.

Haplotype-based noninvasive prenatal diagnosis of methylmalonic acidemia and the discovery of a recurrent pathogenic haplotype associated with c.609G>A.

BACKGROUND: Early diagnosis and intervention are crucial for the prognosis of methylmalonic acidemia (MMA). However, research focused on early prenatal diagnosis of MMA is limited. METHODS: A 161.89kb capture panel was designed for selectively enriching highly heterozygous SNPs. Fetal genotypes were inferred using relative haplotype dosage (RHDO) and Bayes factor, followed by invasive prenatal diagnosis (IPD) for validation. A core pathogenic haplotype associated with c.609G>A was identified based on the frequency differences between pathogenic and normal haplotypes. RESULTS: We recruited 41 pregnancies at risk of MMA with a median gestational age of 8+2  weeks. The assay success rate of NIPD-MMA for maternal variants was 92.7% (38/41), and after incorporating the paternal result, the overall assay success rate reached 100% (41/41). All NIPD results were concordant with IPD. Notably, a core haplotype (hap_2), comprising 28 SNPs, demonstrates significant enrichment within pathogenic haplotypes bearing the c.609G>A variation. On average, c.609G>A carriers had 22.38 heterozygous loci within these 28 SNPs. CONCLUSION: NIPD-MMA presents a viable choice for early, accurate, and safe prenatal diagnosis. Furthermore, the discovery of the recurrent core pathogenic haplotype provides a novel approach for haplotype phasing and has the potential for realizing proband-independent NIPD in the future.

Methodological and reporting quality of systematic reviews on health effects of air pollutants were higher than extreme temperatures: a comparative study.

BACKGROUND: An increasing number of systematic reviews (SRs) in the environmental field have been published in recent years as a result of the global concern about the health impacts of air pollution and temperature. However, no study has assessed and compared the methodological and reporting quality of SRs on the health effects of air pollutants and extreme temperatures. This study aims to assess and compare the methodological and reporting quality of SRs on the health effects of ambient air pollutants and extreme temperatures. METHODS: PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Web of Science, and Epistemonikos databases were searched. Two researchers screened the literature and extracted information independently. The methodological quality of the SRs was assessed through A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The reporting quality was assessed through Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA). RESULTS: We identified 405 SRs (286 for air pollution, 108 for temperature, and 11 for the synergistic effects). The methodological and reporting quality of the included SRs were suboptimal, with major deficiencies in protocol registration. The methodological quality of SRs of air pollutants was better than that of temperature, especially in terms of satisfactory explanations for any heterogeneity (69.6% v. 45.4%). The reporting quality of SRs of air pollution was better than temperature, however, adherence to the reporting of the assessment results of risk of bias in all SRs (53.5% v. 34.3%) was inadequate. CONCLUSIONS: Methodological and reporting quality of SRs on the health effect of air pollutants were higher than those of temperatures. However, deficiencies in protocol registration and the assessment of risk of bias remain an issue for both pollutants and temperatures. In addition, developing a risk-of-bias assessment tool applicable to the temperature field may improve the quality of SRs.

The metabolic origins of non-photorespiratory CO2 release during photosynthesis: a metabolic flux analysis.

Respiration in the light (RL) releases CO2 in photosynthesizing leaves and is a phenomenon that occurs independently from photorespiration. Since RL lowers net carbon fixation, understanding RL could help improve plant carbon-use efficiency and models of crop photosynthesis. Although RL was identified more than 75 years ago, its biochemical mechanisms remain unclear. To identify reactions contributing to RL, we mapped metabolic fluxes in photosynthesizing source leaves of the oilseed crop and model plant camelina (Camelina sativa). We performed a flux analysis using isotopic labeling patterns of central metabolites during 13CO2 labeling time course, gas exchange, and carbohydrate production rate experiments. To quantify the contributions of multiple potential CO2 sources with statistical and biological confidence, we increased the number of metabolites measured and reduced biological and technical heterogeneity by using single mature source leaves and quickly quenching metabolism by directly injecting liquid N2; we then compared the goodness-of-fit between these data and data from models with alternative metabolic network structures and constraints. Our analysis predicted that RL releases 5.2 µmol CO2 g-1 FW h-1 of CO2, which is relatively consistent with a value of 9.3 µmol CO2 g-1 FW h-1 measured by CO2 gas exchange. The results indicated that ≤10% of RL results from TCA cycle reactions, which are widely considered to dominate RL. Further analysis of the results indicated that oxidation of glucose-6-phosphate to pentose phosphate via 6-phosphogluconate (the G6P/OPP shunt) can account for >93% of CO2 released by RL.

Aniline exposure activates receptor-interacting serine/threonineprotein kinase 1 and causes necroptosis of AML12 cells.

With the increased use of aniline, potential impacts on human health cannot be ignored. The hepatotoxicity of aniline is largely unknown and the underlying mechanism remains unclear. Therefore, the aim of the present study was to investigate the hepatotoxicity of aniline and elucidate the underlying mechanism. AML12 cells were exposed to different concentrations of aniline (0, 5, 10, or 20 mM) to observe changes to reactive oxygen species (ROS) production and the expression patterns of necroptosis-related proteins (RIPK1, RIPK3, and MLKL). The potential mechanism underlying aniline-induced hepatotoxicity was explored by knockout of RIPK1. The results showed that aniline induced cytotoxicity in AML12 cells in a dose-dependent manner in addition to the production of ROS and subsequent necroptosis of AML12 cells. Silencing of RIPK1 reversed upregulation of necroptosis-related proteins in AML12 cells exposed to aniline, demonstrating that aniline-induced ROS production was related to necroptosis of AML12. Moreover, aniline promoted intracellular RIPK1 activation, suggesting that the RIPK1/ROS pathway plays an important role in aniline-induced hepatotoxicity. NAC could quench ROS and inhibit necroptosis. These results provide a scientific basis for future studies of aniline-induced hepatotoxicity for the prevention and treatment of aniline-induced cytotoxicity.

Reprogramming of Plant Central Metabolism in Response to Abiotic Stresses: A Metabolomics View.

Abiotic stresses rewire plant central metabolism to maintain metabolic and energy homeostasis. Metabolites involved in the plant central metabolic network serve as a hub for regulating carbon and energy metabolism under various stress conditions. In this review, we introduce recent metabolomics techniques used to investigate the dynamics of metabolic responses to abiotic stresses and analyze the trend of publications in this field. We provide an updated overview of the changing patterns in central metabolic pathways related to the metabolic responses to common stresses, including flooding, drought, cold, heat, and salinity. We extensively review the common and unique metabolic changes in central metabolism in response to major abiotic stresses. Finally, we discuss the challenges and some emerging insights in the future application of metabolomics to study plant responses to abiotic stresses.

How resilient are localities planning for climate change? An evaluation of 50 plans in the United States.

Resilience has increasingly become the principal management priority and planning goal for cities, especially for climate change adaptation. Yet few studies have evaluated whether and how well resilience are integrated into climate change adaptation planning. In this study, we first conceptualized resilience as five key elements (i.e., system, collaboration, uncertainty, coping capacity, and adaptive capacity) and developed a coding protocol based on these key elements. We then used it to evaluate a sample of 50 climate change plans in the United States (US) that has a major adaptation component. We found that the concept of resilience has not been adequately embedded in US climate change plans and that the predominant notions of resilience has limited influence on how well plans integrate resilience. We also found that standalone adaptation plans outperform hybrid plans in addressing uncertainty and fostering systems thinking. Ultimately, major barriers exist in translating the concept of resilience into climate change planning practice. We further offer implications for cities to more effectively plan for climate resilience.

Protective effects of 4-octyl itaconate against inflammatory response in angiotensin II-induced oxidative stress in human primary retinal pigment epithelium.

4-octyl itaconate (OI) is one kind of cell-permeable derivative of itaconate to regulate inflammation and oxidative stress. However, its effects on the angiotensin II (Ang II)-induced inflammatory response and oxidative stress in human primary retinal pigment epithelium (hRPE) cells as well as its underlying mechanisms were unclear. In this study, we found that OI suppressed changes in pro-inflammatory cytokines (MCP-1, IL-8, and IL-6) and reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) via activation of Nrf2 signaling in Ang II-treated hRPE cells. A total of 645 differentially expressed long non-coding RNAs (lncRNAs) and 455 mRNAs were identified by microarray analysis. Ten lncRNAs were analyzed using the Coding-non-coding gene co-expression (CNC) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, revealing that many differentially expressed lncRNAs were enriched in immune response-related pathways, such as IL-17, TNF, and NOD-like receptor signaling. This finding suggested that OI inhibits Ang II-induced inflammatory response and oxidative stress by activating Nrf2 signaling in hRPE cells. We also provided a novel perspective on the role of lncRNAs in the protective effects of OI.

Mitochondrial Fatty Acid Synthase Utilizes Multiple Acyl Carrier Protein Isoforms.

Acyl carrier protein (ACP) is a highly conserved cofactor protein that is required by Type II fatty acid synthases (FASs). Here, we demonstrate that up to three mitochondrial ACP (mtACP) isoforms support the Arabidopsis (Arabidopsis thaliana) mitochondrially localized Type II FAS. The physiological importance of the three mtACPs was evaluated by characterizing the single, double, and triple mutants. The mtACP1 (At2g44620), mtACP2 (At1g65290), and mtACP3 (At5g47630) single mutants showed no discernible morphological growth phenotype. Functional redundancy among the three mtACPs was indicated by the embryo-lethal phenotype associated with simultaneous loss of all three mtACP genes. Characterization of all double mutant combinations revealed that although the mtacp1 mtacp3 and mtacp2 mtacp3 double mutant combinations showed no observable growth defect, the mtacp1 mtacp2 double mutant was viable but displayed delayed growth, reduced levels of posttranslationally lipoylated mitochondrial proteins, hyperaccumulation of photorespiratory Gly, and reduced accumulation of many intermediates in central metabolism. These alterations were partially reversed when the mtacp1 mtacp2 double mutant plants were grown in a nonphotorespiratory condition (i.e. 1% CO2 atmosphere) or in the presence of 2% Suc. In summary, mtACP, as a key component of mitochondrial fatty acid biosynthesis, is important in generating the fatty acid precursor of lipoic acid biosynthesis. Thus, the incomplete lipoylation of mitochondrial proteins in mtacp mutants, particularly Gly decarboxylase, affects the recovery of photorespiratory carbon, and this appears to be critical during embryogenesis.