Accessing 7,8-Dihydroquinoline-2,5-diones via Rh-Catalyzed Olefinic C-H Activation/[4+2] Cyclization.

Herein, we report a rhodium-catalyzed C-H activation/[4+2] cyclization reaction between α,ß-unsaturated amides and iodonium ylides for the synthesis of novel 7,8-dihydroquinoline-2,5-diones and analogues. This protocol provides a series of pyridones fused with saturated cycles with good functional group compatibility, good water and air tolerance, and good to excellent yields under mild and green reaction conditions. Additionally, scale-up synthesis can be smoothly performed with as low as 0.25 mol % catalyst loading. Recycling experiments and different transformation experiments were also carried out to demonstrate the potential synthetic utility of this protocol.

GMP affected assembly behaviors of phosphatidylethanolamine monolayers elucidated by multi-resolved SFG-VS and BAM.

The interaction between nucleotide molecules and lipid molecules plays important roles in cell activities, but the molecular mechanism is very elusive. In the present study, a small but noticeable interaction between the negatively charged phosphatidylethanolamine (PE) and Guanosine monophosphate (GMP) molecules was observed from the PE monolayer at the air/water interface. As shown by the sum frequency generation (SFG) spectra and Pi-A isotherm of the PE monolayer, the interaction between the PE and GMP molecules imposes very small changes to the PE molecules. However, the Brewster angle microscopy (BAM) technique revealed that the assembly conformations of PE molecules are significantly changed by the adsorption of GMP molecules. By comparing the SFG spectra of PE monolayers after the adsorption of GMP, guanosine and guanine, it is also shown that the hydrogen bonding effect plays an important role in the nucleotide-PE interactions. These results provide fundamental insight into the structure changes during the nucleotide-lipid interaction, which may shed light on the molecular mechanism of viral infection, DNA drug delivery, and cell membrane curvature control in the brain or neurons.

Incorporating nonparametric methods for estimating causal excursion effects in mobile health with zero-inflated count outcomes.

In mobile health, tailoring interventions for real-time delivery is of paramount importance. Micro-randomized trials have emerged as the "gold-standard" methodology for developing such interventions. Analyzing data from these trials provides insights into the efficacy of interventions and the potential moderation by specific covariates. The "causal excursion effect," a novel class of causal estimand, addresses these inquiries. Yet, existing research mainly focuses on continuous or binary data, leaving count data largely unexplored. The current work is motivated by the Drink Less micro-randomized trial from the UK, which focuses on a zero-inflated proximal outcome, i.e., the number of screen views in the subsequent hour following the intervention decision point. To be specific, we revisit the concept of causal excursion effect, specifically for zero-inflated count outcomes, and introduce novel estimation approaches that incorporate nonparametric techniques. Bidirectional asymptotics are established for the proposed estimators. Simulation studies are conducted to evaluate the performance of the proposed methods. As an illustration, we also implement these methods to the Drink Less trial data.

Whole-genome Sequencing Reveals Autooctoploidy in Chinese Sturgeon and Its Evolutionary Trajectories.

The order Acipenseriformes, which includes sturgeons and paddlefishes, represents "living fossils" with complex genomes that are good models for understanding whole-genome duplication (WGD) and ploidy evolution in fishes. Here, we sequenced and assembled the first high-quality chromosome-level genome for the complex octoploid Acipenser sinensis (Chinese sturgeon), a critically endangered species that also represents a poorly understood ploidy group in Acipenseriformes. Our results show that A. sinensis is a complex autooctoploid species containing four kinds of octovalents (8n), a hexavalent (6n), two tetravalents (4n), and a divalent (2n). An analysis taking into account delayed rediploidization reveals that the octoploid genome composition of Chinese sturgeon results from two rounds of homologous WGDs, and further provides insights into the timing of its ploidy evolution. This study provides the first octoploid genome resource of Acipenseriformes for understanding ploidy compositions and evolutionary trajectories of polyploid fishes.

Structural and physicochemical effects on the starch quality of the high-quality wheat genotype caused by delayed sowing.

Background: Bread wheat is one of the most important food crops associated with ensuring food security and human nutritional health. The starch quality is an important index of high-quality wheat. It is affected by a complex series of factors; among which, suitable sowing time is a key factor. Aim and methods: To analyze the integrative effects of sowing time on the starch quality of high-quality wheat, in the present study, we selected a high-quality bread wheat cultivar Jinan 17 and investigated the effect of different sowing times on the starch properties and the related genes by analyzing X-ray diffraction patterns, apparent amylose content, thermal properties, pasting properties, in vitro starch digestibility, and qRT-PCR. Meanwhile, we also investigated the agronomic and yield performance that may be associated with the starch properties. Results: Delayed sowing had little effect on starch crystalline morphology, but there was a tendency to reduce the formation of crystals within wheat starch granules: (1) delayed sowing for 15 days altered the thermal properties of starch, including onset, peak and termination temperatures, and enthalpy changes; (2) delayed sowing for 30 days changed the thermal characteristics of starch relatively insignificant; (3) significant differences in pasting characteristics occurred: peak viscosity and hold-through viscosity increased, while final viscosity, breakdown viscosity, and setback viscosity tended to increase and then decrease, suggesting that delayed sowing caused changes in the surface of the starch granules resulting in a decrease in digestibility. Analysis of related genes showed that several key enzymes in starch biosynthesis were significantly affected by delayed sowing, leading to a reduction in apparent straight-chain starch content. In addition to starch properties, thousand-kernel weight also increased under delayed sowing conditions compared with normal sowing. Conclusion: The impact of delayed sowing on starch quality is multifaceted and complex, from the fine structure, and functional properties of the starch to the regulation of key gene expression. Our study holds significant practical value for optimizing wheat planting management and maximizing the potential in both quality and yield.

Ti3C2 nanosheet-induced autophagy derails ovarian functions.

BACKGROUND: Two-dimensional ultrathin Ti3C2 (MXene) nanosheets have gained significant attention in various biomedical applications. Although previous studies have described the accumulation and associated damage of Ti3C2 nanosheets in the testes and placenta. However, it is currently unclear whether Ti3C2 nanosheets can be translocated to the ovaries and cause ovarian damage, thereby impairing ovarian functions. RESULTS: We established a mouse model with different doses (1.25, 2.5, and 5 mg/kg bw/d) of Ti3C2 nanosheets injected intravenously for three days. We demonstrated that Ti3C2 nanosheets can enter the ovaries and were internalized by granulosa cells, leading to a decrease in the number of primary, secondary and antral follicles. Furthermore, the decrease in follicles is closely associated with higher levels of FSH and LH, as well as increased level of E2 and P4, and decreased level of T in mouse ovary. In further studies, we found that exposure toTi3C2 nanosheets increased the levels of Beclin1, ATG5, and the ratio of LC3II/Ι, leading to autophagy activation. Additionally, the level of P62 increased, resulting in autophagic flux blockade. Ti3C2 nanosheets can activate autophagy through the PI3K/AKT/mTOR signaling pathway, with oxidative stress playing an important role in this process. Therefore, we chose the ovarian granulosa cell line (KGN cells) for in vitro validation of the impact of autophagy on the hormone secretion capability. The inhibition of autophagy initiation by 3-Methyladenine (3-MA) promoted smooth autophagic flow, thereby partially reduced the secretion of estradiol and progesterone by KGN cells; Whereas blocking autophagic flux by Rapamycin (RAPA) further exacerbated the secretion of estradiol and progesterone in cells. CONCLUSION: Ti3C2 nanosheet-induced increased secretion of hormones in the ovary is mediated through the activation of autophagy and impairment of autophagic flux, which disrupts normal follicular development. These results imply that autophagy dysfunction may be one of the underlying mechanisms of Ti3C2-induced damage to ovarian granulosa cells. Our findings further reveal the mechanism of female reproductive toxicity induced by Ti3C2 nanosheets.

Ischemic insular damage and stress ulcer in patients of acute ischemic stroke.

BACKGROUND AND AIMS: Stress ulcer (SU) is a common complication in patients with acute ischemic stroke. The relationship of infarction location and the incidence of SU was unclear. Herein, we aim to investigate the association between ischemic insular damage and the development of SU. METHODS: Data were retrieved from the SPARK study (Effect of Cardiac Function on Short-Term Functional Prognosis in Patients with Acute Ischemic Stroke). We included the patients who had experienced an ischemic stroke within 7 days. The diagnosis of SU was based on clinical manifestations, including hematemesis, bloody nasogastric tube aspirate, or hematochezia. Evaluation of ischemic insular damage was conducted through magnetic resonance imaging. Cyclo-oxygenase regression analysis and Kaplan-Meier survival curves were used to assess the relationship between ischemic insular damage and the occurrence of SU. RESULTS: Among the 1357 patients analyzed, 110 (8.1%) developed SUs during hospitalization, with 69 (6.7%) experiencing infarctions in the anterior circulation. After adjusting for potential confounders, patients with ischemic insular damage exhibited a 2.16-fold higher risk of developing SUs compared to those without insular damage (p = .0206). Notably, among patients with infarctions in the anterior circulation, those with insular damage had a 2.21-fold increased risk of SUs (p = .0387). Moreover, right insular damage was associated with a higher risk of SUs compared to left insular damage or no insular damage (p for trend = .0117). Kaplan-Meier curves demonstrated early separation among groups, persisting throughout the follow-up period (all p < .0001). CONCLUSIONS: This study identified a significant independent correlation between ischemic insular damage, particularly on the right side, and the development of SU during hospitalization, indicating the need to consider prophylactic acid-suppressive treatment for patients with ischemic insular damage.

Bulked segregant RNA-seq reveals complex resistance expression profile to powdery mildew in wild emmer wheat W762.

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is one of the most destructive fungal diseases threatening global wheat production. Exploring powdery mildew resistance (Pm) gene(s) and dissecting the molecular mechanism of the host resistance are critical to effectively and reasonably control this disease. Durum wheat (Triticum turgidum L. var. durumDesf.) is an important gene donor for wheat improvement against powdery mildew. In this study, a resistant durum wheat accession W762 was used to investigate its potential resistance component(s) and profile its expression pattern in responding to Bgt invasion using bulked segregant RNA-Seq (BSR-Seq) and further qRT-PCR verification. Genetic analysis showed that the powdery mildew resistance in W762 did not meet monogenic inheritance and complex genetic model might exist within the population of W762 × Langdon (susceptible durum wheat). After BSR-Seq, 6,196 consistently different single nucleotide polymorphisms (SNPs) were called between resistant and susceptible parents and bulks, and among them, 763 SNPs were assigned to the chromosome arm 7B. Subsequently, 3,653 differentially expressed genes (DEGs) between resistant and susceptible parents and bulks were annotated and analyzed by Gene Ontology (GO), Cluster of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The potential regulated genes were selected and analyzed their temporal expression patterns following Bgt inoculation. As a result, nine disease-related genes showed distinctive expression profile after Bgt invasion and might serve as potential targets to regulate the resistance against powdery mildew in W762. Our study could lay a foundation for analysis of the molecular mechanism and also provide potential targets for the improvement of durable resistance against powdery mildew.

THBS1 regulates decidualization in URSA.

Inappropriate endometrial stromal decidualization has been implied as an important reason of many pregnancy-related complications, such as unexplained recurrent spontaneous abortion (URSA), preeclampsia and intrauterine growth restriction. Here, we observed that thrombospondin-1 (THBS1), an adhesive glycoprotein, was significantly downregulated in endometrial decidual cells from patients with URSA. The immortalized human endometrial stromal cell line T-HESC was used to investigate the possible THBS1-mediated regulation of decidualization. In vitro experiments found that the expression level of THBS1 increased with the normal decidualization process. Knockdown of THBS1 could decrease the expression levels of prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP1), two acknowledged human decidualization markers. Whereas, THBS1 overexpression could reverse these effects. The RNA sequencing results demonstrated that the extracellular regulated protein kinases (ERK) signaling pathway was potentially affected by the knockdown of THBS1. And we further confirmed that the regulation of THBS1 on decidualization was achieved through the ERK signaling pathway by the treatment of inhibitors. Moreover, knockdown of THBS1 in pregnant mice could impair decidualization and result in an increased fetus resorption rate. Altogether, our study demonstrated a crucial role of THBS1 in the pathophysiological process of URSA and provided some new insights into the research of pregnancy-related complications.

Can We Differentiate Between Primary Sjögren Syndrome and Idiopathic Multicentric Castleman Disease Based on the Characteristics of Pulmonary Cysts?

PURPOSE: To identify radiological characteristics that could help differentiate cystic lung diseases between primary Sjögren syndrome (pSS) and idiopathic multicentric Castleman disease (iMCD). PATIENTS AND METHODS: Patients with pSS or iMCD who had cysts were enrolled. Cyst characteristics (number, size, morphology, and distribution) and other accompanying manifestations (nodules, ground-glass opacities, calcification, and thickening of the bronchovascular bundles and interlobular septa) were compared between them. RESULTS: Eleven patients with pSS and 25 patients with iMCD were eligible for our study. Eleven patients with pSS (100.0%) and 23 patients with iMCD (92.0%) had round or oval cysts. None of the patients with pSS had irregular cysts, but 21 (84.0%) patients with iMCD had irregular cysts (P = 0.005). Smooth-walled cysts were present in 11 patients with pSS (100.0%) and 18 patients with iMCD (72.0%). Only 1 patient with pSS (9.1%) exhibited non-smooth-walled cysts, whereas 23 patients with iMCD (92.0%) had non-smooth-walled cysts (P = 0.003). The presence of nodules was common in both groups (P = 1.000). However, the nodules were more likely to be larger and more numerous in patients with iMCD (P < 0.001). Cysts with mural nodules (52.2%) and central nodules (47.8%) were only observed in iMCD (P = 0.007). CONCLUSION: Although regular and smooth-walled cysts were common in the 2 diseases, irregular and non-smooth-walled cysts were more often associated with iMCD than pSS. Nodules in iMCD tended to be larger and more numerous, and a close positional relationship between nodules and cysts was only observed in iMCD.

Cardiac commitment driven by MyoD expression in pericardial stem cells.

Cellular therapy holds immense promise to remuscularize the damaged myocardium but is practically hindered by limited allogeneic sources of cardiac-committed cells that engraft stably in the recipient heart after transplantation. Here, we demonstrate that the pericardial tissue harbors myogenic stem cells (pSCs) that are activated in response to inflammatory signaling after myocardial infarction (MI). The pSCs derived from the MI rats (MI-pSCs) show in vivo and in vitro cardiac commitment characterized by cardiac-specific Tnnt2 expression and formation of rhythmic contraction in culture. Bulk RNA-seq analysis reveals significant upregulation of a panel of genes related to cardiac/myogenic differentiation, paracrine factors, and extracellular matrix in the activated pSCs compared to the control pSCs (Sham-pSCs). Notably, we define MyoD as a key factor that governs the process of cardiac commitment, as siRNA-mediated MyoD gene silencing results in a significant reduction of myogenic potential. Injection of the cardiac-committed cells into the infarcted rat heart leads to long-term survival and stable engraftment in the recipient myocardium. Therefore, these findings point to pericardial myogenic progenitors as an attractive candidate for cardiac cell-based therapy to remuscularize the damaged myocardium.

Left ventricular ejection fraction <60 % is associated with short-term functional disability in patients of acute ischemic stroke.

Background and objective: The association between cardiac dysfunction and functional outcome in acute ischemic stroke (AIS) is not clear. We aimed to investigate the relationship between the routinely assessed left ventricular ejection fraction (LVEF) and functional outcomes in patients with AIS. Methods: Data came from a prospective, observational, single-center study (Effect of Cardiac Function on Short-term Functional Prognosis in Patients with Acute Ischemic Stroke, SPARK). The LVEF was assessed with transthoracic echocardiography within 7 days of stroke onset. The primary outcome was functional disability, defined as a modified Rankin Scale score of 3-6 at 90 days (range: 0-6, with higher scores indicating greater disability). We also investigated the association of the LVEF with mortality, early neurological deterioration, hospital stay, and costs. Multivariate logistic regression analysis and 2:1 propensity score matching (PSM) were performed to compare the differences in outcomes. Results: A total of 1181 patients were included in this analysis, of which 87 (7.4 %) patients were found to have LVEF of <60 %. In the entire study population, LVEF<60 % was significantly associated with functional disability at 90 days (odds ratio [OR]: 1.85, 95 % confidence intervals (CI): 1.01-3.40) after adjusting for all confounders. After PSM, the association was consistently significant (OR: 5.32, 95 % CI: 3.04-9.30). However, associations of the LVEF with mortality, early neurological deterioration, hospital stay, and costs were not consistently significant across all analyses. In the subgroup analysis, the association of LVEF of <60 % with functional disability was statistically significant in patients with non-cardioembolic stroke, but not in patients with cardioembolic stroke (P for interaction = 0.872). Conclusions: An LVEF of <60 % will likely increase the risk of functional disability in patients with AIS. Future strategies to prevent cardiac dysfunction in the acute phase are needed.

Relationship between blood cadmium levels and bone mineral density in adults: a cross-sectional study.

Introduction: Osteoporosis, a disease of reduced bone mass and microstructural deterioration leading to fragility fractures, is becoming more prevalent as aging progresses, significantly increasing the socioeconomic burden. In past studies, there has been a growing awareness of the harmful effects of heavy metals on bone, with cadmium being a significant exposure factor. The purpose of this study was to look into the association between adult bone mineral density(BMD) and blood cadmium levels. Methods: Based on information from the 2013-2014, 2017-2018 NHANES, weighted multiple regression, generalized weighted modeling, and smoothed curve fitting were utilized to investigate the association between blood cadmium and femur BMD. Furthermore, subgroup analyses were conducted to investigate any differences in the associations between age, sex, race, chronic kidney disease, and diabetes. Results: In 2,146 participants, blood cadmium levels and total femur [-0.02 (-0.03, -0.01), 0.0027], femoral neck [-0.01 (-0.02, -0.00), 0.0240], femoral trochanter [-0.01 (-0.02, -0.00), 0.0042], and intertrochanteric femoral trochanter [-0.02 (-0.03, -0.00), 0.0101] BMD were negatively correlated. Subgroup analyses showed that this association was more pronounced in women, non-Hispanic white people and other Hispanics, and those with chronic kidney disease and diabetes. Our results pointed to a negative relationship between femoral BMD and blood cadmium. This negative association varied by age, sex, race, diabetes, and chronic kidney disease. In particular, bone mineral density was more significantly negatively affected by blood cadmium levels in groups with diabetes and chronic kidney disease. Conclusion: Our findings demonstrated a significant negative association between blood cadmium levels and bone mineral density in a population of U.S. adults.

Secular trends in the prevalence of meeting 24-hour movement guidelines among U.S. adolescents: evidence from NHANES 2007-2016.

Background: The 24-Hour Movement Guidelines (24-HMG) recommend a balanced combination of physical activity (PA), sedentary behavior (SB) and sleep (SLP) for optimal health. However, there is limited understanding of how well U.S. adolescents adhere to these guidelines. This study aims to analyze the prevalence trends of meeting the 24-HMG among a nationally representative sample of U.S. general adolescents. Methods: The study included 2,273 adolescents (55.3% boys) aged 16-19 who participated in the National Health and Nutrition Examination Surveys (NHANES) from 2007 to 2016. The researchers categorized the adolescents based on whether they met various PA, SB, and SLP recommendations, as well as different combinations of these recommendations, separately for boys and girls. The prevalence rate, weighted by survey data, was calculated along with a 95% confidence interval (CI) to assess the changes in meeting the 24-HMG among U.S. adolescents across different survey years and sociodemographic subgroups. Results: In the 2015-2016 cycle, approximately 6.3% of adolescents did not meet any of the three recommendations, while only 19.2% of adolescents achieved all three guidelines. Compliance with PA and SB recommendations among adolescents has decreased over time, from 72.5% (65.9% to 79.2%) to 64.2% (57.4% to 70.9%) for PA, and from 59.0% (49.6% to 68.4%) to 46.6% (37.8% to 55.5%) for SB, respectively, from 2007-2008 cycle to 2015-2016 cycle. Boys exhibited more favorable patterns in meeting different sets of recommendations compared to girls (p-value <0.001). This includes meeting both PA and SB guidelines (15.5% for boys and 11.1% for girls) and meeting both PA and SLP guidelines (19.5% for boys and 15.7% for girls). The level of parental education was found to have effect on meeting all three guidelines (Ptrend < 0.05). Conclusion: We analyzed ten consecutive years of representative NHANES data to evaluate the prevalence meeting 24-HMG and found that the proportion of adolescents aged 16-19 in the U.S. who adhered to all three movement guidelines simultaneously has consistently remained low throughout each survey cycle. Notably, there has been a significant decline in the proportion of adolescents meeting the SB guideline.

Microbiome features in bronchoalveolar lavage fluid of patients with idiopathic inflammatory myopathy-related interstitial lung disease.

Background: Interstitial lung disease (ILD) is a common complication of idiopathic inflammatory myopathy (IIM), which is one of the connective tissue diseases (CTD). It can lead to poor prognosis and increased mortality. However, the distribution and role of the lower respiratory tract (LRT) microbiome in patients with IIM-ILD remains unclear. This study aimed to investigate the microbial diversity and community differences in bronchoalveolar lavage fluid (BALF) in patients with IIM-ILD. Methods: From 28 June 2021 to 26 December 2023, 51 individual BALF samples were enrolled, consisting of 20 patients with IIM-ILD, 16 patients with other CTD-ILD (including 8 patients with SLE and 8 with RA) and 15 patients with CAP. The structure and function of microbiota in BALF were identified by metagenomic next-generation sequencing (mNGS). Results: The community evenness of LRT microbiota within the IIM-ILD group was marginally lower compared to the other CTD-ILD and CAP groups. Nonetheless, there were no noticeable differences. The species community structure was similar among the three groups, based on the Bray-Curtis distance between the samples. At the level of genus, the IIM-ILD group displayed a considerably higher abundance of Pseudomonas and Corynebacterium in comparison to the CAP group (p < 0.01, p < 0.05). At the species level, we found that the relative abundance of Pseudomonas aeruginosa increased significantly in the IIM-ILD group compared to the CAP group (p < 0.05). Additionally, the relative abundance of Prevotella pallens was significantly higher in other CTD-ILD groups compared to that in the IIM-ILD group (p < 0.05). Of all the clinical indicators examined in the correlation analysis, ferritin level demonstrated the strongest association with LRT flora, followed by Serum interleukin-6 level (p < 0.05). Conclusion: Our research has identified particular LRT microorganisms that were found to be altered in the IIM-ILD group and were significantly associated with immune function and inflammatory markers in patients. The lower respiratory tract microbiota has potential in the diagnosis and treatment of IIM-ILD.

OsbZIP18 Is a Positive Regulator of Phenylpropanoid and Flavonoid Biosynthesis under UV-B Radiation in Rice.

In plants exposed to ultraviolet B radiation (UV-B; 280-315 nm), metabolic responses are activated, which reduce the damage caused by UV-B. Although several metabolites responding to UV-B stress have been identified in plants, the accumulation of these metabolites at different time points under UV-B stress remains largely unclear, and the transcription factors regulating these metabolites have not been well characterized. Here, we explored the changes in metabolites in rice after UV-B treatment for 0 h, 6 h, 12 h, and 24 h and identified six patterns of metabolic change. We show that the rice transcription factor OsbZIP18 plays an important role in regulating phenylpropanoid and flavonoid biosynthesis under UV-B stress in rice. Metabolic profiling revealed that the contents of phenylpropanoid and flavonoid were significantly reduced in osbzip18 mutants compared with the wild-type plants (WT) under UV-B stress. Further analysis showed that the expression of many genes involved in the phenylpropanoid and flavonoid biosynthesis pathways was lower in osbzip18 mutants than in WT plants, including OsPAL5, OsC4H, Os4CL, OsCHS, OsCHIL2, and OsF3H. Electrophoretic mobility shift assays (EMSA) revealed that OsbZIP18 bind to the promoters of these genes, suggesting that OsbZIP18 function is an important positive regulator of phenylpropanoid and flavonoid biosynthesis under UV-B stress. In conclusion, our findings revealed that OsbZIP18 is an essential regulator for phenylpropanoid and flavonoid biosynthesis and plays a crucial role in regulating UV-B stress responses in rice.

Effect of maternal serum albumin level on birthweight and gestational age: an analysis of 39200 singleton newborns.

Background: Serum albumin plays a pivotal role in regulating plasma oncotic pressure and modulating fluid distribution among various body compartments. Previous research examining the association between maternal serum albumin levels and fetal growth yielded limited and inconclusive findings. Therefore, the specific influence of serum albumin on fetal growth remains poorly understood and warrants further investigation. Methods: A retrospective study involved 39200 women who had a singleton live birth at a tertiary-care academic medical center during the period from January 2017 to December 2020. Women were categorized into four groups according to the quartile of albumin concentration during early pregnancy: Q1 group, ≤41.0 g/L; Q2 group, 41.1-42.6 g/L; Q3 group, 42.7-44.3 g/L and Q4 group, >44.3 g/L. The main outcome measures were mid-term estimated fetal weight, birthweight and gestational age. Multivariate linear and logistic regression analysis were performed to detect the independent effect of maternal serum albumin level on fetal growth after adjusting for important confounding variables. Results: In the crude analysis, a significant inverse correlation was found between early pregnancy maternal serum albumin levels and fetal growth status, including mid-term ultrasound measurements, mid-term estimated fetal weight, birthweight, and gestational age. After adjustment for a number of confounding factors, mid-term estimated fetal weight, birthweight, and birth height decreased significantly with increasing albumin levels. Compared to the Q2 group, the Q4 group had higher rates of preterm birth (aOR, 1.16; 95% CI, 1.01-1.34), small-for-gestational-age (aOR, 1.27; 95% CI, 1.11-1.45) and low birthweight (aOR, 1.41; 95% CI, 1.18-1.69), and lower rate of large-for-gestational-age (aOR, 0.85; 95% CI, 0.78-0.94). Moreover, to achieve the optimal neonatal outcome, women with higher early pregnancy albumin levels required a greater reduction in albumin levels in later pregnancy stages. Conclusions: A higher maternal serum albumin level during early pregnancy was associated with poor fetal growth, with the detrimental effects becoming apparent as early as the mid-gestation period. These findings provided vital information for clinicians to predict fetal growth status and identify cases with a high risk of adverse neonatal outcomes early on.

Artificial Methylotrophic Cells via Bottom-Up Integration of a Methanol-Utilizing Pathway.

Methanol has gained substantial attention as a substrate for biomanufacturing due to plentiful stocks and nonreliance on agriculture, and it can be sourced renewably. However, due to inevitable complexities in cell metabolism, microbial methanol conversion requires further improvement before industrial applicability. Here, we present a novel, parallel strategy using artificial cells to provide a simplified and well-defined environment for methanol utilization as artificial methylotrophic cells. We compartmentalized a methanol-utilizing enzyme cascade, including NAD-dependent methanol dehydrogenase (Mdh) and pyruvate-dependent aldolase (KHB aldolase), in cell-sized lipid vesicles using the inverted emulsion method. The reduction of cofactor NAD+ to NADH was used to quantify the conversion of methanol within individual artificial methylotrophic cells via flow cytometry. Compartmentalization of the reaction cascade in liposomes led to a 4-fold higher NADH production compared with bulk enzyme experiments, and the incorporation of KHB aldolase facilitated another 2-fold increase above the Mdh-only reaction. This methanol-utilizing platform can serve as an alternative route to speed up methanol biological conversion, eventually shifting sugar-based bioproduction toward a sustainable methanol bioeconomy.

Transcriptome Analysis of White- and Red-Fleshed Apple Fruits Uncovered Novel Genes Related to the Regulation of Anthocyanin Biosynthesis.

The red flesh coloration of apples is a result of a biochemical pathway involved in the biosynthesis of anthocyanins and anthocyanidins. Based on apple genome analysis, a high number of regulatory genes, mainly transcription factors such as MYB, which are components of regulatory complex MYB-bHLH-WD40, and several structural genes (PAL, 4CL, CHS, CHI, F3H, DFR, ANS, UFGT) involved in anthocyanin biosynthesis, have been identified. In this study, we investigated novel genes related to the red-flesh apple phenotype. These genes could be deemed molecular markers for the early selection of new apple cultivars. Based on a comparative transcriptome analysis of apples with different fruit-flesh coloration, we successfully identified and characterized ten potential genes from the plant hormone transduction pathway of auxin (GH3); cytokinins (B-ARR); gibberellins (DELLA); abscisic acid (SnRK2 and ABF); brassinosteroids (BRI1, BZR1 and TCH4); jasmonic acid (MYC2); and salicylic acid (NPR1). An analysis of expression profiles was performed in immature and ripe fruits of red-fleshed cultivars. We have uncovered genes mediating the regulation of abscisic acid, salicylic acid, cytokinin, and jasmonic acid signaling and described their role in anthocyanin biosynthesis, accumulation, and degradation. The presented results underline the relationship between genes from the hormone signal transduction pathway and UFGT genes, which are directly responsible for anthocyanin color transformation as well as anthocyanin accumulation during apple-fruit ripening.

Reconfigurable Microlens Array Enables Tunable Imaging Based on Shape Memory Polymers.

Microlens arrays (MLAs) with a tunable imaging ability are core components of advanced micro-optical systems. Nevertheless, tunable MLAs generally suffer from high power consumption, an undeformable rigid body, large and complex systems, or limited focal length tunability. The combination of reconfigurable smart materials with MLAs may lead to distinct advantages including programmable deformation, remote manipulation, and multimodal tunability. However, unlike photopolymers that permit flexible structuring, the fabrication of tunable MLAs and compound eyes (CEs) based on transparent smart materials is still rare. In this work, we report reconfigurable MLAs that enable tunable imaging based on shape memory polymers (SMPs). The smart MLAs with closely packed 200 × 200 microlenses (40.0 µm in size) are fabricated via a combined technology that involves wet etching-assisted femtosecond laser direct writing of MLA templates on quartz, soft lithography for MLA duplication using SMPs, and the mechanical heat setting for programmable reconfiguration. By stretching or squeezing the shape memory MLAs at the transition temperature (80 °C), the size, profiles, and spatial distributions of the microlenses can be programmed. When the MLA is stretched from 0 to 120% (area ratio), the focal length is increased from 116 to 283 µm. As a proof of concept, reconfigurable MLAs and a 3D CE with a tunable field of view (FOV, 160-0°) have been demonstrated in which the thermally triggered shape memory deformation has been employed for tunable imaging. The reconfigurable MLAs and CEs with a tunable focal length and adjustable FOV may hold great promise for developing smart micro-optical systems.