The nature of proton-coupled electron transfer in a blue light using flavin domain.

Proton-coupled electron transfer (PCET) is key to the activation of the blue light using flavin (BLUF) domain photoreceptors. Here, to elucidate the photocycle of the central FMN-Gln-Tyr motif in the BLUF domain of OaPAC, we eliminated the intrinsic interfering W90 in the mutant design. We integrated the stretched exponential function into the target analysis to account for the dynamic heterogeneity arising from the active-site solvation relaxation and the flexible H-bonding network as shown in the molecular dynamics simulation results, facilitating a simplified expression of the kinetics model. We find that, in both the functional wild-type (WT) and the nonfunctional Q48E and Q48A, forward PCET happens in the range of 105 ps to 344 ps, with a kinetic isotope effect (KIE) measured to be ∼1.8 to 2.4, suggesting that the nature of the forward PCET is concerted. Remarkably, only WT proceeds with an ultrafast reverse PCET process (31 ps, KIE = 4.0), characterized by an inverted kinetics of the intermediate FMNH˙. Our results reveal that the reverse PCET is driven by proton transfer via an intervening imidic Gln.

Dissecting the Ultrafast Stepwise Bidirectional Proton Relay in a Blue-Light Photoreceptor.

Proton relays through H-bond networks are essential in realizing the functionality of protein machines such as in photosynthesis and photoreceptors. It has been challenging to dissect the rates and energetics of individual proton-transfer steps during the proton relay. Here, we have designed a proton rocking blue light using a flavin (BLUF) domain with the flavin mononucleotide (FMN)-glutamic acid (E)-tryptophan (W) triad and have resolved the four individual proton-transfer steps kinetically using ultrafast spectroscopy. We have found that after the photo-induced charge separation forming FMN·-/E-COOH/WH·+, the proton first rapidly jumps from the bridging E-COOH to FMN- (τfPT2 = 3.8 ps; KIE = 1.0), followed by a second proton transfer from WH·+ to E-COO- (τfPT1 = 336 ps; KIE = 2.6) which immediately rocks back to W· (τrPT1 = 85 ps; KIE = 6.7), followed by a proton return from FMNH· to E-COO- (τrPT2 = 34 ps; KIE = 3.3) with the final charge recombination between FMN·- and WH·+ to close the reaction cycle. Our results revisited the Grotthuss mechanism on the ultrafast timescale using the BLUF domain as a paradigm protein.

Robotic Manipulation Planning for Automatic Peeling of Glass Substrate Based on Online Learning Model Predictive Path Integral.

Autonomous planning robotic contact-rich manipulation has long been a challenging problem. Automatic peeling of glass substrates of LCD flat panel displays is a typical contact-rich manipulation task, which requires extremely high safe handling through the manipulation process. To this end of peeling glass substrates automatically, the system model is established from data and is used for the online planning of the robot motion in this paper. A simulation environment is designed to pretrain the process model with deep learning-based neural network structure to avoid expensive and time-consuming collection of real-time data. Then, an online learning algorithm is introduced to tune the pretrained model according to the real-time data from the peeling process experiments to cover the uncertainties of the real process. Finally, an Online Learning Model Predictive Path Integral (OL-MPPI) algorithm is proposed for the optimal trajectory planning of the robot. The performance of our algorithm was validated through glass substrate peeling tasks of experiments.

Direct Observation of Ultrafast Proton Rocking in the BLUF Domain.

We present direct observation of ultrafast proton rocking in the central motif of a BLUF domain protein scaffold. The mutant design has taken consideration of modulating the proton-coupled electron transfer (PCET) driving forces by replacing Tyr in the original motif with Trp, in order to remove the interference of a competing electron transfer pathway. Using femtosecond pump-probe spectroscopy and detailed kinetics analysis, we resolved an electron-transfer-coupled Grotthuss-type forward and reverse proton rocking along the FMN-Gln-Trp proton relay chain. The rates of forward and reverse proton transfer are determined to be very close, namely 51 ps vs. 52 ps. The kinetic isotope effect (KIE) constants associated with the forward and reverse proton transfer are 3.9 and 5.3, respectively. The observation of ultrafast proton rocking is not only a crucial step towards revealing the nature of proton relay in the BLUF domain, but also provides a new paradigm of proton transfer in proteins for theoretical investigations.

Rare earth element lanthanum protects against atherosclerosis induced by high-fat diet via down-regulating MAPK and NF-κB pathways.

Rare earth elements, which are extensively used in environmental protection, medicine, food, aerospace and other fields, have attracted widespread attention in recent years. However, the effect on atherosclerosis and its biological mechanism remains unclear. To elucidate these problems, here we performed a study that Apolipoprotein E-deficient mice were fed with high-fat diet to promote the development of atherosclerosis, meanwhile, mice were received 0.1, 0.2, 1.0, 2.0 mg/kg lanthanum nitrate (La(NO3)3) for 12 weeks. The results showed that La(NO3)3 prominently inhibited aorta morphological alternations by histopathological examination. Meanwhile, La(NO3)3 regulated serum lipids, including reducing total cholesterol and increasing high-density lipoprotein. Moreover, the oxidative stress was alleviated by La(NO3)3 intervention through enhancing superoxide dismutase and glutathione, and decreasing malondialdehyde levels. In addition, enzyme-linked immunosorbent assay analysis showed La(NO3)3 could ameliorate the dysfunction of vascular endothelium with declined endothelin-1 and increased prostacyclin. Furthermore, Western blot analysis indicated that La(NO3)3 significantly down-regulated inflammation-mediated proteins including phosphorylated p38 mitogen-activated protein kinases (p-p38 MAPK), monocyte chemo-attractant protein, intercellular adhesion molecule-1, nuclear factor-kappa B p65 (NF-κB p65), tumor necrosis factor-α, interleukin-6 and interleukin-1ß, whereas up-regulated the inhibitor of NF-κB protein. In conclusion, La(NO3)3 ameliorates atherosclerosis by regulating lipid metabolism, oxidative stress, endothelial dysfunction and inflammatory response in mice. The potential mechanism associates with the inhibition of MAPK and NF-κB signaling pathways.

Association between total water intake and dietary intake of pregnant and breastfeeding women in China: a cross-sectional survey.

BACKGROUND: Pregnant and lactating women are at high risk of insufficient water intake. The cross-sectional study was mainly designed to evaluate the water intake, including total water intake (TWI), plain water intake, and water intake from beverages and foods of 200 pregnant women and 150 breastfeeding women in Beijing. METHODS: A semi-quantitative Food Frequency Questionnaire (FFQ) was employed to assess their dietary intake, TWI, plain water, and water intake from beverages and foods. Multivariate regression analysis was conducted for evaluating the association between water intake and dietary variables. RESULTS: On average, the TWI of pregnant and breastfeeding women was 2638 mL/day and 3218 mL/day, respectively. Only 28% of pregnant women and 27% of breastfeeding women were complied with the adequate intake (AI). Water from foods was the greatest contributor to TWI both in pregnant and breastfeeding women. TWI was positively related to some dietary variables (P < 0.001). For pregnant women, with each 100 kcal/day increase in energy intake, the TWI increased by 67 mL. With each 5 g increase in daily intake of dietary protein, fat, carbohydrate and fiber, TWI increased by 72 mL, 66 mL, 22 mL, 353 mL, respectively. When the energy contribution of protein increased by 5%, TWI increased by 210 mL. The each 100 mg increase in daily sodium intake was accompanied with 52 mL increase in TWI. For breastfeeding women, with each 100 kcal/day increase in energy intake, the TWI increased by 54 mL. With each 5 g increase in daily intake of dietary protein, fat, carbohydrate and fiber, TWI increased by 53 mL, 58 mL, 16 mL, 212 mL, respectively. The each 100 mg increase in daily sodium intake was accompanied with 54 mL increase in TWI. CONCLUSIONS: A large proportion of pregnant and breastfeeding women in Beijing were not adherent to AI for TWI set by Chinese Nutrition Society. Water intake from foods was the greatest contributor to TWI both in pregnant and breastfeeding women, and maternal dietary intake posed impacts on water intake during pregnancy and lactation. More researches are required to assess the water intake and hydration status of the populations.

Association between dietary inflammatory index and bone density in lactating women at 6 months postpartum: a longitudinal study.

BACKGROUND: Chronic inflammation contributes to the risk of osteoporosis and fracture. Dietary Inflammatory Index (DII), a novel method appraising the inflammatory potential of diet, has been utilized to examine the association between diet and bone health among postmenopausal women or the elderly. However, its relationship with bone density (BD) in lactating women has not been studied. METHODS: The prospective study was conducted to assess the possible association between DII and maternal BD during lactation. We enrolled 150 lactating women in the cohort. Participants were measured ultrasonic BD as baseline values at 1 month postpartum. After five-month follow up, the participants' BD were measured again. DII scores were calculated from semi-quantitative food frequency questionnaires (FFQ) and divided into tertiles. We compared the differences in the changes of BD at 6 months postpartum without or with adjustment for potential covariates across the tertiles. RESULTS: The women in Q1 of DII scores had less bone mass loss than those in Q2 and Q3 without adjustment for any covariates (p < 0.01); after adjusting demographic characteristics such as BMI (kg/m2) at 6 months postpartum, educational level, metabolic equivalent (MET), daily energy intake (kcal/d), we found that participants in the highest tertile of DII scores had much more bone loss than those in the lowest tertile (p = 0.038). However, in the test for trend, no significant association between DII and the changes of maternal BD at 6 months postpartum was observed. CONCLUSIONS: Chinese lactating women with higher DII scores have more bone mass loss; however significant differences and trends are attenuated and/or disappear depending on covariates and confounders that are taken into account in statistical analysis. The further study should be conducted in larger population to explore whether the significant association between DII and BD exists in Chinese lactating women.

Circumdatin-Aspyrone Conjugates from the Coral-Associated Aspergillus ochraceus LCJ11-102.

Ochrazepines A-D (1-4), four new conjugates dimerized from 2-hydroxycircumdatin C (5) and aspyrone (6) by a nucleophilic addition to epoxide, were isolated from the fermentation broth of the coral-associated Aspergillus ochraceus strain LCJ11-102. Their structures including absolute configurations were determined based on spectroscopic analysis and chemical methods. Compounds 1-4 were also obtained by the semisynthesis from a nucleophilic addition of 2-hydroxycircumdatin C (5) to aspyrone (6). New compound 1 exhibited cytotoxic activity against 10 human cancer cell lines while new compounds 2 and 4 selectively inhibited U251 (human glioblastoma cell line) and compound 3 was active against A673 (human rhabdomyoma cell line), U87 (human glioblastoma cell line), and Hep3B (human liver cancer cell line) with IC50 (half maximal inhibitory concentration) values of 2.5-11.3 µM among 26 tested human cancer cell lines.

Complete genome sequence of Paris mosaic necrosis virus, a distinct member of the genus Potyvirus.

The complete genomic sequence of a novel potyvirus was determined from Paris polyphylla var. yunnanensis. Its genomic RNA consists of 9,660 nucleotides (nt) excluding the 3'-terminal poly (A) tail, containing the typical open reading frame (ORF) of potyviruses and encoding a putative large polyprotein of 3030 amino acids. The virus shares 53.9-70.1% nt sequence identity and 43.9-73.2% amino acid sequence identity with other viruses classified within the genus Potyvirus. Proteolytic cleavage sites and conserved motifs of the potyviruses were identified in the polyprotein and within individual proteins. Phylogenetic analysis indicated that the virus is most closely related to members of the BCMV subgroup. The results suggest that the virus should be classified as a novel species within the genus Potyvirus, which we tentatively name "Paris mosaic necrosis virus".

Immunomodulatory Effect of Tremella Polysaccharides against Cyclophosphamide-Induced Immunosuppression in Mice.

Polysaccharides are closely associated with immune regulation, but there are different polysaccharide effects from different sources. In this study, the aim was to investigate the effect of tremella polysaccharides (TP) in cyclophosphamide-induced immunodeficient mice. We observed the thymus and spleen index, liver and spleen pathological changes, and the levels of IL-2, IL-12, INF-γ, TGF-ß and Ig G in serum, and we also noted the mRNA expression of IL-1ß, IL-4, IL-12 and TGF-ß in liver and spleen. Besides, we also measured the best effects of different doses of TP (Low-TP was 20 mg/kg·BW, Middle-TP was 40 mg/kg·BW, and High-TP was 80 mg/kg·BW) on cyclophosphamide-induced immunosuppressed mice. The results were remarkable, and suggested that TP had a significant effect for enhancing immunity in cyclophosphamide-induced immunosuppression, and the immune enhancement of High-TP had the best results in TP-treated mice. It could significantly increase the thymus and spleen index, alleviate pathological features of immunosuppression such as the arrangement of liver sinusoid and hepatic plates was disordered, massive inflammatory cells infiltrated and fatty degeneration of hepatocytes in liver, and red pulp and white pulp were intermixed, splenic corpuscles demolished and disappeared, splenic sinusoid extended, and lymphocytes of spleen were reduced in spleen. Besides, it could also up-regulate serum levels of IL-2, IL-12, INF-γ and Ig G, reduce the level of TGF-ß in serum, markedly promote mRNA expression of IL-1ß, IL-4 and IL-12 in liver and spleen, and suppress mRNA expression of TGF-ß. Above all, TP showed preventive effect for cyclophosphamide-induced immunosuppressed mice.

The HRH4 rs11662595 mutation is associated with histamine H4 receptor dysfunction and with increased epithelial-to-mesenchymal transition progress in non-small cell lung cancer.

We previously demonstrated that histamine H4 receptor (HRH4) played important roles to suppress epithelial-to-mesenchymal transition (EMT) progress in non-small cell lung cancer (NSCLC). Furthermore, recent investigations suggested that genetic variations in HRH4 gene affected HRH4 function and eventually contributed to certain HRH4-related diseases. However, the relations between polymorphisms in HRH4 gene and NSCLC as well as their underlying mechanisms remain largely uninvestigated. This study aims to investigate the genetic effect of a nonsynonymous HRH4 polymorphism (rs11662595) on HRH4 function and its association with NSCLC both basically and clinically. For basic experiments, A549 cells were transfected with either wild type or rs11662595 mutated HRH4 clone and subjected to both in vitro and in vivo experiments. We showed that rs11662595 significantly decreased the ability of HRH4 to activate Gi protein, which resulted in facilitation of EMT progress, cell proliferation, and invasion behavior in vitro. Moreover, in vivo experiments also showed that rs11662595 attenuated the anti-EMT effects of HRH4 agonist in inoculated nu/nu mice. For clinical experiments, we performed a prospective cohort study among 624 NSCLC patients and further proved that rs11662595 was responsible for the prognosis, degree of malignancy and metastasis of NSCLC. In conclusion, these findings reveal that rs11662595 is a loss-of-function polymorphism that results in dysfunction of HRH4 and attenuates the anti-EMT function of HRH4 in NSCLC, which provides a promising biomarker for prognosis and therapy of NSCLC.

Rapid Gelling Chitosan/Polylysine Hydrogel with Enhanced Bulk Cohesive and Interfacial Adhesive Force: Mimicking Features of Epineurial Matrix for Peripheral Nerve Anastomosis.

Prompt and strong reconnection of severed peripheral nerves is crucial to nerve regeneration. The development of biocompatible nerve adhesives that are stronger than commonly used fibrin glue would be extremely beneficial to this field. We designed an in situ forming nerve adhesive hydrogel composed of chitosan and ε-polylysine (PL), which mimics the polysaccharides/protein structure of natural epineurium matrices, thus, enhancing the compatibility with nerves. Michael-type addition between the maleimide and thiol group was employed as a cross-linking reaction to eliminate foreign damage to nerves and to ensure a fast hydrogel formation speed (curing speed). Gelation occurred within 10 s, quick enough to promptly seal the transected nerve. Catechol groups conjugated onto PL molecules were demonstrated to reinforce both the bulk cohesive force of the hydrogel and the interfacial adhesive force between the hydrogel and epineurium. The storage modulus of the hydrogel was elevated to more than 2400 Pa. A superior nerve adhesion property that can tolerate 0.185 N of force (8× higher than fibrin glue) was obtained. After 8 weeks, the morphology of the repaired nerve fiber coapted by our hydrogel was very close to the morphology of normal nerve, and the axon cross ratio of the regenerated nerves coapted using hydrogel (57%) was much higher than employing the suture technique (35%). Thus, the in situ rapid gelling system offers a promising approach to the repair of severed peripheral nerves.

Pu-erh tea has in vitro anticancer activity in TCA8113 cells and preventive effects on buccal mucosa cancer in U14 cells injected mice in vivo.

Pu-erh tea is a functional tea production in China. The functional effects should be proved. The oral cancer preventive and antimetastatic effects of Pu-erh tea in vitro and in vivo have been studied respectively. Pu-erh tea showed an inhibitory effect on human tongue carcinoma TCA8113 cells proliferation tested by 3-(4,5-Dimethyl-2-Thiazolyl)-2,5-Diphenyltetrazolium Bromide assay and induced TCA8113 apoptosis shown anticancer effect. The antimetastatic effect of Pu-erh tea in TCA8113 cells was proved by the decreasing of matrix metalloproteinases (MMPs) and increasing of tissue inhibitors of metalloproteinases (TIMPs) mRNA transcription. In the animal experiments, the tumor volumes and lymph node metastasis rates of Pu-erh tea-treated mice were smaller than control mice. Pu-erh tea reduced the levels of the serum proinflammatory cytokines interleukin (IL)-6, IL-12, tumor necrosis factor-α, and interferon-γ to a greater extent compared with the control mice, and the levels of 200 µg/mL treatment was more close to the normal mice than 100 µg/mL treated mice. Pu-erh tea also significantly induced apoptosis in tissues of mice (P < 0.05) by upregulating Bax and downregulating Bcl-2. These results demonstrate Pu-erh tea has cancer preventive and anti-metastatic effects on buccal mucosa cancer, the higher concentration get better efficiency.

Preventive Effect of Polysaccharide of Larimichthys crocea Swim Bladder on Reserpine Induced Gastric Ulcer in ICR Mice.

This project's aim was to determine the reserpine-induced gastric ulcer preventive effect of polysaccharide of Larimichthys crocea swim bladder (PLCSB) in ICR mice. The anti-gastric ulcer effects of polysaccharide of Larimichthys crocea swim bladder was evaluated in mice model using morphological test, serum levels assay, cytokine levels assay, tissue contents analysis, reverse transcription-polymerase chain reaction (RT-PCR) analysis and western bolt assay. High concentration (50 mg/kg dose) of PLCSB reduced IFN-γ as compared to low concentration (25 mg/kg dose) and control mice. SS and VIP serum levels of PLCSB treated mice were higher than those of control mice, and MOT and SP serum levels were lower than control mice. Gastric ulcer inhibitory index of PLCSB treatment groups mice were much lower than control mice, and the high concentration treated mice were similar to the ranitidine treated mice. The SOD and GSH-Px activities of PLCSB treated mice were higher than control mice, close to normal mice and ranitidine treated mice. PLCSB treated mice also showed the similar contents of NO and MDA to normal group. By RT-PCR and western blot assay, PLCSB significantly induced inflammation in tissues of mice by downregulating NF-κB, iNOS, and COX-2, and upregulating IκB-α. These results suggest that PLCSB showed a good gastric ulcer preventive effect as the gastric ulcer drug of ranitidine. Polysaccharide of Larimichthys crocea swim bladder may be used as a drug material from marine products.

Association between Dietary Inflammatory Index and Bone Mineral Density Changes among Pregnant Women: A Prospective Study in China.

OBJECTIVES: This study aims to examine the relationship between dietary inflammatory index (DII) and bone mineral density (BMD) changes among Chinese pregnant women, offering valuable insights for dietary guidance during pregnancy. METHODS: 289 pregnant women were enrolled in this cohort. Serum inflammatory factors and ultrasonic BMD were measured at the first, second, and the third trimesters. DII scores were calculated based on a semi-quantitative food frequency questionnaire (FFQ) and divided into tertiles. We compared the differences in inflammatory factors in serum across the tertiles of DII and changes in BMD at the second and third trimesters across the tertiles. RESULTS: The participants with higher DII scores had higher total energy intakes than those with lower DII scores. The serum level of interleukin-6 (IL-6) was significantly different across the tertiles of the DII. Women who had lower DII scores had higher T-scores and Z-scores in the BMD assessment. In the test of trends, after adjusting potential covariates, including educational level, physical activity, body mass index, and calcium, vitamin D, or multivitamin supplements, DII values were determined to be positively related to the maternal BMD lost. CONCLUSIONS: DII was positively associated with serum IL-6. Meanwhile, higher DII scores were associated with more bone mass loss in pregnant women. We recommend adhering to a lower-DII diet to preserve BMD during pregnancy.

An investigation of association between human milk mineral patterns and infant growth.

Introduction: Human milk is widely acknowledged as the optimal food for infant aged 0 ~ 6 months. While there has been extensive documentation on the mineral and trace element composition of human milk, results on the relationship between mineral content and infant growth remain mixed. This cross-sectional study aims to explore human milk mineral patterns and to investigate associations between human milk mineral patterns, human milk metabolomic profile and infant growth. Methods: A total of 200 breast milk samples from seven cities in China was included. Human milk mineral and trace elements was detected by inductively coupled plasma mass spectrometer (ICP-MS). K-means cluster analysis was utilized to derived human milk mineral patterns. Untargeted human milk metabolomic profiles was determined using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Differences of infant growth rate and metabolomic profiles were then compared across patterns identified. Results: Three human milk mineral patterns were identified. Cluster I was characterized as the highest levels of potassium, magnesium and calcium, while the lowest levels of copper, zinc, manganese and selenium. Cluster II showed the most abundant sodium, iron, zinc, manganese and selenium. Cluster III had the lowest levels of sodium, potassium, magnesium, iron and calcium. Infants of cluster I showed significantly higher length-for-age z score (0.60 ± 2.03, p = 0.03). Compared with other clusters, samples of cluster I showed lower expression of metabolites of arachidonic acid (ARA) and nicotinate and nicotinamide metabolism pathway. Discussion: A human milk mineral pattern was identified which is related to increased infant growth rate and altered metabolic signature. Future work is needed to understand these human milk patterns in terms of biologic mechanisms and generalization to other populations.

A combination of phospholipids and long chain polyunsaturated fatty acids supports neurodevelopmental outcomes in infants: a randomized, double-blind, controlled clinical trial.

Phospholipids (PLs) and long-chain polyunsaturated fatty acids (LCPUFAs) are naturally present in breast milk and play important roles in promoting the growth of the infant. Several studies have investigated the effects of the combination of PLs and LCPUFAs on neurodevelopment. However, data on the effectiveness of infant formula containing both PLs and LCPUFAs on the neurodevelopment of infants is still scarce. This randomized, double-blind, controlled clinical study was designed to evaluate the effect of an infant formula enriched with PLs and LCPUFAs on growth parameters and neurodevelopmental outcomes in term infants up to 365 days of age. Infants were enrolled within 30 days of birth who were then randomly assigned to either a control group (n = 150) or an investigational group (n = 150). Both groups consist of cow's milk-based formula which were generally identical in terms of composition, except that the investigational formula was additionally supplemented with PLs and LCPUFAs. The infants were followed for the first year of life. Breastfed infants were the reference (n = 150). Bayley Scales of Infant Development [3rd edition (Bayley-III)], Carey Toddler Temperament Scales (TTS), MacArthur-Bates Communicative Development Inventories (CDI), Single Object Attention and Free Play Tasks were used to evaluate neurodevelopmental outcomes of infant at 365 days of age. In addition, Ages and Stages Questionnaires (ASQ) were also conducted at 120, 180, and 275 days of age. Compared to breastfeeding, both infant formulas were well-tolerated and provided adequate growth, with no adverse events being reported throughout the study. Infants of the investigational group showed higher mean scores in Bayley-III cognitive performance (104.3 vs. 99.0, p < 0.05), language (106.9 vs. 104.5, p < 0.05), and motor skills (109.2 vs. 103.9, p < 0.05) compared the control group. Similar results were being reported for other developmental scales including TTS and ASQ. Notably, the test scores of infants fed the investigational formula were similar to those who were breastfed. Our results indicate that PL and LCPUFA supplementation may be beneficial for neurodevelopment of infants throughout the first year of life. Further studies are needed to investigation long-term effects PL and LCPUFA on neurodevelopment in early life.

Origin of the multi-phasic quenching dynamics in the BLUF domains across the species.

Blue light using flavin (BLUF) photoreceptors respond to light via one of nature's smallest photo-switching domains. Upon photo-activation, the flavin cofactor in the BLUF domain exhibits multi-phasic dynamics, quenched by a proton-coupled electron transfer reaction involving the conserved Tyr and Gln. The dynamic behavior varies drastically across different species, the origin of which remains controversial. Here, we incorporate site-specific fluorinated Trp into three BLUF proteins, i.e., AppA, OaPAC and SyPixD, and characterize the percentages for the Wout, WinNHin and WinNHout conformations using 19F nuclear magnetic resonance spectroscopy. Using femtosecond spectroscopy, we identify that one key WinNHin conformation can introduce a branching one-step proton transfer in AppA and a two-step proton transfer in OaPAC and SyPixD. Correlating the flavin quenching dynamics with the active-site structural heterogeneity, we conclude that the quenching rate is determined by the percentage of WinNHin, which encodes a Tyr-Gln configuration that is not conducive to proton transfer.

The Prevalence of Anemia among Pregnant Women in China: A Systematic Review and Meta-Analysis.

The systematic review and meta-analysis were conducted to ascertain the prevalence of anemia, iron deficiency (ID), and iron deficiency anemia (IDA) among Chinese pregnant women. A total of 722 articles on maternal anemia during pregnancy published between January 2010 and December 2020 were compiled, and a systematic review and meta-analysis were conducted on 57 eligible studies including 1,376,204 pregnant women to ascertain the prevalence of anemia and the prevalence in different subgroups. The results showed that the prevalence of anemia, ID, and IDA among pregnant women in China were 30.7% (95% CI: 26.6%, 34.7%), 45.6% (95% CI: 37.0%, 54.2%), and 17.3% (95% CI: 13.9%, 20.7%), respectively. All prevalence increased with the progression of the pregnancy. There were sizable regional variations in the prevalence of anemia, ID, and IDA. Generally, lower prevalence was observed in the economically more advanced eastern region of the country, while the prevalence of ID was higher in the eastern region than that in the western region. The prevalence of anemia and IDA in rural areas was higher than that in urban areas, but ID prevalence was higher in urban areas. In conclusion, the regional differences and urban-rural disparities in the prevalence of anemia indicate the need for more context-specific interventions to prevent and treat anemia. It was found that dietary factors were one of the major causes of anemia, and iron-containing supplements and nutrition counseling could be effective interventions to reduce the prevalence of anemia, ID, and IDA among Chinese pregnant women.

Rapidly in situ forming adhesive hydrogel based on a PEG-maleimide modified polypeptide through Michael addition.

Polyethylene glycol-maleimide modified ε-polylysine (EPL-PEG-MAL) with a unique comb-shaped structure was designed and used as a novel crosslinker for thiolated chitosan (CSS). Novel polysaccharide/polypeptide bionic hydrogels based on CSS and EPL-PEG-MAL could form rapidly in situ within 1 min via Michael addition under physiological conditions. Rheological studies showed that introduction of PEG can dramatically improve the storage modulus (G') of the hydrogels and the optimal hydrogel system showed superior G' of 1,614 Pa. The maximum adhesion strength reached 148 kPa, six times higher than that of fibrin glue. Cytotoxicity test indicated that the hydrogel is nontoxic toward growth of L929 cells. Gelation time, swelling ratio, storage modulus and adhesion strength of the hydrogels can be modulated by the content of PEG-maleimide, CSS concentration and molar ratio of maleimide group to thiol group. Benefiting from the fast gelation behaviors, desirable mechanical properties, relatively high adhesive performance and no cytotoxicity, these hydrogels have the potential applications as promising biomaterials for tissue adhesion and sealing.