Unlocking Diverse π-Bond Enrichment Frameworks by the Synthesis and Conversion of Boronated Phenyldiethynylethylenes.

The π-bond enrichment frameworks not only serve as a crucial building block in organic synthesis but also assume a pivotal role in the fields of materials science, biomedicine, photochemistry, and other related disciplines owing to their distinctive structural characteristics. The incorporation of various substituents into the C═C double bonds of tetrasubstituted alkenes is currently a highly significant research area. However, the synthesis of tetrasubstituted alkenes with diverse substituents on double bonds poses a significant challenge in achieving stereoselectivity. Here, we reported an efficient and convergent route of Cu-catalyzed borylalkynylation of both symmetrical and unsymmetrical 1,3-diynes, B2pin2, and acetylene bromide to the construction of boronated phenyldiethynylethylene (BPDEE) derivatives with excellent chemo-, stereo-, and regioselectivities. BPDEE derivatives could transform into novel tetrasubstituted organic π-conjugated gem-diphenyldiethynylethylene (DPDEE), vinylphenyldiethynylethylene (VPDEE), and phenyltriethynylethylene (PTEE) derivatives by a stepwise process, which provides a flexible platform for the synthesis of complex π-bond enrichment frameworks that were difficult to synthesize by previous methods. The initial optical characterization revealed that the synthesized molecules exhibited aggregation-induced emission (AIE) properties, which further establishes the groundwork for future applications and enriches and advances the field of functional π-conjugated frameworks research.

SARS-CoV-2 Accessory Protein Orf7b Induces Lung Injury via c-Myc Mediated Apoptosis and Ferroptosis.

The pandemic of coronavirus disease 2019 (COVID-19) has been the foremost modern global public health challenge. The airway is the primary target in severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) infection, with substantial cell death and lung injury being signature hallmarks of exposure. The viral factors that contribute to cell death and lung injury remain incompletely understood. Thus, this study investigated the role of open reading frame 7b (Orf7b), an accessory protein of the virus, in causing lung injury. In screening viral proteins, we identified Orf7b as one of the major viral factors that mediates lung epithelial cell death. Overexpression of Orf7b leads to apoptosis and ferroptosis in lung epithelial cells, and inhibitors of apoptosis and ferroptosis ablate Orf7b-induced cell death. Orf7b upregulates the transcription regulator, c-Myc, which is integral in the activation of lung cell death pathways. Depletion of c-Myc alleviates both apoptotic and ferroptotic cell deaths and lung injury in mouse models. Our study suggests a major role of Orf7b in the cell death and lung injury attributable to COVID-19 exposure, supporting it as a potential therapeutic target.

Antimicrobial peptide WAM-1: a promising antibacterial and anti-inflammatory drug against carbapenem-resistant Klebsiella pneumoniae.

BACKGROUND: The emergence and spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) pose a threat to public health. Antimicrobial peptides provide a new treatment option for CRKP infections. OBJECTIVES: We studied antibacterial activities of WAM-1 against CRKP in vitro and in vivo and explored its possible mechanism. We verified safety and factors affecting antibacterial effect. Furthermore, anti-inflammatory effects were investigated. METHODS: We selected eight CRKP and eight carbapenem-susceptible K. pneumoniae to explore the antibacterial activity of WAM-1 by broth microdilution (BMD). The possible mechanism was investigated by alkaline phosphatase leakage and propidium iodide (PI). We evaluated safety of WAM-1 by cytotoxicity and haemolysis and effects of temperature and serum on the antibacterial activity. We investigated in vivo efficacy of WAM-1 by the Galleria mellonella infection model. We investigated the effect of WAM-1 on TNF-α. RESULTS: BMD showed that WAM-1 had a good antibacterial effect with MICs of 2-4 mg/L and MBCs of 4-8 mg/L. RT-qPCR showed that WAM-1 could inhibit the expression of TNF-α. The cytotoxicity and haemolysis test proved that WAM-1 had certain potential application in vivo. Alkaline phosphatase leakage and PI fluorescence showed that WAM-1 was highly likely to exert an antibacterial effect by destroying bacterial membrane. The G. mellonella infection model suggested that WAM-1 may have a good therapeutic effect in vivo. Temperature had little effect on the activity of WAM-1. Serum, however, reduced WAM-1 activity. CONCLUSIONS: WAM-1 has good antibacterial effect and potential anti-inflammatory effect on infection caused by CRKP.

Taohong Siwu decoction promotes the process of fracture healing by activating the VEGF-FAK signal pathway and systemically regulating the gut microbiota.

AIMS: This study aimed to explore the effect of Taohong Siwu Decoction (THSWD) on bone marrow mesenchymal stem cells (BMSCs) at the cellular level and the possible mechanism of systemic regulation of gut microbiota on fracture recovery. METHODS AND RESULTS: Cell Counting Kit-8 (CCK-8) experiments show that THSWD effectively promotes the proliferation of BMSCs. Transwell and wound healing assays show that THSWD effectively promotes the invasion and migration of BMSCs. Alizarin red staining showed that the THSWD model enhanced the osteogenic differentiation of BMSCs. Moreover, the effect of THSWD on BMSCs is time- and concentration-dependent. RT-qPCR and western blot results showed that THSWD treatment up-regulated the expression of vascular endothelial growth factor (VEGF) and focal adhesion kinase (FAK) at mRNA and protein levels, respectively. Haematoxylin-eosin and crocin O-quick green staining showed that after 14 days of THSWD treatment, the area of callus and cartilage regeneration at the fracture site increased significantly in rats with right femoral shaft fractures. Gut microbiota was changed in fractured rats, such as the abundance of Bacteroidetes and Firmicutes was increased. THSWD showed positive regulation of both to a certain extent. CONCLUSION: THSWD up-regulates VEGF and activates the FAK signalling pathway to enhance the development and differentiation of BMSCs, and systematically regulates the gut microbiota to promote fracture healing. SIGNIFICANCE AND IMPACT OF STUDY: This study provides new insights on the cellular and systemic level to understand the mechanism of THSWD in the treatment of fractures.

MOF-Derived Bifunctional Co0.85Se Nanoparticles Embedded in N-Doped Carbon Nanosheet Arrays as Efficient Sulfur Hosts for Lithium-Sulfur Batteries.

Lithium-sulfur batteries possess the merits of low cost and high theoretical energy density but suffer from the shuttle effect of lithium polysulfides and slow redox kinetics of sulfur. Herein, novel Co0.85Se nanoparticles embedded in nitrogen-doped carbon nanosheet arrays (Co0.85Se/NC) were constructed on carbon cloth as the self-supported host for a sulfur cathode using a facile fabrication strategy. The interconnected porous carbon-based structure of the Co0.85Se/NC could facilitate the rapid electron and ion transfer kinetics. The embedded Co0.85Se nanoparticles can effectively capture and catalyze lithium polysulfides, thus accelerating the redox kinetics and stabilizing sulfur cathodes. Therefore, the Co0.85Se/NC-S cathode could maintain a stable cycle performance for 400 cycles at 1C and deliver a high discharge specific capacity of 1361, 1001, and 810 mAh g-1 at current densities of 0.1, 1, and 3C, respectively. This work provides an efficient design strategy for high-performance lithium-sulfur batteries with high energy densities.

Construction of Axially Chiral Arylborons via Atroposelective Miyaura Borylation.

Compared with the well-developed centrally chiral boron chemistry, C-B axially chiral chemistry remains elusive and challenging. Herein we report the first atroposelective Miyaura borylation of bromoarenes with unsymmetrical diboron reagents for the direct catalytic synthesis of optically active atropisomeric arylborons. This reaction features broad substrate scope and produces axially chiral arylborons with high yields and good enantioselectivities.

Tanshinone IIA Ameliorates Inflammation Response in Osteoarthritis via Inhibition of miR-155/FOXO3 Axis.

BACKGROUND: Osteoarthritis (OA) is the most common joint disorder characterized by degeneration of the articular cartilage and joint destruction with an associated risk of mobility disability in elderly people. Although a lot of achievements have been made, OA is still regarded as an incurable disease. Therefore, the pathological mechanisms and novel therapeutic strategies of OA need more investigation. METHODS: MTT assay was conducted to measure the viability of chondrocytes after LPS treatment. Cell apoptosis was analyzed by annexin V/propidium iodide labeling. ELISA was used to determine the concentrations of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in the culture supernatant of chondrocytes. The expression level of miR-155, IL-1ß, FOXO3, TNF-α, IL-6, caspase-3, and caspase-9 in chondrocytes was analyzed by RT-qPCR or Western blot. RESULTS: We found that LPS led to inflammatory responses, cell apoptosis, and increased miR-155 expression in human articular chondrocytes. Tanshinone IIA could inhibit LPS-induced inflammation and cell apoptosis of chondrocytes via regulating the expression of miR-155 and FOXO3. miR-155 directly targeted the 3'-UTR of FOXO3 to regulate its expression. CONCLUSIONS: Taken together, our data suggest tanshinone IIA ameliorates inflammation response in OA via inhibition of the miR-155/FOXO3 axis, and provide some evidences that tanshinone IIA could be designed and developed as a new promising clinical therapeutic drug for OA patients.

Chiral Brønsted Acid from Chiral Phosphoric Acid Boron Complex and Water: Asymmetric Reduction of Indoles.

A new chiral Brønsted acid, generated in situ from a chiral phosphoric acid boron (CPAB) complex and water, was successfully applied to asymmetric indole reduction. This "designer acid catalyst", which is more acidic than TsOH as suggested by DFT calculations, allows the unprecedented direct asymmetric reduction of C2-aryl-substituted N-unprotected indoles and features good to excellent enantioselectivities with broad functional group tolerance. DFT calculations and mechanistic experiments indicates that this reaction undergoes C3-protonation and hydride-transfer processes. Besides, bulky C2-alkyl-substituted N-unprotected indoles are also suitable for this system.

CuO Nanoplates for High-Performance Potassium-Ion Batteries.

Potassium-ion batteries (KIBs) are promising alternatives to lithium-ion batteries because of the abundance and low cost of K. However, an important challenge faced by KIBs is the search for high-capacity materials that can hold large-diameter K ions. Herein, copper oxide (CuO) nanoplates are synthesized as high-performance anode materials for KIBs. CuO nanoplates with a thickness of ≈20 nm afford a large electrode-electrolyte contact interface and short K+ ion diffusion distance. As a consequence, a reversible capacity of 342.5 mAh g-1 is delivered by the as-prepared CuO nanoplate electrode at 0.2 A g-1 . Even after 100 cycles at a high current density of 1.0 A g-1 , the capacity of the electrode remains over 206 mAh g-1 , which is among the best values for KIB anodes reported in the literature. Moreover, a conversion reaction occurs at the CuO anode. Cu nanoparticles form during the first potassiation process and reoxidize to Cu2 O during the depotassiation process. Thereafter, the conversion reaction proceeds between the as-formed Cu2 O and Cu, yielding a reversible theoretical capacity of 374 mAh g-1 . Considering their low cost, easy preparation, and environmental benignity, CuO nanoplates are promising KIB anode materials.

Study of wide-spectrum and high-resolution diffraction optical elements by stacks of binary phase gratings.

This work theoretically investigates wide-spectrum and high-resolution diffraction optical elements that are made of stacks of low-resolution binary phase gratings, whereby the two-dimensional grids in different grating layers are arranged with specified displacements. We remodel the common kinoform algorithm for this multi-scale architecture. Numerical computations show that, by increasing the number of stacking layers, the resolution of the far-field image can be improved and also that the optical elements are more insensitive to variations of incident wavelengths at the cost of part accuracy of the image reconstructions. Practical concern focuses on largely increasing the number of grating layers and efficiency of the optical designs in theory and on the manufacture of stacks of ultra-thin grating films.

Non-invasive biopsy of doped-ions inside optical substrate by modified two-photon microscopy.

Doped-ion based optical elements play key roles in optical signal processes, including amplification, absorption, wavelength-filtering, lighting, and polarizing plate. Non-invasively mapping the spatial distribution of the ion concentrations in these optical elements is highly desirable either during the fabrication process or to determine their optical qualities. In this work, we applied modified two-photon fluorescence (m-TPF) microscopy to trace the ion-distributions deep inside the optical elements. For demonstration purposes, polyvinyl alcohol (PVA) polymer films inside polarizing plates are taken as an example, where the spatial distributions of Iodine-dyed ions were measured by the m-TPF microscope in a fast and non-invasive way. The durability of the polarizer films can be distinguished from the axial distribution of the Iodine-dyed ions, without the need to perform a biopsy. This proposed method and demonstrated results show great potential for monitoring the spatial distributions of doped-ions in the optical elements quickly and non-destructively, which would be of great benefit in both scientific research and industrial applications.

Vitamin D supplementation is associated with higher serum 25OHD in Asian and White infants living in Vancouver, Canada.

To prevent rickets, the Health Canada and the American Academy of Pediatrics recommend that breastfed infants receive a daily vitamin D supplement of 10 µg d(-1) . Compliance with this recommendation is variable and its effect on infant vitamin D status is unclear. We measured serum 25-hydroxyvitamin D (25OHD) in Asian immigrant (n=28) and White (n=37) mothers and their infants aged 2-4 months living in Vancouver (49°N). Mothers completed health and demographic questionnaires. All subjects were term infants who were primarily breastfed. Analysis of variance, χ(2) , multiple regression and logistic regression analysis were performed as appropriate. Mean 25OHD of the infants was 31 (95% confidence interval 28-34) ng mL(-1) . Only two infants had a 25OHD concentration indicative of deficiency, <10 ng mL(-1) . Of the infants, 14% (n=9) and 49% (n=32) were vitamin D insufficient based on two commonly used cut-offs of 20 and 30 ng mL(-1) , respectively. Fifty-eight (89%) infants had been given a vitamin D supplement. Mean 25OHD was 9.4 ng mL(-1) higher in infants consuming ≥10 µg d(-1) of vitamin D from supplements vs. those consuming less (P=0.003). Mother's 25OHD, season, skin colour or ethnicity (Asian vs. White) did not influence infant 25OHD. The infants in our study, most of whom received vitamin D supplements, were generally protected against low 25OHD. The study was limited by sample size and the nature of the cross-sectional study design.

25-Hydroxyvitamin D concentrations in children with Crohn's disease supplemented with either 2000 or 400 IU daily for 6 months: a randomized controlled study.

OBJECTIVES: To assess vitamin D status of pediatric patients with Crohn's disease (CD) and to compare their serum 25-hydroxyvitamin D (s-25OHD) with established cutoffs and assess whether 6 months of supplementation with 2000 IU/d, vs 400 IU/d, would reduce the group prevalence of vitamin D below these cutoffs. STUDY DESIGN: Subjects 8-18 years (n = 83) with quiescent CD were randomized to either 400 or 2000 IU vitamin D3/d for 6 months. RESULTS: Baseline mean ± SD s-25OHD was 24 ± 8 ng/mL; 13 subjects (16%) had an s-25OHD <16 ng/mL, 27 (33%) < 20 ng/mL, and 65 (79%) < 30 ng/mL. There was no significant difference between groups in achieving the cutoffs of 16 ng/mL or 20 ng/mL at 6 months; however, only 35% of the 400 IU group achieved the greater cutoff of 30 ng/mL compared with 74% in the 2000 IU group (P < .001). Baseline adjusted mean s-25OHD concentrations at 6 months were 9.6 ng/mL (95% CI 6.0-13.2, P < .001) greater in the 2000 IU than the 400 IU group. Disease activity was not affected by supplement dose. Few subjects exceeded safety marker cutoffs, and this did not differ by dose. CONCLUSIONS: At baseline, a high proportion of patients had a mean s-25OHD >20 ng/mL. 2000 IU vitamin D3/d is more effective in raising s-25OHD concentrations to > 30 ng/mL in children with CD than 400 IU/d, but both treatments were equally effective at achieving 16 or 20 ng/mL.

Manganese-enriched prussian blue nanohybrids with smaller electrode potential and lower charge transfer resistance to enhance combination therapy.

Prussian blue (PB) is authenticated in clinical treatment, while it generally exhibits unfavorable chemodynamic therapy (CDT) performance. Herein, we developed manganese-doped prussian blue (PBM) nanoparticles to significantly enhance both CDT and photothermal therapy (PTT) effect. The lower redox potential of Mn3+/2+ (0.088 V) in PBM against that of Fe2+/3+ (0.192 V) in PB leads to favorable electron transfer of PBM with respect to PB. Besides, PBM has a lower charge-transfer resistance (Rct) of 2.98 Ω than 4.83 Ω of PB. Once PBM entering the tumor microenvironment (TME), Mn3+ may be readily reduced by glutathione (GSH) and therein to enhance intracellular oxidative stress. Meanwhile, the superoxide dismutase (SOD)-like activity of PBM facilitates the conversion of endogenous superoxide (O2•-) into H2O2. Mn2+ subsequently catalyzes H2O2 to generate toxic hydroxyl radicals (•OH). Notably, the PBM plus laser irradiation can effectively trigger a robust immunogenic cell death (ICD) due to the combination therapy of CDT and PTT. Additionally, the mice treated by PBM followed by laser irradiation efficiently avoided splenomegaly and lung metastasis, along with significant up-regulation of the Stimulator of Interferon Genes (STING) expression. Overall, PBM significantly inhibits tumor growth and metastasis, making it a promising multifunctional nanoplatform for cancer treatment.

Prevalence and risk factors for proximal deep vein thrombosis at admission in patients with traumatic fractures: a multicenter retrospective study.

Objective: This study aimed to determine the associated risk factors for proximal deep vein thrombosis (DVT) in patients with lower extremity and pelvic-acetabular fractures. Methods: The medical records of 4,056 patients with lower extremity and pelvic-acetabular fractures were retrospectively reviewed. The patients were classified into proximal or non-proximal DVT groups. Logistic regression models were used to determine the independent risk variables for proximal DVT. The predictive value of the related risk factors was further analyzed using receiver operating characteristic curves. Results: The prevalence of proximal DVT was 3.16%. Sex, body mass index (BMI), fracture site, injury mechanism, diabetes, coronary heart disease (CHD), injury-to-admission interval, hematocrit, platelet counts, and D-dimer levels differed significantly between the two groups. BMI ≥ 24.0 kg/m2, femoral shaft fractures, high-energy injury, diabetes, injury-to-admission interval >24 h were independent risk factors for proximal DVT. CHD decreased the risk of proximal DVT. The platelet and D-dimer had high negative predictive value for predicting proximal DVT formation, with cut-off values of 174 × 109/L and 2.18 mg/L, respectively. Conclusion: BMI ≥ 24.0 kg/m2, femoral shaft fractures, high-energy injury, diabetes, injury-to-admission interval >24 h were independent risk factors for proximal DVT in patients with lower extremity and pelvic-acetabular fractures. Platelet count and D-dimer level were effective indicators for excluding proximal DVT occurrence. CHD decreased the risk of proximal DVT.

Correlation Analysis between Intrarenal Small Artery Intimal Thickening and Clinicopathological Features and Prognosis in Primary Membranous Nephropathy Patients.

BACKGROUND: Primary membranous nephropathy (PMN) is the most common pathological type of nephrotic syndrome in adults. Intrarenal small artery intimal thickening can be observed in most renal biopsies. The purpose of this study was to investigate the association between intrarenal small artery intimal thickening and clinicopathological features and prognosis in PMN patients. METHODS: Data were continuously collected from patients who were diagnosed with PMN in Shenzhen Second People's Hospital (The First Affiliated Hospital of Shenzhen University) from 2008 to 2021 for a retrospective cohort study. Regression analysis and survival analysis were used to analyze the relationship between intrarenal small artery intimal thickening and renal prognosis in PMN patients. RESULTS: 300 PMN patients were enrolled in this study, including 165 patients (55%) with intrarenal small artery intimal thickening. Patients with intimal thickening were older, with higher BMI, systolic blood pressure and diastolic blood pressure, serum uric acid, a higher proportion of hypertension, acute kidney injury, nephrotic syndrome, more urine protein, and lower eGFR. Multivariate Cox regression analysis showed that after adjusting for age, gender, hypertension, BMI, urine protein, eGFR, and the use of ACEI/ARB and hormone immunosuppressants, intimal thickening was a risk factor for renal prognosis in PMN patients (HR = 3.68, 95% CI 1.36-9.96, p < 0.05). Kaplan-Meier survival curve analysis showed that the incidence of reaching the renal composite outcome was higher in the intimal thickening group (p < 0.05). CONCLUSION: The prognosis of PMN patients with intrarenal small artery intimal thickening is worse, so early intervention is very important for these patients.

Automated Restarting Fast Proximal Gradient Descent Method for Single-View Cone-Beam X-ray Luminescence Computed Tomography Based on Depth Compensation.

Single-view cone-beam X-ray luminescence computed tomography (CB-XLCT) has recently gained attention as a highly promising imaging technique that allows for the efficient and rapid three-dimensional visualization of nanophosphor (NP) distributions in small animals. However, the reconstruction performance is hindered by the ill-posed nature of the inverse problem and the effects of depth variation as only a single view is acquired. To tackle this issue, we present a methodology that integrates an automated restarting strategy with depth compensation to achieve reconstruction. The present study employs a fast proximal gradient descent (FPGD) method, incorporating L0 norm regularization, to achieve efficient reconstruction with accelerated convergence. The proposed approach offers the benefit of retrieving neighboring multitarget distributions without the need for CT priors. Additionally, the automated restarting strategy ensures reliable reconstructions without the need for manual intervention. Numerical simulations and physical phantom experiments were conducted using a custom CB-XLCT system to demonstrate the accuracy of the proposed method in resolving adjacent NPs. The results showed that this method had the lowest relative error compared to other few-view techniques. This study signifies a significant progression in the development of practical single-view CB-XLCT for high-resolution 3-D biomedical imaging.

Chemo-, regio- and stereoselective access to polysubstituted 1,3-dienes via Nickel-catalyzed four-component reactions.

1,2-Difunctionalization of alkynes offers a straightforward approach to access polysubstituted alkenes. However, simultaneous multi-component cascade transformations including difunctionalization of two alkynes with both syn- and anti-selectivity in one catalyst system is undeveloped and proves to be a significant challenge. Herein, we report a Nickel-catalyzed four-component reaction to access polysubstituted 1,3-dienes using two terminal alkynes, aryl boroxines, and perfluoroalkyl iodides, wherein the reaction forms three new C-C bonds in a single vessel and serve as a modular strategy to access polysubstituted 1,3-dienes with excellent chemoselectivity, good regioselectivity and exclusive stereoselectivity. Control experiments reveal the plausible reaction mechanism and DFT calculations explain the cause for the formation of this unusual four-component reaction. Furthermore, we successfully incorporate two biologically active units into 1,2,3,4-tetrasubstituted 1,3-dienes, which greatly increases the diversity of molecular scaffolds and brings more potential values to medicinal chemistry, the synthetic utility of our protocol is further demonstrated by the late-stage transformations.

Drip Fertigation Increases Maize Grain Yield by Affecting Phenology, Grain Filling Process, Biomass Accumulation and Translocation: A 4-Year Field Trial.

Drip fertigation (DF) is a widely used technology to increase grain yield with water and fertilizer conservation. However, the mechanism of high grain yield (GY) under DF is still unclear. Here, a four-year field experiment assessed the impacts of four treatments (i.e., conventional irrigation and nitrogen application, CK; drip irrigation with conventional nitrogen fertilization, DI; split-nitrogen fertigation with conventional irrigation, SF; and drip fertigation, DF) on maize phenology, leaf photosynthetic rates, grain filling processes, plant biomass, and GY. The results showed that DF significantly increased maize GY by affecting phenology, grain filling traits, aboveground biomass (BIO) accumulation, and translocation. Specifically, DF significantly increased leaf chlorophyll content, which enhanced leaf photosynthetic rates, and together with an increase of leaf area index, promoted BIO accumulation. As a result, the BIO at the silking stage of DF increased by 29.5%, transported biomass increased by 109.2% (1.2 t ha-1), and the accumulation of BIO after silking increased by 23.1% (1.7 t ha-1) compared with CK. Meanwhile, DF prolonged grain filling days, significantly increased the grain weight of 100 kernels, and promoted GY increase. Compared with CK, the four-year averaged GY and BIO increased by 34.3% and 26.8% under DF; a 29.7%, 46.1%, and 24.2% GY increase and a 30.7%, 39.5%, and 29.9% BIO increase were contributed by irrigation, nitrogen, and coupling effects of irrigation and nitrogen, respectively. These results reveal the high yield mechanism of drip-fertigated maize, and are of important significance for promoting the application of drip fertigation.

Wheat rolls fortified with microencapsulated L-5-methyltetrahydrofolic acid or equimolar folic acid increase blood folate concentrations to a similar extent in healthy men and women.

Mandatory folic acid fortification of grains such as wheat flour has been introduced in several countries to reduce the incidence of neural tube defects. There are concerns, however, that folic acid could mask the hematologic signs of vitamin B-12 deficiency and lead to other adverse health outcomes in the population. Calcium L-5-methyltetrahydrofolic acid (L-5-MTHF), a synthetic form of reduced folate, should not mask vitamin B-12 deficiency and may be safer than folic acid. Unfortunately, L-5-MTHF is not stable in most food matrices such as bread. Microencapsulation of L-5-MTHF with sodium ascorbate and a modified starch is effective at preventing loss of the vitamin during baking and storage. Our aim was to assess the efficacy of wheat rolls fortified with microencapsulated L-5-MTHF or equimolar folic acid compared with wheat rolls containing no added folate (placebo) at increasing blood folate concentrations during 16 wk. Healthy men and women aged 18-45 y (n = 45) were randomly assigned to consume wheat rolls that contained L-5-MTHF (452 µg/d), the molar equivalent of folic acid (400 µg/d), or placebo. At 16 wk, the mean (95% CI) erythrocyte folate was 0.48 (0.27, 0.71) and 0.37 (0.17, 0.57) µmol/L higher in the L-5-MTHF (P < 0.001) and folic acid wheat roll (P = 0.001) groups, respectively, than in the placebo group. Likewise, the mean plasma folate was 23 (12, 34) and 23 (12, 34) nmol/L higher in the L-5-MTHF (P < 0.001) and folic acid wheat roll (P < 0.001) groups, respectively, than in the placebo group. There were no significant differences in blood folate concentrations between the L-5-MTHF and folic acid wheat roll groups. Both microencapsulated L-5-MTHF and folic acid-fortified wheat rolls increased blood folate concentrations compared with placebo.