Baicalein attenuates rotenone-induced SH-SY5Y cell apoptosis through binding to SUR1 and activating ATP-sensitive potassium channels.

Dopaminergic neurons in the substantia nigra (SN) expressing SUR1/Kir6.2 type ATP-sensitive potassium channels (K-ATP) are more vulnerable to rotenone or metabolic stress, which may be an important reason for the selective degeneration of neurons in Parkinson's disease (PD). Baicalein has shown neuroprotective effects in PD animal models. In this study, we investigated the effect of baicalein on K-ATP channels and the underlying mechanisms in rotenone-induced apoptosis of SH-SY5Y cells. K-ATP currents were recorded from SH-SY5Y cells using whole-cell voltage-clamp recording. Drugs dissolved in the external solution at the final concentration were directly pipetted onto the cells. We showed that rotenone and baicalein opened K-ATP channels and increased the current amplitudes with EC50 values of 0.438 µM and 6.159 µM, respectively. K-ATP channel blockers glibenclamide (50 µM) or 5-hydroxydecanoate (5-HD, 250 µM) attenuated the protective effects of baicalein in reducing reactive oxygen species (ROS) content and increasing mitochondrial membrane potential and ATP levels in rotenone-injured SH-SY5Y cells, suggesting that baicalein protected against the apoptosis of SH-SY5Y cells by regulating the effect of rotenone on opening K-ATP channels. Administration of baicalein (150, 300 mg·kg-1·d-1, i.g.) significantly inhibited rotenone-induced overexpression of SUR1 in SN and striatum of rats. We conducted surface plasmon resonance assay and molecular docking, and found that baicalein had a higher affinity with SUR1 protein (KD = 10.39 µM) than glibenclamide (KD = 24.32 µM), thus reducing the sensitivity of K-ATP channels to rotenone. Knockdown of SUR1 subunit reduced rotenone-induced apoptosis and damage of SH-SY5Y cells, confirming that SUR1 was an important target for slowing dopaminergic neuronal degeneration in PD. Taken together, we demonstrate for the first time that baicalein attenuates rotenone-induced SH-SY5Y cell apoptosis through binding to SUR1 and activating K-ATP channels.

Long-term administration of salvianolic acid A promotes endogenous neurogenesis in ischemic stroke rats through activating Wnt3a/GSK3ß/ß-catenin signaling pathway.

Stroke is the major cause of death and disability worldwide. Most stroke patients who survive in the acute phase of ischemia display various extents of neurological deficits. In order to improve the prognosis of ischemic stroke, promoting endogenous neurogenesis has attracted great attention. Salvianolic acid A (SAA) has shown neuroprotective effects against ischemic diseases. In the present study, we investigated the neurogenesis effects of SAA in ischemic stroke rats, and explored the underlying mechanisms. An autologous thrombus stroke model was established by electrocoagulation. The rats were administered SAA (10 mg/kg, ig) or a positive drug edaravone (5 mg/kg, iv) once a day for 14 days. We showed that SAA administration significantly decreased infarction volume and vascular embolism, and ameliorated pathological injury in the hippocampus and striatum as well as the neurological deficits as compared with the model rats. Furthermore, we found that SAA administration significantly promoted neural stem/progenitor cells (NSPCs) proliferation, migration and differentiation into neurons, enhanced axonal regeneration and diminished neuronal apoptosis around the ipsilateral subventricular zone (SVZ), resulting in restored neural density and reconstructed neural circuits in the ischemic striatum. Moreover, we revealed that SAA-induced neurogenesis was associated to activating Wnt3a/GSK3ß/ß-catenin signaling pathway and downstream target genes in the hippocampus and striatum. Edaravone exerted equivalent inhibition on neuronal apoptosis in the SVZ, as SAA, but edaravone-induced neurogenesis was weaker than that of SAA. Taken together, our results demonstrate that long-term administration of SAA improves neurological function through enhancing endogenous neurogenesis and inhibiting neuronal apoptosis in ischemic stroke rats via activating Wnt3a/GSK3ß/ß-catenin signaling pathway. SAA may be a potential therapeutic drug to promote neurogenesis after stroke.

Study on strategies for alighting and boarding in subway stations.

With its high infection rate, COVID-19 has swept the globe and brought great challenges to social life and economies. As an essential form of public transportation, the Beijing subway plays an important role in transportation systems. In traditional subway organizations, all one-sided doors of a train carriage are employed for passengers' alighting and boarding. A higher risk of COVID-19 infections may be attributed to inevitable bidirectional conflicts at doors with higher passenger volumes. Moreover, quantitative analyses for this problem and corresponding solutions are, limited in recent studies. In this research, conflicts at carriage doors are analyzed using a cellular automaton (CA) based model. Four schemes to separate alighting and passenger boarding into separate doors are investigated. The performances of different schemes with various alighting and boarding passenger ratios are simulated with the software package Legion Studio. Both macroscopic and microscopic parameters to characterize passenger conflicts are obtained for analysis. The separation of alighting and boarding passenger flows yields the desired reduction in bidirectional conflicts, which further limits the probability of infectious disease exposure. This is an important reference to improve current practices and provide specific measurements of passenger organization under abnormal situations.

Cocrystal of Apixaban-Quercetin: Improving Solubility and Bioavailability of Drug Combination of Two Poorly Soluble Drugs.

Drug combinations have been the hotspot of the pharmaceutical industry, but the promising applications are limited by the unmet solubility and low bioavailability. In this work, novel cocrystals, consisting of two antithrombotic drugs with poor solubility and low bioavailability in vivo, namely, apixaban (Apx) and quercetin (Que), were developed to discover a potential method to improve the poor solubility and internal absorption of the drug combination. Compared with Apx, the dissolution behavior of Apx-Que (1:1) and Apx-Que-2ACN (1:1:2) was enhanced significantly, while the physical mixture of the chemicals failed to exhibit the advantages. The dissolution improvements of Apx-Que-2ACN could be explained by the fact that the solid dispersion-like structure and column-shaped cage of Que accelerated the access of the solvent to the inner layer of Apx. The fracture of the hydrogen bonds of Apx, which was the joint of the adjacent Que chains, facilitated the break-up of the structures. Besides, the bioavailability of Apx-Que was increased compared with the physical mixture and Apx, and Apx-Que remained stable in high temperature and illumination conditions. Therefore, a drug-drug cocrystal of two antithrombotic agents with poor solubility was developed, which exhibited greatly improved solubility, bioavailability and superior stability, indicating a novel method to overcome the shortages of drug combination.

Salvianolic Acid D Alleviates Cerebral Ischemia-Reperfusion Injury by Suppressing the Cytoplasmic Translocation and Release of HMGB1-Triggered NF-κB Activation to Inhibit Inflammatory Response.

Inflammatory response participates in the overall pathophysiological process of stroke. It is a promising strategy to develop antistroke drugs targeting inflammation. This study is aimed at investigating the therapeutic effect and anti-inflammatory mechanism of salvianolic acid D (SalD) against cerebral ischemia/reperfusion (I/R) injury. A rat middle cerebral artery occlusion/reperfusion (MCAO/R) injury model was established, and an oxygen-glucose deprivation/reoxygenation (OGD/R) injury model was established in PC12 cells. Neurological deficit score, cerebral infarction, and edema were studied in vivo. Cell viability was achieved using the MTT method in vitro. The Bax, Bcl-2, cytochrome c, HMGB1, TLR4, TRAF6, NF-κB p65, p-NF-κB p65, and cleaved caspase-3 and -9 were tested via the Western blot method. Cytokines and cytokine mRNA, including TNF-α, IL-1ß, and IL-6, were studied via ELISA and PCR methods. The translocation of HMGB1 and NF-κB were studied by immunofluorescence assay. The HMGB1/NeuN, HMGB1/GFAP, and HMGB1/Iba1 double staining was carried out to observe the localization of HMGB1 in different cells. Results showed that SalD alleviated neurological impairment, decreased cerebral infarction, and reduced edema in I/R rats. SalD improved OGD/R-downregulated PC12 cell viability. SalD also promoted Bcl-2 expression and suppressed Bax, cytochrome c, and cleaved caspase-3 and -9 expression. SalD decreased the intensity of TLR4, MyD88, and TRAF6 proteins both in vivo and in vitro, and significantly inhibited the NF-κB nuclear translocation induced by I/R and OGD/R. What's more, SalD inhibited HMGB1 cytoplasmic translocation in neurons, astrocytes, and microglia in both the cortex and hippocampus regions of I/R rats. In conclusion, SalD can alleviate I/R-induced cerebral injury in rats and increase the PC12 cell viability affected by OGD/R. The anti-inflammatory mechanism of SalD might result from the decreased nuclear-to-cytoplasmic translocation of HMGB1 and the inhibition on its downstream TLR4/MyD88/NF-κB signaling.

Effect of different shapes of steel fibers and palygorskite-nanofibers on performance of ultra-high-performance concrete.

Herein, a practical ultra-high-performance concrete (UHPC) was created by adding two different shapes of steel fibers and curing them at ambient temperature using palygorskite-nanofiber (PN) as the modifier. The compressive strength, flexural strength, water absorption capacity, and porosity were analyzed to determine the effects of the steel fibers and PNs on the UHPC mechanical and physical properties. The steel fibers and PNs were found to improve these properties. The UHPC mechanical properties were outstanding at 1.5% fiber dosage, while physical properties were excellent at 1.0% fiber dosage. The mechanical and physical characteristics of UHPC were preferably at a PN dosage of 0.2% and the fiber dosage of 1.0%. The compressive and flexural strengths of straight-steel-fiber UHPC were 145.57 and 19.67 MPa, respectively, i.e., 42.0 and 109.4% higher than those of the reference specimens (i.e., those without fibers or PNs); the water absorption capacity and porosity decreased by 50.1 and 60.7%, respectively. The compressive and flexural strengths of hooked-end-steel-fiber UHPC were 18.3 and 96.0% higher than those of the reference specimens, respectively, and the water absorption capacity and porosity decreased by 43.2 and 29.8%, respectively. These results could provide vital information for the promotion and practical application of UHPC.

Erratum: Author correction to 'Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models' [Acta Pharmaceutica Sinica B 11(2021) 1903-1913].

[This corrects the article DOI: 10.1016/j.apsb.2021.03.002.].

Erratum: Author correction to 'Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models' [Acta Pharmaceutica Sinica B 11 (2021) 1903-1913].

[This corrects the article DOI: 10.1016/j.apsb.2021.03.002.].

Salvianolic acid A alleviates heart failure with preserved ejection fraction via regulating TLR/Myd88/TRAF/NF-κB and p38MAPK/CREB signaling pathways.

Heart failure with preserved ejection fraction (HFpEF) is a morbid, fatal, and common syndrome for which lack of evidence-based therapies. Salvianolic acid A (SAA), a major active ingredient of Salvia miltiorrhiza Burge, has shown potential to protect against cardiovascular diseases. This study aims to elucidate whether SAA possessed therapeutic activity against HFpEF and explore the potential mechanism. HFpEF mouse model was established infusing a combination of high-fat diet (HFD) and Nω-nitro-L-arginine methyl ester (L-NAME) for 14 weeks. After 10 weeks of feeding, HFpEF mice were given SAA (2.5, 5, 10 mg/kg) via oral gavage for four weeks. Body weight, blood pressure, blood lipids, glucose tolerance, exercise performance, cardiac systolic/diastolic function, cardiac pathophysiological changes, and inflammatory factors were assessed. Experimental results showed that SAA reduced HFpEF risk factors, such as body weight gain, glucose intolerance, lipid disorders, and increased exercise tolerance in HFpEF mice. Moreover, SAA not only relieved myocardial hypertrophy and fibrosis by reducing interventricular septal wall thickness, left ventricular posterior wall thickness, left ventricular mass, heart index, cardiomyocyte cross-sectional area and cardiac collagen content, but also improved cardiac diastolic function via reducing E/E' ratio. Finally, SAA inhibited TLR2/TLR4-mediated Myd88 activation and its downstream molecules TRAF6 and IRAK4, which decreases the release of proinflammatory cytokines and mediators through NF-κB and p38 MAPK pathways. In conclusion, SAA could attenuate cardiac inflammation and cardiac disfunction by TLR/Myd88/TRAF/NF-κB and p38MAPK/CREB signaling pathways in HFpEF mice, which provides evidence for SAA as a potential drug for treatment of HFpEF in clinic.

Salvianolic acid A improve mitochondrial respiration and cardiac function via inhibiting apoptosis pathway through CRYAB in diabetic cardiomyopathy.

Salvianolic acid A (SAA) is a traditional Chinese medicine that has a good therapeutic effect on cardiovascular disease. However, the underlying mechanisms by which SAA improves mitochondrial respiration and cardiac function in diabetic cardiomyopathy (DCM) remain unknown. This study aims to elucidate whether SAA had any cardiovascular protection on the pathophysiology of DCM and explored the potential mechanisms. Diabetes was induced in rats by 30 mg/kg of streptozotocin (STZ) treatment. After a week of stability, 5 mg/kg isoprenaline (ISO) was injected into the rats subcutaneously. 3 mg/kg SAA was orally administered for six weeks and 150 mg/kg Metformin was selected as a positive group. At the end of this period, cardiac function was assessed by ultrasound, electrocardiogram, and relevant cardiac injury biomarkers testing. Treatment with SAA improved cardiac function, glucose, and lipid levels, mitochondrial respiration, and suppressed myocardial inflammation and apoptosis. Furthermore, SAA treatment inhibits the apoptosis pathway through CRYAB in diabetic cardiomyopathy rats. As a result, this study not only provides new insights into the mechanism of SAA against DCM but also provides new therapeutic ideas for the discovery of anti-DCM compounds in the clinic.

Automated beam placement for breast radiotherapy using a support vector machine based algorithm.

PURPOSE: To develop an automated beam placement technique for whole breast radiotherapy using tangential beams. We seek to find optimal parameters for tangential beams to cover the whole ipsilateral breast (WB) and minimize the dose to the organs at risk (OARs). METHODS: A support vector machine (SVM) based method is proposed to determine the optimal posterior plane of the tangential beams. Relative significances of including/avoiding the volumes of interests are incorporated into the cost function of the SVM. After finding the optimal 3-D plane that separates the whole breast (WB) and the included clinical target volumes (CTVs) from the OARs, the gantry angle, collimator angle, and posterior jaw size of the tangential beams are derived from the separating plane equation. Dosimetric measures of the treatment plans determined by the automated method are compared with those obtained by applying manual beam placement by the physicians. The method can be further extended to use multileaf collimator (MLC) blocking by optimizing posterior MLC positions. RESULTS: The plans for 36 patients (23 prone- and 13 supine-treated) with left breast cancer were analyzed. Our algorithm reduced the volume of the heart that receives >500 cGy dose (V5) from 2.7 to 1.7 cm(3) (p = 0.058) on average and the volume of the ipsilateral lung that receives >1000 cGy dose (V10) from 55.2 to 40.7 cm(3) (p = 0.0013). The dose coverage as measured by volume receiving >95% of the prescription dose (V95%) of the WB without a 5 mm superficial layer decreases by only 0.74% (p = 0.0002) and the V95% for the tumor bed with 1.5 cm margin remains unchanged. CONCLUSIONS: This study has demonstrated the feasibility of using a SVM-based algorithm to determine optimal beam placement without a physician's intervention. The proposed method reduced the dose to OARs, especially for supine treated patients, without any relevant degradation of dose homogeneity and coverage in general.

Bioremediation of petroleum-contaminated saline soil by Acinetobacter baumannii and Talaromyces sp. and functional potential analysis using metagenomic sequencing.

Microbial remediation is a potential remediation method for petroleum-contaminated soil. In order to explore the petroleum degradation mechanism by microorganisms, the oilfield soil was remedied by Acinetobacter baumannii combined with Talaromyces sp. The degradation mechanism was studied by analyzing soil microbial community and functional genes through metagenomics during the degradation process. The result showed the degradation rate of petroleum was 65.6% after 28 days. The concentration of petroleum decreased from 1220 mg/kg to 420 mg/kg. In the co-culture group, Acinetobacter baumannii became the dominant species, the annotated genes of it at the species level accounted for 7.34% while that of Talaromyces sp. accounted for only 0.34%. Meanwhile, the annotated genes of Bacillus, Halomonas, and Nitriliruptor at the genus level were up-regulated by 1.83%, 0.90%, and 0.71%, respectively. In addition, large functional genes were significantly up-regulated, including the peroxisome, P450 enzyme (CYP53, CYP116, CYP102, CYP645), and biofilm formulation, promoting the oxidation and hydroxylation, and catalyzing the epoxidation of aromatic and aliphatic hydrocarbons. Meanwhile, the degrading genes of alkanes and aromatic hydrocarbons were expressed promotionally, and degradation pathways were deduced. In conclusion, the inoculation of Acinetobacter baumannii combined with Talaromyces sp. accelerated the degradation of petroleum in oilfield soil and improved the growth of indigenous petroleum-degrading bacteria. Many functional genes related to petroleum degradation were promoted significantly. These results proved the co-culture of bacteria-fungi consortium contributes to the bioremediation of petroleum-contaminated soil.

Reliable preimplantation genetic diagnosis in thawed human embryos vitrified at cleavage stages without biopsy.

PURPOSE: To evaluate preimplantation genetic diagnosis (PGD) efficiency in thawed human embryos vitrified without biopsy. METHODS: In this retrospective clinical study, 21 PGD cycles were carried out using fresh and vitrified-thawed embryos collected from 21 patients. RESULTS: One hundred and ninety-nine embryos from patients with aneuploidy, single gene defects, or chromosomal translocations were vitrified at the cleavage stages; 93.5% of the embryos survived the vitrification procedure. Conclusive FISH results were obtained in 98.4% of the fresh and 99% of the frozen-thawed embryos screened for aneuploidy or chromosomal translocations. Conclusive PCR test results were obtained in 100% of the fresh and 93.9% of the frozen-thawed embryos screened for single gene defects. The overall clinical pregnancy rate per cycle was 57.1%. To date, 13 healthy children have been born. CONCLUSION: Reliable genetic diagnosis can be performed in thawed human embryos vitrified without biopsy. However, further research is required to support this conclusion.

Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models.

Nicotinic α4ß2 receptor antagonists have drawn increasing attention in the development of new antidepressants. In this study, we aimed to investigate the protective effect of VMY-2-95, the new selective antagonist of α4ß2 nicotinic acetylcholine receptor (nAChR) on corticosterone (CORT) injured mice and cellular models. Fluoxetine was applied as a positive control, and the effects of VMY-2-95 were investigated with three different doses or concentrations (1, 3, 10 mg/kg in mice, and 0.003, 0.03, 0.1 µmol/L in cells). As a result, VMY-2-95 showed significant antidepressant-like effects in the CORT injured mice by improving neuromorphic function, promoting hippocampal nerve proliferation, and regulating the contents of monoamine transmitters. Meanwhile, VMY-2-95 exhibited protective effects on cell viability, cell oxidant, cell apoptosis, and mitochondrial energy metabolism on corticosterone-impaired SH-SY5Y cells. Also, the PKA-CREB-BDNF signaling pathway was up-regulated by VMY-2-95 both in vitro and in vivo, and pathway blockers were also combined with VMY-2-95 to verify the effects furtherly. Therefore, we preliminarily proved that VMY-2-95 had protective effects in depressed mice and SH-SY5Y cells against injuries induced by corticosterone. This work indicated that the application of VMY-2-95 is a potential pharmacological solution for depression. This study also supported the development of α4ß2 nAChR antagonists towards neuropsychiatric dysfunctions.

A novel green substrate made by sludge digestate and its biochar: Plant growth and greenhouse emission.

Anaerobic digestion of sludge produces a large amount of sewage sludge anaerobic digestate (SSAD) that can be reused. A novel green substrate was prepared by mixing SSAD and its biochar (SSBC) filled with perlite and quartz sand for plant growth, as a replacement of soil. We carried out pot experiment, measured ryegrass biomass, seedling survival rate, and evaluated the emission of greenhouse gas (GHG), NH3 volatilization. The results showed that the seedling survival rate and individual biomass of ryegrass in green substrate were 100% and 100.02 mg, which were 14.4% and 231.4% higher than those in only SSAD, but were 1.3% and 19.6% higher than those in soil. SSBC significantly reduced N2O and CO2 emission, inhibited the NH3 volatilization, but increased CH4 emission. However, the cumulative emission of N2O and CH4 was approximation to that in soil. Global warming potential of CH4 and N2O (GWP(CH4+N2O)) green substrate was 11,842.01 kg CO2·hm-2, which was 1.35-fold higher than that of soil. Microbial community structure analysis showed that fermentative bacteria and methanogenic archaeal had a higher abundance in green substrate than in soil, which caused the different gas emission. This study will provide an effective and economical way to dispose excessive SSAD.

Baicalein alleviates depression-like behavior in rotenone- induced Parkinson's disease model in mice through activating the BDNF/TrkB/CREB pathway.

BACKGROUND: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in the world. In addition to motor symptoms, a variety of non-motor symptoms seriously affect the life quality of PD patients. Baicalein, a flavonoid extracted from the herb Scutellaria baicalensis Georgi, exhibits anti-PD activity through alleviation of its motor symptoms. However, its effects on non-motor symptoms were barely reported. This study aimed to investigate the therapeutic effects of baicalein on PD-related depression. METHODS: After a 2-week injection of rotenone, mice with PD-related depression behavior were selected, divided into three groups, and administrated saline, baicalein, or madopar orally for four weeks. Behavior, neuroinflammation, neurotransmitters, and synaptic plasticity were evaluated. RESULTS: Our results showed that 4-week baicalein treatment significantly alleviated the depression-like behavior in the rotenone-induced mice model. Repeated baicalein treatment reduced α-synuclein aggregation, inhibited neuroinflammation, and maintained neurotransmitters homeostasis. Moreover, we found that baicalein treatment could remarkably protect the synaptic plasticity and activate the BDNF/TrkB/CREB pathway in the PD-related depression mice model. As traditional dopamine replacement therapy unleashed few effects on depression-like symptom amelioration and synaptic function protection, baicalein might be a more appropriate choice for PD-related depression. CONCLUSIONS: The current results suggested that baicalein could act as a treatment for PD-related depression.

Combined microbial degradation of crude oil under alkaline conditions by Acinetobacter baumannii and Talaromyces sp.

The purpose of this work was to study the biodegradation of crude oil under alkaline condition by defined co-culture of Acinetobacter baumannii and Talaromyces sp. The n-alkanes in crude oil could be completely degraded by bacteria and fungi with the ratio of 1:1 at pH 9 in 14 d water simulation experiment. Meanwhile, the total degradation rate of crude oil could reach 80%. Fungi had stronger ability to degrade n-alkanes, while bacteria could better degrade other components such as aromatics and branched alkanes. The two strains were both capable of producing a small amount of biosurfactant. High cell viability was the main factor for strains to exert high degradation ability in alkaline environment. It was preliminarily verified that bacteria and fungi rely on the differences of enzyme systems to achieve synergy in the degradation process. These results indicated that the defined co-culture had great potential for bioremediation in alkaline soils.

Synergistic degradation of crude oil by indigenous bacterial consortium and exogenous fungus Scedosporium boydii.

The purpose of this study was to investigate the potential of defined co-culture of indigenous bacterial consortium and exogenous fungus Scedosporium boydii for biodegradation of crude oil. After 7 days of incubation, residual oil, n-alkanes and aromatic fraction were analyzed. The degradation rate of crude oil was increased from 61.06% to 81.45% by the defined co-culture according to the 3:1 inoculation ratio of bacteria to fungi. The microbial activity was enhanced markedly and the formation of biofilms was accelerated after suitable inoculation of Scedosporium boydii. High throughput analysis showed that bacterial evenness and diversity were increased and the relative abundance of Paraburkholderia tropica was increased observably from 7.67% to 56.13% in the defined co-culture. These results indicated that synergistic degradation of crude oil in the bacteria-fungi consortium may be advantageous for bioremediation of petroleum-contaminated site.

Preimplantation genetic diagnosis of leukocyte adhesion deficiency type I.

OBJECTIVE: To describe the application of preimplantion genetic diagnosis (PF to a carrier couple for leukocyte adhesion deficiency type I disease (LAD-1), to achieve a healthy pregnancy. DESIGN: Case report. SETTING: Reproductive center and university hospital. PATIENT(S): A couple in which both partners were carriers for LAD-1; the female partner carried a G400A substitution in exon 4, and the male partner carried a C562T substitution in exon 5 in the CD18 gene. INTERVENTION(S): Day-3 cleavage-stage biopsy after standard in vitro fertilization (IVF) and genetic analysis of blastomeres for two mutations, along with a marker from chromosome 21. MAIN OUTCOME MEASURE(S): Birth of a child unaffected with LAD-1. RESULT(S): Fifteen oocytes were retrieved, of which 10 were fertilized; eight embryos were suitable for embryo biopsy. After genetic analysis, three embryos were found to be unaffected. According to embryo morphology, two embryos were transferred, resulting in the birth of an unaffected child. CONCLUSION(S): This is the first report of preimplantion genetic diagnosis for LAD-1. The successful birth of a healthy child provides evidence that for carrier couples of diseases for which traditional prenatal diagnosis and the decision of whether to terminate a pregnancy might not be acceptable, the application of PGD provides an alternative.