High-yield porphyrin production through metabolic engineering and biocatalysis.

Porphyrins and their derivatives find extensive applications in medicine, food, energy and materials. In this study, we produced porphyrin compounds by combining Rhodobacter sphaeroides as an efficient cell factory with enzymatic catalysis. Genome-wide CRISPRi-based screening in R. sphaeroides identifies hemN as a target for improved coproporphyrin III (CPIII) production, and exploiting phosphorylation of PrrA further improves the production of bioactive CPIII to 16.5 g L-1 by fed-batch fermentation. Subsequent screening and engineering high-activity metal chelatases and coproheme decarboxylase results in the synthesis of various metalloporphyrins, including heme and the anti-tumor agent zincphyrin. After pilot-scale fermentation (200 L) and setting up the purification process for CPIII (purity >95%), we scaled up the production of heme and zincphyrin through enzymatic catalysis in a 5-L bioreactor, with CPIII achieving respective enzyme conversion rates of 63% and 98% and yielding 10.8 g L-1 and 21.3 g L-1, respectively. Our strategy offers a solution for high-yield bioproduction of heme and other valuable porphyrins with substantial industrial and medical applications.

Improving electron transportation and operational lifetime of full color organic light emitting diodes through a "weak hydrogen bonding cage" structure.

Efficient electron-transporting materials (ETMs) are critical to achieving excellent performance of organic light-emitting diodes (OLEDs), yet developing such materials remains a major long-term challenge, particularly ETMs with high electron mobilities (µeles). Herein, we report a short conjugated ETM molecule (PICN) with a dipolar phenanthroimidazole group, which exhibits an electron mobility of up to 1.52 × 10-4 cm2 (V-1 s-1). The origin of this high µele is long-ranged, regulated special cage-like interactions with C-H⋯N radii, which are also favorable for the excellent efficiency stability and operational stability in OLEDs. It is worth noting that the green phosphorescent OLED operation half-lifetimes can reach up to 630 h under unencapsulation, which is 20 times longer than that based on the commonly used commercial ETM TPBi.

Risk Factors of New Symptomatic Fractures After Vertebroplasty: A Retrospective Cohort Study of 268 Patients with Painful Osteoporotic Vertebral Compression Fracture.

OBJECTIVE: To evaluate the risk factors of new osteoporotic vertebral compression fractures (OVCFs) after percutaneous vertebroplasty (PVP). METHODS: From January 2016 to November 2019, patients suffering from OVCFs were retrospectively reviewed. The independent influence factors for new OVCFs after PVP were assessed, from following variables: age, sex, body mass index, bone mineral density (BMD), history of alcoholism, smoking, hypertension, diabetes, glucocorticoid use, and prior vertebral fractures, the number of initial fractures, mean cement volume, method of puncture, D-type of cement leakage, and regular antiosteoporosis treatment. RESULTS: A total of 268 patients with 347 levels met the inclusion criteria and were finally included in this study. Forty-nine levels of new OVCFs among 33 patients (12.31%) were observed during the follow-up period. It indicated that female (adjusted odds ratio [OR]: 6.812, 95% confidence interval {CI}: [1.096, 42.337], P = 0.040), lower BMD (adjusted OR: 0.477, 95% CI: [0.300, 0.759], P = 0.002), prior vertebral fractures (adjusted OR: 16.145, 95% CI: [5.319, 49.005], P = 0.000), and regular antiosteoporosis treatment (adjusted OR: 0.258, 95% CI: [0.086, 0.774], P = 0.016) were independent influence factors for new OVCF. The cut-off value of BMD to reach new OVCF was -3.350, with a sensitivity of 0.660 and a specificity of 0.848. CONCLUSION: Female, lower BMD (T-score of lumbar), prior vertebral fractures, and regular antiosteoporosis treatment were independent influencing factors. BMD (T-score of lumbar) lower than -3.350 would increase risk for new OVCF, and none osteoporotic treatment has detrimental effect on new onset fractures following PVP.

Structural and aggregation changes of silver carp myosin induced with alcohols: Effects of ethanol, 1,2-propanediol, and glycerol.

This study investigated the effects of ethanol, 1,2-propanediol, and glycerol on the structure and aggregation behavior of silver carp (Hypophthalmichthys molitrix) myosin. All alcohols induced extensive alteration in the tertiary structure of myosin. Both ethanol and 1,2-propanediol further promoted an increase in the content of ß-sheets in myosin and induced myosin aggregation. While glycerol had almost no impact on the secondary structure of myosin. Molecular dynamics simulations revealed that increasing the concentration of ethanol and 1,2-propanediol affected the overall structural changes in the myosin heavy chain (MHC), while glycerol exerted a more pronounced effect on the MHC tail when compared to the MHC head. Disruption of the hydration layers induced by ethanol and 1,2-propanediol contributed to local structural changes in myosin. Glycerol at a concentration of 20% induced the formation of a larger hydration layer around the MHC tail, which facilitated the stabilization of the protein structure.

Effects of 'bask in sunlight and dewed at night' on the formation of fermented flavor in shrimp paste after maturation.

The purpose of the study was to illustrate the roles of three primary indexes, namely sunlight, ventilation and stirring, in the 'bask in sunlight and dewed at night' technique on the quality of shrimp paste, through a laboratory-scale design. The results showed that changes in the post-ripening fermentation conditions, especially sunlight, was instrumental in the physicochemical properties of the shrimp paste. E-nose and SPME-GC-MS were employed to assess the volatile flavor of post-ripening fermentation. A total of 29 key volatile aroma components played a crucial role in the development of post-ripening flavor in shrimp paste with or without sunlight. Lipidomic analysis revealed that sunlight promoted the oxidative degradation of FA, resulting in the production of a diverse range of flavor compounds that imparted the unique aroma of shrimp paste. The findings of this study will establish a theoretical basic for better control of the post-ripening fermentation of traditional shrimp paste.

Pregnane X receptor (PXR) deficiency promotes hepatocarcinogenesis via induction of Akr1c18 expression and prostaglandin F2α (PGF2α) levels.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Pregnane X receptor (PXR), a xenobiotic-sensing nuclear receptor, plays a critical role in the metabolism of endogenous and exogenous substances in the liver. Here, we investigate whether PXR plays a role in pathogenesis of HCC. We show that liver tumors were developed in diethylnitrosamine (DEN)-treated in PXR knockout (KO) mice. Hepatic levels of prostaglandin F2α (PGF2α) and aldo-keto reductase family 1 member C18 (Akr1c18), a prostaglandin synthase of catalyzing reduction of PGH2 to PGF2α, were significantly elevated in DEN-treated PXR KO mice. Hepatic mRNA levels of alpha fetoprotein (AFP), cyclin D1 (Ccnd1), fibroblast growth factor 21 (FGF21), and inflammatory cytokine interleukin 6 (IL-6) were significantly increased in DEN-treated PXR KO mice. Other members of Akr1c family, liver metabolizing enzymes including Cyp1a2, Cyp2b10 and Cyp3a11, and bile acid synthesis enzyme Cyp7a1 mRNA levels were significantly decreased in DEN-treated PXR KO mice. Our findings revealed that PXR deficiency promoted DEN-induced HCC in mice via induction of Akr1c18 expression and PGF2α levels and the increased PGF2α levels synthetized by Akr1c18 enhanced hepatocytes proliferation and induced inflammatory cytokine production, which accelerated liver tumor development after DEN treatment, suggesting that PXR deficiency may create a microenvironment that is more prone to DEN-induced liver tumors and targeting PXR and Akr1c18 to reduce PGF2α biosynthesis may be a potential and novel therapeutic strategy for HCC.

Combination administration of alprazolam and N-Ethylmaleimide synergistically enhances sleep behaviors in mice with no potential CNS side effects.

Background: N-Ethylmaleimide (NEM), an agonist of the potassium chloride cotransporters 2 (KCC2) receptor, has been correlated with neurosuppressive outcomes, including decreased pain perception and the prevention of epileptic seizures. Nevertheless, its relationship with sleep-inducing effects remains unreported. Objective: The present study aimed to investigate the potential enhancement of NEM on the sleep-inducing properties of alprazolam (Alp). Methods: The test of the righting reflex was used to identify the appropriate concentrations of Alp and NEM for inducing sleep-promoting effects in mice. Total sleep duration and sleep quality were evaluated through EEG/EMG analysis. The neural mechanism underlying the sleep-promoting effect was examined through c-fos immunoreactivity in the brain using immunofluorescence. Furthermore, potential CNS-side effects of the combination Alp and NEM were assessed using LABORAS automated home-cage behavioral phenotyping. Results: Combination administration of Alp (1.84 mg/kg) and NEM (1.0 mg/kg) significantly decreased sleep latency and increased sleep duration in comparison to administering 1.84 mg/kg Alp alone. This effect was characterized by a notable increase in REM duration. The findings from c-fos immunoreactivity indicated that NEM significantly suppressed neuron activation in brain regions associated with wakefulness. Additionally, combination administration of Alp and NEM showed no effects on mouse neural behaviors during automated home cage monitoring. Conclusions: This study is the first to propose and demonstrate a combination therapy involving Alp and NEM that not only enhances the hypnotic effect but also mitigates potential CNS side effects, suggesting its potential application in treating insomnia.

Peroxynitrite-Triggered Carbon Monoxide Donor Improves Ischemic Stroke Outcome by Inhibiting Neuronal Apoptosis and Ferroptosis.

Cerebral ischemia-reperfusion injury produces excessive reactive oxygen and nitrogen species, including superoxide, nitric oxide, and peroxynitrite (ONOO-). We recently developed a new ONOO--triggered metal-free carbon monoxide donor (PCOD585), exhibiting a notable neuroprotective outcome on the rat middle cerebral artery occlusion model and rendering an exciting intervention opportunity toward ischemia-induced brain injuries. However, its therapeutic mechanism still needs to be addressed. In the pharmacological study, we found PCOD585 inhibited neuronal Bcl2/Bax/caspase-3 apoptosis pathway in the peri-infarcted area of stroke by scavenging ONOO-. ONOO- scavenging further led to decreased Acyl-CoA synthetase long-chain family member 4 and increased glutathione peroxidase 4, to minimize lipoperoxidation. Additionally, the carbon monoxide release upon the ONOO- reaction with PCOD585 further inhibited the neuronal Iron-dependent ferroptosis associated with ischemia-reperfusion. Such a synergistic neuroprotective mechanism of PCOD585 yields as potent a neuroprotective effect as Edaravone. Additionally, PCOD585 penetrates the blood-brain barrier and reduces the degradation of zonula occludens-1 by inhibiting matrix metalloproteinase-9, thereby protecting the integrity of the blood-brain barrier. Our study provides a new perspective for developing multi-functional compounds to treat ischemic stroke.

Metabolomic profile of muscles from tilapia cultured in recirculating aquaculture systems and traditional aquaculture in ponds and protein stability during freeze-thaw cycles.

Muscle protein stability during freeze-thaw (F-T) cycles was investigated with tilapia cultured in recirculating aquaculture systems (RAS) and traditional aquaculture in ponds (TAP). This study found that fatty acids (eg., palmitic acid) were enriched in TAP, while antioxidants (eg., glutathione) were enriched in RAS. Generally, proteins in the RAS group exhibited greater stability against denaturation during the F-T cycle, suggested by a less decrease in haem protein content (77% in RAS and 86% in TAP) and a less increase in surface hydrophobicity of sarcoplasmic protein (63% in RAS and 101% in TAP). There was no significant difference in oxidative stability of myofibrillar protein between the two groups. This study provides a theoretical guide for the quality control of tilapia cultured in RAS during frozen storage.

Laparoscopic pyeloplasty for newborns with severe hydronephrosis.

Aim: We aimed to investigate the short-term efficacy and safety of laparoscopic pyeloplasty for treating newborns with severe hydronephrosis due to ureteropelvic junction obstruction (UPJO). Methods: A retrospective analysis was performed on 16 newborn patients with severe neonatal hydronephrosis who underwent laparoscopic pyeloplasty at our hospital from January 2021 to November 2022. All patients were regularly followed up. Laparoscopic pyeloplasty with double J stent placement was performed after the presence of severe hydronephrosis was confirmed. Results: Among the 16 pediatric patients (13 males, 3 females), the left side was affected in 13 cases and the right side in 3. The average age at surgery was 9.50 (8.50-12.00) days, with an average weight of 3.30 ± 0.95 kg. Laparoscopic pyeloplasty was performed in all cases without the need for open conversion. The mean surgery duration was 292.06 ± 73.60 min, with minimal blood loss (2.50, 2.00-5.00 ml). Postoperative hospital stays averaged 13.44 ± 4.70 days. No anastomotic leakage occurred, and follow-ups at 1, 3, 6, and 12 months showed no stent displacement, except for one case where the stent was removed at 1 month, and the others at 3 months. There were no cases of worsened hydronephrosis, except for one with renal atrophy at the 6-month follow-up. Changes in renal pelvis anteroposterior diameter exhibited a time effect (F = 49.281, P < 0.001), with significant differences at 1, 3, 6, and 12 months postoperatively compared to preoperative values (P < 0.05). Notably, differences were observed between 6 and 3 months, as well as between 12 and 3 months postoperatively (P < 0.05). Similarly, renal parenchymal thickness changes showed a time effect Pediatric urology, Guangdong Women and Children Hospital, Guangzhou, China (F = 49.281, P < 0.001), with significant differences at 1, 3, 6, and 12 months postoperatively compared to preoperative values (P < 0.05). Significant differences were also noted between 6 and 1 month, as well as between 12 and 1 month postoperatively (P < 0.05). There was one case of urinary tract infection after surgery, and no case of recurrence was observed. Conclusion: Severe neonatal hydronephrosis must be treated promptly. Laparoscopic pyeloplasty is a safe and feasible treatment with minimal complications for newborn patients with severe hydronephrosis due to UPJO.

Multi-stage aeration regime to regulate organic conversion toward gas alleviation and humification in food waste digestate composting.

Aerobic composting has been considered as a pragmatic technique to convert food waste digestate into high-quality biofertiliser. Nevertheless, massive gaseous emission and immature product remain the primary challenges in food waste digestate composting. Thus, the performance of multi-stage aeration regimes to improve gaseous emissions and organic humification during food waste digestate composting was investigated in this study. In addition to continuous aeration with a constant intensity of 0.3 L kg·dry mass (DM)-1·min-1, two multi-stage decreased aeration regimes were designed as "0.3-0.2-0.1" and "0.3-0.1-0.1" L·kg·DM-1·min-1 from the thermophilic to cooling and then mature stages, respectively. Results showed that the decreased aeration regimes could alleviate nitrous oxide (N2O) and ammonia (NH3) emission and slightly enhance humification during composting. The alleviated N2O and NH3 emission were mainly contributed by abiotically reducing gaseous release potential as well as biotically inactivating denitrifers (Pusillimonas and Pseudidiomarina) and proliferating Atopobium to reduce nitrate availability under lower aeration supply. The "0.3-0.2-0.1 L kg·DM-1·min-1" regime exhibited a more excellent performance to alleviate N2O and NH3 emission by 27.5% and 16.3%, respectively. Moreover, the decreased aeration regimes also favored the enrichment of functional bacteria (Caldicoprobacter and Syntrophomonas) to accelerate lignocellulosic biodegradation and thus humic acid synthesis by 6.5%-11.2%. Given its better performance to improve gaseous emissions and humification, the aeration regime of "0.3-0.2-0.1 L kg·DM-1·min-1" are recommended in food waste digestate composting in practice.

Efficient near-infrared emission benefits from slowing down the internal conversion process.

Organic deep-red (DR) and near-infrared (NIR) emitters with high photoluminescence quantum yield (PLQY) are rare due to the strong non-radiative (knr) decay. Here, we report two DR/NIR emitters with high PLQY, TPANZPyPI and TPANZ3PI. Interestingly, the TPANZPyPI film exhibits 46.5% PLQY at 699 nm. Theoretical calculations indicate that TPANZPyPI can achieve this high PLQY in the near-infrared emission region due to its small S1 to S0 internal conversion (IC) rate. Meanwhile, research has found that, compared to TPANZ3PI, TPANZPyPI with a more rigid structure can effectively suppress the T2 to T1 IC process, which is conducive to higher exciton utilization efficiency (EUE). TPANZPyPI's non-doped OLED shows NIR emission with 4.6% @ 684 nm maximum external quantum efficiency (EQEmax). Its doped OLEDs radiate DR with an EQEmax of 6.9% @ 666 nm. These EQEs are among the highest values for hybridized local charge transfer state materials emitting more than 640 nm. This work demonstrates for the first time, based on a combination of theory and experiment, that increasing the molecular rigidity can inhibit the excited state IC process in addition to the S1 to S0 IC, realizing efficient electroluminescence.

Exploring the role of flavin-dependent monooxygenases in the biosynthesis of aromatic compounds.

Hydroxylated aromatic compounds exhibit exceptional biological activities. In the biosynthesis of these compounds, three types of hydroxylases are commonly employed: cytochrome P450 (CYP450), pterin-dependent monooxygenase (PDM), and flavin-dependent monooxygenase (FDM). Among these, FDM is a preferred choice due to its small molecular weight, stable expression in both prokaryotic and eukaryotic fermentation systems, and a relatively high concentration of necessary cofactors. However, the catalytic efficiency of many FDMs falls short of meeting the demands of large-scale production. Additionally, challenges arise from the limited availability of cofactors and compatibility issues among enzyme components. Recently, significant progress has been achieved in improving its catalytic efficiency, but have not yet detailed and informative viewed so far. Therefore, this review emphasizes the advancements in FDMs for the biosynthesis of hydroxylated aromatic compounds and presents a summary of three strategies aimed at enhancing their catalytic efficiency: (a) Developing efficient enzyme mutants through protein engineering; (b) enhancing the supply and rapid circulation of critical cofactors; (c) facilitating cofactors delivery for enhancing FDMs catalytic efficiency. Furthermore, the current challenges and further perspectives on improving catalytic efficiency of FDMs are also discussed.

Transforming Thermally Activated Delayed Fluorescence to Room-Temperature Phosphorescence through Modulation of the Donor in Charge-Transfer Cocrystals.

A cocrystallization strategy is used through incorporation of 1,2,4,5-tetracyanobenzene (TCNB) as an acceptor with halogen-substituent thioxanthone (TX) derivatives as donors. The resulting cocrystals TT-R (R = H, F, Cl, Br, or I) transform the thermally activated delayed fluorescence emission in the TT-H, TT-F, and TT-Cl cocrystals to room-temperature phosphorescence in the TT-Br and TT-I cocrystals. Definite crystal packing structures demonstrate a 1:1 alternative donor-acceptor stacking in the TT-H cocrystal, a 2:1 alternative donor-acceptor stacking in the TT-F and TT-Cl cocrystals, and a separate stacking of donor and acceptor in the TT-Br and TT-I cocrystals. A transformation law can be revealed that with an increase in atomic number from H, F, Cl, Br, to I, the cocrystals show the structural transformation of the number of aggregated TX-R molecules from monomers to dimers and finally to multimers. This work will facilitate an understanding of the effect of halogen substituents on the crystal packing structure and luminescence properties in the cocrystals.

Isolated anterior cerebral artery occlusion: an atypical form of moyamoya disease.

BACKGROUND: The relationship between anterior cerebral artery (ACA) occlusion and moyamoya disease (MMD) has rarely been studied. In this study, we focused on a special type of MMD: isolated ACA-occlusive MMD. We investigated clinical attributes, genotypes and progression risk factors in patients with ACA-occlusive MMD, providing initial insights into the relationship between ACA occlusion and MMD. METHODS: We retrospectively analysed digital subtraction angiography (DSA) from 2486 patients and diagnosed 139 patients with ACA-occlusive MMD. RNF213 p.R4810K (rs112735431) mutation analysis was performed. Patients were categorised into progression and non-progression groups based on whether they progressed to typical MMD. Differences in clinical characteristics, neuropsychological assessment, radiological findings and genotypes were evaluated. Logistic regression analyses identified risk factors for ACA-occlusive MMD progression. RESULTS: The median age of patients with ACA-occlusive MMD was 36 years, and the primary symptom was transient ischaemic attack (TIA). 72.3% of ACA-occlusive MMD patients had cognitive decline. Of 116 patients who underwent RNF213 gene mutation analysis, 90 patients (77.6%) carried the RNF213 p.R4810K GG allele and 26 (22.4%) carried the GA allele. Of 102 patients with follow-up DSA data, 40 patients (39.2%) progressed. Kaplan-Meier curve estimates indicated a higher incidence of ischaemic stroke in the progression group during follow-up (p=0.035). Younger age (p=0.041), RNF213 p.R4810K GA genotype (p=0.037) and poor collateral compensation from the middle cerebral artery (MCA) to ACA (p<0.001) were risk factors of ACA-occlusive MMD progression to typical MMD. CONCLUSIONS: Cognitive decline and TIA might be the main manifestations of ACA-occlusive MMD. Isolated ACA occlusion may be an early signal of MMD. The initial lesion site of MMD is not strictly confined to the terminal portion of the internal carotid artery. Younger patients, patients with RNF213 p.R4810K GA genotype or those with inadequate MCA-to-ACA compensation are more likely to develop typical MMD.

Ferroptosis-Based Therapeutic Strategies toward Precision Medicine for Cancer.

Ferroptosis is a type of iron-dependent programmed cell death characterized by the dysregulation of iron metabolism and the accumulation of lipid peroxides. This nonapoptotic mode of cell death is implicated in various physiological and pathological processes. Recent findings have underscored its potential as an innovative strategy for cancer treatment, particularly against recalcitrant malignancies that are resistant to conventional therapies. This article focuses on ferroptosis-based therapeutic strategies for precision cancer treatment, covering the molecular mechanisms of ferroptosis, four major types of ferroptosis inducers and their inhibitory effects on diverse carcinomas, the detection of ferroptosis by fluorescent probes, and their implementation in image-guided therapy. These state-of-the-art tactics have manifested enhanced selectivity and efficacy against malignant carcinomas. Given that the administration of ferroptosis in cancer therapy is still at a burgeoning stage, some major challenges and future perspectives are discussed for the clinical translation of ferroptosis into precision cancer treatment.

A surface strategy boosting the ethylene selectivity for CO2 reduction and in situ mechanistic insights.

Electrochemical reduction of carbon dioxide into ethylene, as opposed to traditional industrial methods, represents a more environmentally friendly and promising technical approach. However, achieving high activity of ethylene remains a huge challenge due to the numerous possible reaction pathways. Here, we construct a hierarchical nanoelectrode composed of CuO treated with dodecanethiol to achieve elevated ethylene activity with a Faradaic efficiency reaching 79.5%. Through on in situ investigations, it is observed that dodecanethiol modification not only facilitates CO2 transfer and enhances *CO coverage on the catalyst surfaces, but also stabilizes Cu(100) facet. Density functional theory calculations of activation energy barriers of the asymmetrical C-C coupling between *CO and *CHO further support that the greatly increased selectivity of ethylene is attributed to the thiol-stabilized Cu(100). Our findings not only provide an effective strategy to design and construct Cu-based catalysts for highly selective CO2 to ethylene, but also offer deep insights into the mechanism of CO2 to ethylene.

A modified, single-incision, gasless, endoscopic thyroidectomy and bilateral central neck dissection via axillary approach technique for bilateral papillary thyroid microcarcinoma: A preliminary report.

Background: Our objective was to assess the viability and oncological security of a gasless, transaxillary single-incision endoscopic procedure for performing total thyroidectomy and bilateral central neck dissection (TT + BCND). This study focused on patients diagnosed with bilateral papillary thyroid microcarcinoma (PTMC). Method: Between April 2020 and November 2021, 22 patients with bilateral PTMC underwent single-incision, gasless, transaxillary endoscopic TT + BCND. The patients' clinicopathologic characteristics, surgical completeness and complications were analyzed. Result: Single-incision, gasless, transaxillary endoscopic TT + BCND was successful performed in all patients. The median (IQR) total surgical time was 143 (85-160) min. Only two patients experienced transient unilateral RLN palsy or transient hypocalcemia. All these complications resolved within 1 month after surgery. The median duration of hospital stay after surgery was 4 (3-4.5) days. The median hospitalization expense for these patients was 3848 (3781-4145) USD. The median number of lymph node yielded was 10.5 (8-15). The cosmetic outcomes were well-received by all individuals. Conclusion: In certain cases, gasless, transaxillary endoscopic TT + BCND procedure performed through a single incision proved to be a secure alternative for managing bilateral PTMC.

Repair of a rat calvaria defect with injectable strontium (Sr)-doped polyphosphate dicalcium phosphate dehydrate (P-DCPD) ceramic bone grafts.

The trace element strontium (Sr) enhances new bone formation. However, delivering Sr, like other materials, in a sustained manner from a ceramic bone graft substitute (BGS) is difficult. We developed a novel ceramic BGS, polyphosphate dicalcium phosphate dehydrate (P-DCPD), which delivers embedded drugs in a sustained pattern. This study assessed the in vitro and in vivo performance of Sr-doped P-DCPD. In vitro P-DCPD and 10%Sr-P-DCPD were nontoxic and eluents from 10%Sr-P-DCPD significantly enhanced osteoblastic MC3T3 cell differentiation. A sustained, zero-order Sr release was observed from 10%Sr-P-DCPD for up to 70 days. When using this BGS in a rat calvaria defect model, both P-DCPD and 10% Sr-P-DCPD were found to be biocompatible and biodegradable. Histologic data from decalcified and undecalcified tissue showed that 10%Sr-P-DCPD had more extensive new bone formation compared with P-DCPD 12-weeks after surgery and the 10%Sr-P-DCPD had more organized new bone and much less fibrous tissue at the defect margins. The new bone was formed on the surface of the degraded ceramic debris within the bone defect area. P-DCPD represented a promising drug-eluting BGS for repair of critical bone defects.