Efficient circularly polarized multiple resonance thermally activated delayed fluorescence from B,N-embedded hetero[8]helicene enantiomers.

Helicene-based circularly polarized multiple resonance thermally activated delayed fluorescence (CP-MR-TADF) materials are promising for ultra-high-definition and 3D displays, but most of them encounter potential problems such as easy racemization during the thermal deposition process, low luminous efficiency, and low luminescence dissymmetry factor (g lum), making the development of efficient circularly polarized organic light-emitting diodes (CP-OLEDs) a significant challenge. Here, we report a pair of CP-MR-TADF enantiomers with high-order B,N-embedded hetero[8]helicene, (P/M)-BN-TP-ICz, by fusing two MR chromophores, DtCzB and indolo[3,2,1-jk]carbazole (ICz). BN-TP-ICz exhibits green emission in toluene with a peak of 531 nm and a full-width at half-maximum (FWHM) of 36 nm. The optimized CP-OLEDs with enantiomers (P/M)-BN-TP-ICz exhibit green emission with peaks of 540 nm, FWHMs of 38 nm and Commission Internationale de L'Eclairage coordinates of (0.33, 0.65). Moreover, they showcase maximum external quantum efficiencies (EQEs) of 32.0%, with g ELs of +6.49 × 10-4 and -7.74 × 10-4 for devices based on (P)-BN-TP-ICz- and (M)-BN-TP-ICz, respectively.

Optimization of oral isavuconazole dose for population in special physiological or pathological state: a physiologically based pharmacokinetics model-informed precision dosing.

OBJECTIVE: To recommend precision dosing and improve therapeutic efficacy against invasive fungal disease, a physiologically based pharmacokinetic model (PBPK) of oral isavuconazole (ISA) was established and used to explore its disposition across populations in different physiological and pathological states. METHODS: Twenty-five pharmacokinetic (PK) studies of oral ISA were identified through a systematic search of PubMed. Concentration-time data were extracted using WebPlotDigitizer. Physiochemical parameters were obtained from published literature and DrugBank. Model development and simulation used the Simcyp population-based simulator, and visual predictive check and predictive error were used for the model evaluation. Probability of target attainment and the cumulative fraction of response analyses were performed for dose optimization. RESULTS: The developed PBPK model was successfully validated in different populations. Most predicted concentration-time points aligned with the observed data, with acceptable predictive errors for the critical parameters. We predicted the PK profiles and parameters of ISA in a population with severe hepatic impairment (HI), a population with obesity and paediatric patients aged 1 to less than 6 years old. The probability of target attainment and cumulative fraction of response analyses indicated that the population with severe HI should have half the maintenance dose. The population with obesity and population with severe HI should have a loading dose of 300 mg every 8 h for 2 days. For paediatric patients aged 1 to less than 6 years old, a weight-based dosing regimen (5.38 mg/kg) of ISA was suggested. CONCLUSION: The predicted value aligns with observations, suggesting ISA's potential predictability in PK profiles for other populations. The recommended dosing regimens increase our understanding of the use of ISA in special populations.

Multiple-resonance thermally activated delayed fluorescence materials based on phosphorus central chirality for efficient circularly polarized electroluminescence.

Circularly polarized organic light-emitting diodes (CP-OLEDs) hold great potential for naked-eye 3D displays, necessitating efficient chiral luminescent materials with an optimal CP luminescence (CPL) dissymmetry factor (g). Herein, we present the first chiral multiple resonance thermally activated delayed fluorescence (MR-TADF) materials containing a phosphorus chiral center by incorporating 5-phenylbenzo[b]phosphindole-5-oxide into the para-position of two MR-TADF cores. The compounds, NBOPO and NBNPO, exhibit photoluminescence peaks at 462 and 498 nm with narrow full-width at half-maximum values of 25 and 24 nm in toluene, respectively. Notably, (R/S)-NBOPO and (R/S)-NBNPO enantiomers display high quantum yields of 87% and 93% and symmetric CPL with |gPL| factors of 1.18 × 10-3 and 4.30 × 10-3, respectively, in doped films. Moreover, the corresponding CP-OLEDs show impressive external quantum efficiencies of 16.4% and 28.3%, along with symmetric CP electroluminescence spectra with |gEL| values of 7.0 × 10-4 and 1.4 × 10-3, respectively.

Identification and Validation of JAM-A as a Novel Prognostic and Immune Factor in Human Tumors.

Junctional adhesion molecule-A (JAM-A), also known as F11 receptor (F11R), is a transmembrane glycoprotein that is involved in various biological processes, including cancer initiation and progression. However, the functional characteristics and significance of JAM-A in pan-cancer remain unexplored. In this study, we used multiple databases to gain a comprehensive understanding of JAM-A in human cancers. JAM-A was widely expressed in various tissues, mainly located on the microtubules and cell junctions. Aberrant expression of JAM-A was detected in multiple cancers at both mRNA and protein levels, which can be correlated with poorer prognosis and may be attributed to genetic alterations and down-regulated DNA methylation. JAM-A expression was also associated with immune infiltration and may affect immunotherapy responses in several cancers. Functional enrichment analysis indicated that JAM-A participated in tight junction and cancer-related pathways. In vitro experiments verified that JAM-A knockdown suppressed the proliferation and migration abilities of breast cancer cells and liver cancer cells. Overall, our study suggests that JAM-A is a pan-cancer regulator and a potential biomarker for predicting prognosis and immune-therapeutic responses for different tumors.

Efficient narrowband yellow organic light-emitting diodes based on iridium(III) complexes with the rigid indolo[3,2,1-jk]carbazole unit.

Phosphorescent material with narrowband emission is crucial for advancing wide-color-gamut organic light-emitting diodes (OLEDs). In this work, two iridium(III) complexes, (PhthzICz)2Ir(tmd) and (thzICz)2Ir(tmd), using rigid 2-(benzothiazole-2-yl)indolo[3,2,1-jk]carbazole (PhthzICz) and 2-(thiazole-2-yl)indolo[3,2,1-jk]carbazole (thzICz) as cyclometalated ligands and 2,2,6,6-tetramethyl-3,5-heptanedione (tmd) as ancillary ligands, were synthesized. When these complexes were doped into the host material 3,3'-di(9H-carbazol-9-yl)-1,1'-biphenyl, the doped films exhibited yellow photoluminescence (PL) peaking at 537 and 531 nm, full width at half maximum (FWHM) bands of 35 and 60 nm, and PL quantum yields of 89.9% and 85.9%, respectively. OLEDs based on these two emitters display moderate performance characteristics with maximum external quantum efficiencies of 25.2% and 22.7%. Notably, the device based on (PhthzICz)2Ir(tmd) exhibits a narrow FWHM of 31 nm. Overall, the study highlights the practicality of incorporating rigid groups into the cyclometalated ligands of Ir(III) complexes as a viable strategy for achieving efficient Ir(III) complexes for OLEDs with narrow emission and high efficiency.

Two Different Chiral Groups Based Thermally Activated Delayed Fluorescence Materials for Circularly Polarized OLEDs.

Circularly polarized organic light-emitting diodes (CP-OLEDs) hold significant promise for applications in 3D displays due to the ability to generate circularly polarized luminescence (CPL) directly. In this study, two pairs of circularly polarized thermally activated delayed fluorescence (CP-TADF) enantiomers, named RR/SS-ONCN and RS/SR-ONCN, were synthesized by integrating two distinct chiral groups into the dicyanobenzene unit. The RR/SS-ONCN and RS/SR-ONCN enantiomers show CPL properties with dissymmetry photoluminescence factors (|gPL|) of 1.3 × 10-3 and 2.0 × 10-3 in doped films, respectively. Notably, RR/SS-ONCN exhibit higher |gPL| values than that of RS/SR-ONCN, especially in doped films, indicating that when the configurations of the two chiral groups are identical, the |gPL| value of the CP-TADF materials can be enhanced, demonstrating a certain stacking effect. Moreover, the corresponding CP-OLEDs demonstrate good performances, achieving maximum external quantum efficiencies of up to 21.9% and notable CP electroluminescence with |gEL| factors of up to 1.0 × 10-3.

The versatile binding landscape of the TAAR1 pocket for LSD and other antipsychotic drug molecules.

Increasing global concerns about psychoactive substance addiction and psychotic disorders highlight the need for comprehensive research into the structure-function relationship governing ligand recognition between these substances and their receptors in the brain. Recent studies indicate the significant involvement of trace amine-associated receptor 1 (TAAR1) in the signaling regulation of the hallucinogen lysergic acid diethylamide (LSD) and other antipsychotic drugs. This study presents structures of the TAAR1-Gs protein complex recognizing LSD, which exhibits a polypharmacological profile, and the partial agonist RO5263397, which is a drug candidate for schizophrenia and addiction. Moreover, we elucidate the cross-species recognition and partial activation mechanism for TAAR1, which holds promising implications from a drug discovery perspective. Through mutagenesis, functional studies, and molecular dynamics (MD) simulations, we provide a comprehensive understanding of a versatile TAAR1 pocket in recognizing various ligands as well as in the ligand-free state, underpinning the structural basis of its high adaptability. These findings offer valuable insights for the design of antipsychotic drugs.

The complete chloroplast genomes of Polygonatum hunanense, P. verticillatum, and P. caulialatum and their phylogenetic positions.

Polygonatum hunanense H.H. Liu & B.Z. Wang (2021) and P. verticillatum (L.) All. (1875) have been widely used as foods and as folk medicines in China and India, and P. caulialatum S. R. Yi (2021) has recently been described as a new medical plant in China. There is at present a lack of genome information regarding the species. Hence, this study reports the complete chloroplast genomes of the three species. The genomes of P. hunanense, P. verticillatum, and P. caulialatum were 155,583 bp, 155,650 bp, and 155,352 bp in length, respectively. They contained large single-copy (LSC) regions of 84,412 bp, 84,404 bp, and 84,285 bp, small single-copy (SSC) regions of 18,427 bp, 18,416 bp, and 18,463 bp, and a pair of inverted repeats of 26,372 bp, 26,415 bp, and 26,302 bp, respectively. The chloroplast genomes of P. hunanense, P. verticillatum, and P. caulialatum had 133 (103 unique) genes, consisting of 87 protein-coding genes, 38 ribosomal ribonucleic acid (RNA) genes, and eight transfer RNA genes, respectively. A maximum-likelihood phylogenetic tree showed that P. kingianum Coll. et Hemsl. var. grandifolium D.M. Liu & W.Z. Zeng (1991) was closer to P. cyrtonema Hua (1892) rather than to P. kingianum Coll. et Hemsl. (1890), further supporting its status as a unique species of the genus. Moreover, P. verticillatum was separated from the easily confused herb P. cirrhifolium (Wall.) Royle (1839), while P. caulialatum was closest to P. humile Fisch. ex Maxim. (1859). This research provides a foundation for further study of these herbs.

Three methods to optimise polymyxin B dosing using estimated AUC after first dose: validation with the data generated by Monte Carlo simulation.

To achieve the AUC-guided dosing, we proposed three methods to estimate polymyxin B AUC across 24 h at steady state (AUCSS,24h) using limited concentrations after its first dose.Monte Carlo simulation based on a well-established population PK model was performed to generate the PK profiles of 1000 patients with normal or abnormal renal function. Polymyxin B AUCSS,24h was estimated for each subject using three methods (two-point PK approach, three-point PK approach, and four-point PK approach) based on limited concentration data in its first dose and compared with the actual AUC at steady state calculated using the linear-trapezoidal formula.In patients with normal renal function, the mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was -8.73%, 1.37%, and -0.48%, respectively. The corresponding value was -11.15%, 1.99%, and -0.28% in patients with renal impairment, respectively. The largest mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was -12.63%, -6.47%, and -0.54% when the sampling time shifted.The Excel calculators designed based on the three methods can be potentially used to optimise the dosing regimen of polymyxin B in the clinic.

Benefit of cardiac rehabilitation in acute heart failure patients with cognitive impairment.

Aims: This study aimed to evaluate the prevalence of cognitive impairment among patients with acute heart failure (AHF), its prognosis, and the effects of cardiac rehabilitation (CR) on these patients' outcomes. Methods: Overall, 247 consecutive AHF patients (median age, 60 years; males, 78.5 %) were evaluated from March 2015 to May 2021. Patients received an AHF disease management program coordinated by an HF specialist nurse and underwent a Luria-Nebraska Neuropsychological battery-screening test (LNNB-S) assessment during admission. Cognitive impairment was defined as an LNNB-S score ≥10. Patients who underwent at least one session of phase II CR and continued with the home-based exercise program were considered to have received CR. The primary endpoint was composite all-cause mortality or readmission after a 3.30-year follow-up (interquartile range, 1.69-5.09 years). Results: Cognitive impairment occurred in 53.0 % and was associated with significantly higher composite endpoint, all-cause mortality, and readmission rates (p=<0.001, 0.001, and 0.015, respectively). In the total cohort, 40.9 % of patients experienced the composite endpoint. Multivariate analysis showed that the peak VO2 was a significant predictor of the composite endpoint. After adjustment, CR significantly decreased the event rate of the composite endpoint and the all-cause mortality in patients with cognitive impairment (log-rank p = 0.024 and 0.009, respectively). However, CR did not have a significant benefit on the composite endpoint and the all-cause mortality in patients without cognitive impairment (log-rank p = 0.682 and 0.701, respectively). Conclusion: Cognitive impairment is common in AHF patients and can lead to poor outcomes. CR is a standard treatment to improve prognosis.

Tetraborated Intrinsically Axial Chiral Multi-resonance Thermally Activated Delayed Fluorescence Materials.

Chiral multi-resonance thermally activated delayed fluorescence (CP-MR-TADF) materials hold promise for circularly polarized organic light-emitting diodes (CP-OLEDs) and 3D displays. Herein, we present two pairs of tetraborated intrinsically axial CP-MR-TADF materials, R/S-BDBF-BOH and R/S-BDBT-BOH, with conjugation-extended bidibenzo[b,d]furan and bidibenzo[b,d]thiophene as chiral sources, which effectively participate in the distribution of the frontier molecular orbitals. Due to the heavy-atom effect, sulfur atoms are introduced to accelerate the reverse intersystem crossing process and increase the efficiency of molecules. R/S-BDBF-BOH and R/S-BDBT-BOH manifest ultra-pure blue emission with a maximum at 458/459 nm with a full width at half maximum of 27 nm, photoluminescence quantum yields of 90 %/91 %, and dissymmetry factors (|gPL|) of 6.8×10-4/8.5×10-4, respectively. Correspondingly, the CP-OLEDs exhibit good performances with an external quantum efficiency of 30.1 % and |gEL| factors of 1.2×10-3.

Utilizing Nearest-Neighbor Clustering for Addressing Imbalanced Datasets in Bioengineering.

Imbalance classification is common in scenarios like fault diagnosis, intrusion detection, and medical diagnosis, where obtaining abnormal data is difficult. This article addresses a one-class problem, implementing and refining the One-Class Nearest-Neighbor (OCNN) algorithm. The original inter-quartile range mechanism is replaced with the K-means with outlier removal (KMOR) algorithm for efficient outlier identification in the target class. Parameters are optimized by treating these outliers as non-target-class samples. A new algorithm, the Location-based Nearest-Neighbor (LBNN) algorithm, clusters one-class training data using KMOR and calculates the farthest distance and percentile for each test data point to determine if it belongs to the target class. Experiments cover parameter studies, validation on eight standard imbalanced datasets from KEEL, and three applications on real medical imbalanced datasets. Results show superior performance in precision, recall, and G-means compared to traditional classification models, making it effective for handling imbalanced data challenges.

Bridging Ionic Current Rectification and Resistive-Pulse Sensing for Reliable Wide-Linearity Detection.

As two mainstream ionic detection techniques, ionic current rectification (ICR) suffers from large fluctuations in trace level detection, while resistive-pulse sensing (RPS) encounters easy clogs in high-concentration detection. By rationally matching the nanopore size with the DNA tetrahedron (TDN), this work bridges the two techniques to achieve reliable detection with wide linearity. As a representative analyte, miRNA-10b could specifically combine with and release TDN from the interior wall, which thus induced the simultaneous generation of distinct ICR and RPS signals. The ICR signals could be attributed to the balance between the effective orifice and surface charge density of the inner wall, while the RPS signals were induced by the complex of miRNA-10b and TDN passing through the nanopore. Such an operation contributed to a wide detection range of 1 fM-1 nM with a good linearity. The feasibility of this method is also validated in single-cell and real plasma detection.

Proteomics-Based Investigation of Different Live Prey Administered to Freshwater Dark Sleeper (Odontobutis potamophila): Examining the Effects on Glycolipids and Energy Metabolism.

Live prey is characterized by balanced rich nutrients and high palatability and is widely used for the seedling cultivation of freshwater dark sleeper (Odontobutis potamophila) larvae. In this study, we evaluated the effects of four groups of paired feeding regimens (group C (Daphnia magna), group L (Limnodrilus hoffmeisteri), group H (Hypophthalmichthys molitrix fry), and group M (mixed groups C, L, and H)) on glycolipid and energy metabolism in O. potamophila larvae. We observed that fatty acid synthase (FAS) and sterol-regulatory-element-binding protein-1 (SREBP-1) mRNA levels were significantly lower in group H when compared to mRNA levels in the other three groups (p < 0.05) and that carnitine palmitoyltransferase 1α (CPT1-α) mRNA levels were significantly lower in group L when compared to group M (p < 0.05). Relative glucokinase (GK) expression levels were significantly lower in group M when compared to the other three groups (p < 0.05). Using proteomics, we analyzed and compared groups H and L and identified 457 differentially expressed proteins (DEPs), of which 151 were significantly up-regulated and 306 were significantly down-regulated. In the comparison of group M with groups C, L, and H, we found significant enrichment in glycolytic processes, the endoplasmic reticulum lumen, NAD binding, intermediate filaments, and nutrient reservoir activity. Our results provide a theoretical guidance for bait selection during larvae cultivation stages in carnivorous fish.

Exploration of the potential association between GLP-1 receptor agonists and suicidal or self-injurious behaviors: a pharmacovigilance study based on the FDA Adverse Event Reporting System database.

BACKGROUND: Establishing whether there is a potential relationship between glucagon-like peptide 1 receptor agonists (GLP-1RAs) and suicidal or self-injurious behaviors (SSIBs) is crucial for public safety. This study investigated the potential association between GLP-1RAs and SSIBs by exploring the FDA Adverse Event Reporting System (FAERS) database. METHODS: A disproportionality analysis was conducted using post-marketing data from the FAERS repository (2018 Q1 to 2022 Q4). SSIB cases associated with GLP-1RAs were identified and analyzed through disproportionality analysis using the information component. The parametric distribution with a goodness-of-fit test was employed to analyze the time-to-onset, and the Ω shrinkage was used to evaluate the potential effect of co-medication on the occurrence of SSIBs. RESULTS: In total, 204 cases of SSIBs associated with GLP-1RAs, including semaglutide, liraglutide, dulaglutide, exenatide, and albiglutide, were identified in the FAERS database. Time-of-onset analysis revealed no consistent mechanism for the latency of SSIBs in patients receiving GLP-1RAs. The disproportionality analysis did not indicate an association between GLP-1RAs and SSIBs. Co-medication analysis revealed 81 cases with antidepressants, antipsychotics, and benzodiazepines, which may be proxies of mental health comorbidities. CONCLUSIONS: We found no signal of disproportionate reporting of an association between GLP-1RA use and SSIBs. Clinicians need to maintain heightened vigilance on patients premedicated with neuropsychotropic drugs. This contributes to the greater acceptance of GLP-1RAs in patients with type 2 diabetes mellitus or obesity.

Recent progress in multi-resonance thermally activated delayed fluorescence emitters with an efficient reverse intersystem crossing process.

Multi-resonance thermally activated delayed fluorescence (MR-TADF) emitters have become an active research topic at the forefront of organic light-emitting diodes (OLEDs) owing to their excellent photophysical properties such as high efficiency and narrow emission characteristics. However, MR-TADF materials always exhibit slow reverse intersystem crossing rates (kRISC) due to the large energy gap and small spin-orbit coupling values between singlet and triplet excited states. In order to optimize the RISC process, strategies such as heavy-atom-integration, metal perturbation, π-conjugation extension and peripheral decoration of donor/acceptor units have been proposed to construct efficient MR-TADF materials for high-performance OLEDs. This article provides an overview of the recent progress in MR-TADF emitters with an efficient RISC process, focusing on the structure-activity relationship between the molecular structure, optoelectronic feature, and OLED performance. Finally, the potential challenges and future prospects of MR-TADF materials are discussed to gain a more comprehensive understanding of the opportunities for efficient narrowband OLEDs.

Effectiveness and Safety of Chinese Herbal Injections Combined with SOX Chemotherapy Regimens for Advanced Gastric Cancer: a Bayesian Network Meta-Analysis.

Background: Randomized controlled trials (RCTs) have demonstrated that combining Chinese herbal injections (CHIs) with oxaliplatin plus tegafur (SOX) chemotherapy regimens improves clinical effectiveness and reduces adverse reactions in patients with advanced gastric cancer (AGC). These RCTs highlight the potential applications of CHIs and their impact on AGC patient prognosis. However, there is insufficient comparative evidence on the clinical effectiveness and safety of different CHIs when combined with SOX. Therefore, we performed a network meta-analysis to rank the clinical effectiveness and safety of different CHIs when combined with SOX chemotherapy regimens. This study aimed to provide evidence for selecting appropriate CHIs in the treatment of patients with AGC. Methods: We searched eight databases from their inception until March 2023. Surface Under the Cumulative Ranking Curve (SUCRA) probability values were used to rank the treatment measures, and the Confidence in Network Meta-Analysis (CINeMA) software assessed the grading of evidence. Results: A total of 51 RCTs involving 3,703 AGC patients were identified. Huachansu injections + SOX demonstrated the highest clinical effectiveness (SUCRA: 78.17%), significantly reducing the incidence of leukopenia (93.35%), thrombocytopenia (80.19%), and nausea and vomiting (95.15%). Shenfu injections + SOX improved Karnofsky's Performance Status (75.59%) and showed a significant reduction in peripheral neurotoxicity incidence (88.26%). Aidi injections + SOX were most effective in reducing the incidence of liver function damage (75.16%). According to CINeMA, most confidence rating results were classified as "low". Conclusion: The combination of CHIs and SOX shows promising effects in the treatment of AGC compared to SOX alone. Huachansu and Shenfu injections offer the greatest overall advantage among the CHIs, while Aidi injections are optimal for reducing the incidence of liver damage. However, further rigorous RCTs with larger sample sizes and additional pharmacological studies are necessary to reinforce these findings.

Circularly Polarized Organic Light-Emitting Diodes Based on Chiral Hole Transport Enantiomers.

The circularly polarized organic light-emitting diodes (CP-OLEDs) demonstrate promising application in 3D display due to the direct generation of circularly polarized electroluminescence (CPEL). But the chiral luminescence materials face challenges as intricated synthetic route, enantiomeric separation, etc. Herein, fresh CP-OLEDs are designed based on chiral hole transport material instead of chiral emitters. A pair of hole transport enantiomers (R/S-NPACZ) exhibit intense dissymmetry factors (|gPL|) about 5.0 × 10-3. With R/S-NPACZ as hole transport layers, CP-OLEDs are fabricated employing six achiral phosphorescence and thermally activated delayed fluorescence (TADF) materials with different wavelengths, in consistence with the generated CPEL spectra. The CP-OLEDs based on achiral red, green, and blue iridium(III) complexes exhibit external quantum efficiencies (EQEs) of 14.9%, 30.7%, and 14.1% with |gEL| factors of 8.8 × 10-4, 2.3 × 10-3, and 2.0 × 10-3, respectively. Moreover, the devices using achiral blue, blueish-green, and green TADF materials display EQEs of 24.1%, 17.9%, and 25.4% with |gEL| factors of 1.0 × 10-3, 3.6 × 10-3, and 2.2 × 10-3, respectively. As far as known, it is the first example of CP-OLEDs based on chiral hole transport materials, which act as the organic circularly polarizers and have potential to generate CPEL from achiral luminescence materials.

Limited Sampling Strategies for Estimating Busulfan Area Under the Concentration-Time Curve: Based on Peak and Trough Concentrations in Saliva.

Therapeutic drug monitoring for busulfan is currently performed by multiple plasma sampling. Saliva is considered a noninvasive therapeutic drug monitoring matrix. This study aimed to investigate intravenous busulfan pharmacokinetics (PK) in plasma and saliva, and establish a limited sampling strategy (LSS) for predicting the area under the concentration-time curve from time zero to infinity in plasma (AUC0-∞,p) by using saliva samples. Therefore, the PK of busulfan was studied in 37 Chinese patients. Pearson correlation analysis was used to evaluate the correlation between the AUC of busulfan in plasma and saliva. LSS models were established by the multiple linear regression analysis. The prediction error, the mean prediction error, and the root mean square error were used to evaluate the predictive accuracy. The agreement between the predicted and observed AUC0-∞ in saliva was investigated by the intraclass correlation coefficient and Bland-Altman analysis. The accuracy and robustness of the models were evaluated by using the bootstrap procedure. The result of PK analysis 62.2% of patients (23/37) was within the target range of AUC0-∞,p . A good correlation between saliva and plasma busulfan AUC0-∞ was observed (r = 0.63, p < .01). The bias and precision of the models 7 and 13 were less than 15%. The intraclass correlation coefficient exceeded 0.9, and the limits of agreement were within ±15%. The 2-point LSS model in saliva is a convenient and desirable approach to predict the AUC0-∞ of 4 times daily intravenous busulfan in plasma, which can be used to design personalized dosing for busulfan.