Eltrombopag can promote platelet implantation after allogeneic hematopoietic stem cell transplantation as safely and similarly to thrombopoietin.

Background: Eltrombopag has demonstrated efficacy in treating low platelet (PLT) levels, but it remains unclear whether eltrombopag can promote PLT engraftment after hematopoietic stem cell transplantation (HSCT). Methods: Forty-one HSCT patients received eltrombopag 50 mg/d from +1 day until PLT >50 × 109/L or 1 month after HSCT. Fifty-one patients in the same period received thrombopoietin (TPO) to promote PLT graft after HSCT and served as a control group. Results: A total of 51 patients who applied TPO during the same period were treated as a control. In the eltrombopag group, the median time to white blood cells (WBC) graft was 12 days (range, 10-17 days) and the PLT graft was 15 days (range, 10-30 days), whereas for the patients in the TPO group, the median time to WBC and PLT graft was 12 days (range, 9-23 days) and 15.5 days (range, 9-41 days), respectively. In the first month after HSCT, the median WBC count in the eltrombopag group was 4.41 × 109/L (range, 0.87-40.01 × 109/L) and the median PLT was 89x109/L (range, 30-401 × 109/L); the median WBC and PLT \counts in the TPO group were 4.65 × 109/L (range, 0.99-23.63 × 109/L) and 86 × 109/L (range, 5-512 × 109/L), respectively. Patients in the TPO or eltrombopag group did not experience serious side effects after drug administration, and the difference in side effects on liver and kidney function between the two groups was not statistically significant. Conclusion: Eltrombopag is safe and similarly promotes platelet engraftment to thrombopoietin after allogeneic HSCT.

NCAPD3 promotes diffuse large B-cell lymphoma progression through modulating SIRT1 expression in an H3K9 monomethylation-dependent manner.

INTRODUCTION: Condensin, a family of structural maintenance of chromosome complexes, has been shown to regulate chromosome compaction and segregation during mitosis. NCAPD3, a HEAT-repeat subunit of condensin II, plays a dominant role in condensin-mediated chromosome dynamics but remains unexplored in lymphoma. OBJECTIVES: The study aims to unravel the molecular function and mechanism of NCAPD3 in diffuse large B-cell lymphoma (DLBCL). METHODS: The expression and clinical significance of NCAPD3 were assessed in public database and clinical specimens. Chromosome spreads, co-immunoprecipitation (co-IP), mass spectrometry (MS), and chromatin immunoprecipitation (ChIP) assays were conducted to untangle the role and mechanism of NCAPD3 in DLBCL. RESULTS: NCAPD3 was highly expressed in DLBCL, correlated with poor prognosis. NCAPD3 deficiency impeded cell proliferation, induced apoptosis and increased the chemosensitivity. Instead, NCAPD3 overexpression facilitated cell proliferation. In vivo experiments further indicated targeting NCAPD3 suppressed tumor growth. Noteworthily, NCAPD3 deficiency disturbed the mitosis, triggering the formation of aneuploids. To reveal the function of NCAPD3 in DLBCL, chromosome spreads were conducted, presenting that chromosomes became compact upon NCAPD3 overexpression, instead, loose, twisted and lacking axial rigidity upon NCAPD3 absence. Meanwhile, the classical transcription-activated marker, H3K4 trimethylation, was found globally upregulated after NCAPD3 knockout, suggesting that NCAPD3 might participate in chromatin remodeling and transcription regulation. MS revealed NCAPD3 could interact with transcription factor, TFII I. Further co-IP and ChIP assays verified NCAPD3 could be anchored at the promoter of SIRT1 by TFII I and then supported the transcription of SIRT1 via recognizing H3K9 monomethylation (H3K9me1) on SIRT1 promoter. Function reversion assay verified the oncogenic role of NCAPD3 in DLBCL was partially mediated by SIRT1. CONCLUSION: This study demonstrated that dysregulation of NCAPD3 could disturb chromosome compaction and segregation and regulate the transcription activity of SIRT1 in an H3K9me1-dependent manner, which provided novel insights into targeted strategy for DLBCL.

Chiral ligands and photothermal synergistic effects of inorganic nanoparticles for bacteria-killing.

As the drawbacks of antibiotics in treating bacterial infections emerged, physical methods such as near-infrared-activated (NIR-activated) bacterial killing, have attracted great interests for their advantages of no resistance, short action time and few side effects. In this manuscript, NIR-activated bacteria-killing performance of chiral copper sulphide nanoparticles (L-/d-CuS NPs) was investigated using linearly polarized light (LPL) and circularly polarized light (CPL) as illumination sources, respectively. Chiral CuS NPs showed enhanced NIR-activated bacteria-killing effect compared with achiral CuS NPs under the same conditions. Moreover, these chiral CuS NPs showed obvious chirality-related antibacterial effect: the bacterial killing was more efficient under CPL activation, and L- and d-CuS NPs had higher antibacterial efficiency under left circularly polarized light (LCPL) and right circularly polarized light (RCPL), respectively. The possible mechanism of bacteria-killing performance for chiral CuS NPs was discussed in detailed. Photothermal bacteria-killing tests of chiral CuS NPs "sealed" in polydimethylsiloxane (PDMS) demonstrated the individual influence of photothermal effect. These observations in this paper could provide ideas for the potential applications of chiral nanostructures with enhanced photothermal effect in efficient bacterial killing.

Interfacial Electron Transfer in PbI2@Single-Walled Carbon Nanotube van der Waals Heterostructures for High-Stability Self-Powered Photodetectors.

Acquiring a deep insight into the electron transfer mechanism and applications of one-dimensional (1D) van der Waals heterostructures (vdWHs) has always been a significant challenge. Herein, through direct observation using aberration-corrected transmission electron microscopy (AC-TEM), we verify the stable formation of a high-quality 1D heterostructure composed of PbI2@single-walled carbon nanotubes (SWCNTs). The phenomenon of electron transfer between PbI2 and SWCNT is elucidated through spectroscopic investigations, including Raman and X-ray photoelectron spectroscopy (XPS). Electrochemical testing indicates the electron transfer and enduring stability of 1D PbI2 within SWCNTs. Moreover, leveraging the aforementioned electron transfer mechanism, we engineer self-powered photodetectors that exhibit exceptional photocurrent and a 3-order-of-magnitude switching ratio. Subsequently, we reveal its unique electron transfer behavior using Kelvin probe force microscopic (KPFM) tests. According to KPFM, the average surface potential of SWCNTs decreases by 80.6 mV after filling. Theoretical calculations illustrate a charge transfer of 0.02 e per unit cell. This work provides an effective strategy for the in-depth investigation and application of electron transfer in 1D vdWHs.

Ferroelectric-Optoelectronic Hybrid System for Photodetection.

Photodetectors (PDs), as functional devices based on photon-to-electron conversion, are an indispensable component for the next-generation Internet of Things system. The research of advanced and efficient PDs that meet the diverse demands is becoming a major task. Ferroelectric materials can develop a unique spontaneous polarization due to the symmetry-breaking of the unit cell, which is switchable under an external electric field. Ferroelectric polarization field has the intrinsic characteristics of non-volatilization and rewritability. Introducing ferroelectrics to effectively manipulate the band bending and carrier transport can be non-destructive and controllable in the ferroelectric-optoelectronic hybrid systems. Hence, ferroelectric integration offers a promising strategy for high-performance photoelectric detection. This paper reviews the fundamentals of optoelectronic and ferroelectric materials, and their interactions in hybrid photodetection systems. The first section introduces the characteristics and applications of typical optoelectronic and ferroelectric materials. Then, the interplay mechanisms, modulation effects, and typical device structures of ferroelectric-optoelectronic hybrid systems are discussed. Finally, in summary and perspective section, the progress of ferroelectrics integrated PDs is summed up and the challenges of ferroelectrics in the field of optoelectronics are considered.

Characteristics of Molecular Genetic Mutations and Their Correlation with Prognosis in Adolescent and Adult Patients with Acute Lymphoblastic Leukemia.

INTRODUCTION: The prognosis of acute lymphoblastic leukemia (ALL) in adolescents and adults is poor, and recurrence is an important cause of their death. Changes of genetic information play a vital role in the pathogenesis and recurrence of ALL; however, the impact of molecular genetic mutations on disease diagnosis and prognosis remains unexplored. This study aimed to explore the frequency spectrum of gene mutations and their prognostic significance, along with the minimal residual disease (MRD) level and hematopoietic stem cell transplantation (HSCT), in adolescent and adult patients aged ≥15 years with ALL. METHODS: The basic characteristics, cytogenetics, molecular genetics, MRD level, treatment regimen, and survival outcome of patients with untreated ALL (≥15 years) were collected, and the correlation and survival analysis were performed using the SPSS 25.0 and R software. RESULTS: This study included 404 patients, of which 147 were selected for next-generation sequencing (NGS). NGS results revealed that 91.2% of the patients had at least one mutation, and 67.35% had multiple (≥2) mutations. NOTCH1, PHF6, RUNX1, PTEN, JAK3, TET2, and JAK1 were the most common mutations in T-ALL, whereas FAT1, TET2, NARS, KMT2D, FLT3, and RELN were the most common mutations in B-ALL. Correlation analysis revealed the mutation patterns, which were significantly different between T-ALL and B-ALL. In the prognostic analysis of 107 patients with B-ALL, multivariate analysis showed that the number of mutations ≥5 was an independent risk factor for overall survival and the RELN mutation was an independent poor prognostic factor for event-free survival. DISCUSSION: The distribution of gene mutations and the co-occurrence and repulsion of mutant genes in patients with ALL were closely related to the immunophenotype of the patients. The number of mutations ≥5 and the RELN mutation were significantly associated with poor prognosis in adolescent and adult patients with ALL.

Waterproof and Flexible Perovskite Photodetector Enabled By P-type Organic Molecular Rubrene with High Moisture and Mechanical Stability.

Metal halide perovskite films have gained significant attention because of their remarkable optoelectronic performances. However, their poor stability upon the severe environment appears to be one of the main facets that impedes their further commercial applications. Herein, a method to improve the stability of flexible photodetectors under water and humidity environment without encapsulation is reported. The devices are fabricated using the physical vapor deposition method (Pulse Laser Deposition & Thermal Evaporation) under high-vacuum conditions. An amorphous organic Rubrene film with low molecular polarity and high elastic modulus serves as both a protective layer and hole transport layer. After immersed in water for 6000 min, the photoluminescence intensity attenuation of films only decreased by a maximum of 10%. The demonstrator device, based on Rubrene/CsPbBr3/ZnO heterojunction confirms that the strategy not only enhances device moisture and mechanical stability but also achieves high sensitivity in optoelectronic detection. In self-powered mode, it has a fast response time of 79.4 µs /207.6 µs and a responsivity 124 mA W-1. Additionally, the absence of encapsulation simplifies the fabrication of complex electrodes, making it suitable for various applications. This study highlights the potential use of amorphous organic films in improving the stability of perovskite-based flexible devices.

Maintenance and consolidation strategies for patients with untreated advanced follicular lymphoma: A systematic review and network meta-analysis of randomized trials.

BACKGROUND: The emergence of novel and efficient antibody maintenance approaches has provided more options for post-induction treatment of advanced follicular lymphoma (FL), and further comparisons are required to determine the most clinically beneficial regimen. The authors conducted a systematic review and meta-analysis to evaluate the maintenance or consolidation strategy. METHODS: The authors performed two independent searches in PubMed, Web of Science, the Cochrane library databases, Scopus, and Embase for randomized controlled trials (RCTs) evaluating maintenance or consolidation therapy in untreated FL patients. Extracted data included the clinical characteristics, treatment regimen, progression-free survival (PFS), overall survival (OS), and adverse effects. They then pooled the data and used a Bayesian random-effects model to combine direct comparisons with indirect evidence. RESULTS: The authors screened 1515 records and identified 13 eligible RCTs that assessed nine different regimens in 5681 advanced FL patients. Reconstructed individual survival data presented that obinutuzumab had the highest effect sizes and certainty of the evidence for PFS (hazard ratio, 0.43; 95% confidence interval, 0.22-0.79) and tolerability compared with observation. However, no benefit was observed in patients according to the OS, regardless of which regimen was taken. Considering other regimens, although an extended course of rituximab maintenance and consolidation therapies presented PFS benefits compared with standard rituximab maintenance, they were also associated with higher toxicity. CONCLUSIONS: Although obinutuzumab and rituximab maintenance treatment improved PFS significantly, its clinical benefit requires further validation in larger populations. Furthermore, because few trials informed each treatment comparison, research is needed to refine the understanding of this complex and rapidly evolving treatment landscape.

Activation of STING by SAMHD1 Deficiency Promotes PANoptosis and Enhances Efficacy of PD-L1 Blockade in Diffuse Large B-cell Lymphoma.

Genomic instability is a significant driver of cancer. As the sensor of cytosolic DNA, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a critical role in regulating anti-tumor immunity and cell death. However, the role and regulatory mechanisms of STING in diffuse large B-cell lymphoma (DLBCL) are still undefined. In this study, we reported that sterile alpha motif and HD domain-containing protein 1 (SAMHD1) deficiency induced STING expression and inhibited tumor growth in DLBCL. High level of SAMHD1 was associated with poor prognosis in DLBCL patients. Down-regulation of SAMHD1 inhibited DLBCL cell proliferation both in vitro and in vivo. Moreover, we found that SAMHD1 deficiency induced DNA damage and promoted the expression of DNA damage adaptor STING. STING overexpression promoted the formation of Caspase 8/RIPK3/ASC, further leading to MLKL phosphorylation, Caspase 3 cleavage, and GSDME cleavage. Up-regulation of necroptotic, apoptotic, and pyroptotic effectors indicated STING-mediated PANoptosis. Finally, we demonstrated that the STING agonist, DMXAA, enhanced the efficacy of a PD-L1 inhibitor in DLBCL. Our findings highlight the important role of STING-mediated PANoptosis in restricting DLBCL progression and provide a potential strategy for enhancing the efficacy of immune checkpoint inhibitor agents in DLBCL.

The synergy of the XPO1 inhibitors combined with the BET inhibitor INCB057643 in high-grade B-cell lymphoma via downregulation of MYC expression.

High grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH) represents an uncommon B-cell lymphoma (BCL) with aggressive clinical courses and poor prognosis. Despite revolutionary therapeutic advances in BCL, there has been limited treatment progress in HGBCL-DH, thus necessitating additional therapeutic strategies for HGBCL-DH. This study demonstrated that the BET antagonist INCB057643 synergized with the XPO1 inhibitors (selinexor and eltanexor) to decrease cell viability and increase cell apoptosis in HGBCL-DH cells with or without TP53 mutations. As anticipated, the combined treatment of INCB057643 with selinexor slowed tumor growth and reduced the tumor burden in TP53-mutated HGBCL-DH xenografts. Mechanistically, MYC functional inhibition was a potential molecular mechanism underlying the synergy of the combined INCB057643 and selinexor treatment in HGBCL-DH cells independent of TP53 mutation status. In TP53 mutated HGBCL-DH cells, inducing DNA damage and impairing the DNA damage response (DDR) were involved in the therapeutic interaction of the combined regimen. In TP53 wild-type cells, the molecular mechanism was linked with upregulation of p53 levels and activation of its targeted pathways, rather than dysregulation of the DDR. Collectively, we might provide a potential promising combination therapy regimen for the management of HGBCL-DH. Clinical evaluations are warranted to confirm this conclusion.

Designing Ordered Organic Small-Molecule Domains for Ultraviolet Detection and Micrometer-Sized Flexible Imaging.

Photodetectors displaying an ultraviolet (UV) spectral response window are typically based on wide-bandgap semiconductors that have long been dominated by inorganic materials that suffer from bottlenecks of low flexibility and a limited material family. Here, we synthesized a novel organic small molecule and controlled its crystallization to suppress leakage currents and facilitate separation of the carriers, and the relationship between the nanoscale phase separation morphology and the optoelectrical performance of the photodetectors is disclosed. Our optimized organic photodetector (OPD) presents a UV spectral response window, with superior self-powered responsivities of 45 mA/W (under 250 nm light) and 70 mA/W (under 300 nm light), outperforming the Si photodiode and rivaling other reported UV self-powered photodetectors. Finally, an imaging system was constructed to demonstrate the application potential of the OPD in UV flexible imaging with high-resolution arrays of 400 pixels × 400 pixels (5 µm × 5 µm per pixel), which could work in bent states and successfully output images of micrometer-sized objects.

ETS1 phosphorylation at threonine 38 is associated with the cell of origin of diffuse large B cell lymphoma and sustains the growth of tumour cells.

The transcriptional factor ETS1 is upregulated in 25% of diffuse large B cell lymphoma (DLBCL). Here, we studied the role of ETS1 phosphorylation at threonine 38, a marker for ETS1 activation, in DLBCL cellular models and clinical specimens. p-ETS1 was detected in activated B cell-like DLBCL (ABC), not in germinal centre B-cell-like DLBCL (GCB) cell lines and, accordingly, it was more common in ABC than GCB DLBCL diagnostic biopsies. MEK inhibition decreased both baseline and IgM stimulation-induced p-ETS1 levels. Genetic inhibition of phosphorylation of ETS1 at threonine 38 affected the growth and the BCR-mediated transcriptome program in DLBCL cell lines. Our data demonstrate that ETS1 phosphorylation at threonine 38 is important for the growth of DLBCL cells and its pharmacological inhibition could benefit lymphoma patients.

A Dual-Functional Perovskite-Based Photodetector and Memristor for Visual Memory.

The imitation of human visual memory demands the multifunctional integration of light sensors similar to the eyes, and image memory, similar to the brain. Although humans have already implemented electronic devices with visual memory functions, these devices require a combination of various components and logical circuits. However, the combination of visual perception and high-performance information storage capabilities into a single device to achieve visual memory remains challenging. In this study, inspired by the function of human visual memory, a dual-functional perovskite-based photodetector (PD) and memristor are designed to realize visual perception and memory capacities. As a PD, it realizes an ultrahigh self-powered responsivity of 276 mA W-1 , a high detectivity of 4.7 × 1011  Jones (530 nm; light intensities, 2.34 mW cm-2 ), and a high rectification ratio of ≈100 (±2 V). As a memristor, an ultrahigh on/off ratio (≈105 ), an ultralow power consumption of 3 × 10-11  W, a low setting voltage (0.15 V), and a long retention time (>7000 s) are realized. Moreover, the dual-functional device has the capacity to perceive and remember light paths and store data with good cyclic stability. This device exhibits perceptual and cyclic erasable memory functions, which provides new opportunities for mimicking human visual memory in future multifunctional applications.

The epidemiological patterns of non-Hodgkin lymphoma: global estimates of disease burden, risk factors, and temporal trends.

Background: The incidence of non-Hodgkin's lymphoma (NHL) has increased steadily over the past few decades. Elucidating its global burden will facilitate more effective disease management and improve patient outcomes. We explored the disease burden, risk factors, and trends in incidence and mortality in NHL globally. Methods: The up-to-date data on age-standardized incidence and mortality rates of NHL were retrieved from the GLOBOCAN 2020, CI5 volumes I-XI, WHO mortality database, and Global Burden of Disease (GBD) 2019, focusing on geographic disparities worldwide. We reported incidence and mortality by sex and age, along with corresponding age-standardized rates (ASRs), the average annual percentage change (AAPC), and future burden estimates to 2040. Results: In 2020, there were an estimated 545,000 new cases and 260,000 deaths of NHL globally. In addition, NHL resulted in 8,650,352 age-standardized DALYs in 2019 worldwide. The age-specific incidence rates varied drastically across world areas, at least 10-fold in both sexes, with the most pronounced increase trend found in Australia and New Zealand. By contrast, North African countries faced a more significant mortality burden (ASR, 3.7 per 100,000) than highly developed countries. In the past decades, the pace of increase in incidence and mortality accelerated, with the highest AAPC of 4.9 (95%CI: 3.6-6.2) and 6.8 (95%CI: 4.3-9.2) in the elderly population, respectively. Considering risk factors, obesity was positively correlated with age-standardized incidence rates (P< 0.001). And North America was the high-risk region for DALYs due to the high body mass index in 2019. Regarding demographic change, NHL incident cases are projected to rise to approximately 778,000 by 2040. Conclusion: In this pooled analysis, we provided evidence for the growing incidence trends in NHL, particularly among women, older adults, obese populations, and HIV-infected people. And the marked increase in the older population is still a public health issue that requires more attention. Future efforts should be directed at cultivating health awareness and formulating effective and locally tailored cancer prevention strategies, especially in most developing countries.

Photoimaging with Color-Sensing Abilities by Tuning the Band Gap of a Single-Crystal Lead-Free Perovskite.

Photodetectors (PDs) composed of lead-free metal halide perovskites have been a shining topic in optoelectronics. However, it is debatable whether perovskites are an n-type or p-type semiconductor with a direct or indirect band gap. Furthermore, to date, little research has been conducted on lead-free metal halide perovskites with color-sensing abilities. Herein, for the first time, single-crystal MA3Bi2I3xBr9-3x (x = 0, 1, 2, and 3) perovskites were systematically studied, and the results showed that MA3Bi2I9 is a p-type direct-band-gap semiconductor, whereas MA3Bi2Br9 is an n-type indirect-band-gap semiconductor. Furthermore, the band gap of MA3Bi2I3xBr9-3x (x = 0, 1, 2, and 3) perovskites can be systematically tuned from 2.06 to 2.55 eV, affording it with color-sensing abilities from 450 to 580 nm, respectively. The representative Au-MA3Bi2I9-ITO (ITO = indium tin oxide) PD exhibits a superior self-powered photodetecting performance with a high responsivity (15.8 mA W-1; 580 nm, 1.0 mW cm-2), detectivity (8.1 × 1011 Jones), an on/off ratio (4231), LDR (72.5 dB) and a fast response speed (rise time of 2 µs and decay time of 29 µs). This study not only facilitates the theoretical understanding of the band gap of perovskite materials but also sheds light on the application of lead-free perovskites in object interaction and color perception.

Derivation and validation of a nutrition-covered prognostic scoring system for extranodal NK/T-cell lymphoma.

Introduction: Patients with aggressive lymphomas are at high risk of losing body resources, resulting in malnutrition, immunodeficiency and inferior outcomes. Nutritional status is closely associated with survival, but often neglected in the prognostic assessment. This study aimed to explore the significance of nutritional status in extranodal NK/T-cell lymphoma (ENKTL). Methods: Univariate and multivariate Cox regression analyses were conducted to examine the significance of nutritional index on overall survival (OS) and progression-free survival (PFS). A nutrition-incorporated score system was constructed based on the multivariate results, and its calibration, discrimination and clinical utility were tested in the training and validation cohort. Results: Multivariate analysis revealed controlling nutritional status (CONUT) score could independently predict OS (HR 10.247, P=0.001) and PFS (HR 5.587, P=0.001) in addition to prognostic index of natural killer lymphoma plus EBV (PINK-E). Herein, a reformative model, CONUT-PINK-E, was developed and further verified in external validation cohort. CONUT-PINK-E classified patients into three risk grades with significant survival differences (P < 0.001). Compared with the current models, CONUT-PINK-E presented superior discrimination, calibration and clinical benefit. Discussion: In this study, we firstly verified that CONUT score was efficient to screen prognosis-related malnutrition in ENKTL. Moreover, we developed the first nutritional assessment-covered scoring system, CONUT-PINK-E, which might be a promising tool to provide references for clinical decision-making of ENKTL patients.

Intelligent Multifunctional Sensing Systems based on Ordered Macro-Microporous Metal Organic Framework and Its Derivatives.

Compared with nanomaterials-based sensors with single function, the development of multifunctional sensors shows high potential in comprehensive monitoring of personal health and environment, intelligent human-machine interfaces, and realistic imitation of human skin in prosthetics. Ordered macro-microporous metal-organic frameworks (MOFs)-enabled flexible and stretchable electronics are promising candidates for integrated multifunctional sensing systems. Herein, a three-dimensional ordered macro-microporous zeolite imidazolate framework-8 (3DOM ZIF-8) for humidity sensing and the derived ZnO within a hierarchically ordered macroporous-mesoporous-microporous carbon matrix (ZnO@HOMC) for gas sensor is constructed. Benefit from hierarchically ordered macroporous-mesoporous-microporous structure, the active site is fully exposed, and the charge transfer is accelerated. As a result, the multifunctional sensing systems show ultrafast response and recovery speed (10 s and 34 s), high sensitivity (Rair /Rgas = 38.6@50 ppm) to acetone, rapid humidity response speed (0.23 s) within changing humidity (RH 21%-99%), excellent stability and repeatability. Furthermore, in order to realize real-time monitoring of gas concentrations and humidity on mobile devices, an intelligent and portable sensor module is fabricated and wirelessly connected to a smartphone to effectively detect acetone concentration and humidity. This sensing technology shows fascinating applications in personal health, fitness tracking, electronic skins, artificial nervous systems, and human-machine interactions.

Dyslipidemia in the First 100 days and the Association with Acute Graft-versus-host Disease after Allogeneic Stem Cell Transplantation: A Single-center Retrospective Study in China.

Dyslipidemia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The interaction between post-transplant hyperlipidemia and acute graft-versus-host disease (aGVHD) is uncertain. In this study, we performed a retrospective study to explore the relationship between dyslipidemia and aGVHD and the potential mechanism of aGVHD on dyslipidemia in 147 recipients who underwent allo-HSCT. The lipid profiles, transplantation details, and other laboratory data of the subjects were collected in the first 100 days post-transplantation. Our results indicated 63 patients with new-onset hypertriglyceridemia and 39 patients with new-onset hypercholesterolemia. A total of 57 (38.8%) patients developed aGVHD after transplantation. In a multifactorial analysis, aGVHD was an independent factor in the development of dyslipidemia in recipients (P < 0.05). After transplantation, the median LDL-C level of patients with aGVHD was 3.04 mmol/L (standard deviation value (SD): 1.36 mmol/L, 95% confidence interval (CI): 2.62, 3.45 mmol/L), and the LDL-C level in patients without aGVHD was 2.51 mmol/L (SD: 1.38 mmol/L, CI: 2.67, 3.40 mmol/L) (P < 0.05). Female recipients had higher lipid levels than males (P < 0.05). LDL levels (≥ 3.4 mmol/L) post-transplant were an independent risk factor for the development of aGVHD (OR = 0.311, P < 0.05). In conclusion, larger sample studies are anticipated to confirm our preliminary result, and an accurate mechanism between lipid metabolism and aGVHD needs to be determined in the future.

Simultaneous quantification of venetoclax and voriconazole in human plasma by UHPLC-MS/MS and its application in acute myeloid leukemia patients.

Venetoclax, an orally bioavailable BCL-2 inhibitor, has been regarded as a breakthrough for the treatment of leukemia but has a wide interindividual variability and drug-drug interaction in pharmacokinetics. In this study, a simple and sensitive ultra-high performance liquid chromatography-tandem with mass spectrometry method was established and fully validated to quantify venetoclax and voriconazole simultaneously in human plasma. After protein precipitation, the analytes were separated on a Hypersil GOLD C18 column (3 µm, 2.1 × 50 mm) by gradient elution. The mass detection was operated under multiple reaction monitoring mode at m/z 868.5 →636.2 for venetoclax, 350.0 → 127.0 for voriconazole and 353.0 → 127.0 for voriconazole-D3(Internal Standard). The calibration ranges were 0.1-10 µg/mL for venetoclax and 0.05-10 µg/mL for voriconazole with correlation coefficients (r2)＞0.998. The validated method was successfully applied to the pharmacokinetic study in acute myeloid leukemia patients receiving venetoclax with or without voriconazole. The results suggested that co-treatment with 200 mg q12h voriconazole, the peak concentration of venetoclax (100 mg qd) could be raised to the same level as the 400 mg qd group. However, the trough concentration of venetoclax (100 mg qd) was much higher than that of the 400 mg qd group. Therapeutic drug monitoring might give some guidance for the adjustment of dosing regimens to guarantee the drug efficacy and safety of patients to some extent.