Model-based precision dosing and remedial dosing recommendations for delayed or missed doses of isoniazid in Chinese patients with tuberculosis.

AIMS: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients. METHODS: In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed-effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. RESULTS: A 2-compartmental model, including first-order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally. CONCLUSION: PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.

Copy number variants landscape of multiple cancers and clinical applications based on NGS gene panel.

BACKGROUND: The rapid adoption of next-generation sequencing in clinical oncology has enabled detection of molecular biomarkers which are shared between multiple tumour types. Intra-tumour heterogeneity is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the tumour-related copy number variants (CNVs), as key regulators of cancer origination, development, and progression, across various types of cancers are poorly understood. METHODS: We performed pan-cancer CNV analysis of cancer-related genes in 15 types of cancers including 1438 cancerous patients by next-generation sequencing using a commercially available pan-cancer panel (Onco PanScan™). Downstream bioinformatics analysis was performed in order to detect CNVs, cluster analysis of the found CNVs, and comparison of the frequency of gained CNVs between different types of cancers. LASSO analysis was used for identification of the most important CNVs. RESULTS: We also identified 523 CNVs among which 16 CNVs were common while 22 CNVs were caner-specific CNVs. Meanwhile, FAM58A was most commonly found in all studied cancers in this study and significant differences were found in FAM58A between female and male patients (p = .001). Common CNVs, such as FOXA1, NFKBIA, HEY1, MECOM, CHD7, AGO2, were mutated in 6.79%, 8.45%, 7.51%, 6.43%, 7.59%, 8.16% of tumours, while most of these mutations have proven roles in positive regulation of transcription from RNA polymerase II promoter. 11 features including sex, DIS3, EPHB1, ERBB2, FLT1, HCK, KEAP1, MYD88, PARP3, TBX3, and TOP2A were found as the key features for classification of cancers using CNVs. CONCLUSION: The 16 common CNVs between cancers can be used to identify the target of pan-cancer drug design and targeted therapies. Additionally, 22 caner-specific CNVs can be used as unique diagnostic markers for each cancer type.

Diagnostic validity of MRI for central nervous system tuberculosis: protocol for a systematic review and meta-analysis.

INTRODUCTION: Central nervous system tuberculosis (CNSTB) is a severe condition, sometimes associated with a poor prognosis. Early diagnosis of CNSTB remains challenging, considering that conventional methods lack sensitivity or might lead to certain side effects. Herein, we presented a protocol for a systematic review and meta-analysis to assess the diagnostic efficacy of MRI for CNSTB. METHODS AND ANALYSIS: SinoMed, Wanfang database, China National Knowledge Infrastructure, Embase, the Cochrane Library and PubMed will be searched to identify studies reporting on the use of MRI in the diagnosis of CNSTB from database inception to December 2023. The following keywords will be applied: 'Intracranial tuberculosis', 'Cerebral tuberculosis', 'Central nervous system tuberculosis', 'Spinal tuberculous arachnoiditis' and 'Magnetic Resonance Imaging'. Studies that evaluate the diagnostic accuracy of MRI for the diagnosis of CNSTB and report clear reference criteria will be included. Studies from which full true positive, false positive, false negative and true negative values cannot be extracted, those published in languages other than English or Chinese, abstracts not reporting the full text, and case reports will be excluded. Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) will be used to evaluate the methodological quality of each included study. Stata V.15.0 and RevMan V.5.3 will be used to perform a meta-analysis and generate forest plots and summary receiver operating characteristic curves. In case of significant heterogeneity between studies, possible sources of heterogeneity will be explored through subgroup and meta-regression analyses. ETHICS AND DISSEMINATION: This research is based on public databases and does not require ethical approval. Results will be submitted for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023415690.

Carbon Dots in Hydroxy Fluorides: Achieving Multicolor Long-Wavelength Room-Temperature Phosphorescence and Excellent Stability via Crystal Confinement.

Carbon dots (CDs) have aroused widespread interest in the construction of room-temperature phosphorescent (RTP) materials. However, it is a great challenge to obtain simultaneous multicolor long-wavelength RTP emission and excellent stability in CD-based RTP materials. Herein, a novel and universal "CDs-in-YOHF" strategy is proposed to generate multicolor and long-wavelength RTP by confining various CDs in the Y(OH)xF3-x (YOHF) matrix. The mechanism of the triplet emission of CDs is related to the space confinement, the formation of hydrogen bonds and C-F bonds, and the electron-withdrawing fluorine atoms. Remarkably, the RTP lifetime of orange-emissive CDs-o@YOHF is the longest among the reported single-CD-matrix composites for emission above 570 nm. Furthermore, CDs-o@YOHF exhibited higher RTP performance at long wavelength in comparison to CDs-o@matrix (matrix = PVA, PU, urea, silica). The resulting CDs@YOHF shows excellent photostability, thermostability, chemical stability, and temporal stability, which is rather favorable for information security, especially in a complex environment.

Exciton Emissions in Bilayer WSe2 Tuned by the Ferroelectric Polymer.

In this work, a hybrid structure of multilayer transition-metal dichalcogenides (TMDs) and a ferroelectric polymer is designed to achieve passive control of optical properties in situ. The electrical polarization in the ferroelectric poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) polymer can regulate the photoluminescence (PL) in bilayer WSe2. The total PL emission intensity is substantially suppressed or enhanced under large gate voltage in bilayer WSe2. This is because electrons transfer between the conduction band K valley and the conduction band Λ valley by the electrostatic field in the P(VDF-TrFE) polymer. This electron transfer further adjusts the proportion of direct and indirect excitons and, in turn, changes the overall optical radiation efficiency. We also illustrate that the engineered PL originates from the external electric-field-dependent transferred electron effect. The theoretical result matches the experimental data well. This work demonstrates a device platform in which passive regulation is achieved using 2D TMDs modulated by polarized ferroelectric materials.

Lanthanide Yb/Er co-doped semiconductor layered WSe2 nanosheets with near-infrared luminescence at telecommunication wavelengths.

Atomically thin layers of transition metal dichalcogenides (TMDs) have recently drawn great attention. However, doping strategies and controlled synthesis for wafer-scale TMDs are still in their early stages, greatly hindering the construction of devices and further basic studies. In this work, we develop the fast deposition of wafer-scale layered lanthanide ion Yb/Er co-doped WSe2 using pulsed laser deposition. WSe2 nanosheets were chosen as the host, while Yb3+ and Er3+ ions served as the sensitizer and activator, respectively. The obtained Yb/Er co-doped WSe2 layers exhibit good uniformity and high crystallinity with highly textured features. Under the excitation of a diode laser at 980 nm, down-conversion emission is observed at around 1540 nm, assigned to the emission transition between the 4I13/2 and 4I15/2 states of Er3+. Considering the significance of 1540 nm luminescence in the application of photonic technologies, this observation in the WSe2:Yb/Er nanosheets down to the monolayer provides a new opportunity for developing photonic devices at the 2D limit. Our work not only offers a general method to prepare wafer-scale lanthanide doped TMDs, but also to widely modulate the luminescence of atomically layered TMDs by introducing lanthanide ions.

Wafer-Scale Synthesis of High-Quality Semiconducting Two-Dimensional Layered InSe with Broadband Photoresponse.

Large-scale synthesis of two-dimensional (2D) materials is one of the significant issues for fabricating layered materials into practical devices. As one of the typical III-VI semiconductors, InSe has attracted much attention due to its outstanding electrical transport property, attractive quantum physics characteristics, and dramatic photoresponse when it is reduced to atomic scale. However, scalable synthesis of single phase 2D InSe has not yet been achieved so far, greatly hindering further fundamental studies and device applications. Here, we demonstrate the direct growth of wafer-scale layered InSe nanosheets by pulsed laser deposition (PLD). The obtained InSe layers exhibit good uniformity, high crystallinity with macro texture feature, and stoichiometric growth by in situ precise control. The characterization of optical properties indicates that PLD grown InSe nanosheets have a wide range tunable band gap (1.26-2.20 eV) among the large-scale 2D crystals. The device demonstration of field-effect transistor shows the n-type channel feature with high mobility of 10 cm2 V-1 s-1. Upon illumination, InSe-based phototransistors show a broad photoresponse to the wavelengths from ultraviolet to near-infrared. The maximum photoresponsivity attains 27 A/W, plus a response time of 0.5 s for the rise and 1.7 s for the decay, demonstrating the strong and fast photodetection ability. Our findings suggest that the PLD grown InSe would be a promising choice for future device applications in the 2D limit.

Tuning of near-infrared-to-near-infrared luminescence from one-photon to two-photon anti-Stokes shift in Ca3Ga2- xCrxGe3O12 via varying Cr3+ content.

Near-infrared-to-near-infrared (NIR-to-NIR) anti-Stokes luminescence from Cr3+ singly doped Ca3Ga2Ge3O12 (CGGG) occurs under the excitation of an 808 nm diode laser. The anti-Stokes processes vary from one photon to two photon, depending on the Cr3+ content (x) in Ca3Ga2-xCrxGe3O12. The results suggest that phonon-assisted anti-Stokes excitation and cooperative energy transfer are involved in the observed upconversion (UC) processes of CGGG:Cr3+. The relevant Cr3+-doping-concentration-dependent NIR-to-NIR anti-Stokes luminescent mechanism, either one-photon or two-photon UC, is investigated. Such an observation on modulating the UC process via varying the doping concentration is helpful in broadening the understanding of UC phenomena.

Luminescence and site occupancies of Eu3+ in La2CaB10O19.

Eu(3+)-activated La2CaB10O19 phosphors with nominal chemical formulae La(2-x)Eu(x)CaB10O19 and La2Ca(1-2x)Eu(x)Na(x)B10O19 were prepared. The luminescence properties under VUV-UV excitation were investigated. Luminescence spectra reveal Eu(3+) ions occupy both Ca(2+) and La(3+) sites in all samples. The O(2-)→ Eu(3+) charge transfer bands (CTBs) and the (5)D0→(7)F0 emissions of Eu(3+) at Ca (2+) site and La(3+) site are identified, respectively. The schematic energy levels for Eu(3+) in two sites were achieved. Luminescence decays of the (5)D0→(7)F0 transitions were measured for both sites.

[Luminescence of Sr2Mg(BO3)2:Tb3+ under vacuum ultraviolet excitation].

The phosphors of Tb3+ activated Sr2 Mg(B03)2 were prepared by high temperature solid-state reaction technique. The phase purity was characterized by the powder X-ray diffraction (XRD). The luminescence properties in VUV-Vis range as well as the decay curves were investigated. The results demonstrate that the band near 178 nm in the VUTV excitation spectra is ascribed to the host-related absorption. The bands of lowest spin-allowed and spin-forbidden f--d transition are located at 235 and 278 nm, respectively. The strongest emission is at 543 nm upon 172 nm excitation and with the color coordinate (0.30, 0.45). The decay time is about 2.8 ms.