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.

Constructing Hollow Multishelled Microreactors with a Nanoconfined Microenvironment for Ofloxacin Degradation through Peroxymonosulfate Activation: Evolution of High-Valence Cobalt-Oxo Species.

This study constructed hollow multishelled microreactors with a nanoconfined microenvironment for degrading ofloxacin (OFX) through peroxymonosulfate (PMS) activation in Fenton-like advanced oxidation processes (AOPs), resulting in adequate contaminant mineralization. Among the microreactors, a triple-shelled Co-based hollow microsphere (TS-Co/HM) exhibited optimal performance; its OFX degradation rate was 0.598 min-1, which was higher than that of Co3O4 nanoparticles by 8.97-fold. The structural tuning of Co/HM promoted the formation of oxygen vacancies (VO), which then facilitated the evolution of high-valence cobalt-oxo (Co(IV)═O) and shifted the entire t2g orbital of the Co atom upward, promoting catalytic reactions. Co(IV)═O was identified using a phenylmethyl sulfoxide (PMSO) probe and in situ Raman spectroscopy, and theoretical calculations were conducted to identify the lower energy barrier for Co(IV)═O formation on the defect-rich catalyst. Furthermore, the TS-Co/HM catalyst exhibited remarkable stability in inorganic (Cl-, H2PO4-, and NO3-), organic (humic acid), real water samples (tap water, river water, and hospital water), and in a continuous flow system in a microreactor. The nanoconfined microenvironment could enrich reactants in the catalyst cavities, prolong the residence time of molecules, and increase the utilization efficiency of Co(IV)═O. This work describes an activation process involving Co(IV)═O for organic contaminants elimination. Our results may encourage the use of multishelled structures and inform the design of nanoconfined catalysts in AOPs.

Modulating tumour vascular normalisation using triptolide-loaded NGR-functionalized liposomes for enhanced cancer radiotherapy.

Radiotherapy is an effective therapy in tumour treatment. However, the characteristics of the tumour microenvironment, including hypoxia, low pH, and interstitial fluid pressure bring about radioresistance. To improve the anti-tumour effect of radiotherapy, it has been demonstrated that antiangiogenic therapy can be employed to repair the structural and functional defects of tumour angiogenic vessels, thereby preventing radioresistance or poor therapeutic drug delivery. In this study, we prepared triptolide (TP)-loaded Asn-Gly-Arg (NGR) peptide conjugated mPEG2000-DSPE-targeted liposomes (NGR-PEG-TP-LPs) to induce tumour blood vessel normalisation, to the end of increasing the sensitivity of tumour cells to radiotherapy. Further, to quantify the tumour vessel normalisation window, the structure and functionality of tumour blood vessels post NGR-PEG-TP-LPs treatment were evaluated. Thereafter, the anti-tumour effect of radiotherapy following these treatments was evaluated using HCT116 xenograft-bearing mouse models based on the tumour vessel normalisation period window. The results obtained showed that NGR-PEG-TP-LPs could modulate tumour vascular normalisation to increase the oxygen content of the tumour microenvironment and enhance the efficacy of radiotherapy. Further, liver and kidney toxicity tests indicated that NGR-PEG-TP-LPs are safe for application in cancer treatment.

Research and Application of Energy-Efficient Management Approach for Wireless Sensor Networks.

Wireless sensor networks (WSNs) are widely used in industrial applications. However, many of them have limited lifetimes, which has been a considerable constraint on their widespread use. As a typical application of WSNs, distributed measurement of the electric field under high-voltage direct-current (HVDC) transmission lines also suffers from this issue. This paper first introduces the composition of the electric-field measurement system (EFMS) and its working principle. Considering the actual power supply of the system, this paper mainly introduces the composition of the wireless sensor node (WSND) and analyzes the power consumption and potential working state transformation of the WSND, together with a comprehensive study on parameters affecting the power consumption of the wireless communication unit. Moreover, an energy-efficient scheduling approach is proposed after specially designing a working sequence and the study on system parameters. The proposed approach is verified by experiments on not only the experimental line of the national HVDC test base, but also a commercial operation HVDC transmission line with the challenge of long endurance, which is considered in this paper with a new strategy. The results show that the proposed method can greatly extend the lifetime of the WSND.

Dual-Role of Polyelectrolyte-Tethered Benzimidazolium Cation in Promoting CO2 /Pure Water Co-Electrolysis to Ethylene.

Electrochemical CO2 reduction reaction (CO2 RR), as a promising route to realize negative carbon emissions, is known to be strongly affected by electrolyte cations (i.e., cation effect). In contrast to the widely-studied alkali cations in liquid electrolytes, the effect of organic cations grafted on alkaline polyelectrolytes (APE) remains unexplored, although APE has already become an essential component of CO2 electrolyzers. Herein, by studying the organic cation effect on CO2 RR, we find that benzimidazolium cation (Beim+ ) significantly outperforms other commonly-used nitrogenous cations (R4 N+ ) in promoting C2+ (mainly C2 H4 ) production over copper electrode. Cyclic voltammetry and in situ spectroscopy studies reveal that the Beim+ can synergistically boost the CO2 to *CO conversion and reduce the proton supply at the electrocatalytic interface, thus facilitating the *CO dimerization toward C2+ formation. By utilizing the homemade APE ionomer, we further realize efficient C2 H4 production at an industrial-scale current density of 331 mA cm-2 from CO2 /pure water co-electrolysis, thanks to the dual-role of Beim+ in synergistic catalysis and ionic conduction. This study provides a new avenue to boost CO2 RR through the structural design of polyelectrolytes.

Fabrication and in vitro evaluation of 3D printed porous silicate substituted calcium phosphate scaffolds for bone tissue engineering.

Silicate-substituted calcium phosphate (Si-CaP) ceramics, alternative materials for autogenous bone grafting, exhibit excellent osteoinductivity, osteoconductivity, biocompatibility, and biodegradability; thus, they have been widely used for treating bone defects. However, the limited control over the spatial structure and weak mechanical properties of conventional Si-CaP ceramics hinder their wide application. Here, we used digital light processing (DLP) printing technology to fabricate a novel porous 3D printed Si-CaP scaffold to enhance the scaffold properties. Scanning electron microscopy, compression tests, and computational fluid dynamics simulations of the 3D printed Si-CaP scaffolds revealed a uniform spatial structure, appropriate mechanical properties, and effective interior permeability. Furthermore, compared to Si-CaP groups, 3D printed Si-CaP groups exhibited sustained release of silicon (Si), calcium (Ca), and phosphorus (P) ions. Furthermore, 3D printed Si-CaP groups had more comprehensive and persistent osteogenic effects due to increased osteogenic factor expression and calcium deposition. Our results show that the 3D printed Si-CaP scaffold successfully improved bone marrow mesenchymal stem cells (BMSCs) adhesion, proliferation, and osteogenic differentiation and possessed a distinct apatite mineralization ability. Overall, with the help of DLP printing technology, Si-CaP ceramic materials facilitate the fabrication of ideal bone tissue engineering scaffolds with essential elements, providing a promising approach for bone regeneration.

Low-level laser therapy with different irradiation methods modulated the response of bone marrow mesenchymal stem cells in vitro.

Low-level laser therapy (LLLT) also known as photobiomodulation is a treatment to change cellular biological activity. The exact effects of LLLT remain unclear due to the different irradiation protocols. The purpose of this study was to investigate the effects of LLLT by three different irradiation methods on the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. BMSCs were inoculated in 24-well plates and then irradiated or not (control) with a laser using three different irradiation methods. The irradiation methods were spot irradiation, covering irradiation, and scanning irradiation according to different spot areas (0.07 cm2 or 1.96 cm2) and irradiation areas (0.35 cm2 or 1.96 cm2), respectively. The laser was applied three times at energy densities of 4 J/cm2. The cell proliferation by CCK-8. ALP activity assay, alizarin red, and quantitative real-time polymerase chain reaction (RT-PCR) were performed to assess osteogenic differentiation and mineralization. Increases in cell proliferation was obvious following irradiation, especially for covering irradiation. The ALP activity was significantly increased in irradiated groups compared with non-irradiated control. The level of mineralization was obviously improved following irradiation, particularly for covering irradiation. RT-PCR detected significantly higher expression of ALP, OPN, OCN, and RUNX-2 in the group covering than in the others, and control is the lowest. The presented results indicate that the biostimulative effects of LLLT on BMSCs was influenced by t he irradiation method, and the covering irradiation is more favorable method to promote the proliferation and osteogenic differentiation of BMSCs.

Preparation and surface-enhanced Raman scattering properties of GO/Ag/Ta2O5 composite substrates.

The composite substrate composed of precious metal, semiconductor and graphene has not only high sensitivity and uniform Raman signal but also stable chemical properties, which is one of the important topics in the field of surface-enhanced Raman scattering (SERS). In this paper, a sandwich SERS substrate based on tantalum oxide (Ta2O5) is designed and fabricated. The substrate has high sensitivity, stable performance and high quantification capability. The composite substrate can achieve a high sensitivity Raman detection of crystal violet (CV) with a detection limit of 10-11 M and an enhancement factor of 1.5 × 109. This is the result of the synergistic effect of electromagnetic enhancement and chemical enhancement, in which the chemical enhancement is the cooperative charge transfer in the system composed of probe molecules, silver nanoparticles (AgNPs) and Ta2O5, and the electromagnetic enhancement comes from the strong local surface plasmon resonance between the adjacent AgNPs. After exposing the composite substrate to the air for one month, the Raman signal did not weaken, indicating that the performance of the composite substrate is stable. In addition, there is an excellent linear relationship between the intensity of Raman characteristic peak and the concentration of probe molecules, which proves that the composite substrate has high quantification capability. In practical application, the composite SERS substrate can be used to detect harmful malachite green quickly and sensitively and has a broad application prospect in the field of food safety and chemical analysis.

Fibroblast growth factor 21 alleviates acute pancreatitis via activation of the Sirt1-autophagy signalling pathway.

Fibroblast growth factor 21 (FGF21), a metabolic hormone with pleiotropic effects on glucose and lipid metabolism and insulin sensitivity, alleviates the process of acute pancreatitis (AP). However, its mechanism remains elusive. The pathological and physiological characteristics of FGF21 are observed in both patients with AP and cerulein-induced AP models, and the mechanisms of FGF21 in response to AP are investigated by evaluating the impact of autophagy in FGF21-treated mice and cultured pancreatic cells. Circulating levels of FGF21 significantly increase in both AP patients and cerulein-induced AP mice, which is accompanied by the change of pathology in pancreatic injury. Replenishment of FGF21 distinctly reverses cerulein-induced pancreatic injury and improves cerulein-induced autophagy damage in vivo and in vitro. Mechanically, FGF21 acts on pancreatic acinar cells to up-regulate Sirtuin-1 (Sirt1) expression, which in turn repairs impaired autophagy and removes damaged organs. In addition, blockage of Sirt1 accelerates cerulein-induced pancreatic injury and weakens the regulative effect in FGF21-activated autophagy in mice. These results showed that FGF21 protects against cerulein-induced AP by activation of Sirtuin-1-autophagy axis.

Prdx1 promotes the loss of primary cilia in esophageal squamous cell carcinoma.

BACKGROUND: Loss of primary cilia is frequently observed in tumor cells, suggesting that the absence of this organelle may promote tumorigenesis through aberrant signal transduction, the inability to exit the cell cycle, and promotion of tumor cell invasion. Primary cilia loss also occurs in esophageal squamous cell carcinoma (ESCC) cells, but the molecular mechanisms that explain how ESCC cells lose primary cilia remain poorly understood. METHODS: Inhibiting the expression of Prdx1 in the ESCC cells to detect the up-regulated genes related to cilium regeneration and down-regulated genes related to cilium disassembly by Gene chip. And, mice and cell experiments were carried to confirm the role of the HEF1-Aurora A-HDAC6 signaling axis in ESCC. RESULTS: In this study, we found that silencing Peroxiredoxin 1 (Prdx1) restores primary cilia formation, and over-expressing Prdx1 induces primary cilia loss in ESCC cells. We also showed that the expression of Prdx1 regulates the action of the HEF1-Aurora A-HDAC6 signaling axis to promote the disassembly of primary cilia, and suppression of Prdx1 results in decreased tumor formation and tumor mass volume in vivo. CONCLUSIONS: These results suggest that Prdx1 is a novel regulator of primary cilia formation in ESCC cells.

CXCL16 deficiency attenuates diabetic nephropathy through decreasing oxidative stress and inflammation.

Soluble C-X-C chemokine ligand 16 (CXCL16) is related to the inflammatory response in liver injury and involved in the pathogenesis of renal dysfunction in diabetes patients. However, the exact role of elevated CXCL16 in diabetic nephropathy (DN) remains unclear. In this study, we investigated the role of CXCL16 in streptozcin (STZ)-induced diabetic nephropathy (DN) in mice. The results showed that fasting blood glucose (FBG) and 24 h urinary protein, triglyceride, and cholesterol levels increased in diabetic mice, and these changes were partially ameliorated in CXCL16 KO mice. Meanwhile, the results also showed that ROS generation was suppressed and the expression levels of inflammatory factors and infiltration factors were inhibited both in vivo and in vitro using DN models. In addition, the total AKT protein and p-AKT levels were decreased in CXCL16-depleted HK-2 cells that were treated with LPS. These findings suggest that the CXCL16 gene product promotes inflammatory factors and cell infiltration factors, and inhibits the expression of antioxidant factors to accelerate the development of DN, and CXCL16 deficiency attenuates DN may be involved in the AKT signaling pathway.

Streptomyces lasiicapitis sp. nov., an actinomycete that produces kanchanamycin, isolated from the head of an ant (Lasius fuliginosus L.).

During a screening for novel and biotechnologically useful actinobacteria in insects, a kanchanamycin-producing actinomycete with antifungal activity, designated strain 3H-HV17(2)T, was isolated from the head of an ant (Lasius fuliginosus L.) and characterized using a polyphasic approach. 16S rRNA gene sequence similarity studies showed that strain 3H-HV17(2)T belongs to the genus Streptomyces with the highest sequence similarities to Streptomyces spectabilis NBRC 13424T (98.90 %, with which it phylogenetically clustered, Streptomyces alboflavus NRRL B-2373T (98.65 %) and Streptomyces flavofungini NBRC 13371T (98.36 %). Phylogenetic analysis based on the gyrB gene also supported the close relationship of these strains. The morphological and chemotaxonomic properties of the strain are also consistent with those members of the genus Streptomyces. A combination of DNA-DNA hybridization experiments and phenotypic tests were carried out between strain 3H-HV17(2)T and its phylogenetically closely related strains, which further clarified their relatedness and demonstrated that strain 3H-HV17(2)T could be distinguished from these strains. Therefore, strain 3H-HV17(2)T is concluded to represent a novel species of the genus Streptomyces, for which the name Streptomyces lasiicapitis sp. nov. is proposed. The type strain is 3H-HV17(2)T (=CGMCC 4.7349T=DSM 103124T).

Plantactinosporasoyae sp. nov., an endophytic actinomycete isolated from soybean root [Glycine max (L.) Merr].

A novel actinomycete, designated strain NEAU-gxj3T, was isolated from soybean root [Glycine max (L.) Merr.] collected from Harbin, Heilongjiang Province, China, and characterized using a polyphasic approach. The 16S rRNA gene sequence of strain NEAU-gxj3T showed highest similarity to those of Micromonospora equina Y22T (98.2 %) and Plantactinospora endophytica YIM 68255T (98.0 %). Phylogenetic analysis based on the 16S rRNA gene and gyrB gene demonstrated that the isolate clustered with the members of the genus Plantactinospora. The chemotaxonomic properties of strain NEAU-gxj3Twere also consistent with those of members of the genus Plantactinospora. The cell wall contained meso-diaminopimelic acid and whole-cell sugars were xylose, glucose and galactose. The predominant menaquinones were MK-10(H6), MK-9(H8), MK-10(H2) and MK-10(H4). The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The major fatty acids were identified as anteiso-C17 : 0, iso-C16 : 0, iso-C15 : 0 and C15 : 0. A combination of DNA-DNA hybridization result and some phenotypic characteristics indicated that strain NEAU-gxj3Tcould be differentiated clearly from its closest phylogenetic relatives. Therefore, the strain is concluded to represent a novel species of the genus Plantactinospora, for which the name Plantactinospora soyae sp. nov. is proposed. The type strain is NEAU-gxj3T (=CGMCC 4.7221T=DSM 46832T).

Baia soyae gen. nov., sp. nov., a mesophilic representative of the family Thermoactinomycetaceae, isolated from soybean root [Glycine max (L.) Merr].

A mesophilic, endophytic, filamentous bacterium, designated strain NEAU-gxj18T, was isolated from soybean root [Glycine max (L.) Merr.] collected from Harbin, Heilongjiang Province, China and characterized using a polyphasic approach. Growth was observed at 20­40 °C (optimum 37 °C). Aerial mycelium was absent on all the media tested. Substrate mycelia were well-developed and formed abundant single endospores with smooth surfaces. The only menaquinone was MK-7.The diagnostic diamino acid was meso-diaminopimelic acid. The whole-cell sugars were ribose, glucose and galactose. The major fatty acids were iso-C15 : 0, C13 : 0 and iso-C17 : 0. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminophospholipid and one undientified phospholipid. The DNA G+C content was 49.9 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NEAU-gxj18T was phylogenetically related to members of the family Thermoactinomycetaceae, with the highest sequence similarity to Geothermomicrobium terrae YIM 77562T (93.35 %). On the basis of morphological and chemotaxonomic characteristics, phylogenetic analysis and characteristic patterns of 16S rRNA gene signature nucleotides, strain NEAU-gxj18T represents a novel species of a new genus within the family Thermoactinomycetaceae, for which the name Baia soyae gen. nov., sp. nov. is proposed. The type strain of the type species is NEAU-gxj18T ( = CGMCC 4.7223T = DSM 46831T).

Dactylosporangium cerinum sp. nov., a novel actinobacterium isolated from the rhizosphere of Pinus koraiensis Sieb. et Zucc.

A novel actinobacterium, designated strain NEAU-TPG4(T) was isolated from rhizosphere soil of Pinus koraiensis Sieb. et Zucc. collected from Luobei, Heilongjiang Province, north China, and characterized using a polyphasic approach. Morphological and chemotaxonomic properties of strain NEAU-TPG4(T) were consistent with the description of the genus Dactylosporangium. The strain formed finger-shaped sporangia on short sporangiophores that emerged directly from substrate hyphae. The cell-wall peptidoglycan consisted of meso- and 3-hydroxy-diaminopimelic acids; arabinose, xylose and glucose were found as whole-cell sugars. The phospholipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylinositol. The predominant menaquinones were identified as MK-9(H8) and MK-9(H6). The predominant cellular fatty acids were identified as iso-C16:0, anteiso-C15:0, anteiso-C17:0 and C18:0. Phylogenetic analysis using 16S rRNA gene sequences also indicated that the strain should be classified in the genus Dactylosporangium and showed that the closest relatives were Dactylosporangium maewongense Japan Collection of Microorganism (JCM) 15933(T) (99.6 %), Dactylosporangium siamense NBRC 106093(T) (99.6 %), Dactylosporangium aurantiacum JCM 3083(T) (99.5 %) and Dactylosporangium luteum JCM 17685(T) (99.5 %). However, the low level of DNA-DNA relatedness and several cultural and physiological characteristics allowed the strain to be distinguished from its closest relatives. Thus, it is proposed that strain NEAU-TPG4(T) represents a novel Dactylosporangium species. Dactylosporangium cerinum sp. nov. The type strain of D. cerinum is NEAU-TPG4(T) (=CGMCC 4.7152(T) = DSM 46712(T)).

[Estimation and Visualization of Nitrogen Content in Citrus Canopy Based on Two Band Vegetation Index (TBVI)].

Nitrogen is a necessary and important element for the growth and development of fruit orchards. Timely, accurate and nondestructive monitoring of nitrogen status in fruit orchards would help maintain the fruit quality and efficient production of the orchard, and mitigate the pollution of water resources caused by excessive nitrogen fertilization. This study investigated the capability of hyperspectral imagery for estimating and visualizing the nitrogen content in citrus canopy. Hyperspectral images were obtained for leaf samples in laboratory as well as for the whole canopy in the field with ImSpector V10E (Spectral Imaging Ltd., Oulu, Finland). The spectral datas for each leaf sample were represented by the average spectral data extracted from the selected region of interest (ROI) in the hyperspectral images with the aid of ENVI software. The nitrogen content in each leaf sample was measured by the Dumas combustion method with the rapid N cube (Elementar Analytical, Germany). Simple correlation analysis and the two band vegetation index (TBVI) were then used to develop the spectra data-based nitrogen content prediction models. Results obtained through the formula calculation indicated that the model with the two band vegetation index (TBVI) based on the wavelengths 811 and 856 nm achieved the optimal estimation of nitrogen content in citrus leaves (R2 = 0.607 1). Furthermore, the canopy image for the identified TBVI was calculated, and the nitrogen content of the canopy was visualized by incorporating the model into the TBVI image. The tender leaves, middle-aged leaves and elder leaves showed distinct nitrogen status from highto low-levels in the canopy image. The results suggested the potential of hyperspectral imagery for the nondestructive detection and diagnosis of nitrogen status in citrus canopy in real time. Different from previous studies focused on nitrogen content prediction at leaf level, this study succeeded in predicting and visualizing the nutrient content of fruit trees at canopy level. This would provide valuable information for the implementation of individual tree-based fertilization schemes in precision orchard management practices.

[Development of prediction models for determining N content in citrus leaves based on hyperspectral imaging technology].

The present study presents prediction models for determining the N content in citrus leaves by using hyperspectral imaging technology combined with several chemometrics methods. The steps followed in this study are: hyperspectral image scanning, extracting average spectra curves, pretreatment of raw spectra data, extracting characteristic wavelengths with successive projection algorithm and developing prediction models for determining N content in citrus leaves. The authors obtained three optimal pretreatment methods through comparing eleven different pretreatment methods including Savitzky-Golay (SG) smoothing, standard normal variate (SNV), multiplicative scatter correction (MSC), first derivative (1-Der) and so on. These selected pretreatment methods are SG smoothing, detrending and SG smoothing-detrending. Based on these three pretreatment methods, the authros first extracted the characteristic wavelengths respectively with successive projection algorithm, and then used the spectral reflectance of the extracted characteristic wavelengths as input variables of partial least squares regression (PLS), multiple linear regression (MLR) and back propagation neural network (BPNN) modeling. Hence, the authors developed three prediction models with each pretreatment method, and obtained nine models in total. Among all the nine prediction models, the two models based on the methods of SG smoothing-detrending-SPA-BPNN (R(p): 0.8513, RMSEP: 0.1881) and detrending-SPABPNN (R(p): 0.8609, RMSEP: 0.1595) were found to have achieved the best prediction results. The final results show that using hyperspectra data to determine N content in citrus leaves is feasible. This would provide a theoretical basis for real-time and accurate monitoring of N content in citrus leaves as well as rational N fertilizer application during the plant's growth.

Machine-learning-based classification of diffuse large B-cell lymphoma patients by a 7-mRNA signature enriched with immune infiltration and cell cycle.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) exhibits remarkable heterogeneity but still remains undiagnosed in identifying the subpopulation of DLBCL to predict the prognosis and guide clinical treatment. METHODS: Molecular subgroups were identified in gene expression data from GSE10846 by a consensus clustering algorithm. And gene set enrichment analysis, immune infiltration, and the proposed cell cycle algorithm were applied to explore the biological functions of different subtypes. Meanwhile, univariate and multivariate Cox regression analyses were used to evaluate independent prognostic factors of DLBCL. Finally, the prognostic model, including some key genes screened by Lasso regression, Random Forest algorithm, and point-biserial correlation, was constructed by an optimal classifier from seven machine learning algorithms and validated by another three external datasets (GSE34171, GSE87371, GSE31312). RESULTS: Comprehensive genomic analysis of 1,143 DLBCL samples identify 2 molecularly, prognostically relevant subtypes: immune-enriched (IME) and cell-cycle-enriched (CCE). Then a new predictive model including seven key genes (SERPING1, TIMP2, NME1, DCTPP1, RFC4, POLE2, and SNRPD1) was developed with high prediction accuracy (88.6%) and strong predictive power (AUC = 0.973) based on the Support Vector Machine (SVM) algorithm in 414 patients from GSE10846. The predictive power was similar in another three testing sets (HR > 1.400, p < 0.05). CONCLUSION: This model could evaluate survival independently with strong predictive power compared with other clinical risk factors. Our study constructed a reliable model to predict two new subtypes of DLBCL patients, which could guide the implementation of individualized treatment.

Therapeutic Drug Monitoring of Linezolid in Drug-Resistant Tuberculosis Patients: Clinical Factors and Hematological Toxicities.

Purpose: Previous studies have indicated that the development of severe adverse events is associated with linezolid peak concentration (Cmax), but the factors affecting linezolid Cmax and evidences on therapeutic drug monitoring to anticipate toxicity in drug-resistant tuberculosis (DR-TB) patients have not been clarified clearly. This study aimed to explore the factors influencing linezolid Cmax and investigate the association between linezolid concentration and hematological toxicity. Patients and Methods: This study included patients with drug-resistant tuberculosis treated with linezolid from January 2022 to September 2023. We analyzed the factors affecting linezolid Cmax using chi-squared and binary logistic regression. The diagnostic utility of linezolid Cmax in predicting hematological toxicity was evaluated using receiver operating characteristic (ROC) analysis. Results: A total of 76 patients were enrolled in the study. 63.20% met the standard rates for linezolid Cmax. Age (P=0.036), weight (P=0.0016), and creatinine clearance (P=0.0223) significantly correlated with the Cmax. Hematological toxicity was observed in 46.05% (35/76) of patients, characterized by thrombocytopenia (31.58%, 24/76), anemia (6.58%, 5/76), and leukopenia (21.05%, 16/76). ROC curve analysis confirmed the predictive value of linezolid Cmax for thrombocytopenia with an area under curve of 0.728. Conclusion: Suboptimal linezolid Cmax was prevalent among patients with DR-TB, with age, weight, and renal function emerging as influential factors. Elevated linezolid Cmax increases the risk of thrombocytopenia. Meticulous monitoring of linezolid Cmax is imperative during anti-DR-TB therapy to tailor treatment and mitigate hematological toxicity.

Individualized Pharmaceutical Care for Antifungal Therapy in a Patient with Aspergillus tubingensis Spondylitis After Discontinuation of Rifampicin: A Case Report.

Aspergillus tubingensis spondylitis (AS) is a rare spinal infectious disease with severe clinical symptoms and a challenging diagnosis. Treatment of AS is challenging due to its prolonged duration, substantial side effects, and complex drug-drug interactions. However, there is a lack of experience in individualized pharmaceutical care of AS by clinical pharmacists, especially in the presence of rifampicin, which has sustained liver enzyme induction after discontinuation. Our case described an immunocompetent patient infected with Aspergillus tubingensis spondylitis. Clinical pharmacists proposed an individualized treatment regimen for AS, after considering the effects of sustained liver enzyme induction of rifampicin (after discontinuation) on voriconazole, and utilized caspofungin as a bridge-connection scheme. We also paid attention to changes in indicators during treatment and managed adverse reactions. Therapeutic drug monitoring of voriconazole was also used to optimize the dosing regimen. With the individualized pharmaceutical care of clinical pharmacists and the efforts of clinicians, the patient's incision healed well after 33 days of hospitalization, and she was discharged with significant improvement. Therefore, individualized pharmaceutical care by a clinical pharmacist can help optimize the treatment of Aspergillus tubingensis spondylitis. In clinical practice, drug-drug and drug-diet interactions may affect voriconazole efficacy, and individualized dose adjustment using therapeutic drug monitoring (TDM) is critical to improve efficacy and reduce adverse reactions.