Kinetic Analysis of the Reaction of Micrometer-Sized Al-Mg Alloy Particles in a Water Vapor Atmosphere.

This study investigated the reaction mechanism of aluminum-magnesium (Al-Mg) alloy particles with water (Al-Mg/H2O) through thermogravimetric analysis-differential scanning calorimetry experiments and kinetic analysis using isoconversional methods and the master plot technique to determine the reaction mechanism function, with the aim of providing insights to support metal powder/water ramjet engine design and combustion characteristics. The results showed that the Al-Mg/H2O reaction occurred in two distinct stages, with stage 1 primarily involving the reaction of Mg elements in the L(Al-Mg) alloy with water while Al played a leading role in stage 2. Notably, the reaction temperatures of Al-Mg particles were significantly lower than those for either Al or Mg particles alone in a water vapor environment. Additionally, the activation energy of stage 1 was lower than that for the individual Al and Mg particles and decreased with increasing Mg content in stage 2. Furthermore, the concentration of Mg in the alloy was found to have a major influence on the reaction mechanism, which followed a random nucleation and growth model. Overall, this work elucidated an alternating endothermic and exothermic staged reaction process for Al-Mg/H2O dominated first by Mg and then Al with kinetic insights providing theoretical support for optimizing Al-Mg alloy compositions for improved ignition and combustion performance in metal powder/water ramjet engines.

Identification and functional study of a novel variant of PAX9 causing tooth agenesis.

OBJECTIVES: To search for pathogenic gene of a family with non-syndromic tooth agenesis, and explore the possible pathogenesis. MATERIALS AND METHODS: A Chinese family with non-syndromic tooth agenesis was recruited and screened for the pathogenic variants by whole exome sequencing technology and co-segregation analysis. The subcellular localization of wild-type and mutant protein was detected by immunofluorescence assay. Cycloheximide chase assay was performed to examine the difference in degradation rate between mutant protein and wild-type one. Dual-luciferase reporter assays were conducted to explore the alterations of mutant protein in the regulation of downstream target genes. RESULTS: A novel missense variant of PAX9 (c.296C>A:p.A99D) was found in this family. Bioinformatics software showed ß-return and the random coil were shortened in the p.A99D. The variant did not affect the subcellular localization of PAX9, but the degradation rate of p.A99D was accelerated (p < 0.05). p.A99D inhibited the activation of downstream target gene BMP4 (p < 0.05). CONCLUSIONS: This novel variant expands the pathogenic gene spectrum. The variant impaired the protein structure, accelerated the degradation of protein, and inhibited the activation of the downstream target gene BMP4, an upstream molecule in the TGF-ß/BMP pathway, which may contribute to tooth agenesis in this family.

Oxaliplatin related lncRNAs prognostic models predict the prognosis of patients given oxaliplatin-based chemotherapy.

BACKGROUND: Oxaliplatin-based chemotherapy is the first-line treatment for colorectal cancer (CRC). Long noncoding RNAs (lncRNAs) have been implicated in chemotherapy sensitivity. This study aimed to identify lncRNAs related to oxaliplatin sensitivity and predict the prognosis of CRC patients underwent oxaliplatin-based chemotherapy. METHODS: Data from the Genomics of Drug Sensitivity in Cancer (GDSC) was used to screen for lncRNAs related to oxaliplatin sensitivity. Four machine learning algorithms (LASSO, Decision tree, Random-forest, and support vector machine) were applied to identify the key lncRNAs. A predictive model for oxaliplatin sensitivity and a prognostic model based on key lncRNAs were established. The published datasets, and cell experiments were used to verify the predictive value. RESULTS: A total of 805 tumor cell lines from GDSC were divided into oxaliplatin sensitive (top 1/3) and resistant (bottom 1/3) groups based on their IC50 values, and 113 lncRNAs, which were differentially expressed between the two groups, were selected and incorporated into four machine learning algorithms, and seven key lncRNAs were identified. The predictive model exhibited good predictions for oxaliplatin sensitivity. The prognostic model exhibited high performance in patients with CRC who underwent oxaliplatin-based chemotherapies. Four lncRNAs, including C20orf197, UCA1, MIR17HG, and MIR22HG, displayed consistent responses to oxaliplatin treatment in the validation analysis. CONCLUSION: Certain lncRNAs were associated with oxaliplatin sensitivity and predicted the response to oxaliplatin treatment. The prognostic models established based on the key lncRNAs could predict the prognosis of patients given oxaliplatin-based chemotherapy.

Tumor microenvironment characterization in colorectal cancer to identify prognostic and immunotherapy genes signature.

BACKGROUND: The tumor microenvironment (TME) plays a crucial role in tumorigenesis, progression, and therapeutic response in many cancers. This study aimed to comprehensively investigate the role of TME in colorectal cancer (CRC) by generating a TMEscore based on gene expression. METHODS: The TME patterns of CRC datasets were investigated, and the TMEscores were calculated. An unsupervised clustering method was used to divide samples into clusters. The associations between TMEscores and clinical features, prognosis, immune score, gene mutations, and immune checkpoint inhibitors were analyzed. A TME signature was constructed using the TMEscore-related genes. The results were validated using external and clinical cohorts. RESULTS: The TME pattern landscape was for CRC was examined using 960 samples, and then the TMEscore pattern of CRC datasets was evaluated. Two TMEscore clusters were identified, and the high TMEscore cluster was associated with early-stage CRC and better prognosis in patients with CRC when compared with the low TMEscore clusters. The high TMEscore cluster indicated elevated tumor cell scores and tumor gene mutation burden, and decreased tumor purity, when compared with the low TMEscore cluster. Patients with high TMEscore were more likely to respond to immune checkpoint therapy than those with low TMEscore. A TME signature was constructed using the TMEscore-related genes superimposing the results of two machine learning methods (LASSO and XGBoost algorithms), and a TMEscore-related four-gene signature was established, which had a high predictive value for discriminating patients from different TMEscore clusters. The prognostic value of the TMEscore was validated in two independent cohorts, and the expression of TME signature genes was verified in four external cohorts and clinical samples. CONCLUSION: Our study provides a comprehensive description of TME characteristics in CRC and demonstrates that the TMEscore is a reliable prognostic biomarker and predictive indicator for patients with CRC undergoing immunotherapy.

Multiple refractory intracellular pathogen infections in a human immunodeficiency virus-negative patient with anti-interferon-γ autoantibodies: a case report.

BACKGROUND: The clinical presentation of adult-onset immunodeficiency with anti-interferon (IFN)-γ autoantibodies with intracellular pathogens can be highly variable, which can lead to misdiagnosis during the early stage of disease. CASE PRESENTATION: We report a complex case of a 54-year-old Chinese male who was human immunodeficiency virus-negative. He had a presence of anti-IFN-γ autoantibodies and suffered from various intracellular pathogenic infections. The patient was admitted to our hospital for the first time in July 2016 with severe pneumonia, and he experienced multiple pneumonia infections between 2017 and 2019. In March 2019, the patient was hospitalized due to pulmonary lesions and multiple-bone destruction. During hospitalization, the patient was confirmed to have disseminated Talaromyces marneffei infection and was successfully treated with antifungal therapy for 1 year. In June 2021, Mycobacterium kansasii infection was detected by positive culture and progressive bone destruction. A high concentration of anti-IFN-γ antibodies was observed in the patient's serum. In addition, Listeria monocytogenes was isolated by blood culture, and the presence of L. monocytogenes in cerebrospinal fluid was confirmed by next-generation sequencing. Following anti-non-tuberculous mycobacteria (NTM) therapy and anti-bacterial therapy, the patient's symptoms, pulmonary lesions, and bone destruction gradually improved. CONCLUSIONS: Although the clinical presentation of adult-onset immunodeficiency with anti-IFN-γ autoantibodies can be highly variable, the diagnosis should be considered if patients suffer from unexplained repeated bacterial or opportunistic infections. Conventional and advanced molecular testing should be used, as needed, for microbiological diagnoses among this special immunodeficient population.

Nanopore/Illumina Hybrid Whole-Genome Sequence Resource of Plenodomus lindquistii Strain US01 Infecting Sunflower.

Plenodomus lindquistii (basionym: Leptosphaeria lindquistii) is the most prevalent fungus pathogen causing the black stem disease in sunflower. To date, only one whole-genome sequence is reported in NCBI, but no complete gene annotation has been submitted. Herein, we sequenced a Leptosphaeria lindquistii isolate from sunflower seeds imported from the United States using Oxford Nanopore long-read sequencing and Illumina short-read sequencing. We generated a 38.6-Mb genome assembly consisting of 29 contigs with an N50 of 1.689 Mb and a maximum length of 5.316 Mb. In the genome assembly, we identified 13,481 protein-coding genes, of which 12,531 were annotated. The high-quality assembly and annotation of the Leptosphaeria lindquistii genome will allow us to conduct further studies for the specific identification of pathogens causing sunflower black stem disease and provide a better understanding of the infection mechanisms of Leptosphaeria lindquistii.

Sex hormone levels in females of different ages suffering from depression.

BACKGROUND: There are only a few studies on sex hormones in females of different ages suffering from depression, and their conclusions are not uniform until now. This study aimed to investigate the correlation between the severity of depression in females and factors such as sex hormones and differences in sex hormone levels in females of different ages, exploring variations after treatment. METHODS: A total of 169 females with depression were selected and divided into the first-episode (91 cases) and recurrent (78 cases) groups. Then, on the basis of their age, the first-episode patients were divided into the young (48 cases, age < 45 years), perimenopausal (20 cases, 45-55 years), and elderly groups (23 cases, age > 55 years); the patients with recurrent depression were classified into the young (37 cases, age < 45 years), perimenopausal (19 cases, 45-55 years), and elderly groups (22 cases, age > 55 years). The patients were assessed in accordance with the International Classification of Diseases of mental and behavioral disorders. The serum progesterone, prolactin, estradiol, and testosterone levels in the patients were measured, and differences in sex hormone levels of the groups were analyzed. RESULTS: The estradiol level was negatively correlated with age and the prolactin level was positively correlated with occupation. The severity of depression in females was found to be negatively correlated with age. The serum progesterone and estradiol levels in the young group were significantly higher than those in the elderly group, regardless of the first episode or recurrence. Estradiol levels in the perimenopausal and elderly groups with first-episode depression were significantly higher than those in the same group with recurrent depression. However, there was no significant difference in the serum progesterone, prolactin, estradiol, and testosterone levels in the recurrent group before and after treatment. CONCLUSIONS: Sex hormone levels, especially estradiol, varied among females of different ages suffering from depression. Recurrent depression also has a certain effect on sex hormone levels in females. Not only should the age and relapse be considered when studying the sex hormone levels of females with depression, but also attention should be paid to whether the patients have used antidepressants before their sexual hormonal testing.

Blue Native/SDS-PAGE and iTRAQ-Based Chloroplasts Proteomics Analysis of Nicotiana tabacum Leaves Infected with M Strain of Cucumber Mosaic Virus Reveals Several Proteins Involved in Chlorosis Symptoms.

Virus infection in plants involves necrosis, chlorosis, and mosaic. The M strain of cucumber mosaic virus (M-CMV) has six distinct symptoms: vein clearing, mosaic, chlorosis, partial green recovery, complete green recovery, and secondary mosaic. Chlorosis indicates the loss of chlorophyll which is highly abundant in plant leaves and plays essential roles in photosynthesis. Blue native/SDS-PAGE combined with mass spectrum was performed to detect the location of virus, and proteomic analysis of chloroplast isolated from virus-infected plants was performed to quantify the changes of individual proteins in order to gain a global view of the total chloroplast protein dynamics during the virus infection. Among the 438 proteins quantified, 33 showed a more than twofold change in abundance, of which 22 are involved in the light-dependent reactions and five in the Calvin cycle. The dynamic change of these proteins indicates that light-dependent reactions are down-accumulated, and the Calvin cycle was up-accumulated during virus infection. In addition to the proteins involved in photosynthesis, tubulin was up-accumulated in virus-infected plant, which might contribute to the autophagic process during plant infection. In conclusion, this extensive proteomic investigation on intact chloroplasts of virus-infected tobacco leaves provided some important novel information on chlorosis mechanisms induced by virus infection.

Mitophagy Plays a Protective Role in Iodinated Contrast-Induced Acute Renal Tubular Epithelial Cells Injury.

BACKGROUND/AIMS: Contrast induced-acute kidney injury (CI-AKI) is one of the most common causes of acute kidney injury (AKI) in hospitalized patients. Mitophagy, the selective elimination of mitochondria via autophagy, is an important mechanism of mitochondrial quality control in physiological and pathological conditions. In this study, we aimed to determine effects of iohexol and iodixanol on mitochondrial reactive oxygen species (ROS), mitophagy and the potential role of mitophagy in CI-AKI cell models. METHODS: Cell viability was measured by cell counting kit-8. Cell apoptosis, mitochondrial ROS and mitochondrial membrane potential were detected by western blot, MitoSOX fluorescence and TMRE staining respectively. Mitophagy was detected by the colocalization of LC3-FITC with MitoTracker Red, western blot and electronic microscope. RESULTS: The results showed that mitophagy was induced in human renal tubular cells (HK-2 cells) under different concentrations of iodinated contrast media. Mitochondrial ROS displayed increased expression after the treatment. Rapamycin (Rap) enhanced mitophagy and alleviated contrast media induced HK-2 cells injury. In contrast, autophagy inhibitor 3-methyladenine (3-MA) down-regulated mitophagy and aggravated cells injury. CONCLUSIONS: Together, our finding indicates that iohexol and iodixanol contribute to the generation of mitochondrial ROS and mitophagy. The enhancement of mitophagy can effectively protect the kidney from iodinated contrast (iohexol)-induced renal tubular epithelial cells injury.

The cucumber mosaic virus movement protein suppresses PAMP-triggered immune responses in Arabidopsis and tobacco.

Cucumber Mosaic Virus (CMV) has a small RNA genome that encodes a limited number of proteins, but can infect many plant species, including Arabidopsis thaliana and Nicotiana benthamiana. Virus proteins thus have multiple means of conferring their pathogenicity during the infection process. However, the pathogenic mechanism of CMV remains unclear. Here we discovered that the expression of the CMV movement protein (MP) in A. thaliana and N. benthamiana can suppress reactive oxygen species (ROS) production triggered by multiple pathogen-associated molecular patterns (PAMPs), such as bacteria-derived peptide flg22, elf18, and fungal-derived chitin. Transgenic Arabidopsis plants expressing the MP were compromised in flg22-induced immune activation and were more susceptible to Pseudomonas syringae pv. tomato (Pst) DC3000 hrcC- strain infection. Further analysis revealed that flg22-induced resistance gene expression was also compromised in MP transgenic plants. The CMV MP protein was previously reported to function in cell-to-cell movement processes, and our findings offer a new molecular mechanism for the CMV MP protein in suppression of host PAMP-triggered immune responses.

Probing Adsorption Behaviors of BSA onto Chiral Surfaces of Nanoparticles.

Chiral properties of nanoscale materials are of importance as they dominate interactions with proteins in physiological environments; however, they have rarely been investigated. In this study, a systematic investigation is conducted for the adsorption behaviors of bovine serum albumin (BSA) onto the chiral surfaces of gold nanoparticles (AuNPs), involving multiple techniques and molecular dynamic (MD) simulation. The adsorption of BSA onto both L- and D-chiral surfaces of AuNPs shows discernible differences involving thermodynamics, adsorption orientation, exposed charges, and affinity. As a powerful supplement, MD simulation provides a molecular-level understanding of protein adsorption onto nanochiral surfaces. Salt bridge interaction is proposed as a major driving force at protein-nanochiral interface interaction. The spatial distribution features of functional groups (COO- , NH3+ , and CH3 ) of chiral molecules on the nanosurface play a key role in the formation and location of salt bridges, which determine the BSA adsorption orientation and binding strength to chiral surfaces. Sequentially, BSA corona coated on nanochiral surfaces affects their uptake by cells. The results enhance the understanding of protein corona, which are important for biological effects of nanochirality in living organisms.

Association Between C1q/TNF-Related Protein-1 Levels in Human Plasma and Epicardial Adipose Tissues and Congestive Heart Failure.

BACKGROUND/AIMS: C1q and tumour necrosis factor-related protein 1 (CTRP1) possesses anti-atherogenic and anti-inflammatory effects. This study investigated whether the CTRP1 levels in the plasma and epicardial adipose tissue (EAT) were associated with congestive heart failure (CHF) and to disclose possible molecular mechanisms. METHODS: Plasma and tissue samples were obtained from subjects with or without CHF. Plasma levels of CTRP1 were measured by ELISA. The mRNA levels of CTRP1 and inflammatory cytokines were detected by RT-PCR. The protein levels of CTRP1, aldosterone synthase (CYP11B2) and mitogen-activated protein kinase were examined by Western blotting. RESULTS: The levels of CTRP1 in the plasma and EAT were higher in the CHF patients than those in the controls. There were no differences in the CTRP1 levels in cardiomyocytes between the CHF group and the non-CHF group. An exploratory survival analysis showed that higher CTRP1 values at admission were associated with a worse prognosis after discharge. CTRP1 increased the IL-6 mRNA level in H295R cells. CTRP1 recruited ERK1/2 and Jak-2 for aldosterone release by modulating the CYP11B2 protein level, and brain natriuretic peptide repressed the CTRP1-induced aldosterone release through the JAK2-STAT3 signalling pathways. CONCLUSION: The CTRP1 levels in the plasma and EAT were increased in the CHF patients. CTRP1 is involved in the pathogenesis of CHF by modulating IL-6 levels and aldosterone release.

Chlorophyll fluorescence lifetime imaging provides new insight into the chlorosis induced by plant virus infection.

KEY MESSAGE: Leaf chlorosis induced by plant virus infection has a short fluorescence lifetime, which reflects damaged photosynthetic complexes and degraded chloroplasts. Plant viruses often induce chlorosis and necrosis, which are intimately related to photosynthetic functions. Chlorophyll fluorescence lifetime measurement is a valuable noninvasive tool for analyzing photosynthetic processes and is a sensitive indicator of the environment surrounding the fluorescent molecules. In this study, our central goal was to explore the effect of viral infection on photosynthesis by employing chlorophyll fluorescence lifetime imaging (FLIM), steady-state fluorescence, non-photochemical quenching (NPQ), transmission electron microscopy (TEM), and pigment analysis. The data indicated that the chlorophyll fluorescence lifetime of chlorotic leaves was significantly shorter than that of healthy control leaves, and the fitted short lifetime component of chlorophyll fluorescence of chlorotic leaves was dominant. This dominant short lifetime component may result from damage to the structure of thylakoid, which was confirmed by TEM. The NPQ value of chlorotic leaves was slightly higher than that of healthy green leaves, which can be explained by increased neoxanthin, lutein and violaxanthin content relative to chlorophyll a. The difference in NPQ is slight, but FLIM can provide simple and direct characterization of PSII structure and photosynthetic function. Therefore, this technique shows great potential as a simple and rapid method for studying mechanisms of plant virus infection.

Serum cystatin c is not superior to serum creatinine for early diagnosis of contrast-induced nephropathy in patients who underwent angiography.

BACKGROUND: Iodiated contrast-induced nephropathy (CIN) is a serious complication of contrast-enhanced imaging. The aim of this study was to evaluate the diagnostic sensitivities and specificities of serum cystatin C (sCys C) and serum creatinine (sCr) for CIN and to further investigate difference of the incidence, risk factors, and in-hospital and 3-month prognosis of CIN according to sCys C criteria and sCr criteria. METHODS: We prospectively evaluated 213 patients who underwent angiography. The sCr and sCys C concentrations were detected before and at 48 hours, 72 hours after the procedure. The incidence, risk factors, and in-hospital and 3-month prognosis of CIN were analyzed. Receiver operating characteristic curve (ROC) analysis was performed for sCr and sCys C 48 hours after procedure. RESULTS: The incidence of CIN was 24.4% (sCys C criteria) and 8% (sCr criteria). Diabetes mellitus, dehydration, and hypoalbuminemia were independent risk factors for CIN. Area under the ROC of sCys C 48 hours after procedure was not superior to sCr (0.715 vs 0.790, P=.178). The mortality of patients with CIN in sCr criteria increased significantly (P<.05). CONCLUSION: In this study, the incidence and risk factors of CIN were related to diagnostic criteria. The sCys C was not superior to sCr for predicting CIN in the patients who underwent angiography.

The detection of hydrogen peroxide involved in plant virus infection by fluorescence spectroscopy.

The production of reactive oxygen species (ROS) forms part of the defense reaction of plants against invading pathogens. ROS have multifaceted signaling functions in mediating the establishment of multiple responses. To verify whether hydrogen peroxide (H2 O2 ) contributes to plant virus infection and the development of induced symptoms, we used fluorescence to monitor the generation of H2 O2 and confocal laser scanning microscopy (CLSM) to investigate the subcellular distribution of H2 O2 in leaves. In this study, the M strain of Cucumber mosaic virus (M-CMV) induced heavy chlorotic symptoms in Nicotiana tabacum cv. white burley during systemic infection. Compared with mock-inoculated leaves, H2 O2 accumulation in inoculated leaves increased after inoculation, then decreased after 4 days. For systemically infected leaves that showed chlorotic symptoms, H2 O2 accumulation was always higher than in healthy leaves. Subcellular H2 O2 localization observed using CLSM showed that H2 O2 in inoculated leaves was generated mainly in the chloroplasts and cell wall, whereas in systemically infected leaves H2 O2 was generated mainly in the cytosol. The levels of coat protein in inoculated and systemically infected leaves might be associated with changes in the level of H2 O2 and symptom development. Further research is needed to elucidate the generation mechanism and the relationship between coat protein and oxidative stress during infection and symptom development. Copyright © 2016 John Wiley & Sons, Ltd.

[Evaluation of risk factors and prognosis on diodone-induced acute kidney injury according to ESUR and KDIGO criteria].

OBJECTIVE: To investigate the incidence, risk factors and prognosis for contrast-induced acute kidney injury (CI-AKI) according to ESUR and KDIGO criteria in patients undergoing angiography.
 METHODS: We evaluated 260 patients undergoing angiography and/or intervention therapy from April 2011 to January 2012 in the Second Xiangya Hospital of Central South University. All patients received low-osmolality contrast agent (ioversol). Serum creatinine was measured before angiography or at 48 or 72 h after procedure. The multivariate logistic regression was used to analyze the risk factors of CI-AKI. The major adverse events were observed in a year of follow-up.
 RESULTS: Among the 260 patients, 23 experienced CI-AKI and the incidence was 8.8% according to ESUR criteria. Twelve patients experienced CI-AKI and the incidence was 4.6% according to KDIGO criteria. The multivariate logistic regression analysis showed that diabetes mellitus and dehydration were the independent risk factors for CI-AKI according to ESUR criteria; In another KDIGO criteria, chronic kidney disease (CKD), hypercholesterolemia and diabetes mellitus were the independent risk factors for CI-AKI. The prognosis study showed that the mortality of patients with CI-AKI were significantly higher than those without CI-AKI (P<0.05).
 CONCLUSION: The incidence of CI-AKI is associated with diagnostic criteria. Diabetes mellitus, CKD, dehydration and hypercholesterolemia were the independent risk factors for CI-AKI. CI-AKI is a relevant factor for mortality in a year after angiography and/or intervention therapy.

Rapid synthesis of isoquinolinones by intramolecular coupling of amides and ketones.

Amides and ketones were intramolecularly coupled in the presence of KOt-Bu/DMF. The reaction provided good yields of a variety of isoquinolinones. A reaction mechanism of radical addition and subsequent E2-elimination is proposed.

Skewer: a fast and accurate adapter trimmer for next-generation sequencing paired-end reads.

BACKGROUND: Adapter trimming is a prerequisite step for analyzing next-generation sequencing (NGS) data when the reads are longer than the target DNA/RNA fragments. Although typically used in small RNA sequencing, adapter trimming is also used widely in other applications, such as genome DNA sequencing and transcriptome RNA/cDNA sequencing, where fragments shorter than a read are sometimes obtained because of the limitations of NGS protocols. For the newly emerged Nextera long mate-pair (LMP) protocol, junction adapters are located in the middle of all properly constructed fragments; hence, adapter trimming is essential to gain the correct paired reads. However, our investigations have shown that few adapter trimming tools meet both efficiency and accuracy requirements simultaneously. The performances of these tools can be even worse for paired-end and/or mate-pair sequencing. RESULTS: To improve the efficiency of adapter trimming, we devised a novel algorithm, the bit-masked k-difference matching algorithm, which has O(kn) expected time with O(m) space, where k is the maximum number of differences allowed, n is the read length, and m is the adapter length. This algorithm makes it possible to fully enumerate all candidates that meet a specified threshold, e.g. error ratio, within a short period of time. To improve the accuracy of this algorithm, we designed a simple and easy-to-explain statistical scoring scheme to evaluate candidates in the pattern matching step. We also devised scoring schemes to fully exploit the paired-end/mate-pair information when it is applicable. All these features have been implemented in an industry-standard tool named Skewer (https://sourceforge.net/projects/skewer). Experiments on simulated data, real data of small RNA sequencing, paired-end RNA sequencing, and Nextera LMP sequencing showed that Skewer outperforms all other similar tools that have the same utility. Further, Skewer is considerably faster than other tools that have comparative accuracies; namely, one times faster for single-end sequencing, more than 12 times faster for paired-end sequencing, and 49% faster for LMP sequencing. CONCLUSIONS: Skewer achieved as yet unmatched accuracies for adapter trimming with low time bound.

Distribution of active ingredients and quality control of Forsythia suspensa with AP-MALDI mass spectrometry imaging.

The fruits of Forsythia suspensa (F. suspensa) have been used as a traditional Chinese medicine for 2000 years. Currently, the quality control of F. suspensa strictly follows the instructions of Chinese Pharmacopeia, which mainly controls the content of forsythoside A, phillyrin, and volatile oil. In this study, air pressure MALDI mass spectrometry imaging (AP-MALDI MSI) was used to evaluate the quality of F. suspensa fruits and the distribution of dozens of active ingredients. The variation of active ingredients was measured for more than 30 batches of samples, regarding harvest time, cultivated environment, shelf-life, and habitat. Fifty-three active ingredients could be detected in F. suspensa fruits with AP-MALDI MSI. Seven active ingredients were upregulated, four ingredients downregulated, and 15 ingredients did not change in ripe fruits. A sharp variation of active ingredients in late September was observed for the Caochuan fruits harvested in 2019, which is closely related to the appearance of the ginger color of the pericarp under the microscope observation. The microscope observation is a reliable way to classify ripe and green fruits instead of outlook. Just considering forsythoside A and phillyrin, it is found that wild fruits are better than cultivated fruits, but cultivated fruits have high contents of other ingredients. The shelf-life of F. suspensa fruits is proposed to be 3 years, considering the 26 ingredients investigated. It was found that Luoning wild fruits are better than those from Caochuan with a new evaluation method. Mass spectrometry imaging is an easy, objective, and effective method to evaluate the quality of F. suspensa fruits.

A rapid and simple HPLC-MS/MS method for the therapeutic drug monitoring of six special-grade antimicrobials in pediatric patients.

Meropenem, linezolid, fluconazole, voriconazole, posaconazole, and vancomycin are six important antimicrobials used for severe infections in critically ill patients listed in special-grade antimicrobials in China. The six antimicrobials' highly variable pharmacodynamics and pharmacokinetics in critically ill pediatric patients present significant challenges to clinicians in ensuring optimal therapeutic targets. Therefore, therapeutic drug monitoring of these antimicrobials in human plasma is necessary to obtain their plasma concentration. A rapid, simple, and sample-saving high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed, which could simultaneously determine all six antimicrobials. It required only 10 µL of plasma and a one-step protein precipitation process. Chromatographic separation was achieved on a reversed-phase column (C18, 30 × 2.1 mm, 2.6 µm) via gradient elution using water and acetonitrile containing 0.1 % formic acid as mobile phase. The injection volume was 2 µL, and the total run time was only 2.5 min. Detection was done using a Triple Quad™ 4500MD tandem mass spectrometer coupled with an electrospray ionization (ESI) source in positive mode. The calibration curves ranged from 0.5 to 64 µg/mL for meropenem and fluconazole, 0.2-25.6 µg/mL for linezolid and voriconazole, 0.1-12.8 µg/mL for posaconazole and 1-128 µg/mL for vancomycin, with the coefficients of correlation all greater than 0.996. Furthermore, the method was validated rigorously according to the European Medicines Agency (EMA) guidelines, demonstrating excellent accuracy (from 93.0 % to 110.6 %) and precision (from 2.0 % to 12.8 %). Moreover, its applicability to various matrices (including serum, hemolytic plasma, and hyperlipidemic plasma) was evaluated. Thus, this method was successfully applied to routine therapeutic drug monitoring for critically ill pediatric patients and other patients in need.