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Fangyuan Lai,1,* Xiuqiong Huang,2,* Jiao Peng,3 Nannan He,4 Zhongqiang Cao,1 Yuhui Wu,4 Wei Li,5 Zebin Chen,1 Xuejuan Li1 1Department of Pharmacy, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 2Department of Pharmacy, The First People’s Hospital of Zhaoqing, Zhaoqing, People’s Republic of China; 3Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 4Department of Pediatric Intensive Care Unit, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 5Department of Pharmacy, The Third People’s Hospital of Shenzhen, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuejuan Li, Department of Pharmacy, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China, Email xuejuanli@126.comObjective: The first-line treatment for severe Pneumocystis carinii pneumonia (PCP) is trimethoprim-sulfamethoxazole (TMP/SMZ). Here, we report a case involving 6-month-old child with a PCP infection, highlighting the role of clinical pharmacists in providing individualized pharmaceutical care and guidance through the process of therapeutic drug monitoring (TDM).Methods: The clinical pharmacist monitored the concentration of TMP/SMZ in the serum, urine and sputum of a 6-month-old child with PCP infection. To improve the serum levels of TMP/SMZ, the dose of TMP/SMZ was increased, while infusions of other medications were reduced to decrease the rate of drug excretion. Additionally, the patient received other supportive medications to enhance clinical therapeutic efficacy.Results: Clinical pharmacists observed that, despite administration of a sufficient dose of TMP/SMZ, plasma concentration of TMP/SMZ remained below the therapeutic window, while urine concentrations were extremely high. This phenomenon was attributed to Augmented Renal Clearance (ARC), often seen in critically ill patients and associated with increased renal clearance. Throughout treatment, the concentrations of SMZ remained below the minimum effective concentration, while the concentrations of TMP fell within the effective target range. However, sufficient therapeutic effects were ultimately achieved and observed in the patient, likely due to improved drug distribution in lung tissue (sputum) and the patient’s recovering immune functions. Finally, thanks to individualized pharmaceutical care from clinical pharmacists and the combined efforts of clinicians, the patient was discharged after 58 days of hospitalization.Conclusion: Throughout treatment, the clinical pharmacist played a vital role in optimizing the treatment plan based on the serum, urine and sputum concentrations of TMP/SMZ and providing pharmaceutical care to ensure a safe, rational and effective medications in children. Individualized dose adjustments, particularly high-dose TMP/SMZ guided by TDM, can significantly enhance the management of PCP in pediatric patients and support clinical pharmacists in delivering individualized pharmaceutical care.Keywords: Pneumocystis carinii pneumonia, trimethoprim/sulfamethoxazole, therapeutic drug monitoring, plasma drug concentration

Nagongbilige He,1 Siqing Tunala,2 Rihan Wu,1 Changbao Zhao,1 Tuya Wuren,1 Caihela Hushuud1 1Department of Mongolian Psychosomatic Medicine, Ordos Mongolian Hospital, Ordos, 017000, People’s Republic of China; 2Department of Gastroenterology, Ordos Mongolian Hospital, Ordos, 017000, People’s Republic of ChinaCorrespondence: Siqing Tunala, Department of Gastroenterology, Ordos Mongolian Hospital, Ordos, 017000, People’s Republic of China, Tel +86-1864774591, Email tutu88600@126.comPurpose: This study aimed to assess the knowledge, attitudes and practices (KAP) among community populations toward Long COVID.Patients and Methods: This cross-sectional study was conducted between March 2023 and June 2023 at the Ordos Mongolian hospital and Ordos Central Hospital in Ordos, Inner Mongolia, China, employing a self-designed questionnaire to collect demographic data from community populations and evaluate their knowledge, attitudes, and practices toward Long COVID.Results: A total of 591 participants were enrolled in this study. Among them, 343 (58.04%) were female and 317 (53.64%) aged 40 to 59 years. The mean knowledge, attitudes and practices scores were 6.02± 1.19 (possible range: 0– 7), 26.83± 2.96 (possible range: 7– 35), and 45.91± 7.20 (possible range: 11– 55), respectively. The Pearson’s correlation analysis indicated significant positive correlations between knowledge and attitudes (r=0.210, P< 0.001), and attitudes and practices (r=0.476, P< 0.001). The structural equation model demonstrated that knowledge positively affect attitudes, as indicated by a path coefficient of 1.028 (P< 0.001), and attitudes positively affect practices, with a path coefficient of 0.817 (P< 0.001).Conclusion: Although our findings indicate that community populations generally have adequate knowledge, active attitudes, and proactive practices regarding Long COVID, there is still a need for healthcare providers to further enhance Long COVID awareness in the community. This involves fostering positive attitudes through open communication, emphasizing the importance of early intervention and treatment adherence, and encouraging continued adherence to preventive measures.Keywords: knowledge, attitudes, practices, long COVID, cross-sectional study, community, China, questionnaire, structural equation model

The lung macrophages play a crucial role in health and disease. Sexual dimorphism significantly impacts the phenotype and function of tissue-resident macrophages. The primary mechanisms responsible for sexually dimorphic outcomes in bronchopulmonary dysplasia (BPD) remain unidentified. We tested the hypothesis that biological sex plays a crucial role in the transcriptional state of alveolar macrophages, using neonatal murine hyperoxia-induced lung injury as a relevant model for human BPD. The effects of neonatal hyperoxia exposure (95 % FiO2, PND1-5: saccular stage) on the lung myeloid cells acutely after injury and during normoxic recovery were measured. Alveolar macrophages (AM) from room air- and hyperoxia exposed from male and female neonatal murine lungs were subjected to bulk-RNA Sequencing. AMs are significantly depleted in the hyperoxia-exposed lung acutely after injury, with subsequent recovery in both sexes. The transcriptome of the alveolar macrophages is impacted by neonatal hyperoxia exposure and by sex as a biological variable. Pathways related to DNA damage and interferon-signaling were positively enriched in female AMs. Metabolic pathways related to glucose and carbohydrate metabolism were positively enriched in the male AMs, while oxidative phosphorylation was negatively enriched. These pathways were shared with monocytes and airway macrophages from intubated male and female human premature neonates.

Hua Bai,1 Na He,2 Yan Zhang,3 Aqsa Ahmad,3 Xing-Xing Yang,3 Yan Ma,3 Li-Jun Liang1 1Department of Pediatrics, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 2PKUFH-NINGXIA Women Children’s Hospital, Yinchuan, 750001, People’s Republic of China; 3The First Clinical Medical College of Ningxia Medical University General Hospital, Yinchuan, 750004, People’s Republic of ChinaCorrespondence: Li-Jun Liang, Department of Pediatrics, General Hospital of Ningxia Medical University, 804 Shengli South Street, Yinchuan, Ningxia, 750004, People’s Republic of China, Tel +86 137 0959 6527, Email lianglijunlj@126.comObjective: In this study, we aimed to evaluate the current status of the quality of life (QOL) of pediatric patients and plasma glucose concentration regulation in children with type 1 diabetes (T1DM) in the Ningxia Hui autonomous region.Methods: The study involved children with T1DM admitted to the General Hospital of Ningxia Medical University between October 2011 and October 2021. The children and their parents completed general information and quality of life (QOL) questionnaires. The regulation of plasma glucose concentration was assessed based on HbA1c levels, and plasma glucose and QOL-influencing components were investigated.Results: Among the 136 pediatric patients diagnosed with T1DM, the mean glycated hemoglobin (HbA1c) level was recorded at 8.7% (7.2%, 10.5%). A breakdown of the patient cohort revealed that 44 patients (32.4%) demonstrated good regulation of plasma glucose, 33 patients (24.3%) exhibited acceptable glycemic control, and 59 patients (43.3%) displayed poor regulation of plasma glucose. The control of plasma glucose in pediatric patients diagnosed with T1DM was affected by the duration of the disease, the patient’s age, the frequency of daily plasma glucose measurements, the use of CGM, diabetic ketoacidosis (DKA), and the education level of the mother. The control of plasma glucose, dietary management, DKA, the ability to learn, and health education are interfering factors of quality of life in children diagnosed with T1DM. Effective control of plasma glucose may ensure the QOL in children with T1DM, and DKA was the risk factor for QOL.Conclusion: In Ningxia, the regulation of plasma glucose in pediatric and adolescent patients with T1DM remains suboptimal, leading to poor QOL. There is a pressing need to enhance glucose regulation and QOL through comprehensive strategies, which include reinforced dietary management, rigorous monitoring of plasma glucose levels, and heightened health education levels.Keywords: current status of regulation of plasma glucose concentration, influencing factors, QOL, type 1 diabetes

Jiakang Chen,1,&ast; Kasim Allel,2– 4,&ast; Chuyue Zhuo,1,&ast; Wenwei Luo,5 Nanhao He,1 Xu Yang,1 Yingyi Guo,1 Jiong Wang,1 Likang Yao,1 Jiahui Li,1 Yexin Lin,1 Ruiyang Tu,6 Laith Yakob,2,3 Chao Zhuo1 1State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Disease Control, Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK; 3Antimicrobial Resistance Centre, London School of Hygiene & Tropical Medicine, London, UK; 4Institute for Global Health, University College London, London, UK; 5Department of Clinical Laboratory, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 6Department of Science and Technology Studies, University College London, London, UK&ast;These authors contributed equally to this workCorrespondence: Chao Zhuo, State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, Guangdong, People’s Republic of China, Email chaosheep@gzhmu.edu.cnIntroduction: Although Extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) significantly contribute to bloodstream infections, their economic repercussions remain largely unquantified.Data Source and Methods: We performed a retrospective analysis of inpatients diagnosed with Escherichia coli or Klebsiella pneumoniae bacteremia in a tertiary hospital from January 2020 to December 2022 in Guangzhou, China. We employed the chi-square test to examine ESBL risk factors and utilized propensity score matching (PSM) to negate baseline confounding factors, assessing economic burden through disability-adjusted life years (DALYs), hospital costs and productivity losses. We employed mediation analysis to eliminate confounding factors and better identify ESBL sources of burden related.Results: We found 166 ESBL-EC/KP BSI patients (52.2% of the total examined 318 patients). Post-PSM analysis revealed that ESBL-producing EC/KP will reduce the effectiveness of empirical medication by 19.8%, extend the total length of hospitalization by an average of 3 days, and increase the patient’s financial burden by US&dollar;2047. No significant disparity was found in overall mortality and mean DALYs between the groups. Mediation analysis showed that the link between ESBL and hospital costs is predominantly, if not entirely, influenced by the appropriateness of empirical antibiotic treatment and length of hospital stay.Conclusion: Patients with BSI due to ESBL-producing ESBL-EK incur higher costs compared to those with non-ESBL-EK BSI. This cost disparity is rooted in varying rates of effective empirical antimicrobial therapy and differences in hospital stay durations. A nuanced approach, incorporating a thorough understanding of regional epidemiological trends and judicious antibiotic use, is crucial for mitigating the financial impact on patients.Keywords: Escherichia coli, Klebsiella pneumoniae, bacteremia, ESBL, risk factors, medical costs

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Mingtang Zeng,1 Yao Wang,1 Maozhu Liu,1 Yuxun Wei,2 Jie Wen,3 Yuchen Zhang,1 Tao Chen,4 Nianyu He,1 Ping Fan,1 Xinhua Dai5 1Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Pharmacy, Zhongjiang County People’s Hospital, Deyang, 618000, People’s Republic of China; 3Department of Pharmacy, Shehong Municipal Hospital of Traditional Chinese Medicine, Shehong, 629600, People’s Republic of China; 4Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Xinhua Dai, Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Email dxh9123@163.com Ping Fan, Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Email m13980602288@163.comAbstract: Carbon dots (CDs), a crucial component of nanomaterials, are zero-dimensional nanomaterials with carbon as the backbone structure and smaller than 10 nm. Due to their beneficial characteristics, they are widely used in biomedical fields such as biosensors, drug delivery, bio-imaging, and interactions with DNA. Interestingly, a novel type of carbon dot, generated by using herbal medicines as synthetic raw materials, has emerged as the most recent incomer in the family of CDs with the extensive growth in the number of materials selected for carbon dots synthesis. Herbal medicine-derived carbon dots (HM-CDs) have been employed in the biomedical industry, and are rapidly emerging as “modern nanomaterials” due to their unique structures and exceptional capabilities. Emerging trends suggest that their specific properties can be used in bleeding disorders, gastrointestinal disorders, inflammation-related diseases, and other common intractable diseases including cancer, menopausal syndrome, central nervous system disorders, and pain of various forms and causes. In addition, HM-CDs have been found to have organ-protective and antioxidant properties, as evidenced by extensive studies. This research provides a more comprehensive understanding of the biomedical applications of HM-CDs for the aforementioned disorders and investigates the intrinsic pharmacological activities and mechanisms of these HM-CDs to further advance their clinical applications. Keywords: herbal medicine, carbon dots, disease treatment, nanomaterials, potential mechanism

Zeng M, Wang Y, Liu M, et al. Int J Nanomedicine. 2023;18:6503–6525. The authors have advised that Figure 2 on page 6510 was published in error. The correct Figure 2 is as follows. Figure 2 HM-CDs significantly improved blood-brain barrier (BBB) permeability. HM-CD-1 has an ultra-tiny size and abundance surface functional groups. The covalent binding of HM-CD-2 to the drug facilitates passive transport of the drug. HM-CD-3 has a strong affinity for the BBB endothelial cell membrane. The authors apologize for this error.

Adenine nucleotide translocator (ANT) is a mitochondrial protein involved in the exchange of ADP and ATP across the mitochondrial inner membrane. It plays a crucial role in cellular energy metabolism by facilitating the transport of ATP synthesized within the mitochondria to the cytoplasm. The isoform ANT1 predominately expresses in cardiac and skeletal muscles. Mutations or dysregulation in ANT1 have been implicated in various mitochondrial disorders and neuromuscular diseases. We aimed to examine whether ANT1 deletion may affect mitochondrial redox state in our established ANT1-deficient mice. Hearts and quadriceps resected from age-matched wild type (WT) and ANT1-deficient mice were snap-frozen in liquid nitrogen. The Chance redox scanner was utilized to perform 3D optical redox imaging. Each sample underwent scanning across 3–5 sections. Global averaging analysis showed no significant differences in the redox indices (NADH, flavin adenine dinucleotide containing-flavoproteins Fp, and the redox ratio Fp/(NADH+Fp) between WT and ANT1-deficient groups. However, quadriceps had higher Fp than hearts in both groups ([Formula: see text] and 0.01, respectively). Furthermore, the quadriceps were also more oxidized (a higher redox ratio) than hearts in WT group ([Formula: see text]). NADH levels were similar in all cases. Our data suggest that under non-stressful physical condition, the ANT1-deficient muscle cells were in the same mitochondrial state as WT ones and that the significant difference in the mitochondrial redox state between quadriceps and hearts found in WT might be diminished in ANT1-deficient ones. Redox imaging of muscles under physical stress can be conducted in future.

We report herein the preparation, characterization, and catalytic performance of a series of heterogeneous catalysts featuring highly dispersed zinc sites on zeolitic SSZ-13 and ZSM-5 frameworks. The materials are evaluated in the CO2-assisted oxidative ethane dehydrogenation, a very important reaction for the synthesis of platform chemicals. In particular, we find that Zn2.92/SSZ-13 exhibits high reactivity in the conversion of C2H6 and CO2 and high ethene selectivity. In line with the experimental results, we show that the selective character of the catalyst is due to the characteristic compositional structure of the support and its topology that can effectively confine CO2 molecules. An in-depth molecular analysis via operando studies and DFT calculations shows that the rate-limiting step of the reaction with CO2 is the second C-H bond dissociation to give C2H4. The addition of CO2 effectively reduces the energy barrier of this step, favoring desorption of C2H4 while limiting byproduct formation. Overall, this work demonstrates the breakthrough potential of catalysts made of highly dispersed zinc species on zeolites in relevant transformations.

BACKGROUND: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. METHODS: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. RESULTS: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). CONCLUSIONS: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

Emerging data indicate that lung macrophages (LM) may provide a novel biomarker to classify disease endotypes in bronchopulmonary dysplasia (BPD), a form of infant chronic lung disease, and that augmentation of the LM phenotype may be a potential therapeutic target. To contribute to this area of research, we first used Optical Redox Imaging (ORI) to characterize the responses to H2O2-induced oxidative stress and caffeine treatment in an in vitro model of mouse alveolar macrophages (AM). H2O2 caused a dose-dependent decrease in NADH and an increase in FAD-containing flavoproteins (Fp) and the redox ratio Fp/(NADH + Fp). Caffeine treatment did not affect Fp but significantly decreased NADH with doses of ≥50 µM, and 1000 µM caffeine treatment significantly increased the redox ratio and decreased the baseline level of mitochondrial ROS (reactive oxygen species). However, regardless of whether AM were pretreated with caffeine or not, the mitochondrial ROS levels increased to similar levels after H2O2 challenge. We then investigated the feasibility of utilizing ORI to examine macrophage redox status in tracheal aspirate (TA) samples obtained from premature infants receiving invasive ventilation. We observed significant heterogeneity in NADH, Fp, Fp/(NADH + Fp), and mitochondrial ROS of the TA macrophages. We found a possible positive correlation between gestational age and NADH and a negative correlation between mean airway pressure and NADH that provides hypotheses for future testing. Our study demonstrates that ORI is a feasible technique to characterize macrophage redox state in infant TA samples and supports further use of this method to investigate lung macrophage-mediated disease endotypes in BPD.

Ling Li,1,2,&ast; Yaoyao Du,1,&ast; Yang Wang,3 Ning He,2 Bing Wang,1,4 Tong Zhang1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2School of Pharmacy, Anhui University of Chinese Medicine, Hefei, People’s Republic of China; 3Metabo-Profile Biotechnology (Shanghai) Co. Ltd, Shanghai, People’s Republic of China; 4Chinese Academy of Sciences, Shanghai Institute of Materia Medica, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bing Wang; Tong Zhang, Email bwang@simm.ac.cn; zhangtdmj@hotmail.comBackground: Gastric ulcer (GU) is the most common multifactor gastrointestinal disorder affecting millions of people worldwide. There is evidence that gut microbiota is closely related to the development of GU. Atractylone (ATR) has been reported to possess potential biological activities, but research on ATR alleviating GU injury is unprecedented.Methods: Helicobacter pylori (H. pylori)-induced GU model in zebrafish and ethanol-induced acute GU model in rat were established to evaluate the anti-inflammatory and ulcer inhibitory effects of ATR. Then, 16S rRNA sequencing and metabolomics analysis were performed to investigate the effect of ATR on the microbiota and metabolites in rat feces and their correlation.Results: Therapeutically, ATR inhibited H. pylori-induced gastric mucosal injury in zebrafish. In the ulceration model of rat, ATR mitigated the gastric lesions damage caused by ethanol, decreased the ulcer area, and reduced the production of inflammatory factors. Additionally, ATR alleviated the gastric oxidative stress injury by increasing the activity of superoxide dismutase (SOD) and decreasing the level of malondialdehyde (MDA). Furthermore, ATR played a positive role in relieving ulcer through reshaping gut microbiota composition including Parabacteroides and Bacteroides and regulating the levels of metabolites including amino acids, short-chain fatty acids (SCFAs), and bile acids.Conclusion: Our work sheded light on the mechanism of ATR treating GU from the perspective of the gut microbiota and explored the correlation between gut microbiota, metabolites, and host phenotype.Keywords: atractylone, gastric ulcer, inflammation, oxidative stress, gut microbiota, metabolomics

Huabin Wang,1,2,&ast; Junbin Huang,1,2,&ast; Wenfang Yi,1,2,&ast; Jiahong Li,3 Nannan He,4 Liangliang Kang,4 Zhijie He,5 Chun Chen1,2 1Division of Hematology/Oncology, Department of Pediatrics, the Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, People’s Republic of China; 2Department of Pediatric Intensive Care Unit, the Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, People’s Republic of China; 3Department of Neonatal Intensive Care Unit, the Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, 518107, People’s Republic of China; 4Department of Pediatric Intensive Care Unit, Shenzhen Children’s Hospital, Shenzhen, 518000, People’s Republic of China; 5Department of Intensive Care Unit, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijie He; Chun Chen, Email hezhijie@mail.sysu.edu.cn; chenchun69@126.comObjective: The pathogenesis of sepsis is still unclear due to its complexity, especially in children. This study aimed to analyse the immune microenvironment and regulatory networks related to sepsis in children at the molecular level and to identify key immune-related genes to provide a new basis for the early diagnosis of sepsis.Methods: The GSE145227 and GSE26440 datasets were downloaded from the Gene Expression Omnibus. The analyses included differentially expressed genes (DEGs), functional enrichment, immune cell infiltration, the competing endogenous RNA (ceRNA) interaction network, weighted gene coexpression network analysis (WGCNA), protein–protein interaction (PPI) network, key gene screening, correlation of sepsis molecular subtypes/immune infiltration with key gene expression, the diagnostic capabilities of key genes, and networks describing the interaction of key genes with transcription factors and small-molecule compounds. Finally, real-time quantitative PCR (RT–qPCR) was performed to verify the expression of key genes.Results: A total of 236 immune-related DEGs, most of which were enriched in immune-related biological functions, were found. Further analysis of immune cell infiltration showed that M0 macrophages and neutrophils infiltrated more in the sepsis group, while fewer activated memory CD4+ T cells, resting memory CD4+ T cells, and CD8+ T cells did. The interaction network of ceRNA was successfully constructed. Six key genes (FYN, FBL, ATM, WDR75, FOXO1 and ITK) were identified by WGCNA and PPI analysis. We found strong associations between key genes and constructed septic molecular subtypes or immune cell infiltration. Receiver operating characteristic analysis showed that the area under the curve values of the key genes for diagnosis were all greater than 0.84. Subsequently, we successfully constructed an interaction network of key genes and transcription factors/small-molecule compounds. Finally, the key genes in the samples were verified by RT–qPCR.Conclusion: Our results offer new insights into the pathogenesis of sepsis in children and provide new potential diagnostic biomarkers for the disease.Keywords: sepsis in children, key immune-related genes, transcriptomic analysis, Gene Expression Omnibus, diagnostic biomarkers

This study investigates the characteristics of submerged vortices in an intake sump through a combination of numerical simulations, experimental validations, and advanced modeling techniques. The aim of this study is to gain insights into the complex flow patterns and vortex structures within the sump, focusing on their behavior under varying flow rates. The Shear Stress Transfer (SST) k-ω model is utilized to capture turbulence, and the Volume of Fluid (VOF) method is employed to visualize the water-air interface. Model tests are conducted to validate the simulations. The findings suggest that under low flow conditions, the flow beneath the bell mouth becomes highly turbulent, leading to the formation of a complex vortex system with three distinct high-pressure zones. With increasing flow rates, the shape and strength of these high-pressure zones fluctuate, and a quadrupole vortex structure emerges at the sump bottom. This quadrupole vortex plays a pivotal role in the transformation of a floor-attached vortex upward, culminating in a dual vortex column structure. This structure, in turn, generates additional low-amplitude pressure pulsations. Wall-attached vortices are also observed on both sides of the inlet pipe, a result of flow stratification due to velocity disparities. The insights gained from this study contribute to a deeper understanding of intake sump dynamics and offer valuable guidance for designing and optimizing fluid systems to mitigate potential turbulence-related issues. [ABSTRACT FROM AUTHOR]

Despite important progress in understanding the influence of deforestation on the bacterial α diversity and community structure at local scales, little is known about deforestation impacts in terms of spatial turnover and soil bacterial community network interactions, especially at regional or global scales. To address this research gap, we examined the bacterial spatial turnover rate and the species networks in paired primary and secondary forest soils along a 3700-km north-south transect in eastern China using high-throughput 16S rRNA gene sequencing. The spatial turnover rate of bacterial communities was higher in primary forests than in secondary, suggesting deforestation increased biotic homogenization at a large geographic scale. Multiple regression on matrices analysis revealed that both geographic distance and soil properties (especially soil pH and organic matter availability) strongly affected bacterial spatial turnover. Through the phylogenetic molecular ecological network approach, we demonstrate that the bacterial network of primary forests was more intricate than in secondary forests. This suggests that microbial species have greater niche-sharing and more interactions in primary forests as compared to secondary forests. On the other hand, the bacterial network in secondary forests was more modular, and the taxa tended to co-occur, with positive correlations accounting for 82% of all potential interactions. In conclusion, our findings demonstrate that anthropogenic deforestation has clear effects on bacterial spatial turnover and network interactions, with potential for serious consequences such as microbial diversity loss in primary forests.

Bacteria are one of the most abundant and diverse groups of micro-organisms and mediate many critical terrestrial ecosystem processes. Despite the crucial ecological role of bacteria, our understanding of their large-scale biogeography patterns across forests, and the processes that determine these patterns lags significantly behind that of macroorganisms. Here, we evaluated the geographic distributions of bacterial diversity and their driving factors across nine latitudinal forests along a 3,700-km north–south transect in eastern China, using high-throughput 16S rRNA gene sequencing. Four of 32 phyla detected were dominant: Acidobacteria, Actinobacteria, Alphaproteobacteria and Chloroflexi (relative abundance > 5%). Significant increases in bacterial richness and phylogenetic diversity were observed for temperate forests compared with subtropical or tropical forests. The soil organic matter (SOM) mineralisation rate (SOMmin, an index of SOM availability) explained the largest significant variations in bacterial richness. Variation partition analysis revealed that the bacterial community structure was closely correlated with environmental variables and geographic distance, which together explained 80.5% of community variation. Among all environmental factors, climatic features (MAT and MAP) were the best predictors of the bacterial community structure, whereas soil pH and SOMmin emerged as the most important edaphic drivers of the bacterial community structure. Plant functional traits (community weighted means of litter N content) and diversity resulted in weak but significant correlations with the bacterial community structure. Our findings provide new evidence of bacterial biogeography patterns from tropical to cold temperate forests. Additionally, the results indicated a close linkage among soil bacterial diversity, climate and SOM decomposition, which is critical for predicting continental-scale responses under future climate change scenarios and promoting sustainable forest ecosystem services. A plain language summary is available for this article.

Na He,1,2 Fei Dong,3 Wei Liu,1 Suodi Zhai1 1Department of Pharmacy, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Science, Peking University, Beijing, People’s Republic of China; 3Department of Hematology, Peking University Third Hospital, Beijing, People’s Republic of ChinaCorrespondence: Suodi Zhai; Wei LiuDepartment of Pharmacy, Peking University Third Hospital, 49 Huayuan North Road, Haidian District, Beijing 100191, People’s Republic of ChinaTel +86 10-82266686; +86 10-82265740Email zhaisuodi@163.com; andthen0023@163.comObjective: To provide a comprehensive review of vancomycin dosing in patients with hematologic malignancies or neutropenia.Methods: PubMed, Embase and the Cochrane Library were searched through April 2, 2020. Original studies relevant to vancomycin dosing regimen in adults with hematologic malignancies or neutropenia were included. No restriction was applied in study design and language. A descriptive analysis was performed.Results: Twenty-three studies were included eventually, of which eighteen were case series studies, four were cohort studies and another one was a randomized controlled trial. Five case series studies made a clinical audit of conventional vancomycin dosing in patients with malignancies or neutropenia, showing that the proportion of patients with sub-therapeutic trough levels remained high, ranging from 32% to 88%. Seven case series studies and four cohort studies demonstrated that vancomycin clearance (CLva) tended to be higher in patients with hematologic malignancies or neutropenia, whereas volume of distribution (V) seemed to be comparable to the control group. Five studies proposed individualized initial dosing regimen per the pharmacokinetic changes; however, no prospective validation has been conducted in clinical setting. Additionally, four case series studies suggested that the correlation between vancomycin clearance and estimated creatinine clearance was relatively poor, bringing a great challenge to proper dosing strategy. A randomized controlled trial stated that therapeutic drug monitoring (TDM) of vancomycin could decrease the incidence of nephrotoxicity in immunocompromised febrile patients with hematologic malignancies.Conclusion: The available evidence indicates that conventional vancomycin dosing leads to suboptimal concentration in patients with hematologic malignancy or neutropenia. TDM accompanied by pharmacokinetic interpretation can decrease the risk of nephrotoxicity. The individualization of the initial dosing regimen and mechanisms of augmented clearance require further research.Keywords: vancomycin, hematologic malignancy, neutropenia, pharmacokinetics, evidence-based practice

Abstract: We examined the association between adolescent sexual debut and age at new-type drug initiation among a sample of young adult new-type drug users. A total of 276 participants were recruited using respondent-driven sampling (RDS) in Shanghai, China. The analyses were restricted to a total of 201 participants aged between 18 and 30 years. The average age at sexual debut and age at first new-type drug use were 18.8 and 20.9 years, respectively. About 94% of participants reported having sexual experience (n = 188); of those, 137 (72.9%) had sexual debut before they first used new-type drugs, while 32 (17.0%) initiated both events at the same age. After adjustment for age, income, education, and sexual orientation, adolescent sexual debut was independently associated with younger age at new-type drug initiation. Adolescent sexual debut is associated with early onset of new-type drug use. Our findings underscore the importance of implementing sex-education programs for adolescents in schools in China.

Breast cancer is the most diagnosed cancer type in women, with it being the second most deadly cancer in terms of total yearly mortality. Due to the prevalence of this disease, better methods are needed for both detection and treatment. Reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are autofluorescent biomarkers that lend insight into cell and tissue metabolism. As such, we developed an endoscopic device to measure these metabolites in tissue to differentiate between malignant tumors and normal tissue. We performed initial validations in liquid phantoms as well as compared to a previously validated redox imaging system. We also imaged ex vivo tissue samples after modulation with carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) and a combination of rotenone and antimycin A. We then imaged the rim and the core of MDA-MB-231 breast cancer tumors, with our results showing that the core of a cancerous lesion has a significantly higher optical redox ratio ([FAD]/([FAD] + [NADH])) than the rim, which agrees with previously published results. The mouse muscle tissues exhibited a significantly lower FAD, higher NADH, and lower redox ratio compared to the tumor core or rim. We also used the endoscope to measure NADH and FAD after photodynamic therapy treatment, a light-activated treatment methodology. Our results found that the NADH signal increases in the malignancy rim and core, while the core of cancers demonstrated a significant increase in the FAD signal.

Nong He, Fu-Shan Xue, Cheng-Wen Li Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Fu-Shan Xue, Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong-An Road, Xi-Cheng District, Beijing, 100050, People’s Republic of China, Tel +86 13911177655, Fax +86 10-63138362, Email xuefushan@aliyun.com; fushanxue@outlook.com View the original paper by Prof. Dr. Kang and colleagues

Simple Summary: Use of cancer biomarkers for tumor aggressiveness is an unmet clinical need. Differentiation of high-risk versus low-risk tumors may guide physicians to select appropriate treatment strategies tailored to the risk level of individual patients. This study aimed to evaluate the value of an optical redox imaging technique for differentiating a human melanoma mouse xenograft model with a high risk of metastasis from a low-risk mouse model. Several imaging indices were found to be significantly different between the two models. The high-risk model was found to be in a more oxidized status and to have a higher intratumor redox heterogeneity. These findings may inform further research development of the optical redox imaging approach into translatable cancer biomarkers in the future. To develop imaging biomarkers for tumors aggressiveness, our previous optical redox imaging (ORI) studies of the reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp, containing flavin adenine dinucleotide, i.e., FAD) in tumor xenografts of human melanoma associated the high optical redox ratio (ORR = Fp/(Fp + NADH)) and its heterogeneity to the high invasive/metastatic potential, without having reported quantitative results for NADH and Fp. Here, we implemented a calibration procedure to facilitate imaging the nominal concentrations of tissue NADH and Fp in the mouse xenografts of two human melanoma lines, an indolent less metastatic A375P and a more metastatic C8161. Images of the redox indices (NADH, Fp, ORR) revealed the existence of more oxidized areas (OAs) and more reduced areas (RAs) within individual tumors. ORR was found to be higher and NADH lower in C8161 compared to that of A375P xenografts, both globally for the whole tumors and locally in OAs. The ORR in the OA can differentiate xenografts with a higher statistical significance than the global averaged ORR. H&E staining of the tumors indicated that the redox differences we identified were more likely due to intrinsically different cell metabolism, rather than variations in cell density. [ABSTRACT FROM AUTHOR]

Emerging data indicate that lung macrophages (LM) may provide a novel biomarker to classify disease endotypes in bronchopulmonary dysplasia (BPD), a form of infant chronic lung disease, and that augmentation of the LM phenotype may be a potential therapeutic target. To contribute to this area of research, we first used Optical Redox Imaging (ORI) to characterize the responses to H2O2-induced oxidative stress and caffeine treatment in an in vitro model of mouse alveolar macrophages (AM). H2O2 caused a dose-dependent decrease in NADH and an increase in FAD-containing flavoproteins (Fp) and the redox ratio Fp/(NADH + Fp). Caffeine treatment did not affect Fp but significantly decreased NADH with doses of ≥50 µM, and 1000 µM caffeine treatment significantly increased the redox ratio and decreased the baseline level of mitochondrial ROS (reactive oxygen species). However, regardless of whether AM were pretreated with caffeine or not, the mitochondrial ROS levels increased to similar levels after H2O2 challenge. We then investigated the feasibility of utilizing ORI to examine macrophage redox status in tracheal aspirate (TA) samples obtained from premature infants receiving invasive ventilation. We observed significant heterogeneity in NADH, Fp, Fp/(NADH + Fp), and mitochondrial ROS of the TA macrophages. We found a possible positive correlation between gestational age and NADH and a negative correlation between mean airway pressure and NADH that provides hypotheses for future testing. Our study demonstrates that ORI is a feasible technique to characterize macrophage redox state in infant TA samples and supports further use of this method to investigate lung macrophage-mediated disease endotypes in BPD. [ABSTRACT FROM AUTHOR]