Modulatory interactions of T-2 and deoxynivalenol mycotoxins on murine femoral development and osteological integrity.

In this study, we conducted a systematic assessment of the effectsof Deoxynivalenol (DON) and T-2 mycotoxins on the developmental processes and structural integrity of murine femurs, considering both the isolated and synergistic effects of these toxins. To this end, we divided 72 male mice into nine groups, each subjected to varying dosages of T-2, DON, or their combinations. Over a four-week experimental period, meticulous monitoring was undertaken regarding the mice's body weight, biochemical markers of bone formation and resorption, and the activity of relevant cells. To comprehensively evaluate alterations in bone structure, we employed biomechanical analysis, micro-computed tomography (micro-CT), and transmission electron microscopy.Our findings unveiled a significant revelation: the mice exhibited a dose-dependent decrease in body weight upon exposure to individual mycotoxins, while the combined use of these toxins manifested an atypical antagonistic effect. Furthermore, we observed variations in the levels of calcium, phosphorus, and vitamin D, as well as adjustments in the activities of osteoblasts and osteoclasts, all intricately linked to the dosage and ratio of the toxins. Alterations in biomechanical properties were also noted to correlate with the dosage and combination of toxins. Analyses via micro-CT and transmission electron microscopy further corroborated the substantial impact of toxin dosage and combinations on both cortical and trabecular bone structures.In summation, our research unequivocally demonstrates the dose- and ratio-dependent detrimental effects of DON and T-2 mycotoxins on the growth and structural integrity of murine femurs. These insights accentuate the importance of a profound understanding of the potential risks these toxins pose to bone health, offering pivotal guidance for future toxicological research and public health preventative strategies.

Antigen-specific chemokine profiles as biomarkers for detecting Mycobacterium tuberculosis infection.

Background: Latent tuberculosis (TB) infection can progress to active TB, which perpetuates community transmission that undermines global TB control efforts. Clinically, interferon-γ release assays (IGRAs) are commonly used for active TB case detection. However, low IGRA sensitivity rates lead to false-negative results for a high proportion of active TB cases, thus highlighting IGRA ineffectiveness in differentiating MTB-infected individuals from healthy individuals. Methods: Participants enrolled at Beijing Chest Hospital from May 2020-April 2022 were assigned to healthy control (HC), LTBI, IGRA-positive TB, and IGRA-negative TB groups. Screening cohort MTB antigen-specific blood plasma chemokine concentrations were measured using Luminex xMAP assays then were verified via testing of validation cohort samples. Results: A total of 302 individuals meeting study inclusion criteria were assigned to screening and validation cohorts. Testing revealed significant differences in blood plasma levels of CXCL9, CXCL10, CXCL16, CXCL21, CCL1, CCL19, CCL27, TNF-α, and IL-4 between IGRA-negative TB and HC groups. Levels of CXCL9, CXCL10, IL-2, and CCL8 biomarkers were predictive for active TB, as reflected by AUC values of ≥0.9. CXCL9-based enzyme-linked immunosorbent assay sensitivity and specificity rates were 95.9% (95%CI: 91.7-98.3) and 100.0% (92.7-100.0), respectively. Statistically similar AUC values were obtained for CXCL9 and CXCL9-CXCL10 assays, thus demonstrating that combined analysis of CXCL10 and CXCL9 levels did not improve active TB diagnostic performance. Conclusion: The MTB antigen stimulation-based CXCL9 assay may compensate for low IGRA diagnostic accuracy when used to diagnose IGRA-negative active TB cases and thus is an accurate and sensitive alternative to IGRAs for detecting MTB infection.

Heavy metal pollution in agricultural soils from surrounding industries with low emissions: Assessing contamination levels and sources.

The potential for heavy metal (HM) pollution in agricultural soils adjacent to industries with elevated HM emissions has long been recognized. However, industries with relatively lower levels of HM emissions, such as alumina smelting and glass production, may still contribute to the pollution of surrounding agricultural soils through continuous, albeit low-level, emissions. Despite this, this issue has not garnered adequate attention thus far. Therefore, this study aimed to assess the extent of HM pollution in agricultural soils adjacent to an alumina smelting and a glass production factory, identifying contamination levels and potential sources through the analysis of input fluxes, isotope fingerprints, and receptor models. Results showed moderate cadmium (Cd) contamination in surface soil, exceeding standards at a rate of 86.36 %. Further analysis revealed that atmospheric deposition was the primary route for Cd input in both paddy fields (89.20 %) and dryland soils (91.61 %). Additionally, the δ114/110Cd values in surface soils indicated that dust played a role in influencing Cd levels in distant surface soils, while raw materials and slags were identified as primary sources near the factory. Industrial sources were considered the primary contributors of Cd in soil accounting for approximately 73.38 % and 82.67 %, respectively, according to the positive matrix factorization model (PMF) and absolute principal component scores-multiple linear regression model (APCS-MLR). Overall, this study underscores the importance of monitoring HMs from industries with relatively low emissions and provides a scientific basis for effectively managing HMs pollution in agricultural soils, ensuring the preservation of agricultural soil quality.

The relationship between serum prolactin levels and cognitive function in drug-naïve schizophrenia patients: a cross-sectional study.

This study aimed to investigate the association between serum prolactin levels and psychiatric symptoms and cognitive function in drug-naïve schizophrenia patients. The study recruited 91 drug-naïve schizophrenia patients and 67 healthy controls. Sociodemographic and clinical data were collected, and cognitive function was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). Serum prolactin levels were measured, and statistical analyses were performed to examine the relationship between prolactin levels, clinical symptoms, and cognitive function. The study found that drug-naïve schizophrenia patients had severe cognitive deficits compared to healthy controls across all seven domains of the MCCB. However, no correlation was found between these patients' serum prolactin levels and clinical severity or cognitive function. The drug-naïve schizophrenia patients had significant cognitive deficits compared to healthy controls. However, there was no significant relationship between prolactin levels and symptomatology and cognition in drug-naïve schizophrenia patients.

In vitro susceptibility of nontuberculous mycobacteria in China.

OBJECTIVES: This study aimed to measure the prevalence of resistance to antimicrobial agents, and explore the risk factors associated with drug resistance by using nontuberculous Mycobacteria (NTM) isolates from China. METHODS: A total of 335 NTM isolates were included in our analysis. Broth dilution method was used to determine in vitro drug susceptibility of NTM isolates. RESULTS: Clarithromycin (CLA) was the most potent drug for Mycobacterium intracellulare (MI). The resistance rate of 244 MI isolates to CLA was 21%, yielding a minimum inhibitory concentrations (MIC)50 and MIC90 of 8 and 64 mg/L, respectively. 51% of 244 MI isolates exhibited resistance to amikacin (AMK). For 91 Mycobacterium abscessus complex (MABC) isolates, 6 (7%) and 49 (54%) isolates were categorized as resistant to CLA at day 3 and 14, respectively. The resistance rate to CLA for Mycobacterium abscessus subspecies abscessus (MAA) was dramatically higher than that for Mycobacterium abscessus subspecies massiliense (MAM). Additionally, the percentage of patients presenting fever in the CLA-susceptible group was significantly higher than that in the CLA-resistant group. CONCLUSIONS: Our data demonstrate that approximate one fifth of MI isolates are resistant to CLA. We have identified a higher proportion of CLA-resistant MAA isolates than MAM. The patients caused by CLA-resistant MI are at low risk for presenting with fever relative to CLA-susceptible group.

Autophagy markers, cognitive deficits and depressive symptoms in Parkinson's disease.

Depressive symptoms are common in Parkinson's disease (PD). The relationships between autophagy and PD or depression have been documented. However, no studies explored the role of autophagy markers associated with depressive symptoms in PD. Our study aimed to investigate the relationships between autophagy markers, cognitive impairments and depressive symptoms in PD patients. A total of 163 PD patients aged 50-80 years were recruited. Plasma concentrations of autophagy markers (LC3-I, LC3-II and p62/SQSTM1) and glycolipid parameters were measured. Depressive symptoms, cognitive impairments, and motor function were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA), and the Movement Disorders Society Unified Parkinson's Rating Scale Part III (MDS-UPDRS-III), respectively. There were no significant differences between depressed and non-depressed PD patients for LC3-I, LC3-II, LC3-II/LC3-I and p62/SQSTM1. After controlling confounding variables, LC3-II/LC3-I showed an independent relationship with depressive symptoms in PD patients (Beta = 10.082, t = 2.483, p = 0.014). Moreover, in depressive PD patients, p62/SQSTM1 was associated with MoCA score (Beta = - 0.002, t = - 2.380, p = 0.020); Further, p62/SQSTM1 was related to naming ability; in addition, p62/SQSTM1 was independently associated with delayed recall (Beta = - 0.001, t = - 2.452, p = 0.017). LC3-II/LC3-I was related to depressive symptoms in PD patients. In depressive PD patients, p62/SQSTM1 was associated with cognitive function, especially naming ability and delayed recall.

Epidemiological and clinical profile of pediatric hepatitis B virus infections in Wuhan: a retrospective cohort study.

BACKGROUND: Hepatitis B virus (HBV) remains a substantial public health safety concern drawing considerable attention in China and globally. The detection of HBV serological markers can enable the assessment of HBV infection and replication status in vivo and evaluate the body's protection against HBV. Therefore, this study aims to identify the epidemiological and clinical characteristics of HBV infection in children to prevent and control HBV infection in Wuhan areas. METHODS: We conducted an extensive retrospective cohort analysis of 115,029 individuals aged 0-18 years who underwent HBV serological markers detection for HBV infection in hospital between 2018 and 2021 using Electrochemiluminescence immunoassay. We generated descriptive statistics and analysed HBV infection's epidemiological and clinical characteristics between different sex and age groups. RESULTS: The overall positive detection rates of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb in all participants were 0.13%, 79.09%, 0.17%, 2.81%, and 5.82%, respectively. The positive rate of HBeAb and HBcAb in males was significantly lower than that in females (2.64% vs. 3.13%, 5.56% vs. 6.29%) (P < 0.05). Twenty-two distinct HBV serological expression patterns were revealed. Among them, 8 common expression patterns accounted for 99.63%, while the remaining 14 uncommon expression patterns were primarily observed in neonatal patients with HBV infection. There are no significant differences in serological patterns based on sex (P < 0.05). The overall HBV infection detection rate was 5.82% [range 5.68-5.95] and showed a declining yearly trend. The rate in females was higher than that in males 6.29% [6.05, 6.35] vs. 5.56% [5.39, 5.59]. The overall HBV diagnostic rate over 4 years was 0.20% [0.17, 0.22], and the rate declined yearly. The prevalence of acute infection was higher than that of other infection types before 2019, but the incidence of unclassified infection showed a significant upward trend after 2019. CONCLUSIONS: While the overall HBV infection detection rate in children has decreased year by year, the infection rate remains high in children under one year and between 4 and 18 years. This continued prevalence warrants heightened attention and vigilance.

Prevalence and influencing factors of sleep disturbance among medical students under the COVID-19 pandemic.

BACKGROUND: Medical students may feel severe psychological stress during COVID-19, which might impair their ability to sleep. This research aimed to look at the risk factors for sleep disturbance and the prevalence of sleep disturbance among medical students. METHODS: 538 medical students in total were recruited for this research. Anxiety, depression, and sleep disturbance were assessed using the Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and Pittsburgh Sleep Quality Index (PSQI). To evaluate the possible risk variables, we computed descriptive statistics for each assessment item and ran univariate and logistic regression analyses. RESULTS: Medical students had a 63.6% prevalence of sleep disturbance (n = 342). According to logistic regression, introverted students are 1.77 times more likely than extroverted students to have sleep disturbance (OR = 1.77, 95% CI 1.08-2.91). Medical students with depression had a 5.6-times higher risk of sleep disturbance than those without depression (OR = 5.60, 95% CI 3.43-9.15). Additionally, medical students with anxiety were 3.95 times more likely than those without anxiety to have sleep disturbance (OR = 3.95, 95% CI 2.04-7.64). CONCLUSIONS: According to this research, the COVID-19 pandemic caused significant sleep disturbance among medical students. Additionally, among medical students, introversion, anxiety, and depression were risk factors for sleep disturbance.

Gender differences and clinical correlates in the age of the first hospitalization in patients with drug-naïve schizophrenia in China: a cross-sectional study.

Gender differences in the onset age of schizophrenia have been reported in many studies, but differences in the age of the first hospitalization and associated factors have not been explored. The present study investigated gender differences and clinical correlates in the age of the first hospitalization in drug-naïve schizophrenia (DNS). A total of 144 DNS patients and 67 health controls were included. Demographic information, duration of untreated psychosis (DUP), Positive and Negative Symptom Scale (PANSS) scores, the Brief Psychiatric Rating Scale (BPRS) scores, Global Assessment of Functioning (GAF) scores, and MATRICS Consensus Cognitive Battery (MCCB) scores were collected and analyzed. The age of the first hospitalization was significantly earlier in males than in females (P < 0.01). In addition, there were significant differences in the age of the first hospitalization in terms of marital status, occupation, family ranking, suicide attempt, and place of residence (all P < 0.05). After Bonferroni correction, only DUP had a positive correlation with the age of the first hospitalization (PBonferroni < 0.05/6 = 0.0083). Multivariate linear regression analysis showed that gender (ß = 0.141, t = 2.434, P = 0.016), marital status (ß = 0.219, t = 3.463, P = 0.001), family ranking (ß = 0.300, t = 4.918, P < 0.001), suicide attempt (ß = 0.348, t = 5.549, P < 0.001), and DUP (ß = 0.190, t = 2.969, P < 0.004) positively predicted the age of the first hospitalization. The age of the first hospitalization in male DNS was earlier than in females. In addition, gender, marital status, suicide attempt, DUP, and family rank were independent risk factors for the age of the first hospitalization.

Advancing Intelligent Organ-on-a-Chip Systems with Comprehensive In Situ Bioanalysis.

In vitro models are essential to a broad range of biomedical research, such as pathological studies, drug development, and personalized medicine. As a potentially transformative paradigm for 3D in vitro models, organ-on-a-chip (OOC) technology has been extensively developed to recapitulate sophisticated architectures and dynamic microenvironments of human organs by applying the principles of life sciences and leveraging micro- and nanoscale engineering capabilities. A pivotal function of OOC devices is to support multifaceted and timely characterization of cultured cells and their microenvironments. However, in-depth analysis of OOC models typically requires biomedical assay procedures that are labor-intensive and interruptive. Herein, the latest advances toward intelligent OOC (iOOC) systems, where sensors integrated with OOC devices continuously report cellular and microenvironmental information for comprehensive in situ bioanalysis, are examined. It is proposed that the multimodal data in iOOC systems can support closed-loop control of the in vitro models and offer holistic biomedical insights for diverse applications. Essential techniques for establishing iOOC systems are surveyed, encompassing in situ sensing, data processing, and dynamic modulation. Eventually, the future development of iOOC systems featuring cross-disciplinary strategies is discussed.

Metabolic modulation of mitochondrial mass during CD4+ T cell activation.

Mitochondrial biogenesis initiates within hours of T cell receptor (TCR) engagement and is critical for T cell activation, function, and survival; yet, how metabolic programs support mitochondrial biogenesis during TCR signaling is not fully understood. Here, we performed a multiplexed metabolic chemical screen in CD4+ T lymphocytes to identify modulators of metabolism that impact mitochondrial mass during early T cell activation. Treatment of T cells with pyrvinium pamoate early during their activation blocks an increase in mitochondrial mass and results in reduced proliferation, skewed CD4+ T cell differentiation, and reduced cytokine production. Furthermore, administration of pyrvinium pamoate at the time of induction of experimental autoimmune encephalomyelitis, an experimental model of multiple sclerosis in mice, prevented the onset of clinical disease. Thus, modulation of mitochondrial biogenesis may provide a therapeutic strategy for modulating T cell immune responses.

Sex- and age-specific prevalence and risk factors of depressive symptoms in Parkinson's disease.

Although depressive symptoms are common in PD, few studies investigated sex and age differences in depressive symptoms. Our study aimed to explore the sex and age differences in the clinical correlates of depressive symptoms in patients with PD. 210 PD patients aged 50-80 were recruited. Levels of glucose and lipid profiles were measured. The Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA) and the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) assessed depressive symptom, cognition and motor function, respectively. Male depressive PD participants had higher fasting plasma glucose (FPG) levels. Regarding the 50-59 years group, depressive patients had higher TG levels. Moreover, there were sex and age differences in the factors associated with severity of depressive symptoms. In male PD patients, FPG was an independent contributor to HAMD-17 (Beta = 0.412, t = 4.118, p < 0.001), and UPDRS-III score was still associated with HAMD-17 in female patients after controlling for confounding factors (Beta = 0.304, t = 2.961, p = 0.004). Regarding the different age groups, UPDRS-III (Beta = 0.426, t = 2.986, p = 0.005) and TG (Beta = 0.366, t = 2.561, p = 0.015) were independent contributors to HAMD-17 in PD patients aged 50-59. Furthermore, non-depressive PD patients demonstrated better performance with respect to visuospatial/executive function among the 70-80 years group. These findings suggest that sex and age are crucial non-specific factors to consider when assessing the relationship between glycolipid metabolism, PD-specific factors and depression.

Integrated plasma and exosome long noncoding RNA profiling is promising for diagnosing non-small cell lung cancer.

OBJECTIVES: Non-small cell lung cancer (NSCLC) accounts for more than 80 % of all lung cancers, and its 5-year survival rate can be greatly improved by early diagnosis. However, early diagnosis remains elusive because of the lack of effective biomarkers. In this study, we aimed to develop an effective diagnostic model for NSCLC based on a combination of circulating biomarkers. METHODS: Tissue-deregulated long noncoding RNAs (lncRNAs) in NSCLC were identified in datasets retrieved from the Gene Expression Omnibus (GEO, n=727) and The Cancer Genome Atlas (TCGA, n=1,135) databases, and their differential expression was verified in paired local plasma and exosome samples from NSCLC patients. Subsequently, LASSO regression was used to screen for biomarkers in a large clinical population, and a logistic regression model was used to establish a multi-marker diagnostic model. The area under the receiver operating characteristic (ROC) curve (AUC), calibration plots, decision curve analysis (DCA), clinical impact curves, and integrated discrimination improvement (IDI) were used to evaluate the efficiency of the diagnostic model. RESULTS: Three lncRNAs-PGM5-AS1, SFTA1P, and CTA-384D8.35 were consistently expressed in online tissue datasets, plasma, and exosomes from local patients. LASSO regression identified nine variables (Plasma CTA-384D8.35, Plasma PGM5-AS1, Exosome CTA-384D8.35, Exosome PGM5-AS1, Exosome SFTA1P, Log10CEA, Log10CA125, SCC, and NSE) in clinical samples that were eventually included in the multi-marker diagnostic model. Logistic regression analysis revealed that Plasma CTA-384D8.35, exosome SFTA1P, Log10CEA, Exosome CTA-384D8.35, SCC, and NSE were independent risk factors for NSCLC (p<0.01), and their results were visualized using a nomogram to obtain personalized prediction outcomes. The constructed diagnostic model demonstrated good NSCLC prediction ability in both the training and validation sets (AUC=0.97). CONCLUSIONS: In summary, the constructed circulating lncRNA-based diagnostic model has good NSCLC prediction ability in clinical samples and provides a potential diagnostic tool for NSCLC.

Serum level of S100A8/A9 as a biomarker for establishing the diagnosis and severity of community-acquired pneumonia in children.

Background: S100A8/A9, which is a member of S100 proteins, may be involved in the pathophysiology of Community-acquired pneumonia (CAP) that seriously threatens children's health. However, circulating markers to assess the severity of pneumonia in children are yet to be explored. Therefore, we aimed to investigate the diagnostic performance of serum S100A8/A9 level in determining the severity of CAP in children. Methods: In this prospective and observational study, we recruited 195 in-hospital children diagnosed with CAP. In comparison, 63 healthy children (HC) and 58 children with non-infectious pneumonia (pneumonitis) were included as control groups. Demographic and clinical data were collected. Serum S100A8/A9 levels, serum pro-calcitonin concentrations, and blood leucocyte counts were quantified. Results: The serum S100A8/A9 levels in patients with CAP was 1.59 ± 1.32 ng/mL, which was approximately five and two times higher than those in healthy controls and those in children with pneumonitis, respectively. Serum S100A8/A9 was elevated parallelly with the clinical pulmonary infection score. The sensitivity, specificity, and Youden's index of S100A8/A9 ≥1.25 ng/mL for predicting the severity of CAP in children was optimal. The area under the receiver operating characteristic curve of S100A8/A9 was the highest among the indices used to evaluate severity. Conclusions: S100A8/A9 may serve as a biomarker for predicting the severity of the condition in children with CAP and establishing treatment grading.

Real-time recombinase-aided amplification assay for rapid amplification of the IS1081 gene of Mycobacterium tuberculosis.

Mycobacterium tuberculosis (MTB), the etiological agent of tuberculosis (TB), is the leading cause of death due to a single infectious agent worldwide. Rapid and accurate diagnosis of MTB is critical for controlling TB especially in resource-limited countries, since any diagnosis delay increases the chances of transmission. Here, a real-time recombinase-aided amplification (RAA) assay targeting conserved positions in IS1081 gene of MTB, is successfully established to detect MTB. The intact workflow was completed within 30 min at 42 °C with no cross-reactivity observed for non-tuberculous mycobacteria and other clinical bacteria, and the detection limit for recombinant plasmid of MTB IS1081 was 163 copies/reaction at 95% probability, which was approximately 1.5-fold increase in analytical sensitivity for the detection of MTB, compared to conventional quantitative real-time PCR (qPCR; 244 copies/reaction). Furthermore, the result of clinical performance evaluation revealed an increased sensitivity of RAA assay relative to qPCR was majorly noted in the specimens with low bacteria loads. Our results demonstrate that the developed real-time RAA assay is a convenient, sensitive, and low-cost diagnostic tool for the rapid detection of MTB.

Prevalence of overweight and obesity in patients with major depressive disorder with anxiety: Mediating role of thyroid hormones and metabolic parameters.

BACKGROUNDS: Anxiety is a common comorbidity in major depressive disorder (MDD); however, its role in overweight and obesity in MDD patients remains unclear. We examined the relationship between severe anxiety and overweight and obesity, as well as the mediating role of thyroid hormones and metabolic parameters in MDD patients. METHODS: This cross-sectional study recruited 1718 first-episode drug-naïve MDD outpatients. All participants were rated on the Hamilton Depression Rating Scale for depression and Hamilton Anxiety Rating Scale for anxiety and measured in thyroid hormones and metabolic parameters. RESULTS: A total of 218 (12.7 %) individuals had severe anxiety. The prevalence of overweight and obesity in patients with severe anxiety was 62.8 % and 5.5 %, respectively. Severe anxiety symptoms were associated with overweight (Odds Ratio [OR]: 1.47, 95 % CI: 1.08, 2.00) and obesity (OR: 2.10, 95 % CI: 1.07, 4.15). The association between severe anxiety and overweight was mainly attenuated by thyroid hormones (40.4 %), blood pressure (31.9 %), and plasma glucose (19.1 %). For obesity, the association with severe anxiety was mainly attenuated by thyroid hormones (48.2 %), blood pressure (39.1 %), and total cholesterol (28.2 %). LIMITATIONS: Due to the cross-sectional design, no causal relationship could be derived. CONCLUSIONS: Thyroid hormones and metabolic parameters can explain the risk of overweight and obesity associated with severe anxiety in MDD patients. These findings add to the knowledge of the pathological pathway of overweight and obesity in MDD patients with comorbid severe anxiety.

Application value of antibody titres and RNA detection in the early prediction of Mycoplasma pneumoniae pneumonia in children: a retrospective study.

BACKGROUND: Children with Mycoplasma pneumoniae pneumonia (MPP) are prone to a missed diagnosis at the early stages of the disease, which greatly affects the prognosis of children. In this study, the application value of Mycoplasma pneumoniae (MP) antibody titres and RNA detection for diagnosing MP infection in children with community-acquired pneumonia (CAP) was evaluated. The present study aimed to seek appropriate detection methods and strategies for early rapid diagnosis in children with MPP. METHODS: A retrospective study was conducted on 563 paediatric patients aged 1 month to 15 years with CAP who were admitted to Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology between July 2021 and February 2022. In all patients, throat swabs were collected for MP-RNA detection (simultaneous amplification and testing, SAT), and paired serum samples were collected for MP total antibody detection (particle agglutination, PA). RESULTS: The classification as MPP or non-MPP was based on clinical diagnosis, serum MP antibody titre, and clinical or laboratory evidence of infection by other pathogen(s). Among the 563 patients with pneumonia, 187 patients were in the MPP group, and 376 patients were in the non-MPP group. The Kappa values between the particle agglutination test at different titres (1:80, 1:160) and MP-RNA detection were 0.612 and 0.660 (P<0.01), and the consistency of the three methods was acceptable. When the single screening method was used, MP-RNA had the highest sensitivity (93.05%), while PA (1:160) had the highest specificity (100%). PA (1:80), with an area under the curve (AUC) of 0.822, was better than PA (1:160), with an AUC of 0.783, and there was a significant difference. When the combined screening methods were used, the AUC of MP-RNA parallel PA (1:160) was significantly higher than that of titres (1:80) (z=-4.906, P < 0.01). Except for MP-80, the efficacy of the other three test methods in females was slightly better than that in males. Among the differences in age distribution, PA (1:80) was slightly less effective in the 13-72 months age group than at other ages, and MP-RNA parallel PA (1:160) was slightly better than the younger age group (≤ 36 m). In the older age group (> 36 m), PA (1:160) was just the opposite, while MP-RNA was slightly better than other age groups in the 13-72 months age group. CONCLUSIONS: For the diagnosis of MPP in children at the early of the disease, the antibody titre (1:160) parallel MP-RNA should be given preference, and then the disease should be further classified according to the antibody titre level and the age of the child. The combined application of the two detection methods could complement each other and strengthen the advantages, providing reliable laboratory evidence for the clinical diagnosis and timely treatment of MPP. When using the PA method alone to provide a reference standard to clarify MP infection, the differential diagnosis ability of 1:80 for MPP is better than 1:160, especially for children younger than 36 months.

Uncoupled glycerol-3-phosphate shuttle in kidney cancer reveals that cytosolic GPD is essential to support lipid synthesis.

The glycerol-3-phosphate shuttle (G3PS) is a major NADH shuttle that regenerates reducing equivalents in the cytosol and produces energy in the mitochondria. Here, we demonstrate that G3PS is uncoupled in kidney cancer cells where the cytosolic reaction is ∼4.5 times faster than the mitochondrial reaction. The high flux through cytosolic glycerol-3-phosphate dehydrogenase (GPD) is required to maintain redox balance and support lipid synthesis. Interestingly, inhibition of G3PS by knocking down mitochondrial GPD (GPD2) has no effect on mitochondrial respiration. Instead, loss of GPD2 upregulates cytosolic GPD on a transcriptional level and promotes cancer cell proliferation by increasing glycerol-3-phosphate supply. The proliferative advantage of GPD2 knockdown tumor can be abolished by pharmacologic inhibition of lipid synthesis. Taken together, our results suggest that G3PS is not required to run as an intact NADH shuttle but is instead truncated to support complex lipid synthesis in kidney cancer.

Analysis of Xpert MTB/RIF results in retested patients with very low initial bacterial loads: A retrospective study in China.

BACKGROUND: The Xpert MTB/RIF (Xpert) assay has been widely used to diagnose suspected active tuberculosis (TB) and rifampicin-resistant TB cases. Despite its excellent performance record, false-positive Xpert rifampicin (RIF) resistance results are obtained for specimens with extremely low bacterial loads. OBJECTIVE: We aimed to study the feasibility of repeat Xpert testing as a strategy for reducing the odds of obtaining false-positive results when testing paucibacillary TB patients. METHODS: We enrolled previously tested TB patients with very low initial bacterial loads from May 2016 to February 2022 for Xpert retesting. A total of 251 TB patients were retested using the Xpert assay. RESULTS: RIF resistance was noted in 65 (25.9 %) patients when tested by Xpert at initial diagnosis. Only 107 (42.6 %) of 251 patients tested positive for MTB when retested via Xpert. The majority (98.6 %) of RIF-susceptible cases were still susceptible to RIF when retested. Initial Xpert testing yielded 35 positive results for MTB in the RIF-resistant group, of whom 25 (71.4 %) still exhibited RIF resistance when retested. All culture-positive MTB isolates in the RIF-susceptible group were also RIF-susceptible by phenotypic DST. In the RIF-resistant group, 10 of 14 culture-positive MTB isolates exhibited RIF resistance, of which 4 isolates were deemed RIF-susceptible by phenotypic DST. The proportion of double mutations within the MTB rpoB RRDR sequence, as detected by hybridization of Xpert D and E probes, was significantly higher in the RIF-susceptible group than in the RIF-susceptible group. CONCLUSIONS: Our results demonstrated that initial RIF-susceptible results were more accurate than RIF-resistant results. Additionally, patients with double mutations that delayed probe D/E hybridization were more likely to have false-positive Xpert results. Our findings emphasize that repeat Xpert MTB/RIF testing is necessary for TB patients with extremely low bacterial loads who are at high risk for RIF-resistant TB.