Immune cells mediated the causal relationship between the gut microbiota and lung cancer: a Mendelian randomization study.

Introduction: The gut microbiota (GM) influences the occurrence and progression of lung cancer (LC), with potential involvement of immune cells (IC). We aimed to investigate the causal impact of GM on LC and identify potential immune cell mediators. Methods: The utilized data for the Genome-Wide Association Studies (GWAS) were summarized as follows: gut microbiota data from the Dutch Microbiome Project (DMP) (N = 7,738), lung cancer data from the Transdisciplinary Research in Cancer of the Lung (TRICL) and International Lung Cancer Consortium (ILCCO) (Ncase = 29,266, Ncontrol = 56,450) included four types of cancer: NSCLC, LUAD, LUSC, and SCLC, and immune cell data from European populations (N = 3,757). We employed bi-directional two-sample univariable Mendelian randomization (UVMR), multivariable Mendelian randomization (MVMR), and mediation analysis to assess the causal relationship between GM and LC and potential immune cell mediators. Results: Bi-directional UVMR analysis revealed that 24 gut microbiota species can affect LC, while LC can affect the abundance of 17 gut microbiota species. Mediation analysis demonstrated that six immune cells mediated the causal relationships of seven gut microbiota species on LC: "CCR7 on naive CD8+ T cell" mediated the causal relationship between s_Alistipes_putredinis and LUAD, with a mediation proportion of 9.5% and P = 0.018; "IgD- CD27- B cell %lymphocyte" mediated the causal relationships between g_Gordonibacter and s_Gordonibacter_pamelaeae with LUSC, with mediation proportions of 11.8% and 11.9%, respectively and P = 0.029; "CD20- CD38- B cell %lymphocyte" mediated the causal relationship between s_Bacteroides_clarus and SCLC, with a mediation proportion of 13.8% and P = 0.005; "CD20 on IgD+ CD38- unswitched memory B cell" mediated the causal relationship between s_Streptococcus_thermophilus and SCLC, with a mediation proportion of 14.1% and P = 0.023; "HLA DR on CD14- CD16+ monocyte" mediated the causal relationship between s_Bifidobacterium_bifidum and SCLC, with a mediation proportion of 8.7% and P = 0.012; "CD45 on Granulocytic Myeloid-Derived Suppressor Cells" mediated the causal relationship between f_Lactobacillaceae and SCLC, with a mediation proportion of 4.0% and P = 0.021. Conclusion: This Mendelian randomization study identified several specific gut microbiotas that exhibit causal relationships with lung cancer and potentially mediate immune cells.

Prognosis and immunotherapy efficacy in dMMR&MSS colorectal cancer patients and an MSI status predicting model.

The inconsistency between mismatch repair (MMR) protein immunohistochemistry (IHC) and microsatellite instability PCR (MSI-PCR) methods has been widely reported. We aim to investigate the prognosis and the effect of immunotherapy in dMMR by IHC but MSS by MSI-PCR (dMMR&MSS) colorectal cancer (CRC) patients. A microsatellite instability (MSI) predicting model was established to help find dMMR&MSS patients. MMR and MSI states were detected by the IHC and MSI-PCR in 1622 CRC patients (ZS6Y-1 cohort). Logistic regression analysis was used to screen clinical features to construct an MSI-predicting nomogram. We propose a new nomogram-based assay to find patients with dMMR&MSS, in which the MSI-PCR assay only detects dMMR patients with MSS predictive results. We applied the new strategy to a random cohort of 248 CRC patients (ZS6Y-2 cohort). The consistency of MMR IHC and MSI-PCR in the ZS6Y-1 cohort was 95.7% (1553/1622). Both pMMR&MSS and dMMR&MSS groups experienced significantly shorter overall survival (OS) than those in dMMR by IHC and MSI-H by MSI-PCR (dMMR&MSI-H) group (hazard ratio [HR] = 2.429, 95% confidence interval [CI]: 1.89-3.116, p < .01; HR = 21.96, 95% CI: 7.24-66.61, p < .01). The dMMR&MSS group experienced shorter OS than the pMMR&MSS group, but the difference did not reach significance (log rank test, p = .0686). In the immunotherapy group, the progression-free survival of dMMR&MSS patients was significantly shorter than that of dMMR&MSI-H patients (HR = 13.83, 95% CI: 1.508-126.8, p < .05). The ZS6Y-MSI-Pre nomogram (C-index = 0.816, 95% CI: 0.792-0.841, already online) found 66% (2/3) dMMR&MSS patients in the ZS6Y-2 cohort. There are significant differences in OS and immunotherapy effect between dMMR&MSI-H and dMMR&MSS patients. Our prediction model provides an economical way to screen dMMR&MSS patients.

Chemotherapy versus chemotherapy plus immune checkpoint inhibitors for the first-line treatment of unresectable thymic carcinoma: A multicenter retrospective study.

Thymic carcinoma (TC) is a rare malignant tumor with a poor prognosis, and there is currently limited data on the use of immunotherapy in patients with unresectable TC. In this study, data of patients with unresectable TC diagnosed from January 2017 were retrospectively collected from multiple centers. Treatment response, progression-free survival (PFS), overall survival (OS), survival-independent prognostic factor, and adverse events (AEs) were further analyzed. As a result, a total of 93 patients with unresectable TC were enrolled, of which 54 received first-line chemotherapy, and 39 received chemotherapy plus immune checkpoint inhibitors (ICIs). The objective response rate was 50% (27/54) in the chemotherapy group and 76.9% (30/39) in the chemotherapy plus ICIs group. The chemotherapy plus ICIs group achieved significant median PFS benefit (8.8 vs. 34.9 months, p < .001) and median OS benefit (41.8 months vs. not reached, p = .025). Multivariate analysis showed that ICIs and local therapy were independent prognostic factors for PFS. In addition, 17 patients developed immune-related AEs (IRAEs), of which 15 (38.5%) had Grade 1 or 2 IRAEs and 2 (5.1%) had Grade 3 IRAEs in the chemotherapy plus ICIs group. In conclusion, the efficacy of chemotherapy plus ICIs is superior to chemotherapy, and the adverse effects are manageable in patients with unresectable TC.

RAS Dataset: A 3D Cardiac LGE-MRI Dataset for Segmentation of Right Atrial Cavity.

The current challenge in effectively treating atrial fibrillation (AF) stems from a limited understanding of the intricate structure of the human atria. The objective and quantitative interpretation of the right atrium (RA) in late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) scans relies heavily on its precise segmentation. Leveraging the potential of artificial intelligence (AI) for RA segmentation presents a promising solution. However, the successful implementation of AI in this context necessitates access to a substantial volume of annotated LGE-MRI images for model training. In this paper, we present a comprehensive 3D cardiac dataset comprising 50 high-resolution LGE-MRI scans, each meticulously annotated at the pixel level. The annotation process underwent rigorous standardization through crowdsourcing among a panel of medical experts, ensuring the accuracy and consistency of the annotations. Our dataset represents a significant contribution to the field, providing a valuable resource for advancing RA segmentation methods.

Testing region selection and prognostic analysis of MLH1 promoter methylation in colorectal cancer in China.

Background: MLH1 promoter methylation analysis is recommended in screening for Lynch syndrome (LS) in patients with MLH1-deficient colorectal cancer (CRC). The study aims to identify specific methylation regions in the MLH1 promoter and to evaluate the clinicopathologic characteristics of and prognosis for patients with MLH1 methylation. Methods: A total of 580 CRC cases were included. The DNA mismatch repair (MMR) protein expression was assessed by using immunohistochemistry (IHC). The methylation status of the Regions A, B, C, D, and E in the MLH1 promoter was tested by using bisulfite sequencing PCR. The specificities of the five regions were calculated. Associations between MLH1 methylation and clinicopathologic characteristics were evaluated. Kaplan-Meier analyses for overall survival (OS) were carried out. Results: In 580 CRC cases, the specificities of the methylation test in Regions D and E were both 97.8%. In the MLH1-deficient CRCs, the frequencies of MLH1 methylation and BRAFV600E mutation were 52.6% and 14.6%, respectively; BRAFV600E mutation occurred in 27.7% of patients with MLH1-methylated CRC. In the MMR-deficient patients, compared with MLH1 unmethylation, MLH1 methylation was more common in patients who were aged ≥50 years, female, had no family history of LS-related tumors, and had tumors located at the right colon. In the MMR-deficient patients, the MLH1-methylated cases had lower OS rates than the unmethylated cases with a family history of LS-related tumors (P = 0.047). Conclusions: Regions D and E in the MLH1 promoter are recommended for determining the MLH1 methylation status in screening for LS in MLH1-deficient CRC. In MMR-deficient patients, the MLH1-methylated cases had a worse OS than the unmethylated cases with a family history of LS-related cancer.

Insight into microbial adaptability in continuous flow anaerobic ammonium oxidation process for low-strength sewage treatment.

Organic matter concentration is a critical factor influencing the adaptability of anaerobic ammonium oxidation (anammox) bacteria to low-strength sewage treatment. To address this challenge and achieve stable anammox activity, a micro-aeration partial nitrification-anammox process was developed for continuous-flow municipal sewage treatment. Under limited ammonium conditions, the effective utilization of organics in denitrification promoted the stable accumulation of nitrite and enhanced anammox activity. This, in turn, led to enhanced nitrogen removal efficiency, reaching approximately 87.7%. During the start-up phase, the protein content of extracellular polymeric substances (EPS) increased. This enhanced EPS intensified the inhibitory effect of denitrifying bacteria (DNB) on nitrite-oxidizing bacteria through competition for nitrite, thereby facilitating the proliferation of anammox bacteria (AnAOB). Additionally, several types of DNB capable of utilizing slowly biodegradable organics contributed to the adaptability of AnAOB. These findings provide valuable insights for ensuring efficient anammox performance and robust nitrogen removal in the treatment of low-strength sewage.

Netrin-1 protects blood-brain barrier (BBB) integrity after cerebral ischemia-reperfusion by activating the Kruppel-like factor 2 (KLF2)/occludin pathway.

Ischemia/reperfusion (I/R)-induced neural damage and neuroinflammation have been associated with pathological progression during stroke. Netrin-1 is an important member of the family of laminin-related secreted proteins, which plays an important role in governing axon elongation. However, it is unknown whether Netrin-1 possesses a beneficial role in stroke. Here, we employed the middle cerebral artery occlusion (MCAO) model to study the function of Netrin-1 in alleviating brain injuries. Our results demonstrate that Netrin-1 rescued poststroke neurological deficits and inhibited production of the inflammatory cytokines such as interleukin 6 (IL-6) and endothelial chemokine (C-X-C motif) ligand 1 (Cxcl1). Importantly, Netrin-1 protected against MCAO-induced dysfunction of the blood-brain barrier (BBB) in mice and a reduction in the expression of the tight junction (TJ) protein occludin. Additionally, we report that Netrin-1 could ameliorate oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury and prevent aggravation in endothelial monolayer permeability in bEnd.3 human brain microvascular endothelial cells (HBMVECs). Mechanistically, Netrin-1 ameliorated OGD/R-induced decrease in occludin and Kruppel-like factor 2 (KLF2) in HBMVECs. Notably, silencing of KLF2 abolished the beneficial effects of Netrin-1 in protecting endothelial permeability and occludin expression, suggesting that these effects are mediated by KLF2. In conclusion, our findings suggest that Netrin-1 could constitute a novel therapeutic strategy for ischemic stroke.

Soft Materials for Photoelectrochemical Fuel Production.

Polymer semiconductors are fascinating materials that could enable delivery of chemical fuels from water and sunlight, offering several potential advantages over their inorganic counterparts. These include extensive synthetic tunability of optoelectronic and redox properties and unique opportunities to tailor catalytic sites via chemical control over the nanoenvironment. Added to this is proven functionality of polymer semiconductors in solar cells, low-cost processability, and potential for large-area scalability. Herein we discuss recent progress on soft photoelectrochemical systems and define three critical knowledge gaps that must be closed for these materials to reach their full potential. We must (1) understand the influence of electrolyte penetration on photoinduced charge separation, transport, and recombination, (2) learn to exploit the swollen polymer/electrolyte interphase to drive selective fuel formation, and (3) establish co-design criteria for soft materials that sustain function in the face of harsh chemical challenges. Achieving these formidable goals would enable tailorable systems for driving photoelectrochemical fuel production at scale.

Head-to-head comparative study: evaluating three panels for MSI-PCR testing in patients with colorectal and gastric cancer.

AIMS: Due to the lack of large clinical cohorts in the Chinese populations with colorectal cancer (CRC) and gastric cancer (GC), there is no consensus among the preferred panel for microsatellite instability (MSI)-PCR testing. This study aims to evaluate a more appropriate panel. METHODS: We tested the MSI status of 2572 patients with CRC and GC using the NCI panel and 2 mononucleotide panels (5 and 6 mononucleotide panels). Immunohistochemistry (IHC) was employed to perform mismatch repair protein testing in 1976 samples. RESULTS: We collected 2572 patients with CRC and GC. The National Cancer Institute (NCI) panel failed to detect 13 cases. Of the 2559 cases that received results from all three panels, 2544 showed consistent results. In the remaining 15 cases, 9 showed discrepancies between MSI-H and MSI-L, and 6 showed discrepancies between MSI-L and microsatellite stability (MSS). The misdiagnosis rate of MSI-L was significantly lower in two mononucleotide panels than in the NCI panel (12.5% vs 87.5%, p=0.010) in CRC. In patients with GC, only the NCI panel detected three MSI-L cases, while the results of the two mononucleotide panels were one MSI-H and two MSS. Based on their IHC results, the MSI-L misdiagnosis rate of the NCI panel was 33.3%. Furthermore, compared with two mononucleotide panels, the NCI panel had a much lower rate of all loci instability in CRC (90.8% and 90.3% vs 25.2%) and GC (89.5% and 89.5% vs 12.0%). CONCLUSION: In Chinese patients with CRC and GC, the five and six mononucleotide panels have advantages for detecting MSI over the NCI panel.

Evaluation of ferritin and TfR level in plasma neural-derived exosomes as potential markers of Parkinson's disease.

Introduction: Early diagnosis of Parkinson's disease (PD) remains challenging. It has been suggested that abnormal brain iron metabolism leads to excessive iron accumulation in PD, although the mechanism of iron deposition is not yet fully understood. Ferritin and transferrin receptor (TfR) are involved in iron metabolism, and the exosome pathway is one mechanism by which ferritin is transported and regulated. While the blood of healthy animals contains a plentiful supply of TfR-positive exosomes, no studies have examined ferritin and TfR in plasma neural-derived exosomes. Methods: Plasma exosomes were obtained from 43 patients with PD and 34 healthy controls. Neural-derived exosomes were isolated with anti-human L1CAM antibody immunoabsorption. Transmission electron microscopy and western blotting were used to identify the exosomes. ELISAs were used to quantify ferritin and TfR levels in plasma neural-derived exosomes of patients with PD and controls. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of ferritin and TfR. Independent predictors of the disease were identified using logistic regression models. Results: Neural-derived exosomes exhibited the typical exosomal morphology and expressed the specific exosome marker CD63. Ferritin and TfR levels in plasma neural-derived exosomes were significantly higher in patients with PD than controls (406.46 ± 241.86 vs. 245.62 ± 165.47 ng/µg, P = 0.001 and 1728.94 ± 766.71 vs. 1153.92 ± 539.30 ng/µg, P < 0.001, respectively). There were significant positive correlations between ferritin and TfR levels in plasma neural-derived exosomes in control group, PD group and all the individuals (rs = 0.744, 0.700, and 0.752, respectively). The level of TfR was independently associated with the disease (adjusted odds ratio 1.002; 95% CI 1.000-1.003). ROC performances of ferritin, TfR, and their combination were moderate (0.730, 0.812, and 0.808, respectively). However, no relationship was found between the biomarkers and disease progression. Conclusion: It is hypothesized that ferritin and TfR in plasma neural-derived exosomes may be potential biomarkers for PD, and that they may participate in the mechanism of excessive iron deposition in PD.

The predictive utility of atherosclerosis-related risk factors as predictors of the prognosis of idiopathic sudden sensorineural hearing loss in older adults.

BACKGROUND: There have been few studies to date exploring prognostic outcomes associated with idiopathic sudden sensorineural hearing loss (ISSNHL) in order adults. OBJECTIVE: This investigation was designed to explore the relationship between atherosclerosis-related risk factors and ISSNHL outcomes among older individuals. MATERIAL AND METHODS: In total, 172 older adults diagnosed ISSNHL from 2016 to 2021 were retrospectively evaluated to compare demographic and clinical test results. RESULTS: Relative to healthy controls, ISSNHL patients exhibited significant differences in hypertension incidence and factors related to coagulation. With respect to prognosis, age, onset days, hypertension, the degree of hearing loss, type of hearing curve, fibrinogen and D-dimer levels were significant univariate prognostic factors, whereas multivariate logistic analysis showed that hypertension (p = .005) and D-dimer concentration (p = .000) were related to the treatment outcome of older ISSNHL patients. The area under the curve (AUC) for D-dimer levels was 0.795 (95% CI: 0.724-0.866). When using a D-dimer cut-off threshold value of 107.5 ng/mL, the sensitivity and specificity values of 77.0% and 76.7%. CONCLUSIONS: The present results indicate that hypertension incidence and D-dimer levels may be presented as an important prognostic indicator in older affected ISSNHL individuals.

Hybrid bismuth oxide-graphine oxide nanomaterials improve the signal-to-noise response of small molecules analyzed by matrix assisted laser desorption ionization-time-of-flight mass spectrometry.

Matrix-assisted laser desorption ionization (MALDI) has received increasing attention for the analysis small molecules. Nanomaterials are frequently used as the matrix in LDI, and various inorganic materials have been developed, particularly those based on thermally-driven positive DI mechanisms. However, the unwanted detection of alkali metal ion adducts in the positive ion mode can compromise small molecule identification. Here, we report the synthesis and application of a novel hybrid bismuth oxide-graphene oxide (Bi2O3@GO) semiconductor matrix for the analysis of small molecules by LDI-time-of-flight mass spectrometry (TOF-MS) operating in the negative ion mode. The structure of the semiconductor nanomaterial was characterized using conventional methods and its performance for the detection of small molecules (e.g., amino acids, fatty acids, sugars and other small molecules) was compared with traditional DI matrices (e.g., cyano-4-hydroxycinnamic acid, 2,5-dihydroxybenzoic acid, 9-aminoacridine and GO). The results showed that the negative ion LDI-TOF MS of small molecules on Bi2O3@GO were free of matrix-related interferences, and possessed good signal intensity and repeatability. Application of Bi2O3@GO to the quantitative determination of glucose in human serum and soft drinks confirmed that the hybrid matrix could also be applied to complex samples. Conclusions drawn from the experimental results, computational chemistry calculations, and previous studies, suggesting that interfacial photogenerated thermal electron transfer and capture are key processes in the LDI mechanism.

Corrigendum: Evaluation of ferritin and TfR level in plasma neural-derived exosomes as potential markers of Parkinson's disease.

[This corrects the article DOI: 10.3389/fnagi.2023.1216905.].

Potential Zoning of Construction Land Consolidation in the Loess Plateau Based on the Evolution of Human-Land Relationship.

Towns serve as the basic unit of implementation for comprehensive land consolidation and rehabilitation. The utilization of scaling law can provide a new perspective for construction land consolidation. From two perspectives of the town hierarchic system and the growth of a single town, this research applies the Rank-Size Rule and Allometric Scaling Law to analyze the scale structure, hierarchy and allometric scaling evolution relationship of population and construction land in the Loess Plateau at the town scale in 2000, 2010, and 2017. Furthermore, the consolidation potential of construction land is divided into five zones and puts forward recommendations for the comprehensive consolidation of the construction land. The results indicate: (1) The majority of towns have small or medium populations and 62% of the towns in the study show negative population growth. Geographically, the northern part has a smaller population size compared with the southern part. 96% of the towns show an increasing trend in the quantity of construction land, and the south and north parts of the study area have more construction land compared with the center part. The zone of the Valley Plain has the largest population size, and the zone of the Sandy and Desert Area has the largest quantity of construction land. (2) The rank-size distributions of both population and construction land comply with the power-law relation. The population hierarchy has changed from equilibrium to concentration, while the hierarchy of construction land shows an opposite pattern. So, the whole town hierarchic system of the Loess Plateau is gradually tending to the optimal distribution, which is the town hierarchic system gradually forming an ideal sequence structure. (3) The population-construction land relationship obeys the allometric scaling law, and the major allometric type is positive allometry. The human-land relationship tends to be coordinated, and the town system tends to be reasonable. The allometric scaling coefficient is not robust in different geographical areas, especially in Irrigated Agricultural Areas. Furthermore, 90% of the towns have weak coordination of human-land relationships, and 60% of the towns have a relatively faster growth rate of construction land than the relative growth (decline) rate of population. (4) The consolidation potential of construction land is divided into five types. High Consolidation Potential Area concentrates in the Eastern Loess Plateau, while Medium and Low Consolidation Potential Area concentrically distribute in the Western Loess Plateau. The Human-land Coordination Area has a small number and scattered spatial distribution. The land use of towns that are concentrated around prefecture-level cities or with unique resources is not intensive enough. The zoning of construction land consolidation potential based on the results of the allometric scale is in line with reality, and local governments should make use of the characteristics and trends of the town system to formulate planning schemes to promote the integrated development of urban and rural areas.

Determinants for a low dose of alteplase and its relationship to a lower intracerebral bleeding risk in acute ischemic stroke.

Background: Factors for the utilization of intravenous thrombolysis with a low-dose of alteplase (0.6mg/kg) and whether the low-dose of alteplase could reduce the risk of intracerebral bleeding in acute ischemic stroke (AIS) remains uncertain. Aims: We aimed to investigate determinants for the utilization of intravenous thrombolysis with a low-dose of alteplase. We further assessed the association between the low-dose of alteplase and the intracerebral bleeding risk in AIS patients. Method: We included AIS patients who received intravenous thrombolysis using alteplase in this multicenter retrospective observational study. We investigated the association between baseline characteristics and the utilization of a low-dose of alteplase to identify determinants. We assessed the association of the low-dose of alteplase with the risk of symptomatic intracranial hemorrhage (sICH) using a multivariable logistic regression model. We further compared the rate of sICH and any ICH in patients in the low-dose group to those in the standard-dose group, using propensity score-matching data. Results: A total of 506 AIS patients were included in this study. The mean age was 67 (interquartile range [IQR] 59-75), and 178 (35.2%) were women. A total of 96 patients were treated with the low-dose. Age (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 1.00 -1.04, p = 0.042), having a previous ischemic stroke (adjusted OR 2.01, 95%CI 1.11 - 3.64 p = 0.021) and increasing baseline systolic blood pressure (adjusted OR 1.12, 95%CI 1.00 - 1.26, p = 0.049) were determinants for the utilization of the low-dose. Multivariable logistic regression analysis showed that the low-dose was significantly associated with a reduced risk of sICH (adjusted OR 0.13, 95%CI 0.03 - 0.62, p = 0.01). Propensity score analysis showed that the rate of sICH was significantly lower in the low-dose group compared to standard-dose group (2 [2.3%] vs 10 [11.4%], p = 0.032). There was no significant difference in the rate of any ICH between two groups (14 [15.9%] vs 18 [20.5%], p = 0.434). Conclusions: Patients with increasing age, a higher baseline systolic blood pressure, and previous ischemic stroke were at a higher odd of receiving a low-dose of alteplase. The low-dose was associated with a lower risk of developing symptomatic intracranial hemorrhage.

[Chiral separation of new chiral insecticide pyraquinil isomers and establishment of analytical methods in vegetables].

Pyraquinil (Pyr), with a new skeleton of pyrazolo[1,5-a]quinazoline fused heterocycle, is a new chiral insecticide independently developed by South China Agricultural University in 2017. In previous studies, we found that pyraquinil can effectively control the lepidopteran pest population on cruciferous crops. Remarkably, the insecticidal activity of pyraquinil was 64-fold better than that of fipronil against the fipronil-resistant Plutella xylostella field population. Pesticides with new active mechanisms should be developed in the future to cope with the development of resistance to Plutella xylostella. Therefore, pyraquinil with new active sites has the potential to be the main rotation variety for the control of Plutella xylostella. Thus, pyraquinil has a broad prospect for application in the future. However, a chiral separation and analysis method for pyraquinil and oxidation products using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has not been established yet. Based on the physical and chemical properties of the new chiral pesticide pyraquinil, we screened chiral chromatographic columns and optimized the mobile phase ratio in this study. The separation and analysis methods for pyraquinil were developed based on the QuEChERS (quick, easy, cheap, effective, rugged, safe) system. Simultaneously, we also established oxidation metabolites. These methods were used for the simultaneous determination of the chiral isomers of pyraquinil and oxidation products in pakchoi (Brassica rapa ssp. chinensis L.) and water spinach (Ipomoea aquatica Forsk) via HPLC-MS/MS. The Chiral INC column (250 mm×4.6 mm, 5 µm) was used for separation. Ammonium formate aqueous solution (2 mmol/L) and acetonitrile were used as the mobile phases. The column temperature was 28 ℃. The injection volume was 1 µL, and the flow rate was 0.5 mL/min. MS analysis was performed using an electrospray ionization source in the negative and multiple reaction monitoring modes. We found that under the optimized conditions, the resolution of the four isomers of pyraquinil were 1.63, 2.83, and 1.74, respectively, and the resolution of the isomers of the pyraquinil oxidation product was 5.82, which achieved baseline separation. Then, the absolute configuration and peak order of pyraquinil and oxidation product isomers were determined by derivatization. The order of the peaks was RS-Pyr, SS-Pyr, RR-Pyr, SR-Pyr, S-Pyr+O, and R-Pyr+O. The purification conditions of sample pretreatment were optimized; 1 g (0.835 g MgSO4+0.150 g PSA+0.015 g GCB) was determined to be the optimal purification agent; and the average recoveries ranged from 80% to 110%. The chiral isomers of pyraquinil and oxidation products showed good linearity in the concentration range of 1.25 to 1250 µg/L and 2.5 to 2500 µg/L respectively. The square of the regression coefficient of the linear equation (R2) was greater than 0.99. The matrix effects of the pyraquinil and oxidation product isomers in pakchoi ranged from 6.1 to 30.6. In the water spinach, the matrix effect of the pyraquinil and oxidation product isomers were in the range of 0.7-26.8. The average recoveries of pyraquinil isomer at three spiked levels of 0.25, 5, 100 µg/kg in samples (pakchoi and water spinach) ranged from 90.2% to 110.6%. The oxidation product isomer average recoveries in samples (pakchoi and water spinach) spiked with 0.5, 10, 200 µg/kg ranged from 72.6% to 100.1%. Further, the relative standard deviations (RSDs) were 0.5%-9.4%. In water spinach, the intra-day and inter-day repeatability RSDs ranged from 0.5% to 8.7% and 1.0%to 8.6%, respectively. In pakchoi, the intra-day and inter-day repeatability RSDs ranged from 0.6% to 9.4% and 1.0% to 7.6%, respectively. These results indicate that the proposed method has satisfactory sensitivity, accuracy, and precision. This study can provide analytic technology for a novel chiral pesticide for environmental behavior studies, quality control, and pharmacodynamics evaluation, as well as significant technical support for the development and application of new pesticides.

Rosmarinic Acid Inhibits Mitochondrial Damage by Alleviating Unfolded Protein Response.

Mitochondria are essential organelles that perform important roles in cell biologies such as ATP synthesis, metabolic regulation, immunomodulatory, and apoptosis. Parkinson's disease (PD) is connected with mitochondrial neuronal damage related to mitochondrial unfolded protein response (mtUPR). Rosmarinic acid (RA) is a naturally occurring hydroxylated polyphenolic chemical found in the Boraginaceae and the Labiatae subfamily Nepetoideae. This study looked into RA's protective effect against mitochondrial loss in the substantia nigra (SN) caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the underlying mechanism associated with the mtUPR. Pretreatment with RA reduced motor impairments and dopaminergic neuronal degeneration in the SN of a mouse model injected with MPTP. Pretreatment of SH-SY5Y cells from cell viability loss, morphological damage, and oxidative stress. Furthermore, RA pre-injection suppressed MPTP-induced mtUPR, lowered the expression of HSPA9, HSPE1, CLPP, LONP1, and SIRT 4, and protected the MPTP-mice and SH-SY5Y cells from mitochondrial failure. These findings imply that RA can prevent Parkinson's disease by preventing mitochondrial damage in dopaminergic neurons in Parkinson's disease via alleviating mitochondrial unfolded protein response.

Changes in Corporate Social Responsibility Efficiency in Chinese Food Industry Brought by COVID-19 Pandemic-A Study With the Super-Efficiency DEA-Malmquist-Tobit Model.

Coronavirus disease 2019 (COVID-19) has brought about a significant and far-reaching impact on the world's business environment, corporations, and individuals. In the face of the general shortage of funds caused by the pandemic, assuming corporate social responsibility (CSR) is a problem for every enterprise manager. In the recent years, as corporate social responsibility (CSR) has become a hot topic globally, many enterprises have chosen to incorporate social responsibility into their development strategies. The food industry is a basic industry related to people's livelihood, especially in the pandemic. Its social responsibility efficiency deserves our attention. This article takes 17 sample enterprises whose CSR performance between 2012 and 2020 in China and reports are above the industry level as examples. Constructing the super-efficiency data envelopment analysis (DEA)-Malmquist-Tobit model explores the social responsibility efficiency of these enterprises. It analyzes the pandemic's impact on CSR efficiency. The results show that COVID-19 has promoted the social responsibility efficiency of the sample enterprises in the food industry. Besides, the level of technical efficiency and technological progress in the food industry is relatively high. Still, most enterprises are below the industry's average level. Before the outbreak of the pandemic, the size of enterprises is the key factor affecting the efficiency of CSR. After then, the listing years of enterprises then become the key factor.

Visualizing the spatial distribution of metabolites in Clausena lansium (Lour.) skeels using matrix-assisted laser desorption/ionization mass spectrometry imaging.

Clausena lansium (Lour.) Skeels (Rutaceae) is a natural bioactive plant. Its roots, stems, leaves, and seeds are widely used in Chinese traditional and folk medicine. Although the characterization and functional analysis of bioactive components in Clausena lansium (Lour.) Skeels has been widely reported, the spatial distribution of these compounds within the main plant tissues remains undefined. Here, we adopted matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to reveal the spatial distribution of active alkaloids, coumarins, sugars and organic acids in C. lansium. Using a combined wet and dry matrix covering method to enhance sensitivity, we detected alkaloids throughout the fruit including 3-methylcarbazole and murrastinine which were especially rich in the kernel tissues but were restricted to the stem xylem and medulla and in the leaf epidermal region. Interestingly, murrayanine and heptaphylline were mainly found in pulp tissues with very low content in the stems and leaves while girinimbine was only distributed within the outer kernel skin. Coumarins were mainly distributed in the fruit pericarp and leaf vein tissues but with no clear spatial specificity in stems. Lastly, hexoses were mainly evident in the fruit pulp, although sucrose was also found in the pericarp, pulp, and pulp fibers with citric acid being distributed throughout the fruit. The accurate spatial and chemical information obtained provides new insights into the specific accumulation of metabolites in individual tissues.