NeuroD1 administration ameliorated neuroinflammation and boosted neurogenesis in a mouse model of subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) causes significant long-term neurocognitive dysfunction, which is associated with hippocampal neuroinflammation. Growing evidences have shown that astrocytes played a significant role in mediating neuroinflammation. Recently, in vivo reprogramming of astrocytes to neurons by NeuroD1 or PTBP1 administration has generated a lot of interests and controversies. While the debates centered on the source of neurogenesis, no attention has been paid to the changes of the astrocytes-mediated neuroinflammation and its impact on endogenous neurogenesis after NeuroD1 administration. METHODS: 80 adult male C57BL/6 mice were used in this study. SAH was established by pre-chiasmatic injection of 100 µl blood. AAV-NeuroD1-GFP virus was injected to the hippocampus 3 day post-SAH. Neurocognitive function, brain water content, in vivo electrophysiology, Golgi staining, western blot and immunofluorescent staining were assessed at day 14 post-virus injection. RESULTS: NeuroD1 administration markedly attenuated reactive astrocytes-mediated neuroinflammation by reversing neurotoxic A1 astrocytes transformation, decreasing the secretion of neuroinflammatory cytokines, and reducing the activation of harmful microglia. NeuroD1 treatment significantly reversed the brain-blood barrier impairment and promoted the release of neurotrophic factors pleiotrophin (PTN), all of which contributed to the improvement of cellular microenvironment and made it more suitable for neurogenesis. Interestingly, besides neurogenesis in the hippocampus from cells transfected with NeuroD1 at the early phase of SAH, NeuroD1 administration significantly boosted the endogenous neurogenesis at the late phase of SAH, which likely benefited from the improvement of the neuroinflammatory microenvironment. Functionally, NeuroD1 treatment significantly alleviated neurocognitive dysfunction impaired by SAH. CONCLUSIONS: NeuroD1 significantly promoted neurofunctional recovery by attenuating reactive astrocytes-mediated neuroinflammation and boosting neurogenesis decimated by SAH. Specifically, NeuroD1 efficiently converted transfected cells, most likely astrocytes, to neurons at the early phase of SAH, suppressed astrocytes-mediated neuroinflammation and boosted endogenous neurogenesis at the late phase of SAH.

Determination of carbonate content in barite ore by headspace gas chromatography.

This paper reports a method for determining the carbonate content in barite ore using headspace gas chromatography. Based on the acidification reaction, the carbonate in the barite ore was converted to CO2 in a closed headspace vial. When the carbonate content was significant, the pressure caused changes in the CO2 and O2 signals and affected the measurement accuracy. It was found that carbonate content is proportional to the intensity ratio of the CO2 to O2 signals. Thus, the carbonate content in barite ore can be measured indirectly using a theoretical model. The results showed that the carbonate in 3 g of barite ore sample with a particle size of 74 µm could react completely with a hydrochloric acid solution (2 mol/L) at 65°C for 5 min. The method described herein had good precision (relative standard deviation < 4.14%) and accuracy (relative differences < 6.12%). Further, the limit of quantification was 0.07 mol/L. Owing to its simplicity and speed, this method can be used for the batch determination of carbonate content in barite ore.

Omega-3 fatty acids impair miR-1-3p-dependent Notch3 down-regulation and alleviate sepsis-induced intestinal injury.

BACKGROUND: Sepsis is a troublesome syndrome that can cause intestinal injury and even high mortality rates. Omega-3 fatty acids (FAs) are known to protect against intestinal damage. Accordingly, the current study set out to explore if omega-3 FAs could affect sepsis-induced intestinal injury with the involvement of the microRNA (miR)-1-3p/Notch3-Smad axis. METHODS: First, cecal ligation and perforation (CLP) was performed to establish septic mouse models in C57BL/6J mice, and mouse intestinal epithelial MODE-K cells were induced by lipopolysaccharide (LPS) to establish sepsis cell models. The CLP-induced septic mice or LPS-exposed cells were subjected to treatment with Omega-3 FAs and activin (Smad signaling activator), miR-1-3p inhibitor and over-expressed/short hairpin RNA (oe-/sh)-Notch3 to explore their roles in inflammation, intestinal oxidative stress and cell apoptosis. A dual-luciferase reporter gene assay was further performed to verify the regulatory relationship between miR-1-3p and Notch3. RESULTS: Omega-3 FAs inhibited CLP-induced intestinal injury and ameliorated LPS-induced intestinal epithelial cell injury by down-regulating miR-1-3p, as evidenced by decreased levels of tumor necrosis factor-α, interleukin-1ß (IL-1ß) and IL-6, in addition to diminished levels of reactive oxygen species, malondialdehyde levels and superoxide dismutase activity. Furthermore, miR-1-3p could down-regulate Notch3, which inactivated the Smad pathway. CONCLUSION: Collectively, our findings indicated that omega-3 FAs elevate the expression of Notch3 by down-regulating miR-1-3p, and then blocking the Smad pathway to alleviate intestinal epithelial inflammation and oxidative stress injury caused by sepsis.

Efficient construction of diverse spiro[indoline-3,4'-pyrrolo[3,4-b]pyridines] via [3 + 3] cycloaddition of MBH carbonates of isatins with ß-enamino maleimides.

An efficient method to construct unique spiro[indoline-3,4'-pyrrolo[3,4-b]pyridines] was successfully developed via a DABCO promoted formal [3 + 3] cycloaddition reaction of MBH carbonates of isatins with ß-enamino maleimides in acetonitrile at room temperature. This reaction afforded multifunctionalized spiro[indoline-3,4'-pyrrolo[3,4-b]pyridines] and spiro[dipyrrolo[3,4-b:3',4'-e]pyridine-8,3'-indolines] in good yields and with lower diastereoselectivity. The relative configuration of the two diasteromers of the spiro compounds was clearly elucidated by the determination of eight single crystal structures.

Significant contributions of combustion-related NH3 and non-fossil fuel NOx to elevation of nitrogen deposition in southwestern China over past five decades.

Anthropogenic nitrogen (N) emissions and deposition have been increasing over past decades. However, spatiotemporal variations of N deposition levels and major sources remain unclear in many regions, which hinders making strategies of emission mitigation and evaluating effects of elevated N deposition. By investigating moss N contents and δ15 N values in southwestern (SW) China in 1954-1964, 1970-1994, and 2005-2015, we reconstructed fluxes and source contributions of atmospheric ammonium ( NH 4 + ) and nitrate ( NO 3 - ) deposition and evaluated their historical changes. For urban and non-urban sites, averaged moss N contents did not differ between 1954-1964 and 1970-1994 (1.2%-1.3%) but increased distinctly in 2005-2015 (1.6%-2.3%), and averaged moss δ15 N values decreased from +0.4‰ to +3.3‰ in 1954-1964 to -1.9‰ to -0.7‰ in 1974-1990, and to -4.8‰ to -3.6‰ in 2005-2015. Based on quantitative estimations, N deposition levels from the 1950s to the 2000s did not change in the earlier 20 years but were elevated substantially in the later 30 years. Moreover, the elevation of NH 4 + deposition (by 12.2 kg-N/ha/year at urban sites and 4.6 kg-N/ha/year at non-urban sties) was higher than that of NO 3 - deposition (by 6.0 and 2.9 kg-N/ha/year, respectively) in the later 30 years. This caused a shifted dominance from NO 3 - to NH 4 + in N deposition. Based on isotope source apportionments, contributions of combustion-related NH3 sources (vehicle exhausts, coal combustion, and biomass burning) to the elevation of NH 4 + deposition were two times higher than volatilization NH3 sources (wastes and fertilizers) in the later 30 years. Meanwhile, non-fossil fuel NOx sources (biomass burning, microbial N cycles) contributed generally more than fossil fuel NOx sources (vehicle exhausts and coal combustion) to the elevation of NO 3 - deposition. These results revealed significant contributions of combustion-related NH3 and non-fossil fuel NOx emissions to the historical elevation of N deposition in SW China, which is useful for emission mitigation and ecological effect evaluation of atmospheric N loading.

Completed absorption of coronavirus disease 2019 (COVID-19) pneumonia lesions: a preliminary study.

Background: Complete absorption of coronavirus disease 2019 (COVID-19) pneumonia in a short term was not detailedly reported. We aimed to investigate the clinical and imaging characteristics of COVID-19 patients with complete absorption of pulmonary lesions. Methods: Retrospectively collected the clinical and chest CT data of 224 patients with COVID-19 in one regional medical center. Currently, pulmonary lesions in 37 patients were completely absorbed. The clinical manifestations, laboratory examinations, and CT findings of lesions for these patients were summarized. Results: Among the 37 patients (age, 39.0 ± 12.4 [14-63] years, 20 males), disease in 36 (97.3%) was mild and in 1 (2.7%) was from severe to mild. The most common symptoms were cough (24/37, 64.9%) and fever (23/37, 62.2%). Their laboratory indicators at admission were usually normal, while the white blood cell and neutrophil count significantly increased at discharge (p = 0.004, p = 0.006). On initial CT images, all patients had various pulmonary lesions (mean involved lobes: 2.8 ± 1.5, range: 1-5; mean involved segments: 6.6 ± 4.3, range: 1-16), which mainly manifested as multiple patchy and or spherical ground glass opacities (GGOs) (30/37, 81.1%) with fibrous strips (19/30, 63.3%) or consolidation (11/30, 36.7%). After treatment, lesions in most (33/37, 89.2%) patients were continuously absorbed. At discharge, previous lesions were mostly absorbed in 11 patients (11/37, 29.7%), the main residues were GGOs (24/37, 64.9%), followed by fibrous strips (13/37, 35.1%). On the latest CT, all the pulmonary lesions were completely absorbed, the duration of lesions was 31.6 ± 11.4 days (range: 5-50 days). Conclusion: The pulmonary lesions in some mild COVID-19 patients (generally with normal laboratory indicators at admission, GGOs as the main manifestation on initial CT, and representation of continuous absorption after treatment) could be completely absorbed with a mean duration of 31.6 days.

Nitrate is an important nitrogen source for Arctic tundra plants.

Plant nitrogen (N) use is a key component of the N cycle in terrestrial ecosystems. The supply of N to plants affects community species composition and ecosystem processes such as photosynthesis and carbon (C) accumulation. However, the availabilities and relative importance of different N forms to plants are not well understood. While nitrate (NO3-) is a major N form used by plants worldwide, it is discounted as a N source for Arctic tundra plants because of extremely low NO3- concentrations in Arctic tundra soils, undetectable soil nitrification, and plant-tissue NO3- that is typically below detection limits. Here we reexamine NO3- use by tundra plants using a sensitive denitrifier method to analyze plant-tissue NO3- Soil-derived NO3- was detected in tundra plant tissues, and tundra plants took up soil NO3- at comparable rates to plants from relatively NO3--rich ecosystems in other biomes. Nitrate assimilation determined by 15N enrichments of leaf NO3- relative to soil NO3- accounted for 4 to 52% (as estimated by a Bayesian isotope-mixing model) of species-specific total leaf N of Alaskan tundra plants. Our finding that in situ soil NO3- availability for tundra plants is high has important implications for Arctic ecosystems, not only in determining species compositions, but also in determining the loss of N from soils via leaching and denitrification. Plant N uptake and soil N losses can strongly influence C uptake and accumulation in tundra soils. Accordingly, this evidence of NO3- availability in tundra soils is crucial for predicting C storage in tundra.

Development of a risk scoring system for prognostication in HIV-related toxoplasma encephalitis.

BACKGROUND: This study aims to evaluate specific risk factors influencing prognosis of HIV-infected patients with toxoplasma encephalitis (TE) in order to develop a prognostic risk scoring system for them. METHODS: This is a six-center retrospective study of hospitalized HIV/TE patients. Data including six-week mortality after diagnosis, baseline characteristics, clinical features, laboratory tests and radiological characteristics of eligible patients were assimilated for risk model establishing. RESULTS: In this study, the six-week mortality among 94 retrospective cases was 11.7% (11/94). Seven specific risk factors, viz. time from symptom onset to presentation, fever, dizziness, CD4+ T-cell counts, memory deficits, patchy brain lesions, and disorders of consciousness were calculated to be statistically associated with mortality. A criterion value of '9' was selected as the optimal cut-off value of the established model. The AUC of the ROC curve of this scoring model was 0.976 (p < 0.001). The sensitivity and specificity of the risk scoring model was 100.0 and 86.9%, respectively, which were 81.8 and 94.1% of this scoring model in the verification cohort, respectively. CONCLUSIONS: The developed scoring system was established with simple risk factors, which also allows expeditious implementation of accurate prognostication, and appropriate therapeutic interventions in HIV-infected patients with TE.

microRNA-30a inhibits the liver cell proliferation and promotes cell apoptosis through the JAK/STAT signaling pathway by targeting SOCS-1 in rats with sepsis.

Sepsis is a systemic inflammatory response that may be induced by trauma, infection, surgery, and burns. With the aim of discovering novel treatment targets for sepsis, this current study was conducted to investigate the effect and potential mechanism by which microRNA-30a (miR-30a) controls sepsis-induced liver cell proliferation and apoptosis. Rat models of sepsis were established by applying the cecal ligation and puncture (CLP) method to simulate sepsis models. The binding site between miR-30a and suppressor of cytokine signaling protein 1 (SOCS-1) was determined by dual luciferase reporter gene assay. The gain-of-and-loss-of-function experiments were applied to analyze the effects of miR-30a and SOCS-1 on liver cell proliferation and apoptosis of the established sepsis rat models. The expression of miR-30a, SOCS-1, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), Bcl-2 associated X protein (Bax), B cell lymphoma-2 (Bcl-2), toll-like receptor 4 (TLR4), and high-mobility group box 1 (HMGB1), and the extent of JAK2 and STAT3 phosphorylation were all determined. Sepsis led to an elevation of miR-30a and also a decline of SOCS-1 in the liver cells. SOCS-1 was negatively regulated by miR-30a. Upregulated miR-30a and downregulated SOCS-1 increased the expression of JAK2, STAT3, Bax, TLR4, and HMGB1 as well as the extent of JAK2 and STAT3 phosphorylation whereas impeding the expression of SOCS-1 and Bcl-2. More important, either miR-30a elevation or SOCS-1 silencing suppressed liver cell proliferation and also promoted apoptosis. On the contrary, the inhibition of miR-30a exhibited the opposite effects. Altogether, we come to the conclusion that miR-30a inhibited the liver cell proliferation and promoted cell apoptosis by targeting and negatively regulating SOCS-1 via the JAK/STAT signaling pathway in rats with sepsis.

Discrimination of opium from Afghanistan and Myanmar by infrared spectroscopy coupled with machine learning methods.

Afghanistan and Myanmar are two overwhelming opium production places. In this study, rapid and efficient methods for distinguishing opium from Afghanistan and Myanmar were developed using infrared spectroscopy (IR) coupled with multiple machine learning (ML) methods for the first time. A total of 146 authentic opium samples were analyzed by mid-IR (MIR) and near-IR (NIR), within them 116 were used for model training and 30 were used for model validation. Six ML methods, including partial least squares discriminant analysis (PLS-DA), orthogonal PLS-DA (OPLS-DA), k-nearest neighbour (KNN), support vector machine (SVM), random forest (RF), and artificial neural networks (ANNs) were constructed and compared to get the best classification effect. For MIR data, the average of precision, recall and f1-score for all classification models were 1.0. For NIR data, the average of precision, recall and f1-score for different classification models ranged from 0.90 to 0.94. The comparison results of six ML models for MIR and NIR data showed that MIR was more suitable for opium geography classification. Compared with traditional chromatography and mass spectrometry profiling methods, the advantages of MIR are simple, rapid, cost-effective, and environmentally friendly. The developed IR chemical profiling methodology may find wide application in classification of opium from Afghanistan and Myanmar, and also to differentiate them from opium originating from other opium producing countries. This study presented new insights into the application of IR and ML to rapid drug profiling analysis.

Risk factors and prediction model construction for peripherally inserted central catheter-related infections.

Objective: To establish a predictive modeling for the risk of bloodstream infection associated with peripherally inserted central catheter (PICC). Methods: Patients receiving PICC treatment in Shenzhen People's Hospital from June 2020 to December 2020 were retrospectively enrolled and divided into the infection group and the non-infection group according to the presence and absence of PICC-related infections. Then, relevant clinical information of patients was collected and the predictors of PICC-related infection were screened by the least absolute shrinkage and selection operator regression (LASSO) model. Besides, multivariate logistic regression was used to analyze the influencing factors of PICC-related infection, A nomogram was constructed based on the results of the multivariate analysis. Ultimately, a receiver operating characteristic (ROC) curve was plotted to analyze the application value of influencing factors to predict PICC-related infections. Results: A total of 505 patients were included, including 75 patients with PICC-related infections (14.85%). The main pathogen was gram-positive cocci. The predictors screened by LASSO included age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Multivariate logistic regression analysis showed that independent risk factors of infections related to PICC included age >60 years [odds ratio (OR) = 1.722; 95% confidence interval (CI) = 1.312-3.579; P = 0.006], catheter movement (OR = 1.313; 95% CI = 1.119-3.240; P = 0.014), catheter maintenance cycle >7 days (OR = 2.199; 95% CI = 1.677-4.653; P = 0.000), direct insertion (OR = 1.036; 95% CI = 1.019-2.743; P = 0.000), poor immune function (OR = 2.322; 95% CI = 2.012-4.579; P = 0.000), complications (OR = 1.611; 95% CI = 1.133-3.454; P = 0.019), and body temperature ≥37.2 °C before PICC placement (OR = 1.713; 95% CI = 1.172-3.654; P = 0.012). Besides, the area under the ROC curve was 0.889. Conclusion: PICC-related infections are associated with factors such as age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Additionally, the LASSO model is moderately predictive for predicting the occurrence of PICC-related infections.

Ammonium first: natural mosses prefer atmospheric ammonium but vary utilization of dissolved organic nitrogen depending on habitat and nitrogen deposition.

Mosses, among all types of terrestrial vegetation, are excellent scavengers of anthropogenic nitrogen (N), but their utilization of dissolved organic N (DON) and their reliance on atmospheric N remain uncharacterized in natural environments, which obscures their roles in N cycles. Natural (15) N abundance of N sources (nitrate (NO(3)(-)), ammonium (NH(4)(+)) and DON in deposition and soil) for epilithic and terricolous mosses was analyzed at sites with different N depositions at Guiyang, China. Moss NO(3)(-) assimilation was inhibited substantially by the high supply of NH(4)(+) and DON. Therefore, contributions of NH(4)(+) and DON to moss N were partitioned using isotopic mass-balance methods. The N contributions averaged 56% and 46% from atmospheric NH(4)(+), and 44% and 17% from atmospheric DON in epilithic and terricolous mosses, respectively. In terricolous mosses, soil NH(4)(+) and soil DON accounted for 16% and 21% of bulk N, which are higher than current estimations obtained using (15) N-labeling methods. Moreover, anthropogenic NH(4)(+) deposition suppressed utilization of DON and soil N because of the preference of moss for NH(4)(+) under elevated NH(4)(+) deposition. These results underscore the dominance of, and preference for, atmospheric NH(4)(+) in moss N utilization, and highlight the importance of considering DON and soil N sources when estimating moss N sequestration and the impacts of N deposition on mosses.

LPS induces cardiomyocyte injury through calcium-sensing receptor.

Calcium-sensing receptor (CaSR) belongs to the family C of G-protein coupled receptors. We have previously demonstrated that CaSR could induce apoptosis of cultured neonatal rat ventricular cardiomyocytes in simulated ischemia/reperfusion. It remains unknown whether the CaSR has function in lipopolysaccharide (LPS)-induced myocardial injure. The aim of this study was to investigate whether the CaSR plays a role in LPS-induced myocardial injury. Cultured neonatal rat cardiomyocytes were treated with LPS, with or without pretreatment with the CaSR-specific agonist gadolinium chloride (GdCl3) or the CaSR-specific antagonist NPS2390. Release of TNF-α and IL-6 from cardiomyocytes was observed. Levels of malonaldehyde (MDA), lactate dehydrogenase (LDH), and activity of superoxide dismutase (SOD) were measured. In addition, apoptosis of the cardiomyocytes, [Ca(2+)]i and level of CaSR expression were determined. The results showed that LPS increased cardiomyocytes apoptosis, [Ca(2+)]i, MDA, LDH, TNF-α, IL-6 release, and CaSR protein expression. Compared with LPS treatment alone, pretreatment with GdCl3 further increased apoptosis of cardiomyocytes, MDA, LDH, TNF-α, IL-6 release, [Ca(2+)]i, and the expression of the CaSR protein. Conversely, pretreatment with NPS2390 decreased apoptosis of cardiomyocytes, MDA, LDH, TNF-α, IL-6 release, [Ca(2+)]i and the expression of the CaSR protein. These results demonstrate that LPS could induce cardiomyocyte injury. Moreover, LPS-induced cardiomyocyte injury was related to CaSR-mediated cardiomyocytes apoptosis, TNF-α, IL-6 release, and increase of intracellular calcium.

Source oxygen contributions of primary nitrate emitted from biomass burning.

Atmospheric nitrate (NO3-) produced by photochemical oxidation in the atmosphere has high oxygen isotope ratios (δ18O values). Recently, the primary NO3- emitted from combustion sources was found to have much lower δ18O values. However, it is unclear how and to what extents the low δ18O signatures were controlled by major O sources during the primary NO3- formation of combustion processes. Here, we first measured concentrations and δ18O values of NO3- from burning five biomass materials (bb-NO3- and δ18Obb-NO3-, respectively) in China. Distinctly higher concentration levels of the bb-NO3- emissions (42.1 ± 8.1 µmol m-3) than ambient NO3- suggest it is a potential source of atmospheric NO3- pollution. Much lower δ18Obb-NO3- signatures (27.6 ± 2.7 ‰) than ambient NO3- support it as a primary emission source with different O sources and formation mechanism from secondary NO3-. Isotope mass-balance modeling revealed that atmospheric O2 and the biomass O dominated the O of bb-NO3- (53 ± 7 % and 40 ± 4 %, respectively) over the aqueous vapor (7 ± 3 %). Besides, we found increasing δ18Obb-NO3- values with the biomass N contents and relatively lower δ18Obb-NO3- values for biomasses with higher carbon (C) and lower O contents, indicating that biomass C, N, and O contents may influence the source O contributions of the bb-NO3-. This work provides a novel isotope analysis on the O source contribution of the bb-NO3-, which is useful for understanding the formation mechanism of combustion-related NO3- sources and evaluating the primary NO3- emissions.

Geographical classification of opium samples from Myanmar and Afghanistan by NMR profiling and chemometrics.

This study presents a new strategy to discriminate between opium samples obtained from different geographical regions. Nuclear magnetic resonance (NMR) profiling and chemometrics were applied to geographical classification of opium originating from Myanmar and Afghanistan, which are two major opium producing countries in the world. A total of 50 Myanmar and 46 Afghanistan authentic opium samples were analyzed by 1 H-NMR, and the chemical profiles were characterized. Different sample preparation procedures, data processing methods, and chemometrics were compared to obtain the best classification effect. It was found that drying and the addition of buffer solutions were unnecessary for classification purposes; thus, the gum opium samples were extracted directly with CD3 OD, which shortened sample preparation time. A full discrimination between the two geographical origins was achieved by 1 H-NMR profiling and orthogonal partial least squares discriminant analysis. All 30 opium samples were classified correctly by the developed orthogonal partial least squares discriminant analysis model. Compared with traditional chromatography and mass spectrometry profiling methods, the 1 H-NMR profiling method was faster (with instrument analysis time of less than 3 min) and reproducible. This study provides new insights into the applying of NMR profiling and chemometrics to rapid drug profiling analysis.

Clinical and Computed Tomography Features Associated with Multidrug-Resistant Pulmonary Tuberculosis: A Retrospective Study in China.

Purpose: To explore the value of integrating clinical and computed tomography (CT) features to predict multidrug-resistant pulmonary tuberculosis (MDR-PTB). Patients and Methods: The study included 212 patients with MDR-PTB and 180 patients with drug-sensitive pulmonary tuberculosis (DS-PTB) who referred to our institute in China between January 2016 and March 2021. The clinical and CT characteristics were analyzed and compared between both groups. Multivariable logistic regression analysis was performed to identify independent factors that can be used to predict MDR-PTB. Furthermore, 115 patients admitted to another center from January 2019 to January 2022 were included as external validation cohort. Results: For clinical characteristics, five parameters were significantly different between the two groups (all P < 0.05). With regard to CT features, nine parameters were significantly different between the two groups (all P < 0.05). Multivariable logistic regression analysis using the aforementioned differential features showed that male sex, retreated history, longer duration of previous anti-TB treatment, lower CD4+ T lymphocyte count, thick-walled cavity, centrilobular micronodules and tree-in-bud sign, bronchial stenosis, pleural and pericardial thickening were the most effective variations associated with MDR-PTB with an area under the curve (AUC) of 0.849 and accuracy of 78.6%. Furthermore, the external validation cohort that contains 115 patients obtained an AUC of 0.933 and accuracy of 81.7%. Conclusion: MDR-PTB and DS-PTB have different clinical and imaging characteristics. A combined model incorporating these differential features can promptly diagnose MDR-PTB and develop subsequent therapeutic strategies.

Pitfalls and new mechanisms in moss isotope biomonitoring of atmospheric nitrogen deposition.

Moss N isotope (δ(15)N(bulk)) has been used to monitor N deposition, but it remains questionable whether inhibition of nitrate reductase activity (NRA) by reduced dissolved N (RDN) engenders overestimation of RDN in deposition when using moss δ(15)N(bulk). We tested this question by investigation of δ(15)N(bulk) and δ(15)NO(3)(-) in mosses under the dominance of RDN in N depositions of Guiyang, SW China. The δ(15)N(bulk) of mosses on bare rock (-7.9‰) was unable to integrate total dissolved N (TDN) (δ(15)N = -6.3‰), but it reflected δ(15)N-RDN (-7.5‰) exactly. Moreover, δ(15)N-NO(3)(-) in mosses (-1.7‰) resembled that of wet deposition (-1.9‰). These isotopic approximations, together with low isotopic enrichment with moss [NO(3)(-)] variations, suggest the inhibition of moss NRA by RDN. Moreover, isotopic mixing modeling indicated a negligible contribution from NO(3)(-) to moss δ(15)N(bulk) when the RDN/NO(3)(-) reaches 3.8, at which maximum overestimation (21%) of RDN in N deposition can be generated using moss δ(15)N(bulk) as δ(15)N-TDN. Moss δ(15)N-NO(3)(-) can indicate atmospheric NO(3)(-) under distinctly high RDN/NO(3)(-) in deposition, although moss δ(15)N(bulk) can reflect only the RDN therein. These results reveal pitfalls and new mechanisms associated with moss isotope monitoring of N deposition and underscore the importance of biotic N dynamics in biomonitoring studies.

Plant nitrogen-use strategies and their responses to the urban elevation of atmospheric nitrogen deposition in southwestern China.

The elevation of nitrogen (N) deposition by urbanization profoundly impacts the structure and function of surrounding forest ecosystems. Plants are major biomass sinks of external N inputs into forests. Yet, the N-use strategies of forest plants in many areas remain unconstrained in city areas, so their responses and adapting mechanisms to the elevated N deposition are open questions. Here we investigated concentrations and N isotope (δ15N) of total N (TN) and nitrate (NO3-) in leaves and roots of four plant species in subtropical shrubberies and pine forests under N deposition levels of 13 kg-N ha-1 yr-1 and 29 kg-N ha-1 yr-1 at the Guiyang area of southwestern China, respectively. The δ15N differences between plant NO3- and soil NO3- revealed a meager NO3- reduction in leaves but a preferentially high NO3- reduction in roots. δ15N mass-balance analyses between plant TN and soil dissolved N suggested that soil NO3- contributed more than reduced N, and dissolved organic N contributed comparably with ammonium to plant TN, and the study plants preferred NO3- over reduced N. The elevation of N deposition induced root but not leaf NO3- reduction and enhanced the contribution of soil NO3- to plant TN, but plant NO3- preference decreased due to much higher magnitudes of soil NO3- enrichment than plant NO3- utilization. We conclude that plants in subtropical forests of southwestern China preferred NO3- over reduced N, and NO3- was reduced more in roots than in leaves, anthropogenic N pollution enhanced soil NO3- enrichment and plant NO3- utilization but reduced plant NO3- preference.

Effectiveness of perampanel in the treatment of pediatric patients with focal epilepsy and ESES: A single-center retrospective study.

Objective: To investigate the therapeutic effect and influencing factors of perampanel (PER) on electrical status epilepticus during sleep (ESES). Methods: We retrospectively analyzed the clinical data of pediatric patients with focal epilepsy and ESES who were treated at the Epilepsy Center of Shengjing Hospital of China Medical University between January 2016 and March 2022. Changes in the spike wave index (SWI) after 24 weeks of PER add-on treatment were compared. Kaplan‒Meier survival analysis, the log-rank test and multivariate Cox regression analysis were performed. Results: A total of 54 pediatric patients met the inclusion criteria, including 33 males and 21 females. The mean age at the diagnosis of epilepsy was 6.41 ± 2.14 years and at ESES diagnosis was 7.58 ± 2.40 years. The mean ESES duration before add-on PER was 25.31 ± 15.12 months. The mean age of the patients at add-on PER initiation was 9.69 ± 2.12 years. The ESES resolved in 29 children after 6 months of PER add-on treatment, and the response rate was 53.7%. Univariate analysis with the log-rank test showed that the therapeutic effect of PER differed according to the age at ESES diagnosis and ESES duration before add-on PER treatment. Multivariate Cox regression analysis showed that only ESES duration before PER administration was a risk factor for PER treatment failure, and the other factors had no effect on the therapeutic effect. Conclusion: PER add-on treatment has a good therapeutic effect on ESES and can be used as an alternative to corticosteroid and benzodiazepines. The therapeutic effect of PER add-on treatment was not related to the dose. A longer ESES duration results in a worse therapeutic effect. Therefore, more aggressive treatment measures should be implemented for ESES.

Isotopic constraints confirm the significant role of microbial nitrogen oxides emissions from the land and ocean environment.

Nitrogen oxides (NOx, the sum of nitric oxide (NO) and N dioxide (NO2)) emissions and deposition have increased markedly over the past several decades, resulting in many adverse outcomes in both terrestrial and oceanic environments. However, because the microbial NOx emissions have been substantially underestimated on the land and unconstrained in the ocean, the global microbial NOx emissions and their importance relative to the known fossil-fuel NOx emissions remain unclear. Here we complied data on stable N isotopes of nitrate in atmospheric particulates over the land and ocean to ground-truth estimates of NOx emissions worldwide. By considering the N isotope effect of NOx transformations to particulate nitrate combined with dominant NOx emissions in the land (coal combustion, oil combustion, biomass burning and microbial N cycle) and ocean (oil combustion, microbial N cycle), we demonstrated that microbial NOx emissions account for 24 ± 4%, 58 ± 3% and 31 ± 12% in the land, ocean and global environment, respectively. Corresponding amounts of microbial NOx emissions in the land (13.6 ± 4.7 Tg N yr-1), ocean (8.8 ± 1.5 Tg N yr-1) and globe (22.5 ± 4.7 Tg N yr-1) are about 0.5, 1.4 and 0.6 times on average those of fossil-fuel NOx emissions in these sectors. Our findings provide empirical constraints on model predictions, revealing significant contributions of the microbial N cycle to regional NOx emissions into the atmospheric system, which is critical information for mitigating strategies, budgeting N deposition and evaluating the effects of atmospheric NOx loading on the world.