Characterizing microstructural patterns within the cortico-striato-thalamo-cortical circuit in Parkinson's disease.

PURPOSE: Parkinson's disease (PD) involves pathological alterations that include cortical impairments at levels of region and network. However, its microstructural abnormalities remain to be further elucidated via an appropriate diffusion neuroimaging approach. This study aimed to comprehensively demonstrate the microstructural patterns of PD as mapped by diffusion kurtosis imaging (DKI). METHODS: The microstructure of grey matter in both the PD group and the matched healthy control group was quantified by a DKI metric (mean kurtosis). The intergroup difference and classification performance of global microstructural complexity were analyzed in a voxelwise manner and via a machine learning approach, respectively. The patterns of information flows were explored in terms of structural connectivity, network covariance and modular connectivity. RESULTS: Patients with PD exhibited global microstructural impairments that served as an efficient diagnostic indicator. Disrupted structural connections between the striatum and cortices as well as between the thalamus and cortices were widely distributed in the PD group. Aberrant covariance of the striatocortical circuitry and thalamocortical circuitry was observed in patients with PD, who also showed disrupted modular connectivity within the striatum and thalamus as well as across structures of the cortex, striatum and thalamus. CONCLUSION: These findings verified the potential clinical application of DKI for the exploration of microstructural patterns in PD, contributing complementary imaging features that offer a deeper insight into the neurodegenerative process.

Diffusion Kurtosis Imaging in Diagnosing Parkinson's Disease: A Preliminary Comparison Study Between Kurtosis Metric and Radiomic Features.

RATIONALE AND OBJECTIVES: Parkinson's disease (PD) shows small structural changes in nigrostriatal pathways, which can be sensitively captured through diffusion kurtosis imaging (DKI). However, the value of DKI and its radiomic features in the classification performance of PD still need confirmation. This study aimed to compare the diagnostic efficiency of DKI-derived kurtosis metric and its radiomic features with different machine learning models for PD classification. MATERIALS AND METHODS: 75 people with PD and 80 healthy individuals had their brains scanned using DKI. These images were pre-processed and the standard atlas were non-linearly registered to them. With the labels in atlas, different brain regions in nigrostriatal pathways, including the caudate nucleus, putamen, pallidum, thalamus, and substantia nigra, were chosen as the region of interests (ROIs) to warped to the native space to measure the mean kurtosis (MK). Additionally, new radiomic features were developed for comparison. To handle the large amount of data, a statistical method called Z-score normalization and another method called LASSO regression were used to simplify the information. From this, a few most important features were chosen, and a combined score called Radscore was calculated using LASSO regression. For the comprehensive analyses, three different conventional machine learning models were then created: logistic regression (LR), support vector machine (SVM), and random forest (RF). To ensure the models were accurate, a process called 10-fold cross-validation was used, where the data were split into 10 parts for training and testing. RESULTS: Using MK alone, the models achieved good results in correctly identifying PD in the validation set, with LR at 0.90, RF at 0.93, and SVM at 0.90. When the radiomic features were added, the models performed even better, with LR at 0.92, RF at 0.95, and SVM at 0.91. Additionally, a nomogram combining all the information was created to predict the likelihood of someone having PD, which had an AUC of 0.91. CONCLUSION: These findings suggest that the combination of DKI measurements and radiomic features can effectively diagnose PD by providing more detailed information about the brain's condition and the processes involved in the disease.

The effect of matrine and glycyrrhizic acid on porcine reproductive and respiratory syndrome virus in Vitro and in vivo.

Porcine reproductive and respiratory syndrome (PRRS) is endemic worldwide, seriously affecting the development of the pig industry, but vaccines have limited protective effects against PRRSV transmission. The aim of this study was to identify potential anti-PRRSV drugs. We examined the cytotoxicity of seven compounds formulated based on the mass ratio of glycyrrhizic acid to matrine and calculated their inhibition rates against PRRSV in vitro. The results showed that the seven compounds all had direct killing and therapeutic effects on PRRSV, and the compounds inhibited PRRSV replication in a time- and dose-dependent manner. The compound with the strongest anti-PRRSV effect was selected for subsequent in vivo experiments. Pigs were divided into a control group and a medication group for the in vivo evaluation. The results showed that pigs treated with the 4:1 compound had 100% morbidity after PRRSV challenge, and the mortality rate reached 75% on the 8th day of the virus challenge. These results suggest that this compound has no practical anti-PRRSV effect in vivo and can actually accelerate the death of infected pigs. Next, we further analyzed the pigs that exhibited semiprotective effects following vaccination with the compound to determine whether the compound can synergize with the vaccine in vivo. The results indicated that pigs treated with the compound had higher mortality rates and more severe clinical reactions after PRRSV infection (p < 0.05). The levels of proinflammatory cytokines (IL-6, IL-8, IL-1ß, IFN-γ, and TNF-α) were significantly greater in the compound-treated pigs than in the positive control-treated pigs (p < 0.05), and there was no synergistic enhancement with the live attenuated PRRSV vaccine (p < 0.05). The compound enhanced the inflammatory response, prompted the body to produce excessive levels of inflammatory cytokines and caused body damage, preventing a therapeutic effect. In conclusion, the present study revealed that the in vitro effectiveness of these agents does not indicate that they are effective in vivo or useful for developing anti-PRRSV drugs. Our findings also showed that, to identify effective anti-PRRSV drugs, comprehensive drug screening is needed, for compounds with solid anti-inflammatory effects both in vitro and in vivo. Our study may aid in the development of new anti-PRRSV drugs.

Hydrochemical characterization and health risk assessment of different types of water bodies in Fenghuang Mountain Area, Northeast China.

Groundwater, as an essential resource, holds significant importance for human production and livelihoods. With the deterioration of the water environment, the issue of groundwater quality has become an urgent international concern. This study focused on the Fenghuang Mountain Area (FMA) and collected a total of 41 sets of samples including pore groundwater (PGW), fissure groundwater (FGW), karst groundwater (KGW), and river water (RW). Hydrochemical analysis methods were employed to identify the hydrochemical characteristics and controlling factors. The entropy-weighted water quality index (EWQI) and health risk assessment model were utilized to assess the groundwater quality and nitrate health risk, respectively. The results indicated that the dominant anion and cation in both groundwater and surface water in the FMA were HCO3- and Ca2+, respectively, with the main hydrochemical type being HCO3-Ca. Groundwater and surface water in the FMA were primarily controlled by rock weathering process, with ion concentrations influenced mainly by the dissolution of halite, sylvite, carbonates (calcite and dolomite), silicates, and gypsum, as well as by reverse anion exchange process. PGW was significantly affected by agricultural activities, with NO3- concentration closely related to human activities. The water quality of FGW was relatively good, with Class I and Class II water accounting for the highest proportion, reaching 84.62%. The high-value area of EWQI in PGW was influenced by human activities. The impact of nitrate health risk on children was significantly greater than on adults, with FGW having the lowest health risk and PGW having the highest health risk. The research results can provide important guarantees for the rational development and utilization of water resources in the FMA and the sustainable development of the economy in Northeast China.

Exploring the Underlying Mechanisms of Qingxing Granules Treating H1N1 Influenza Based on Network Pharmacology and Experimental Validation.

BACKGROUND: H1N1 is one of the major subtypes of influenza A virus (IAV) that causes seasonal influenza, posing a serious threat to human health. A traditional Chinese medicine combination called Qingxing granules (QX) is utilized clinically to treat epidemic influenza. However, its chemical components are complex, and the potential pharmacological mechanisms are still unknown. METHODS: QX's effective components were gathered from the TCMSP database based on two criteria: drug-likeness (DL ≥ 0.18) and oral bioavailability (OB ≥ 30%). SwissADME was used to predict potential targets of effective components, and Cytoscape was used to create a "Herb-Component-Target" network for QX. In addition, targets associated with H1N1 were gathered from the databases GeneCards, OMIM, and GEO. Targets associated with autophagy were retrieved from the KEGG, HAMdb, and HADb databases. Intersection targets for QX, H1N1 influenza, and autophagy were identified using Venn diagrams. Afterward, key targets were screened using Cytoscape's protein-protein interaction networks built using the database STRING. Biological functions and signaling pathways of overlapping targets were observed through GO analysis and KEGG enrichment analysis. The main chemical components of QX were determined by high-performance liquid chromatography (HPLC), followed by molecular docking. Finally, the mechanism of QX in treating H1N1 was validated through animal experiments. RESULTS: A total of 786 potential targets and 91 effective components of QX were identified. There were 5420 targets related to H1N1 and 821 autophagy-related targets. The intersection of all targets of QX, H1N1, and autophagy yielded 75 intersecting targets. Ultimately, 10 core targets were selected: BCL2, CASP3, NFKB1, MTOR, JUN, TNF, HSP90AA1, EGFR, HIF1A, and MAPK3. Identification of the main chemical components of QX by HPLC resulted in the separation of seven marker ingredients within 195 min, which are amygdalin, puerarin, baicalin, phillyrin, wogonoside, baicalein, and wogonin. Molecular docking results showed that BCL2, CASP3, NFKB1, and MTOR could bind well with the compounds. In animal studies, QX reduced the degenerative alterations in the lung tissue of H1N1-infected mice by upregulating the expression of p-mTOR/mTOR and p62 and downregulating the expression of LC3, which inhibited autophagy. CONCLUSIONS: According to this study's network pharmacology analysis and experimental confirmation, QX may be able to treat H1N1 infection by regulating autophagy, lowering the expression of LC3, and increasing the expression of p62 and p-mTOR/mTOR.

Rapid detection of Mycobacterium tuberculosis based on cyp141 via real-time fluorescence loop-mediated isothermal amplification (cyp141-RealAmp).

Background: The rapid detection of Mycobacterium tuberculosis (MTB) is essential for controlling tuberculosis. Methods We designed a portable thermocycler-based real-time fluorescence loop-mediated isothermal amplification assay (cyp141-RealAmp) using six oligonucleotide primers derived from cyp141 to detect MTB. A combined number of 213 sputum samples (169 obtained from clinically diagnosed cases of pulmonary TB and 44 from a control group without tuberculosis) underwent Acid-fast bacillus (AFB) smear, culture, Xpert MTB/RIF assays, and cyp141-RealAmp assay. Results: By targeting MTB cyp141, this technique could detect as low as 10 copies/reaction within 30 min, and it was successfully rejected by other mycobacteria and other bacterial species tested. Of the 169 patients, there was no statistical difference between the detection rate of cyp141-RealAmp (92.90%, 95% CI: 89.03-96.07) and that of Xpert MTB/RIF (94.67%, 95% CI: 91.28-98.06) (P > 0.05), but both were statistically higher than that of culture (65.68%, 95% CI: 58.52-72.84) (P< 0.05) and AFB (57.40%, 95% CI: 49.94-64.86) (P< 0.05). Both cyp141-RealAmp and Xpert MTB/RIF had a specificity of 100%. Furthermore, a high concordance between cyp141-RealAmp and Xpert MTB/RIF was found (Kappa = 0.89). Conclusion: The cyp141-RealAmp assay was shown to be effective, responsive, and accurate in this study. This method offers a prospective strategy for the speedy and precise detection of MTB.

The multi-kinase inhibitor CG-806 exerts anti-cancer activity against acute myeloid leukemia by co-targeting FLT3, BTK, and aurora kinases.

Despite the development of several Fms-like tyrosine kinase 3 (FLT3) inhibitors that have improved outcomes in patients with FLT3-mutant acute myeloid leukemia (AML), drug resistance is frequently observed, which may be associated with the activation of additional pro-survival pathways, such as those regulated by BTK, aurora kinases (AuroK), and potentially others, in addition to acquired tyrosine kinase domain (TKD) mutations of FLT3 gene. FLT3 may not always be a driver mutation. We evaluated the anti-leukemia efficacy of the novel multi-kinase inhibitor CG-806, which targets FLT3 and other kinases, to circumvent drug resistance and target FLT3 wild-type (WT) cells. The anti-leukemia activity of CG-806 was investigated by measuring apoptosis induction and analyzing the cell cycle using flow cytometry in vitro. CG-806 demonstrated superior anti-leukemia efficacy compared to commercially available FLT3 inhibitors, both in vitro and in vivo, regardless of FLT3 mutational status. The mechanism of action of CG-806 may involve its broad inhibitory profile against FLT3, BTK, and AuroK. In FLT3 mutant cells, CG-806 induced G1 phase blockage, whereas in FLT3 WT cells, it resulted in G2/M phase arrest. Targeting FLT3 and Bcl-2 and/or Mcl-1 simultaneously results in a synergistic pro-apoptotic effect in FLT3 mutant leukemia cells. The results of this study suggest that CG-806 is a promising multi-kinase inhibitor with anti-leukemic efficacy regardless of FLT3 mutational status. A phase 1 clinical trial of CG-806 for the treatment of AML has been initiated (NCT04477291).Key pointsThe multi-kinase inhibitor CG-806 exerts superior anti-leukemic activity in AML, regardless of its FLT3 status.CG-806 triggered G1 arrest in FLT3 mutated cells and G2/M arrest in FLT3 WT cells through the suppression of FLT3/BTK and aurora kinases.Concomitantly targeting FLT3 and Bcl-2 and/or Mcl-1 exerted synergistic pro-apoptotic effects on both FLT3 WT and mutated AML cells.

Antiviral activity and underlying mechanisms of baicalin against porcine reproductive and respiratory syndrome virus in vitro.

Porcine reproductive and respiratory syndrome (PRRS) is a major challenge for the global swine industry, causing huge economic losses worldwide. To date, there are no effective measures to prevent and control the spread of PRRS virus (PRRSV). Baicalin (BA) is a natural flavonoid with various pharmacological effects, including antiviral, anti-inflammatory, antioxidant and immunomodulatory. Here, we demonstrate that BA exhibits potent anti-PRRSV activity in vitro, BA concentrations in the range of 5-20 µg/mL significantly inhibited PRRSV infection in a dose-dependent manner and were independent of PRRSV strain. Mechanistically, BA inhibited PRRSV replication by directly interacting with virions, thereby affecting multiple stages of the virus life cycle. Meanwhile, the preventive effect of BA on PRRSV could be realized by inhibiting CD151 and CD163 expression. Furthermore, BA reduced the PRRSV-induced expression of PAMs cytokines (IFN-α, IL-6, IL-8, and TNF-α), suggesting that BA-induced antiviral cytokines may help BA inhibit PRRSV infection. Taken together, BA can be used as an inhibitor of PRRSV infection in vitro, which provides a theoretical basis for the clinical application of BA and the prevention and control of PRRSV infection, which is worthy of further in vivo studies in swine.

Grass carp (Ctenopharyngodon idella) NIK up-regulates the expression of IL-8 by activating the NF-κB canonical pathway.

NIK (NF-κB inducing kinase) belongs to the mitogen-activated protein kinase family, which activates NF-κB and plays a vital role in immunology, inflammation, apoptosis, and a series of pathological responses. In NF-κB noncanonical pathway, NIK and IKKα have been often studied in mammals and zebrafish. However, few have explored the relationship between NIK and other subunits of the IKK complex. As a classic kinase in the NF-κB canonical pathway, IKKß has never been researched with NIK in fish. In this paper, the full-length cDNA sequence of grass carp (Ctenopharyngodon idella) NIK (CiNIK) was first cloned and identified. The expression level of CiNIK in grass carp cells was increased under GCRV stimuli. Under the stimulation of GCRV, poly (I:C), and LPS, the expression of NIK in various tissues of grass carp was also increased. This suggests that CiNIK responds to viral stimuli. To study the relationship between CiNIK and CiIKKß, we co-transfected CiNIK-FLAG and CiIKKB-GFP into grass carp cells in coimmunoprecipitation and immunofluorescence experiments. The results revealed that CiNIK interacts with CiIKKß. Besides, the degree of autophosphorylation of CiNIK was enhanced under poly (I:C) stimulation. CiIKKß was phosphorylated by CiNIK and then activated the activity of p65. The activity change of p65 indicates that NF-κB downstream inflammatory genes will be functioning. CiNIK or CiIKKß up-regulated the expression of IL-8. It got higher when CiNIK and CiIKKß coexisted. This paper revealed that NF-κB canonical pathway and noncanonical pathway are not completely separated in generating benefits.

NtHD9 modulates plant salt tolerance by regulating the formation of glandular trichome heads in Nicotiana tabacum.

Salt stress is one of the main abiotic factor affecting plant growth. We have previously identified a key gene (NtHD9) in Nicotiana tabacum L. that positively regulates the formation of long glandular trichomes (LGTs). Here, we verified that both abiotic stress (aphids, drought and salt stress) could restore the phenotype lacking LGTs in NtHD9-knockout (NtHD9-KO) plants. The abiotic stress response assays indicated that NtHD9 is highly sensitive to salt stress. Compared with cultivated tobacco "K326" (CK) plants, NtHD9-overexpressing (NtHD9-OE) plants with more LGTs exhibited stronger salt tolerance, whereas NtHD9-KO with no LGTs showed weaker tolerance to salt. The densities and sizes of the glandular heads gradually increased with increasing NaCl concentrations in NtHD9-KO plants. Mineral element determination showed that leaves and trichomes of NtHD9-OE plants accumulated less Na+ but had higher K+ contents under salt stress, thus maintaining ion homeostasis in plants, which could contribute to a robust photosynthetic and antioxidant system under salt stress. Therefore, NtHD9-OE plants maintained a larger leaf area and root length under high-salt conditions than CK and NtHD9-KO plants. We verified that NtHD9 could individually interact with NtHD5, NtHD7, NtHD12, and NtJAZ10 proteins. Salt stress led to an increase in jasmonic acid (JA) levels and activated the expression of NtHDs while inhibiting the expression of NtJAZ. This study suggests that the glandular heads play an important role in plant resistance to salt stress. The activation of JA signaling leading to JAZ protein degradation may be key factors regulating the glandular heads development under salt stress.

Knowledge, attitude and practice on ovarian reserve function among women of childbearing age: a prospective cross-sectional study in Chongqing and surrounding regions.

OBJECTIVES: To evaluate the knowledge, attitudes and practice (KAP) on ovarian reserve function among women of childbearing age in Chongqing and surrounding regions, China. DESIGN: Cross-sectional study. SETTING: Chongqing and surrounding regions, China. PARTICIPANTS: Women of childbearing age (18-48 years) by convenience sampling. PRIMARY AND SECONDARY OUTCOME MEASURES: The demographic characteristics of the respondents and their KAP on ovarian reserve function were collected by administering 38-item questionnaires. RESULTS: A total of 510 valid questionnaires were collected. The mean knowledge score of all respondents was 7.56±2.03 (possible range: 0-10), the mean attitude score was 29.12±3.98 (possible range: 8-40) and the mean practice score was 23.45±3.58 (possible range: 6-30). The multivariable analysis showed knowledge level (OR 1.175, 95% CI 1.049 to 1.317, p=0.002), attitude level (OR 1.249, 95% CI 1.167 to 1.337, p<0.001) and eating habits (self-cooked vs eating out, OR 1.958, 95% CI 1.201 to 3.190, p=0.007) were independently associated with better practice level. The structural equation modelling analysis showed that knowledge had a direct influence on attitude (ß=0.487, p=0.030) and practice (ß=0.312, p=0.012) and an indirect influence on practice (ß=0.213, p=0.016). Attitude had a direct influence on practice (ß=0.438, p=0.007). The total influence of knowledge on practice was significant (ß=0.525, p=0.012). CONCLUSIONS: The women living in Chongqing and surrounding regions had good knowledge, moderate attitude and good practice towards ovarian reserve function. The knowledge aspect can be further improved by education, which in turn might also improve practice among women of childbearing age.

CT-based radiomics models predict spontaneous intracerebral hemorrhage expansion and are comparable with CT angiography spot sign.

Background and purpose: This study aimed to investigate the efficacy of radiomics, based on non-contrast computed tomography (NCCT) and computed tomography angiography (CTA) images, in predicting early hematoma expansion (HE) in patients with spontaneous intracerebral hemorrhage (SICH). Additionally, the predictive performance of these models was compared with that of the established CTA spot sign. Materials and methods: A retrospective analysis was conducted using CT images from 182 patients with SICH. Data from the patients were divided into a training set (145 cases) and a testing set (37 cases) using random stratified sampling. Two radiomics models were constructed by combining quantitative features extracted from NCCT images (the NCCT model) and CTA images (the CTA model) using a logistic regression (LR) classifier. Additionally, a univariate LR model based on the CTA spot sign (the spot sign model) was established. The predictive performance of the two radiomics models and the spot sign model was compared according to the area under the receiver operating characteristic (ROC) curve (AUC). Results: For the training set, the AUCs of the NCCT, CTA, and spot sign models were 0.938, 0.904, and 0.726, respectively. Both the NCCT and CTA models demonstrated superior predictive performance compared to the spot sign model (all P < 0.001), with the performance of the two radiomics models being comparable (P = 0.068). For the testing set, the AUCs of the NCCT, CTA, and spot sign models were 0.925, 0.873, and 0.720, respectively, with only the NCCT model exhibiting significantly greater predictive value than the spot sign model (P = 0.041). Conclusion: Radiomics models based on NCCT and CTA images effectively predicted HE in patients with SICH. The predictive performances of the NCCT and CTA models were similar, with the NCCT model outperforming the spot sign model. These findings suggest that this approach has the potential to reduce the need for CTA examinations, thereby reducing radiation exposure and the use of contrast agents in future practice for the purpose of predicting hematoma expansion.

Early endoscopic management of an infected acute necrotic collection misdiagnosed as a pancreatic pseudocyst: A case report.

BACKGROUND: Infected acute necrotic collection (ANC) is a fatal complication of acute pancreatitis with substantial morbidity and mortality. Drainage plays an exceedingly important role as the first step in invasive intervention for infected necrosis; however, there is great controversy about the optimal drainage time, and better treatment should be explored. CASE SUMMARY: We report the case of a 43-year-old man who was admitted to the hospital with severe intake reduction due to early satiety 2 wk after treatment for acute pancreatitis; conservative treatment was ineffective, and a pancreatic pseudocyst was suspected on contrast-enhanced computed tomography (CT). Endoscopic ultrasonography (EUS) suggested hyperechoic necrotic tissue within the cyst cavity. The wall was not completely mature, and the culture of the puncture fluid was positive for A-haemolytic Streptococcus. Thus, the final diagnosis of ANC infection was made. The necrotic collection was not walled off and contained many solid components; therefore, the patient underwent EUS-guided aspiration and lavage. Two weeks after the collection was completely encapsulated, pancreatic duct stent drainage via endoscopic retrograde cholangiopancreatography (ERCP) was performed, and the patient was subsequently successfully discharged. On repeat CT, the pancreatic cysts had almost disappeared during the 6-month follow-up period after surgery. CONCLUSION: Early EUS-guided aspiration and lavage combined with late ERCP catheter drainage may be effective methods for intervention in infected ANCs.

Enhanced electromagnetic wave absorption properties of SiCN(Ni)/BN ceramics by in situ generated Ni and Ni3Si.

In this paper, the SiCN(Ni)/BN ceramic with excellent electromagnetic wave (EMW) absorption performance was successfully prepared. The Ni and Ni3Si were in situ formed by the introduction of nickel acetylacetonate (NA), which effectively improved the impedance matching performance of SiCN(Ni)/BN ceramics. The EMW absorption properties of the SiCN(Ni)/BN ceramics showed a trend of first increasing and then decreasing with the increase in content of NA. When the NA content reached 7 wt%, the impedance matching range of SiCN-7 was optimal. The minimum reflection loss (RLmin) of SiCN-7 reached -53.47 dB at 4.2 mm and the effective absorption bandwidth (EAB) was 2.32 GHz at 3.48 mm. Through the analysis of electrical conductivity, it was found that the proportion of polarization loss in dielectric loss was more than 99%. It is worth noting that the radar cross section (RCS) value of SiCN-7 absorber was lower than that of the perfect electrical conductor (PEC) plate in the range of -90-90°, and showed a larger coverage angle, indicating that it possessed a good practical application prospect in the field of electromagnetic wave absorption.

Identification of a cis-element for long glandular trichome-specific gene expression, which is targeted by a HD-ZIP IV protein.

Glandular trichomes are epidermal outgrowths that secret a variety of secondary metabolites, which not only help plants adapt to environmental stresses but also have important commercial value in fragrances, pharmaceuticals, and pesticides. In Nicotiana tabacum, it has been confirmed that a B-type cyclin, CycB2, negatively regulates the formation of long glandular trichomes (LGTs). This study aimed to identify the upstream regulatory gene involved in LGT formation by screening LGT-specific cis-elements within the NtCycB2 promoter. Using GUS as a reporter gene, the tissue-driven ability of NtCycB2 promoter showed that NtCycB2 promoter could drive GUS expression specifically in LGTs. Function analysis of a series of successive 5' truncations and synthetic segments of the NtCycB2 promoter indicated that the 87-bp region from -1221 to -1134 of the NtCycB2 promoter was required for gene expression in LGTs, and the L1-element (5'-AAAATTAATAAGAG-3') located in the 87-bp region contributed to the gene expression in the stalk of LGTs. Further Y1H and LUC assays confirmed that this L1-element exclusively binds to a HD-Zip IV protein, NtHD13. Gene function analysis revealed that NtHD13 positively controlled LGT formation, as overexpression of NtHD13 resulted in a high number of LGTs, whereas knockout of NtHD13 led to a decrease in LGTs. These findings demonstrate that NtHD13 can bind to an L1-element within the NtCycB2 promoter to regulate LGT formation.

Intracerebral hemodynamic abnormalities in patients with Parkinson's disease: Comparison between multi-delay arterial spin labelling and conventional single-delay arterial spin labelling.

PURPOSE: The purpose of this study was to analyze the intracerebral abnormalities of hemodynamics in patients with Parkinson's disease (PD) through arterial spin labelling (ASL) technique with multi-delay ASL (MDASL) and conventional single-delay ASL (SDASL) protocols and to verify the potential clinical application of these features for the diagnosis of PD. MATERIALS AND METHODS: Perfusion data of the brain obtained using MDASL and SDASL in patients with PD were compared to those obtained in healthy control (HC) subjects. Intergroup comparisons of z-scored cerebral blood flow (zCBF), arterial transit time (zATT) and cerebral blood volume (zCBV) were performed via voxel-based analysis. Performance of these perfusion metrics were estimated using area under the receiver operating characteristic curve (AUC) and compared using Delong test. RESULTS: A total of 47 patients with PD (29 men; 18 women; mean age, 69.0 ± 7.6 (standard deviation, [SD]) years; range: 50.0-84.0 years) and 50 HC subjects (28 men; 22 women; mean age, 70.1 ± 6.2 [SD] years; range: 50.0-93.0 years) were included. Relative to the uncorrected-zCBF map, the corrected-zCBF map further refined the distributed brain regions in the PD group versus the HC group, manifested as the extension of motor-related regions (PFWE < 0.001). Compared to the HC subjects, patients with PD had elevated zATT and zCBV in the right putamen, a shortened zATT in the superior frontal gyrus, and specific zCBV variations in the left precuneus and the right supplementary motor area (PFWE < 0.001). The corrected-zCBF (AUC, 0.90; 95% confidence interval [CI]: 0.84-0.96) showed better classification performance than uncorrected-zCBF (AUC, 0.84; 95% CI: 0.75-0.92) (P = 0.035). zCBV achieved an AUC of 0.89 (95% CI: 0.82-0.96) and zATT achieved an AUC of 0.66 (95% CI: 0.55-0.77). The integration model of hemodynamic features from MDASL provided improved performance (AUC, 0.97; 95% CI: 0.95-0.98) for the diagnosis of PD by comparison with each perfusion model (P < 0.001). CONCLUSION: ASL identifies impaired hemodynamics in patients with PD including regional abnormalities of CBF, CBV and ATT, which can better be mapped with MDASL compared to SDASL. These findings provide complementary depictions of perfusion abnormalities in patients with PD and highlight the clinical feasibility of MDASL.

Innovative overview of the occurrence, aging characteristics, and ecological toxicity of microplastics in environmental media.

Microplastics (MPs), pollutants detected at high frequency in the environment, can be served as carriers of many kinds of pollutants and have typical characteristics of environmental persistence and bioaccumulation. The potential risks of MPs ecological environment and health have been widely concerned by scholars and engineering practitioners. Previous reviews mostly focused on the pollution characteristics and ecological toxicity of MPs, but there were few reviews on MPs analysis methods, aging mechanisms and removal strategies. To address this issue, this review first summarizes the contamination characteristics of MPs in different environmental media, and then focuses on analyzing the detection methods and analyzing the aging mechanisms of MPs, which include physical aging and chemical aging. Further, the ecotoxicity of MPs to different organisms and the associated enhanced removal strategies are outlined. Finally, some unresolved research questions related to MPs are prospected. This review focuses on the ageing and ecotoxic behaviour of MPs and provides some theoretical references for the potential environmental risks of MPs and their deep control.

Nanopore targeted sequencing-based diagnosis of central nervous system infections in HIV-infected patients.

BACKGROUND: Early and accurate etiological diagnosis is very important for improving the prognosis of central nervous system (CNS) infections in human immunodeficiency virus (HIV)-infected patients. The goal is not easily achieved by conventional microbiological tests. We developed a nanopore targeted sequencing (NTS) platform and evaluated the diagnostic performance for CNS infections in HIV-infected patients, with special focus on cryptococcal meningitis (CM). We compared the CM diagnostic performance of NTS with conventional methods and cryptococcal polymerase chain reaction (PCR). METHODS: This study included 57 hospitalized HIV-infected patients with suspected CNS infections from September 2018 to March 2022. The diagnosis established during hospitalization includes 27 cases of CM, 13 CNS tuberculosis, 5 toxoplasma encephalitis, 2 cytomegalovirus (CMV) encephalitis and 1 Varicella-zoster virus (VZV) encephalitis. The 2 cases of CMV encephalitis also have co-existing CM. Target-specific PCR amplification was used to enrich pathogen sequences before nanopore sequencing. NTS was performed on stored cerebrospinal fluid (CSF) samples and the results were compared with the diagnosis during hospitalization. RESULTS: 53 (93.0%) of the patients were male. The median CD4 cell count was 25.0 (IQR: 14.0-63.0) cells/uL. The sensitivities of CSF culture, India ink staining, cryptococcal PCR and NTS for CM were 70.4% (95%CI: 51.5 - 84.1%), 76.0% (95%CI: 56.6 - 88.5%), 77.8% (59.2 - 89.4%) and 85.2% (95%CI: 67.5 - 94.1%), respectively. All those methods had 100% specificity for CM. Our NTS platform could identify Cryptococcus at species level. Moreover, NTS was also able to identify all the 5 cases of toxoplasma encephalitis, 2 cases of CMV encephalitis and 1 VZV encephalitis. However, only 1 of 13 CNS tuberculosis cases was diagnosed by NTS, and so did Xpert MTB/RIF assay. CONCLUSIONS: NTS has a good diagnostic performance for CM in HIV-infected patients and may have the ability of simultaneously detecting other pathogens, including mixed infections. With continuing improving of the NTS platform, it may be a promising alterative microbiological test for assisting with the diagnosis of CNS infections.

Convergent and divergent genes expression profiles associated with brain-wide functional connectome dysfunction in deficit and non-deficit schizophrenia.

Deficit schizophrenia (DS) is a subtype of schizophrenia characterized by the primary and persistent negative symptoms. Previous studies have identified differences in brain functions between DS and non-deficit schizophrenia (NDS) patients. However, the genetic regulation features underlying these abnormal changes are still unknown. This study aimed to detect the altered patterns of functional connectivity (FC) in DS and NDS and investigate the gene expression profiles underlying these abnormal FC. The study recruited 82 DS patients, 96 NDS patients, and 124 healthy controls (CN). Voxel-based unbiased brain-wide association study was performed to reveal altered patterns of FC in DS and NDS patients. Machine learning techniques were used to access the utility of altered FC for diseases diagnosis. Weighted gene co-expression network analysis (WGCNA) was employed to explore the associations between altered FC and gene expression of 6 donated brains. Enrichment analysis was conducted to identify the genetic profiles, and the spatio-temporal expression patterns of the key genes were further explored. Comparing to CN, 23 and 20 brain regions with altered FC were identified in DS and NDS patients. The altered FC among these regions showed significant correlations with the SDS scores and exhibited high efficiency in disease classification. WGCNA revealed associations between DS/NDS-related gene expression and altered FC. Additionally, 22 overlapped genes, including 12 positive regulation genes and 10 negative regulation genes, were found between NDS and DS. Enrichment analyses demonstrated relationships between identified genes and significant pathways related to cellular response, neuro regulation, receptor binding, and channel activity. Spatial and temporal gene expression profiles of SCN1B showed the lowest expression at the initiation of embryonic development, while DPYSL3 exhibited rapid increased in the fetal. The present study revealed different altered patterns of FC in DS and NDS patients and highlighted the potential value of FC in disease classification. The associations between gene expression and neuroimaging provided insights into specific and common genetic regulation underlying these brain functional changes in DS and NDS, suggesting a potential genetic-imaging pathogenesis of schizophrenia.

Astragaloside IV targeting autophagy of T cells improves inflammation of asthma.

Astragaloside IV (AST) has been confirmed to have antiasthmatic effects. However, the underline mechanism is unclear. The study aimed to explore the treatment mechanism of AST based on autophagy of memory T cells. AST treatment significantly decreased the number of T effector cells in asthma mice blood and the nude mice that received AST-treated TCMs had relieved inflammation compared with the untreated group; meanwhile, we found that AST significantly decreased the autophagy level and inhibited OX40/OX40L signal pathway of lymphocytes. The results highlighted that AST regulated autophagy to inhibit differentiation of effector T-cell phenotype.