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Conventional bulk molecular approaches, often limited by their destructive nature and low spatial resolution, face challenges when probing the intricate dynamics of the plastisphere. Here, we outline a framework employing Raman spectroscopy combined with stable isotope profiling (SIP) to interrogate the physiological function of the plastisphere microbiome and track its evolutionary trajectories.
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Background: About 20% of on-treatment patients with chronic hepatitis B (CHB) experienced low-level viraemia (LLV), which is associated with persistent low-grade inflammation, fibrosis progression, and increased risk of hepatocellular carcinoma. We aimed to investigate the high-risk factors related to LLV. Methods: In this retrospective study, patients receiving entecavir (ETV) treatment from January 2018 to January 2023 were enrolled, and were divided into a LLV (HBV DNA 20-2000 IU/mL) cohort and a complete virological response (CVR) (HBV DNA < 20 IU/mL) cohort according to the virological response at week 48 posttreatment. Treatment baseline characteristics were retrieved from electronic medical records. Multivariate logistic regression was performed. Results: Totally, 1653 patients were enrolled, male patients accounted for 73.0%; the median age was 44 years; the mean HBV DNA level was 5.9 Log10 IU/ml. Among them, 472 (28.6%) experienced LLV. Multivariate analysis showed that HBeAg positivity (OR = 2.650, 95% CI: 2.000-3.511, p < 0.001), HBV DNA ≥ 6.0 Log10 IU/mL (OR = 1.370, 95% CI: 1.054-1.780, p = 0.019), qHBsAg ≥ 9000 IU/mL (OR = 4.472, 95% CI: 3.410-5.866, p < 0.001), cirrhosis (OR = 1.650, 95% CI: 1.234-2.207, P = 0.001), LSM ≥ 13.0 kPa (OR = 1.644, 95% CI: 1.203-2.246, p = 0.002), and PLT < 100×109/L (OR = 1.450, 95% CI: 1.094-1.922, p = 0.010) at baseline were related to the development of LLV. Conclusions: High HBV DNA/HBsAg quantification/LSM, low PLT, HBeAg positivity, and liver cirrhosis were high-risk factors associated with LLV in patients receiving entecavir treatment.
Subject(s)
Antiviral Agents , DNA, Viral , Guanine , Hepatitis B virus , Hepatitis B, Chronic , Viremia , Humans , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/complications , Male , Guanine/analogs & derivatives , Guanine/therapeutic use , Female , Adult , Risk Factors , Antiviral Agents/therapeutic use , Retrospective Studies , Middle Aged , Hepatitis B virus/genetics , Hepatitis B virus/drug effects , DNA, Viral/blood , Hepatitis B e Antigens/blood , Liver Cirrhosis/virology , Viral Load/drug effectsABSTRACT
RNA-binding protein (RBP) phase separation in oncology reveals a complex interplay crucial for understanding tumor biology and developing novel therapeutic strategies. Aberrant phase separation of RBPs significantly influences gene regulation, signal transduction, and metabolic reprogramming, contributing to tumorigenesis and drug resistance. Our review highlights the integral roles of RBP phase separation in stress granule dynamics, mRNA stabilization, and the modulation of transcriptional and translational processes. Furthermore, interactions between RBPs and non-coding RNAs add a layer of complexity, providing new insights into their collaborative roles in cancer progression. The intricate relationship between RBPs and phase separation poses significant challenges but also opens up novel opportunities for targeted therapeutic interventions. Advancing our understanding of the molecular mechanisms and regulatory networks governing RBP phase separation could lead to breakthroughs in cancer treatment strategies.
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Phosphate-solubilizing bacteria (PSB) are crucial for enhancing phosphorus bioavailability and regulating phosphorus transformation processes. However, the in situ phosphorus-solubilizing activity and the link between phenotypes and genotypes for PSB remain unidentified. Here we employed single-cell Raman spectroscopy combined with heavy water to discern and quantify soil active PSB. Our results reveal that PSB abundance and in situ activity differed significantly between soil types and fertilization treatments. Inorganic fertilizer input was the key driver for active PSB distribution. Targeted single-cell sorting and metagenomic sequencing of active PSB uncovered several low-abundance genera that are easily overlooked within bulk soil microbiota. We elucidate the underlying functional genes and metabolic pathway, and the interplay between phosphorus and carbon cycling involved in high phosphorus solubilization activity. Our study provides a single-cell approach to exploring PSB from native environments, enabling the development of a microbial solution for the efficient agronomic use of phosphorus and mitigating the phosphorus crisis.
Subject(s)
Bacteria , Fertilizers , Phosphates , Phosphorus , Soil Microbiology , Soil , Phosphorus/metabolism , Bacteria/metabolism , Bacteria/genetics , Phosphates/metabolism , Soil/chemistry , Fertilizers/analysis , Single-Cell Analysis , Microbiota/physiology , SolubilityABSTRACT
OBJECTIVES: Intracranial arterial dolichoectasia (IADE) is characterized by the dilation, elongation, and tortuosity of intracranial arteries. We aimed to investigate the association between variations of the Circle of Willis (COW) and IADE in the general population, as well as estimate the genetic correlation between COW variations and IADE. METHODS: A total of 981 individuals from a population-based cohort were included. Brain magnetic resonance angiography was performed to assess COW variants and measure the diameters of intracranial arteries. IADE was defined as a total intracranial volume-adjusted diameter ≥ 2 standard deviations. Logistic regression models were used to analyze the association between COW variations and IADE. The heritability and genetic correlation were estimated using genome-wide complex trait analysis (GCTA) based on single nucleotide polymorphism (SNP) array data. RESULTS: The prevalence of IADE was 6.2â¯%. Hypoplastic/absent A1 segments were associated with an increase in contralateral ICA diameter (ß ± SE, 0.279 ± 0.049; p = 0.001) and a decrease in ipsilateral ICA diameter (ß ± SE, -0.300 ± 0.050; p = 0.001). Fetal-type posterior cerebral artery (FTP) was associated with a larger ICA diameter (ß ± SE, 0.326 ± 0.048; p = 0.001) and a smaller BA diameter (ß ± SE, -0.662 ± 0.043; p = 0.001). FTP revealed a positive genetic correlation with ICA dilation (rG = 0.259 ± 0.175; p = 0.0009) and a negative genetic correlation with BA dilation (rG = -0.192 ± 0.153, p = 0.015). CONCLUSIONS: There was an association between COW variations and larger intracranial arterial diameters in the general population. Genetic factors may play a role in the development of intracranial arterial dilation and the formation of COW variants.
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Quantum chemical calculations are reported for the complexes of alkaline earth metals AeOLi2 (Ae = Be-Ba) at the BP86-D3(BJ)/def2-QZVPP and CCSD(T)/def2-QZVPPQZVPP levels. The nature of the Ae-OLi2 bond has been analyzed with a variety of methods. The AeOLi2 molecules exhibit an unprecedented σ donor bond AeâOLi2 where the (n)s2 lone-pair electrons of the Ae atom are donated to vacant O-Li2 antibonding orbitals having the largest coefficient at lithium. This is a covalent bond where the accumulation of the associated electronic charge is located at two positions above and below the Ae-OLi2 axis. The bifurcated component of orbital interactions is structurally related to the recently proposed collective bonding model, but exhibits a completely different type of bonding. The most stable isomer of AeOLi2 has a C 2v geometry and a singlet (1A1) electronic ground state. The bond dissociation energy (BDE) of the Ae-OLi2 bonds exhibits a zig-zag trend from BeOLi2 to BaOLi2, with BeOLi2 having the largest BDE (D e = 73.0 kcal mol-1) and MgOLi2 possessing the lowest BDE (D e = 42.3 kcal mol-1) at the CCSD(T) level. The calculation of the atomic partial charges by the Hirshfeld and Voronoi methods suggests that Be and Mg carry small negative charges in the lighter molecules whereas the heavier atoms Ca-Ba have small positive charges. In contrast, the NBO and QTAIM methods give positive charges for all Ae atoms that are larger for Ca-Ba than that calculated by the Hirshfeld and Voronoi approaches. The molecules AeOLi2 have large dipole moments where the negative end is at the Ae atom with the polarity AeâOLi2. The largest dipole moments are predicted for the lighter species BeOLi2 and MgOLi2 and the smallest value is calculated for BaOLi2. The calculation of the vibrational spectra shows a significant red-shift toward lower wave numbers for the Ae-OLi2 stretching mode in comparison to diatomic AeO. Besides the AeâOLi2 σ-donor bonds there are also three dative bonds due to AeâOLi2 backdonation which consist of one σ bond and two π bonds. The appearance of strong AeâOLi2 σ donation leads to quadruple bonds AeOLi2 in all systems AeOLi2, even for the lightest species with Ae = Be, Mg. The valence orbitals of Ca, Sr, and Ba, which are involved in the dative interactions, are the (n)s and (n-1)d AOs whereas Be and Mg use their (n)s and (n)p AOs. The EDA-NOCV results are supported by the AdNDP calculations which give four 2c-2e bonding orbitals. Three bonding orbitals have occupation numbers â¼2. One σ orbital has smaller occupation numbers between 1.32 and 1.73 due to the delocalization to the lithium atoms. The analysis of the electronic structure with the ELF method suggests multicenter bonds with mainly trisynaptic and tetrasynaptic basins, which also support the results of the EDA-NOCV calculations.
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In order to determine the appropriate harvesting period of Carya illinoinensis planted in Nanjing city of China, this study analyzed the phenotypic characteristics and inclusions, including single fruit quality, fruit transverse and vertical diameter, kernel rate, water content, color, respiratory strength, crude fat, soluble sugar, soluble protein, and total phenols, of two cultivars 'Pawnee' and 'Wichita' during September and October, respectively. Results showed that the respiration intensity and IAD values of pecan fruits decreased as the harvest date was delayed. 'Pawnee' fruits exhibited the highest seed kernel fullness, ∆E value, fruit transverse diameter, shape index, kernel yield, crude fat, and total phenolic content in late September and early October, while the quality of 'Wichita' fruits reached its peak in late October. The appropriate harvest period is conducive to the material accumulation of Carya illinoinensis, which is of great practical significance for improving the commodity value of pecans. The optimal harvesting period for 'Pawnee' in Nanjing is from the end of September to the beginning of October, and the optimal harvesting period for 'Wichita' is from mid- to late-October to the end of October.
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BACKGROUND: Bivalirudin, a direct thrombin inhibitor, is used in anticoagulation therapies as a substitute for heparin, especially during cardiovascular procedures such as percutaneous coronary intervention. AIM: To explore the effect of bivalirudin on myocardial microcirculation following an intervention and its influence on adverse cardiac events in elderly patients with acute coronary syndrome (ACS). METHODS: In total, 165 patients diagnosed with acute myocardial at our hospital between June 2020 and June 2022 were enrolled in this study. From June 2020 to June 2022, elderly patients with ACS with complete data were selected and treated with interventional therapy. The study cohort was randomly divided into a study group (n = 80, administered bivalirudin) and a control group (n = 85, administered unfractionated heparin). Over a 6-mo follow-up period, differences in emergency processing times, including coronary intervention, cardiac function indicators, occurrence of cardiovascular events, and recurrence rates, were analyzed. RESULTS: Significant differences were observed between the study cohorts, with the observation group showing shorter emergency process times across all stages: Emergency classification; diagnostic testing; implementation of coronary intervention; and conclusion of emergency treatment (P < 0.05). Furthermore, the left ventricular ejection fraction in the observation group was significantly higher (P < 0.05), and the creatine kinase-MB and New York Heart Association scores were notably lower than those in the control group (P < 0.05). CONCLUSION: In elderly patients receiving interventional therapy for ACS, bivalirudin administration led to increased activated clotting time achievement rates, enhanced myocardial reperfusion, and reduced incidence of bleeding complications and adverse cardiac events.
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OBJECTIVES: Seeking a noninvasive predictor for BRAF V600E mutation status of pleomorphic xanthoastrocytomas (PXAs) is essential for their prognoses and therapeutic use of BRAF inhibitors. We aimed to noninvasively diagnose BRAF V600E-mutated PXAs using MRI morphologic, DWI and clinical parameters. METHODS: The clinical findings, anatomical MRI characteristics, and diffusion parameters of 36 pathologically confirmed PXAs were retrospectively analyzed, and BRAF V600E-mutated (n = 16) and wild-type (n = 20) groups were compared. A binary logistic-regression analysis was performed, and a ROC curve was calculated to determine the independent predictors of BRAF V600E mutation status, diagnostic accuracy, and optimal cut-off value. RESULTS: A comparison of findings between groups showed that BRAF V600E-mutated PXAs were more frequent in children and young adults (≤ 35 years; P = 0.042) who often had histories of seizures (P = 0.004). Furthermore, BRAF V600E-mutated PXAs generally presented as solitary masses (P = 0.024), superficial locations with meningeal attachment (P < 0.001), predominantly cystic with mural nodules (P = 0.005), and had greater minimal ADC ratio (ADCratio) values of the tumor and peritumoral edema (P < 0.001). Binary logistic regression showed that age ≤ 35 years, solitary mass, superficial locations with meningeal attachment, and a greater minimal ADCratio of the tumor were independent predictors of BRAF V600E-mutated PXAs. The combination of all four independent predictors resulted in the highest sensitivity (100%) and specificity (90%), with AUC = 0.984. CONCLUSION: The BRAF V600E mutation status of PXAs could be noninvasively predicted using clinical and MRI characteristics. CRITICAL RELEVANCE STATEMENT: The noninvasive diagnostic criteria for BRAF V600E-mutated PXAs could offer guidance for the administration of BRAF V600E mutation inhibitors in the future.
Subject(s)
Astrocytoma , Brain Neoplasms , Diffusion Magnetic Resonance Imaging , Mutation , Proto-Oncogene Proteins B-raf , Humans , Proto-Oncogene Proteins B-raf/genetics , Female , Male , Astrocytoma/genetics , Astrocytoma/diagnostic imaging , Astrocytoma/pathology , Adult , Diffusion Magnetic Resonance Imaging/methods , Child , Adolescent , Retrospective Studies , Young Adult , Middle Aged , Brain Neoplasms/genetics , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Child, Preschool , Magnetic Resonance Imaging/methods , Prognosis , ROC CurveABSTRACT
The Zn dendrite limits the practical application of aqueous zinc-ion batteries in the large-scale energy storage systems. To suppress the growth of Zn dendrites, a zinc ionophore of hydroxychloroquine (defined as HCQ) applied in vivo treatment is investigated as the electrolyte additive. HCQ dynamically regulates zinc ion concentration in the outer Helmholtz layer, promoting even Zn plating at the anode/electrolyte interface. This is evidenced by the scanning electron microscopy, which delivers planar Zn plating after cycling. It is further supported by the X-ray diffraction spectroscopy, which reveals the growth of Zn (002) plane. Additionally, the reduced production of H2 during Zn plating/stripping is detected by the in-situ differential electrochemical mass spectrometry (DEMS), which shows the resistance of Zn (002) to hydrogen evolution reaction. The mechanism of dynamic regulation for zinc ion concentration is demonstrated by the in-situ optical microscopy. The hydrated zinc ion can be further plated more rapidly to the uneven location than the case in other regions, which is resulted from the dynamic regulation for zinc ion concentration. Therefore, the uniform Zn plating is formed. A cycling life of 1100 h is exhibited in the Zn||Zn symmetric cell at 1.6 mA cm-2 with the capacity of 1.6 mAh cm-2. The Zn||Cu battery exhibits a cycling life of 200 cycles at 4 mA cm-2 with a capacity of 4 mAh cm-2 and the average Coulombic efficiency is larger than 99 %. The Zn||VO2 battery with HCQ modified electrolyte can operate for 1500 cycles at 4 A g-1 with a capacity retention of 90 %. This strategy in the present work is wished to advance the development of zinc-ion batteries for practical application.
Subject(s)
Antirheumatic Agents , Arthritis, Psoriatic , Arthritis, Rheumatoid , Female , Humans , Antirheumatic Agents/therapeutic use , Arthritis, Psoriatic/drug therapy , Arthritis, Psoriatic/diagnosis , Arthritis, Psoriatic/therapy , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/diagnosis , Immunosorbent Techniques , Remission Induction , Treatment Outcome , AgedABSTRACT
Food waste is one of the important reservoirs of antibiotic resistance genes ï¼ARGsï¼, and its resource utilization has potential environmental risks. Anaerobic digestion ï¼ADï¼ technology can concurrently achieve resource recovery and ARGs removal, which is one of the popular resource technologies for food waste management. However, the removal efficiency of ARGs during the AD process is limited, and thus the safety of digestate for agricultural use is still questioned. Therefore, how to improve the performance of ARGs removal during the AD process is critical for efficient and environmentally friendly bioconversion of food waste. This study summarized the transmission pathways and mechanisms of ARGs in food wasteï¼ discussed the effects of different operation parameters on the transmission of ARGs in food waste during the AD processï¼ described the research progress of exogenous addition of conductive materials, feedstock pretreatment, etc., strategies to enhance the removal of ARGsï¼ and analyzed the migration regularity and removal mechanism of ARGs in food waste during the AD process, which mainly included microbial community structure evolution, mobile genetic element changes, and environmental factor changes. Finally, this study prospected the future improvement of methane yield and ARGs removal in the AD process of food waste based on the existing research.
Subject(s)
Drug Resistance, Microbial , Anaerobiosis , Drug Resistance, Microbial/genetics , Refuse Disposal/methods , Bioreactors/microbiology , Food , Biodegradation, Environmental , Food Loss and WasteABSTRACT
Sorghum (Sorghum bicolor), the fifth most important cereal crop globally, serves as a staple food, animal feed, and a bioenergy source. Paclobutrazol-Resistance (PRE) genes play a pivotal role in the response to environmental stress, yet the understanding of their involvement in pest resistance remains limited. In the present study, a total of seven SbPRE genes were found within the sorghum BTx623 genome. Subsequently, their genomic location was studied, and they were distributed on four chromosomes. An analysis of cis-acting elements in SbPRE promoters revealed that various elements were associated with hormones and stress responses. Expression pattern analysis showed differentially tissue-specific expression profiles among SbPRE genes. The expression of some SbPRE genes can be induced by abiotic stress and aphid treatments. Furthermore, through phytohormones and transgenic analyses, we demonstrated that SbPRE4 improves sorghum resistance to aphids by accumulating jasmonic acids (JAs) in transgenic Arabidopsis, giving insights into the molecular and biological function of atypical basic helix-loop-helix (bHLH) transcription factors in sorghum pest resistance.
Subject(s)
Aphids , Gene Expression Regulation, Plant , Plant Proteins , Sorghum , Stress, Physiological , Triazoles , Sorghum/genetics , Sorghum/metabolism , Aphids/genetics , Aphids/physiology , Animals , Triazoles/pharmacology , Stress, Physiological/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified , Oxylipins/metabolism , Oxylipins/pharmacology , Cyclopentanes/metabolism , Cyclopentanes/pharmacology , Arabidopsis/genetics , Promoter Regions, Genetic , Multigene Family , Plant Growth Regulators/metabolism , Plant Growth Regulators/pharmacology , Phylogeny , Plant Diseases/parasitology , Plant Diseases/genetics , Genome, PlantABSTRACT
Importance: Chronic pelvic pain (CPP) is the main sequela of pelvic inflammatory disease (PID), with no established treatment. ZY5301 tablets, an effective part preparation extracted from Ajuga decumbens Thunb. (jingucao), are being tested as a treatment for CPP caused by PID. Objective: To evaluate whether ZY5301 tablets are effective and safe for CPP treatment in women with PID. Design, Setting, and Participants: This placebo-controlled double-blind, dose-parallel, phase 2 randomized clinical trial was conducted in 9 hospitals in China. Female participants with CPP after PID were enrolled between October 16, 2020, and August 31, 2021. The data analysis was performed between December 2021 and March 2022. Interventions: Participants were randomized 1:1:1 to receive ZY5301 300 mg/d, ZY5301 600 mg/d, or placebo orally 3 times a day for 12 weeks. Main Outcomes and Measures: Visual analog scale (VAS) scores were the main measure used to evaluate the efficacy of ZY5301 in reducing CPP. The evaluation end points for VAS score included changes in mean weekly VAS score from baseline, area under the VAS score-time curve, pain remission (VAS score of 0 and 1) rate, and median time to pain remission. Safety was evaluated by the occurrence of treatment-emergent and treatment-related adverse events. Results: In total, 180 women were randomly assigned, and 177 were included in the efficacy analysis; thus, the full analysis set included 60 participants in the ZY5301 mg/d group (mean [SD] age, 37.4 [8.1] years), 58 in the ZY5301 600 mg/d group (mean [SD] age, 37.1 [7.9] years), and 59 in the placebo group (mean [SD] age, 38.9 [7.3] years). Participant characteristics at baseline were similar among the groups. After 12 weeks of treatment, the mean (SD) change in VAS score from the baseline was -2.1 (1.7) points, -3.5 (1.5) points, and -3.8 (1.7) points in the placebo, ZY5301 300 mg/d, and ZY5301 600 mg/d groups, respectively (P < .001). The pain remission rates at week 12 were 43.3% and 53.5% in the ZY5301 300 mg/d and ZY5301 600 mg/d groups, respectively, a significant difference compared with the placebo group (11.9%; P < .001). All the other end points showed similar improvements. The ZY5301 600 mg/d group had better efficacy than the ZY5301 300 mg/d group, but the difference was not significant. The safety analysis revealed no significant differences among groups. Conclusions and Relevance: These findings show that ZY5301 tablet is efficacious for the relief of CPP with acceptable tolerability. Trial Registration: ClinicalTrials.gov Identifier: NCT05460546.
Subject(s)
Pelvic Inflammatory Disease , Pelvic Pain , Humans , Female , Pelvic Pain/drug therapy , Pelvic Pain/etiology , Adult , Pelvic Inflammatory Disease/drug therapy , Double-Blind Method , Tablets , Chronic Pain/drug therapy , Chronic Pain/etiology , Middle Aged , Treatment Outcome , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/administration & dosage , Pain Measurement , ChinaABSTRACT
This study investigated the impact of novel copper ionophores on the prognosis of clear cell renal cell carcinoma (ccRCC) and the tumor microenvironment (TME). The differential expression of 10 cuproptosis and 40 TME-pathway-related genes were measured in 531 tumor samples and 71 adjacent kidney samples in The Cancer Genome Atlas database. A risk score model was constructed with LASSO cox to predict the prognosis of ccRCC patients. Forest plot and function enrichment were used to study the biological function of the key genes in depth. The study found that the risk score model accurately predicted the prognosis of ccRCC patients. Patients with high scores had higher immune responses with a higher proportion of anti-tumor lymphocytes and a lower proportion of immunosuppressive M2-like macrophages. However, the high-score group also exhibited a higher proportion of T follicular helper cells and regulatory T cells. These results suggest that cuproptosis-based therapy may be worth further investigation for the treatment of ccRCC and TME. Subsequently, by using RNAi, we established the stable depletion models of FDX1 and PDHB in ccRCC cell lines 786-O and ACHN. Through CCK8, colony formation, and Transwell assays, we observed that the knockdown of FDX1 and PDHB could significantly reduce the capabilities of proliferation and migration in ccRCC cells. In conclusion, this study illuminates the potential effectiveness of copper ionophores in the treatment of ccRCC, with higher risk scores correlating with better TME immune responses. It sets the stage for future cuproptosis-based therapy research in ccRCC and other cancers, focusing on copper's role in TME.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Tumor Microenvironment , Humans , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/metabolism , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/metabolism , Prognosis , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Cell Proliferation , Copper/metabolism , Female , Male , Cell MovementABSTRACT
The recent report of planar tetracoordinate hydrogen (ptH) in In4H+ is very intriguing in planar hypercoordinate chemistry. Our high-level CCSD(T) calculations revealed that the proposed D4h-symmetric ptH In4H+ is a first-order saddle point with an imaginary frequency in the out-of-plane mode of the hydrogen atom. In fact, at the CCSD(T)/aug-cc-pV5Z/aug-cc-pV5Z-PP level, the C4v isomer, with the H atom located 0.70 Å above the In4 plane, is 0.5 kcal/mol more stable than the D4h isomer. However, given the small perturbation from planarity and essentially barrierless C4v â D4h â C4v transition, the vibrationally averaged structure can still be considered as a planar. Extending our exploration to the InnTl4-nH+ (n = 0-3) systems, we found all these ptH structures, except for In2Tl2H+, to be the putative global minimum. The single σ-delocalized interaction between the central hydrogen atom and InnTl4-n ligand rings proves pivotal in establishing planarity and aromaticity and conferring substantial stability upon these rule-breaking ptH species.
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Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non-invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large-scale population remains under-investigated. In this cross-sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion-weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662-0.898). We found that those with older age and male sex had lower automated ALPS values (ß = -0.051, SE = 0.004, p < .001, per 10 years, and ß = -0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (ß = -2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002-0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (ß = 0.067, SE = 0.007, p < .001 and ß = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction.
Subject(s)
Diffusion Magnetic Resonance Imaging , Glymphatic System , Humans , Male , Female , Glymphatic System/diagnostic imaging , Glymphatic System/pathology , Glymphatic System/physiopathology , Middle Aged , Cross-Sectional Studies , Aged , Diffusion Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Brain/pathology , White Matter/diagnostic imaging , White Matter/pathology , Image Processing, Computer-Assisted/methods , Adult , Cohort StudiesABSTRACT
Plastic pollution represents a critical threat to soil ecosystems and even humans, as plastics can serve as a habitat for breeding and refuging pathogenic microorganisms against stresses. However, evaluating the health risk of plastispheres is difficult due to the lack of risk factors and quantification model. Here, DNA sequencing, single-cell Raman-D2O labeling, and transformation assay were used to quantify key risk factors of plastisphere, including pathogen abundance, phenotypic resistance to various stresses (antibiotic and pesticide), and ability to acquire antibiotic resistance genes. A Bayesian network model was newly introduced to integrate these three factors and infer their causal relationships. Using this model, the risk of pathogen in the plastisphere is found to be nearly 3 magnitudes higher than that in free-living state. Furthermore, this model exhibits robustness for risk prediction, even in the absence of one factor. Our framework offers a novel and practical approach to assessing the health risk of plastispheres, contributing to the management of plastic-related threats to human health.
Subject(s)
Bayes Theorem , Bacteria/genetics , Bacteria/isolation & purification , Phenotype , Soil Microbiology , Humans , Anti-Bacterial Agents/pharmacologyABSTRACT
Purkinje cell cytoplasmic antibody type 2 (PCA-2), identified in 2000, targets the widely distributed microtubule-associated protein 1B in the central and peripheral nervous systems, leading to diverse clinical phenotypes of neurological disorders. We report two cases of PCA-2-associated encephalitis, each presenting with distinct onset forms and clinical manifestations, thereby illustrating the phenotypic variability of PCA-2-related diseases. The first patient was diagnosed with PCA-2-associated autoimmune cerebellitis and undifferentiated small cell carcinoma with metastasis in mediastinal lymph nodes of unknown primary origin. The second patient was diagnosed with PCA-2-associated limbic encephalitis. Our findings underscore the superior sensitivity of positron emission tomography-computed tomography over brain magnetic resonance imaging in the early detection of PCA-2-associated encephalitis. Given the high risk of relapse and suboptimal response to traditional immunotherapy in PCA-2-related neurological disorders, this study highlights the need for a deeper understanding of their pathogenesis to develop more effective treatments to control symptoms and improve patient prognosis.
Subject(s)
Phenotype , Humans , Male , Middle Aged , Autoantibodies/immunology , Autoantibodies/blood , Female , Encephalitis/diagnosis , Encephalitis/immunology , Positron Emission Tomography Computed Tomography , Magnetic Resonance Imaging , Aged , Limbic Encephalitis/diagnosis , Limbic Encephalitis/immunology , Antigens, Neoplasm/immunologyABSTRACT
Observational studies have shown gut microbiota changes in sporadic Creutzfeldt-Jakob disease patients, but the causal relationship remains unknown. We aimed to determine any causal links between gut microbiota and this prion disease. Using Mendelian randomization analysis, we examined the causal relationship between gut microbiota composition and sporadic Creutzfeldt-Jakob disease. Data on gut microbiota (N = 18,340) and disease cases (5208) were obtained. Various analysis methods were used, including inverse variance weighted, Mendelian randomization-Egger, weighted median, simple mode, and weighted mode. In addition, MR-PRESSO was used to evaluate horizontal pleiotropy and detect outliers. Pleiotropy and heterogeneity were assessed, and reverse analysis was conducted. Negative associations were found between sporadic Creutzfeldt-Jakob disease and family Defluviitaleaceae, family Ruminococcaceae, genus Butyricicoccus, genus Desulfovibrio, and genus Eubacterium nodatum. Genus Lachnospiraceae UCG010 showed a positive correlation. Reverse analysis indicated genetic associations between the disease and decreased levels of family Peptococcaceae, genus Faecalibacterium, and genus Phascolarctobacterium, as well as increased levels of genus Butyrivibrio. No pleiotropy, heterogeneity, outliers, or weak instrument bias were observed. This study revealed bidirectional causal effects between specific gut microbiota components and sporadic Creutzfeldt-Jakob disease. Certain components demonstrated inhibitory effects on disease pathogenesis, while others were positively associated with the disease. Modulating gut microbiota may provide new insights into prion disease therapies. Further research is needed to clarify mechanisms and explore treatments for sporadic Creutzfeldt-Jakob disease.