ABSTRACT
BACKGROUND: The common cause of sodium nitrite poisoning has shifted from previous accidental intoxication by exposure or ingestion of contaminated water and food to recent alarming intentional intoxication as an employed method of suicide/exit. The subsequent formation of methemoglobin (MetHb) restricts oxygen transport and utilization in the body, resulting in functional hypoxia at the tissue level. In clinical practice, a mismatch of cyanotic appearance and oxygen partial pressure usually contributes to the identification of methemoglobinemia. Prompt recognition of characteristic mismatch and accurate diagnosis of sodium nitrite poisoning are prerequisites for the implementation of standardized systemic interventions. CASE SUMMARY: A pregnant woman was admitted to the Department of Critical Care Medicine at the First Affiliated Hospital of Harbin Medical University due to consciousness disorders and drowsiness 2 h before admission. Subsequently, she developed vomiting and cyanotic skin. The woman underwent orotracheal intubation, invasive mechanical ventilation (IMV), and correction of internal environment disturbance in the ICU. Her premature infant was born with a higher-than-normal MetHb level of 3.3%, and received detoxification with methylene blue and vitamin C, supplemental vitamin K1, an infusion of fresh frozen plasma, as well as respiratory support via orotracheal intubation and IMV. On day 3 after admission, the puerpera regained consciousness, evacuated the IMV, and resumed enteral nutrition. She was then transferred to the maternity ward 24 h later. On day 7 after admission, the woman recovered and was discharged without any sequelae. CONCLUSION: MetHb can cross through the placental barrier. Level of MetHb both reflects severity of the sodium nitrite poisoning and serves as feedback on therapeutic effectiveness.
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Background: Parabacteroides goldsteinii, a member of the Parabacteroides genus, was initially discovered in the feces and abdominal tissue of patients with appendicitis, peritonitis, and abdominal abscesses. In recent years, P. goldsteinii has been widely regarded as a gut probiotic, and human infections have been extremely rare. In 2010, P. goldsteinii was first isolated from the blood culture of a patient with abdominal infection, confirming its ability to cause bacteremia. In this study, we report a rare case of puerperal infection with septic shock caused by P. goldsteinii infection in a pregnant woman. Case presentation: A 31-year-old female experienced perineal lacerations, cervical lacerations, and postpartum hemorrhage during childbirth. Nine days postpartum, the patient developed septic shock, and P. goldsteinii infection was identified through blood culture and mass spectrometry. We administered broad-spectrum antibiotics, including meropenem/nalidixic acid and piperacillin tazobactam, intravenously, but the antimicrobial effect was not satisfactory. Upon ultrasound examination, we identified a focus of infection in the patient's uterus. Subsequently, uterine curettage was performed, followed by uterine cavity irrigation with metronidazole and intramuscular injection of gentamicin and dexamethasone. Following treatment, the patient's physiological parameters gradually returned to normal, and she was discharged 30 days after admission. Conclusion: Parabacteroides goldsteinii bacteraemia is extremely rare, and clinically, the postinfection toxicity of this bacterium appears to be significant. In this report, we review the research history of P. goldsteinii and relevant infection cases, aiming to enhance awareness among clinical practitioners, particularly obstetricians and gynecologists, regarding P. goldsteinii bloodstream infections, facilitating early diagnosis and timely treatment.
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Loss of phosphatase and tensin homolog (PTEN) has been linked to an immunosuppressive tumor microenvironment, but its underlying mechanisms remain largely enigmatic. Here, we report that PTEN can be secreted by the transmembrane emp24 domain-containing protein 10 (TMED10)-channeled protein secretion pathway. Inhibiting PTEN secretion from tumor cells contributes to immunosuppression and impairs the tumor-suppressive role of PTEN, while intratumoral injection of PTEN protein promotes antitumor immunity and suppresses tumor growth in mice. Mechanistically, extracellular PTEN binds to the plexin domain-containing protein 2 (PLXDC2) on macrophages, triggering subsequent activation of JAK2-STAT1 signaling, which switches tumor-associated macrophages (TAMs) from the immunosuppressive to inflammatory phenotype, leading to enhanced activation of CD8+ T and natural killer cells. Importantly, PTEN treatment also enhances the therapeutic efficacy of anti-PD-1 treatment in mice and reverses the immune-suppressive phenotype of patient-derived primary TAMs. These data identify a cytokine-like role of PTEN in immune activation and tumor suppression and demonstrate the therapeutic potential for extracellular administration of PTEN in cancer immunotherapy.
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PFOA has garnered heightened scrutiny for its impact on denitrification, especially given its frequent detection in secondary effluent discharged from wastewater treatment plants. However, it is still unclear what potential risk PFOA release poses to a typical advanced treatment process, especially the sulfur-based autotrophic denitrification (SAD) process. In this study, different PFOA concentration were tested to explore their impact on denitrification kinetics and microbial dynamic responses of the SAD process. The results showed that an increase PFOA concentration from 0 to 1000 µg/L resulted in a decrease in nitrate removal rate from 9.52 to 7.73 mg-N/L·h. At the same time, it increased nitrite accumulation and N2O emission by 6.11 and 2.03 times, respectively. The inhibitory effect of PFOA on nitrate and nitrite reductase activity in the SAD process was linked to the observed fluctuations in nitrate and nitrite levels. It is noteworthy that nitrite reductase was more vulnerable to the influence of PFOA than nitrate reductase. Furthermore, PFOA showed a significant impact on gene expression and microbial community. Metabolic function prediction revealed a notable decrease in nitrogen metabolism and an increase in sulfur metabolism under PFOA exposure. This study highlights that PFOA has a considerable inhibitory effect on SAD performance.
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Nerve transfer surgery utilizes the redundant and synergistic innervation of intact muscle groups to rehabilitate motor function. This is achieved by transferring functional nerves or fascicles to damaged nerves near the target area, thereby reducing the reinnervation distance and time. The techniques encompass both proximal and distal nerve transfers, customized according to the specific injury. Successful nerve transfer hinges on accurate diagnosis, innovative surgical approaches, and the judicious choice of donor nerves to maximize functional restoration. This study explores nerve transfer strategies and their integration with other procedures, emphasizing their importance in enhancing outcomes in brachial plexus injury management.
Subject(s)
Brachial Plexus , Nerve Transfer , Humans , Nerve Transfer/methods , Brachial Plexus/injuries , Brachial Plexus/surgery , Brachial Plexus Neuropathies/surgery , Recovery of FunctionABSTRACT
Plant-sucking insects have intricate associations with a diverse array of microorganisms to facilitate their adaptation to specific ecological niches. The midgut of phytophagous true bugs is generally structured into four distinct compartments to accommodate their microbiota. Nevertheless, there is limited understanding regarding the origins of these gut microbiomes, the mechanisms behind microbial community assembly, and the interactions between gut microbiomes and their insect hosts. In this study, we conducted a comprehensive survey of microbial communities within the midgut compartments of a bean bug Riptortus pedestris, soybean plant, and bulk soil across 12 distinct geographical fields in China, utilizing high-throughput sequencing of the 16 S rRNA gene. Our findings illuminated that gut microbiota of the plant-sucking insects predominantly originated from the surrounding soil environment, and plants also play a subordinate role in mediating microbial acquisition for the insects. Furthermore, our investigation suggested that the composition of the insect gut microbiome was probably shaped by host selection and/or microbe-microbe interactions at the gut compartment level, with marginal influence from soil and geographical factors. Additionally, we had unveiled a noteworthy dynamic in the acquisition of core bacterial taxa, particularly Burkholderia, which were initially sourced from the environment and subsequently enriched within the insect midgut compartments. This bacterial enrichment played a significant role in enhancing insect host reproduction. These findings contribute to our evolving understanding of microbiomes within the insect-plant-soil ecosystem, shedding additional light on the intricate interactions between insects and their microbiomes that underpin the ecological significance of microbial partnerships in host adaptation.
Subject(s)
Bacteria , Gastrointestinal Microbiome , RNA, Ribosomal, 16S , Soil Microbiology , Animals , RNA, Ribosomal, 16S/genetics , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , China , Glycine max/microbiology , High-Throughput Nucleotide Sequencing , Heteroptera/microbiology , Heteroptera/physiology , Reproduction , Phylogeny , Host Microbial Interactions , Burkholderia/genetics , Burkholderia/physiology , Burkholderia/classificationABSTRACT
Despite the promising potential of elemental sulfur-based denitrification (ESDeN) packed-bed progresses, challenges such as excessive biofilm growth and gas entrapment persist, leading to denitrification deterioration. Water flush (WF) is recognized as an effective strategy, yet its effects remain underexplored. To address this knowledge gap, this study systematically investigated WF effects on ESDeN packed-bed denitrification. Results demonstrated that controlling WF effectively regulated denitrification, achieving superior and stable rates. Compared to no WF (0.45 kgN·m-3·d-1), rates improved by 1.20 â¼ 1.56 times under low-frequency (weekly WF, 0.54 kgN·m-3·d-1) and low-intensity WF (0.54 â¼ 0.70 kgN·m-3·d-1). High-frequency (hours WF) and high-intensity WF (30 & 50 m/h) further amplified denitrification rates by 1.73 â¼ 2.29 times. The enhanced denitrifications under low-frequency/intensity WF were mainly attributed to prolonged actual hydraulic retention time (AHRT), while high-frequency/intensity WF improved both AHRT prolonging and biofilm thinning, facilitating mass transfer. This study offers a promising avenue for fine-tuning denitrification rates via strategic WF adjustments.
Subject(s)
Biofilms , Denitrification , Sulfur , Water/chemistry , Bioreactors , Water Purification/methods , Waste Disposal, Fluid/methodsABSTRACT
Nerve autografts involve the transplantation of a segment of the patient's own nerve to bridge a nerve gap. Autografts provide biological compatibility, support for axonal regeneration, and the ability to provide an anatomic scaffold for regrowth that other modalities may not match. Disadvantages of the autograft include donor site morbidity and the extra operative time needed to harvest the graft. Nevertheless, nerve autografts such as the sural nerve remain the gold standard in reconstructing nerve gaps, but a multitude of factors need to be favorable in order to garner reliable, consistent outcomes.
Subject(s)
Autografts , Nerve Regeneration , Sural Nerve , Humans , Sural Nerve/transplantation , Transplantation, Autologous , Peripheral Nerve Injuries/surgery , Peripheral Nerves/transplantationABSTRACT
In this paper, the oxidation-exfoliation process of graphite is studied experimentally by the mixed-solvent method, the oxidation-exfoliation process of graphite is simulated theoretically, and it is found that Graphene Oxide (GO) is a Janus structure with inconsistent oxidation on both surfaces; hydrophilic on one side and hydrophobic on the other side. This layer structure and layer spacing are due to the inconsistent oxidation on both sides which changes with the polarity of different solvent mixtures. We used a two-phase system of benzyl alcohol and water, as well as controlling the polarity of the surface of the substrate, to achieve (using a mixed solution of GO which has a selectivity more inclined to the oil phase when the aqueous phase is present) the preparation of reduced graphene oxide patterns. We also used a complex solution of hydrogen iodide and a sodium-iodide complex solution for secondary reduction to enhance its conductivity to 8653 S/m.
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BACKGROUND: The combined use of CDK4/6 inhibitors and mTOR inhibitors has achieved some clinical success in ccRCC. Exploring the underlying mechanism of the CDK4/6 pathway in cancer cells and the drug interactions of CDK4/6 inhibitors in combination therapy could help identify new therapeutic strategies for ccRCC. Notably, CDK4/6 inhibitors inactivate the mTOR pathway by increasing the protein levels of TSC1, but the mechanism by which CDK4/6 inhibitors regulate TSC1 is still unclear. METHODS: Mass spectrometry analysis, coimmunoprecipitation analysis, GST pull-down assays, immunofluorescence assays, Western blot analysis and RTâqPCR analysis were applied to explore the relationships among CDK4, RNF26 and TSC1. Transwell assays, tube formation assays, CCK-8 assays, colony formation assays and xenograft assays were performed to examine the biological role of RNF26 in renal cancer cells.TCGA-KIRC dataset analysis and RTâqPCR analysis were used to examine the pathways affected by RNF26 silencing. RESULTS: CDK4/6 inhibitors stabilized TSC1 in cancer cells. We showed that CDK4 enhances the interaction between TSC1 and RNF26 and that RNF26 activates the mTOR signaling pathway in ccRCC, contributes to ccRCC progression and angiogenesis, and promotes tumorigenesis. We then found that RNF26 functions as an E3 ligase of TSC1 to regulate CDK4-induced TSC1. This finding suggested that RNF26 promotes ccRCC progression and angiogenesis to some extent by negatively regulating TSC1. CONCLUSION: Our results revealed a novel CDK4/RNF26/TSC1 axis that regulates the anticancer efficacy of CDK4/6 inhibitors and mTOR inhibitors in ccRCC.
Subject(s)
Carcinoma, Renal Cell , Cyclin-Dependent Kinase 4 , Cyclin-Dependent Kinase 6 , Kidney Neoplasms , TOR Serine-Threonine Kinases , Tuberous Sclerosis Complex 1 Protein , Ubiquitin-Protein Ligases , Humans , Cyclin-Dependent Kinase 4/antagonists & inhibitors , TOR Serine-Threonine Kinases/antagonists & inhibitors , TOR Serine-Threonine Kinases/metabolism , Cyclin-Dependent Kinase 6/antagonists & inhibitors , Tuberous Sclerosis Complex 1 Protein/genetics , Ubiquitin-Protein Ligases/metabolism , Mice , Animals , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/metabolism , Kidney Neoplasms/genetics , Cell Line, Tumor , Protein Kinase Inhibitors/pharmacology , Xenograft Model Antitumor Assays , Signal Transduction/drug effects , Cell Proliferation/drug effects , Mice, Nude , Phosphorylation/drug effectsABSTRACT
AIM: To investigate systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) levels in patients with type 2 diabetes at different stages of diabetic retinopathy (DR). METHODS: This retrospective study included 141 patients with type 2 diabetes mellitus (DM): 45 without diabetic retinopathy (NDR), 47 with non-proliferative diabetic retinopathy (NPDR), and 49 with proliferative diabetic retinopathy (PDR). Complete blood counts were obtained, and NLR, PLR, and SII were calculated. The study analysed the ability of inflammatory markers to predict DR using receiver operating characteristic (ROC) curves. The relationships between DR stages and SII, PLR, and NLP were assessed using multivariate logistic regression. RESULTS: The average NLR, PLR, and SII were higher in the PDR group than in the NPDR group (P=0.011, 0.043, 0.009, respectively); higher in the NPDR group than in the NDR group (P<0.001 for all); and higher in the PDR group than in the NDR group (P<0.001 for all). In the ROC curve analysis, the NLR, PLR, and SII were significant predictors of DR (P<0.001 for all). The highest area under the curve (AUC) was for the PLR (0.929 for PLR, 0.925 for SII, and 0.821 for NLR). Multivariate regression analysis indicated that NLR, PLR, and SII were statistically significantly positive and independent predictors for the DR stages in patients with DM [odds ratio (OR)=1.122, 95% confidence interval (CI): 0.200-2.043, P<0.05; OR=0.038, 95%CI: 0.018-0.058, P<0.05; OR=0.007, 95%CI: 0.001-0.01, P<0.05, respectively). CONCLUSION: The NLR, PLR, and SII may be used as predictors of DR.
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Remediating soil contaminated with polycyclic aromatic hydrocarbons (PAHs) presents a significant environmental challenge due to their toxic and carcinogenic properties. Traditional PAHs remediation methods-chemical, thermal, and bioremediation-along with conventional soil-washing agents like surfactants and cyclodextrins face challenges of cost, ecological harm, and inefficiency. Here we show an effective and environmentally friendly calixarene derivative for PAHs removal through soil washing. Thiacalix[4]arene tetrasulfonate (TCAS) has a unique molecular structure of a sulfonate group and a sulfur atom, which enhances its solubility and facilitates selective binding with PAHs. It forms host-guest complexes with PAHs through π-π stacking, OH-π interactions, hydrogen bonding, van der Waals forces, and electrostatic interactions. These interactions enable partial encapsulation of PAH molecules, aiding their desorption from the soil matrix. Our results show that a 0.7% solution of TCAS can extract approximately 50% of PAHs from contaminated soil while preserving soil nutrients and minimizing adverse environmental effects. This research unveils the pioneering application of TCAS in removing PAHs from contaminated soil, marking a transformative advancement in resource-efficient and sustainable soil remediation strategies.
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BACKGROUND: Glenoid bone loss is proposed to be an important risk factor for recurrent anterior shoulder instability. The purpose of the present study was to develop an accurate and reproducible method for quantifying a bone loss in patients with anterior shoulder instability. METHODS: A total of 66 sets of computed tomography images of the glenoid were acquired and en face view was established. Based on the contour of the inferior half and posteroinferior quadrant of the glenoid, the best-fit circle was drawn using the least-squares method with a comparison of the radii. A bone loss was created via a simulated osteotomy, and a method for estimating the bone loss based on the contour of the posteroinferior quadrant was developed. RESULTS: The radii of the best-fit circle were 29.30 ± 1.84 mm and 33.76 ± 2.04 mm, based on the inferior half and posteroinferior quadrant of the glenoid, respectively (P < .01). Bone loss quantification using the contour of the inferior half or posteroinferior quadrant with simulated osteotomy showed a significant difference (P < .01). For a 25% of glenoid bone loss, the estimated value using the traditional method on the contour of the posteroinferior quadrant was 34%. A new method for accurate bone loss quantification was developed based on the contour of the posteroinferior quadrant of the glenoid. CONCLUSION: Estimation of the glenoid bone loss based on the rim of the posteroinferior quadrant may overestimate the glenoid bone loss due to the difference in the radius of the curvature of the inferior half and posteroinferior quadrant. A mathematical method developed to correct this error and may aid in more accurately, measuring the glenoid bone loss using the contour of the posteroinferior quadrant in patients with anterior shoulder instability.
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Volkmann ischemic contracture (VIC) is a devastating condition that results from neglected compartment syndrome, which leads to prolonged ischemia, irreversible tissue necrosis, and various degrees of muscle and nerve damage, causing serious motor and sensory functional implications for the limb and a spectrum of diseases associated with worsening deformities. A thorough understanding of the anatomy and VIC pathophysiology is needed to plan an appropriate strategy. Functioning free muscle transplantation (FFMT) can restore finger movement in a paralyzed limb but requires a three-staged approach to maximize the benefits of FFMT, leading to meaningful finger extrinsic function.
Subject(s)
Compartment Syndromes , Contracture , Ischemic Contracture , Humans , Ischemic Contracture/surgery , Compartment Syndromes/complications , Fingers/surgery , Muscles , Contracture/surgery , Contracture/etiologyABSTRACT
Chemoselective protein modification plays extremely important roles in various biological, medical, and pharmaceutical investigations. Mimicking the mechanism of the chemoselective reaction between natural azaphilones and primary amines, this work successfully simplified the azaphilone scaffold into much simpler 3-acyl-4-pyranones. Examinations confirmed that these slim-size mimics perfectly kept the unique reactivity for selective conjugation with the primary amines including lysine residues of peptides and proteins. The newly developed pyranone tool presents remarkably increased aqueous solubility and compatible second-order rate constant by comparison with the original azaphilone. Additional advantages also include the ease of biorthogonal combinative use with a copper-catalyzed azide-alkyne Click reaction, which was conveniently applied to decorate lysozyme with neutral-, positive- and negative-charged functionalities in parallel. Moderate-degree modification of lysozyme with positively charged quaternary ammoniums was revealed to increase the enzymatic activities.
Subject(s)
Lysine , Muramidase , Lysine/chemistry , Indicators and Reagents , Peptides/chemistry , Amines , Azides/chemistry , Click Chemistry , Alkynes/chemistryABSTRACT
Background: Initial choices of antimicrobial therapy for most cases of community-acquired pneumonia (CAP) in children under 5 years of age are typically based on local epidemiology, risk factors assessment, and subsequent clinical parameters and positive cultures, which can lead to the underdiagnosis and underestimation of lung infections caused by uncommon pathogens. Contezolid, an orally administered oxazolidinone antibiotic, gained approval from the National Medical Products Administration (NMPA) of China in June 2021 for managing complicated skin and soft tissue infections (cSSTI) caused by staphylococcus aureus (SA), streptococcus pyogenes, or streptococcus agalactis. Owing to its enhanced safety profile and ongoing clinical progress, the scope of contezolid's clinical application continues to expand, benefiting a growing number of patients with Gram-positive bacterial infections. Case summary: In this report, we present the first use of contezolid in a toddler with severe CAP caused by SA, aiming to avoid potential adverse drug reactions (ADRs) associated with vancomycin and linezolid. Conclusion: Although contezolid has not been officially indicated for CAP, it has been shown to be effective and safe in the management of SA-induced severe CAP in this toddler, suggesting its potential as an alternative option in the dilemma, especially for patients who are susceptible or intolerant to ADRs associated with first-line anti-methicillin-resistant staphylococcus aureus (MRSA) antimicrobial agents.
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Circular RNAs (circRNAs) have been extensively studied for their critical roles as noncoding RNAs (ncRNAs) in gastric cancer (GC). In this study, we focused on the expression, function and molecular mechanism of circRNA_0023685 in gastric cancer (GC) to provide new ways for the diagnosis and treatment of GC. Firstly, a novel differentially expressed circRNA, circRNA_0023685, was identified, and its differential expression in GC plasma, tissue, and cell lines was further verified by RT-qPCR. Next, circRNA_0023685 was verified to promote the proliferation, migration and apoptosis of GC cells in vitro. CircRNA_0023685 was also proved to enhance the growth of GC tumors in xenograft models. Finally, for excavating the mechanism to promote GC, downstream microRNAs (miRNAs) and mRNAs were screened by bioinformatics analyses. After intersecting the target genes and genes enriched in GO analysis, a circRNA competing endogenous RNAs (ceRNAs) network was built. A protein-protein interaction (PPI) network was then constructed to find the candidate gene, APP. Our study confirmed that the highly expressed circRNA_0023685 could promote GC, which provided a new clinical diagnostic biomarker and therapeutic target for GC.
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Background: Observational studies have indicated associations between type 2 diabetes mellitus (T2DM) and both colorectal cancer (CRC) and inflammatory bowel disease (IBD). However, the underlying causality and biological mechanisms between these associations remains unclear. Methods: We conducted a bidirectional Mendelian randomization (MR) analysis employing summary statistics from genome-wide association studies involving European individuals. The inverse variance weighting (IVW) method was the primary method used to assess causality. Additionally, we applied MR Egger, Weighted median, Simple mode, and Weighted mode to evaluate the robustness of the results. Outliers were identified and eliminated using the MR-PRESSO, while the MR-Egger intercept was used to assess the horizontal pleiotropic effects of single nucleotide polymorphisms (SNPs). The heterogeneity was evaluated using the Cochrane Q test, and sensitivity analysis was performed using leave-one-out method. The F statistic was calculated to evaluate weak instrumental variable bias. Finally, a pilot bioinformatics analysis was conducted to explore the underlying biological mechanisms between T2DM and IBD/UC. Results: The IVW results demonstrated that T2DM significantly reduced risks of IBD (OR=0.885, 95% CI: 0.818-0.958, P=0.002) and ulcerative colitis (UC) (OR=0.887, 95% CI: 0.812-0.968, P=0.007). Although the 95% CIs of MR Egger, Weighted median, Simple mode, and Weighted mode were broad, the majority of their estimates were consistent with the direction of IVW. Despite significant heterogeneity among SNPs, no horizontal pleiotropy was observed. The leave-one-out analysis showed that the causality remained consistent after each SNP was removed, underscoring the reliability of the results. Reverse MR analysis indicated that genetic susceptibility to both CRC and IBD had no significant effect on the relative risk of T2DM. Ten hub genes were identified, which mainly enriched in pathways including maturity onset diabetes of the young, thyroid cancer, gastric acid secretion, longevity regulating pathway, melanogenesis, and pancreatic secretion. Conclusion: The presence of T2DM does not increase the risk of CRC or IBD. Moreover, T2DM might reduce risk of IBD, including UC. Conversely, the occurrence of CRC or IBD does not influence the risk of T2DM. The association between T2DM and IBD/UC may be related to the changes in multiple metabolic pathways and CTLA-4-mediated immune response.
Subject(s)
Colitis, Ulcerative , Diabetes Mellitus, Type 2 , Inflammatory Bowel Diseases , Humans , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/genetics , Genome-Wide Association Study , Mendelian Randomization Analysis , Reproducibility of Results , Inflammatory Bowel Diseases/genetics , Computational BiologyABSTRACT
Sulfur disproportionation (S0DP) poses a challenge to the robust application of sulfur autotrophic denitrification due to unpredictable sulfide production, which risks the safety of downstream ecosystems. This study explored the S0DP occurrence boundaries with nitrate loading and temperature effects. The boundary values increased with the increase in temperature, exhibiting below 0.15 and 0.53 kg-N/m3/d of nitrate loading at 20 and 30 °C, respectively. A pilot-scale sulfur-siderite packed bioreactor (150 m3/d treatment capacity) was optimally designed with multiple subunits to dynamically distribute the loading of sulfur-heterologous electron acceptors. Operating two active and one standby subunit achieved an effective denitrification rate of 0.31 kg-N/m3/d at 20 °C. For the standby subunit, involving oxygen by aeration effectively transformed the facultative S0DP functional community from S0DP metabolism to aerobic respiration, but with enormous sulfur consumption resulting in ongoing sulfate production of over 3000 mg/L. Meanwhile, acidification by the sulfur oxidation process could reduce the pH to as low as 2.5, which evaluated the Gibbs free energy (ΔG) of the S0DP reaction to +2.56 kJ, thermodynamically suppressing the S0DP occurrence. Therefore, a multisubunit design along with S0DP inhibition strategies of short-term aeration and long-term acidification is suggested for managing S0DP in various practical sulfur-packed bioreactors.
Subject(s)
Carbonates , Ecosystem , Ferric Compounds , Nitrates , Nitrates/metabolism , Autotrophic Processes , Temperature , Sulfur/metabolism , Bioreactors , Denitrification , NitrogenABSTRACT
Executive function, including working memory, attention and inhibitory control, is crucial for decision making, thinking and planning. Lisdexamfetamine, the prodrug of d-amphetamine, has been approved for treating attention-deficit hyperactivity disorder and binge eating disorder, but whether it improves executive function under non-disease condition, as well as the underlying pharmacokinetic and neurochemical properties, remains unclear. Here, using trial unique non-matching to location task and five-choice serial reaction time task of rats, we found lisdexamfetamine (p.o) enhanced spatial working memory and sustained attention under various cognitive load conditions, while d-amphetamine (i.p) only improved these cognitive performances under certain high cognitive load condition. Additionally, lisdexamfetamine evoked less impulsivity than d-amphetamine, indicating lower adverse effect on inhibitory control. In vivo pharmacokinetics showed lisdexamfetamine produced a relative stable and lasting release of amphetamine base both in plasma and in brain tissue, whereas d-amphetamine injection elicited rapid increase and dramatical decrease in amphetamine base levels. Microdialysis revealed lisdexamfetamine caused lasting release of dopamine within the medial prefrontal cortex (mPFC), whereas d-amphetamine produced rapid increase followed by decline to dopamine level. Moreover, lisdexamfetamine elicited more obvious efflux of noradrenaline than that of d-amphetamine. The distinct neurochemical profiles may be partly attributed to the different action of two drugs to membranous catecholamine transporters level within mPFC, detecting by Western Blotting. Taken together, due to its certain pharmacokinetic and catecholamine releasing profiles, lisdexamfetamine produced better pharmacological action to improving executive function. Our finding provided valuable evidence on the ideal pharmacokinetic and neurochemical characteristics of amphetamine-type psychostimulants in cognition enhancement.