Regulation of the NF-κB/NLRP3 signalling pathway by Shenghui Yizhi decoction reduces neuroinflammation in mice with Alzheimer's disease.

BACKGROUND: Shenghui Yizhi Decoction (SHYZD) has exhibited the capacity to enhance cognitive function and learning abilities in individuals diagnosed with Alzheimer's disease (AD) while ameliorating pre-existing neuroinflammation. Nevertheless, the precise mechanism underlying its therapeutic effects on AD remains to be elucidated. METHODS: Twenty-four male SAMP8 mice were randomly divided into three groups, and eight male SAMR1 mice were used as a blank control, to examine their learning and spatial memory abilities. The expression of amyloid ß1-42 (Aß1-42) was detected by immunohistochemical staining of hippocampal tissue. ELISA was used to detect the interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) expressions. Real time PCR was used to detect NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteine protease-1 (Caspase-1), and IL-1ß mRNA expression. Western blot was used to detect nuclear factor kappa-B (NF-κB), inhibitor of NF-κB α (IκBα), IκB kinase α (IKKα), NLRP3, Caspase-1, and IL-1ß protein expression. RESULTS: In this study, SAMP8 mice, employed as an AD model, displayed markedly diminished abilities in terms of spatial localization, navigation, and spatial exploration when compared to the blank control group. Additionally, there was a substantial upregulation of Aß1-42 expression in the hippocampus of these mice, along with a significant increase in the levels of inflammation-associated factors, including IL-1ß, IL-6, TNF-α, NLRP3, Caspase-1, as well as the NF-κB pathway-related proteins, namely, NF-κB, IκBα, and IKKα. Moreover, after treatment with positive drugs (donepezil hydrochloride) and SHYZD, the learning abilities of the mice exhibited significant improvements. Furthermore, the hallmark AD protein Aß1-42, inflammatory factors, and NF-κB/NLRP3 signalling pathway proteins were significantly reduced. These findings collectively suggest that SHYZD exerts a therapeutic effect on AD. CONCLUSION: In summary, the specific molecular mechanisms through which SHYZD alleviates AD and the potential role for SHYZD in the NF-κB/NLRP3 signalling pathway are identified in this study.

Efficient cleavage of CαCß bonds in lignin using tetrabutylammonium tetrafluoroborate as both the catalyst and auxiliary electrolyte.

Lignin is a promising alternative to fossil resources due to its abundance of benzene ring monomers. However, the stability of the CαCß bond in lignin has hindered its efficient depolymerization. Electrochemical methods for breaking this bond are not well-studied. This paper presents a novel approach for catalytic depolymerization of lignin to produce acetals under mild conditions, without the need for additional catalysts. Under room temperature and in an air atmosphere, the combination of tetrabutylammonium tetrafluoroborate (TBABF4) as an auxiliary electrolyte and methanol (MeOH) as a solvent has shown high selectivity in catalyzing the cleavage of CαCß bonds in lignin. Over 90.0 % of the resulting products are acetals, with the optimal conditions being a substrate concentration of 0.02 M, TBABF4 concentration of 0.008 M, a constant current of 30 mA, and a reaction time of 3 h. This led to a substrate conversion rate of 95.8 % and a product yield of 98.0 % for benzaldehyde dimethyl acetal (Bda). The mechanism study reveals that the tributyl ammonium radical cation decomposed by TBABF4 is adsorbed on the electrode surface. Subsequently, the adsorbed O2 is activated to form superoxide anion radical active species through single electron transfer, which plays a crucial catalytic role. TBABF4 acts as both an auxiliary electrolyte and a catalyst in this process. This research introduces a novel approach for electrocatalytic depolymerization of inert CαCß bonds in lignin, leading to the selective conversion into acetal chemicals.

Bioaccessibility and bioavailability assessment of cadmium in rice: In vitro simulators with/without gut microbiota and validation through in vivo mouse and human data.

Assessing the bioaccessibility and bioavailability of cadmium (Cd) is crucial for effective evaluation of the exposure risk associated with intake of Cd-contaminated rice. However, limited studies have investigated the influence of gut microbiota on these two significant factors. In this study, we utilized in vitro gastrointestinal simulators, specifically the RIVM-M (with human gut microbial communities) and the RIVM model (without gut microbial communities), to determine the bioaccessibility of Cd in rice. Additionally, we employed the Caco-2 cell model to assess bioavailability. Our findings provide compelling evidence that gut microbiota significantly reduces Cd bioaccessibility and bioavailability (p<0.05). Notably, strong in vivo-in vitro correlations (IVIVC) were observed between the in vitro bioaccessibilities and bioavailabilities, as compared to the results obtained from an in vivo mouse bioassay (R2 = 0.63-0.65 and 0.45-0.70, respectively). Minerals such as copper (Cu) and iron (Fe) in the food matrix were found to be negatively correlated with Cd bioaccessibility in rice. Furthermore, the results obtained from the toxicokinetic (TK) model revealed that the predicted urinary Cd levels in the Chinese population, based on dietary Cd intake adjusted by in vitro bioaccessibility from the RIVM-M model, were consistent with the actual measured levels (p > 0.05). These results indicated that the RIVM-M model represents a potent approach for measuring Cd bioaccessibility and underscore the crucial role of gut microbiota in the digestion and absorption process of Cd. The implementation of these in vitro methods holds promise for reducing uncertainties in dietary exposure assessment.

Iron­carbon complex types and bonding forms jointly control organic carbon mineralization in paddy soils.

The crucial role of iron (Fe) oxides in stabilizing soil organic carbon (SOC) is well recognized, but their effects on SOC mineralization remain poorly understood. To address this knowledge gap, we evaluated the effects of four typical Fe-bound OC (Fe-OC) complexes including adsorbed ferrihydrite (Fh)- and goethite (Goe)- 13C, coprecipitated Fh/Goe-13C and 13C-glucose as the control, on OC mineralization during an 80-day anaerobic incubation in a paddy soil. 13C-tracing indicated that Fe-13C complexes significantly stimulated CO2 emissions from both the input 13C and SOC compared with glucose alone. In contrast, the addition of Fh- and Goe-C complexes consistently inhibited CH4 emissions by 72-91 % and 21-61 % compared with glucose addition, respectively. Fe-OC complexes reduced the CO2 equivalent by 62-71 % and 17-41 % in soils with Fh-C and Goe-C complexes, respectively. We concluded that Fe crystallinity and its bonding forms with organic carbon jointly control SOC mineralization. The coprecipitated Goe-C complexes had the lowest OC mineralization rate and highest OC residence time among four Fe-OC complexes. These findings highlighted that promoting the formation of coprecipitated well-ordered minerals would increase SOC sequestration by reducing OC mineralization and mitigating the global warming effect in paddy management.

Modulation of m6A RNA modification by DAP3 in cancer cells.

N6-methyladenosine (m6A) RNA methylation is a prevalent RNA modification that significantly impacts RNA metabolism and cancer development. Maintaining the global m6A levels in cancer cells relies on RNA accessibility to methyltransferases and the availability of the methyl donor S-adenosylmethionine (SAM). Here, we reveal that death associated protein 3 (DAP3) plays a crucial role in preserving m6A levels through two distinct mechanisms. First, although DAP3 is not a component of the m6A writer complex, it directly binds to m6A target regions, thereby facilitating METTL3 binding. Second, DAP3 promotes MAT2A's last intron splicing, increasing MAT2A protein, cellular SAM, and m6A levels. Silencing DAP3 hinders tumorigenesis, which can be rescued by MAT2A overexpression. This evidence suggests DAP3's role in tumorigenesis, partly through m6A regulation. Our findings unveil DAP3's complex role as an RNA-binding protein and tumor promoter, impacting RNA processing, splicing, and m6A modification in cancer transcriptomes.

Nickel-Catalyzed Enantioselective Alkylation of Primary Phosphines.

Functional molecules derived from stereogenic phosphorus centers have important applications in the discovery of drugs and agrochemicals. They are also widely utilized as chiral ligands or organocatalysts for diverse asymmetric transformations. However, access to P-stereogenic motifs has always been regarded as a highly challenging yet desirable goal in organic synthesis. The development of general and practical methods for the stereoselective construction of synthetically versatile P(III)-stereogenic phosphines is particularly appealing but remains elusive. Herein, we describe a nickel-catalyzed asymmetric alkylation of primary phosphines with alkyl halides for the synthesis of P-stereogenic secondary phosphine-boranes with high enantioselectivity and broad substrate scope. The resulting optically active secondary phosphine-boranes allow for further stereospecific transformations, thereby establishing a modular and efficient platform for the diversity-oriented construction of P-stereogenic phosphine compounds.

Acute mesenteric ischaemia: a rare complication mimicking necrotising enterocolitis in a premature infant.

Acute mesenteric ischaemia (AMI) is a life-threatening gastrointestinal complication uncommonly described in premature infants. The diagnosis of AMI is challenging and may be delayed due to the limitation of accurate diagnostic imaging and non-specific clinical signs. Furthermore, AMI can be misdiagnosed as necrotising enterocolitis (NEC) due to the overlapping clinical and radiological features. Though known to be associated with high mortality rates, early recognition and intervention can improve the survival rates in infants with AMI. We describe a case of a premature infant who presented with an acute abdomen and haemodynamic collapse, initially treated for NEC but later diagnosed with AMI intraoperatively. Due to the extensive bowel necrosis, surgical intervention was rendered futile and the infant finally succumbed to the disease.

Trapezius Island Myocutaneous Flap for Head, Neck, and Facial Reconstruction in Neurofibromatosis Type 1-Associated Plexiform Neurofibromas.

BACKGROUND: Reconstruction of significant soft tissue defects in the head and neck region after resection of extensive plexiform neurofibromas, as well as preservation and restoration of cosmetic and functional aspects, presents a considerable challenge. AIMS: The purpose is to evaluate the feasibility of eTMF in repairing substantial defects after the complete resection of NF1 PN. PATIENTS AND METHODS: Patients diagnosed with substantial neurofibromatosis (NP) type 1 (NF1), according to the revised criteria, underwent complete resection and remodeling of the facial aesthetic unit. An extended vertical lower trapezius island myocutaneous flap (eTIMF) was used for the defect reconstruction. Perioperative complications were evaluated using the Clavien-Dindo classification. ECOG PS was assessed. Postoperative follow-up at 6 months and completion of UW-QOL. The questionnaire included swallowing, chewing, speech, and quality of life scores. Two patients had pathogenic missense variants: c.5609G>A (p.Arg1870Gln) in exon 38 of NF1 in the first case, and c.4600C>T (p.Arg1534*) in exon 35 in the second case. RESULTS: Two eTMFs were harvested successfully. Five facial esthetic units were remodeled, and 4 units were remodeled. Two extensive tumors were nearly entirely removed. No severe complications were noted. The ECOG PS improved from grade 3 in the first week postsurgery to grade 0 by the eighth week. The UW-QOL results indicated that swallowing, chewing, and speaking functions returned to their preoperative levels, with a 40% improvement in quality of life, reaching 60% and 80%, respectively. CONCLUSIONS: eTMF to repair substantial defects following total resection of NF1 PN and facial esthetic unit remodeling enhances appearance, function, and psychosocial outcomes. This technique is safe, efficient, resource-conserving, and simple to implement.

Delayed oral health care due to cost among US adults with diabetes, 2018-2019.

BACKGROUND: Although untreated periodontitis increases the risk of developing diabetic complications, people with diabetes are less likely to use dental services. The authors estimated the prevalence of reporting delayed needed oral health care due to cost and associated risk indicators by diabetes status. METHODS: The authors analyzed data for 43,291 adults who participated in the 2018 and 2019 Medical Expenditure Panel Surveys. The authors used t tests to compare crude estimates of delayed oral health care by diabetes status. Adjusted estimates were obtained from logistic regression models that controlled for sociodemographic, medical and dental insurance, health status, and geographic variables. Multivariable logistic regression models were run separately for adults with and without diabetes to identify factors that were associated with delayed oral health care. RESULTS: After controlling for covariates, the difference in delayed oral health care prevalence between adults with diabetes (18%) and without diabetes (16%) remained significant. Lack of medical insurance and fair or poor self-rated health status were the highest predictors of delayed oral health care among those with diabetes. CONCLUSIONS: Despite guidelines, factors other than biology and perceived need may impede access to oral health care for people with diabetes. PRACTICAL IMPLICATIONS: For uninsured adults, policies should prioritize enhancing access to regular ambulatory care and promoting awareness about the importance of preventing and treating dental conditions. In addition, addressing the medical and psychosocial aspects of diabetes in affected patients could affect positively their overall sense of well-being and self-rated health status, potentially encouraging greater use of oral health care services.

Study on the efficient electrocatalytic depolymerization of α-O-4 bond in lignin assisted by simple electrolyte.

Lignin is anticipated to serve as a replacement for dwindling fossil fuel resources owing to its abundant sources and renewable nature. The electrochemical oxidation technique for depolymerizing lignin has garnered significant interest for its environmentally friendly and mild operating conditions. Nevertheless, the current utilization of auxiliary electrolytes, predominantly organic bases, ionic liquids, and other specialized substances, poses a constraint on the widespread adoption of this approach. Furthermore, there is a scarcity of instances where electrochemical technology has been employed to depolymerize the α-O-4 bond in lignin for the production of highly selective acetals. In this study, a sodium chloride/methanol (NaCl/MeOH) system was utilized for the direct depolymerization of the α-O-4 bond in a lignin model molecule, specifically benzyl phenyl ether (BPE). The optimal conditions resulted in a 95.2 % conversion rate of the BPE substrate and a high yield of 94.5 % for the main product, benzaldehyde dimethyl acetal(Bda). This research offers a promising approach for the electrocatalytic depolymerization of α-O-4 bonds in lignin, leading to the selective production of acetal chemicals using a common auxiliary electrolyte at room temperature in just 2 h.

Classification and Treatment of Complications Related to Titanium and Biodegradable Miniplates Using the Lip-Split Transmandibular Approach for Oral and Oropharyngeal Oncological Surgery.

BACKGROUND: There is a lack of classified definitions and corresponding treatment principles for complications related to titanium miniplate (TMP) and biodegradable miniplate (BMP). AIMS: This study proposes a classification system for complications related to TMP and BMP osteosynthesis and evaluates the effectiveness of the classification system in the treatment of the complications. METHODS: One hundred forty-two patients with advanced-stage oral cavity and oropharynx squamous cell carcinoma (SCC) underwent oncological surgery via lip-split transmandibular (LTM) approach including midline, paramedian, stair-step, and triangle. 54.9% of patients were treated with TMP, and 45.1% were treated with BMP for osteosynthesis. The classification of complications is divided into grades 0, 1, 2, and 3. Grade 0 is defined as having no complications. The evaluation criteria for treating complications were significant improvement, partial improvement, and no improvement. RESULTS: All patients underwent en bloc resection of the tumor with histologically negative margins via the LTM approach. The overall success rate of the flap is 98.6%. 25.3%, 48.6%, 14.8%, and 11.3% of patients were treated with midline, paramedian, stair-step, and triangular osteotomy approaches, respectively. A significant increase in the number of paramedian osteotomies was observed compared with other types of osteotomy (P < 0.05). Grades 0, 1, 2, and 3 developed in 54.2%, 12.0%, 14.8%, and 19.0% of patients, respectively. No significant differences in the grade of complications were observed between the TMP group and the BMP group. Sixty-five patients with complications, grades 1, 2, and 3 occurred in 26.2%, 32.3%, and 41.5% of patients. The midline, paramedian, stair-step, and triangle osteotomy approaches were used in 26.1%, 47.7%, and 10.8%, respectively. The incidence of complications in the paramedian osteotomy was significantly higher than that in the other osteotomy (P < 0.05). 83.1% of patients showed significant improvement, 10.8% showed partial improvement, and 6.1% showed no improvement. No significant differences in the treatment outcomes were observed between the TMP group and the BMP group. CONCLUSIONS: The incidence of complications in paramedian osteotomy is also significantly higher than 3 types of osteotomy, and 83.1% of patients showed significant improvement in complications. The complication classification system related to TMP and BMP osteosynthesis are easy to implement and feasible in clinical practice.

Artificial intelligence software for assessing brain ischemic penumbra/core infarction on computed tomography perfusion: A real-world accuracy study.

BACKGROUND: With the increasingly extensive application of artificial intelligence (AI) in medical systems, the accuracy of AI in medical diagnosis in the real world deserves attention and objective evaluation. AIM: To investigate the accuracy of AI diagnostic software (Shukun) in assessing ischemic penumbra/core infarction in acute ischemic stroke patients due to large vessel occlusion. METHODS: From November 2021 to March 2022, consecutive acute stroke patients with large vessel occlusion who underwent mechanical thrombectomy (MT) post-Shukun AI penumbra assessment were included. Computed tomography angiography (CTA) and perfusion exams were analyzed by AI, reviewed by senior neurointerventional experts. In the case of divergences among the three experts, discussions were held to reach a final conclusion. When the results of AI were inconsistent with the neurointerventional experts' diagnosis, the diagnosis by AI was considered inaccurate. RESULTS: A total of 22 patients were included in the study. The vascular recanalization rate was 90.9%, and 63.6% of patients had modified Rankin scale scores of 0-2 at the 3-month follow-up. The computed tomography (CT) perfusion diagnosis by Shukun (AI) was confirmed to be invalid in 3 patients (inaccuracy rate: 13.6%). CONCLUSION: AI (Shukun) has limits in assessing ischemic penumbra. Integrating clinical and imaging data (CT, CTA, and even magnetic resonance imaging) is crucial for MT decision-making.

Multimodal Management of Ruptured Internal Carotid Artery Blood Blister-like Aneurysm: Technical Notes and Case Series of Surgical Muscle Wrapping and Fenestration Clipping Combined with Flow-Diverter Embolization.

OBJECTIVE: To evaluate the effects of a multimodal management technique combining surgical muscle wrapping, clipping, and flow-diverter stent (FDS) placement in patients with ruptured blood blister-like aneurysms (BBAs) in the internal carotid artery (ICA). METHODS: In a retrospective case series review from 2020 to 2023, 3 patients with ruptured ICA BBAs underwent multimodal management, an approach combining muscle wrapping, surgical clipping, and FDS embolization. The aneurysm sac was initially packed and wrapped with multiple tailored temporalis muscle grafts and then secured using fenestration clips, with good preservation of the ICA branches. The FDS was placed 2-3 weeks after the clipping. RESULTS: All 3 patients had right ICA BBAs (mean age, 52 years). The modified Hunt and Hess grades ranged from 2 to 3, and the Fisher grades ranged from 3 to 4. The mean angiography follow-up time was 27.7 months (15, 31, and 37 months). There were no instances of symptomatic vasospasm or visible ischemic stroke during follow-up computed tomography. No patient required cerebrospinal fluid shunt implantation, and all achieved favorable neurological outcomes (modified Rankin scale 0-1). Follow-up digital subtraction angiography revealed no evidence of aneurysm recurrence or significant ICA stenosis. CONCLUSIONS: We discuss a promising multimodal management approach for ruptured ICA BBAs combining muscle wrapping, surgical clipping, and FDS embolization. This technique was safe and effective in preventing re-rupture, achieving positive short-term clinical outcomes. Further research and more extensive studies are required to validate the long-term efficacy of this approach.

Xylooligosaccharides alleviate the carbohydrate-enriched diet-induced intestinal barrier dysfunction in carp Megalobrama amblycephala by promoting intestinal development, immunity and gut microbiota.

To date, although the high-carbohydrate (HC) feed has been extensively adopted in the aquaculture industry, its effects on the intestinal function and development of aquatic animals still remain unclear. In addition, the corresponding nutritional intervention is still barely reported. This study aimed to evaluate the influence of xylooligosaccharides (XOS) on the intestinal health of Megalobrama amblycephala subjected to a HC feeding. Fish (average weight: 44.55 ± 0.15 g) were randomly offered 3 diets, including a control one (29 % carbohydrate), a HC one (41 % carbohydrate), and a XOS supplemented one (HC + 1.0 % XOS, HCX) respectively for 12 weeks. The HC feeding caused morphological abnormalities of intestine, an increased intestinal permeability, and the intestinal immunosuppression, all of which were markedly reversed by XOS administration. In addition, compared with the HC group, HCX feeding remarkably promoted the intestinal activities of digestive and brush border enzymes, and the expressions of cell proliferation-related proteins (Wnt10b and Cyclin D1). The 16s rDNA sequencing also revealed that XOS administration increased the abundance of beneficial bacteria, and decreased that of pathogenic ones. In conclusion, dietary supplementation of XOS improved the intestinal histomorphology, barrier function, cell proliferation and bacterial communities of carbohydrate-overloaded fish Megalobrama amblycephala.

Luteolin-7-diglucuronide, a novel PTP1B inhibitor, ameliorates hepatic stellate cell activation and liver fibrosis in mice.

Liver fibrosis, one of the leading causes of morbidity and mortality worldwide, lacks effective therapy. The activation of hepatic stellate cells (HSCs) is the dominant event in hepatic fibrogenesis. Luteolin-7-diglucuronide (L7DG) is the major flavonoid extracted from Perilla frutescens and Verbena officinalis. Their beneficial effects in the treatment of liver diseases were well documented. In this study we investigated the anti-fibrotic activities of L7DG and the potential mechanisms. We established TGF-ß1-activated mouse primary hepatic stellate cells (pHSCs) and human HSC line LX-2 as in vitro liver fibrosis models. Co-treatment with L7DG (5, 20, 50 µM) dose-dependently decreased TGF-ß1-induced expression of fibrotic markers collagen 1, α-SMA and fibronectin. In liver fibrosis mouse models induced by CCl4 challenge alone or in combination with HFHC diet, administration of L7DG (40, 150 mg·kg-1·d-1, i.g., for 4 or 8 weeks) dose-dependently attenuated hepatic histopathological injury and collagen accumulation, decreased expression of fibrogenic genes. By conducting target prediction, molecular docking and enzyme activity detection, we identified L7DG as a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 2.10 µM. Further studies revealed that L7DG inhibited PTP1B activity, up-regulated AMPK phosphorylation and subsequently inhibited HSC activation. This study demonstrates that the phytochemical L7DG may be a potential therapeutic candidate for the treatment of liver fibrosis.

Optimizing ABA-based chemically induced proximity for enhanced intracellular transcriptional activation and modification response to ABA.

Abscisic acid (ABA)-based chemically induced proximity (CIP) is primarily mediated by the interaction of the ABA receptor pyrabactin resistance 1-like 1 (PYL1) and the 2C-type protein phosphatase ABI1, which confers ABA-induced proximity to their fusion proteins, and offers precise temporal control of a wide array of biological processes. However, broad application of ABA-based CIP has been limited by ABA response intensity. In this study, we demonstrated that ABA-induced interaction between another ABA receptor pyrabactin resistance 1 (PYR1) and ABI1 exhibited higher ABA response intensity than that between PYL1 and ABI1 in HEK293T cells. We engineered PYR1-ABI1 and PYL1-ABI1 into ABA-induced transcriptional activation tools in mammalian cells by integration with CRISPR/dCas9 and found that the tool based on PYR1-ABI1 demonstrated better ABA response intensity than that based on PYL1-ABI1 for both exogenous and endogenous genes in mammalian cells. We further achieved ABA-induced RNA m6A modification installation and erasure by combining ABA-induced PYR1-ABI1 interaction with CRISPR/dCas13, successfully inhibiting tumor cell proliferation. We subsequently improved the interaction of PYR1-ABI1 through phage-assisted continuous evolution (PACE), successfully generating a PYR1 mutant (PYR1m) whose interaction with ABI1 exhibited a higher ABA response intensity than that of the wild-type. In addition, we tested the transcriptional activation tool based on PYRm-ABI1 and found that it also showed a higher ABA response intensity than that of the wild type. These results demonstrate that we have developed a novel ABA-based CIP and further improved upon it using PACE, providing a new approach for the modification of other CIP systems.

A radiomics nomogram based on multiparametric MRI for diagnosing focal cortical dysplasia and initially identifying laterality.

BACKGROUND: Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation. The diagnosis of FCD is challenging. We generated a radiomics nomogram based on multiparametric magnetic resonance imaging (MRI) to diagnose FCD and identify laterality early. METHODS: Forty-three patients treated between July 2017 and May 2022 with histopathologically confirmed FCD were retrospectively enrolled. The contralateral unaffected hemispheres were included as the control group. Therefore, 86 ROIs were finally included. Using January 2021 as the time cutoff, those admitted after January 2021 were included in the hold-out set (n = 20). The remaining patients were separated randomly (8:2 ratio) into training (n = 55) and validation (n = 11) sets. All preoperative and postoperative MR images, including T1-weighted (T1w), T2-weighted (T2w), fluid-attenuated inversion recovery (FLAIR), and combined (T1w + T2w + FLAIR) images, were included. The least absolute shrinkage and selection operator (LASSO) was used to select features. Multivariable logistic regression analysis was used to develop the diagnosis model. The performance of the radiomic nomogram was evaluated with an area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration and clinical utility. RESULTS: The model-based radiomics features that were selected from combined sequences (T1w + T2w + FLAIR) had the highest performances in all models and showed better diagnostic performance than inexperienced radiologists in the training (AUCs: 0.847 VS. 0.664, p = 0.008), validation (AUC: 0.857 VS. 0.521, p = 0.155), and hold-out sets (AUCs: 0.828 VS. 0.571, p = 0.080). The positive values of NRI (0.402, 0.607, 0.424) and IDI (0.158, 0.264, 0.264) in the three sets indicated that the diagnostic performance of Model-Combined improved significantly. The radiomics nomogram fit well in calibration curves (p > 0.05), and decision curve analysis further confirmed the clinical usefulness of the nomogram. Additionally, the contrast (the radiomics feature) of the FCD lesions not only played a crucial role in the classifier but also had a significant correlation (r = -0.319, p < 0.05) with the duration of FCD. CONCLUSION: The radiomics nomogram generated by logistic regression model-based multiparametric MRI represents an important advancement in FCD diagnosis and treatment.

Unraveling the Link: Seizure Characteristics and Ammonia Levels in Urea Cycle Disorder During Hyperammonemic Crises.

BACKGROUND: This retrospective clinical study performed at a single clinical center aimed to identify the prevalence of seizures in individuals with urea cycle disorders (UCDs) with and without hyperammonemic (HA) crises. In addition, we sought to correlate the utility of biochemical markers and electroencephalography (EEG) in detecting subclinical seizures during HA. METHODS: Medical records of individuals with UCDs enrolled in Urea Cycle Disorders Consortium Longitudinal Study (UCDC-LS) (NCT00237315) at Children's National Hospital between 2006 and 2022 were reviewed for evidence of clinical and subclinical seizuress during HA crises, and initial biochemical levels concurrently. RESULTS: Eighty-five individuals with UCD were included in the analyses. Fifty-six of the 85 patients (66%) experienced HA crises, with a total of 163 HA events. Seizures are observed in 13% of HA events. Among all HA events with concomitant EEG, subclinical seizures were identified in 27% of crises of encephalopathy without clinical seizures and 53% of crises with clinical seizures. The odds of seizures increases 2.65 (95% confidence interval [CI], 1.51 to 4.66) times for every 100 µmol/L increase in ammonia and 1.14 (95% CI, 1.04 to 1.25) times for every 100 µmol/L increase in glutamine. CONCLUSIONS: This study highlights the utility of EEG monitoring during crises for patients presenting with clinical seizures or encephalopathy with HA. During HA events, measurement of initial ammonia and glutamine can help determine risk for seizures and guide EEG monitoring decisions.

Visible-light promoted radical cascade cyclization of 3-allyl-2-arylquinazolinones for the synthesis of phosphorylated dihydroisoquinolino[1,2-b]quinazolinones.

A novel visible-light promoted metal-free radical cascade cyclization reaction has been developed with 3-allyl-2-arylquinazolinones as a new class of radical acceptor. This photocatalytic protocol represents an efficient approach to construct phosphorylated dihydroisoquinolino[1,2-b]quinazolinones featuring mild conditions, broad substrate scope, and gram-scale synthesis.

Long-term agricultural cultivation decreases microbial nutrient limitation in coastal saline soils.

Soil enzyme activities are pivotal for diverse biochemical processes and are sensitive to land use changes. They can indicate soil microbial nutrient limitations. Nonetheless, the mechanism governing the response of soil microbial nutrient limitation to land use alterations in coastal regions remains elusive. We assessed soil nutrients, microbial biomass, and extracellular enzyme activities across various land use types-natural (wasteland and woodland) and agricultural (farmland and orchard)-in the Hangzhou Bay area, China. All four land use types experience co-limitation by carbon (C) and phosphorus (P). However, the extent of microbial resource limitations varies among them. Long-term agricultural practices diminish microbial C and P limitations in farmland and orchard soils compared to natural soils, as evidenced by lower ecoenzymatic C:N ratios and vector lengths, alongside higher microbial carbon use efficiency (CUE). Soil nutrient stoichiometric ratios and CUE are primary factors influencing microbial C and P limitations. Thus, fostering appropriate land use and management practices proves imperative to regulate soil nutrient cycles and foster the sustainable management of coastal areas.