A diagnostic model for differentiating tuberculous spondylodiscitis from pyogenic spondylodiscitis based on pathogen-confirmed patients.

OBJECTIVE: This study aimed to distinguish tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) based on laboratory, magnetic resonance imaging (MRI) and computed tomography (CT) findings. Further, a novel diagnostic model for differential diagnosis was developed. METHODS: We obtained MRI, CT and laboratory data from TS and PS patients. Predictive models were built using binary logistic regression analysis. The receiver operating characteristic curve was analyzed. Both internal and external validation was performed. RESULTS: A total of 81 patients with PS (n = 46) or TS (n = 35) were enrolled. All patients had etiological evidence from the focal lesion. Disc signal or height preservation, skip lesion or multi segment (involved segments ≥ 3) involvement, paravertebral calcification, massive sequestra formation, subligamentous bone destruction, bone erosion with osteosclerotic margin, higher White Blood Cell Count (WBC) and positive result of tuberculosis infection T cell spot test (T-SPOT.TB) were more prevalent in the TS group. A diagnostic model was developed and included four predictors: WBC<7.265 * (10^9/L), skip lesion or involved segments ≥ 3, massive sequestra formation and subligamentous bone destruction. The model showed good sensitivity, specificity, and total accuracy (91.4%, 95.7%, and 93.8%, respectively); the area under the receiver operating characteristic curve (AUC) was 0.981, similar to the results of internal validation using bootstrap resampling (1000 replicates) and external validation set, indicating good clinical predictive ability. CONCLUSIONS: This study develop a good diagnostic model based on both CT and MRI, as well as laboratory findings, which may help clinicians distinguish between TS and PS.

Synthesis of Carboxyl-Functionalized COFs with Alternate Stable ß-Ketoenamine and Benzimidazole Linkages: Unraveling Exceptional Solvent Effects for Efficient Uranium Separation.

The prevalent π-π interactions in 2D covalent organic frameworks (COFs) impart a certain flexibility to the structures, making the stacking of COF layers susceptible to external stimuli and introducing some structural disorder. Recent research indicates that the flexibility between COF layers and the associated disorder significantly influence their selective adsorption performance toward gas molecules. However, the adsorption process in a solution environment is more complex compared to gas-phase adsorption, involving interactions between adsorbents and adsorbates, as well as the solvation effects of flexible 2D COFs. Therefore, the inherent flexibility and disorder in 2D COFs under solution conditions and their impact on the adsorption performance of metal ions have not been observed yet. Herein, the synthesis of a novel carboxyl-functionalized COF featuring stable ß-ketoenamine and benzimidazole linkages, named DMTP-COOH, is presented. DMTP-COOH exhibits excellent selective adsorption capability for uranium, with significantly different adsorption capacities observed after treatment with different solvents. This notable difference in adsorption capacity is observed under varying pH, concentration, time, and even in the presence of multiple competing ions. This work represents the first observation of the significant impact of solvent soaking treatment on the selective adsorption performance of COFs for uranium under liquid conditions.

Folic acid for the primary prevention of stroke: a systematic review and meta-analysis.

Objectives: Results from studies were inconsistent with regard to the effect of folic acid on the primary prevention of stroke. The aim of this study was to analyze the association between folic acid and the primary prevention of stroke using the data from observational studies and randomized controlled trials (RCTs). Methods: Eligible publications published until June 2024 were searched in the database of PubMed, Web of Science and Embase. This study included all observational studies and RCTs of folic acid with first stroke as the reporting endpoints. Relative risks (RRs) and 95% confidence intervals (CIs) were pooled in the random-effects model to assess the effect of folic acid on the primary prevention of stroke. Results: Results from 12 observational publications with 16 research, including 312,320 participants, were combined to explore the association between dietary folic acid intake and the primary prevention of stroke. The results showed that high dietary folic acid intake was associated with a 17% reduction in stroke incidence (RR:0.83; 95% CI: 0.73-0.94), and the effect of dietary folic acid was greater in areas without grain fortification (RR:0.80; 95% CI: 0.67-0.95). The pooled results from 12 RCTs, totaling 75,042 participants, indicated that folic acid supplementation was not associated with the stroke primary prevention (RR:0.92; 95% CI: 0.80-1.05), but folic acid supplementation was effective in areas without grain fortification (RR:0.78; 95% CI: 0.68-0.89). Conclusion: Our meta-analysis demonstrated that dietary folic acid is effective in stroke primary prevention, and folic acid supplementation is effective in stroke primary prevention only in areas without grain fortification. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier CRD42024516991.

Role of glycosylation-related gene MGAT1 in pancreatic ductal adenocarcinoma.

Background: pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with a very poor prognosis and a complex tumor microenvironment, which plays a key role in tumor progression and treatment resistance. Glycosylation plays an important role in processes such as cell signaling, immune response and protein stability. Materials and methods: single-cell RNA sequencing data and spatial transcriptome data were obtained from GSE197177 and GSE224411, respectively, and RNA-seq data and survival information were obtained from UCSC Xena and TCGA. Multiple transcriptomic data were comprehensively analyzed to explore the role of glycosylation processes in tumor progression, and functional experiments were performed to assess the effects of MGAT1 overexpression on PDAC cell proliferation and migration. Results: In PDAC tumor samples, the glycosylation level of macrophages was significantly higher than that of normal samples. MGAT1 was identified as a key glycosylation-related gene, and its high expression was associated with better patient prognosis. Overexpression of MGAT1 significantly inhibited the proliferation and migration of PDAC cells and affected intercellular interactions in the tumor microenvironment. Conclusion: MGAT1 plays an important role in PDAC by regulating glycosylation levels in macrophages, influencing tumor progression and improving prognosis.MGAT1 is a potential therapeutic target for PDAC and further studies are needed to develop targeted therapeutic strategies against MGAT1 to improve clinical outcomes.

Origin of the Efficiency Roll-off in Quantum Dot Light-Emitting Diodes: An Electrically Excited Transient Absorption Spectroscopy Study.

In situ characterizations of charge injection dynamics, equilibrated concentration, and electric field distributions shed light on the critical mechanisms of quantum dot light-emitting diodes (QD-LEDs). In this work, we developed electrically excited transient absorption spectroscopy, which can provide the above key information, to investigate the efficiency roll-off of QD-LEDs. We found that the average electron populations per QD are low when QD-LEDs exhibit efficiency roll-off, excluding Auger recombination as the main cause. We also revealed that the weak electrical field inside the QD layer under forward biases has a negligible impact on the efficiency. Interestingly, we found that as the voltage increases the electron concentration in the QD layer saturates at very low levels. When combined with the concomitant efficiency roll-off, we propose electron leakage is the main loss at elevated driving voltages. We further demonstrate that increasing the electron confinement potential with the ZnS shell enables us to efficiently mitigate the efficiency roll-off.

Small Nuclear Ribonucleoprotein Polypeptides B and B1 Promote Osteosarcoma Progression via Activating the ATM Signaling Pathway through Ribonucleotide Reductase Subunit M2.

Osteosarcoma is a malignant bone tumor characterized by high metastatic potential and recurrence rates after therapy. The small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB), core components of a spliceosome, have been reported to exhibit up-regulation across several cancer types. However, the precise role of SNRPB in osteosarcoma progression remains poorly elucidated. Herein, we explored SNRPB expression in human osteosarcoma tissues and normal bone tissues by immunohistochemical staining, revealing a notable up-regulation of SNRPB in osteosarcoma, correlating with diminished survival rates. Moreover, the in vitro loss-of-function experiments showed that SNRPB knockdown significantly suppressed the osteosarcoma cell proliferation and migration, as well as tubule formation of human umbilical vascular endothelial cells, while enhancing osteosarcoma cell apoptosis. Mechanistically, we revealed that SNRPB promoted the transcription of ribonucleotide reductase subunit M2 via E2F transcription factor 1. Further rescue experiments indicated that ribonucleotide reductase subunit M2 was required for SNRPB-induced malignant behaviors in osteosarcoma. Additionally, we confirmed that the function of SNRPB in osteosarcoma cell growth and apoptosis was associated with ATM signaling pathway activation. In conclusion, our findings provide initial insights into the underlying mechanisms governing SNRPB-induced osteosarcoma progression, and we proposed SNRPB as a novel therapeutic target in osteosarcoma management.

Combined non-targeted and targeted metabolomics reveals the mechanism of delaying aging of Ginseng fibrous root.

Background: The fibrous root of ginseng (GFR) is the dried thin branch root or whisker root of Ginseng (Panax ginseng C. A. Mey). It is known for its properties such as tonifying qi, producing body fluid, and quenching thirst. Clinically, it is used to treat conditions such as cough, hemoptysis, thirst, stomach deficiency, and vomiting. While GFR and Ginseng share similar metabolites, they differ in their metabolites ratios and efficacy. Furthermore, the specific role of GFR in protecting the body remains unclear. Methods: We employed ultra-high performance liquid chromatography-triple quadrupole mass spectrometry to examine alterations in brain neurotransmitters and elucidate the impact of GFR on the central nervous system. Additionally, we analyzed the serum and brain metabolic profiles of rats using ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry to discern the effect and underlying mechanism of GFR in delaying aging in naturally aged rats. Results: The findings of the serum biochemical indicators indicate that the intervention of GFR can enhance cardiovascular, oxidative stress, and energy metabolism related indicators in naturally aging rats. Research on brain neurotransmitters suggests that GFR can augment physiological functions such as learning and memory, while also inhibiting central nervous system excitation to a certain degree by maintaining the equilibrium of central neurotransmitters in aged individuals. Twenty-four abnormal metabolites in serum and seventeen abnormal metabolites in brain could be used as potential biomarkers and were involved in multiple metabolic pathways. Among them, in the brain metabolic pathways, alanine, aspartate and glutamate metabolism, arginine and proline metabolism, histidine metabolism, and tyrosine metabolism were closely related to central neurotransmitters. Butanoate metabolism improves energy supply for life activities in the aging body. Cysteine and methionine metabolism contributes to the production of glutathione and taurine and played an antioxidant role. In serum, the regulation of glycerophospholipid metabolism pathway and proline metabolism demonstrated the antioxidant capacity of GFR decoction. Conclution: In summary, GFR plays a role in delaying aging by regulating central neurotransmitters, cardiovascular function, oxidative stress, energy metabolism, and other aspects of the aging body, which lays a foundation for the application of GFR.

Impact of lower limb alignment abnormality (physiologic knee valgus) on the functional recovery outcome of athletes with meniscal injuries.

OBJECTIVE: This study aimed to investigate the impact of lower limb alignment abnormalities, specifically physiological knee valgus, on the functional recovery outcomes of athletes with meniscal injuries. It also examined the factors influencing these abnormalities to provide scientific evidence for treatment and rehabilitation of related sports injuries. METHODS: We conducted a retrospective study of 118 athletes from Guizhou Normal University, who were divided into two groups based on the presence or absence of lower limb alignment abnormalities. The Simple group comprised athletes with isolated meniscal injuries, while the Combined group included athletes with meniscal injuries and concurrent lower limb alignment abnormalities. We assessed the functional status of both groups and analyzed factors influencing lower limb alignment abnormalities. RESULTS: Of the 118 athletes, 46 (38.98%) exhibited lower limb alignment abnormalities, and 72 (61.02%) did not. No significant differences in general characteristics were found between the groups (all P > 0.05). The Combined group displayed higher Visual Analog Scale (VAS) scores and Functional Performance Test (FPT) results (coordinated contraction, shuttle run, CarioCa) compared to the Simple group (P < 0.05). Conversely, joint range of motion (ROM), knee muscle strength (flexors), and International Knee Documentation Committee (IKDC) scores were lower in the Combined group (all P < 0.05). Multivariate logistic regression analysis identified active ROM < 105.32°, passive ROM < 101.66°, and knee muscle strength (flexors) < 84.41 N as risk factors for lower limb alignment abnormalities (P < 0.05), while FPT acted as a protective factor (P < 0.05). The combined testing model demonstrated higher predictive efficacy (AUC = 0.903, 95% CI: 0.852-0.955, P < 0.001). CONCLUSION: Lower limb alignment abnormalities significantly affect the functional recovery outcomes of athletes with meniscal injuries. Factors such as ROM, knee muscle strength, and IKDC score may pose risks for these abnormalities, whereas FPT can provide protective benefits. Timely detection and correction of lower limb alignment abnormalities during the rehabilitation process from meniscal injuries are crucial to enhance recovery and improve prognosis.

Improved mapping of heavy metals in agricultural soils using machine learning augmented with spatial regionalization indices.

The accurate spatial mapping of heavy metal levels in agricultural soils is crucial for environmental management and food security. However, the inherent limitations of traditional interpolation methods and emerging machine-learning techniques restrict their spatial prediction accuracy. This study aimed to refine the spatial prediction of heavy metal distributions in Guangxi, China, by integrating machine learning models and spatial regionalization indices (SRIs). The results demonstrated that random forest (RF) models incorporating SRIs outperformed artificial neural network and support vector regression models, achieving R2 values exceeding 0.96 for eight heavy metals on the test data. Hierarchical clustering for feature selection further improved the model performance. The optimized RF models accurately predicted the heavy metal distributions in agricultural soils across the province, revealing higher levels in the central-western regions and lower levels in the north and south. Notably, the models identified that 25.78 % of agricultural soils constitute hotspots with multiple co-occurring heavy metals, and over 6.41 million people are exposed to excessive soil heavy metal levels. Our findings provide valuable insights for the development of targeted strategies for soil pollution control and agricultural soil management to safeguard food security and public health.

General Post-Regulation Strategy of AIEgens' Photophysical Properties for Intravital Two-Photon Fluorescence Imaging.

Fluorogens with aggregation-induced emission (AIEgens) are promising agents for two-photon fluorescence (TPF) imaging. However, AIEgens' photophysical properties are fixed and unoptimizable once synthesized. Therefore, it is urgent and meaningful to explore an efficient post-regulation strategy to optimize AIEgens' photophysical properties. Herein, a general and efficient post-regulation strategy is reported. By simply tuning the ratio of inert AIEgens within binary nanoparticles (BNPs), the fluorescence quantum yield and two-photon absorption cross-section of functional AIEgens are enhanced by 8.7 and 5.4 times respectively, which are not achievable by conventional strategies, and the notorious phototoxicity is almost eliminated. The experimental results, theoretical simulation, and mechanism analysis demonstrated its feasibility and generality. The BNPs enabled deep cerebrovascular network imaging with ≈1.10 mm depth and metastatic cancer cell detection with single-cell resolution. Furthermore, the TPF imaging quality is improved by the self-supervised denoising algorithm. The proposed binary molecular post-regulation strategy opened a new avenue to efficiently boost the AIEgens' photophysical properties and consequently TPF imaging quality.

Harnessing Metal-Organic Frameworks for NIR-II Light-Driven Multiphoton Photocatalytic Water Splitting in Hydrogen Therapy.

The construction of near-infrared (NIR) light-activated hydrogen-producing materials that enable the controlled generation and high-concentration release of hydrogen molecules in deep tumor tissues and enhance the effects of hydrogen therapy holds significant scientific importance. To address the key technical challenge of low-efficiency oxidation-reduction reactions for narrow-bandgap photocatalytic materials, this work proposes an innovative approach for the controllable fabrication of multiphoton photocatalytic materials to overcome the limitations imposed by traditional near-infrared photocatalysts with "narrow-bandgap" constraints. Herein, an NIR-responsive multiphoton photocatalyst, ZrTc-Co, is developed by utilizing a post-synthetic coordination modification strategy to introduce hydrogenation active site CoII into a multiphoton responsive MOF (ZrTc). The results reveal that with the introduction of the CoII site, electron-hole recombination can be efficiently suppressed, thus promoting the efficiency of hydrogen evolution reaction. In addition, the integration of CoII can effectively enhance charge transfer and improve static hyperpolarizability, which endows ZrTc-Co with excellent multiphoton absorption. Moreover, hyaluronic acid modification endows ZrTc-Co with cancer cell-specific targeting characteristics, laying the foundation for tumor-specific elimination. Collectively, the proposed findings present a strategy for constructing NIR-II light-mediated hydrogen therapeutic agents for deep tumor elimination.

Loss of clear cell characteristics in aggressive clear cell odontogenic carcinoma: a case report.

BACKGROUND: Clear cell odontogenic carcinoma (CCOC) is an odontogenic carcinoma characterized by sheets and islands of vacuolated and clear cells. The diagnosis of atypical CCOC can pose a challenge when tumor cells deviate from their characteristic clear morphology, even with the aid of genetic profiling for CCOC identification. CASE PRESENTATION: In this manuscript, we detailed the inaugural instance of a recurrently recurring clear cell odontogenic carcinoma (CCOC) with pronounced squamous differentiation in a 64-year-old male. The primary tumor in this individual initially displayed a biphasic clear cell phenotype. However, subsequent to the third recurrence, the clear tumor cells were entirely supplanted by epidermoid cells characterized by eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli. Notable aggressive attributes such as necrosis, conspicuous cytological malignancy, perineural dissemination, and vascular invasion were noted. Additionally, the tumor progressed to manifest lung metastases. The tumor cells exhibited positive immunoreactivity for AE1/AE3, KRT19, Pan-CK, EMA, P40, P63, CK34ßE12, and P53, while they tested negative for CK35ßH11, KRT7, S-100, and neuroendocrine markers. The Ki-67 proliferation index was calculated at an average of 15%. Furthermore, FISH analysis unveiled the presence of the EWSR1::ATF1 gene fusion. CONCLUSIONS: This case illustrated a rare and aggressive case of CCOC characterized by significant squamous differentiation upon recurrence of the tumor.

The amplitude of low-frequency fluctuations is correlated with birth trauma in patients with postpartum post-traumatic stress disorder.

Postpartum post-traumatic stress disorder (PP-PTSD) is a severe mental disorder worldwide. In recent years, some studies have reported that PP-PTSD stems from birth trauma. The present study was dedicated in finding ways to predict the occurrence of emergency caesarean section (ECS), trying to analyze the methods to reduce incidence of PP-PTSD on this basis, further exploring the neuroimaging changes in PP-PTSD. A total of 245 primiparas with intention of vaginal delivery were recruited. The internal tocodynamometry measurement was performed during labor for all mothers, and respectively taken at 3-5 cm, 5-8 cm, and 8-10 cm of cervical dilation. The receiver operating characteristic (ROC) curve and Binary logistic regression analyses were also performed to identify fetal head descending thrust that might help in the prediction of ECS. Resting-state magnetic resonance imaging (MRI) was performed on 26 patients diagnosed with PP-PTSD of 245 mothers, the amplitude of low-frequency fluctuations (ALFF) technology was used to observe the spontaneous neural activity of all PP-PTSD patients and correlation analyses were performed. We found that the natural delivery rate of mothers with fetal head descending thrust <16.29 N (5-8 cm), 26.36 N (8-10 cm) were respectively lower than other mothers with fetal head descending thrust ≥16.29 N (5-8 cm), 26.36 N (8-10 cm) (P < 0.05). The ROC curve analysis showed that the area under the receiver operating characteristic curve (AUC) value of thrust (5-8 cm) was 0.896 (95% CI: 0.854-0.938, p < 0.001), AUC of thrust(8-10 cm) was 0.786 (95% CI: 0.714-0.858, p < 0.001), which showed strong potential for predicting ECS. In addition, the Binary logistic regression analysis showed thrust (5-8 cm) and thrust (8-10 cm) were independent correlates of ECS. The resting-state functional magnetic resonance imaging (rs-fMRI) results indicated that PP-PTSD group showed decreased ALFF in the bilateral insula cortex (IC), right anterior cingulate cortex (ACC), and left midcingulate cortex (MCC) compared with healthy postpartum women (HPW) (false discovery rate (FDR) correction q-value < 0.05). The ALFF value of the right ACC was positively correlated with the Perinatal Post-traumatic stress disorder Questionnaire (PPQ) score (r = 0.4046 p = 0.0403) and Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C) score (r = 0.3909 p = 0.0483). The internal tocodynamometry measurement can serve as a predictive tool for ECS, on this basis, the implementation of effective emotional support may help to reduce the incidence of PP-PTSD. Besides, this study has verified the presence of altered ALFF in the brain regions of PP-PTSD patients, mainly involving the bilateral IC, right ACC, and left MCC, that might be associated with emotion, cognition, and memory disorders functions in PP-PTSD patients.

Systemic conversion therapies for initially unresectable hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Systemic conversion therapy provides patients with initially unresectable hepatocellular carcinoma (HCC) the chance to salvage radical liver resection and superior survival outcomes, but the optimal conversion strategy is unclear. METHODS: A systematic literature search was conducted on PubMed, EMBASE, Web of Science, Scopus, and the Cochrane Library between 2007 and 2024 focusing on studies reporting conversion therapy for HCC. The treatment groups were divided into Tyrosine kinase inhibitors (TKI), TKI plus loco-regional therapy (LRT), TKI plus anti-PD-1 therapy (TKI + PD-1), TKI + PD-1 + LRT, immune checkpoint inhibitors (ICI) plus LRT, and Atezolizumab plus bevacizumab (A + T) groups. The conversion to surgery rate (CSR), objective response rate (ORR), grade ≥ 3 treatment-related adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were analyzed. RESULTS: 38 studies and 4,042 patients were included. The pooled CSR were 8% (95% CI, 5-12%) in TKI group, 13% (95% CI, 8-19%) in TKI + LRT group, 28% (95% CI, 19-37%) in TKI + PD-1 group, 33% (95% CI, 25-41%) in TKI + PD-1 + LRT group, 23% (95% CI, 1-46%) in ICI + LRT group, and 5% (95% CI, 3-8%) in A + T group, respectively. The pooled HR for OS (0.45, 95% CI, 0.35-0.60) and PFS (0.49, 95% CI, 0.35-0.70) favored survival benefit of conversion surgery. Subgroup analysis revealed that lenvatinib + PD-1 + LRT conferred higher CSR of 35% (95% CI, 26-44%) and increased ORR of 70% (95% CI, 56-83%). CONCLUSIONS: The current study indicates that TKI + PD-1 + LRT, especially lenvatinib + PD-1 + LRT, may be the superior conversion therapy with a manageable safety profile for patients with initially unresectable HCC. The successful conversion therapy favors the superior OS and PFS compared with systemic treatment alone. TRIAL REGISTRATION: International prospective register of systematic reviews (PROSPERO) (registration code: CRD 42024495289).

[Effects of Meteorological Conditions in Summer and Early Autumn on PM2.5 and O3 Pollution in Beijing-Tianjin-Hebei and Surrounding Areas].

PM2.5 pollution remains prominent in autumn, whereas O3 pollution gradually manifests in summer. To understand the dual high characteristics and meteorological effects of PM2.5 and O3 in the summer and early autumn of 2021 in the Beijing-Tianjin-Hebei and surrounding areas, the spatiotemporal distribution characteristics of PM2.5 and O3 concentrations, as well as meteorological conditions, subtropical high index, and weather situation in the Beijing-Tianjin-Hebei and surrounding areas were analyzed. The results showed that PM2.5 concentration and DPO3 （O3 daily maximum 8h mean minus O3 concentration at 06：00） from June to September 2021 decreased compared with those in the same period in 2020 and 2022, and high concentrations were mainly occurring in June. The overall PM2.5 concentration and DPO3 showed a gradual decrease from the middle to the north and south, with synchronous spatiotemporal changes. The hourly value of PM2.5 concentration presented a multimodal distribution, reaching the peak at 07：00-10：00 and 22：00-24：00. O3 concentration showed an opposite trend of change with PM2.5 concentration, reaching their peak from 14：00-16：00. When DPO3 and the concentration of PM2.5 were high, the characteristics of near-surface meteorological elements were characterized by temperatures ranging from 24.0-28.0℃, relative humidity concentrated at 58.4%-76.3%, and wind speeds ranging from 1.5-3 m·s-1. There was a high lag correlation between the subtropical high index and DPO3. When the subtropical high was farther and stronger from the Beijing-Tianjin-Hebei and surrounding areas, DPO3 was higher. The major weather patterns with both high PM2.5 and O3 concentrations in the study area were near surface low-pressure front, high-pressure type, and frontal type. The high altitude was controlled by high-pressure ridges, and the subtropical high ridge line was stable between 21°-28°N.

Distribution Control and Environmental Fate of PFAS in the Offshore Region Adjacent to the Yangtze River Estuary─A Study Combining Multiple Phases Analysis.

The Yangtze River Estuary is the terminal sink of terrestrial per- and polyfluoroalkyl substances (PFAS) from the Yangtze River, while the environmental fate characteristics of legacy and emerging PFAS around this region have rarely been discussed. Here, 24 targeted PFAS in seawater, sediments, suspended particulate matter (SPM), and plankton in the offshore region adjacent to this estuary were investigated. The three dominant PFAS in all phases were perfluorooctanoic acid (PFOA, 23.8-61.9%), perfluorobutanoic acid (PFBA, 23.6-42.8%), and perfluoro(2-methyl-3-oxahexanoic) acid (HFPO-DA, 6.1-12.1%), and perfluoro-1-butane sulfonamide (FBSA, 0.1-7.3%) was first detected. The horizontal distributions of PFAS were dependent on salinity and disturbed by multiple water masses, while the vertical variations could be explained by their different partitioning characteristics in the water-SPM-sediment system (partition coefficients, Log Kd and Log Koc) and plankton (bioaccumulation factors, Log BAF). Although physical mixing was the major driver for PFAS settling (>83.7%), the absolute settling amount caused by the biological pump was still high (150.00-41994.65 ng m-2 day-1). More importantly, we found unexpected high Log Kd values of PFBA (2.24-4.55) and HFPO-DA (2.26-4.67), equal to PFOA (2.28-4.72), which brought concerns about their environmental persistence. Considering the increased detection of short-chain and emerging PFAS, more comprehensive environmental behaviors analysis is required urgently.

TPOAb Indicates Neuroendocrine Tumor in Autoimmune Gastritis:A Retrospective Study of 91 Patients.

BACKGROUND: The association between serological indexes and occurrence of complications in patients with autoimmune gastritis (AIG) remains unclear. METHODS: 91 patients with AIG were recruited and their clinical information were collected. The differences between serological indexes and complications of AIG were analyzed. And potential biomarker for early prediction and diagnosis of AIG with complications was explored. RESULTS: AIG patients in our study was 58.12±11.68 years old, containing 31 males and 60 females. G17 was elevated in 49 of 52; PGI/II decreased in 43/49; GPA positive in 48/61; Anemia presented 28 in 80; Vitamin B12 deficiency occurred 23 in 58. Neuroendocrine tumor (NET) was the most common complication in AIG patients, accounting for 27/91. The second was polyps, making up for 14/91. There is also 9/91 of gastric mucosa neoplasia happened in AIG. No significant difference of G7, PGI, PGII, PGI/II and VB12 in AIG was found in different gastric mucosal lesions (P > 0.05). However, AIG patients with TPOAb positive had a higher risk in the occurrence of NET simultaneously (P = 0.0212). Those AIG with NET patients exhibited a significantly higher TPOAb level (P = 0.0078). ROC curve suggested that TPOAb can predict the existence of NET in AIG (AUC = 0.7410, P < 0.05). CONCLUSION: We found that TPOAb can serve as a predictive biomarker of NET in AIG. This accessible test is helpful for endoscopy specialists to pay attention to gastric mucosal lesions in TPOAb-positive AIG patients, improving early diagnosis and intervention of comorbidities ability.

The potential of RNA methylation in the treatment of cardiovascular diseases.

RNA methylation has emerged as a dynamic regulatory mechanism that impacts gene expression and protein synthesis. Among the known RNA methylation modifications, N6-methyladenosine (m6A), 5-methylcytosine (m5C), 3-methylcytosine (m3C), and N7-methylguanosine (m7G) have been studied extensively. In particular, m6A is the most abundant RNA modification and has attracted significant attention due to its potential effect on multiple biological processes. Recent studies have demonstrated that RNA methylation plays an important role in the development and progression of cardiovascular disease (CVD). To identify key pathogenic genes of CVD and potential therapeutic targets, we reviewed several common RNA methylation and summarized the research progress of RNA methylation in diverse CVDs, intending to inspire effective treatment strategies.

Cationic Foldamer-Catalyzed Asymmetric Synthesis of Inherently Chiral Cages.

The stereochemistry of shape-persistent molecular cages, particularly those resembling prisms, exerts significant influence on their application-specific functionalities. Although methods exist for fabricating inherently chiral prism-like cages, strategies for catalytic asymmetric synthesis of these structures in a diversity-oriented fashion remain unexplored. Herein, we introduce an unprecedented organocatalytic desymmetrization approach for the generation of inherently chiral prism-like cages via phosphonium-containing foldamer-catalyzed SNAr reactions. This methodology establishes a topological connection, enabling the facile assembly of a wide range of versatile stereogenic-at-cage building blocks possessing two highly modifiable groups. Furthermore, subsequent stereospecific transformations of the remaining chlorides and/or ethers afford convenient access to numerous functionally relevant chiral-at-cage molecules.

Targeted degradation of KRAS protein in non-small cell lung cancer: Therapeutic strategies using liposomal PROTACs with enhanced cellular uptake and pharmacokinetic profiles.

The role of KRAS mutation in non-small cell lung cancer (NSCLC) initiation and progression is well-established. However, "undruggable" KRAS protein poses the research of small molecule inhibitors a significant challenge. Addressing this, proteolysis-targeting chimeras (PROTACs) have become a cutting-edge treatment method, emphasizing protein degradation. A modified ethanol injection method was employed in this study to formulate liposomes encapsulating PROTAC drug LC-2 (LC-2 LPs). Precise surface modifications using cell-penetrating peptide R8 yielded R8-LC-2 liposomes (R8-LC-2 LPs). Comprehensive cellular uptake and cytotoxicity studies unveiled that R8-LC-2 LPs depended on concentration and time, showcasing the superior performance of R8-LC-2 LPs compared to normal liposomes. In vivo pharmacokinetic profiles demonstrated the capacity of DSPE-PEG2000 to prolong the circulation time of LC-2, leading to higher plasma concentrations compared to free LC-2. In vivo antitumor efficacy research underscored the remarkable ability of R8-LC-2 LPs to effectively suppress tumor growth. This study contributed to the exploration of enhanced therapeutic strategies for NSCLC, specifically focusing on the development of liposomal PROTACs targeting the "undruggable" KRAS protein. The findings provide valuable insights into the potential of this innovative approach, offering prospects for improved drug delivery and heightened antitumor efficacy.