In Vitro Detection of S100B and Severity Evaluation of Traumatic Brain Injury Based on Biomimetic Peptide-Modified Nanochannels.

The diagnosis and evaluation of traumatic brain injury (TBI) are crucial steps toward the treatment and prognosis of patients. A common question remains as to whether it is possible to introduce an ideal device for signal detection and evaluation that can directly connect digital signals with TBI, thereby enabling prompt response of the evaluation signal and sensitive and specific functioning of the detection process. Herein, a method is presented utilizing polymetric porous membranes with TRTK-12 peptide-modified nanochannels for the detection of S100B (a TBI biomarker) and assessment of TBI severity. The method leverages the specific bonding force between TRTK-12 peptide and S100B protein, along with the nanoconfinement effect of nanochannels, to achieve high sensitivity (LOD: 0.002 ng mL-1) and specificity (∆I/I0: 44.7%), utilizing ionic current change as an indicator. The proposed method, which is both sensitive and specific, offers a simple yet responsive approach for real-time evaluation of TBI severity. This innovative technique provides valuable scientific insights into the advancement of future diagnostic and therapeutic integration devices.

Constructing Thermal Convection Film for Low Heat Loss and High Salt Resistance in Wood-Based Solar Evaporators.

Unique suspension solar evaporator is one of the effective measures to address the major bottleneck of the emerging interfacial evaporators, i.e., the accumulation of salts on the surface. Yet, it remains a considerable challenge to avoid substantial heat loss underwater. Herein, a suspension wood-based evaporator is proposed with a thermal convection structure that effectively balances the contradiction between salt-resistance ability and heat loss. Benefitting from the heat centralization due to thermal convection, such suspension evaporator exhibits an excellent steam generation rate, which increases from 1.23 to 1.63 kg m-2 h-1 compared to the conventional suspension evaporator. Simultaneously, the steam generation rate retention improves from 64.9% over 20 test cycles to nearly 100% compared to the interfacial evaporator. This work provides an effective pathway for exploring efficient and stable suspension evaporators, offering essential directions for the future development and application of solar-driven evaporation technologies.

Cation-Triggered Growth of Nanowires for Enhanced Oxygen Evolution Reaction.

The oxygen evolution reaction (OER), which occurs in a variety of energy-related devices, necessitates optimization of the reaction pathways for efficient and scalable deployment. Nevertheless, fully harnessing the advanced structure of synthetic electrocatalysts remains a significant challenge due to the inevitable surface reconstruction process during OER. Here we present an efficient and flexible method to control the surface reconstruction process by engineering an electrolyte containing trace Co2+ cation. This controllable reconstruction process enhances fast charge transfer, facilitates electroactive species transport, and exposes the inner active site, significantly improving the OER kinetics. An impressive 60% increase in current density at an applied potential of 2.2 V (vs RHE) confirms its remarkable contribution to the performance. The identification of cation-triggered reconstruction for the formation of a well-defined surface provides a novel insight into understanding electrolyte engineering and offers a viable pathway to address activity and stable concerns in electrocatalysts.

Thyrotoxic Effects of Mixed Exposure to Perfluorinated Compounds: Integrating Population-Based, Toxicogenomic, Animal, and Cellular Evidence to Elucidate Molecular Mechanisms and Identify Potential Effector Targets.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are emerging environmental endocrine disruptors that may adversely affect the human endocrine system, particularly the thyroid gland, the largest endocrine gland in the human body. An epidemiologic survey was conducted involving 318 community residents in Shanghai, China, to assess PFAS exposure levels. The relationship between PFAS exposure and five thyroid function indicators was analyzed using Bayesian Kernel Regression (BKMR) and Weighted Quantile Sum Regression (WQS). Ten effector genes related to PFAS and thyroid diseases were identified through the Comparative Toxicogenomics Database (CTD) for bioinformatics analysis and pathways involved were explored through mediation analysis. In vivo validation of these effector genes was conducted using PCR, complemented by in vitro cellular experiments involving transcriptome sequencing and the construction of animal models to simulate mixed PFAS exposure in the general population. Mixed PFAS exposure was found to impact thyroid health primarily through pathways related to lipid metabolism in toxicogenomic studies and resulted in the upregulation of key genes associated with lipid metabolism in animal models. Our results demonstrate that PFAS exposure could affect the expression of lipid metabolism pathways through the modulation of transcription factors, contributing to the development of thyroid disease.

Quench-Induced Surface Engineering Boosts Alkaline Freshwater and Seawater Oxygen Evolution Reaction of Porous NiCo2 O4 Nanowires.

The electrochemical oxygen evolution reaction (OER) by efficient catalysts is a crucial step for the conversion of renewable energy into hydrogen fuel, in which surface/near-surface engineering has been recognized as an effective strategy for enhancing the intrinsic activities of the OER electrocatalysts. Herein, a facile quenching approach is demonstrated that can simultaneously enable the required surface metal doping and vacancy generation in reconfiguring the desired surface of the NiCo2 O4 catalyst, giving rise to greatly enhanced OER activities in both alkaline freshwater and seawater electrolytes. As a result, the quenched-engineered NiCo2 O4 nanowire electrode achieves a current density of 10 mA cm-2 at a low overpotential of 258 mV in 1 m KOH electrolyte, showing the remarkable catalytic performance towards OER. More impressively, the same electrode also displays extraordinary activity in an alkaline seawater environment and only needs 293 mV to reach 10 mA cm-2 . Density functional theory (DFT) calculations reveal the strong electronic synergies among the metal cations in the quench-derived catalyst, where the metal doping regulates the electronic structure, thereby yielding near-optimal adsorption energies for OER intermediates and giving rise to superior activity. This study provides a new quenching method to obtain high-performance transition metal oxide catalysts for freshwater/seawater electrocatalysis.

Synthesis, preclinical evaluation, and first-in-human study of Al18F-PSMA-Q for prostate cancer imaging.

PURPOSE: To investigate the potential of a novel Al18F-labeled PSMA-targeted radiotracer for PCa diagnosis through both preclinical and pilot clinical studies. METHODS: Al18F-PSMA-Q was prepared automatically. The binding affinity to PSMA was evaluated in vitro using the 22Rv1 (PSMA +) and PC-3 (PSMA -) cell lines. Pharmacokinetics evaluation, biodistribution study, Micro-PET imaging of Al18F-PSMA-Q in normal mice and tumor-bearing mice, and a comparison with 18F-DCFPyL were performed. PET/CT imaging was performed on 8 healthy volunteers and 20 newly diagnosed PCa patients at 1 h post-injection (p.i.). The biodistribution in human and preliminary diagnostic efficacy of Al18F-PSMA-Q were evaluated, and the radiation dosimetry was estimated using OLINDA/EXM 2.0 software. RESULT: Qualified Al18F-PSMA-Q was efficiently prepared with a non-decay-corrected radiochemical yield (RCY) of 22.0-28.3%, a specific activity (SA) of > 50 GBq/µmol. The hydrophilicity was comparably high with a log P value of - 3.69 ± 0.39. Al18F-PSMA-Q was found to bind to PSMA specifically with a Ki value of 17.05 ± 1.14 nM. The distribution and elimination half-lives of Al18F-PSMA-Q were 3.93 min and 14.22 min, respectively, which were shorter than those of 18F-DCFPyL. Micro-PET imaging of Al18F-PSMA-Q can clearly differentiate 22Rv1 tumors from PC-3 tumors and background with a high SUVmax of 2.17 ± 0.42 and a tumor-to-muscle ratio of 84.37 ± 31.62, which were higher than those of 18F-DCFPyL (1.79 ± 0.39 and 13.25 ± 1.65). The uptake of Al18F-PSMA-Q in 22Rv1 cells and tumors can be substantially blocked by 2-PMPA. High level accumulation of Al18F-PSMA-Q was observed in organs physiologically expressing PSMA. Twenty-six tumor lesions were detected in 20 PCa patients, and the mean SUVmax values of primary tumors, lymph node metastasis, bone metastases, and tumor-muscle ratios were 19.71 ± 16.52, 5.11, 31.30 ± 29.85, and 44.77 ± 22.29, respectively. The mean SUVmax of tumors in patients with PSA > 10 ng/mL was significantly higher than that in patients with PSA ≤ 10 ng/mL (25.97 ± 18.64 vs. 10.33 ± 3.74). Meanwhile, the mean SUVmax of tumors in patients with a Gleason score ≥ 8 was significantly higher than that in patients with a Gleason score < 8 (31.85 ± 22.09 vs. 13.18 ± 11.58). The kidneys received the highest estimated dose of 0.098 ± 0.006 mGy/MBq, and the effective dose was calculated as 0.0128 ± 0.007 mGy/MBq. CONCLUSION: The novel qualified PSMA-targeted radiotracer Al18F-PSMA-Q was conveniently prepared with favorable yield and SA. The results of preclinical and pilot clinical studies exhibited a high specific uptake in PCa lesions and an excellent tumor-to-background ratio with a reasonable radiation exposure, which indicated the great potential of Al18F-PSMA-Q for PCa imaging. TRIAL REGISTRATION: Chinese Clinical trial registry ChiCTR2100053507, Registered 23 November 2021, retrospectively registered.

Targeted fluorescent imaging of a novel FITC-labeled PSMA ligand in prostate cancer.

In this study, we synthesized a novel fluorescein isothiocyanate (FITC)-labeled prostate-specific membrane antigen (PSMA) ligand (PSMA-FITC) via the Fmoc solid-phase synthesis method, and the application value of PSMA-FITC in targeted fluorescence imaging of PSMA-positive prostate cancer was evaluated. The PSMA ligand developed based on the Glu-urea-Lys structure was linked to FITC by aminocaproic acid (Ahx) to obtain PSMA-FITC. The new probe was evaluated in vitro and in vivo. Fluorescence microscopy examination of PSMA-FITC in PSMA(+) LNCaP cells, PSMA(-) PC3 cells, and blocked LNCaP cells showed that the binding of PSMA-FITC with PSMA was target-specific. For in vivo optical imaging, PSMA-FITC exhibited rapid 22Rv1 tumor targeting within 30 min of injection, and the highest tumor-background ratio (TBR) was observed 60 min after injection. The TBR was 3.45 ± 0.31 in the nonblocking group and 0.44 ± 0.13 in the blocking group, which was consistent with the in vitro results. PSMA-FITC is a promising probe and has important reference value for the development of PSMA fluorescent probes. In the future, it can be applied to obtain accurate tumor images for radical prostatectomy.

Rs884225 polymorphism is associated with primary hypertension by compromising interaction between epithelial growth factor receptor (EGFR) and miR-214.

Genetic variations in the 3'UTR of mRNAs as well as sequences of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) can affect gene expression by interfering with the binding between them. In this study, we investigated the role of the following polymorphisms in the risk of hypertension: the 774T > C (rs17337023) polymorphism located in the EGFR 3' untranslated region (3'UTR), the rs884225 polymorphism located in the sequence of miR-214, and the single nucleotide polymorphisms (SNPs) rs325797437, rs344501106, rs81286029 and rs318656749 located in the promoter of lncRNA MEG3. Taqman genotyping assays and haplotype analysis tools were used to measure the MEG3 haplotypes and the rs17337023 and rs884225 polymorphisms genotypes. The relationship between MEG3, miR-214 and EGFR was validated using computational analysis and luciferase assays. Unlike other polymorphisms, only patients grouped according to their rs884225 genotypes exhibited varied EGFR mRNA and protein levels, which indicated that the rs884225 genotype is associated with the expression of EGFR mRNA and protein levels. MiR-214 was confirmed to bind to MEG3 and 3'UTR of EGFR by showing that the transfection of exogenous miR-214 significantly down-regulated the luciferase activity of A549 and H460 cells transfected with wild-type MEG3 or wild-type EGFR 3' UTR. Additionally, MEG3 overexpression inhibited miR-214 expression while elevating the EGFR mRNA and protein expressions. Meanwhile, MEG3 down-regulation demonstrated an opposite result, thus establishing the MEG3/miR-214/EGRF signalling pathway. Our study confirmed that the T > C substitution of rs884225 polymorphism located in miR-214 binding site in the 3'UTR of EGFR is associated with increased risk of primary hypertension.

Knockdown of HIF1A-AS2 suppresses TRIM44 to protect cardiomyocytes against hypoxia-induced injury.

Myocardial infarction (MI) is a common cardiovascular disease characterized by an interruption of blood and oxygen supply to the heart, which results in gradual damage to the myocardial tissue and ultimately heart failure. The role of long non-coding RNAs in the pathology of MI remains in its infancy, but has been implicated in MI and other heart conditions. For example, the expression of a non-coding RNA hypoxia-inducible factor 1α (HIF1A)-antisense RNA 2 (HIF1A-AS2) has previously been linked to coronary heart disease, however, whether HIF1A-AS2 expression is also high in MI has not been addressed. Here, we report that HIF1A-AS2 is upregulated in hypoxia-treated human cardiomyocytes (HMCs) compared with normal cardiomyocytes, and that silenced HIF1A-AS2 inhibited apoptosis and facilitated viability, migration, and invasion of HMCs. Our data suggested that in MI, HIF1A-AS2 upregulation was associated with miR-623, which promoted expression of tripartite motif containing 44 (TRIM44). Moreover, by upregulating TRIM44 we were able to remedy the HIF1A-AS2 repression of apoptosis in HMCs. Thus, we conclude that cardiomyocytes can be protected against hypoxic-treated injury by knockdown of HIF1A-AS2, which suppresses TRIM44, and that HIF1A-AS2 overexpression is a prognostic indicator of MI.

[Serum Uric Acid and Islet ß-cell Function in Patients with Pre-diabetes and Type 2 Diabetes Mellitus].

OBJECTIVE: To determine the correlation between serum uric acid (SUA) and insulin secretion function in patients with pre-diabetes and type-2 diabetes mellitus (T2DM). METHODS: A total of 4 112 adult people participated in this study. They were divided into three groups according to the results of oral glucose tolerance test (OGTT): 493 with normal glucose regulation (NGR),1 251 with impaired glucose regulation (IGR),and 2 368 with T2DM. Their levels of SUA,fasting insulin (FIns),2 h post-meal insulin (2 h-Ins),and insulin resistance index (HOMA-IR) were determined. Correlations between SUA and insulin secretion and HOMA-IR were estimated. RESULTS: IGR patients had higher levels of SUA and 2 h-Ins compared with those with NGR and T2DM ( P<0.000 1). T2DM patients had higher levels of FIns,glucosylated hemoglobin (HbA1c) and HOMA-IR compared with those with NGR and IGR ( P<0.000 1). In both male and female participants,the highest level of 2 h-Ins appeared in those with IGR,while T2DM had the highest level of HOMA-IA and HbA1c. FIns,2 h-Ins and HOMA-IR increased with SUA in both patients with IGR and T2DM. HbA1c decreased with SUA in T2DM patients. CONCLUSION: High serum SUA is correlated with islet ß-cell dysfunction. It may become an indicator of progression from pre-diabetes to T2DM.

[Preliminary Study on the Wnt5a Expression in Obese Mice with Hepatocellular Carcinoma].

OBJECTIVES: To investigate the Wnt5a expression in obese mice with hepatocellular carcinoma. METHODS: Two groups of 6-week C57BL/6J mice were fed with chow-diet and high-fat-diet for 8 weeks respectively, to establish obesity model in the latter group. Mice in Hepal-6 group (including normal-body mass mice and obese mice) were injected with Hepa1-6 hepatocarcinoma cell lines through caudal vein, while the controls were given NS. Serum and tissue samples were taken at the age of 18 weeks for serological and morphological study. The expression of Wnt5a and ß-catenin in liver were examined by immunohistochemistry. RESULTS: At the age of 18-week, tatty degeneration was observed in the livers of obese control mice. Tumor cell masses were found in the livers of both obese and (including normal-body mass mice and obese mice) control mice by inoculation with Hepal-6, while focal necrosis was only observed in the obese+Hepal-6 group. The levels of serum transaminases, cholesterol and alpha-fetoprotein (AFP) were significantly different between groups ( P<0.05). The immunohistochemistry showed that the highest expression of Wnt5a was observed in liver tissues of normal control group, followed in sequence by obese control group, normal+Hepal-6 group, and obese+Hepal-6 group ( P<0.05). The expression of ß-catenin was just opposite ( P<0.05). CONCLUSIONS: The expression of Wnt5a was decreased, and the ß-catenin was abnormal accumulation. It may be closely related to the formation and progression of hepatocellular carcinoma.

Preclinical evaluation of the theranostic potential of 89Zr/177Lu-labeled anti-TROP-2 antibody in triple-negative breast cancer model.

BACKGROUND: Triple-negative breast cancer (TNBC) is one of the most lethal malignant tumors among women, characterized by high invasiveness, high heterogeneity, and lack of specific therapeutic targets such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Trophoblast cell-surface antigen-2 (TROP-2) is a transmembrane glycoprotein over-expressed in 80% of TNBC patients and is associated with the occurrence, progress, and poor prognosis of TNBC. The TROP-2 targeted immunoPET imaging allows non-invasive quantification of the TROP-2 expression levels of tumors, which could help to screen beneficiaries most likely to respond to SG and predict the response. This study aimed to develop a 89Zr/177Lu-radiolabeled anti-TROP-2 antibody (NY003) for immunoPET and SPECT imaging, as well as radioimmunotherapy (RIT) in TROP-2 (+)TNBC tumor-bearing model. Based on the camelid antibody, we developed a TROP-2 targeted recombinant antibody NY003. NY003 was conjugated with DFO and DTPA for 89Zr and 177Lu radiolabelling, respectively. The theranostic potential of [89Zr]Zr-DFO-NY003/[177Lu]Lu-DTPA-NY003 was evaluated through immunoPET, SPECT imaging, and RIT studies in the subcutaneous TROP-2 positive TNBC xenograft mice model. RESULTS: The high binding affinity of NY003 to TROP-2 was verified through ELISA. The radiochemical purity of [89Zr]Zr-DFO-NY003/[177Lu]Lu-DTPA-NY003 exceeded 95% and remained stable within 144h p.i. in vitro. ImmunoPET and SPECT imaging showed the specific accumulation of [89Zr]Zr-DFO-NY003/[177Lu]Lu-DTPA-NY003 in MDA-MB-231 tumors and gradually increased with the time tested, significantly higher than that in control groups (P < 0.05). The strongest anti-tumor efficacy was observed in the high-dose of [177Lu]Lu-DTPA-NY003 group, followed by the low-dose group, the tumor growth was significantly suppressed by [177Lu]Lu-DTPA-NY003, the tumor volumes of both high- and low-dose groups were smaller than the control groups (P < 0.05). Ex vivo biodistribution and histological staining verified the results of in vivo imaging and RIT studies. CONCLUSION: As a drug platform for radiotheranostics, 89Zr/177Lu-radiolabeled anti-TROP-2 antibody NY003 could not only non-invasively screen the potential beneficiaries for optimizing SG ADC treatment but also suppressed the growth of TROP-2 positive TNBC tumors, strongly supporting the theranostic potential of [89Zr]Zr-DFO-NY003/[177Lu]Lu-DTPA-NY003.

Evaluation of aspartame effects at environmental concentration on early development of zebrafish: Morphology and transcriptome1.

The use of aspartame as an artificial sweetener is prevalent in a wide range of everyday food products, potentially leading to health complications such as obesity, diabetes mellitus, autism spectrum disorders, and neurodegeneration. Aspartame has also been detected in natural water bodies at a concentration of 0.49 µg/L, yet research on its ecotoxicological effects on aquatic life remains scarce. This study aimed to investigate the potential negative effects of environmentally relevant concentrations of aspartame on the development of various tissues and organs in zebrafish embryos. We used a zebrafish model to treat embryos with aspartame at environmental concentration and those higher than in the environment-up to 1000 times. We observed that after exposure to aspartame body length increased, pigmentation was delayed, and neutrophil production inhibited in zebrafish. Furthermore, transcriptome analysis revealed that early exposure of zebrafish embryos to aspartame affected the transcriptomics of various systems, primarily by downregulating genes related to immune cell production, eye and optic nerve development, nervous system development, and growth hormone-related transcription. Most of the genes associated with ferroptosis were upregulated. This study provides new insights into the ecotoxicological effects of aspartame on aquatic environments.

Using teach-back in patient education to improve patient satisfaction and the clarity of magnetic resonance imaging.

OBJECTIVE: To explore the effects of using the teach-back method prior to contrast-enhanced magnetic resonance imaging (MRI) on patients' knowledge and satisfaction as well as the clarity of the resulting scans. METHODS: A total of 254 patients who underwent contrast-enhanced MRI examination from July 4, 2022 to September 19, 2022 were enrolled and assigned to the intervention and control groups. Patients in the intervention group received education using the teach-back method, while those in the control group were given routine health education. A questionnaire that included patients' knowledge of contrast-enhanced MRI examination was answered before and after patient education. Data on patient satisfaction with nursing services were also collected. The clarity of the MRI images of all patients was assessed. RESULTS: The scores of knowledge related to MRI after receiving education were significantly higher than those before receiving education (P < 0.001), and there were no significant differences between the intervention and control groups (11.27 ± 9.74 vs. 12.07 ± 8.71, P = 0.498). The score of satisfaction with nursing service in the teach-back group was significantly higher than that in the control group (39.82 ± 0.86 vs. 38.59 ± 3.73, P < 0.001), as was the image clarity score (96.4 ± 0.5 vs. 95.0 ± 0.4, P = 0.039). CONCLUSION: Teach-back improves patient satisfaction and contrast-enhanced MRI clarity. PRACTICE IMPLICATIONS: Including teach-back in patient education improves patient satisfaction and contrast-enhanced MRI clarity.

A nanofluidic chemoelectrical generator with enhanced energy harvesting by ion-electron Coulomb drag.

A sufficiently high current output of nano energy harvesting devices is highly desired in practical applications, while still a challenge. Theoretical evidence has demonstrated that Coulomb drag based on the ion-electron coupling interaction, can amplify current in nanofluidic energy generation systems, resulting in enhanced energy harvesting. However, experimental validation of this concept is still lacking. Here we develop a nanofluidic chemoelectrical generator (NCEG) consisting of a carbon nanotube membrane (CNTM) sandwiched between metal electrodes, in which spontaneous redox reactions between the metal and oxygen in electrolyte solution enable the movement of ions within the carbon nanotubes. Through Coulomb drag effect between moving ions in these nanotubes and electrons within the CNTM, an amplificated current of 1.2 mA cm-2 is generated, which is 16 times higher than that collected without a CNTM. Meanwhile, one single NCEG unit can produce a high voltage of ~0.8 V and exhibit a linear scalable performance up to tens of volts. Different from the other Coulomb drag systems that need additional energy input, the NCEG with enhanced energy harvesting realizes the ion-electron coupling by its own redox reactions potential, which provides a possibility to drive multiple electronic devices for practical applications.

Bioinspired carbon nanotube-based nanofluidic ionic transistor with ultrahigh switching capabilities for logic circuits.

The voltage-gated ion channels, also known as ionic transistors, play substantial roles in biological systems and ion-ion selective separation. However, implementing the ultrafast switchable capabilities and polarity switching of ionic transistors remains a challenge. Here, we report a nanofluidic ionic transistor based on carbon nanotubes, which exhibits an on/off ratio of 104 at operational gate voltage as low as 1 V. By controlling the morphology of carbon nanotubes, both unipolar and ambipolar ionic transistors are realized, and their on/off ratio can be further improved by introducing an Al2O3 dielectric layer. Meanwhile, this ionic transistor enables the polarity switching between p-type and n-type by controlled surface properties of carbon nanotubes. The implementation of constructing ionic circuits based on ionic transistors is demonstrated, which enables the creation of NOT, NAND, and NOR logic gates. The ionic transistors are expected to have profound implications for low-energy consumption computing devices and brain-machine interfacing.

Radiomics Model of Dynamic Contrast-Enhanced MRI for Evaluating Vessels Encapsulating Tumor Clusters and Microvascular Invasion in Hepatocellular Carcinoma.

RATIONALE AND OBJECTIVES: To develop and validate a clinical-radiomics model of dynamic contrast-enhanced MRI (DCE-MRI) for the preoperative discrimination of Vessels encapsulating tumor clusters (VETC)- microvascular invasion (MVI) and prognosis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: 219 HCC patients from Institution 1 were split into internal training and validation groups, with 101 patients from Institution 2 assigned to external validation. Histologically confirmed VETC-MVI pattern categorizing HCC into VM-HCC+ (VETC+/MVI+, VETC-/MVI+, VETC+/MVI-) and VM-HCC- (VETC-/MVI-). The regions of intratumor and peritumor were segmented manually in the arterial, portal-venous and delayed phase (AP, PP, and DP, respectively) of DCE-MRI. Six radiomics models (intratumor and peritumor in AP, PP, and DP of DCE-MRI) and one clinical model were developed for assessing VM-HCC. Establishing intra-tumoral and peri-tumoral models through combining intratumor and peritumor features. The best-performing radiomics model and the clinical model were then integrated to create a Combined model. RESULTS: In institution 1, pathological VM-HCC+ were confirmed in 88 patients (training set: 61, validation set: 27). In internal testing, the Combined model had an AUC of 0.85 (95% CI: 0.76-0.93), which reached an AUC of 0.75 (95% CI: 0.66-0.85) in external validation. The model's predictions were associated with early recurrence and progression-free survival in HCC patients. CONCLUSIONS: The clinical-radiomics model offers a non-invasive approach to discern VM-HCC and predict HCC patients' prognosis preoperatively, which could offer clinicians valuable insights during the decision-making phase.

Association between PFAS exposure and thyroid health: A systematic review and meta-analysis for adolescents, pregnant women, adults and toxicological evidence.

A burgeoning body of epidemiological and toxicological evidence suggests that thyroid health may be significantly impacted by exposure to both long- and short-chain perfluoroalkyl substances (PFAS) compounds. We conducted a meta-analysis to examine the association between 16 PFAS compounds and five thyroid hormones (TSH, TT3, TT4, FT3, and FT4) in the serum of a pregnant women, adolescents, and adults. The dose-response relationship between some PFAS and thyroid hormones in different population subpopulation was found and the model was fitted. We also amalgamated data from 18 animal experiments with previously published in vitro studies to elucidate the toxicological mechanisms underlying the impact of PFAS on the thyroid gland. The results of the study showed that (a) both conventional and emerging PFAS compounds were identified in human samples and exhibited associations with thyroid health outcomes; (b) in animal studies, PFAS have been found to impact thyroid gland health through two primary mechanisms: by influencing the hypothalamic-pituitary-thyroid axis and by binding to thyroid receptors. This study provides a systematic description of the health effects and risk assessment associated with PFAS exposure on the thyroid gland. Furthermore, dose-response relationships were established through the Hill model in python.

The effect of different prebiotics on intestinal probiotics in newly diagnosed diabetic patients.

Prebiotics exert favorable effects on the host through interactions with probiotics, and their beneficial impacts have been extensively validated across various chronic ailments, including diabetes. This study presents findings from a case-control investigation involving 10 individuals with type 2 diabetes mellitus (T2DM) and 10 healthy counterparts. Fresh stool specimens were collected from all participants. Following a 24-h fermentation period in mediums containing xylitol and mannitol, the observed increase in Lactobacillus abundance within the case group exceeded that of the control group. Similarly, in mediums containing soluble starch, choline, and L-carnitine, the augmentation of Bifidobacterium within the case group surpassed that of the controls. Notably, a statistically significant divergence in sugar degradation rate emerged between the case and control groups, specifically in the medium harboring lactulose and isomalto-oligosaccharides. Remarkably, the degradation rate of lactulose exhibited a positive correlation with the expansion of Bifidobacterium (R 2 = .147, p = .037). Likewise, the degradation rate of isomalto-oligosaccharides demonstrated a positive correlation with Bifidobacterium proliferation (R 2 = .165, p = .041). In conclusion, prebiotics like xylitol and mannitol exhibit the capacity to enhance intestinal probiotic populations in individuals newly diagnosed with diabetes. The modifications in the intestinal flora homeostasis of diabetic patients may be evidenced by alterations in the degradation rate of specific prebiotic substrates.

99mTc-Labeled FAPI SPECT Imaging in Idiopathic Pulmonary Fibrosis: Preliminary Results.

AIM: Idiopathic pulmonary fibrosis (IPF) is associated with a poor prognosis, presenting the most aggressive form of interstitial lung diseases (ILDs). Activated fibroblasts are crucial for pathological processes. Fibroblast activation protein (FAP) inhibitor (FAPI) tracers would be promising imaging agents for these diseases. The purpose of this study was to evaluate a 99mTc-labeled FAPI tracer, 99mTc-HFAPI imaging in IPF patients. METHODS: Eleven IPF patients (nine males and two females; age range 55-75 year) were included in this pilot study. 99mTc-HFAPI serial whole-body scintigraphy at 5 min, 20 min, 40 min, 1 h, 2 h, 3 h, 4 h, and 6 h was acquired for dynamic biodistribution and dosimetry estimation in seven representative patients. SPECT/CT tomography fusion imaging of the chest region was performed in all patients at 4 h post-injection, which was considered as the optimal acquisition time. Dosimetry was calculated using OLINDA/EXM software (version 2.0; HERMES Medical Solutions). The quantified or semi-quantified standardized uptake values (SUVs) and lesion-to-background ratios (LBRs) of affected lung parenchyma were also calculated. The high-resolution CT (HRCT) stage was determined with visual evaluation, and the total HRCT score of each patient was measured using a weighting factor formula. Pulmonary function tests (PFTs) were recorded as well. Then, the relationships between the 99mTc-HFAPI results, disease extent on HRCT, and PFT results were investigated. RESULTS: Normal physiological uptake of 99mTc-HFAPI was observed mainly in the liver, intestinal tract, pancreas, gallbladder, and to a lesser extent in the spleen, kidneys, and thyroid, with no apparent retention in the blood circulation at the late time point. The mean injected activity of 99mTc-HFAPI was 813.4 MBq (range 695.6-888.0 MBq). No subjective side effects were noticed. The average whole-body effective dose was 0.0041 mSv/MBq per patient. IPF patients exhibited elevated pulmonary 99mTc-HFAPI uptake in abnormal lung regions, which was correlated with fibrotic regions on HRCT. Among different HRCT stage groups, both SUVmax and LBR showed significant differences (p < 0.001). The higher HRCT stage demonstrated significantly higher SUVmax and LBR. A linear correlation between 99mTc-HFAPI uptake and total HRCT score was observed for SUVmax (r = 0.7839, F = 54.41, p = 0.0094) and LBR (r = 0.7402, F = 56.33, p = 0.0092). 99mTc-HFAPI uptake also had moderate correlations with PFT results. CONCLUSIONS: Our preliminary data show that the 99mTc-HFAPI SPECT imaging is a promising new imaging modality in IPF patients. Investigations of its clinical value in monitoring disease progression and treatment response are needed in the future.