Rational Design and Comparison of Novel 99mTc-Labeled FAPI Dimers for Visualization of Multiple Tumor Types.

Recognizing the significance of SPECT in nuclear medicine and the pivotal role of fibroblast activation protein (FAP) in cancer diagnosis and therapy, this study focuses on the development of 99mTc-labeled dimeric HF2 with high tumor uptake and image contrast. The dimeric HF2 was synthesized and radiolabeled with 99mTc in one pot using various coligands (tricine, TPPTS, EDDA, and TPPMS) to yield [99mTc]Tc-TPPTS-HF2, [99mTc]Tc-EDDA-HF2, and [99mTc]Tc-TPPMS-HF2 dimers. SPECT imaging results indicated that [99mTc]Tc-TPPTS-HF2 exhibited higher tumor uptake and tumor-to-normal tissue (T/NT) ratio than [99mTc]Tc-EDDA-HF2 and [99mTc]Tc-TPPMS-HF2. Notably, [99mTc]Tc-TPPTS-HF2 exhibited remarkable tumor accumulation and retention in HT-1080-FAP and U87-MG tumor-bearing mice, thereby surpassing the monomeric [99mTc]Tc-TPPTS-HF. Moreover, [99mTc]Tc-TPPTS-HF2 achieved acceptable T/NT ratios in the hepatocellular carcinoma patient-derived xenograft (HCC-PDX) model, which provided identifiable contrast and imaging quality. In conclusion, this study presents proof-of-concept research on 99mTc-labeled FAP inhibitor dimers for the visualization of multiple tumor types. Among these candidate compounds, [99mTc]Tc-TPPTS-HF2 showed excellent clinical potential, thereby enriching the SPECT tracer toolbox.

Rational Design and Pharmacomodulation of 18F-Labeled Biotin/FAPI-Conjugated Heterodimers.

Due to the complex heterogeneity in different cancer types, the heterodimeric strategy has been intensively practiced to improve the effectiveness of tumor diagnostics. In this study, we developed a series of novel 18F-labeled biotin/FAPI-conjugated heterobivalent radioligands ([18F]AlF-NSFB, [18F]AlF-NSFBP2, and [18F]AlF-NSFBP4), synergistically targeting both fibroblast activation protein (FAP) and biotin receptor (BR), to enhance specific tumor uptake and retention. The in vitro and in vivo biological properties of these dual-targeting tracers were evaluated, with a particular focus on positron emission tomography imaging in A549 and HT1080-FAP tumor-bearing mice. Notably, in comparison to the corresponding FAP-targeted monomer [18F]AlF-NSF, biotin/FAPI-conjugated heterodimers exhibited a high uptake in tumor and prolong retention. In conclusion, as a proof-of-concept study, the findings validated the superiority of biotin/FAPI-conjugated heterodimers and the positive influence of biotin and linker on pharmacokinetics of radioligands. Within them, the bispecific [18F]AlF-NSFBP4 holds significant promise as a candidate for further clinical translational studies.

Mn(II)-Based Metal Halide with Near-Unity Quantum Yield for White LEDs and High-Resolution X-ray Imaging.

Metal halides have drawn great interest as luminescent materials and scintillators due to their outstanding optical properties. Exploring new types of phosphors with easy production processes, excellent photophysical properties, high light yields, and environmentally friendly compositions is crucial and quite challenging. Herein, a novel Mn(II)-based metal halide (4-BTP)2MnBr4 was produced using a facile solvent evaporation method, which exhibited a strong green emission peaking at 524 nm from the d-d transition of tetrahedral-coordinated Mn2+ ion and a near-unity quantum yield. The prepared white light-emitting diode device has a wide color gamut of 100.7% NTSC with CIE chromaticity coordinates of (0.32, 0.32). In addition, (4-BTP)2MnBr4 demonstrates excellent characteristics in X-ray scintillation, including a high light yield of 98 000 photons/MeV, a sensitive detection limit of 37.4 nGy/s, excellent resistance to radiation damage, and successful demonstration of X-ray imaging with high resolution at 21.3 lp/mm, revealing the potential for application in diagnostic X-ray medical imaging and industry radiation detection.

Evaluation of the prediction effectiveness for geochemical mapping using machine learning methods: A case study from northern Guangdong Province in China.

This study compares seven machine learning models to investigate whether they improve the accuracy of geochemical mapping compared to ordinary kriging (OK). Arsenic is widely present in soil due to human activities and soil parent material, posing significant toxicity. Predicting the spatial distribution of elements in soil has become a current research hotspot. Lianzhou City in northern Guangdong Province, China, was chosen as the study area, collecting a total of 2908 surface soil samples from 0 to 20 cm depth. Seven machine learning models were chosen: Random Forest (RF), Support Vector Machine (SVM), Ridge Regression (Ridge), Gradient Boosting Decision Tree (GBDT), Artificial Neural Network (ANN), K-Nearest Neighbors (KNN), and Gaussian Process Regression (GPR). Exploring the advantages and disadvantages of machine learning and traditional geological statistical models in predicting the spatial distribution of heavy metal elements, this study also analyzes factors affecting the accuracy of element prediction. The two best-performing models in the original model, RF (R2 = 0.445) and GBDT (R2 = 0.414), did not outperform OK (R2 = 0.459) in terms of prediction accuracy. Ridge and GPR, the worst-performing methods, have R2 values of only 0.201 and 0.248, respectively. To improve the models' prediction accuracy, a spatial regionalized (SR) covariate index was added. Improvements varied among different methods, with RF and GBDT increasing their R2 values from 0.4 to 0.78 after enhancement. In contrast, the GPR model showed the least significant improvement, with its R2 value only reaching 0.25 in the improved method. This study concluded that choosing the right machine learning model and considering factors that influence prediction accuracy, such as regional variations, the number of sampling points, and their distribution, are crucial for ensuring the accuracy of predictions. This provides valuable insights for future research in this area.

18F-Labeled Amidobenzimidazole Analogue for Visualizing STING Expression in Tumor.

The stimulator of interferon genes (STING) is pivotal in mediating STING-dependent type I interferon production, which is crucial for enhancing tumor rejection. Visualizing STING within the tumor microenvironment is valuable for STING-related treatments, yet the availability of suitable STING imaging probes is limited. In this study, we developed [18F]AlF-ABI, a novel 18F-labeled agent featuring an amidobenzimidazole core structure, for positron emission tomography (PET) imaging of STING in B16F10 and CT26 tumors. [18F]AlF-ABI was synthesized with a decay-corrected radiochemical yield of 38.0 ± 7.9% and radiochemical purity exceeding 97%. The probe exhibited a nanomolar STING binding affinity (KD = 35.6 nM). Upon administration, [18F]AlF-ABI rapidly accumulated at tumor sites, demonstrating significantly higher uptake in B16F10 tumors compared to CT26 tumors, consistent with STING immunofluorescence patterns. Specificity was further validated through in vitro cell experiments and in vivo blocking PET imaging. These findings suggest that [18F]AlF-ABI holds promise as an effective agent for visualizing STING in the tumor microenvironment.

Environmental-related doses of afidopyropen induced toxicity effects in earthworms (Eisenia fetida).

Afidopyropen has high activity against pests. However, it poses potential risks to the soil ecology after entering the environment. The toxicity of afidopyropen to earthworms (Eisenia fetida) was studied for the first time in this study. The results showed that afidopyropen had low level of acute toxicity to E. fetida. Under the stimulation of chronic toxicity, the increase of reactive oxygen species (ROS) level activated the antioxidant and detoxification system, which led to the increase of superoxide dismutase (SOD) and glutathione S-transferase (GST) activities. Lipid peroxidation and DNA damage were characterized by the increase of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) contents. Meanwhile, the functional genes SOD, CAT, GST, heat shock protein 70 (HSP70), transcriptionally controlled tumor protein (TCTP), and annetocin (ANN) played a synergistic role in antioxidant defense. However, the comprehensive toxicity of high concentration still increased on the 28th day. In addition, strong histopathological damage in the body wall and intestine was observed, accompanied by weight loss, which indicated that afidopyropen inhibited the growth of E. fetida. The molecular docking revealed that afidopyrene combined with the surface structure of SOD and GST proteins, which made SOD and GST become sensitive biomarkers reflecting the toxicity of afidopyropen to E. fetida. Summing up, afidopyropen destroys the homeostasis of E. fetida through chronic toxic. These results provide theoretical data for evaluating the environmental risk of afidopyropen to soil ecosystem.

Insight into Multiphase Interlayer Molecular Packing and Stepwise Phase Transition in 4-(Phenylazo)benzoate Anion-Intercalated Layered Zinc Hydroxide.

The properties of layered intercalation hybrids are closely related to interlayer molecular packing. To develop functional intercalation hybrids, it is essential to gain deep insights into interlayer molecular packing. This work reports a new comprehensive insight into the controllable multiphase interlayer molecular packing in 4-(phenylazo)benzoate anion-intercalated layered zinc hydroxide (LZH-4-PAB intercalation hybrids). The new insight breaks up the general understanding that the interlayer molecular packing of anions is usually single-phase, lacking diversity and controllability. Furthermore, it uncovers an interesting stepwise rather than the generally expected continuous phase transition of the interlayer molecular packing. The intercalated 4-PAB anions initially organize into the horizontal monolayer packing (θ = 0°, Phase I), which stepwise transforms to the tilted interdigitated antiparallel bilayer packing (θ ≈ 50°, Phase II) along with an increased intercalation loading and eventually to the vertical interdigitated antiparallel bilayer packing (θ = 90°, Phase III). The LZH-4-PAB hybrids exhibited a greatly enhanced interlayer molecular packing-dependent UV-vis absorption. This study provides helpful guidance for developing property-tailored intercalation hybrids. It may attract new interest in more layered intercalation hybrids. New and rich intercalation chemistry might be discovered in more functional intercalation hybrids beyond the 4-PAB anion-intercalated layered zinc hydroxide.

Cross-linked α-Ni(OH)2 nanosheets with a Ni3+-rich structure for accelerating electrochemical oxidation of 5-hydroxymethylfurfural.

Electrochemical oxidation of biomass-based 5-hydroxymethylfurfural (HMF) is an effective approach for achieving the high-value products of 2,5-furandicarboxylic acid (FDCA). However, the restricted formation of high-valence metal active species for electrocatalysts results in a sluggish kinetic process of HMF oxidation reaction (HMFOR). Herein, we fabricated the Ni3+-rich cross-linked α-Ni(OH)2 nanosheets for accelerating the HMFOR through an anion-mediated strategy. It is identified that the Cl- ions with strong penetrability replace a portion of lattice oxygen atoms in α-Ni(OH)2 to form Ni-Cl bonds, contributing to breaking the inherent lattice order and generating a special Ni3+-rich structure. Owing to the promoted adsorption and accelerated oxidation of hydroxyl and aldehyde groups by the affluent Ni3+ active species, the large oxidation current density of 116.5 mA cm-2 and HMFOR kinetic constant of 0.067 min-1 has been achieved at 1.45 V (vs. RHE). By analyzing the oxidation products, the FDCA yield and Faradic efficiency are both higher than 99.25 % and 99.36 % for five successive determinations. Therefore, this work provides an insightful anion-mediated strategy for designing high-performance electrocatalysts for biomass conversion application.

FOXP2 suppresses the proliferation, invasion, and aerobic glycolysis of hepatocellular carcinoma cells by regulating the KDM5A/FBP1 axis.

The Warburg effect is the preference of cancer cells to use glycolysis rather than oxidative phosphorylation to generate energy. Accumulating evidence suggests that aerobic glycolysis is widespread in hepatocellular carcinoma (HCC) and closely related to tumorigenesis. The purpose of this study was to investigate the role and mechanism of forkhead box P2 (FOXP2) in aerobic glycolysis and tumorigenesis in HCC. Here, we found that FOXP2 was lower expressed in HCC tissues and cells than in nontumor tissues and normal hepatocytes. Overexpression of FOXP2 suppressed cell proliferation and invasion of HCC cells and promoted cell apoptosis in vitro, and hindered the growth of mouse xenograft tumors in vivo. Further researches showed that FOXP2 inhibited the Warburg effect in HCC cells. Moreover, we demonstrated that FOXP2 up-regulated the expression of fructose-1, 6-diphosphatase (FBP1), and the inhibitory effect of FOXP2 on glycolysis was dependent on FBP1. Mechanistically, as a transcription factor, FOXP2 negatively regulated the transcription of lysine-specific demethylase 5A (KDM5A), and then blocked KDM5A-induced H3K4me3 demethylation in FBP1 promoter region, thereby promoting the expression of FBP1. Consistently, overexpressing KDM5A or silencing FBP1 effectively reversed the inhibitory effect of FOXP2 on HCC progression. Together, our findings revealed the mechanistic role of the FOXP2/KDM5A/FBP1 axis in glycolysis and malignant progression of HCC cells, providing a potential molecular target for the therapy of HCC.

Boosting the Catalase-Like Activity of SAzymes via Facile Tuning of the Distances between Neighboring Atoms in Single-Iron Sites.

A nanozyme with neighboring single-iron sites (Fe2 -SAzyme) was introduced as a bioinspired catalase mimic, featuring excellent activity under varied conditions, twice as high as that of random Fe1 -SAzyme and ultrahigh H2 O2 affinity as that of bioenzymes. Surprisingly, the interatomic spacing tuning between adjacent iron sites also suppressed the competitive peroxidase pathway, remarkably increasing the catalase/peroxidase selectivity up to ~6 times compared to Fe1 -SAzyme. This dramatically switched the catalytic activity of Fe-SAzymes from generating (i.e. Fe1 -SAzymes, preferably mimicking peroxidase) to scavenging ROS (i.e. Fe2 -SAzymes, dominantly mimicking catalase). Theoretical and experimental investigations suggested that the pairwise single-iron sites may serve as a robust molecular tweezer to efficiently trap and decompose H2 O2 into O2 , via cooperative hydrogen-bonding induced end-bridge adsorption. The versatile mechano-assisted in situ MOF capsulation strategy enabled facile access to neighboring M2 -SAzyme (M=Fe, Ir, Pt), even up to a 1000 grams scale, but with no obvious scale-up effect for both structures and performances.

Curcumin nanocrystals-in-nanofibres as a promising platform for the management of periodontal disease.

It is estimated that nearly a half of the world's population over 30 years old suffer from some kind of periodontal disease (PD). Although preventable, PD can pose a significant health burden to patients, causing from pain and discomfort to disfigurement and death. The management of PD often requires surgical procedures accompanied of systemic antibiotic and anti-inflammatory treatments. Curcumin (CUR), a potent anti-inflammatory and antimicrobial active, has shown great promise in the management of PD; however, its effects are often limited by its low bioavailability. In this work, we report the development of electrospun nanofibres (NFs) loaded with CUR nanocrystals (NCs) for the management of PD. NCs of 100 nm were obtained by media milling and loaded into dissolving polyvinyl alcohol NFs using electrospinning. The resultant NCs-in-NFs dissolved in water spontaneously, releasing NCs with a particle size of âˆ¼120 nm. The physiochemical characterisation of the systems indicated the absence of chemical interactions between drug and polymer, and nanofibres with an amorphous nature. In vitro release profiles demonstrated that the NCs had a significantly higher dissolution rate (∼100 % at day 40) than the control group (approximately 6 % at day 40), which consisted of NFs containing a physical mixture of the drug and stabiliser. Finally, mucosal deposition studies demonstrated a 10-fold higher capacity of the novel NCs-in-NFs system to deposit CUR ex vivo using excised neonatal porcine mucosal tissue, when compared to the control group.

Radiographic and Patient-Reported Outcomes of a Low-Cost Modified Lapidus Bunion Correction Technique.

Background: The modified Lapidus (ML) is a powerful procedure for correction of hallux valgus (HV) with emerging techniques. Studies considering patient-reported outcomes, radiographic measures, complications, and implant costs are currently limited. Methods: Retrospective cohort with prospectively collected Patient Reported Outcome Information System Physical Function (PROMIS-PF) Computerized Adaptive Test (CAT) scores, radiographic parameters (intermetatarsal angle, IMA; hallux valgus angle, HVA; and tibial sesamoid position, TSP), complications, and total operative time and implant costs were reviewed from 2014 to 2019. Results: Seventy-three feet (68 patients) underwent bunion correction by ML with lag-screw fixation. Median age was 55.8 years (IQR 45.6, 53.9), 4 of 73 (5.5%) were male, 11 of 73 (15.1%) were smokers, and 15 of 73 (20.6%) were diabetic (median HbA1c 6.4% [IQR 6.0, 7.4], none insulin dependent, 5 of 15 with neuropathy). Complications included 6 of 73 (8.2%) wound issues resolved with topical or oral treatment, 9 of 73 (12.3%) painful or broken hardware requiring hardware removal. Two of 73 (2.7%) had persistent pain despite union. One of 73 (1.4%) was overcorrected and required first MTP arthrodesis. Of 3 nonunions (2.7%), 1 resolved with corrected hypothyroidism, 1 was asymptomatic and required no treatment, 1 had a hallux valgus recurrence and sought revision surgery elsewhere. Preoperative radiographic angles were HVA 35 degrees, IMA 14 degrees which improved at final postoperative follow up to HVA 10 degrees, IMA 6 degrees. Tibial sesamoid position improved from 6.05 ± 1.00 to 2.22 ± 1.38. Thirty-two patients had preoperative and 42 had 1-year postoperative outcomes. PROMIS-PF (51% collection rate) was 43 (IQR 37,52) preoperatively, 37 (31, 39) at 6 weeks, 46 (42, 51) at 3 months, and 49 (41, 53) at >360 days postoperatively. The drop in PROMIS-PF between preoperative and 6 weeks and the rise from 6 weeks to 3 months were statistically significant. Pre- and postoperative PROMIS-PF scores were not significantly different. Implant cost averaged US$146. Discussion/Conclusion: We report low complication rates and costs with high patient postoperative functional and radiographic outcomes. PROMIS-PF decreased acutely postoperatively but recovered and maintained high levels by 3 months postoperatively. Level of Evidence: Level IV, case series.

Highly Selective and Fast Response/Recovery Cataluminescence Sensor Based on SnO2 for H2S Detection.

In the present work, three kinds of nanosized SnO2 samples were successfully synthesized via a hydrothermal method with subsequent calcination at temperatures of 500 °C, 600 °C, and 700 °C. The morphology and structure of the as-prepared samples were characterized using X-ray diffraction, transmission electron microscopy, selected area electron diffraction, Brunauer-Emmett-Teller analysis, and X-ray photoelectron spectroscopy. The results clearly indicated that the SnO2 sample calcined at 600 °C had a higher amount of chemisorbed oxygen than the SnO2 samples calcined at 500 °C and 700 °C. Gas sensing investigations revealed that the cataluminescence (CTL) sensors based on the three SnO2 samples all exhibited high selectivity toward H2S, but the sensor based on SnO2-600 °C exhibited the highest response under the same conditions. At an operating temperature of 210 °C, the SnO2-600 °C sensor showed a good linear response to H2S in the concentration range of 20-420 ppm, with a detection limit of 8 ppm. The response and recovery times were 3.5 s/1.5 s for H2S gas within the linear range. The study on the sensing mechanism indicated that H2S was oxidized into excited states of SO2 by chemisorbed oxygen on the SnO2 surface, which was mainly responsible for CTL emission. The chemisorbed oxygen played an important role in the oxidation of H2S, and, as such, the reason for the SnO2-600 °C sensor showing the highest response could be ascribed to the highest amount of chemisorbed oxygen on its surface. The proposed SnO2-based gas sensor has great potential for the rapid monitoring of H2S.

Association of Subjective Sleep Pattern with Self-reported Diabetes in China.

There is limited research investigating the relationship between self-reported diabetes mellitus and subjective sleep patterns. Our study aims to explore this association by analyzing trends in a cohort study conducted in China using data from the China Health and Nutrition Survey longitudinal research (CHNS). We used multilevel logistic regression models to analyze the relationship. Our findings indicate that the prevalence of self- reported diabetes in China increased from 1.10% in 2004 to 3.36% in 2015, with an increase in the prevalence of short-term sleep from 7.03-10.24%. The prevalence of self-reported diabetes increased with increasing BMI levels (Normal and below: 0.67-2.16%, Overweight: 1.58-4.35%, Obesity: 2.68-6.57%, p < 0.01). The short-term sleep subgroup had the highest prevalence (2.14-5.64%). Additionally, we found significant associations between age, education level, ethnicity, coffee, smoking, drinking and the self-reported diabetes. Interestingly, the risk ratios for self-reported diabetes differed between sleep durations. With 6-8hours as the reference group, the risk ratios for self-reported diabetes in the short-term, and long-term sleep subgroups were 1.80 (95% CI: 1.23-2.63), and 1.41 (95%CI: 1.01-1.96), respectively. Raising awareness about the impact of irregular sleep duration on diabetes risk is essential, and these initiatives may serve as effective policies for diabetes control.

Plant resistance against whitefly and its engineering.

Plants face constant threats from insect herbivores, which limit plant distribution and abundance in nature and crop productivity in agricultural ecosystems. In recent decades, the whitefly Bemisia tabaci, a group of phloem-feeding insects, has emerged as pests of global significance. In this article, we summarize current knowledge on plant defenses against whitefly and approaches to engineer plant resistance to whitefly. Physically, plants deploy trichome and acylsugar-based strategies to restrain nutrient extraction by whitefly. Chemically, toxic secondary metabolites such as terpenoids confer resistance against whitefly in plants. Moreover, the jasmonate (JA) signaling pathway seems to be the major regulator of whitefly resistance in many plants. We next review advances in interfering with whitefly-plant interface by engineering of plant resistance using conventional and biotechnology-based breeding. These breeding programs have yielded many plant lines with high resistance against whitefly, which hold promises for whitefly control in the field. Finally, we conclude with an outlook on several issues of particular relevance to the nature and engineering of plant resistance against whitefly.

Study on the China's real interest rate after including housing price factor into CPI.

The Chinese economy has undergone a long-term transition reform, but there is still a planned economy characteristic in the financial sector, which is financial repression. Due to the existence of financial repression, China's actual interest rate level should be lower than the Consumer Price Index (CPI). However, based on official China's interest rates and CPI, over half of the years China's actual interest rate remained higher than CPI by our calculation from 1999 to 2022. This is inconsistent with the financial repression that exists in China, and the main reason is the calculation methods of China's CPI. China's CPI measurement system originated from the planned economy era, which did not fully consider the rise in housing purchase prices, so the current CPI measurement system can be more realistically presented by taking the rise in housing prices into consider. The core idea of this study is to mining relevant official statistical data and calculate the proportion of Chinese residents' expenditure on purchasing houses to their total expenditure. By taking the proportion of house purchases as the weight of house price factor, and taking the proportion of other consumption as the weight of official CPI, the Generalized CPI (GCPI) is formulated. The GCPI is then compared with market interest rates to determine the actual interest rate situation in China over the past 20 years. This study has found that if GCPI is used as a measure, China's real interest rates have been negative for most years since 1999. Chinese residents have suffered the negative effects of financial repression over the past 20 years, and their property income cannot keep up with the actual losses caused by inflation. Therefore, it is believed that China's CPI calculation method should be adjusted to take into account the rise in housing prices, so China's actual inflation level could be more accurately reflected. In view of the above, deepening interest rate marketization reform and expand channels for financial investment are the future development goals of China's financial system.

Mitochondrial apoptosis-related gene polymorphisms are associated with responses to anthracycline-based chemotherapy in acute myeloid leukaemia.

Background: Although anthracyclines are the first-line chemotherapy drugs for treating non-M3 acute myeloid leukaemia (AML), their efficacy remains limited. It is important to identify factors that influence the efficacy of anthracyclines against AML. Mitochondrial apoptosis-related genes play significant roles in the pathogenesis, treatment, and prognosis of AML. Methods: We utilized the CRISPR/Cas9 screening system to find AML anthracyclines resistance related genes and several mitochondrial apoptosis-related genes, such as BCL2L11, CASP8, TP63, TP53BP2, PLAUR, SOD2, BNIP3L, and MMP9, were screened out. Then, DNA from 279 patients with AML and 321 healthy individuals were extracted and the contributions of single nucleotide polymorphisms (SNPs) within these genes to the patient's chemotherapy response, susceptibility to AML, and overall survival were investigated. Results: Our findings indicated that SNP rs4251864 in the PLAUR gene was associated with an increase in complete remission after anthracycline-based induction chemotherapy. rs4880 in SOD2 was associated with the response to the second course of chemotherapy, whereas rs3789068 in BCL2L11 was associated with susceptibility to AML. Conclusions: Our results about the association of SNPs in mitochondrial apoptosis-related genes with the response to anthracycline-based chemotherapy in AML provide an important reference for predicting the treatment outcomes in patients with this disease.

Curcumin inhibits proliferation of hepatocellular carcinoma cells by blocking PTPN1 and PTPN11 expression.

The antitumor mechanism of curcumin is unclear, especially in hepatocellular carcinoma (HCC) cells. To clarify the mechanism of action of curcumin in the effective treatment of HCC, the targets of curcumin were screened and validated. Candidate genes of curcumin for HCC were screened using the traditional Chinese medicine systems pharmacology (TCMSP) database and validated using The Cancer Genome Atlas (TCGA) database. The correlation of mRNA expression levels between key candidate genes was identified in the TCGA liver hepatocellular carcinoma (LIHC) dataset. The effects on prognosis were analyzed to identify the target gene of curcumin, which inhibits HCC cell proliferation. Based on the subcutaneous xenograft model of human HCC in nude mice, the expression levels of target proteins were observed using immunohistochemistry. The analysis results of the present study identified the target genes of curcumin, which were obtained by screening the TCSMP database. The protein tyrosine phosphatase non-receptor type 1 (PTPN1) was obtained from TCGA database analysis of the targeted genes. The expression levels of PTPN1 and its homologous sequence genes in TCGA LIHC project was analyzed to identify the potential target gene of curcumin, for use in HCC treatment. Next, xenograft experiments were performed to investigate the therapeutic effects of curcumin in an animal model. Curcumin was demonstrated to inhibit the growth of HCC xenograft tumors in mice. Immunohistochemistry results demonstrated that the protein expression levels of PTPN1 and PTPN11 in the curcumin group were significantly lower compared with those in the control group. In conclusion, these results demonstrated that curcumin inhibits the proliferation of HCC cells by inhibiting the expression of PTPN1 and PTPN11.

Bioaccumulation and risk mitigation of legacy and novel perfluoroalkyl substances in seafood: Insights from trophic transfer and cooking method.

Per- and polyfluoroalkyl substances (PFAS) have widespread application in industrial and civil areas due to their unique physical and chemical properties. With the increasingly stringent regulations of legacy PFAS, various novel alternatives have been developed and applied to meet the market demand. Legacy and novel PFAS pose potential threats to the ecological safety of coastal areas, however, little is known about their accumulation and transfer mechanism, especially after cooking treatment. This study investigated the biomagnification and trophic transfer characteristics of PFAS in seafood from the South China Sea, and assessed their health risks after cooking. Fifteen target PFAS were all detected in the samples, of which perfluorobutanoic acid (PFBA) was dominant with concentrations ranging from 0.76 to 4.12 ng/g ww. Trophic magnification factors (TMFs) > 1 were observed for perfluorooctane sulfonate (PFOS) and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (F-53B), indicating that these compounds experienced trophic magnification in the food web. The effects of different cooking styles on PFAS occurrence were further explored and the results suggested that ΣPFAS concentrations increased in most organisms after baking, while ΣPFAS amounts decreased basically after boiling and frying. Generally, there is a low health risk of exposure to PFAS when cooked seafood is consumed. This work provided quantitative evidence that cooking methods altered PFAS in seafood. Further, suggestions to mitigate the health risks of consuming PFAS-contaminated seafood were provided.

Can we buffer them? Supporting healthy levels of stress and anxiety in first year international students.

First-year international tertiary students face numerous challenges, with the COVID-19 pandemic shifting many to online learning. These challenges can lead to higher than ideal stress and anxiety, negatively impacting mental health. Applying a 'writing across curriculum' approach this study examines whether a 'writing in discipline' intervention influences stress/anxiety for such students studying Tourism, Hospitality and Events in Australia. A modified DASS was administered to four cohorts during 2020 and 2021, and pre-post-tests conducted. The intervention helped buffer significant increases in stress, promoted skill development, and enhanced academic confidence. This scaffolded-learning approach is applicable at course/subject, degree, and university levels.