Ketogenesis attenuated KLF5 disrupts iron homeostasis via LIF to confer oxaliplatin vulnerability in colorectal cancer.

Oxaliplatin has been included as a basal drug in various chemotherapy regimens for colorectal cancer (CRC), a global health concern. However, acquired resistance to oxaliplatin affects the prognosis. This study aimed to determine whether the consumption of a KD increases the sensitivity of CRC cells to oxaliplatin via the inhibition of a classical stem cell marker, Krupple-like factor 5 (KLF5). KLF5 functions as a transcription factor for the leukemia inhibitory factor (LIF) and directly binds to its promoter region. LIF upregulation induces dephosphorylation of metal regulatory transcription factor 1 (MTF1), which is recruited to the promoter area of Ferroportin (FPN1), the only cellular iron exporter. FPN1 upregulation reduces the labile iron pool (LIP) and ferroptosis in CRC cells. KLF5 knockdown inhibits the LIF/MTF1/FPN1 axis and induces iron overload, thereby conferring sensitivity to oxaliplatin to CRC cells. KD mimicked KLF5 silencing and sensitized CRC cells to oxaliplatin via a similar mechanism. Thus, potential correlations were observed among ketogenesis, stemness, and iron homeostasis. This finding can be used to formulate a new strategy for overcoming oxaliplatin resistance in patients with CRC.

Postoperative lenvatinib + PD-1 blockade reduces early tumor recurrence in hepatocellular carcinoma with microvascular invasion (Barcelona Clinic Liver Cancer stage 0 or A): a propensity score matching analysis.

BACKGROUND: This study aimed to determine the effectiveness of postoperative adjuvant lenvatinib + PD-1 blockade for patients with early-stage hepatocellular carcinoma (HCC) with microvascular invasion (MVI). METHODS: A total of 393 patients with HCC (Barcelona Clinic Liver Cancer stage 0 or A) who underwent curative hepatectomy with histopathologically proven MVI were enrolled according to the inclusion and exclusion criteria and assigned to 2 groups: surgery alone (surgery-alone group) and surgery with lenvatinib and PD-1 blockade (surgery + lenvatinib + PD-1 group) to compare recurrence-free survival (RFS), overall survival (OS), recurrence type, and annual recurrence rate after the application of propensity score matching (PSM). The Cox proportional hazards model was used for univariate and multivariate analyses. RESULTS: Overall, 99 matched pairs were selected using PSM. Patients in the surgery + lenvatinib + PD-1 group had significantly higher 3-year RFS rates (76.8%, 65.7%, and 53.5%) than patients in the surgery-alone group (60.6%, 45.5%, and 37.4%) (P = .012). The 2 groups showed no significant difference in recurrence types and OS. Surgery alone, MVI-M2, and alpha-fetoprotein of ≥200 ng/mL were independent risk factors for RFS (P < .05), and history of alcohol use disorder was an independent risk factor for OS (P = .022). CONCLUSION: Postoperative lenvatinib + PD-1 blockade improved the RFS in patients with HCC with MVI and was particularly beneficial for specific individuals.

Impact of Empowerment Theory-Based Nursing Intervention on the Quality of Life and Negative Emotions of Patients Diagnosed with Brain Metastasis Post Breast Cancer Surgery.

Objective: This study explores the impact of a nursing intervention grounded in empowerment theory, focusing on behavioral change, on brain metastasis patients post-breast cancer surgery. Methods: Between June 2021 and June 2023, 102 patients diagnosed with brain metastasis after breast cancer surgery at Bao Ding No.1 Central Hospital were randomized into two groups. The control group (51 patients) received standard nursing care, while the observation group (51 patients) participated in a behavioral change nursing intervention influenced by empowerment theory. The evaluation metrics included measures of negative emotions, compliance with treatment protocols, overall quality of life, and nursing satisfaction, assessed at multiple time points during the study period. Results: The intervention led to significant reductions in negative emotions for all patients when compared to their pre-intervention statuses, with the observation group exhibiting notably lower depression and anxiety scores at one and three months post-intervention (P < 0.05). Additionally, this group achieved higher compliance scores and demonstrated greater improvements in quality of life than the control group (P < 0.05). Nursing satisfaction was also significantly higher in the observation group, with 96.08% reporting high satisfaction compared to 80.39% in the control group (P < 0.05). Conclusion: Implementing a nursing intervention that emphasizes behavioral changes and leverages empowerment theory significantly enhances the quality of life, reduces negative emotions, boosts compliance with treatment, and increases nursing satisfaction among patients with brain metastasis following breast cancer surgery. This suggests that such interventions could be a valuable component of postoperative care for this patient population.

Elevated histone deacetylase 10 expression promotes the progression of clear cell renal cell carcinoma by Notch-1-PTEN signaling axis.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the most common pathological subtype of kidney cancer, accounts for approximately 70% to 80% of all cases. Histone deacetylase 10 (HDAC10) belongs to the HDAC class IIb subgroup, one of the histone deacetylases (HDAC) family. Previous studies suggest that HDAC10 may regulate the development of multiple tumor types. The specific molecular mechanisms employed by HDAC10 in the etiology of ccRCC still need to be discovered. METHODS: The analysis included examining HDAC10 expression levels and their clinical importance within a cohort of inpatients and ccRCC patients documented in the Tumor Genome Atlas (TCGA). Moreover, the biological functions and underlying molecular mechanisms of HDAC10 were investigated. RESULTS: HDAC10 showed increased expression in ccRCC tumor tissues. Subsequent analysis revealed overexpression of HDAC10 was associated with advanced clinical phenotype and unfavorable prognosis. The absence of HDAC10 significantly decreased ccRCC cell proliferation and migration capabilities. Mechanistic research suggests that HDAC10 may promote RCC development by activating the Notch-1 pathway and downregulating PTEN expression levels. CONCLUSION: In summary, HDAC10 can modulate critical biological processes in ccRCC, including proliferation, migration, and apoptosis. Notably, the Notch-1 pathway and PTEN serve as crucial signaling pathways and target genes through which HDAC10 regulates the progression of ccRCC. These findings offer a novel outlook for ccRCC treatment.

Association of Overweight and Inflammatory Indicators with Breast Cancer: A Cross-Sectional Study in Chinese Women.

Objective: This cross-sectional study aimed to explore the association of overweight and inflammatory indicators with breast cancer risk in Chinese patients. Methods: Weight, height, and peripheral blood inflammatory indicators, including white blood cell count (WBC), neutrophil count (NE), lymphocyte count (LY), platelet count (PLT) and the concentration of hypersensitivity C-reactive protein (hsCRP), were collected in 383 patients with benign breast lumps (non-cancer) and 358 patients with malignant breast tumors (cancer) at the First Affiliated Hospital of Soochow University, China, from March 2018 to July 2020. Body mass index (BMI), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were determined according to the ratio equation. The correlations among overweight, inflammatory indicators, and the proportion of non-cancer or cancer cases were analyzed. Results: BMI is associated with an increased breast cancer risk. Compared with non-cancer patients, the average WBC count, NE count, NLR, and level of hsCRP were significantly higher in cancer patients. The level of hsCRP was closely associated with the size of malignant breast tumors. Conclusion: We conclude that overweight and high levels of hsCRP may serve as putative risk factors for malignant breast tumors in Chinese women.

Haemoglobin, albumin, lymphocyte, and platelet score as an independent predictor for renal prognosis in IgA nephropathy.

Objective: The haemoglobin, albumin, lymphocyte, and platelet (HALP) score, a convenient and composite laboratory biomarker, can reflect inflammation and systemic nutritional status. This study was performed to investigate the effect of the HALP score on the prognosis of patients with IgA nephropathy (IgAN). Methods: This is a retrospective single centre study that enrolled 895 biopsy-confirmed IgAN patients from June 2019 to June 2022 who were followed for more than 1 year. Kaplan-Meier curves and Cox regression analyses were performed to determine the relationship between HALP and adverse outcomes. The restricted cubic splines was used to identify the possible associations. The optimal cut-off value of HALP for renal poor outcome was identified by the area under the receiver operating characteristic curve (AUC). Results: A total of 895 patients finally participated in the study and were divided into three groups (tertial 1-3) according to the baseline HALP score. More severe clinicopathologic features were observed in the lower HALP group, and Kaplan-Meier analysis showed patients in tertial 1 had a higher risk of kidney failure than the other groups (log-rank=11.02, P= 0.004). Multivariate Cox regression revealed that HALP score was an independent risk factor for renal prognosis in IgAN (adjusted HR: 0.967, 95% CI: 0.945-0.990, P = 0.006). The results of subgroup analysis suggested that HALP was more important in patients under the age of 50, BMI ≤ 23.9 and eGFR ≤ 90 mL/min/1.73 m2. The best cut-off HALP for renal survival was 38.83, sensitivity 72.1%, and specificity 55.9% (AUC: 0.662). Patients were further grouped according to HALP cut-off values and propensity matched. Multivariate Cox regression analysis revealed that HALP remained an independent predictor of IgAN in the matched cohort (HR 0.222, CI: 0.084-0.588, P=0.002). Conclusion: HALP is a novel and potent composite parameter to predict kidney outcome in patients with IgAN.

The 6-kilodalton peptide 1 in plant viruses of the family Potyviridae is a viroporin.

Potyviridae, the largest family of plant RNA viruses, includes many important pathogens that significantly reduce the yields of many crops worldwide. In this study, we report that the 6-kilodalton peptide 1 (6K1), one of the least characterized potyviral proteins, is an endoplasmic reticulum-localized protein. AI-assisted structure modeling and biochemical assays suggest that 6K1 forms pentamers with a central hydrophobic tunnel, can increase the cell membrane permeability of Escherichia coli and Nicotiana benthamiana, and can conduct potassium in Saccharomyces cerevisiae. An infectivity assay showed that viral proliferation is inhibited by mutations that affect 6K1 multimerization. Moreover, the 6K1 or its homologous 7K proteins from other viruses of the Potyviridae family also have the ability to increase cell membrane permeability and transmembrane potassium conductance. Taken together, these data reveal that 6K1 and its homologous 7K proteins function as viroporins in viral infected cells.

Accelerated infected wound healing by probiotic-based living microneedles with long-acting antibacterial effect.

Delays in infected wound healing are usually a result of bacterial infection and local inflammation, which imposes a significant and often underappreciated burden on patients and society. Current therapies for chronic wound infection generally suffer from limited drug permeability and frequent drug administration, owing to the existence of a wound biofilm that acts as a barrier restricting the entry of various antibacterial drugs. Here, we report the design of a biocompatible probiotic-based microneedle (MN) patch that can rapidly deliver beneficial bacteria to wound tissues with improved delivery efficiency. The probiotic is capable of continuously producing antimicrobial substances by metabolizing introduced glycerol, thereby facilitating infected wound healing through long-acting antibacterial and anti-inflammatory effects. Additionally, the beneficial bacteria can remain highly viable (>80 %) inside MNs for as long as 60 days at 4 °C. In a mouse model of Staphylococcus aureus-infected wounds, a single administration of the MN patch exhibited superior antimicrobial efficiency and wound healing performance in comparison with the control groups, indicating great potential for accelerating infected wound closure. Further development of live probiotic-based MN patches may enable patients to better manage chronically infected wounds.

A Highly Sensitive and Selective Fluorescent Sensor for Folic Acid Detection Based on D-penicillamine Stabilized Ag/Cu Alloy Nanoclusters.

In this work, a highly sensitive and selective method for detecting folic acid (FA) was developed using D-penicillamine (DPA) stabilized Ag/Cu alloy nanoclusters (DPA@Ag/Cu NCs). The yellow emission of DPA@Ag/Cu NCs was found to be quenched upon the addition of FA to the system. The fluorescence intensity quenching value demonstrated a linear relationship with FA concentrations ranging from 0.01 to 1200 µM, with a limit of detection (LOD) of 5.3 nM. Furthermore, the detection mechanism was investigated through various characterization analyses, including high resolution transmission electron microscopy, fluorescence spectra, ultraviolet-visible absorption spectra, and fluorescence lifetime. The results indicated that the fluorescence quenching induced by FA was a result of electron transfer from FA to the ligands of DPA@Ag/Cu NCs. The selectivity of the FA sensor was also evaluated, showing that common amino acids and inorganic ions had minimal impact on the detection of FA. Moreover, the standard addition method was successfully applied to detect FA in human serum, chewable tablets and FA tablets with promising results. The use of DPA@Ag/Cu NCs demonstrates significant potential for detecting FA in complex biological samples.

Mentalising imagery therapy for family dementia caregivers: protocol for a scoping review.

INTRODUCTION: Dementia is a growing public health concern, and providing long-term care for individuals affected by this condition is challenging for their family caregivers. While researchers have explored various intervention options to provide psychological support for dementia caregivers, mentalising imagery therapy (MIT) has gained significant recognition as an effective programme. Despite its significance and effectiveness, there is a lack of comprehensive scoping reviews of MIT in dementia caregiving. Thus, conducting such a review can provide valuable insights into the status and outcomes of MIT, identify gaps in existing research and provide recommendations for a more effective clinical practice. METHODS AND ANALYSIS: This study proposes a scoping review conducted according to the Joanna Briggs Institute, Arksey and O'Malley's methodological framework, as well as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review Extension. PubMed, Web of Science, Embase, Scopus, CINAHL and PsycINFO databases will be searched while grey literature will be retrieved via Google Scholar. Covidence will be used to manage the literature selection process and remove duplicate publications. Two researchers will independently screen the literature according to the inclusion criteria, with any discrepancies resolved through discussions with a third researcher. Data will be presented in a structured tabular format, with a narrative synthesis providing an overview of the findings on the identified research gaps and the effectiveness of MIT in the field of dementia caregiving. ETHICS AND DISSEMINATION: In a scoping review, no ethical approval is necessary. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: The scoping review protocol has been registered with Open Science Framework (https://doi.org/10.17605/OSF.IO/FHRG8).

Constructing an Asymmetric Covalent Triazine Framework to Boost the Efficiency and Selectivity of Visible-Light-Driven CO2 Photoreduction.

The photocatalytic reduction of CO2 represents an environmentally friendly and sustainable approach for generating valuable chemicals. In this study, a thiophene-modified highly conjugated asymmetric covalent triazine framework (As-CTF-S) is developed for this purpose. Significantly, single-component intramolecular energy transfer can enhance the photogenerated charge separation, leading to the efficient conversion of CO2 to CO during photocatalysis. As a result, without the need for additional photosensitizers or organic sacrificial agents, As-CTF-S demonstrates the highest photocatalytic ability of 353.2 µmol g-1 and achieves a selectivity of ≈99.95% within a 4 h period under visible light irradiation. This study provides molecular insights into the rational control of charge transfer pathways for high-efficiency CO2 photoreduction using single-component organic semiconductor catalysts.

Possible sarcopenia and risk of chronic kidney disease: a four-year follow-up study and Mendelian randomization analysis.

INTRODUCTION: Chronic kidney disease (CKD) is a common risk factor for sarcopenia. However, whether sarcopenia increases the risk of CKD remains unclear. To investigate the longitudinal and causal associations between possible sarcopenia and CKD, this study was performed. METHODS: Possible sarcopenia was defined according to the Asian Working Group for Sarcopenia in 2019. Participants aged ≥ 40 years were recruited from the baseline survey of the China Health and Retirement Longitudinal Study and followed up for four years. Binary logistic regression was used to evaluate the cross-sectional and longitudinal associations between possible sarcopenia, low muscle strength, low physical performance and CKD. Propensity score matching was used to balance the intergroup differences. Subgroup and interactive analyses were adopted to identify potential interactive effects. Mendelian Randomization analysis was used to assess the causal association between appendicular lean mass (ALM) and CKD. RESULTS: After data cleansing, a total of 7296 participants were included in the baseline survey. In the cross-sectional analyses, the odds ratios (ORs) of prevalent CKD were 1.50 (95% CI = 1.23-1.84, p < 0.001) for possible sarcopenia, 1.37 (95% CI = 1.10-1.70, p < 0.01) for low muscle strength and 1.42 (95% CI = 1.16-1.74, p < 0.001) for low physical performance in the full models. No significant interaction effects of covariates were detected (all P for interaction > 0.05). After four years of follow-up, an increased risk of incident CKD was also observed in participants with possible sarcopenia (OR = 1.66, 95% CI = 1.13-2.44, p = 0.010) and low physical performance (OR = 1.69, 95% CI = 1.16-2.45, p = 0.006), but not in participants with low muscle strength (OR = 1.19, 95% CI = 0.75-1.88, p = 0.469). In the Mendelian Randomization analysis, the inverse variance weighted estimator showed that a 1-standard deviation increase of genetically predicted ALM was associated with a lower risk of CKD (OR = 0.92, 95% CI = 0.85-0.99, p = 0.035). All the sensitivity analyses supported the main findings. CONCLUSIONS: Possible sarcopenia is an independent risk factor for CKD and may serve as a predictor of CKD for early identification and intervention.

Comprehensive review for non-coding RNAs: From mechanisms to therapeutic applications.

Non-coding RNAs (ncRNAs) are an assorted collection of transcripts that are not translated into proteins. Since their discovery, ncRNAs have gained prominence as crucial regulators of various biological functions across diverse cell types and tissues, and their abnormal functioning has been implicated in disease. Notably, extensive research has focused on the relationship between microRNAs (miRNAs) and human cancers, although other types of ncRNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are also emerging as significant contributors to human disease. In this review, we provide a comprehensive summary of our current knowledge regarding the roles of miRNAs, lncRNAs, and circRNAs in cancer and other major human diseases, particularly cancer, cardiovascular, neurological, and infectious diseases. Moreover, we discuss the potential utilization of ncRNAs as disease biomarkers and as targets for therapeutic interventions.

Revealing the Incidence-Angle-Independent Frequency Shift in the Acoustic Rotational Doppler Effect.

The Doppler effect is a universal wave phenomenon that has inspired various applications due to the induced frequency shift. In the case of the linear Doppler effect, the frequency shift depends on the incident frequency and angle. Here, we unveil the frequency shift dependence induced by the acoustic rotational Doppler effect in the wave-object scattering process. We experimentally demonstrate that this frequency shift is exclusively determined by the angular speed and rotational symmetry of the spinning scatterer while remaining independent of the incident angular momentum and angle. We derive the analytical relationship between the frequency shift and the scatterer's helicity, presenting a novel approach for helical feature recognition. The angle-independent nature of the frequency shift inherently prevents spectrum broadening and offers a solution for precise motion measurement through the rotational Doppler effect. This work provides a rigorous and comprehensive understanding of the acoustic Doppler effect, enriching its applications in helicity and motion detection.

Causal relationship between nutritional assessment phenotypes and heart failure: A Mendelian randomization study.

Introduction: Malnutrition is strongly associated with heart failure (HF); however, the causal link remains unclear. We used Mendelian randomization (MR) to infer causal associations between different nutritional assessment phenotypes and HF and to analyze whether these associations were mediated by common HF risk factors. Methods: Two-sample bidirectional MR was used to infer causal associations between nutritional assessment phenotypes and HF. Mutual influences between different nutritional assessment phenotypes and potential correlations were estimated using multivariate MR methods. Two-step MR was used to quantify the mediating effects of common HF risk factors on the causal associations. Results: Three phenotypes were positively associated with the development of HF: waist circumference (WC) (odds ratio [OR] = 1.74; 95% confidence interval [CI], 1.60-1.90; P = 3.95 × 10-39), body mass index (BMI) (OR = 1.70; 95%CI, 1.60-1.80; P = 1.35 × 10-73), and whole body fat mass (WBFM) (OR = 1.54; 95%CI, 1.44-1.65; P = 4.82 × 10-37). Multivariate MR indicated that WBFM remained positively associated with HF after conditioning on BMI and WC (OR = 2.05; 95%CI, 1.27-3.31; P = 0.003). Three phenotypes were negatively correlated with the development of HF: usual walking pace (UWP) (OR = 0.40; 95%CI, 0.27-0.60; P = 8.41 × 10-6), educational attainment (EA) (OR = 0.73; 95%CI, 0.67-0.79; P = 2.27 × 10-13), and total cholesterol (TC) (OR = 0.90; 95%CI, 0.84-0.96; P = 4.22 × 10-3). There was a bidirectional causality between HF and UWP (Effect estimate = -0.03; 95%CI, -0.05 to -0.01; P = 1.95 × 10-3). Mediation analysis showed that common risk factors for HF (hypertension, coronary artery disease, cardiomyopathy, and valvular heart disease) mediated these causal associations (all P < 0.05). Conclusions: BMI, WC, and WBFM are potential risk factors for HF, and the correlation between WBFM and HF was significantly stronger than that between BMI and WC, and HF. EA, UWP, and TC are potential protective factors against HF. Common risk factors for HF mediate these causal pathways. Early identification of potential risk or protective factors for HF patients from the dimension of nutritional status is expected to further improve patient outcomes.

Alloying Driven Antiferromagnetic Skyrmions on NiPS3 Monolayer: A First-Principles Calculation.

Topological magnetic states are promising information carriers for ultrahigh-density and high-efficiency magnetic storage. Recent advances in two-dimensional (2D) magnets provide powerful platforms for stabilizing various nanometer-size topological spin textures within a wide range of magnetic field and temperature. However, non-centrosymmetric 2D magnets with broken inversion symmetry are scarce in nature, making direct observations of the chiral spin structure difficult, especially for antiferromagnetic (AFM) skyrmions. In this work, it is theoretically predicted that intrinsic AFM skyrmions can be easily triggered in XY-type honeycomb magnet NiPS3 monolayer by alloying of Cr atoms, due to the presence of a sizable Dzyaloshinskii-Moriya interaction. More interestingly, the diameter of the AFM skyrmions in Ni3/4Cr1/4PS3 decreases from 12 to 4.4 nm as the external magnetic field increases and the skyrmion phases remain stable up to an external magnetic field of 4 T. These results highlight an effective strategy to generate and modulate the topological spin texture in 2D magnets by alloying with magnetic element.

Potential global distribution of Setaria italica, an important species for dryland agriculture in the context of climate change.

Setaria italica (S. italica, Linnaeus, 1753) is a drought-resistant, barren-tolerant, and widely adapted C-4 crop that plays a vital role in maintaining agricultural and economic stability in arid and barren regions of the world. However, the potential habitat of S. italica under current and future climate scenarios remains to be explored. Predicting the potential global geographic distribution of S. italica and clarifying its ecological requirements can help promote sustainable agriculture, which is crucial for addressing the global food crisis. In this study, we predicted the potential global geographic distribution of S. italica based on 3,154 global distribution records using the Maxent model and ArcGIS software. We assessed the constraints on its potential distribution based on the contribution of environmental factors variables. The predictive accuracy of the Maxent model was evaluated using AUC values, TSS values, and Kappa statistics, respectively. The results showed that the Maxent model had a high prediction accuracy, and the simulation results were also reliable; the total suitable habitats of S. italica is 5.54×107 km2, which mainly included the United States (North America), Brazil (South America), Australia (Oceania), China, India (Asia), and the Russian Federation (Europe). The most suitable habitat of S. italica was 0.52×107 km2, accounting for 9.44% of the total areas, mainly in the United States, India, the Russian Federation, and China. Soil and precipitation (driest monthly precipitation, hottest seasonal precipitation) are the most critical factors limiting the potential distribution of S. italica. Compared with the modern potential distribution, we predict that the four future climate change scenarios will result in varying reductions in the possible geographic ranges of S. italica. Overall, climate change may significantly affect the global distribution of S. italica, altering its worldwide production and trade patterns.

Gate-Tunable Quantum Acoustoelectric Transport in Graphene.

Transport probes the motion of quasi-particles in response to external excitations. Apart from the well-known electric and thermoelectric transport, acoustoelectric transport induced by traveling acoustic waves has rarely been explored. Here, by adopting hybrid nanodevices integrated with piezoelectric substrates, we establish a simple design of acoustoelectric transport with gate tunability. We fabricate dual-gated acoustoelectric devices based on hBN-encapsulated graphene on LiNbO3. Longitudinal and transverse acoustoelectric voltages are generated by launching a pulsed surface acoustic wave. The gate dependence of zero-field longitudinal acoustoelectric signal presents strikingly similar profiles to that of Hall resistivity, providing a valid approach for extracting carrier density without magnetic field. In magnetic fields, acoustoelectric quantum oscillations appear due to Landau quantization, which are more robust and pronounced than Shubnikov-de Haas oscillations. Our work demonstrates a feasible acoustoelectric setup with gate tunability, which can be extended to the broad scope of various van der Waals materials.

Tao-Hong-Si-Wu-Tang Improves the Depressive-like Behaviors in Mice Experiencing Perimenopausal Depression Through Modulating Activity of the Hypothalamic-Pituitary-Adrenal-Ovary Axis and Activating the BDNF-TrkB-CREB Signaling Pathway.

Tao-Hong-Si-Wu-Tang (THSWT), a traditional Chinese herbal remedy, is commonly utilized for the treatment of female perimenopausal depression through regulating menstruation, but the mechanism remains unknown. In this study, ICR mice were randomly divided into six groups: low, medium, and high dose of THSWT (0.5, 1.5, and 4.5 g/kg), soy isoflavone (250 mg/kg), ovariectomy group, and control group. All mice, except the control group, had ovaries removed and were exposed to hypoxic stimulation for 28 days to establish a perimenopausal depression mice model. The mice, having unrestricted access to food and water, were administered THSWT treatment for a duration of 14 days. The Western blotting and Enzyme linked immunosorbent assay kits were used to determine protein and hormone levels, respectively. Experimental results showed that THSWT reduced the immobility time of mice from 150.8 s to 104.9 s in the tail suspension test, and it decreased the immobility time of mice from 165.7 s to 119.0 s in the forced swimming test, outperforming the results obtained with soy isoflavones. In addition, THSWT upregulated the protein expression of follicle-stimulating hormone receptor and downregulated the protein expression of corticotropin-releasing hormone-receptor 1 in the hippocampus. Compared with the oophorectomized group, treatment with THSWT decreased the levels of corticosterone and adrenocorticotropic hormone in serum by 173.7 and 23.4 ng/mL, respectively. These findings showed that THSWT could stimulate the perimenopausal nerve tissue and regulate the level of serum hormones in mice. THSWT exhibited promising potential as a viable alternative drug for hormone treatment of perimenopause in clinical use.

Novel Isoalantolactone-Based Derivatives as Potent NLRP3 Inflammasome Inhibitors: Design, Synthesis, and Biological Characterization.

The NLRP3 inflammasome has been recognized as a promising therapeutic target in drug discovery for inflammatory diseases. Our initial research identified a natural sesquiterpene isoalantolactone (IAL) as the active scaffold targeting NLRP3 inflammasome. To improve its activity and metabolic stability, a total of 64 IAL derivatives were designed and synthesized. Among them, compound 49 emerged as the optimal lead, displaying the most potent inhibitory efficacy on nigericin-induced IL-1ß release in THP-1 cells, with an IC50 value of 0.29 µM, approximately 27-fold more potent than that of IAL (IC50: 7.86 µM), and exhibiting higher metabolic stability. Importantly, 49 remarkably improved DSS-induced ulcerative colitis in vivo. Mechanistically, we demonstrated that 49 covalently bound to cysteine 279 in the NACHT domain of NLRP3, thereby inhibiting the assembly and activation of NLRP3 inflammasome. These results provided compelling evidence to further advance the development of more potent NLRP3 inhibitors based on this scaffold.