Inhibition of lysine acetyltransferase KAT6 in ER+HER2- metastatic breast cancer: a phase 1 trial.

Inhibition of histone lysine acetyltransferases (KATs) KAT6A and KAT6B has shown antitumor activity in estrogen receptor-positive (ER+) breast cancer preclinical models. PF-07248144 is a selective catalytic inhibitor of KAT6A and KAT6B. In the present study, we report the safety, pharmacokinetics (PK), pharmacodynamics, efficacy and biomarker results from the first-in-human, phase 1 dose escalation and dose expansion study (n = 107) of PF-07248144 monotherapy and fulvestrant combination in heavily pretreated ER+ human epidermal growth factor receptor-negative (HER2-) metastatic breast cancer (mBC). The primary objectives of assessing the safety and tolerability and determining the recommended dose for expansion of PF-07248144, as monotherapy and in combination with fulvestrant, were met. Secondary endpoints included characterization of PK and evaluation of antitumor activity, including objective response rate (ORR) and progression-free survival (PFS). Common treatment-related adverse events (any grade; grades 3-4) included dysgeusia (83.2%, 0%), neutropenia (59.8%, 35.5%) and anemia (48.6%, 13.1%). Exposure was approximately dose proportional. Antitumor activity was observed as monotherapy. For the PF-07248144-fulvestrant combination (n = 43), the ORR (95% confidence interval (CI)) was 30.2% (95% CI = 17.2-46.1%) and the median PFS was 10.7 (5.3-not evaluable) months. PF-07248144 demonstrated a tolerable safety profile and durable antitumor activity in heavily pretreated ER+HER2- mBC. These findings establish KAT6A and KAT6B as druggable cancer targets, provide clinical proof of concept and reveal a potential avenue to treat mBC. clinicaltrial.gov registration: NCT04606446 .

Zinc hexacyanoferrate/g-C3N4 nanocomposites with enhanced photothermal and photodynamic properties for rapid sterilization and wound healing.

Photoactivated therapy has gradually emerged as a promising and rapid method for combating bacteria, aimed at overcoming the emergence of drug-resistant strains resulting from the inappropriate use of antibiotics and the subsequent health risks. In this work, we report the facile fabrication of Zn3[Fe(CN)6]/g-C3N4 nanocomposites (denoted as ZHF/g-C3N4) through the in-situ loading of zinc hexacyanoferrate nanospheres onto two-dimensional g-C3N4 sheets using a simple metal-organic frameworks construction method. The ZHF/g-C3N4 nanocomposite exhibits enhanced antibacterial activity through the synergistic combination of the excellent photothermal properties of ZHF and the photodynamic capabilities of g-C3N4. Under dual-light irradiation (420 nm + 808 nm NIR), the nanocomposites achieve remarkable bactericidal efficacy, eliminating 99.98% of Escherichia coli and 99.87% of Staphylococcus aureus within 10 minutes. Furthermore, in vivo animal experiments have demonstrated the outstanding capacity of the composite in promoting infected wound healing, achieving a remarkable wound closure rate of 99.22% after a 10-day treatment period. This study emphasizes the potential of the ZHF/g-C3N4 nanocomposite in effective antimicrobial applications, expanding the scope of synergistic photothermal/photodynamic therapy strategies.

Transcriptomic and genomic characteristics of intrahepatic metastases of primary liver cancer.

BACKGROUND: Patients with primary multifocal hepatocellular carcinoma (HCC) have a poor prognosis and often experience a high rate of treatment failure. Multifocal HCC is mainly caused by intrahepatic metastasis (IM), and though portal vein tumor thrombosis (PVTT) is considered a hallmark of IM, the molecular mechanism by which primary HCC cells invade the portal veins remains unclear. Therefore, it is necessary to recognize the early signs of metastasis of HCC to arrange better treatment for patients. RESULTS: To determine the differential molecular features between primary HCC with and without phenotype of metastasis, we used the CIBERSORTx software to deconvolute cell types from bulk RNA-Seq based on a single-cell transcriptomic dataset. According to the relative abundance of tumorigenic and metastatic hepatoma cells, VEGFA+ macrophages, effector memory T cells, and natural killer cells, HCC samples were divided into five groups: Pro-T, Mix, Pro-Meta, NKC, and MemT, and the transcriptomic and genomic features of the first three groups were analyzed. We found that the Pro-T group appeared to retain native hepatic metabolic activity, whereas the Pro-Meta group underwent dedifferentiation. Genes highly expressed in the group Pro-Meta often signify a worse outcome. CONCLUSIONS: The HCC cohort can be well-typed and prognosis predicted according to tumor microenvironment components. Primary hepatocellular carcinoma may have obtained corresponding molecular features before metastasis occurred.

Food-borne bacteria analysis using a diatomite bioinspired SERS platform.

Rapid and sensitive detection of food-borne bacteria has remained challenging over the past few decades. We propose a surface-enhanced Raman scattering sensing strategy based on a novel bioinspired surface-enhanced Raman scattering substrate, which can directly detect dye molecular residues and food-borne pathogen microorganisms in the environment. The surface-enhanced Raman scattering platform consists of a natural diatomite microporous array decorated with a metal-phenolic network that enables the in situ reduction of gold nanoparticles. The as-prepared nanocomposites display excellent surface-enhanced Raman scattering activity with the lowest limit of detection and the maximum Raman enhancement factor of dye molecules up to 10-11 M and 1.18 × 107, respectively. For food-borne bacterial detection, a diatomite microporous array decorated with a metal polyphenol network and gold nanoparticle-based surface-enhanced Raman scattering analysis is capable of distinguishing the biochemical fingerprint information of Staphylococcus aureus and Escherichia coli, indicating the great potential for strain identification.

Performance and protein conformation of thermally treated silver carp (Hypophthalmichthys molitrix) and scallop (Argopecten irradians) blended gels.

BACKGROUND: The quality of surimi-based products can be improved by combining the flesh of different aquatic organisms. The present study investigated the effects of incorporating diverse ratios of unwashed silver carp (H) and scallop (A) and using various thermal treatments on the moisture, texture, microstructure, and conformation of the blended gels and myofibrillar protein of surimi. RESULTS: A mixture ratio of A:H = 1:3 yielded the highest gel strength, which was 60.4% higher than that of scallop gel. The cooking losses of high-pressure heating and water-bath microwaving were significantly higher than those of other methods (P < 0.05). Moreover, the two-step water bath and water-bath microwaving samples exhibited a more regular spatial network structure compared to other samples. The mixed samples exhibited a microstructure with a uniform and ordered spatial network, allowing more free water to be trapped by the internal structure, resulting in more favorable gel properties. The thermal treatments comprehensively modified the tertiary and quaternary structures of proteins in unwashed mixed gel promoted protein unfurling, provided more hydrophobic interactions, enhanced protein aggregation and improved the gel performance. CONCLUSION: The findings of the present study improve our understanding of the interactions between proteins from different sources. We propose a new method for modifying surimi's gel properties, facilitating the development of mixed surimi products, as well as enhancing the efficient utilization of aquatic resources. © 2024 Society of Chemical Industry.

Clinical features and prognosis of idiopathic inflammatory myopathies with coexistent multiple myositis-specific antibodies.

OBJECTIVES: This study aimed to evaluate the clinical significance of the coexistence of 2 or more myositis-specific antibodies (multiple MSAs) in adult patients with idiopathic inflammatory myopathies (IIM). METHODS: We assessed a cohort of 202 consecutive patients with IIM. Clinical features and survival rates were compared between patients with and without multiple MSAs. RESULTS: Of those 202 patients, 44 (21.8%) were found to have multiple MSAs. 63.6% of the 44 patients tested positive for anti-aminoacyl-tRNA synthetase antibodies (anti-ARS+) and 52.3% positive for anti-melanoma differentiation-associated protein-5 antibody (anti-MDA5+). The presence of multiple MSAs was associated with less rapidly progressive interstitial lung disease (RP-ILD), fever, rash, periungual erythema, more muscle involvement and dysphagia, higher albumin level, and higher positive rate of ANA antibody in anti-MDA5+ population. In anti-ARS+ population with multiple MSAs, there were more V-neck sign, skin ulcers, dysphagia and peripheral edema. No differences in survival rates were observed between patients with or without multiple MSAs in the overall and anti-ARS+ populations. However, the survival rate in anti-MDA5+ population with multiple MSAs was significantly higher than those without multiple MSAs (p = 0.003). Moreover, multiple MSAs remained an independent protective factor against mortality in multivariable Cox regression analysis of anti-MDA5+ population [HR 0.108 (95% CI 0.013, 0.908), p=0.041]. CONCLUSIONS: Multiple MSAs coexist in some IIM patients and their existence indicates mixed features from concomitant MSAs in anti-MDA5+ population and anti-ARS+ population. Identifying multiple MSAs could help to discover a more favourable disease phenotype with decreased mortality in anti-MDA5+ population.

Seedling root system adaptation to water availability during maize domestication and global expansion.

The maize root system has been reshaped by indirect selection during global adaptation to new agricultural environments. In this study, we characterized the root systems of more than 9,000 global maize accessions and its wild relatives, defining the geographical signature and genomic basis of variation in seminal root number. We demonstrate that seminal root number has increased during maize domestication followed by a decrease in response to limited water availability in locally adapted varieties. By combining environmental and phenotypic association analyses with linkage mapping, we identified genes linking environmental variation and seminal root number. Functional characterization of the transcription factor ZmHb77 and in silico root modeling provides evidence that reshaping root system architecture by reducing the number of seminal roots and promoting lateral root density is beneficial for the resilience of maize seedlings to drought.

[Antibiotic bone cement covered reconstruction plate for infected anterior pelvic ring fractures].

OBJECTIVE: To explore the clinical efficacy of antibiotic bone cement covered reconstruction steel plate in the treatment of infected anterior pelvic ring fracture. METHODS: From January 2017 to March 2022, 11 patients with infected anterior pelvic ring fracture were treated with antibiotic bone cement covered reconstruction steel plate including 7 males and 4 females and the age ranged from 27 to 49 years old. The pelvic fractures were classified according to the Tile typology: 4 cases of C1 type, 4 cases of C2 type, and 3 cases of C3 type. Among them, 2 cases of infected anterior ring were infected after internal fixation of anterior ring, and 9 patients were infected with infected anterior ring due to incomplete early debridement, which was classified as infected according to the injury severity score(ISS) for 24 to 38 scores. The anterior ring was internally fixed by extended debridement, irrigation, and antibiotic bone cement covered reconstruction plate, and the posterior ring fractures were all closed reduction and internally fixed with sacroiliac screws. RESULTS: All 11 cases obtained follow-up from 13 to 20 months. Among them, 2 patients had recurrence of postoperative infection, 1 case was re-dissected and replaced with antibiotic bone cement-coated internal fixation, and 1 case had a milder infection without accumulation of the medullary cavity, and the infection was controlled by retaining the plate and replacing the antibiotic bone cement only after dissecting. Two cases developed incisional oozing, which healed after removal of the internal fixation three months postoperatively. All patients did not show pelvic fracture redisplacement or reinfection during the follow-up period. All 11 cases eventually healed bony. At the final follow-up, according to the Matta score, the fracture reduction was excellent in 6 cases, good in 4, and possible in 1. According to the Majeed functional score, it was excellent in 6, good in 3, and possible in 2. CONCLUSION: Antibiotic bone cement covered reconstruction plate is effective in the treatment of infected anterior pelvic ring fracture, with high intraoperative safety and low recurrence rate of infection, which is conducive to the early postoperative rehabilitation and significantly shortens the course of the disease.

Determination of pulmonary vessel alteration in Chinese male smokers by quantitative computed tomography measurements: a retrospective study.

Background: The blood volume of intraparenchymal vessels is reported to be increased in smokers. However, the blood volume can be affected by many confounders besides tobacco exposure. This study aimed to investigate the association between cigarette smoking and pulmonary blood volume after adjusting the related factors in a large cohort of Chinese males. Methods: In this retrospective study, male participants admitted to the First Affiliated Hospital of Xi'an Jiaotong University for annual health assessment between February 2017 and February 2018 were enrolled. All subjects underwent non-contrast chest computed tomography (CT) scans, and 152 subjects underwent a review CT scan 2-3 years later. A three-dimensional approach was employed to segment the lung and intrapulmonary vessels and quantitative CT (QCT) measurements, including lung volume (LV), intrapulmonary vessel volume (IPVV), low-attenuation area <-950 Hounsfield unit (LAA-950 and LAA-950%), and mean lung density (MLD). Linear regression was used to estimate the association between IPVV and the smoking index (SI). A paired t-test was used to compare the QCT parameters between the initial and follow-up CT scans. Results: A total of 656 male participants were enrolled and classified into three subgroups: non-smokers (n=311), current smokers (n=267), and former smokers (n=78). The IPVV of current smokers (134.62±23.96 vs. 120.76±25.52 mL) and former smokers (130.79±25.13 vs. 120.76±25.52 mL) were significantly larger than that of non-smokers (P<0.05). A higher SI was associated with greater IPVV [non-standardized coefficient: 0.167, 95% confidence interval (CI): 0.086-0.248]. For current smokers, the IPVV of the follow-up scan significantly increased compared to its baseline scan (135.49±28.60 vs. 129.73±29.75 mL, t=-2.326, P=0.02), but for the non-smokers and former smokers, the IPVV of the follow-up scan did not increase or decrease compared to the baseline scan (P>0.05). Conclusions: Pulmonary vascular volumes detectable on non-contrast CT are associated with cigarette exposure, and smoking cessation may prevent pulmonary vasculature remodeling.

A 3D pseudo-continuous arterial spin labeling study of altered cerebral blood flow correlation networks in mild cognitive impairment and Alzheimer's disease.

Objective: To investigate the abnormalities of the three-dimensional pseudo-continuous arterial spin labeling (3D PCASL) based cerebral blood flow (CBF) correlation networks in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods: 3D PCASL images of 53 cognitive normal (CN) subjects, 43 subjects with MCI, and 30 subjects with AD were acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Whole-brain CBF maps were calculated using PCASL and proton density-weighted images (PDWI). The 246 regional CBF values, including the cortex and subcortex, were obtained after registering the Brainnetome Atlas to the individual CBF maps. The Pearson correlation coefficient between every two regions across subjects was calculated to construct the CBF correlation network. Then the topologies of CBF networks with regard to global properties (global network efficiency, clustering coefficient, characteristic path length, and small-world properties), hub regions, nodal properties (betweenness centrality, BC), and connections were compared among CN, MCI, and AD. Significant changes in the global and nodal properties were observed in the permutation tests, and connections with significant differences survived after the z-statistic and false discovery rate (FDR) correction. Results: The CBF correlation networks of CN, MCI, and AD all showed small-world properties. Compared with CN, global efficiency decreased significantly in AD. Significant differences in nodal properties and a loss of hub regions are noted in the middle temporal lobe in both MCI and AD. In the frontal lobe, BC is reduced in MCI while it is increased in the occipital lobe in AD. The identified altered hub regions with significant differences in MCI and AD were mainly distributed in the hippocampus and entorhinal cortex. In addition, disrupted hub regions in AD with significantly decreased connections were mainly found in the precuneus/posterior cingulate cortex (PCC) and hippocampus-cortical cortex. Conclusions: Noninvasive 3D PCASL-based CBF correlation networks are capable of showing changes in topological organization in subjects with MCI and AD, and the observed disruption in the topological organization may underlie cognitive decline in MCI and AD.

Pelvic packing or endovascular interventions: Which should be given priority in managing hemodynamically unstable pelvic fractures? A systematic review and a meta-analysis.

Background: Pelvic fractures in trauma patients can be associated with substantial massive hemorrhage. Hemostasis interventions mainly consist of pelvic packing (PP) and endovascular intervention (EI), such as angiography-embolization (AE) and resuscitative endovascular balloon occlusion of the aorta (REBOA). Whether PP or EI should be prioritized for the management of hemodynamic unstable patients with pelvic fractures remains under debate. This meta-analysis aimed to establish the evidence-based recommendations for the management of hemodynamic unstable patients. Materials and methods: PubMed, CENTRAL, and EMBASE databases were searched for articles published from January 1, 2000 to January 31, 2023. Eligible studies, such as retrospective cohort studies, propensity score matching studies, prospective cohort studies, observational cohort studies, quasi-randomized clinical trials evaluating PP and EI (AE or REBOA) for the management of patients with hemodynamically unstable pelvic fractures, were included. Mean Difference (MD), relative risk (RR), and 95 % confidence intervals (CI) were calculated using fixed- or random-effects models depending on the heterogeneity of included trials. We compared the effectiveness of the two methods in terms of mortality, unstable fracture pattens, injury severity score (ISS), systolic blood pressure (SBP), lactate (LA), base deficiency (BE), hemoglobin preoperatively, blood transfusion requirement, the time to and of operation, complications. Results: Overall, 15 trials enrolling 1136 patients were analyzed, showing a total mortality rate of 28.4 % (323/1136). No effect of PP preference on the ISS (PP 36.4 ± 10.4 vs. EI 34.5 ± 12.7), SBP (PP 81.1 ± 24.3 mmHg vs. EI 94.2 ± 32.4 mmHg), LA (PP 4.66 ± 2.72 mmol/L vs. 4.85 ± 3.45 mmol/L), BE (PP 8.14 ± 5.64 mmol/L vs. 6.66 ± 5.68 mmol/L), and unstable fracture patterns (RR = 1.10, 95 % CI [0.63, 1.92]) was observed. PP application was associated with lower preoperative hemoglobin level (PP 8.11 ± 2.28 g/dL vs. EI 8.43 ± 2.43 g/dL, p < 0.05), more preoperative transfusion (MD = 2.53, 95 % CI [0.01, 5.06]), less postoperative transfusion within the first 24 h (MD = -1.09, 95 % CI [-1.96, -0.22]), shorter waiting time to intervention (MD = -0.93, 95 % CI [-1.54, -0.31]), and shorter operation time of intervention (MD = -0.41, 95 % CI [-0.52, -0.30]). PP had lower mortality rate owing to uncontrolled hemorrhage in the acute phase (RR = 0.41, 95 % CI [0.22, 0.79]). There was neither difference in mortality due to other complications (RR = 1.60, 95 % CI [0.79, 3.24]), nor in total mortality (RR = 0.92, 95%CI [0.49, 1.74]) (p > 0.05). Conclusions: PP showed advantages of reducing the amount of postoperative transfusion, shortening the time of waiting and operating, and decreasing mortality due to uncontrolled hemorrhage in the acute phase without raising the odds of mortality due to complications. PP, a reliable hemostatic method, should be prioritized for resuscitating most pelvic fractures with hemodynamically unstable, especially in case of bleeding from veins and fracture sites, as well as inadequate EI.

Evaluating the Effectiveness of Radiofrequency Therapy and Manual Pelvic Fascial Release in Treating Myofascial Pelvic Pain.

INTRODUCTION AND HYPOTHESIS: Myofascial pelvic pain (MFPP), characterized by sensitive trigger points in the pelvic floor muscles, leads to chronic pain and affects various aspects of life. Despite the availability of different treatment modalities, there is limited comparative research on their effectiveness. This study compares radiofrequency (RF) therapy and myofascial manual therapy (MMT) in treating MFPP. We aimed to evaluate pelvic floor muscle strength changes, clinical symptoms, and patient comfort during treatment. METHODS: The study involved 176 participants, divided equally into RF and MMT groups. We assessed pelvic floor pain using the Visual Analogue Scale (VAS), muscle strength using the Modified Oxford Scale (MOS) and surface electromyography (sEMG), clinical symptom improvement through questionnaires, and patient discomfort during treatment. RESULTS: Both RF and MMT groups significantly reduced pelvic floor and paraurethral muscle pain (VAS scores, p < 0.001). RF treatment significantly decreased vaginal laxity in its group (p < 0.001), with no notable change in the MMT group (p = 0.818). RF therapy also resulted in greater patient comfort than MMT (p < 0.001). Although both treatments improved clinical symptoms, there was no significant difference between the two (p = 0.692). MOS scores and pelvic floor sEMG values showed no significant differences between the groups before and after treatment (p > 0.05). CONCLUSIONS: Both RF and MMT effectively alleviate pelvic floor pain and improve clinical symptoms in MFPP patients. RF therapy, however, offers additional benefits in reducing vaginal laxity and enhancing treatment comfort.

The finite element analysis study of the impact of single and double lag screw fixation on ankle fractures of different sizes.

In clinical practice, the choice of single vs. double screw fixation for posterior malleolus fractures (PMF) is theoretically unclear, particularly concerning the size-stability relationship. This study, employing Finite Element Analysis (FEA), assesses biomechanical stability in PMF of varying sizes under both fixation methods. Utilizing a 3D model based on CT scans, we simulated fractures with 10-50% fragment sizes and applied a 600 N force to mimic the single-leg stance. Our evaluation focused on screw Von Mises stress (VMS) and fracture relative displacement (RD). Results show that stability increases with fragment size for both fixation types. Single screw fixation is comparable to double screw in fragments up to 25%, but in larger fragments, double screw significantly enhances stability. This suggests that for fragments over 25%, double screw fixation is preferable, marking a critical threshold for PMF stability.

A submicron forest-like silicon surface promotes bone regeneration by regulating macrophage polarization.

Introduction: Silicon is a major trace element in humans and a prospective supporting biomaterial to bone regeneration. Submicron silicon pillars, as a representative surface topography of silicon-based biomaterials, can regulate macrophage and osteoblastic cell responses. However, the design of submicron silicon pillars for promoting bone regeneration still needs to be optimized. In this study, we proposed a submicron forest-like (Fore) silicon surface (Fore) based on photoetching. The smooth (Smo) silicon surface and photoetched regular (Regu) silicon pillar surface were used for comparison in the bone regeneration evaluation. Methods: Surface parameters were investigated using a field emission scanning electron microscope, atomic force microscope, and contact angle instrument. The regulatory effect of macrophage polarization and succedent osteogenesis was studied using Raw264.7, MC3T3-E1, and rBMSCs. Finally, a mouse calvarial defect model was used for evaluating the promoting effect of bone regeneration on the three surfaces. Results: The results showed that the Fore surface can increase the expression of M2-polarized markers (CD163 and CD206) and decrease the expression of inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Fore surface can promote the osteogenesis in MC3T3-E1 cells and osteoblastic differentiation of rBMSCs. Furthermore, the volume fraction of new bone and the thickness of trabeculae on the Fore surface were significantly increased, and the expression of RANKL was downregulated. In summary, the upregulation of macrophage M2 polarization on the Fore surface contributed to enhanced osteogenesis in vitro and accelerated bone regeneration in vivo. Discussion: This study strengthens our understanding of the topographic design for developing future silicon-based biomaterials.

Visual analysis of global research on the transient receptor potential ankyrin 1 channel: A literature review from 2002 to 2022.

Background and aims: The transient receptor potential ankyrin 1 (TRPA1) channel has become a focus in pain research. However, there are no bibliometric studies that systematically analyze the existing research in this area. This study aimed to provide a systematic review of the existing literature on TRPA1 using a bibliometric analysis. Methods: Published literature in the field of TRPA1 was collected from the Web of Science Core Collection database. Quantitative and qualitative analyses of publications, countries, institutions, authors, journals, and other entries were conducted using Excel, VOSview, and Citespace software to provide insight into global research hotspots and trends in the TRPA1 field. Results: This study included 1189 scientific products published in 398 journals from 52 countries. The United States of America (n = 367) had the most publications, ahead of Japan (n = 212) and China (n = 199). The University of Florence (n = 55) was the most productive institution and Pierangelo Geppetti (n = 46) was the most productive author. PLoS One (n = 40) published the most articles on TRPA1. Pain, cold, inflammation, covalent modification, hyperalgesia, and oxidative stress were the most common keywords used in the studies. Conclusion: This study provides the first bibliometric analysis of TRPA1 publications. The physiological functions of TRPA1, TRPA1, and neuropathic pain, TRPA1 as a therapeutic target, and agonists of TRPA1 are trending in TRPA1 research. Neuropathic pain, apoptosis, and sensitization could be focus areas of future research. This study provides important insight in the field of TRPA1 research.

Optical Control of Insect Behavior and Receptors with Azobenzene-Bridged Fipronil and Imidacloprid.

Photopharmacology can be implemented in a way of regulating drug activities by light-controlling the molecular configuations. Three photochromic ligands (PCLs) that bind on one or two sites of GABARs and nAChRs were reported here. These multiphoton PCLs, including FIP-AB-FIP, IMI-AB-FIP, and IMI-AB-IMI, are constructed with an azobenzene (AB) bridge that covalently connects two fipronil (FIP) and imidacloprid (IMI) molecules. Interestingly, the three PCLs as well as FIP and IMI showed great insecticidal activities against Aedes albopictus larvae and Aphis craccivora. IMI-AB-FIP in both trans/cis isomers can be reversibly interconverted depending on light, accompanied by insecticidal activity decrease or increase by 1.5-2.3 folds. In addition, IMI-AB-FIP displayed synergistic effects against A. craccivora (LC50, IMI-AB-FIP = 14.84-22.10 µM, LC50, IMI-AB-IMI = 210.52-266.63 µM, LC50, and FIP-AB-FIP = 36.25-51.04 µM), mainly resulting from a conceivable reason for simultaneous targeting on both GABARs and nAChRs. Furthermore, modulations of wiggler-swimming behaviors and cockroach neuron function were conducted and the results indirectly demonstrated the ligand-receptor interactions. In other words, real-time regulations of receptors and insect behaviors can be spatiotemporally achieved by our two-photon PCLs using light.

A Novel Tetramethylpyrazine Chalcone Hybrid- HCTMPPK, as a Potential Anti-Lung Cancer Agent by Downregulating MELK.

Purpose: Lung adenocarcinoma currently ranks the leading causes of cancer-related mortality worldwide. Many anti-inflammation herbs, like tetramethylpyrazine, have shown their anti-tumor potentials. Here, we evaluated the role of a novel chalcone derivative of tetramethylpyrazine ((E) -1- (E) -1- (2-hydroxy-5-chlorophenyl) -3- (3,5,6-trimethylpyrazin-2-yl) -2-propen-1, HCTMPPK) in lung adenocarcinoma. Methods: The effects of HCTMPPK on cell proliferation, apoptosis, and invasion were investigated by in-vitro assays, including CCK-8, colony formation assay, flow cytometry, transwell assay, and wound-healing assay. The therapeutic potential of HCTMPPK in vivo was evaluated in xenograft mice. To figure out the target molecules of HCTMPPK, a network pharmacology approach and molecular docking studies were employed, and subsequent experiments were conducted to confirm these candidate molecules. Results: HCTMPPK effectively suppressed the proliferative activity and migration, as well as enhanced the apoptosis of A549 cells in a concentration-dependent manner. Consistent with this, tumor growth was inhibited by HCTMPPK significantly in vivo. Regarding the mechanisms, HCTMPPK down-regulated Bcl-2 and MMP-9 and up-regulating Bax and cleaved-caspase-3. Subsequently, we identified 601 overlapping DEGs from LUAD patients in TCGA and GEO database. Then, 15 hub genes were identified by PPI network and CytoHubba. Finally, MELK was verified to be the HCTMPPK targeted site, through the molecular docking studies and validation experiments. Conclusion: Overall, our study indicates HCTMPPK as a potential MELK inhibitor and may be a promising candidate for the therapy of lung cancer.

A novel anoikis-related gene signature can predict the prognosis of hepatocarcinoma patients.

Background: Hepatocellular carcinoma (HCC) is a major health problem with more than 850,000 cases per year worldwide. This cancer is now the third leading cause of cancer-related deaths worldwide, and the number is rising. Cancer cells develop anoikis resistance which is a vital step during cancer progression and metastatic colonization. However, there is not much research that specifically addresses the role of anoikis in HCC, especially in terms of prognosis. Methods: This study obtained gene expression data and clinical information from 371 HCC patients through The Cancer Genome Atlas (TCGA) Program and The Gene Expression Omnibus (GEO) databases. A total of 516 anoikis-related genes (ANRGs) were retrieved from GeneCard database and Harmonizome portal. Differential expression analysis identified 219 differentially expressed genes (DEGs), and univariate Cox regression analysis was utilized to select 99 ANRGs associated with the prognosis of HCC patients. A risk scoring model with seven genes was established using the least absolute shrinkage and selection operator (LASSO) regression model, and internal validation of the model was performed. Results: The identified 99 ANRGs are closely associated with the prognosis of HCC patients. The risk scoring model based on seven characteristic genes demonstrates excellent predictive performance, further validated by receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves. The study reveals significant differences in immune cell infiltration, gene expression, and survival status among different risk groups. Conclusions: The prognosis of HCC patients can be predicted using a unique prognostic model built on ANRGs in HCC.

High-performance flexible p-type Ce-filled Fe3CoSb12 skutterudite thin film for medium-to-high-temperature applications.

P-type Fe3CoSb12-based skutterudite thin films are successfully fabricated, exhibiting high thermoelectric performance, stability, and flexibility at medium-to-high temperatures, based on preparing custom target materials and employing advanced pulsed laser deposition techniques to address the bonding challenge between the thin films and high-temperature flexible polyimide substrates. Through the optimization of fabrication processing and nominal doping concentration of Ce, the thin films show a power factor of >100 µW m-1 K-2 and a ZT close to 0.6 at 653 K. After >2000 bending cycle tests at a radius of 4 mm, only a 6 % change in resistivity can be observed. Additionally, the assembled p-type Fe3CoSb12-based flexible device exhibits a power density of 135.7 µW cm-2 under a temperature difference of 100 K with the hot side at 623 K. This work fills a gap in the realization of flexible thermoelectric devices in the medium-to-high-temperature range and holds significant practical application value.