Irradiated microparticles suppress prostate cancer by tumor microenvironment reprogramming and ferroptosis.

Immunogenic cell death (ICD) plays a crucial role in triggering the antitumor immune response in the tumor microenvironment (TME). Recently, considerable attention has been dedicated to ferroptosis, a type of ICD that is induced by intracellular iron and has been demonstrated to change the immune desert status of the TME. However, among cancers that are characterized by an immune desert, such as prostate cancer, strategies for inducing high levels of ferroptosis remain limited. Radiated tumor cell-derived microparticles (RMPs) are radiotherapy mimetics that have been shown to activate the cGAS-STING pathway, induce tumor cell ferroptosis, and inhibit M2 macrophage polarization. RMPs can also act as carriers of agents with biocompatibility. In the present study, we designed a therapeutic system wherein the ferroptosis inducer RSL-3 was loaded into RMPs, which were tested in in vitro and in vivo prostate carcinoma models established using RM-1 cells. The apoptosis inducer CT20 peptide (CT20p) was also added to the RMPs to aggravate ferroptosis. Our results showed that RSL-3- and CT20p-loaded RMPs (RC@RMPs) led to ferroptosis and apoptosis of RM-1 cells. Moreover, CT20p had a synergistic effect on ferroptosis by promoting reactive oxygen species (ROS) production, lipid hydroperoxide production, and mitochondrial instability. RC@RMPs elevated dendritic cell (DC) expression of MHCII, CD80, and CD86 and facilitated M1 macrophage polarization. In a subcutaneously transplanted RM-1 tumor model in mice, RC@RMPs inhibited tumor growth and prolonged survival time via DC activation, macrophage reprogramming, enhancement of CD8+ T cell infiltration, and proinflammatory cytokine production in the tumor. Moreover, combination treatment with anti-PD-1 improved RM-1 tumor inhibition. This study provides a strategy for the synergistic enhancement of ferroptosis for prostate cancer immunotherapies.

Podiatrist intervention could reduce the incidence of foot ulcers in patients with diabetes: a hospital survey in China.

OBJECTIVE: This study aimed to evaluate the effectiveness of podiatrists in preventing diabetic foot ulcers (DFUs) in China. METHOD: The study was a prospective investigation. A total of 300 patients were enrolled from May 2016 to May 2018 in Handan Central Hospital, China. All patients who participated in this study had been diagnosed with type 2 diabetes, according to the International Classification of Diseases (ICD-10). All participants underwent our survey, which included basic patient data and information about DFUs. The patients were followed for one year, during which time they received appropriate intervention from podiatrists, including lifestyle guidance, callus resection, tinea grinding and ingrown nail correction. At the end of the year all the patients were surveyed again. The data before and after the year were statistically compared. RESULTS: The results showed that the incidence of DFUs in patients with diabetes was significantly decreased after one year of intervention from podiatrists (20.7% versus 6.7%, p<0.001). Additionally, there was a negative correlation between the number of intervention visits and the number of DFU occurrences (Spearman correlation coefficient: -0.496, p<0.001). Furthermore, we found that 68 patients with a history of DFUs or amputation had an obviously reduced incidence of DFUs after intervention by a podiatrist (89.7% versus 27.9%, p<0.001). We also investigated other foot risk factors in all participants, such as limb neuropathy (76.3%), lower extremity vascular disease (65.7%) and foot paralysis (43.7%). CONCLUSION: The results of this study help in understanding the situation of patients with diabetes in China and to prove that standardised podiatrist intervention has an important role in inhibiting the occurrence and development of DFUs.

Autophagy-related long non-coding RNAs act as prognostic biomarkers and associate with tumor microenvironment in prostate cancer.

Aberrant autophagy could promote cancer cells to survive and proliferate in prostate cancer (PCa). LncRNAs play key roles in autophagy regulatory network. We established a prognostic model, which autophagy-related lncRNAs (au-lncRNAs) were used as biomarkers to predict prognosis of individuals with PCa. Depending on au-lncRNAs from the Cancer Genome Atlas and the Human Autophagy Database, a risk score model was created. To evaluate the prediction accuracy, the calibration, Kaplan-Meier, and receiver operating characteristic curves were used. To clarify the biological function, gene set enrichment analyses (GSEA) were performed. Quantitative real-time PCR (qRT-PCR) was employed to determine the au-lncRNAs expression in PCa cell lines and healthy prostate cells for further confirmation. We identified five au-lncRNAs with prognostic significance (AC068580.6, AF131215.2, LINC00996, LINC01125 and LINC01547). The development of a risk scoring model required the utilization of multivariate Cox analysis. According to the model, we categorized PCa individuals into low- and high-risk cohorts. PCa subjects in the high-risk group had a worse disease-free survival rate than those in the low-risk group. The 1-, 3-, and 5-year periods had corresponding areas under curves (AUC) of 0.788, 0.794, and 0.818. The prognosis of individuals with PCa could be predicted by the model with accuracy. Further analysis with GSEA showed that the prognostic model was associated with the tumor microenvironment, including immunotherapy, cancer-related inflammation, and metabolic reprogramming. Four lncRNAs expression in PCa cell lines was greater than that in healthy prostate cells. The au-lncRNA prognostic model has significant clinical implications in prognosis of PCa patient.

A guideline on the molecular ecosystem regulating ferroptosis.

Ferroptosis, an intricately regulated form of cell death characterized by uncontrolled lipid peroxidation, has garnered substantial interest since this term was first coined in 2012. Recent years have witnessed remarkable progress in elucidating the detailed molecular mechanisms that govern ferroptosis induction and defence, with particular emphasis on the roles of heterogeneity and plasticity. In this Review, we discuss the molecular ecosystem of ferroptosis, with implications that may inform and enable safe and effective therapeutic strategies across a broad spectrum of diseases.

Gut microbiota and metabolic biomarkers in metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD), a replacement of the nomenclature employed for NAFLD, is the most prevalent chronic liver disease worldwide. Despite its high global prevalence, NAFLD is often under-recognized due to the absence of reliable noninvasive biomarkers for diagnosis and staging. Growing evidence suggests that the gut microbiome plays a significant role in the occurrence and progression of NAFLD by causing immune dysregulation and metabolic alterations due to gut dysbiosis. The rapid advancement of sequencing tools and metabolomics has enabled the identification of alterations in microbiome signatures and gut microbiota-derived metabolite profiles in numerous clinical studies related to NAFLD. Overall, these studies have shown a decrease in α-diversity and changes in gut microbiota abundance, characterized by increased levels of Escherichia and Prevotella, and decreased levels of Akkermansia muciniphila and Faecalibacterium in patients with NAFLD. Furthermore, bile acids, short-chain fatty acids, trimethylamine N-oxide, and tryptophan metabolites are believed to be closely associated with the onset and progression of NAFLD. In this review, we provide novel insights into the vital role of gut microbiome in the pathogenesis of NAFLD. Specifically, we summarize the major classes of gut microbiota and metabolic biomarkers in NAFLD, thereby highlighting the links between specific bacterial species and certain gut microbiota-derived metabolites in patients with NAFLD.

[Retracted] MicroRNA­30a suppresses the proliferation, migration and invasion of human renal cell carcinoma cells by directly targeting ADAM9.

[This retracts the article DOI: 10.3892/ol.2018.8999.].

Regulation of craving training to support healthy food choices under stress: A randomized control trial employing the hierarchical drift-diffusion model.

Stress increases the likelihood of consuming unhealthy food in some individuals. Previous research has demonstrated that the Regulation of Craving - Training (ROC-T) intervention can reduce unhealthy food intake. However, its effectiveness under stress and the underlying mechanism remained uncertain. This study aimed to assess the efficacy of the ROC-T intervention in improving healthy food choices and to explore the intervention mechanism through computational modeling employing the hierarchical drift-diffusion model (HDDM). This study adopted a 2 (ROC-T intervention vs. control) * 2 (stress vs. no-stress) between-subject experimental design. A total of 118 employees (72 women, Mage  = 28.74) participated in the online experiment. Results show that the ROC-T intervention increases healthy food choices under stress and no-stress conditions. The HDDM results reveal a significant two-way interaction for non-decision time (Bayes factor, BF = 32.722) and initial bias (BF = 27.350). Specifically, in the no-stress condition, the ROC-T intervention resulted in lower non-decision time and higher initial bias compared with the control group. The findings validated the negative impact of stress on healthy food choices, and that the ROC-T intervention promotes healthy food choices both under stress and no-stress conditions.

New Process for Na2CO3 Production from Na2SO4 Based on Modeling the Na2SO4-(NH4)2SO4-MEA-MEG-H2O System.

Alternative means for soda ash (Na2CO3) production from sodium sulfate (Na2SO4) are needed due to the intensive consumption of energy in the conventional Mirabilite-Solvay process (MSP). We demonstrate a new process to produce soda ash using sodium sulfate as a feed material. The new process relies on the antisolvent crystallization of unreacted Na2SO4 to separate it from soluble (NH4)2SO4 in a mixed monoethanolamine (MEA) and monoethylene glycol (MEG) solution. To develop the process, the solubilities of Na2SO4 and (NH4)2SO4 solids in aqueous mixed MEA-MEG solutions were first measured and then modeled using regressed paired-ion interactions from the electrolyte nonrandom two-liquid (E-NRTL) model. Anhydrous dense soda ash with a bulk density of up to 1146 kg/m3 was obtained when the concentrated Na2SO4 brines reacted with CO2 and NH3.

Microelectromechanical system for in situ quantitative testing of tension-compression asymmetry in nanostructures.

Tension-compression asymmetry is a topic of current interest in nanostructures, especially in strain engineering. Herein, we report a novel on-chip microelectromechanical system (MEMS) that can realize in situ quantitative mechanical testing of nanostructures under tension-compression functions. The mechanical properties of three kinds of nanostructures fabricated by focused ion beam (FIB) techniques were systematically investigated with the presented on-chip testing system. The results declare that both Pt nanopillars and C nanowires exhibit plastic deformation behavior under tension testing, with average Young's moduli of 70.06 GPa and 58.32 GPa, respectively. However, the mechanical deformation mechanisms of the two nanostructures changed in compression tests. The Pt nanopillar exhibited in-plane buckling behavior, while the C nanowire displayed 3D twisting behavior with a maximum strain of 25.47%, which is far greater than the tensile strain. Moreover, asymmetric behavior was also observed in the C nanospring during five loading-unloading tension-compression deformation tests. This work provides a novel insight into the asymmetric mechanical properties of nanostructures, with potential applications in nanotechnology research.

Joint effects of gas bubbles and solid particles on sonochemical inhibition in sonicated aqueous solutions.

Wastewater is a multicomponent and multiphase mixture. Gas bubbles and solid particles in the dispersed phase influence sonochemical efficiency during ultrasonic treatment of wastewater, sometimes unfavorably; however, the influencing factors and mechanisms remain unclear. In this paper, the influence of argon gas bubbles (1.2 mm) and monodisperse silica particles (0.1 mm) on sonochemical effects in an aqueous system using a horn-type reactor (20 kHz) is reported. Triiodide formation decreased with an increase in the volume fraction of either or both phases. The two phases started inhibiting sonoreactions as the total volume fraction approached 3.0-4.0 vol% compared to pure water. The effect of the gas-to-solid ratio is also considered. We propose an acoustic attenuation model, which incorporates the scattering effect of solid particles and the thermal effect of gas bubbles. The agreement between the modeling and experimental results demonstrates that the two phases are jointly responsible for sonochemical inhibition by increasing ultrasound attenuation. This enhances the understanding of sonochemistry in gas-solid-liquid systems and helps regulate gases and solids in sonochemical reactors.

High-sensitivity self-powered photodetector based on an in-situ prepared CsPbBr3 microwire/InGaN heterojunction.

Low-dimensional CsPbBr3 perovskite materials have gained widespread attention, derived from their remarkable properties and potential for numerous optoelectronic applications. Herein, the sample of CsPbBr3 microwires were prepared horizontally onto n-type InGaN film substrate using an in-plane solution growth method. The resulting CsPbBr3 microwire/InGaN heterojunction allows for the achievement of a highly sensitive and broadband photodetector. Particularly for the implementation in a self-supplying manner, the best-performing photodetector can achieve a superior On/Off ratio of 4.6×105, the largest responsivity ∼ 800.0 mA/W, a maximum detectivity surpassing 4.6× 1012 Jones, and a high external quantum efficiency approaching 86.5% upon 405 nm light illumination. A rapid response time (∼ 4.48 ms/7.68 ms) was also achieved. The as-designed CsPbBr3 microwire/InGaN heterojunction device without any encapsulation exhibits superior comprehensive stability. Besides, the device featuring as a single pixel imaging unit can readily detect simple images under broadband light illumination with a high spatial resolution, acknowledging its outstanding imaging capability. The robust photodetection properties could be derived from the intense absorption of CsPbBr3 MWs and high-efficiency charge carriers transporting toward the in-situ formed CsPbBr3/InGaN heterointerface. The results may offer an available strategy for the in-situ construction of best-performing low-dimensional perovskite heterojunction optoelectronic devices.

The burden of chronic kidney disease associated with dietary exposure to cadmium in China, 2020.

Cadmium (Cd) exposure increases the risk of chronic kidney disease (CKD). But the contribution of dietary Cd intake, the primary exposure route of Cd in humans, to the CKD burden remains to be evaluated in China. Concentrations of Cd in foods and population glomerular filtration rate (GFR) were retrieved from studies published between January 2000 and February 2023 in China. Daily food consumption in adults aged ≥35 years old was obtained from two nationwide Chinese surveys. Dietary Cd intake and its contribution rate among total Cd exposure from diet, inhalation, smoking and water were evaluated. Urinary Cd (UCd) was estimated using the toxicokinetic (TK) model based on dietary Cd intake. The effect of Cd on kidney function has been quantified with the previously published dose-response relationship between UCd and GFR. The incidence and disability-adjusted life years (DALYs) of CKD attributable to dietary Cd intake were derived considering the contribution rate of dietary Cd intake at the national and provincial levels. The national average dietary Cd intake was 0.6891 µg/kg bw/day, contributing 63.69% of total Cd exposure. The Cd exposure through foods resulted in 2.34 (95% uncertainty interval, UI: 1.54-3.40) stage 4 CKD and 0.37 (95% UI: 0.20-0.59) stage 5 CKD cases per 100,000 persons/year in mainland China, 2020. The corresponding DALYs loss associated with stage 4 and stage 5 CKD due to dietary Cd intake were 5.14 (95% UI: 3.24-7.67) and 4.78 (95% UI: 2.32-8.30) per 100,000 persons/year, together accounting for 2% of total DALYs of CKD. Greater dietary Cd intake and corresponding burden of late-stage CKD were observed in Southern areas than in Northern areas. Diet remains the primary exposure to Cd in Chinese adults. Efforts to reduce dietary Cd exposure would positively impact public health, especially in Southern provinces with high Cd exposure.

Efficacy and safety of pentoxifylline for chronic venous leg ulcers: study protocol for a multicenter randomized controlled trial in China (ESPECT study).

BACKGROUND: Venous leg ulcers (VLUs) are the most severe manifestation of chronic venous disease, with long healing time and a high recurrence rate. It imposes a heavy burden on patients, their families, and the health care system. Chronic inflammation triggered by sustained venous hypertension is now recognized as the hallmark of chronic venous disease. The anti-inflammatory effect of pentoxifylline may offer a promising avenue to treat VLUs. However, current evidence of pentoxifylline for VLUs is relatively small and of low quality. The aim of this study is to evaluate the efficacy and safety of pentoxifylline for VLUs in the Chinese population. METHODS: This is a randomized, double-blinded, double-dummy, multi-center, placebo-controlled clinical trial. A total of 240 patients will be randomized to receive pentoxifylline (400 mg, twice daily) or placebo for 24 weeks. All participants will receive diosmin treatment and standard care of VLUs and other comorbidities. The primary outcome is the difference in the wound healing rate within 12 weeks between pentoxifylline and placebo. Secondary outcomes include (1) percent wound size changes at 12 weeks, (2) the levels of TNF-α and IL-6, (3) venous clinical severity score and chronic venous insufficiency quality of life score, and (4) ulcer recurrence within 24 weeks. DISCUSSION: This study would evaluate the efficacy and safety of pentoxifylline for VLUs in the Chinese population. If confirmed, it wound offer another effective and safe therapeutic option for treatment of VLUs. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry (No. ChiCTR-2100053053). Registered on 10 November, 2021, https://www.chictr.org.cn/showproj.aspx?proj=137010.

The roles of inflammasomes in cancer.

Inflammation is a key characteristic of all stages of tumor development, including tumor initiation, progression, malignant transformation, invasion, and metastasis. Inflammasomes are an important component of the inflammatory response and an indispensable part of the innate immune system. Inflammasomes regulate the nature of infiltrating immune cells by signaling the secretion of different cytokines and chemokines, thus regulating the anti-tumor immunity of the body. Inflammasome expression patterns vary across different tumor types and stages, playing different roles during tumor progression. The complex diversity of the inflammasomes is determined by both internal and external factors relating to tumor establishment and progression. Therefore, elucidating the specific effects of different inflammasomes in anti-tumor immunity is critical for promoting the discovery of inflammasome-targeting drugs. This review focuses on the structure, activation pathway, and identification methods of the NLRP3, NLRC4, NLRP1 and AIM2 inflammasomes. Herein, we also explore the role of inflammasomes in different cancers and their complex regulatory mechanisms, and discuss current and future directions for targeting inflammasomes in cancer therapy. A detailed knowledge of inflammasome function and regulation may lead to novel therapies that target the activation of inflammasomes as well as the discovery of new drug targets.

De novo pyrimidine biosynthetic complexes support cancer cell proliferation and ferroptosis defence.

De novo pyrimidine biosynthesis is achieved by cytosolic carbamoyl-phosphate synthetase II, aspartate transcarbamylase and dihydroorotase (CAD) and uridine 5'-monophosphate synthase (UMPS), and mitochondrial dihydroorotate dehydrogenase (DHODH). However, how these enzymes are orchestrated remains enigmatical. Here we show that cytosolic glutamate oxaloacetate transaminase 1 clusters with CAD and UMPS, and this complex then connects with DHODH, which is mediated by the mitochondrial outer membrane protein voltage-dependent anion-selective channel protein 3. Therefore, these proteins form a multi-enzyme complex, named 'pyrimidinosome', involving AMP-activated protein kinase (AMPK) as a regulator. Activated AMPK dissociates from the complex to enhance pyrimidinosome assembly but inactivated UMPS, which promotes DHODH-mediated ferroptosis defence. Meanwhile, cancer cells with lower expression of AMPK are more reliant on pyrimidinosome-mediated UMP biosynthesis and more vulnerable to its inhibition. Our findings reveal the role of pyrimidinosome in regulating pyrimidine flux and ferroptosis, and suggest a pharmaceutical strategy of targeting pyrimidinosome in cancer treatment.

HPIP is an essential scaffolding protein running through the EGFR-RAS-ERK pathway and drives tumorigenesis.

The EGFR-RAS-ERK pathway plays a key role in cancer development and progression. However, the integral assembly of EGFR-RAS-ERK signaling complexes from the upstream component EGFR to the downstream component ERK is largely unknown. Here, we show that hematopoietic PBX-interacting protein (HPIP) interacts with all classical components of the EGFR-RAS-ERK pathway and forms at least two complexes with overlapping components. Experiments of HPIP knockout or knockdown and chemical inhibition of HPIP expression showed that HPIP is required for EGFR-RAS-ERK signaling complex formation, EGFR-RAS-ERK signaling activation, and EGFR-RAS-ERK signaling-mediated promotion of aerobic glycolysis as well as cancer cell growth in vitro and in vivo. HPIP expression is correlated with EGFR-RAS-ERK signaling activation and predicts worse clinical outcomes in patients with lung cancer. These results provide insights into EGFR-RAS-ERK signaling complex formation and EGFR-RAS-ERK signaling regulation and suggest that HPIP may be a promising therapeutic target for cancer with dysregulated EGFR-RAS-ERK signaling.

ZNF133 is a potent suppressor in breast carcinogenesis through dampening L1CAM, a driver for tumor progression.

Due to the complexity and heterogeneity of breast cancer, the therapeutic effects of breast cancer treatment vary between subtypes. Breast cancer subtypes are classified based on the presence of molecular markers for estrogen or progesterone receptors and human epidermal growth factor 2. Thus, novel, comprehensive, and precise molecular indicators in breast carcinogenesis are urgently needed. Here, we report that ZNF133, a zinc-finger protein, is negatively associated with poor survival and advanced pathological staging of breast carcinomas. Moreover, ZNF133 is a transcription repressor physically associated with the KAP1 complex. It transcriptionally represses a cohort of genes, including L1CAM, that are critically involved in cell proliferation and motility. We also demonstrate that the ZNF133/KAP1 complex inhibits the proliferation and invasion of breast cancer cells in vitro and suppresses breast cancer growth and metastasis in vivo by dampening the transcription of L1CAM. Taken together, the findings of our study confirm the value of ZNF133 and L1CAM levels in the diagnosis and prognosis of breast cancer, contribute to a deeper understanding of the regulation mechanism of ZNF133 for the first time, and provide a new therapeutic strategy and precise intervention target for breast cancer.

Highly-time-resolved FMCW LiDAR with synchronously-nonlinearity-corrected acquisition for dynamic locomotion.

Highly-time-resolved and precise tracking of position, velocity, and acceleration is urgently required when highly dynamic legged robots are walking, trotting, and jumping. Frequency-modulated continuous-wave (FMCW) laser ranging is able to provide precise measurement in short distance. However, FMCW light detection and ranging (LiDAR) suffers from a low acquisition rate and poor linearity of laser frequency modulation in wide bandwidth. A sub-millisecond-scale acquisition rate and nonlinearity correction in the wide frequency modulation bandwidth have not been reported in previous studies. This study presents the synchronous nonlinearity correction for a highly-time-resolved FMCW LiDAR. The acquisition rate of 20 kHz is obtained by synchronizing the measurement signal and the modulation signal of laser injection current with a symmetrical triangular waveform. The linearization of laser frequency modulation is conducted by resampling of 1000 intervals interpolated in every up-sweep and down-sweep of 25 µs, while measurement signal is stretched or compressed in every period of 50 µs. The acquisition rate is demonstrated to be equal to the repetition frequency of laser injection current for the first time to the best of authors' knowledge. This LiDAR is successfully used to track the foot trajectory of a jumping single-leg robot. The high velocity up to 7.15 m/s and high acceleration of 365 m/s2 are measured during the up-jumping phase, while heavy shock takes place with high acceleration of 302 m/s2 as the foot end strikes the ground. The measured foot acceleration of over 300 m/s2, which is more than 30 times gravity acceleration, is reported on a jumping single-leg robot for the first time.

Ultraviolet Exciton-Polariton Light-Emitting Diode in a ZnO Microwire Homojunction.

Low-dimensional ZnO, possessing well-defined side facets and optical gain properties, has emerged as a promising material to develop ultraviolet coherent light sources. However, the realization of electrically driven ZnO homojunction luminescence and laser devices is still a challenge due to the absence of a reliable p-type ZnO. Herein, the sample of p-type ZnO microwires doped by Sb (ZnO:Sb MWs) was synthesized individually. Subsequently, the p-type conductivity was examined using a single-MW field-effect transistor. Upon optical pumping, a ZnO:Sb MW showing a regular hexagonal cross-section and smooth sidewall facets can feature as an optical microcavity, which is evidenced by the achievement of whispering-gallery-mode lasing. By combining an n-type ZnO layer, a single ZnO:Sb MW homojunction light-emitting diode (LED), which exhibited a typical ultraviolet emission at a wavelength of 379.0 nm and a line-width of approximately 23.5 nm, was constructed. We further illustrated that strong exciton-photon coupling can occur in the as-constructed p-ZnO:Sb MW/n-ZnO homojunction LED by researching spatially resolved electroluminescence spectra, contributing to the exciton-polariton effect. Particularly, varying the cross-sectional dimensions of ZnO:Sb wires can further modulate the exciton-photon coupling strengths. We anticipate that the results can provide an effective exemplification to realize reliable p-type ZnO and tremendously promote the development of low-dimensional ZnO homojunction optoelectronic devices.