High Intensity Focused Ultrasound-Driven Nanomotor for Effective Ferroptosis-Immunotherapy of TNBC.

The heterogeneity of triple-negative breast cancers (TNBC) remains challenging for various treatments. Ferroptosis, a recently identified form of cell death resulting from the unrestrained peroxidation of phospholipids, represents a potential vulnerability in TNBC. In this study, a high intensity focused ultrasound (HIFU)-driven nanomotor is developed for effective therapy of TNBC through induction of ferroptosis. Through bioinformatics analysis of typical ferroptosis-associated genes in the FUSCCTNBC dataset, gambogic acid is identified as a promising ferroptosis drug and loaded it into the nanomotor. It is found that the rapid motion of nanomotors propelled by HIFU significantly enhanced tumor accumulation and penetration. More importantly, HIFU not only actuated nanomotors to trigger effective ferroptosis of TNBC cells, but also drove nanomotors to activate ferroptosis-mediated antitumor immunity in primary and metastatic TNBC models, resulting in effective tumor regression and prevention of metastases. Overall, HIFU-driven nanomotors show great potential for ferroptosis-immunotherapy of TNBC.

Erythrocyte-Leveraged Oncolytic Virotherapy (ELeOVt): Oncolytic Virus Assembly on Erythrocyte Surface to Combat Pulmonary Metastasis and Alleviate Side Effects.

Despite being a new promising tool for cancer therapy, intravenous delivery of oncolytic viruses (OVs) is greatly limited by poor tumor targeting, rapid clearance in the blood, severe organ toxicity, and cytokine release syndrome. Herein, a simple and efficient strategy of erythrocyte-leveraged oncolytic virotherapy (ELeOVt) is reported, which for the first time assembled OVs on the surface of erythrocytes with up to near 100% efficiency and allowed targeted delivery of OVs to the lung after intravenous injection to achieve excellent treatment of pulmonary metastases while greatly improving the biocompatibility of OVs as a drug. Polyethyleneimine (PEI) as a bridge to assemble OVs on erythrocytes also played an important role in promoting the transfection of OVs. It is found that ELeOVt approach significantly prolonged the circulation time of OVs and increased the OVs distribution in the lung by more than tenfold, thereby significantly improving the treatment of lung metastases while reducing organ and systemic toxicity. Taken together, these findings suggest that the ELeOVt provides a biocompatible, efficient, and widely available approach to empower OVs to combat lung metastasis.

Low-temperature photothermal-induced alkyl radical release facilitates dihydroartemisinin-triggered "valve-off" starvation therapy.

The high nutrient and energy demand of tumor cells compared to normal cells to sustain rapid proliferation offer a potentially auspicious avenue for implementing starvation therapy. However, conventional starvation therapy, such as glucose exhaustion and vascular thrombosis, can lead to systemic toxicity and exacerbate tumor hypoxia. Herein, we developed a new "valve-off" starvation tactic, which was accomplished by closing the valve of glucose transporter protein 1 (GLUT1). Specifically, dihydroartemisinin (DHA), 2,20-azobis [2-(2-imidazolin-2-yl) propane] dihydrochloride (AI), and Ink were co-encapsulated in a sodium alginate (ALG) hydrogel. Upon irradiation with the 1064 nm laser, AI rapidly disintegrated into alkyl radicals (R•), which exacerbated the DHA-induced mitochondrial damage through the generation of reactive oxygen species and further reduced the synthesis of adenosine triphosphate (ATP). Simultaneously, the production of R• facilitated DHA-induced starvation therapy by suppressing GLUT1, which in turn reduced glucose uptake. Systematic in vivo and in vitro results suggested that this radical-enhanced "valve-off" strategy for inducing tumor cell starvation was effective in reducing glucose uptake and ATP levels. This integrated strategy induces tumor starvation with efficient tumor suppression, creating a new avenue for controlled, precise, and concerted tumor therapy.

Global prevalence and factors affecting the level of Cryptosporidium contamination in soil: A systematic review, meta-analysis, and meta-regression.

Soil contamination with Cryptosporidium is a serious environmental and public health concern. In this systematic review and meta-analysis we estimated the global prevalence of Cryptosporidium contamination in soil and evaluated its association with climatic and hydrometeorological factors. PubMed, Web of Science, Science Direct, China National Knowledge Infrastructure, and Wanfang were searched from database inception up to 24 August 2022. The initial search identified 3220 studies, of which 14 met the inclusion criteria. The results were pooled using a random-effects model, and the statistical heterogeneity among the included studies was examined using Cochrane's Q test and I2 statistic. The estimated pooled global prevalence of Cryptosporidium in soil across all studies was 8.13 % (95 % confidence interval, 1.54-18.44). Meta-regression and subgroup analyses showed that Cryptosporidium prevalence in soil was significantly influenced by continent (p = 0.0002; R2 = 49.99 %), air pressure (p = 0.0154; R2 = 24.01 %), temperature (p = 0.0437; R2 = 14.53 %), and detection method (p = 0.0131; R2 = 26.94 %). These results highlight the need for increased surveillance of Cryptosporidium in soil and its risk factors to inform future development of environmental control interventions and public health policies.

miR-28-5p's Targeting of GAGE12I Inhibits Proliferation, Migration, and Invasion of Gastric Cancer in Vitro.

GAGE12I is a tumor metastasis-promoting factor, which can induce gastric cancer cells to invade and migrate. We investigated the effect of miR-28-5p targeting GAGE12I on proliferation, invasion, and migration of human gastric cancer cell lines SGC-7901, AGS, and MGC-803. The expression levels of miR-28-5p and GAGE12I were detected by real-time PCR and western blot, respectively. Cell proliferation, migration, and invasion were measured by MTT and Transwell chamber. The interaction between miR-28-5p and GAGE12I was investigated by bioinformatics analysis and luciferase assay. Results showed that the expression of miR-28-5p in human gastric cancer cell lines was lower than that in normal gastric epithelial cells (P < 0.05). Overexpression of miR-28-5p suppressed cell proliferation, invasion, and migration (P < 0.05). GAGE12I was confirmed as a target of miR-28-5p. Cell proliferation, invasion, and migration were decreased in cells transfected with shGAGE12I compared with those of the scrambled group (P < 0.05). Collectively, miR-28-5p negatively regulated GAGE12I and reduced the proliferation, invasion, and migration of gastric cancer cells.

Gut Bacteria Erysipelatoclostridium and Its Related Metabolite Ptilosteroid A Could Predict Radiation-Induced Intestinal Injury.

It is difficult to study the intestinal damage induced by space radiation to astronauts directly, and few prediction models exist. However, we can simulate it in patients with pelvic tumor radiotherapy (RT). Radiation-induced intestinal injury (RIII) is common in cancer patients who receieved pelvic and abdominal RT. We dynamically analyzed gut microbiota and metabolites alterations in 17 cervical and endometrial cancer patients after pelvic RT. In patients who later developed grade 2 RIII, dysbiosis of gut microbiota and metabolites were observed. Univariate analysis showed that Erysipelatoclostridium and ptilosteroid A were related to the occurrence of grade 2 RIII. Notably, a strong positive correlation between gut bacteria Erysipelatoclostridium relative abundance and gut metabolite ptilosteroid A expression was found. Furthermore, combinations of Erysipelatoclostridium and ptilosteroid A could provide good diagnostic markers for grade 2 RIII. In conclusion, gut bacteria Erysipelatoclostridium and its related metabolite ptilosteroid A may collaboratively predict RIII, and could be diagnostic biomarkers for RIII and space radiation injury.

Adsorption of Phosphorus Oxyanions at the FeOOH(goethite)/Water Interface: The Importance of Basicity.

PIII-containing H-phosphonate (HPO32-) and its monoethyl ester (fosetyl), essential pesticides for control of oomycete and fungal pathogens, are among the few pesticides transported by both xylem and phloem, making application as folia spray, soil spray, and trunk injection equally effective. To understand bioavailability and efficacy within soils, knowledge of adsorption to soil minerals is important. FeOOH(goethite) is often selected as an archetypal mineral surface. In the present work, H-phosphonate (with pKa values of 1.5 and 6.78) adsorption onto FeOOH is nearly complete below pH 6 and decreases to negligible amounts by pH 11, following an S-shaped curve. Fosetyl (pKa: 0.9), in contrast, does not adsorb to any significant extent, regardless of pH. To place these observations in context, adsorption of six other phosphorus oxyanions was investigated, and fitted using a CD-MUSIC model. Phosphate defines a similar S-shaped curve but adsorbs more strongly than H-phosphonate. Despite moderate differences in basicity, pH dependence and extents of adsorption for the four additional diprotic oxyanions methylphosphonate (pKas: 2.40, 8.00), benzylphosphonate (2.24, 7.93), phenylphosphonate (1.9, 7.47), and phenyl phosphate (1.1, 6.28) are quite similar to those of H-phosphonate. As with fosetyl, the other low pKa monoprotic oxyanion in our study, phenylphosphinate (pKa: 1.75), does not adsorb. Basicity, that is, pKa, is revealed to be the principal determinant of extents of adsorption.

Resveratrol Prevents Cognitive Impairment in Type 2 Diabetic Mice by Upregulating Nrf2 Expression and Transcriptional Level.

PURPOSE: This study aimed to determine whether the natural antioxidant resveratrol (RSV) prevents type 2 diabetes mellitus (T2DM)-induced cognitive impairment and to explore whether redox-associated factor nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in the neuroprotective effect of RSV. MATERIALS AND METHODS: We established a T2DM model with 8-week-old male ICR mice by administration of a high-fat diet for 2 months and low-dose streptozotocin for 3 days. Then, diabetic and age-matched control mice were treated with or without RSV for 4 months every other day and subjected to the Morris water maze test. After the mice were euthanized, whole brains were sectioned for Nissl staining and immunofluorescence labeling. Hippocampal sections were observed by transmission electron microscopy to evaluate the ultrastructure of synapses. Inflammatory factors, oxidative stress-related indexes, and Nrf2 and downstream target gene expression were analyzed in hippocampal tissues by quantitative real-time PCR, Western blotting, and associated quantitative kits. RESULTS: In the Morris water maze test, compared to control mice, T2DM mice showed learning and memory impairments, but RSV treatment prevented the learning and memory decline in T2DM mice. Similarly, RSV prevented T2DM-induced hippocampal neuron destruction and synaptic ultrastructural damage. The expression levels of inflammatory factors and oxidative stress-related indicators were increased in the T2DM group compared with the control group but were decreased significantly by RSV treatment in the T2DM group. Additionally, the expression of Nrf2 and its downstream target genes was decreased in the T2DM group compared with the control group and was significantly increased by RSV treatment in the T2DM group. CONCLUSION: RSV prevented T2DM-induced cognitive impairment through anti-inflammatory and antioxidant activities. This effect was accompanied by the upregulation of Nrf2 transcriptional activity and the increased expression of downstream antioxidant genes.

[Characterization of Volatile Organic Compounds from Cooking Emissions].

Volatile organic compounds (VOCs) do great harm to human health, and also have some impact on air quality. Cooking is one of the important sources of VOCs, so the study of cooking emissions is of great significance. By simulating the heating of oil and cooking, the characteristics and chemical composition of VOCs emissions for different types of oil fumes were analyzed by gas chromatography-mass spectrometry (GC-MS), using different oils, seasonings, and dishes as variables. The results show that the emission factors of the oils range from 0.81 to 2.53 g·kg-1, and the emissions are dominated by halogenated hydrocarbons and alkanes. The emission factors of the seasonings range from 25.06 to 40.18 g·kg-1, and the seasonings mainly emit alkanes. The quantity of emissions from chili fried meat is much higher than that of tomato scrambled eggs, and the chili fried meat mainly emits halogenated hydrocarbons, while tomato scrambled eggs mainly emit aromatic hydrocarbons and alkanes.

Decreased serum undercarboxylated osteocalcin is associated with cognitive impairment in male patients with type 2 diabetes.

BACKGROUND: Basic and clinical researches have suggested that type 2 diabetes (T2DM) is associated with cognitive impairment, and diabetes mellitus increases the risk of cognitive impairment and dementia. Recently, some reports found that undercarboxylated osteocalcin (ucOC) could affect brain functions, and decreased in patients with T2DM. We aimed to investigate the association of serum ucOC with cognitive impairment in T2DM patients. METHODS: A total of 196 male T2DM patients without medications known to affect bone metabolism or history of bone fracture, aged ≥18years were recruited and divided into impaired cognition group and normal cognition group. We use the scores of Minimum Mental State Examination (MMSE) to evaluate the subjects' cognitive function. Detailed cognitive performance was also evaluated by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Serum ucOC was measured by Enzyme-Linked Immunosorbent Assay (ELISA) kit. RESULTS: Compared to male T2DM patients with normal cognition, the mean osteocalcin concentrations were significantly lower in male T2DM patients with impaired cognition (P<0.05). RBANS total and all indexes scores were also lower in patients with impaired cognition (all P<0.05). After adjusted effects of confounding factors, serum ucOC was positively correlated with a variety indexes of RBANS except visuospatial/constructional. CONCLUSIONS: The serum ucOC is positively correlated with RBANS scores in male T2DM patients. It suggests that serum ucOC may be involved in the development and progression of cognitive dysfunction in T2DM patients.

NFAT3/c4-mediated excitotoxicity in hippocampal apoptosis during radiation-induced brain injury.

Whole brain irradiation (WBI) has become an indispensible tool in the treatment of head and neck cancer, and it has greatly improved patient survival rate and total survival time. In addition, prophylactic cranial irradiation (PCI) has dramatically decreased the incidence of brain metastatic carcinoma. However, WBI may induce temporary functional deficits or even progressive, irreversible cognitive dysfunction that compromises the quality of life for survivors. Unfortunately, the exact molecular mechanisms for cognitive damage remain elusive, and no treatment or preventative measures are available for use in the clinic. In the present study, the nuclear factor of activated T cells isoform 4 (NFAT3/c4) was found to play a vital role in excitotoxic hippocampus cell apoptosis induced by radiation. Sprague-Dawley (SD) rats received 20 Gy WBI, after which we detected NFAT3/c4-mediated excitotoxicity. We found that radiation caused hippocampus excitotoxicity, resulting from overactivation of the N-methyl-D-aspartate receptor (NMDAR) and always accompanied by subsequent elevation of the intracellular calcium level and activation of calcineurin (CaN). P-NFAT3/c4 was the principal downstream target of CaN, including regulation of its nuclear translocation as well as transcriptional activities. Radiation recruited NMDAR/NFAT3/c4 activation and subsequent Bax induction in hippocampus cells. Once treated with the NFAT3/c4 inhibitor 11R-VIVIT peptide pre-irradiation, hippocampal proliferation and neuron survival (dentate gyrus cells in particular) were protected from radiation-induced injury, resulting in inhibition of the apoptosis marker Bax. Our principal aim was to illuminate the role of NFAT3/c4-mediated excitotoxicity in hippocampal apoptosis during radiation-induced brain injury. This study is the first time that radiation-induced activation of NFAT3/c4 has been recorded, and our results suggest that NFAT3/c4 may be a novel target for prevention and treatment of radiation-induced brain injury.