Visible-Light-Driven Iron-Catalyzed 1,2-Difluoroalkylthiolation of Alkenes.

The synthesis of medicinally interesting aryldifluoromethylated compounds has drawn significant research attention in recent years. Herein, we report an unprecedented iron-mediated process for the selective defluorination of trifluoromethylarenes to achieve the 1,2-difluoroalkylthiolation of alkenes. Preliminary mechanistic studies revealed that thiolate anion, trifluoromethylarene, and iron cation could form an electron donor-acceptor (EDA) complex, which induced selective defluorination and then difunctionalization of alkenes to obtain aryldifluoromethylated products. The generated aryldifluoromethylated compounds make it difficult to form an EDA complex again, thus avoiding excessive defluorination. This conversion has concise and ambient reaction conditions and provides an alternative solution for obtaining difluorobenzylic intermediates.

Cadmium causes spleen toxicity in chickens by regulating mitochondrial unfolded protein response and nuclear receptors response.

Cadmium (Cd) is a heavy metal that pollutes the environment and threatens human and animal health via the food chain. The spleen is one of the target organs affected by Cd toxicity. However, the mechanism of Cd toxicity is not fully understood. In this study, 80 chicks were allocated into 4 groups (n = 20) and exposed to different doses of CdCl2 (0 mg/kg, 35 mg/kg, 70 mg/kg and 140 mg/kg) for 90 d. The pathological changes in the spleen, mitochondrial dynamics-related factors, cytochrome P450 (CYP450) enzyme system contents, activities, transcription levels, nuclear receptors (NRs) response molecule levels, and mitochondrial unfolded protein-related factors were detected. The findings indicate that exposure to Cd significantly leads to spleen injury. In Cd groups, the total contents of CYP450 and cytochrome b5 (Cyt b5) increased, and the activities of the CYP450 enzyme system (APND, ERND, AH, and NCR) changed. The NRs response was induced, and the gene levels of AHR/CAR and corresponding CYP450 isoforms (CYP1B1, CYP1A5, CYP1A1, CYP2C18, CYP2D6 and CYP3A4) were found altered. The study found that Cd exposure altered the mRNA expression levels of mitochondrial dynamics-related factors, such as OPA1, Fis1, MFF, Mfn1, and Mfn2, breaking mitochondrial fusion and cleavage and ultimately leading to mitochondrial dysfunction. Changes were detected in the gene levels of several mitochondrial unfolded protein response (mtUPR)-related factors, namely (SIRT1, PGC-1α, NRF1, TFAM, SOD2, and HtrA2). Cd also altered the gene levels of mitochondrial function-related factors (VDAC1, Cyt-C, COA6, PRDX3, RAF and SIRT3). It is showed that Cd can initiate the NRs response, influence the homeostasis of the CPY450 enzyme system, trigger the mtUPR, impair mitochondrial function, and ultimately lead to Cd toxicity in the spleen of chickens.

Fluorescent Pdots Facilitate High-Resolution Mapping of the Intact Meningeal Vascular Network and Eye-Brain Connections.

Meningeal vascular network is significant in neurology and neurosurgery. However, high-resolution imaging of intact meningeal vascular network is lacking. In this work, we develop a practical experimental method to ensure that the intact meninges are morphologically unfolded and fixed in an agarose gel. With the help of high-brightness polymer dots (Pdots) as probe, macroscopic and detailed imaging of the vascular network on the intact dorsal meninges can be performed. Meningeal vessels are symmetrically distributed along the superior sagittal sinus, and the distribution of meningeal vessels had a certain degree of hierarchy. The meninges are thicker blood vessels and capillary networks from the outside to the inside. Moreover, the diameter of the capillaries is 3.96 ± 0.89 µm. Interestingly, meningeal primo vessels in the central nervous system of mice is imaged with the diameter of 4.18 ± 1.18 µm, which has not been reported previously. It is worth mentioning that we found that orthotopic xenografts of brain tumors caused the appearance of corneal neovascularization and morphological changes in optic nerve microvessels. In conclusion, our work provides an effective Pdots-based imaging method for follow-up research on meningeal vascular-related diseases, and illustrates that the eye can serve as a window for the prevention and diagnosis of brain diseases.

Correlation and predictive value of pathological complete response and ultrasound characteristic parameters in neoadjuvant chemotherapy for breast.

BACKGROUND: Breast cancer ranks as one of the most prevalent malignant tumors among women, significantly endangering their health and lives. While radical surgery has been a pivotal method for halting disease progression, it alone is insufficient for enhancing the quality of life for patients. AIM: To investigate the correlation between ultrasound characteristic parameters of breast cancer lesions and clinical efficacy in patients undergoing neoadjuvant chemotherapy (NAC). METHODS: Employing a case-control study design, this research involved 178 breast cancer patients treated with NAC at our hospital from July 2019 to June 2022. According to the Miller-Payne grading system, the pathological response, i.e. efficacy, of the NAC in the initial breast lesion after NAC was evaluated. Of these, 59 patients achieved a pathological complete response (PCR), while 119 did not (non-PCR group). Ultrasound characteristics prior to NAC were compared between these groups, and the association of various factors with NAC efficacy was analyzed using univariate and multivariate approaches. RESULTS: In the PCR group, the incidence of posterior echo attenuation, lesion diameter ≥ 2.0 cm, and Alder blood flow grade ≥ II were significantly lower compared to the non-PCR group (P < 0.05). The area under the curve values for predicting NAC efficacy using posterior echo attenuation, lesion diameter, and Alder grade were 0.604, 0.603, and 0.583, respectively. Also, rates of pathological stage II, lymph node metastasis, vascular invasion, and positive Ki-67 expression were significantly lower in the PCR group (P < 0.05). Logistic regression analysis identified posterior echo attenuation, lesion diameter ≥ 2.0 cm, Alder blood flow grade ≥ II, pathological stage III, vascular invasion, and positive Ki-67 expression as independent predictors of poor response to NAC in breast cancer patients (P < 0.05). CONCLUSION: While ultrasound characteristics such as posterior echo attenuation, lesion diameter ≥ 2.0 cm, and Alder blood flow grade ≥ II exhibit limited predictive value for NAC efficacy, they are significantly associated with poor response to NAC in breast cancer patients.

Generation of a human induced pluripotent stem cell line ZZUNEUi030-A from a female patient carrying a heterozygous CALM2 (c.395 A > T) mutation.

Calmodulin mutations can cause life-threatening long QT syndrome involving CALM1, CALM2, and CALM3. In this study, human induced pluripotent stem cells ZZUNEUi030-A were derived from a female patient with heterozygous CALM2 gene c. 395A â†’ T by Sendai virus non-integrated reprogramming technology. The cell line showed a normal female karyotype (46, XX), expressed pluripotency markers, and had the ability to differentiate into three germ layers in vitro. ZZUNEUi030-A can be used as a cell disease model to study the pathogenesis of LQT caused by calmodulin mutations.

Beyond Single-Cycle Autonomous Molecular Machines: Light-Powered Shuttling in a Multi-Cycle Reaction Network.

Biomolecular machines autonomously convert energy into functions, driving systems away from thermodynamic equilibrium. This energy conversion is achieved by leveraging complex, kinetically asymmetric chemical reaction networks that are challenging to characterize precisely. In contrast, all known synthetic molecular systems in which kinetic asymmetry has been quantified are well described by simple single-cycle networks. Here, we report on a unique light-driven [2]rotaxane that enables the autonomous operation of a synthetic molecular machine with a multi-cycle chemical reaction network. Unlike all prior systems, the present one exploits a photoactive macrocycle, which features a different photoreactivity depending on the binding sites at which it resides. Furthermore, E to Z isomerization reverses the relative affinity of the macrocycle for two binding sites on the axle, resulting in a multi-cycle network. Building on the most recent theoretical advancements, this work quantifies kinetic asymmetry in a multi-cycle network for the first time. Our findings represent the simplest rotaxane capable of autonomous shuttling developed so far and offer a general strategy to generate and quantify kinetic asymmetry beyond single-cycle systems.

Computational underwater ghost imaging based on scattering-and-absorption degradation.

In underwater computational ghost imaging, the presence of scattering and absorption introduces significant degradation, leading to blurring and distortion of illuminating patterns. This work proposes an anti-degradation underwater computational ghost imaging (AUGI) method based on the physical degradation model of underwater forward degradation caused by scattering and absorption. Through AUGI, we can enhance the quality of a reconstructed image by about 10% compared to differential ghost imaging (DGI) as measured by peak signal-to-noise ratio (PSNR) and structural similarity (SSIM), as a result of simulations. We experimentally demonstrate the superior effectiveness of this method in the artificial submarine environment. Additionally, benefitting from its simplicity, this method is expected to be applied across a wide range of underwater ghost imaging applications.

Identification of Aggregation Pheromone as an Attractant for Odontothrips loti, A Serious Thrips Pest on Alfalfa.

Odontothrips loti (Haliday) (Thysanoptera: Thripidae) is one of the most serious pests on alfalfa, causing direct damage by feeding and indirect damage by transmitting plant viruses. This damage causes significant loss in alfalfa production. Semiochemicals offer opportunities to develop new approaches to thrips management. In this study, behavioral responses of female and male adults of O. loti to headspace volatiles from live female and male conspecifics were tested in a Y-tube olfactometer. The results showed that both male and female adults of O. loti were attracted to the odors released by conspecific males but not those released by females. Headspace volatiles released by female and male adults were collected using headspace solid-phase microextraction (HS-SPME). The active compound in the volatiles was identified by gas chromatography-mass spectrometry (GC-MS). The analysis showed that there was one major compound, (R)-lavandulyl (R)-2-methylbutanoate. The attractive activity of the synthetic aggregation pheromone compound was tested under laboratory and field conditions. In an olfactometer, both male and female adults showed significant preference for synthetic (R)-lavandulyl (R)-2-methylbutanoate at certain doses. Lures with synthetic (R)-lavandulyl (R)-2-methylbutanoate significantly increased the trap catches of sticky white traps at doses of 40-80 µg in the field. This study confirmed the production of aggregation pheromone by O. loti male adults and identified its active compound as (R)-lavandulyl (R)-2-methylbutanoate, providing a basis for population monitoring and mass trapping of this pest.

Hemodynamic changes for half cover left subclavian artery ostium during thoracic endovascular aortic repair.

Purpose: Some clinicians use endografts to cover half the left subclavian artery (LSA) ostium to cure some cases with insufficient proximal landing zone (PLZ) in thoracic endovascular aortic repair (TEVAR) treatment. We used computational fluid dynamics (CFD) to study the hemodynamic changes in the LSA because they may cause acute thrombosis or arteriosclerosis. Methods: The digital model of the aortic arch was established and named model A, which only included the supraarch branch of the LSA. By directly covering half of the LSA ostium, which was named as model B. All established models were imported into the Gambit grid division software for grid division and were subsequently imported into the Fluent software for hemodynamic numerical simulation and calculation to analyze the related changes in LSA hemodynamic parameters after stent implantation. Results: Under the same aortic inlet flow, in model B, the local blood flow velocity of the LSA ostium increased and the whole blood flow velocity at the distal end decreased. The average wall shear stress (WSS) of the LSA was significantly decreased. Meanwhile there was an obvious turbulent flow in the LSA lumen, and the related blood flow state was disordered. Conclusion: CFD research confirmed that the implantation of an endograft covering half the LSA ostium can cause obvious hemodynamic changes, which is likely to cause a long-term arteriosclerosis or acute thrombosis of the LSA, finally increasing the risk of stroke. Once this operation is performed in some specific clinical cases for simplicity and economy, it seems that we should actively antiplatelet and follow up regularly.

Single-cell transcriptomics reveals writers of RNA modification-mediated immune microenvironment and cardiac resident Macro-MYL2 macrophages in heart failure.

BACKGROUND: Heart failure (HF), which is caused by cardiac overload and injury, is linked to significant mortality. Writers of RNA modification (WRMs) play a crucial role in the regulation of epigenetic processes involved in immune response and cardiovascular disease. However, the potential roles of these writers in the immunological milieu of HF remain unknown. METHODS: We comprehensively characterized the expressions of 28 WRMs using datasets GSE145154 and GSE141910 to map the cardiac immunological microenvironment in HF patients. Based on the expression of WRMs, the immunological cells in the datasets were scored. RESULTS: Single-cell transcriptomics analysis (GSE145154) revealed immunological dysregulation in HF as well as differential expression of WRMs in immunological cells from HF and non-HF (NHF) samples. WRM-scored immunological cells were positively correlated with the immunological response, and the high WRM score group exhibited elevated immunological cell infiltration. WRMs are involved in the differentiation of T cells and myeloid cells. WRM scores of T cell and myeloid cell subtypes were significantly reduced in the HF group compared to the NHF group. We identified a myogenesis-related resident macrophage population in the heart, Macro-MYL2, that was characterized by an increased expression of cardiomyocyte structural genes (MYL2, TNNI3, TNNC1, TCAP, and TNNT2) and was regulated by TRMT10C. Based on the WRM expression pattern, the transcriptomics data (GSE141910) identified two distinct clusters of HF samples, each with distinct functional enrichments and immunological characteristics. CONCLUSION: Our study demonstrated a significant relationship between the WRMs and immunological microenvironment in HF, as well as a novel resident macrophage population, Macro-MYL2, characterized by myogenesis. These results provide a novel perspective on the underlying mechanisms and therapeutic targets for HF. Further experiments are required to validate the regulation of WRMs and Macro-MYL2 macrophage subtype in the cardiac immunological milieu.

Photocatalytic CO2 Reduction to Ethanol by ZnCo2O4/ZnO Janus Hollow Nanofibers.

Photocatalytic carbon dioxide (CO2) reduction for high-value hydrocarbon fuel production is a promising strategy to tackle global energy demand and climate change. However, this technology faces formidable challenges, primarily stemming from low yield and poor selectivity of C2 products of the desired hydrocarbon fuels. This study reported ZnO/ZnCo2O4 Janus hollow nanofibers (ZnO/ZCO JHNFs) prepared by electrospinning and atomic layer deposition. Photocatalytic tests revealed an ethanol yield of 4.99 µmol g-1 h-1 for ZnO/ZnCo2O4 JHNFs, surpassing mixed ZnO/ZnCo2O4 nanofibers (ZnO/ZCO NFs) by 4.35 times and pure ZnO by 12.7 times. The selectivity of 58.8% is 2.38 and 4.49 times higher than those of ZnO/ZnCo2O4 NFs and ZnO, respectively. These enhancements are attributed to efficient carrier separation facilitated by the ordered internal electric field of the Z-scheme heterojunction interface, validated by the energy band evaluations from experimentation and density functional theory (DFT) simulations and charge separation characterizations of photocurrent, impedance, and photoluminescence spectra. The Janus structure also effectively exposes the surface of ZnCo2O4 to CO2 molecules, increasing the active site availability, as confirmed by BET nitrogen adsorption/desorption, temperature-programmed desorption tests, and DFT adsorption energy calculations. This study proposes a novel approach for efficient photocatalytic hydrocarbon fuel production, with potential applications in energy and climate crisis mitigation.

Decoupling the air sensitivity of Na-layered oxides.

Air sensitivity remains a substantial barrier to the commercialization of sodium (Na)-layered oxides (NLOs). This problem has puzzled the community for decades because of the complexity of interactions between air components and their impact on both bulk and surfaces of NLOs. We show here that water vapor plays a pivotal role in initiating destructive acid and oxidative degradations of NLOs only when coupled with carbon dioxide or oxygen, respectively. Quantification analysis revealed that reducing the defined cation competition coefficient (η), which integrates the effects of ionic potential and sodium content, and increasing the particle size can enhance the resistance to acid attack, whereas using high-potential redox couples can eliminate oxidative degradation. These findings elucidate the underlying air deterioration mechanisms and rationalize the design of air-stable NLOs.

Variation in plant functional traits explains the substitution distribution and allocation strategy of Stipa species across natural grasslands of Ningxia, Northern China.

Functional traits reflect plants' adaptability to their environment, and environmental gradients influence their distribution. But few studies have investigated the link between these traits and species substitution patterns or the relevant ecological factors. We measured the aboveground (leaf) and belowground (root) functional traits of Stipa species in 17 plots across natural grasslands in Ningxia in Northern China. Redundancy analysis was used to explore the relationships between Stipa's functional traits and its species substitution distribution. Then, on the species substitution gradient, principal component analysis (PCA) was used to verify and quantify the leaf economic spectrum (LES), root economic spectrum (RES), and whole-plant economic spectrum (WPES), with the relation between these spectra investigated by fitting standardized major axis regressions. The effects of aboveground, belowground, and whole-plant ecological factors were quantified and ranked by variance decomposition and hierarchical partitioning. Our results showed that functional traits drive the substitution distribution of Stipa species, in being variously coupled with its desert, typical, and meadow steppe habitat types. The leaf, root, and whole-plant economic spectra of Stipa species in desert steppe exhibit a "quick investment-acquisition" strategy. In typical steppe, the leaf and whole-plant economic spectra of Stipa species correspond to a "fast investment-acquisition" strategy, whereas the root economic spectrum adopts a "slow investment-acquisition" strategy. On meadow steppe, the leaf, root, and whole-plant economic spectra of Stipa species similarly adopt a "slow investment-acquisition" strategy. Finally, when considering the environmental factors involved, we find that the substitution distribution of Stipa spp. is chiefly a response to shifting soil patterns, these mainly driven by soil total nitrogen and nitrogen/phosphorus ratio. Collectively, these findings provide an important reference for the ecological restoration and reconstruction of grassland ecosystems, to better understand the relationship between plant functional traits and ecological niche attributes, and thus guide the reasonable restoration of grassland vegetation.

Canopy and understory nitrogen additions differently affect soil microbial residual carbon in a temperate forest.

Atmospheric nitrogen (N) deposition in forests can affect soil microbial growth and turnover directly through increasing N availability and indirectly through altering plant-derived carbon (C) availability for microbes. This impacts microbial residues (i.e., amino sugars), a major component of soil organic carbon (SOC). Previous studies in forests have so far focused on the impact of understory N addition on microbes and microbial residues, but the effect of N deposition through plant canopy, the major pathway of N deposition in nature, has not been explicitly explored. In this study, we investigated whether and how the quantities (25 and 50 kg N ha-1 year-1) and modes (canopy and understory) of N addition affect soil microbial residues in a temperate broadleaf forest under 10-year N additions. Our results showed that N addition enhanced the concentrations of soil amino sugars and microbial residual C (MRC) but not their relative contributions to SOC, and this effect on amino sugars and MRC was closely related to the quantities and modes of N addition. In the topsoil, high-N addition significantly increased the concentrations of amino sugars and MRC, regardless of the N addition mode. In the subsoil, only canopy N addition positively affected amino sugars and MRC, implying that the indirect pathway via plants plays a more important role. Neither canopy nor understory N addition significantly affected soil microbial biomass (as represented by phospholipid fatty acids), community composition and activity, suggesting that enhanced microbial residues under N deposition likely stem from increased microbial turnover. These findings indicate that understory N addition may underestimate the impact of N deposition on microbial residues and SOC, highlighting that the processes of canopy N uptake and plant-derived C availability to microbes should be taken into consideration when predicting the impact of N deposition on the C sequestration in temperate forests.

Functional traits of exotic submerged macrophytes mediate diversity-invasibility relationship in freshwater communities under eutrophication.

Plant diversity may respond differently in terms of whether it can drive plant invasions in freshwater ecosystem. Linkages and interactions between diversity and invasibility have not been clearly resolved, and it is unclear how nutrient enrichment (e.g., eutrophication) will affect this relationship. As a key predictor of plant growth, the ability of functional traits to mediate trade-offs in the diversity-invasibility relationship is unknown. Here, we conducted a series of experiments to determine the role of exotic plant functional traits in the diversity-invasibility relationship of submerged macrophyte communities under eutrophication. We selected common native and exotic submerged macrophytes in the subtropics to construct different diverse submerged macrophyte communities to simulate invasion. Meanwhile, to test the adaptability and importance of functional traits, we experimentally verified the differences in functional traits between exotic and native species. Our results showed a positive correlation between native plant diversity and community invasibility. Moreover, the invader's performance was predominantly determined by functional traits of exotic species, such as plant biomass and tissue nutrients, which were significantly altered by species diversity. Furthermore, our results suggested that functional traits contribute significantly more to the invasiveness of exotic submerged macrophytes than the other factors to which they are subjected. Plant functional traits can mediate the diversity-invasibility relationship because of the higher intrinsic dominance of exotic submerged macrophyte species. In summary, our study revealed diversity-invasibility relationship in submerged macrophyte communities and highlighted functional traits as key drivers of invasion of high-risk exotic submerged macrophyte species. Although previous studies have elucidated the importance of functional trait studies for plant invasions, our study provides the only current evidence demonstrating the important role of invaders' functional traits in mediating the diversity-invasibility relationship. This novel perspective offers valuable insights into the management and control of invasive aquatic plants.

Resting-state dynamic functional connectivity in major depressive disorder: A systematic review.

As a novel measure, dynamic functional connectivity (dFC) provides insight into the dynamic nature of brain networks and their interactions in resting-state, surpassing traditional static functional connectivity in pathological conditions such as depression. Since a comprehensive review is still lacking, we then reviewed forty-five eligible papers to explore pathological mechanisms of major depressive disorder (MDD) from perspectives including abnormal brain regions and functional networks, brain state, topological properties, relevant recognition, along with longitudinal studies. Though inconsistencies could be found, common findings are: (1) From different perspectives based on dFC, default-mode network (DMN) with its subregions exhibited a close relation to the pathological mechanism of MDD. (2) With a corrupted integrity within large-scale functional networks and imbalance between them, longer fraction time in a relatively weakly-connected state may be a possible property of MDD concerning its relation with DMN. Abnormal transition frequencies between states were correlated to the severity of MDD. (3) Including dynamic properties in topological network metrics enhanced recognition effect. In all, this review summarized its use for clinical diagnosis and treatment, elucidating the non-stationary of MDD patients' aberrant brain activity in the absence of stimuli and bringing new views into its underlying neuro mechanism.

Pre- vs Post-Operative Levator Ani Subtended Volume in Patients Undergoing Hysterectomy: A Comparative Imaging Study.

INTRODUCTION AND HYPOTHESIS: The effects of hysterectomy on pelvic floor function remain uncertain, with the levator ani muscle (LAM) playing a critical role in pelvic support. The levator ani subtended volume (LASV) is an objective measure of the LAM's anatomical volume, derived from magnetic resonance imaging (MRI). This study was aimed at assessing the consistency between MRI and computed tomography (CT) in quantifying LASV, and to investigate the effect of hysterectomy on the LAM. METHODS: This retrospective study analyzed a cohort of 55 hysterectomy patients, utilizing pre-operative pelvic MRI and post-operative CT scans to measure the LASV. To evaluate the consistency between MRI and CT, the study employed the intraclass correlation coefficient and Bland-Altman agreement analysis in a subset of 32 patients with both pre-operative scans. A paired-samplet test was used to analyze LASV changes pre- and post-hysterectomy, and linear regression analysis was performed to account for potential risk factors that may influence post-operative LASV. RESULTS: High consistency between MRI and CT in measuring LASV was found, with an ICC of 0.911. We observed a significant increase in LASV following hysterectomy, with mean volume pre- and post-operatively of 16.66 cm3 and 18.87 cm3 respectively. Age and body mass index were significant predictors of post-hysterectomy LASV, whereas parity and the type of hysterectomy had no significant impact. CONCLUSIONS: Hysterectomy significantly affects the LAM, resulting in an increase in post-operative LASV. Moreover, this study verifies that MRI and CT can be used interchangeably for LASV measurements in clinical practice.

BSA-stabilized selenium nanoparticles ameliorate intracerebral hemorrhage's-like pathology by inhibiting ferroptosis-mediated neurotoxicology via Nrf2/GPX4 axis activation.

Intracerebral hemorrhage (ICH) is a prevalent hemorrhagic cerebrovascular emergency. Alleviating neurological damage in the early stages of ICH is critical for enhancing patient prognosis and survival rate. A novel form of cell death called ferroptosis is intimately linked to hemorrhage-induced brain tissue injury. Although studies have demonstrated the significant preventive impact of bovine serum albumin-stabilized selenium nanoparticles (BSA-SeNPs) against disorders connected to the neurological system, the neuroprotective effect on the hemorrhage stroke and the mechanism remain unknown. Therefore, based on the favorable biocompatibility of BSA-SeNPs, h-ICH (hippocampus-intracerebral hemorrhage) model was constructed to perform BSA-SeNPs therapy. As expected, these BSA-SeNPs could effectively improve the cognitive deficits and ameliorate the damage of hippocampal neuron. Furthermore, BSA-SeNPs reverse the morphology of mitochondria and enhanced the mitochondrial function, evidenced by mitochondrial respiration function (OCR) and mitochondrial membrane potential (MMP). Mechanistically, BSA-SeNPs could efficiently activate the Nrf2 to enhance the expression of antioxidant GPX4 at mRNA and protein levels, and further inhibit lipid peroxidation production in erastin-induced ferroptotic damages. Taken together, this study not only sheds light on the clinical application of BSA-SeNPs, but also provides its newly theoretical support for the strategy of the intervention and treatment of neurological impairment following ICH.

Dissecting prostate Cancer: Single-Cell insight into Macrophage Diversity, molecular Prognosticators, and the role of Peptidylprolyl Isomerase F.

BACKGROUND: Prostate cancer remains a prominent challenge in oncology, with advanced stages showing poor prognosis. The tumor microenvironment (TME), and particularly tumor-associated macrophages (TAMs), plays a crucial role in disease progression. This study explores the single-cell transcriptomics of prostate cancer, determines macrophage heterogeneity, identifies prognostic gene markers, and assesses the role of PPIF in TAMs. METHODS: Single-cell RNA sequencing data from the GEO database (GSE176031) and transcriptome data from the TCGA were processed to characterize cell populations and identify prognostic genes in prostate cancer. Macrophage subpopulations were examined through clustering, followed by gene set scoring based on migration, activation, and proliferation. PPIF expression in macrophages was investigated using multiplex immunofluorescence staining on matched prostate cancer and adjacent non-tumoral tissues. RESULTS: The single-cell analysis identified 9,178 cells, categorized into 10 principal cell types, with macrophages constituting a significant part of the immune microenvironment. Four macrophage subgroups demonstrated distinct functional pathways: phagocytic, immune-regulatory, and proliferative. A total of 39 genes correlated with prostate cancer prognosis were identified, of which 10 carried the most significant prognostic information. Peptidylprolyl Isomerase F (PPIF) expression was significantly higher in TAMs from tumor tissue than normal tissue, indicating its potential regulatory role in the immune microenvironment. CONCLUSION: The intricate cellular architecture of the prostate cancer TME has been elucidated, with a focus on macrophage heterogeneity and functional specialization. Prognostic genes, including PPIF, were associated with survival outcomes, providing potential therapeutic targets. PPIF's prominent expression in TAMs may serve as a lever in cancer progression, warranting further investigation as a biomarker and a molecule of interest for therapeutic targeting within the prostate cancer milieu.

Simultaneous Detection of Helicobacter pylori and Clarithromycin Resistance Mutations Using RAA-CRISPR/Cas13a Assay.

Background: Infection caused by Helicobacter pylori (H. pylori) affects approximately 50% of the global population. It is a major pathogenic factor for chronic gastritis and gastric cancer. Besides, the resistance to antibiotics such as clarithromycin could reduce the eradication rate. Currently, there is an urgent need for a swift, easy to perform, and highly sensitive detection method for H. pylori and clarithromycin resistance. Methods: We used FAM/Digoxin labeled primers to amplify specific H. pylori 23S rRNA fragments by Recombinase Aided Amplification (RAA), and resistance mutations were distinguished using CRISPR/Cas13a system combined with lateral flow strip. Twenty-eight saliva samples were analyzed using qPCR, gene sequencing and this method to evaluate the detection efficiency. Results: We developed a simultaneous detection method for H. pylori and clarithromycin resistance mutations named sensitive H. pylori easy-read dual detection (SHIELD). The results showed both A2142G and A2143G mutant DNAs causing clarithromycin resistance could be distinguished from the wild type with a concentration of 50 copies/µL, and no cross-reaction with other 5 common gastrointestinal bacteria was observed. For the detection of H. pylori in 28 saliva samples, the positive predictive value of this method was 100% (19/19) in comparison with qPCR. For detecting clarithromycin resistance, the positive predictive value of this method was 84.6% (11/13) compared with gene sequencing. Conclusion: SHIELD assay showed high sensitivity and specificity in detecting H. pylori and clarithromycin resistance mutations. It could be a potential measure in the rapid detection of H. pylori, large-scale screening and guiding clinical medication.