Atomically dispersed ternary FeCoNb active sites anchored on N-doped honeycomb-like mesoporous carbon for highly catalytic degradation of 4-nitrophenol.

In the last decades, 4-nitrophenol is regarded as one of highly toxic organic pollutants in industrial wastewater, which attracts great concern to earth sustainability. Herein, atomically dispersed ternary FeCoNb active sites were incorporated into nitrogen-doped honeycomb-like mesoporous carbon (termed FeCoNb/NHC) by a two-step pyrolysis strategy, whose morphology, structure and size were characterized by a set of techniques. Further, the catalytic activity and reusability of the as-prepared FeCoNb/NHC were rigorously examined by using 4-NP catalytic hydrogenation as a proof-of-concept model. The influence of the secondary pyrolysis temperature on the catalytic performance was investigated, combined by illuminating the catalytic mechanism. The resultant catalyst exhibited significantly enhanced catalytic features with a normalized rate constant (kapp) of 1.2 × 104 min-1g-1 and superior stability, surpassing the home-made catalysts in the control groups and earlier research. This study provides some constructive insights for preparation of high-efficiency and cost-effectiveness single-atom nanocatalysts in organic pollutants environmental remediation.

Ubiquitin-specific protease UBP14 stabilizes HY5 by deubiquitination to promote photomorphogenesis in Arabidopsis thaliana.

Transcription factor ELONGATED HYPOCOTYL5 (HY5) is the central hub for seedling photomorphogenesis. E3 ubiquitin (Ub) ligase CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) inhibits HY5 protein accumulation through ubiquitination. However, the process of HY5 deubiquitination, which antagonizes E3 ligase-mediated ubiquitination to maintain HY5 homeostasis has never been studied. Here, we identified that Arabidopsis thaliana deubiquitinating enzyme, Ub-SPECIFIC PROTEASE 14 (UBP14) physically interacts with HY5 and enhances its protein stability by deubiquitination. The da3-1 mutant lacking UBP14 function exhibited a long hypocotyl phenotype, and UBP14 deficiency led to the failure of rapid accumulation of HY5 during dark to light. In addition, UBP14 preferred to stabilize nonphosphorylated form of HY5 which is more readily bound to downstream target genes. HY5 promoted the expression and protein accumulation of UBP14 for positive feedback to facilitate photomorphogenesis. Our findings thus established a mechanism by which UBP14 stabilizes HY5 protein by deubiquitination to promote photomorphogenesis in A. thaliana.

Low Rh doping accelerated HER/OER bifunctional catalytic activities of nanoflower-like Ni-Co sulfide for greatly boosting overall water splitting.

Facile synthesis of high-efficiency and stable bifunctional electrocatalyst is essential for producing clean hydrogen in energy storage systems. Herein, low Rh-doped flower-like Ni3S2/Co3S4 heterostructures were facilely prepared on porous nickel foam (labeled Rh-Ni3S2/Co3S4/NF) by a hydrothermal method. The correlation of the precursors types with the morphological structures and catalytic properties were rigorously investigated for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in the control groups. The low Rh doping within the catalyst played important role in boosting the catalytic characteristics. The resulting catalyst showed the smaller overpotentials of 197 and 78 mV to drive a current density of 10 mA cm-2 for the OER and HER in alkaline electrolyte, respectively. And the potential only required 1.71 V to drive a current density of 100 mA cm-2 in a water splitting device. It reflects excellent overall water splitting of the home-made Rh-Ni3S2/Co3S4/NF. This strategy shed some constructive light for preparing transition metal sulfide-based electrocatalysts in water splitting devices.

3D chromatin structures associated with ncRNA roX2 for hyperactivation and coactivation across the entire X chromosome.

The three-dimensional (3D) organization of chromatin within the nucleus is crucial for gene regulation. However, the 3D architectural features that coordinate the activation of an entire chromosome remain largely unknown. We introduce an omics method, RNA-associated chromatin DNA-DNA interactions, that integrates RNA polymerase II (RNAPII)-mediated regulome with stochastic optical reconstruction microscopy to investigate the landscape of noncoding RNA roX2-associated chromatin topology for gene equalization to achieve dosage compensation. Our findings reveal that roX2 anchors to the target gene transcription end sites (TESs) and spreads in a distinctive boot-shaped configuration, promoting a more open chromatin state for hyperactivation. Furthermore, roX2 arches TES to transcription start sites to enhance transcriptional loops, potentially facilitating RNAPII convoying and connecting proximal promoter-promoter transcriptional hubs for synergistic gene regulation. These TESs cluster as roX2 compartments, surrounded by inactive domains for coactivation of multiple genes within the roX2 territory. In addition, roX2 structures gradually form and scaffold for stepwise coactivation in dosage compensation.

Revolutionizing Senescence Detection: Advancements from Traditional Methods to Cutting-Edge Techniques.

The accumulation of senescent cells is an important factor in the complex progression of aging, with significant implications for the development of numerous diseases. Thus, understanding the fundamental mechanisms of senescence is paramount for advancing preventive and therapeutic approaches to age-related conditions. Important to this pursuit is the precise identification and examination of senescent cells, contingent upon the recognition of specific biomarkers. Historically, detection methods relied on assessing molecular protein and mRNA levels and various staining techniques. While these conventional approaches have contributed substantially to the field, they possess limitations in capturing the dynamic evolution of cellular aging in real time. The emergence of novel technologies has led to a paradigm shift in senescence research. Gene-edited mouse models and the application of advanced probes have revolutionized our ability to detect senescent cells. These cutting-edge methodologies provide a more detailed and accurate means of dynamically monitoring, characterizing and potentially eliminating senescent cells, thus enhancing our understanding of the complex mechanisms of aging. This review comprehensively explores both traditional and innovative senescent cell detection methods, elucidating their advantages, limitations and implications for future investigations and could serve as a comprehensive guide and catalyst for further advancements in the understanding of aging and associated pathologies.

Genome assembly of redclaw crayfish (Cherax quadricarinatus) provides insights into its immune adaptation and hypoxia tolerance.

BACKGROUND: The introduction of non-native species is a primary driver of biodiversity loss in freshwater ecosystems. The redclaw crayfish (Cherax quadricarinatus) is a freshwater species that exhibits tolerance to hypoxic stresses, fluctuating temperatures, high ammonia concentration. These hardy physiological characteristics make C. quadricarinatus a popular aquaculture species and a potential invasive species that can negatively impact tropical and subtropical ecosystems. Investigating the genomic basis of environmental tolerances and immune adaptation in C. quadricarinatus will facilitate the development of management strategies of this potential invasive species. RESULTS: We constructed a chromosome-level genome of C. quadricarinatus by integrating Nanopore and PacBio techniques. Comparative genomic analysis suggested that transposable elements and tandem repeats drove genome size evolution in decapod crustaceans. The expansion of nine immune-related gene families contributed to the disease resistance of C. quadricarinatus. Three hypoxia-related genes (KDM3A, KDM5A, HMOX2) were identified as being subjected to positive selection in C. quadricarinatus. Additionally, in vivo analysis revealed that upregulating KDM5A was crucial for hypoxic response in C. quadricarinatus. Knockdown of KDM5A impaired hypoxia tolerance in this species. CONCLUSIONS: Our results provide the genomic basis for hypoxic tolerance and immune adaptation in C. quadricarinatus, facilitating the management of this potential invasive species. Additionally, in vivo analysis in C. quadricarinatus suggests that the role of KDM5A in the hypoxic response of animals is complex.

Additional Yield of Random Biopsy in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: There are limited clinical data regarding the additional yields of random biopsies (RBs) during colorectal cancer surveillance in patients with inflammatory bowel disease. To assess the additional yield of RB, a systematic review and meta-analysis was conducted. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies investigating the preferred colonoscopy surveillance approach for inflammatory bowel disease patients. The additional yield, detection rate, procedure time, and withdrawal time were pooled. RESULTS: Thirty-seven studies (48 arms) were included in the meta-analysis with 9051 patients. The additional yields of RB were 10.34% in per-patient analysis and 16.20% in per-lesion analysis. The detection rates were 1.31% and 2.82% in per-patient and per-lesion analysis, respectively. Subgroup analysis showed a decline in additional yields from 14.43% to 0.42% in the per-patient analysis and from 19.20% to 5.32% in the per-lesion analysis for studies initiated before and after 2011. In per-patient analysis, the additional yields were 4.83%, 10.29%, and 56.05% for primary sclerosing cholangitis (PSC) proportions of 0% to 10%, 10% to 30%, and 100%, respectively. The corresponding detection rates were 0.56%, 1.40%, and 19.45%. In the per-lesion analysis, additional yields were 11.23%, 21.06%, and 45.22% for PSC proportions of 0% to 10%, 10% to 30%, and 100%, respectively. The corresponding detection rates were 2.09%, 3.58%, and 16.24%. CONCLUSIONS: The additional yields of RB were 10.34% and 16.20% for per-patient and per-lesion analyses, respectively. Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full high-definition equipment should consider incorporating RB in the standard colonoscopy surveillance for inflammatory bowel disease patients, especially in those with PSC.

[Material basis of kidney Yang deficiency rats before and after salt processing of Dipsacus asper based on spectrum-effect relationship].

This paper aims to study the spectrum-effect relationship between the fingerprints before and after salt processing of Dipsacus asper and the efficacy of warming and tonifying kidney Yang and find the main active components against kidney Yang deficiency before and after salt processing of D. asper, so as to provide the basis for clarifying the effect of salt processing on kidney Yang deficiency. The HPLC fingerprint before and after salt processing of D. asper was established by the HPLC-DAD. 15 common peaks were obtained, and 11 components were identified. The content changes of various components in rat serum were detected, and the difference in efficacy before and after salt processing was compared. The results of pharmacological experiments showed that salt processing of D. asper could enhance the kidney index. At the same dose, there was a significant difference between the raw D. asper and D. asper after salt processing groups. Compared with the model group, the contents of ACTH, cAMP, CORT, E_2, GH, Na~+-K~+-ATPase, T, and T4 in the serum of rats in the administration group increased to a certain extent, and the contents of cGMP and TNF-α decreased to a certain extent. Among them, there were significant differences in the above indexes in the serum of rats in the high-dose group of raw D. asper, middle-dose group of D. asper after salt processing, high-dose group of D. asper after salt processing, and the positive drug group. The overall results showed that D. asper after salt processing was more effective than raw D. asper in preventing kidney yang deficiency. The efficacy of D. asper was evaluated by grey correlation analysis, entropy method, and Pearson correlation analysis, and the components of D. asper after salt processing against kidney yang deficiency were screened out. According to the results of correlation degree ranking, the components with increased ranking before and after salt processing of D. asper were loganin, chlorogenic acid, dipsacoside A, asperosaponin Ⅵ, caffeic acid, and isochlorogenic acid B. It was preliminarily speculated that these compounds may be the potential pharmacodynamic components for the treatment of kidney yang deficiency before and after salt processing of D. asper. The changing components before and after the salt processing of D. asper were determined, which proved that D. asper after salt processing was superior to D. asper in the treatment of kidney yang deficiency. The spectrum-effect relationship between the efficacy of D. asper before and after salt processing and the treatment of kidney yang deficiency was established, which laid a foundation for the subsequent study on the pharmacodynamic components and molecular mechanism of salt processing of D. asper.

Personal exposure to airborne organic pollutants and lung function changes among healthy older adults.

Epidemiological evidence on the impact of airborne organic pollutants on lung function among the elderly is limited, and their underlying biological mechanisms remain largely unexplored. Herein, a longitudinal panel study was conducted in Jinan, Shandong Province, China, involving 76 healthy older adults monitored over a span of five months repetitively. We systematically evaluated personal exposure to a diverse range of airborne organic pollutants using a wearable passive sampler and their effects on lung function. Participants' pulmonary function indicators were assessed, complemented by comprehensive multi-omics analyses of blood and urine samples. Leveraging the power of interaction analysis, causal inference test (CIT), and integrative pathway analysis (IPA), we explored intricate relationships between specific organic pollutants, biomolecules, and lung function deterioration, elucidating the biological mechanisms underpinning the adverse impacts of these pollutants. We observed that bis (2-chloro-1-methylethyl) ether (BCIE) was significantly associated with negative changes in the forced vital capacity (FVC), with glycerolipids mitigating this adverse effect. Additionally, 31 canonical pathways [e.g., high mobility group box 1 (HMGB1) signaling, phosphatidylinositol 3-kinase (PI3K)/AKT pathway, epithelial mesenchymal transition, and heme and nicotinamide adenine dinucleotide (NAD) biosynthesis] were identified as potential mechanisms. These findings may hold significant implications for developing effective strategies to prevent and mitigate respiratory health risks arising from exposure to such airborne pollutants. However, due to certain limitations of the study, our results should be interpreted with caution.

The Kinematic Models of the SINS and Its Errors on the SE(3) Group in the Earth-Centered Inertial Coordinate System.

In this paper, the kinematic models of the Strapdown Inertial Navigation System (SINS) and its errors on the SE(3) group in the Earth-Centered Inertial frame (ECI) are established. On the one hand, with the ECI frame being regarded as the reference, based on the joint representation of attitude and velocity on the SE(3) group, the dynamic of the local geographic coordinate system (n-frame) and the body coordinate system (b-frame) evolve on the differentiable manifold, respectively, and the high-order expansion of the Baker-Campbell-Haussdorff equation compensates for the non-commutative motion errors stimulated by strong maneuverability. On the other hand, the kinematics of the left- and right-invariant errors of the n-frame and the b-frame on the SE(3) group are separately derived, where the errors of the b-frame completely depend on inertial sensor errors, while the errors of the n-frame rely on position errors and velocity errors. In this way, the errors brought by the inconsistency of the reference coordinate system are tackled, and a novel attitude error definition is introduced to separate and decouple the factors affecting the dynamic of the n-frame errors and the b-frame errors for better attitude estimation. Through a turntable experiment and a car-mounted field experiment, the effectiveness of the proposed kinematic models in estimating attitude has been verified, with a remarkable improvement in yaw angle accuracy in the case of large initial misalignment angles, and the models developed have better robustness compared to the traditional SE(3) group-based model.

Palladium-Catalyzed Enantioselective Multicomponent Cross-Coupling of Trisubstituted Olefins.

The development of a catalytic method for stereogenic carbon center formation holds immense significance in organic synthesis. Transition-metal-catalyzed cross-coupling reaction has been regarded as a straightforward and efficient tool for stereoselectively forging C-C bond. Nevertheless, the creation of acyclic all-carbon quaternary-containing vicinal stereocenters remains notoriously challenging within the domain of cross-coupling chemistry despite their prominence in various bioactive small molecules. Herein, we describe a palladium-catalyzed asymmetric multicomponent cross-coupling of trisubstituted alkene with aryl diazonium salts and arylboronic acids to realize the formation of tertiary-quaternary carbon centers with high regio-, distereo-, and enantioselectivity. Specifically, the precise manipulation of the stereoconfiguration of trisubstituted alkenes enables the divergent stereoselective cross-coupling reaction, thus allowing for the facile construction of all four enantiomers. Harnessing the ligand-swap strategy involving a chiral bisoxazoline and an achiral fumarate individually accelerates the enantioselective migratory insertion and reductive elimination step in the cross-coupling process, as supported by density functional theory (DFT) calculations, thus obviating the requirement for a neighboring directing group within the internal olefin skeleton.

NAC transcription factor ATAF1 negatively modulates the PIF-regulated hypocotyl elongation under a short-day photoperiod.

Day length modulates hypocotyl elongation in seedlings to optimize their overall fitness. Variations in cell growth-associated genes are regulated by several transcription factors. However, the specific transcription factors through which the plant clock increases plant fitness are still being elucidated. In this study, we identified the no apical meristem, Arabidopsis thaliana-activating factor (ATAF-1/2), and cup-shaped cotyledon (NAC) family transcription factor ATAF1 as a novel repressor of hypocotyl elongation under a short-day (SD) photoperiod. Variations in day length profoundly affected the transcriptional and protein levels of ATAF1. ATAF1-deficient mutant exhibited increased hypocotyl length and cell growth-promoting gene expression under SD conditions. Moreover, ATAF1 directly targeted and repressed the expression of the cycling Dof factor 1/5 (CDF1/5), two key transcription factors involved in hypocotyl elongation under SD conditions. Additionally, ATAF1 interacted with and negatively modulated the effects of phytochrome-interacting factor (PIF), thus inhibiting PIF-promoted gene expression and hypocotyl elongation. Taken together, our results revealed ATAF1-PIF as a crucial pair modulating the expression of key transcription factors to facilitate plant growth during day/night cycles under fluctuating light conditions.

Eye movement intervention facilitates concurrent perception and memory processing.

A widely used psychotherapeutic treatment for post-traumatic stress disorder (PTSD) involves performing bilateral eye movement (EM) during trauma memory retrieval. However, how this treatment-described as eye movement desensitization and reprocessing (EMDR)-alleviates trauma-related symptoms is unclear. While conventional theories suggest that bilateral EM interferes with concurrently retrieved trauma memories by taxing the limited working memory resources, here, we propose that bilateral EM actually facilitates information processing. In two EEG experiments, we replicated the bilateral EM procedure of EMDR, having participants engaging in continuous bilateral EM or receiving bilateral sensory stimulation (BS) as a control while retrieving short- or long-term memory. During EM or BS, we presented bystander images or memory cues to probe neural representations of perceptual and memory information. Multivariate pattern analysis of the EEG signals revealed that bilateral EM enhanced neural representations of simultaneously processed perceptual and memory information. This enhancement was accompanied by heightened visual responses and increased neural excitability in the occipital region. Furthermore, bilateral EM increased information transmission from the occipital to the frontoparietal region, indicating facilitated information transition from low-level perceptual representation to high-level memory representation. These findings argue for theories that emphasize information facilitation rather than disruption in the EMDR treatment.

3D drift correction for super-resolution imaging with a single laser light.

Single-molecule localization microscopy (SMLM) enables three-dimensional (3D) super-resolution imaging of nanoscale structures within biological samples. However, prolonged acquisition introduces a drift between the sample and the imaging system, resulting in artifacts in the reconstructed super-resolution image. Here, we present a novel, to our knowledge, 3D drift correction method that utilizes both the reflected and scattered light from the sample. Our method employs the reflected light of a near-infrared (NIR) laser for focus stabilization while synchronously capturing speckle images to estimate the lateral drift. This approach combines high-precision active compensation in the axial direction with lateral post-processing compensation, achieving the abilities of 3D drift correction with a single laser light. Compared to the popular localization events-based cross correlation method, our approach is much more robust, especially for datasets with sparse localization points.

[Establishment and transfer management of veno-arterial extracorporeal membrane oxygenation in patients with difficult downtime during cardiopulmonary bypass surgery].

OBJECTIVE: To investigate the establishment method, coordination points and safe transport management strategy of vena-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with downtime difficulties during cardiopulmonary bypass (CPB). METHODS: A observation study was conducted. The patients admitted to the department of critical care medicine of the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) from January 2020 to October 2022 were enrolled. These patients could not be separated from CPB and received VA-ECMO-assisted CPB surgery. The clinical data of the patients were recorded, including the basic information of the patients, the data of VA-ECMO establishment and transport process, the clinical indicators before and after VA-ECMO installation, the operation data of VA-ECMO and clinical outcomes. The experience was summarized from the aspects of extracorporeal membrane oxygenation (ECMO) establishment, transport process, team cooperation, and adverse events during transport. The clinical indicators before and after ECMO operation were compared. According to whether ECMO was successfully weaned, the patients were divided into a successful weaning group and a failure weaning group, and the clinical data between the two groups were compared. RESULTS: Eighteen patients who underwent VA-ECMO-assisted CPB were enrolled, including 10 males and 8 females. The average age was (56.7±12.3) years old. Preoperative left ventricular ejection fraction (LVEF) was 0.46±0.10, and the main reasons for switching to VA-ECMO assistance included right ventricular systolic weakness in 6 cases, total cardiac systolic weakness in 5 cases, left ventricular systolic weakness in 4 cases, high pulmonary arterial pressure in 2 cases, and intractable ventricular fibrillation in 1 case. Among the 18 patients transferred from CPB to VA-ECMO, 10 cases were successfully weaned and 8 cases failed. In ICU, 8 cases survived, 5 cases died, and 5 cases gave up treatment and discharged. The average time for successful CPB to VA-ECMO establishment was (24.6±7.4) minutes, initial blood flow was (3.3±0.4) L/min, and transit time was (8.4±1.5) minutes. ECMO-assisted duration averaged (82.0±69.3) hours. Adverse events occurred in 9 patients during ECMO establishment and transfer. Post-ECMO onboarding for 4 hours, significant improvements were noted in blood lactic acid (Lac), pH value, mean arterial pressure (MAP), central venous oxygen saturation (ScvO2) as compared with pre-ECMO onboarding [Lac (mmol/L): 10.5±7.0 vs. 15.2±6.8, pH value: 7.38±0.92 vs. 7.26±0.87, MAP (mmHg, 1 mmHg ≈ 0.133 kPa): 74.9±13.7 vs. 58.4±17.0, ScvO2: 0.678±0.065 vs. 0.611±0.061, all P < 0.01], and vasoactive-inotropic score (VIS) was also decreased (39.8±29.8 vs. 68.9±64.4, P < 0.01). Compared with successful weaning group, the patients in the failed weaning group exhibited higher pre-machine Lac (mmol/L: 18.8±7.8 vs. 12.3±4.3, P < 0.05), longer CPB time [minutes: 238.0 (208.8, 351.2) vs. 200.0 (185.8, 217.0), P < 0.05], and shorter ECMO-assisted time [hours: 19.5 (11.0, 58.8) vs. 94.5 (65.8, 179.8), P < 0.01]. However, there was no statistically significant difference in pre-machine pH value, ScvO2, MAP, VIS score, and initial blood flow and establishment time of ECMO between the two groups. CONCLUSIONS: VA-ECMO is an effective circulatory aid for CPB surgery that cannot be weaned after CPB. The establishment and transfer of CPB "bridge" to ECMO aid depends on multi-disciplinary treatment (MDT) cooperation. The success rate of ECMO weaning is related to the Lac and CPB duration. If it is not possible to detach from the CPB successfully, VA-ECMO should be initiated as early as possible.

TEAD2 initiates ground-state pluripotency by mediating chromatin looping.

The transition of mouse embryonic stem cells (ESCs) between serum/LIF and 2i(MEK and GSK3 kinase inhibitor)/LIF culture conditions serves as a valuable model for exploring the mechanisms underlying ground and confused pluripotent states. Regulatory networks comprising core and ancillary pluripotency factors drive the gene expression programs defining stable naïve pluripotency. In our study, we systematically screened factors essential for ESC pluripotency, identifying TEAD2 as an ancillary factor maintaining ground-state pluripotency in 2i/LIF ESCs and facilitating the transition from serum/LIF to 2i/LIF ESCs. TEAD2 exhibits increased binding to chromatin in 2i/LIF ESCs, targeting active chromatin regions to regulate the expression of 2i-specific genes. In addition, TEAD2 facilitates the expression of 2i-specific genes by mediating enhancer-promoter interactions during the serum/LIF to 2i/LIF transition. Notably, deletion of Tead2 results in reduction of a specific set of enhancer-promoter interactions without significantly affecting binding of chromatin architecture proteins, CCCTC-binding factor (CTCF), and Yin Yang 1 (YY1). In summary, our findings highlight a novel prominent role of TEAD2 in orchestrating higher-order chromatin structures of 2i-specific genes to sustain ground-state pluripotency.

Efficient energy transport throughout conical implosions.

The double-cone ignition (DCI) scheme has been proposed as one of the alternative approaches to inertial confinement fusion, based on direct-drive and fast-ignition, in order to reduce the requirement for the driver energy. To evaluate the conical implosion energetics from the laser beams to the plasma flows, a series of experiments have been systematically conducted. The results indicate that 89%-96% of the laser energy was absorbed by the target, with moderate stimulated Raman scatterings. Here 2%-6% of the laser energy was coupled into the plasma jets ejected from the cone tips, which was mainly restricted by the mass reductions during the implosions inside the cones. The supersonic dense jets with a Mach number of 4 were obtained, which is favorable for forming a high-density, nondegenerated plasma core after the head-on collisions. These findings show encouraging results in terms of energy transport of the conical implosions in the DCI scheme.

A study on the significance of serine hydroxymethyl transferase expression and its role in bladder cancer.

Bladder cancer (BLCA) is a common malignant tumor in urinary system all over the world. However, due to its high recurrence rate and complex causes, clinicians often have limited options for surgical and drug treatments. Recent researchs on the molecular mechanism of BLCA have reveals its biological progress and potential for early diagnosis. Serine hydroxymethyltransferase 1/2 (SHMT1/2) is a crucial enzyme in the one-carbon metabolism of tumor cells, and the expression levels of these isozymes have been found to be associated with the biological progression of various malignant tumors. However, the impact of SHMT1/2 on the biological progression of bladder cancer and its molecular regulation mechanism remain unclear. In this research utilizes BLCA clinical sample data, the TCGA database, and in vitro cell experiments to predict the expression levels of SHMT1/2 in BLCA. The findings indicate that SHMT1 remained unchanged, while SHMT2 expression is increased in BLCA, which was related to poor prognosis. Additionally, SHMT2 affects the growth, migration, and apoptosis of bladder cancer cells in vitro. It also influences the expression levels of E-cadherin and N-cadherin, ultimately impacting the malignant biological progression of bladder tumors. These results establish a correlation between SHMT2 and the malignant biological progression of BLCA, providing a theoretical basis for the early diagnosis and treatment of bladder cancer.

Bile acids inhibit ferroptosis sensitivity through activating farnesoid X receptor in gastric cancer cells.

BACKGROUND: Gastric cancer (GC) is associated with high mortality rates. Bile acids (BAs) reflux is a well-known risk factor for GC, but the specific mechanism remains unclear. During GC development in both humans and animals, BAs serve as signaling molecules that induce metabolic reprogramming. This confers additional cancer phenotypes, including ferroptosis sensitivity. Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression. However, it is not fully defined if BAs can influence GC progression by modulating ferroptosis. AIM: To reveal the mechanism of BAs regulation in ferroptosis of GC cells. METHODS: In this study, we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis. We used gain and loss of function assays to examine the impacts of farnesoid X receptor (FXR) and BTB and CNC homology 1 (BACH1) overexpression and knockdown to obtain further insights into the molecular mechanism involved. RESULTS: Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells. This effect correlated with increased glutathione (GSH) concentrations, a reduced GSH to oxidized GSH ratio, and higher GSH peroxidase 4 (GPX4) expression levels. Subsequently, we confirmed that BAs exerted these effects by activating FXR, which markedly increased the expression of GSH synthetase and GPX4. Notably, BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR. Finally, our results suggested that FXR could significantly promote GC cell proliferation, which may be closely related to its anti-ferroptosis effect. CONCLUSION: This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSH-GPX4 axis in GC cells. This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.

Addressing climate change with behavioral science: A global intervention tournament in 63 countries.

Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions' effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior-several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people's initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors.