Fluorescent probes based on N-CQDs: For direct detection of food additives STPP and Al3.

Sodium tripolyphosphate (STPP), as one of the many food additives, can cause gastrointestinal discomfort and a variety of adverse reactions when ingested by the human body, which is a great potential threat to human health. Therefore, it is necessary to develop a fast, sensitive and simple method to detect STPP in food. In this study, we synthesized a kind of nitrogen-doped carbon quantum dots (N-CQDs), and were surprised to find that the addition of STPP led to the gradual enhancement of the emission peaks of the N-CQDs, with a good linearity in the range of 0.067-1.96 µM and a low detection limit as low as 0.024 µM. Up to now, there is no report on the use of carbon quantum dots for the direct detection of STPP. Meanwhile, we found that the addition of Al3+ effectively bursts the fluorescence intensity of N-CQDs@STPP solution and has a good linear relationship in the range of 0.33-6.25 µM with a lower detection limit of 0.24 µM. To this end, we developed a fluorescent probe to detect STPP and Al3+. In addition, the probe was successfully applied to the detection of bread samples, which has great potential for practical application.

Solar energy powered electrochemical reduction of CO2 on In2O3 nanosheets with high energy conversion efficiency at a large current density.

Electrochemical CO2 reduction (ECO2R) to value-added chemicals offers a promising approach to both mitigate CO2 emission and facilitate renewable energy conversion. We demonstrate a solar energy powered ECO2R system operating at a relatively large current density (57 mA cm-2) using In2O3 nanosheets (NSs) as the cathode and a commercial perovskite solar cell as the electricity generator, which achieves the high solar to formate energy conversion efficiency of 6.6 %. The significantly enhanced operative current density with a fair solar energy conversion efficiency on In2O3 NSs can be ascribed to their high activity and selectivity for formate production, as well as the fast kinetics for ECO2R. The Faradic efficiencies (FEs) of formate In2O3 NSs are all above 93 %, with the partial current density of formate ranging from 2.3 to 342 mA cm-2 in a gas diffusion flow cell, which is among the widest for formate production on In-based catalysts. In-situ Raman spectroscopy and density functional theory simulations reveal that the exceptional performances of formate production on In2O3 NSs originates from the presence of abundant low coordinated edge sites, which effectively promote the selective adsorption of *OCHO while inhibiting *H adsorption.

Efficient removal of Cr (VI) by Bifunction zinc porphyrin COF: Coupling adsorption with Photocatalysis, performance Evaluation, and mechanism analysis.

HYPOTHESIS: Hexavalent chromium, recognized as one of the most toxic heavy metals, demands the development of advanced materials capable of both adsorption and photocatalysis for effective Cr (VI) removal. EXPERIMENTS: This study successfully synthesized a two-dimensional zinc porphyrin covalent organic framework (ZnPor-COF) via a solvent-based method. Performance evaluations have demonstrated that the ZnPor-COF possesses outstanding capabilities for the adsorptive and/or photocatalytic elimination of Cr (VI). Particularly noteworthy is the observation that when adsorption and photocatalysis are coupled, the ZnPor-COF attains an exceptional 99.7 % removal rate for a Cr (VI) concentration of 30 mg/L within just 60 min, with minimal susceptibility to coexisting ions. After five consecutive cycles, the material sustains a removal efficiency of 90 %, indicative of its robust cyclability. FINDINGS: Theoretical calculations, as well as experimental validations, have indicated that the integration of Zn ions into the porphyrin COF not only results in an expanded specific surface area and an increased count of adsorption sites but also significantly improves the COF's photosensitivity and the capability for charge carrier separation. Furthermore, the core of the synergistic effect between adsorption and photocatalysis lies in the ability of photocatalysis to substantially augment the adsorption process.

Topologically Close-Packed Frank-Kasper C15 Phase Intermetallic Ir Alloy Electrocatalysts Enables High-Performance Proton Exchange Membrane Water Electrolyzer.

Chemical synthesis of unconventional topologically close-packed intermetallic nanocrystals (NCs) remains a considerable challenge due to the limitation of large volume asymmetry between the components. Here, a series of unconventional intermetallic Frank-Kasper C15 phase Ir2M (M = rare earth metals La, Ce, Gd, Tb, Tm) NCs is successfully prepared via a molten-salt assisted reduction method as efficient electrocatalysts for hydrogen evolution reaction (HER). Compared to the disordered counterpart (A1-Ir2Ce), C15-Ir2Ce features higher Ir-Ce coordination number that leads to an electron-rich environment for Ir sites. The C15-Ir2Ce catalyst exhibits excellent and pH-universal HER activity and requires only 9, 16, and 27 mV overpotentials to attain 10 mA cm-2 in acidic, alkaline, and neutral electrolytes, respectively, representing one of the best HER electrocatalysts ever reported. In a proton exchange membrane water electrolyzer, the C15-Ir2Ce cathode achieves an industrial-scale current density of 1 A cm-2 with a remarkably low cell voltage of 1.7 V at 80 °C and can operate stably for 1000 h with a sluggish voltage decay rate of 50 µV h-1. Theoretical investigations reveal that the electron-rich Ir sites intensify the polarization of *H2O intermediate on C15-Ir2Ce, thus lowering the energy barrier of the water dissociation and facilitating the HER kinetics.

Single-cell and spatial omics unravel the spatiotemporal biology of tumour border invasion and haematogenous metastasis.

Solid tumours exhibit a well-defined architecture, comprising a differentiated core and a dynamic border that interfaces with the surrounding tissue. This border, characterised by distinct cellular morphology and molecular composition, serves as a critical determinant of the tumour's invasive behaviour. Notably, the invasive border of the primary tumour represents the principal site for intravasation of metastatic cells. These cells, known as circulating tumour cells (CTCs), function as 'seeds' for distant dissemination and display remarkable heterogeneity. Advancements in spatial sequencing technology are progressively unveiling the spatial biological features of tumours. However, systematic investigations specifically targeting the characteristics of the tumour border remain scarce. In this comprehensive review, we illuminate key biological insights along the tumour body-border-haematogenous metastasis axis over the past five years. We delineate the distinctive landscape of tumour invasion boundaries and delve into the intricate heterogeneity and phenotype of CTCs, which orchestrate haematogenous metastasis. These insights have the potential to explain the basis of tumour invasion and distant metastasis, offering new perspectives for the development of more complex and precise clinical interventions and treatments.

Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Its complexity is influenced by various signal transduction networks that govern cellular proliferation, survival, differentiation, and apoptosis. The pathogenesis of CRC is a testament to the dysregulation of these signaling cascades, which culminates in the malignant transformation of colonic epithelium. This review aims to dissect the foundational signaling mechanisms implicated in CRC, to elucidate the generalized principles underpinning neoplastic evolution and progression. We discuss the molecular hallmarks of CRC, including the genomic, epigenomic and microbial features of CRC to highlight the role of signal transduction in the orchestration of the tumorigenic process. Concurrently, we review the advent of targeted and immune therapies in CRC, assessing their impact on the current clinical landscape. The development of these therapies has been informed by a deepening understanding of oncogenic signaling, leading to the identification of key nodes within these networks that can be exploited pharmacologically. Furthermore, we explore the potential of integrating AI to enhance the precision of therapeutic targeting and patient stratification, emphasizing their role in personalized medicine. In summary, our review captures the dynamic interplay between aberrant signaling in CRC pathogenesis and the concerted efforts to counteract these changes through targeted therapeutic strategies, ultimately aiming to pave the way for improved prognosis and personalized treatment modalities in colorectal cancer.

M3T-LM: A multi-modal multi-task learning model for jointly predicting patient length of stay and mortality.

Ensuring accurate predictions of inpatient length of stay (LoS) and mortality rates is essential for enhancing hospital service efficiency, particularly in light of the constraints posed by limited healthcare resources. Integrative analysis of heterogeneous clinic record data from different sources can hold great promise for improving the prognosis and diagnosis level of LoS and mortality. Currently, most existing studies solely focus on single data modality or tend to single-task learning, i.e., training LoS and mortality tasks separately. This limits the utilization of available multi-modal data and prevents the sharing of feature representations that could capture correlations between different tasks, ultimately hindering the model's performance. To address the challenge, this study proposes a novel Multi-Modal Multi-Task learning model, termed as M3T-LM, to integrate clinic records to predict inpatients' LoS and mortality simultaneously. The M3T-LM framework incorporates multiple data modalities by constructing sub-models tailored to each modality. Specifically, a novel attention-embedded one-dimensional (1D) convolutional neural network (CNN) is designed to handle numerical data. For clinical notes, they are converted into sequence data, and then two long short-term memory (LSTM) networks are exploited to model on textual sequence data. A two-dimensional (2D) CNN architecture, noted as CRXMDL, is designed to extract high-level features from chest X-ray (CXR) images. Subsequently, multiple sub-models are integrated to formulate the M3T-LM to capture the correlations between patient LoS and modality prediction tasks. The efficiency of the proposed method is validated on the MIMIC-IV dataset. The proposed method attained a test MAE of 5.54 for LoS prediction and a test F1 of 0.876 for mortality prediction. The experimental results demonstrate that our approach outperforms state-of-the-art (SOTA) methods in tackling mixed regression and classification tasks.

Safe and potent anti-CD19 CAR T-cells with shRNA-IL-6 gene silencing element in patients with refractory or relapsed B-cell acute lymphoblastic leukemia.

Severe cytokine release syndrome (sCRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have limited the widespread use of chimeric antigen receptor T (CAR T)-cell therapy. We designed a novel anti-CD19 CAR (ssCART-19) with a small hairpin RNA (shRNA) element to silence the interleukin-6 (IL-6) gene, hypothesizing it could reduce sCRS and ICANS by alleviating monocyte activation and proinflammatory cytokine release. In a post hoc analysis of two clinical trials, we compared ssCART-19 with common CAR T-cells (cCART-19) in relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Among 87 patients, 47 received ssCART-19 and 40 received cCART-19. Grade ≥3 CRS occurred in 14.89% (7/47) of the ssCART-19 group versus 37.5% (15/40) in the cCART-19 group (p = 0.036). ICANS occurred in 4.26% (2/47) of the ssCART-19 group (all grade 1) compared to 15% (2/40) of the cCART-19 group. Patients in the ssCART-19 group showed comparable rates of treatment response (calculated with rates of complete remission and incomplete hematological recovery) were 91.49% (43/47) for ssCART-19 and 85% (34/40) for cCART-19 (p = 0.999). With a median follow-up of 21.9 months, cumulative nonrelapse mortality was 10.4% for ssCART-19 and 13.6% for cCART-19 (p = 0.33). Median overall survival was 37.17 months for ssCART-19 and 32.93 months for cCART-19 (p = 0.40). Median progression-free survival was 24.17 months for ssCART-19 and 9.33 months for cCART-19 (p = 0.23). These data support the safety and efficacy of ssCART-19 for r/r B-ALL, suggesting its potential as a promising therapy.

Hydrogen-Bonded Ionic Co-Crystals for Fast Solid-State Zinc Ion Storage.

The development of new ionic conductors meeting the requirements of current solid-state devices is imminent but still challenging. Hydrogen-bonded ionic co-crystals (HICs) are multi-component crystals based on hydrogen bonding and Coulombic interactions. Due to the hydrogen bond network and unique features of ionic crystals, HICs have flexible skeletons. More importantly, anion vacancies on their surface can potentially help dissociate and adsorb excess anions, forming cation transport channels at grain boundaries. Here, it is demonstrated that a HIC optimized by adjusting the ratio of zinc salt and imidazole can construct grain boundary-based fast Zn2+ transport channels. The as-obtained HIC solid electrolyte possesses an unprecedentedly high ionic conductivity at room and low temperatures (≈11.2 mS cm-1 at 25 °C and ≈2.78 mS cm-1 at -40 °C) with ultra-low activation energy (≈0.12 eV), while restraining dendrite growth and exhibiting low overpotential even at a high current density (<200 mV at 5.0 mA cm-2) during Zn symmetric cell cycling. This HIC also allows solid-state Zn||covalent organic framework full cells to work at low temperatures, providing superior stability. More importantly, the HIC can even support zinc-ion hybrid supercapacitors to work, achieving extraordinary rate capability and a power density comparable to aqueous solution-based supercapacitors. This work provides a path for designing facilely prepared, low-cost, and environmentally friendly ionic conductors with extremely high ionic conductivity and excellent interface compatibility.

Atypical Presentation of Congenital Insensitivity to Pain With Anhidrosis Leading to Diagnostic Odyssey.

BACKGROUND: Congenital insensitivity to pain with anhidrosis (CIPA) (OMIM 256800) is a rare autosomal-recessive condition, also known as hereditary sensory and autonomic neuropathy type IV (HSAN-IV). The most commonly reported features include anhidrosis, intellectual disability, self-mutilation, febrile episodes, impaired temperature perception, recurrent infections and/or autonomic nervous system impairment. Major joint destruction and joint deformity known as Charcot (neuropathic) joints are also seen in CIPA patients attributed to insensitivity to joint pain. METHODS: We present a case of a 46-year-old female affected with CIPA with a known NTRK1 variant and previously unidentified variant. Minigene reporter constructs were generated encompassing the exon 8 to exon 13 of the NTRK1 gene using the reference sequence and one harboring c.1483 + 5G > A variant identified in our proband. Minigene constructs were transfected into HEK293T cells, and the transcript was analysed for splicing to evaluate the effect of this variant in splicing. RESULTS: The patient (46-year-old female) exhibited right ankle joint deformity around 5 years of age. Patient also experienced lumbar compression and knee damage in adulthood. She had undergone a significant number of evaluations without clear diagnosis. Her presentation lacked many of the common clinical presentations of CIPA, and therefore, the focus of her evaluation was directed towards her unexplained joint deformities. Exome sequencing revealed a known pathogenic variant in NTRK1 (c.851 - 33T > A:p.? [Intron 7]) and a novel NTRK1 variant (c.1483 + 5G > A:p.? [Intron 11]), which was later re-classified as likely pathogenic. The patient was started on a biologic disease-modifying anti-rheumatic medication (bDMARD) due to a possible inflammatory etiology of her joint deformity. Molecular diagnosis allowed for modification of her treatment and surveillance strategies. Our minigene splicing assay demonstrated that the presence of the c.1483 + 5G > A variant has a negative effect on splicing, supporting the pathogenicity of this novel variant.

SSRI antidepressant citalopram reverses the Warburg effect to inhibit hepatocellular carcinoma by directly targeting GLUT1.

Selective serotonin reuptake inhibitors (SSRIs) have shown promise in cancer therapy, particularly for hepatocellular carcinoma (HCC), but their molecular targets and mechanisms remain unclear. Here, we show that SSRIs exhibit significant anti-HCC effects independent of their classical target, the serotonin reuptake transporter (SERT). Using global inverse gene expression profiling, drug affinity responsive target stability assays, and in silico molecular docking, we demonstrate that citalopram targets glucose transporter 1 (GLUT1), resulting in reduced glycolytic flux. A mutant GLUT1 variant at the citalopram binding site (E380) diminishes the drug's inhibitory effects on the Warburg effect and tumor growth. In preclinical models, citalopram dampens the growth of GLUT1high liver tumors and displays a synergistic effect with anti-PD-1 therapy. Retrospective analysis reveals that SSRI use correlates with a lower risk of metastasis among patients with HCC. Our study describes a role for SSRIs in cancer metabolism, establishing a rationale for their repurposing as potential anti-cancer drugs for HCC.

Gut Bacteroides ovatus ameliorates renal fibrosis by promoting the production of HDCA through upregulation of Clostridium scindens.

Renal fibrosis, inflammation, and gut dysbiosis are all linked to chronic kidney disease (CKD). Here we show that Bacteroides ovatus protects against renal fibrosis. Mechanistically, B. ovatus enhances intestinal hyodeoxycholic acid (HDCA) levels by upregulating a strain of intestinal bacteria, Clostridium scindens, that has the capacity for direct HDCA production in mice. HDCA significantly promoted GLP-1 secretion by upregulating the expression of TGR5 and downregulating the expression of farnesoid X receptor (FXR) in the gut. Activation of renal GLP-1R attenuates renal fibrosis while delaying the subsequent development of CKD. In addition, HDCA can also protect against renal fibrosis by directly upregulating renal TGR5. The natural product neohesperidin (NHP) was found to exert its anti-renal fibrotic effects by promoting the growth of B. ovatus. Our findings provide mechanistic insights into the therapeutic potential of B. ovatus, C. scindens, and HDCA in treating CKD.

Development of a Physiologically Based Pharmacokinetic (PBPK) Model for F-53B in Pregnant Mice and Its Extrapolation to Humans.

Chlorinated polyfluorinated ether sulfonic acid (F-53B), a commonly utilized alternative for perfluorooctane sulfonate, was detected in pregnant women and cord blood recently. However, the lack of detailed toxicokinetic information poses a significant challenge in assessing the human risk assessment for F-53B exposure. Our study aimed to develop a physiologically based pharmacokinetic (PBPK) model for pregnant mice, based on toxicokinetic experiments, and extrapolating it to humans. Pregnant mice were administered 80 µg/kg F-53B orally and intravenously on gestational day 13. F-53B concentrations in biological samples were analyzed via ultraperformance liquid chromatography-mass spectrometry. Results showed the highest F-53B accumulation in the brain, followed by the placenta, amniotic fluid, and liver in fetal mice. These toxicokinetic data were applied to F-53B PBPK model development and evaluation, and Monte Carlo simulations were used to characterize the variability and uncertainty in the human population. Most of the predictive values were within a 2-fold range of experimental data (>72%) and had a coefficient of determination (R2) greater than 0.68. The developed mouse model was then extrapolated to the human and evaluated with human biomonitoring data. Our study provides an important step toward improving the understanding of toxicokinetics of F-53B and enhancing the quantitative risk assessments in sensitive populations, particularly in pregnant women and fetuses.

Long-term breast cancer response to CDK4/6 inhibition defined by TP53-mediated geroconversion.

Inhibition of CDK4/6 kinases has led to improved outcomes in breast cancer. Nevertheless, only a minority of patients experience long-term disease control. Using a large, clinically annotated cohort of patients with metastatic hormone receptor-positive (HR+) breast cancer, we identify TP53 loss (27.6%) and MDM2 amplification (6.4%) to be associated with lack of long-term disease control. Human breast cancer models reveal that p53 loss does not alter CDK4/6 activity or G1 blockade but instead promotes drug-insensitive p130 phosphorylation by CDK2. The persistence of phospho-p130 prevents DREAM complex assembly, enabling cell-cycle re-entry and tumor progression. Inhibitors of CDK2 can overcome p53 loss, leading to geroconversion and manifestation of senescence phenotypes. Complete inhibition of both CDK4/6 and CDK2 kinases appears to be necessary to facilitate long-term response across genomically diverse HR+ breast cancers.

Bidirectional effects of morphine on pancreatic cancer progression via the p38/JNK pathway.

Cancer patients commonly use morphine to alleviate advanced pain. Studies have shown that morphine may influence and intervene in the malignancy of various cancers, but its role and effects on pancreatic cancer are less studied. This study aims to examine how morphine affects pancreatic cancer and its possible mechanisms. In vitro experiments were conducted using the CCK-8 experiment, colony formation experiment, EdU test, wound healing experiment, and transwell migration and invasion experiment. Tumor xenograft tests were employed to investigate the in vivo impact of morphine on pancreatic cancer. The Western blot (WB) assay was used to detect possible changes in key proteins of the related signaling pathway. Our experimental results showed that low concentrations of morphine (25 µM) promoted the progression of pancreatic cancer, while high concentrations of morphine (100 µM) inhibited its progression. Further, we demonstrated that morphine may interfere with the progression of pancreatic cancer by acting on the p38/JNK signaling pathway. Morphine may affect pancreatic cancer progression through the p38/JNK pathway in a bidirectional manner at different concentrations.

Direct mitochondrial import of lactate supports resilient carbohydrate oxidation.

Lactate is the highest turnover circulating metabolite in mammals. While traditionally viewed as a waste product, lactate is an important energy source for many organs, but first must be oxidized to pyruvate for entry into the tricarboxylic acid cycle (TCA cycle). This reaction is thought to occur in the cytosol, with pyruvate subsequently transported into mitochondria via the mitochondrial pyruvate carrier (MPC). Using 13C stable isotope tracing, we demonstrated that lactate is oxidized in the myocardial tissue of mice even when the MPC is genetically deleted. This MPC-independent lactate import and mitochondrial oxidation is dependent upon the monocarboxylate transporter 1 (MCT1/Slc16a1). Mitochondria isolated from the myocardium without MCT1 exhibit a specific defect in mitochondrial lactate, but not pyruvate, metabolism. The import and subsequent mitochondrial oxidation of lactate by mitochondrial lactate dehydrogenase (LDH) acts as an electron shuttle, generating sufficient NADH to support respiration even when the TCA cycle is disrupted. In response to diverse cardiac insults, animals with hearts lacking MCT1 undergo rapid progression to heart failure with reduced ejection fraction. Thus, the mitochondrial import and oxidation of lactate enables carbohydrate entry into the TCA cycle to sustain cardiac energetics and maintain myocardial structure and function under stress conditions.

Effects of bile acids on the growth, composition and metabolism of gut bacteria.

Bile acids (BAs) exert a profound influence on the body's pathophysiology by intricately shaping the composition of gut bacteria. However, the complex interplay between BAs and gut microbiota has impeded a systematic exploration of their impact on intestinal bacteria. Initially, we investigated the effects of 21 BAs on the growth of 65 gut bacterial strains in vitro. Subsequently, we examined the impact of BAs on the overall composition of intestinal bacteria, both in vivo and in vitro. The results unveiled distinct effects of various BAs on different intestinal strains and their diverse impacts on the composition of gut bacteria. Mechanistically, the inhibition of intestinal strains by BAs occurs through the accumulation of these acids within the strains. The intracellular accumulation of deoxycholic acid (DCA) significantly influenced the growth of intestinal bacteria by impacting ribosome transcription and amino-acid metabolism. The metabolomic analysis underscores the pronounced impact of DCA on amino-acid profiles in both in vivo and in vitro settings. This study not only elucidates the effects of BAs on a diverse range of bacterial strains and their role in shaping the gut microbiota but also reveals underlying mechanisms essential for understanding and maintaining a healthy gut microbiota.

SPOT: spatial proteomics through on-site tissue-protein-labeling.

BACKGROUND: Spatial proteomics seeks to understand the spatial organization of proteins in tissues or at different subcellular localization in their native environment. However, capturing the spatial organization of proteins is challenging. Here, we present an innovative approach termed Spatial Proteomics through On-site Tissue-protein-labeling (SPOT), which combines the direct labeling of tissue proteins in situ on a slide and quantitative mass spectrometry for the profiling of spatially-resolved proteomics. MATERIALS AND METHODS: Efficacy of direct TMT labeling was investigated using seven types of sagittal mouse brain slides, including frozen tissues without staining, formalin-fixed paraffin-embedded (FFPE) tissues without staining, deparaffinized FFPE tissues, deparaffinized and decrosslinked FFPE tissues, and tissues with hematoxylin & eosin (H&E) staining, hematoxylin (H) staining, eosin (E) staining. The ability of SPOT to profile proteomes at a spatial resolution was further evaluated on a horizontal mouse brain slide with direct TMT labeling at eight different mouse brain regions. Finally, SPOT was applied to human prostate cancer tissues as well as a tissue microarray (TMA), where TMT tags were meticulously applied to confined regions based on the pathological annotations. After on-site direct tissue-protein-labeling, tissues were scraped off the slides and subject to standard TMT-based quantitative proteomics analysis. RESULTS: Tissue proteins on different types of mouse brain slides could be directly labeled with TMT tags. Moreover, the versatility of our direct-labeling approach extended to discerning specific mouse brain regions based on quantitative outcomes. The SPOT was further applied on both frozen tissues on slides and FFPE tissues on TMAs from prostate cancer tissues, where a distinct proteomic profile was observed among the regions with different Gleason scores. CONCLUSIONS: SPOT is a robust and versatile technique that allows comprehensive profiling of spatially-resolved proteomics across diverse types of tissue slides to advance our understanding of intricate molecular landscapes.

The impact of internet-based cognitive behavioral therapy on mental health outcomes and life in breast cancer patients: a systematic review and meta-analysis.

Background: Internet-based cognitive behavioral therapy(ICBT) improves the impact of breast cancer through online platforms, modular learning, goal setting, relaxation exercises, and other techniques. Compared to traditional cognitive behavioral therapy (CBT), ICBT offers advantages such as the convenience of flexible time and location choices and reduced manpower requirements. In recent years, research exploring the impact of ICBT on breast cancer patients has been increasing, with conflicting results across different studies. Therefore, the purpose of this study was to comprehensively examine the impact of ICBT on the psychological health and quality of life of breast cancer patients through a systematic review and meta-analysis. Methods: We searched ten databases in both English and Chinese, with the search period extending from the inception of the databases to December 30, 2023. Literature screening, bias risk assessment, data extraction, and evidence level evaluation were independently conducted by two researchers. All the data were analyzed using RevMan 5.4 and Stata 17.0 software. Results: A total of 2079 breast cancer patients were included in this study, of which 1171 patients received ICBT treatment. The results show that ICBT can reduce anxiety [SMD=-0.19, 95%CI (-0.37, -0.01), P=0.0008] and depression [SMD=-0.20, 95%CI (-0.37, -0.02), P=0.001], alleviate fatigue [SMD=-0.34, 95%CI (-0.67, -0.01), P=0.04], and improve quality of life [SMD=0.20, 95% CI (0.03, 0.38), P=0.02] in breast cancer patients. However, the intervention effects of ICBT on insomnia [SMD=-0.44, 95%CI (-0.93, 0.06), P=0.08] and sleep quality [SMD=-0.14, 95%CI (-0.30, 0.01), P=0.06] in breast cancer patients are not significant. The subgroup analysis showed that when the intervention period is longer than 8 weeks, the number of intervention modules exceeds 6, and a waitlist control group is included, there is a significant effect on reducing patients' anxiety and depression. However, the method of guidance and whether the intervention period exceeds 12 weeks are not related. Conclusion: ICBT can alleviate anxiety and depression in breast cancer patients, with the intervention effects being independent of the guidance method. Significant results were obtained when the intervention period was >8 weeks and the number of modules was >6. ICBT can reduce fatigue and improve quality of life in breast cancer patients, but its impact on sleep quality was not significant. More high-quality research is needed in the future. Systematic review registration: PROSPERO, identifier CRD42024494744.

The Biomimetic Electrical Stimulation System Inducing Osteogenic Differentiations of BMSCs.

Electrical stimulation has been used clinically as an adjunct therapy to accelerate the healing of bone defects, and its mechanism requires further investigations. The complexity of the physiological microenvironment makes it challenging to study the effect of electrical signal on cells alone. Therefore, an artificial system mimicking cell microenvironment in vitro was developed to address this issue. In this work, a novel electrical stimulation system was constructed based on polypyrrole nanowires (ppyNWs) with a high aspect ratio. Synthesized ppyNWs formed a conductive network in the composited hydrogel which contained modified gelatin with methacrylate, providing a conductive cell culture matrix for bone marrow mesenchymal stem cells. The dual-network conductive hydrogel had improved mechanical, electrical, and hydrophilic properties. It was able to imitate the three-dimensional structure of the cell microenvironment and allowed adjustable electrical stimulations in the following system. This hydrogel was integrated with cell culture plates, platinum electrodes, copper wires, and external power sources to construct the artificial electrical stimulation system. The optimum voltage of the electrical stimulation system was determined to be 2 V, which exhibited remarkable biocompatibility. Moreover, this system had significant promotion in cell spreading, osteogenic makers, and bone-related gene expression of stem cells. RNA-seq analysis revealed that osteogenesis was correlated to Notch, BMP/Smad, and calcium signal pathways. It was proven that this biomimetic system could regulate the osteogenesis procedure, and it provided further information about how the electrical signal regulates osteogenic differentiations.