Pd-Catalyzed Enantioselective Desymmetrizing 1,7-Enyne Cycloisomerization of Alkyne-Tethered Cyclopentenes.

An enantioselective Pd-catalyzed intramolecular desymmetrizing cycloisomerization of N-(cyclopent-3-en-1-yl)propiolamides has been developed by employing a new chiral phosphoramidite ligand. A series of structurally unique bridged azabicycles are achieved in moderate to excellent yields with good E/Z selectivity and high enantioselectivity. Synthetic transformations are conducted to demonstrate the practical utility of this reaction.

Per- and polyfluoroalkyl substances and human health outcomes: An umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated. METHODS: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817). RESULTS: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence. CONCLUSION: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.

VGLL2 and TEAD1 fusion proteins drive YAP/TAZ-independent transcription and tumorigenesis by engaging p300.

Studies on Hippo pathway regulation of tumorigenesis largely center on YAP and TAZ, the transcriptional co-regulators of TEAD. Here, we present an oncogenic mechanism involving VGLL and TEAD fusions that is Hippo pathway-related but YAP/TAZ-independent. We characterize two recurrent fusions, VGLL2-NCOA2 and TEAD1-NCOA2, recently identified in spindle cell rhabdomyosarcoma. We demonstrate that, in contrast to VGLL2 and TEAD1, the fusion proteins are strong activators of TEAD-dependent transcription, and their function does not require YAP/TAZ. Furthermore, we identify that VGLL2 and TEAD1 fusions engage specific epigenetic regulation by recruiting histone acetyltransferase p300 to control TEAD-mediated transcriptional and epigenetic landscapes. We showed that small molecule p300 inhibition can suppress fusion proteins-induced oncogenic transformation both in vitro and in vivo. Overall, our study reveals a molecular basis for VGLL involvement in cancer and provides a framework for targeting tumors carrying VGLL, TEAD, or NCOA translocations.

Optimizing bioelectromethanosynthesis of CO2 and membrane fouling mitigation in MECs via in-situ biogas recirculation.

The CO2 bioelectromethanosynthesis via two-chamber microbial electrolysis cell (MEC) holds tremendous potential to solve the energy crisis and mitigate the greenhouse gas emissions. However, the membrane fouling is still a big challenge for CO2 bioelectromethanosynthesis owing to the poor proton diffusion across membrane and high inter-resistance. In this study, a new MEC bioreactor with biogas recirculation unit was designed in the cathode chamber to enhance secondary-dissolution of CO2 while mitigating the contaminant adhesion on membrane surface. Biogas recirculation improved CO2 re-dissolution, reduced concentration polarization, and facilitated the proton transmembrane diffusion. This resulted in a remarkable increase in the cathodic methane production rate from 0.4 mL/L·d to 8.5 mL/L·d. A robust syntrophic relationship between anodic organic-degrading bacteria (Firmicutes 5.29%, Bacteroidetes 25.90%, and Proteobacteria 6.08%) and cathodic methane-producing archaea (Methanobacterium 65.58%) enabled simultaneous organic degradation, high CO2 bioelectromethanosynthesis, and renewable energy storage.

Polyphenols functionalized MOF encapsulated BPQDs for synergistic photothermal/photodynamic antibacterial properties and multifunctional food preservation.

Active antibacterial materials play an important role in solving food safety problems caused by pathogen contamination. In this study, a composite active antibacterial material with the synergistic antibacterial effectiveness of photothermal, photodynamic and the surface charge of polyphenols was developed, where the multi-porous polyphenol functionalized metal-organic frameworks (ZIF-8-TA) were used as the framework carrier, and black phosphorus quantum dots (BPQDs) were used as the photosensitive source. The resulted ZIF-8-TA/PBQDs possesses excellent photothermal conversion efficiency (27.92%), photodynamic performance and surface charge, and these factors ensure the outstanding broad-spectrum antibacterial performance (100%). Multifunctional characteristics and excellent biocompatibility endow the materials with vast potential for foodstuff packaging. The results showed that the composite antibacterial film produced by doping ZIF-8-TA/PBQDs into chitosan could effectively prolong the shelf life of foodstuff compared with commercial membrane. The successful implementation of this research provides a new idea for controlling microbial contamination and developing multifunctional antibacterial materials.

Co-sensitization of Copper Indium Gallium Disulfide and Indium Sulfide on Zinc Oxide Nanostructures: Effect of Morphology in Electrochemical Carbon Dioxide Reduction.

Recent advances in nanoparticle materials can facilitate the electro-reduction of carbon dioxide (CO2) to form valuable products with high selectivity. Copper (Cu)-based electrodes are promising candidates to drive efficient and selective CO2 reduction. However, the application of Cu-based chalcopyrite semiconductors in the electrocatalytic reduction of CO2 is still limited. This study demonstrated that novel zinc oxide (ZnO)/copper indium gallium sulfide (CIGS)/indium sulfide (InS) heterojunction electrodes could be used in effective CO2 reduction for formic acid production. It has been determined that Faradaic efficiencies for formic acid production using ZnO nanowire (NW) and nanoflower (NF) structures vary due to structural and morphological differences. A ZnO NW/CIGS/InS heterojunction electrode resulted in the highest efficiency of 77.2% and 0.35 mA cm-2 of current density at a -0.24 V (vs. reversible hydrogen electrode) bias potential. Adding a ZTO intermediate layer by the spray pyrolysis method decreased the yield of formic acid and increased the yield of H2. Our work offers a new heterojunction electrode for efficient formic acid production via cost-effective and scalable CO2 reduction.

Solute carrier family 16 member 1 as a potential prognostic factor for pancreatic ductal adenocarcinoma and its influence on tumor immunity.

Background: Solute carrier family 16 member 1 (SLC16A1) serves as a biomarker in numerous types of cancer. Tumor immune infiltration has drawn increasing attention in cancer progression and treatment. The objective of our study was to explore the association between SLC16A1 and the tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC). Methods: Data were obtained from The Cancer Genome Atlas. The xCell web tool was used to calculate the proportion of immune cells according to SLC16A1 expression. To further explore the mechanism of SLC16A1, immunity-related genes were screened from differentially expressed genes through weighted gene coexpression network analysis, examined via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, and filtrated using univariate Cox regression and least absolute shrinkage and selection operator regression model combined correlation analysis (P<0.05). Next, CIBERSORT was used to analyze the correlation between immune cells and five important genes. SLC16A1 expression and its clinical role in pancreatic cancer was clarified via immunohistochemical staining experiments. Finally, the effects of SLC16A1 on the results of cancer immunity were evaluated by in vitro experiments. Results: SLC16A1 was overexpressed in PDAC tissues and could be an independent prognostic factor. SLC16A1 was significantly negatively correlated with overall survival and suppressed the tumor immunity of PDAC. In clinic, SLC16A1 expression was significantly positively correlated with tumor progression and poor prognosis. We also found that SLC16A1 could suppress the antitumor ability of CD8+ T cells. Conclusions: SLC16A1 is a biomarker for the prognosis of PDAC and can influence the immune environment of PDAC. These findings provide new insights into the treatment of PDAC.

Picein alleviates oxidative stress and promotes bone regeneration in osteoporotic bone defect by inhibiting ferroptosis via Nrf2/HO-1/GPX4 pathway.

Osteoporosis (OP) can result in slower bone regeneration than the normal condition due to abnormal oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation, making the OP-related bone healing a significant clinical challenge. As the osteogenic differentiation ability of bone marrow mesenchymal stem cells (BMSCs) is closely related to bone regeneration; currently, this study assessed the effects of Picein on BMSCs in vitro and bone regeneration in osteoporotic bone defect in vivo. Cell viability was determined by CCK-8 assay. The production of (ROS), malonaldehyde, superoxide dismutase activities, and glutathione was evaluated by using commercially available kits, and a flow cytometry analysis was adopted to detect macrophage polarization. Osteogenic capacity of BMSCs was evaluated by alkaline phosphatase (ALP) activity, ALP staining, and Alizarin red S staining. The expression of osteogenic-related proteins (OPN, Runx-2, OCN) and osteogenic-related genes (ALP, BMP-4, COL-1, and Osterix) were evaluated by Western blotting and real-time PCR (RT-PCR). In addition, proliferation, migration ability, and angiogenic capacity of human umbilical vein endothelial cells (HUVECs) were evaluated by EdU staining, scratch test, transwell assay, and tube formation assay, respectively. Angiogenic-related genes (VEGF, vWF, CD31) were also evaluated by RT-PCR. Results showed that Picein alleviated erastin-induced oxidative stress, enhanced osteogenic differentiation capacity of BMSCs, angiogenesis of HUVECs, and protects cells against ferroptosis through Nrf2/HO-1/GPX4 axis. Moreover, Picein regulate immune microenvironment by promoting the polarization of M2 macrophages in vitro. In addition, Picein also reduce the inflammation levels and promotes bone regeneration in osteoporotic bone defect in OP rat models in vivo. Altogether, these results suggested that Picein can promote bone regeneration and alleviate oxidative stress via Nrf2/HO-1/GPX4 pathway, offering Picein as a novel antioxidant agent for treating osteoporotic bone defect.

Research on the facile regeneration of degraded cathode materials from spent LiNi0.5Co0.2Mn0.3O2 lithium-ion batteries.

Rational reusing the waste materials in spent batteries play a key role in the sustainable development for the future lithium-ion batteries. In this work, we propose an effective and facile solid-state-calcination strategy for the recycling and regeneration of the cathode materials in spent LiNi0.5Co0.2Mn0.3O2 (NCM523) ternary lithium-ion batteries. By systemic physicochemical characterizations, the stoichiometry, phase purity and elemental composition of the regenerated material were deeply investigated. The electrochemical tests confirm that the material characteristics and performances got recovered after the regeneration process. The optimal material was proved to exhibit the excellent capacity with a discharge capacity of 147.9 mAh g-1 at 1 C and an outstanding capacity retention of 86% after 500 cycles at 1 C, which were comparable to those of commercial NCM materials.

A Prospective Randomized Trial of Neoadjuvant Chemohormonal Therapy vs Hormonal Therapy in Locally Advanced Prostate Cancer Treated by Radical Prostatectomy.

PURPOSE: Benefits of docetaxel-based neoadjuvant chemohormonal therapy (NCHT) before radical prostatectomy (RP) remain largely unknown. We explored whether docetaxel-based NCHT would bring pathological benefits and improve biochemical progression-free survival (bPFS) over neoadjuvant hormonal therapy (NHT) in locally advanced prostate cancer. MATERIALS AND METHODS: A randomized trial was designed recruiting 141 locally advanced, high-risk prostate cancer patients who were randomly assigned at the ratio of 2:1 to the NCHT group (75 mg/m2 body surface area every 3 weeks plus androgen deprivation therapy for 6 cycles) and the NHT group (androgen deprivation therapy for 24 weeks). The primary end point was 3-year bPFS. Secondary end points were pathological response including pathological downstaging and minimal residual disease rates. RESULTS: The NCHT group showed significant benefits in 3-year bPFS compared to the NHT group (29% vs 9.5%, P = .002). At a median follow-up of 53 months, the NCHT group achieved a significantly longer median bPFS time than the NHT group (17 months vs 14 months). No significant differences were found between the 2 groups in pathological downstaging and minimal residual disease rates. CONCLUSIONS: NCHT plus RP achieved significant bPFS benefits when compared with NHT plus RP in high-risk, locally advanced prostate cancer. A larger cohort with longer follow-up duration is essential in further investigation.

Exploring the effective components of honey-processed licorice (Glycyrrhiza uralensis Fisch.) in attenuating Doxorubicin-induced myocardial cytotoxicity by combining network pharmacology and in vitro experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is widely used clinically as one of the most famous traditional Chinese herbs. Its herb roasted with honey is called honey-processed licorice (HPL). Modern studies have shown that HPL has a stronger cardioprotective ability compared to raw licorice (RL), however the material basis and mechanism of action of the potential cardioprotection have not been fully elucidated. AIM OF THE STUDY: To screen and validate the material basis of cardioprotection exerted by HPL and to preliminarily predict the potential mechanism of action. MATERIALS AND METHODS: UPLC-QTOF-MS/MS was used to analyze HPL samples with different processing levels, and differential compounds were screened out through principal component analysis. Network pharmacology and molecular docking were applied to explore the association between differential compounds and doxorubicin cardiomyopathy and their mechanisms of action were predicted. An in vitro model was established to verify the cardioprotective effects of differential compounds. RESULTS: Six differential compounds were screened as key components of HPL for potential cardioprotection. Based on network pharmacology, 113 potential important targets for the treatment of Dox-induced cardiotoxicity were screened. KEGG enrichment analysis predicted that the PI3K-Akt pathway was closely related to the mechanism of action of active ingredients. Molecular docking results showed that the six differential compounds all had good binding activity with Nrf2 protein. In addition, in vitro experiments had shown that five of the active ingredients (liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, and licochalcone A) can significantly increase Dox-induced H9c2 cell viability, SOD activity, and mitochondrial membrane potential, significantly reduces MDA levels and inhibits ROS generation. CONCLUSION: Liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin and licochalcone A are key components of HPL with potential cardioprotective capabilities. Five active ingredients can alleviate Dox-induced cardiotoxicity by inhibiting oxidative stress and mitochondrial damage.

A Novel Strategy for Mixed Jam Evaluation: Apparent Indicator, Sensory, Metabolomic, and GC-IMS Analysis.

Jam is a popular traditional and modern food product for daily consumption. However, the benefits of mixed jams over single-fruit jams have not been thoroughly explored, with analyses limited to superficial indices. In this study, Xinjiang special Morus nigra L. and Prunus domestica L. were used as raw materials to prepare single-fruit and mixed jams, and their differences in antioxidants, organoleptic qualities, pH, texture, and color were analyzed. The dynamics of metabolites before and after thermal processing were assessed using untargeted metabolomics. The results indicate that the main metabolites were flavonoids, terpenoids, amino acids, phenolic acids, and carbohydrates. Flavonoid metabolites changed significantly after thermal processing, with 40 up-regulated and 13 down-regulated. During storage, polyphenols were the prominent differential metabolites, with fifty-four down-regulated and one up-regulated. Volatile aroma components were analyzed using gas chromatography-ion mobility spectrometry (GC-IMS); the aroma components E-2-hexenal, E-2-pentenal, 3-methylbutanal, 1-penten-3-ol, tetrahydro-linalool, 1-penten-3-one, hexyl propionate, isoamyl acetate, α-pinene, and propionic acid in mixed jam were significantly higher than in single-fruit jam. In this study, untargeted metabolomics and GC-IMS were used to provide a more comprehensive and in-depth evaluation system for jam analysis.

Salvianolic Acid B Reduces Oxidative Stress to Promote Hair-Growth in Mice, Human Hair Follicles and Dermal Papilla Cells.

Background: Existing research links oxidative stress and inflammation to hair loss. Salvianolic acid B (SAB) is known for its anti-oxidative, anti-inflammatory, and other beneficial pharmacological properties. Objective: To assess the efficacy of SAB in modulating hair growth. Methods: In vivo experiments were conducted using C57BL/6 mice to evaluate the effects of SAB on hair and skin parameters. The study involved ex vivo analysis of human hair follicles (HFs) for hair shaft length and hair growth cycle assessment. In vitro, human dermal papilla cells (hDPCs) were cultured with SAB, and their proliferation, protection against H2O2-induced oxidative damage, and gene/protein expression alterations were examined using various analytical techniques, including Real-Time Cell Analysis (RTCA), DCFH-DA Assay, RNA-seq, and KEGG pathway analysis. Results: SAB treatment in mice significantly improved hair growth and vascularization by day 21. In human HFs, SAB extended hair shaft length and delayed the transition to the catagen phase. SAB-treated hDPCs showed a notable decrease in the expression of oxidation-antioxidation-related genes and proteins, including reduced phosphorylation levels of ERK and p38. Conclusion: The study indicates that SAB promotes hDPC proliferation and offers protection against oxidative stress, highlighting its potential as a therapeutic agent for enhancing hair growth and treating hair loss.

Discovery of Alloy Catalysts Beyond Pd for Selective Hydrogenation of Reformate via First-principle Screening with Consideration of H-coverage.

The highly selective hydrogenation to remove olefins is a significant refining approach for the reformate. Herein, a library of transition metal for reformate hydrogenation is tested experimentally to validate the predictive level of catalytic activity from our theoretical framework, which combines ab initio calculations and microkinetic modeling, with consideration of surface H-coverage effect on hydrogenation kinetics. The favorable H coverage of specific alloy surface under relevant hydrogenation condition, is found to be determined by its corresponding alloy composition. Besides, olefin hydrogenation rate is determined as a function of two descriptors, i.e. H coverage and binding energies of atomic hydrogen, paving the way to computationally screen on metal component in the periodic table. Evaluation of 172 bimetallic alloys based on the activity volcano map, as well as benzene hydrogenation rate, identifies prospective superior candidates and experimentally confirms that Zn3Ir1 outperforms pure Pd catalysts for the selective hydrogenation refining of reformate. The insights into H-coverage-related microkinetic modelling have enabled us to both theoretically understand experimental findings and identify novel catalysts, thus, bridging the gap between first-principle simulations and industrial applications. This work provides useful guidance for experimental catalyst design, which can be easily extended to other hydrogenation reaction.

Effects of sanxan on water and ice crystal status of salt free frozen cooked noodles during freeze-thaw cycles.

This study compared four biocolloids (sanxan, xanthan gum, curdlan, and guar gum) in different concentrations to replace NaCl in improving the recooking quality of salt free frozen cooked noodles (SF-FCNs). Sanxan outperformed NaCl and other biocolloids significantly improving the firmness (21.0%), chewiness (63.5%), and toughness (15.4%) of SF-FCNs after 10 freeze-thaw (FT) cycles. The results of the freezing-thawing curves showed SF-FCNs had prior FT stability when sanxan was added at 1.2%. Subsequently, the result of differential scanning calorimetry and nuclear magnetic resonance revealed sanxan reduced the content and mobility of freezable water while increasing the content of bound water. The scanning electron microscope, mercury intrusion, and optical microscopy analyses indicated that sanxan reduced the size and volume of ice crystals and the structural damage of SF-FCNs by controlling the water. The work contributes to a theoretical framework for enhancing SF-FCNs quality through precise water and ice crystal control.

Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute promotes bone regeneration by moderating oxidative stress in osteoporotic bone defect.

The treatment of osteoporotic bone defect remains a big clinical challenge because osteoporosis (OP) is associated with oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation. Anti-oxidative nanomaterials such as selenium nanoparticles (SeNPs) have positive effect on osteogenesis owing to their pleiotropic pharmacological activity which can exert anti-oxidative stress functions to prevent bone loss and facilitate bone regeneration in OP. In the current study a strategy of one-pot method by introducing Poly (lactic acid-carbonate) (PDT) and ß-Tricalcium Phosphate (ß-TCP) with SeNPs, is developed to prepare an injectable, anti-collapse, shape-adaptive and adhesive bone graft substitute material (PDT-TCP-SE). The PDT-TCP-SE bone graft substitute exhibits sufficient adhesion in biological microenvironments and osteoinductive activity, angiogenic effect and anti-inflammatory as well as anti-oxidative effect in vitro and in vivo. Moreover, the PDT-TCP-SE can protect BMSCs from erastin-induced ferroptosis through the Sirt1/Nrf2/GPX4 antioxidant pathway, which, in together, demonstrated the bone graft substitute material as an emerging biomaterial with potential clinical application for the future treatment of osteoporotic bone defect. STATEMENT OF SIGNIFICANCE: Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute was successfully synthesized. Incorporation of SeNPs with PDT into ß-TCP regenerated new bone in-situ by moderating oxidative stress in osteoporotic bone defects area. The PDT-TCP-SE bone graft substitute reduced high ROS levels in osteoporotic bone defect microenvironment. The bone graft substitute could also moderate oxidative stress and inhibit ferroptosis via Sirt1/Nrf2/GPX4 pathway in vitro. Moreover, the PDT-TCP-SE bone graft substitute could alleviate the inflammatory environment and promote bone regeneration in osteoporotic bone defect in vivo. This biomaterial has the advantages of simple synthesis, biocompatibility, anti-collapse, injectable, and regulation of oxidative stress level, which has potential application value in bone tissue engineering.

CIP1, a CIPK23-interacting transporter, is implicated in Cd tolerance and phytoremediation.

Environmental pollution from cadmium (Cd) presents a serious threat to plant growth and development. Therefore, it's crucial to find out how plants resist this toxic metal to develop strategies for remediating Cd-contaminated soils. In this study, we identified CIP1, a transporter protein, by screening interactors of the protein kinase CIPK23. CIP1 is located in vesicles membranes and can transport Cd2+ when expressed in yeast cells. Cd stress specifically induced the accumulation of CIP1 transcripts and functional proteins, particularly in the epidermal cells of the root tip. CIKP23 could interact directly with the central loop region of CIP1, phosphorylating it, which is essential for the efficient transport of Cd2+. A loss-of-function mutation of CIP1 in wild-type plants led to increased sensitivity to Cd stress. Conversely, tobacco plants overexpressing CIP1 exhibited improved Cd tolerance and increased Cd accumulation capacity. Interestingly, this Cd accumulation was restricted to roots but not shoots, suggesting that manipulating CIP1 does not risk Cd contamination of plants' edible parts. Overall, this study characterizes a novel Cd transporter, CIP1, with potential to enhance plant tolerance to Cd toxicity while effectively eliminating environmental contamination without economic losses.

Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration.

Large segmental bone defects are commonly operated with autologous bone grafting, which has limited bone sources and poses additional surgical risks. In this study, we fabricated poly(lactide-co-glycolic acid) (PLGA)/ß-tricalcium phosphate (ß-TCP) composite membranes by electrostatic spinning and further promoted osteogenesis by regulating the release of ß-TCP in the hope of replacing autologous bone grafts in the clinical practice. The addition of ß-TCP improved the mechanical strength of PLGA by 2.55 times. Moreover, ß-TCP could accelerate the degradation of PLGA and neutralize the negative effects of acidification of the microenvironment caused by PLGA degradation. In vitro experiments revealed that PLGA/TCP10 membranes are biocompatible and the released ß-TCP can modulate the activity of osteoblasts by enhancing the calcium ions concentration in the damaged area and regulating the pH of the local microenvironment. Simultaneously, an increase in ß-TCP can moderate the lactate content of the local microenvironment, synergistically enhancing osteogenesis by promoting the tube-forming effect of human umbilical vein endothelial cells. Therefore, it is potential to utilize PLGA/TCP bioactive membranes to modulate the microenvironment at the site of bone defects to promote bone regeneration.

Determining individual suitability for neoadjuvant systemic therapy in breast cancer patients through deep learning.

BACKGROUND: The survival advantage of neoadjuvant systemic therapy (NST) for breast cancer patients remains controversial, especially when considering the heterogeneous characteristics of individual patients. OBJECTIVE: To discern the variability in responses to breast cancer treatment at the individual level and propose personalized treatment recommendations utilizing deep learning (DL). METHODS: Six models were developed to offer individualized treatment suggestions. Outcomes for patients whose actual treatments aligned with model recommendations were compared to those whose did not. The influence of certain baseline features of patients on NST selection was visualized and quantified by multivariate logistic regression and Poisson regression analyses. RESULTS: Our study included 94,487 female breast cancer patients. The Balanced Individual Treatment Effect for Survival data (BITES) model outperformed other models in performance, showing a statistically significant protective effect with inverse probability treatment weighting (IPTW)-adjusted baseline features [IPTW-adjusted hazard ratio: 0.51, 95% confidence interval (CI), 0.41-0.64; IPTW-adjusted risk difference: 21.46, 95% CI 18.90-24.01; IPTW-adjusted difference in restricted mean survival time: 21.51, 95% CI 19.37-23.80]. Adherence to BITES recommendations is associated with reduced breast cancer mortality and fewer adverse effects. BITES suggests that patients with TNM stage IIB, IIIB, triple-negative subtype, a higher number of positive axillary lymph nodes, and larger tumors are most likely to benefit from NST. CONCLUSIONS: Our results demonstrated the potential of BITES to aid in clinical treatment decisions and offer quantitative treatment insights. In our further research, these models should be validated in clinical settings and additional patient features as well as outcome measures should be studied in depth.