PNBACE: an ensemble algorithm to predict the effects of mutations on protein-nucleic acid binding affinity.

BACKGROUND: Mutations occurring in nucleic acids or proteins may affect the binding affinities of protein-nucleic acid interactions. Although many efforts have been devoted to the impact of protein mutations, few computational studies have addressed the effect of nucleic acid mutations and explored whether the identical methodology could be applied to the prediction of binding affinity changes caused by these two mutation types. RESULTS: Here, we developed a generalized algorithm named PNBACE for both DNA and protein mutations. We first demonstrated that DNA mutations could induce varying degrees of changes in binding affinity from multiple perspectives. We then designed a group of energy-based topological features based on different energy networks, which were combined with our previous partition-based energy features to construct individual prediction models through feature selections. Furthermore, we created an ensemble model by integrating the outputs of individual models using a differential evolution algorithm. In addition to predicting the impact of single-point mutations, PNBACE could predict the influence of multiple-point mutations and identify mutations significantly reducing binding affinities. Extensive comparisons indicated that PNBACE largely performed better than existing methods on both regression and classification tasks. CONCLUSIONS: PNBACE is an effective method for estimating the binding affinity changes of protein-nucleic acid complexes induced by DNA or protein mutations, therefore improving our understanding of the interactions between proteins and DNA/RNA.

BRD9 promotes the progression of gallbladder cancer via CST1 upregulation and interaction with FOXP1 through the PI3K/AKT pathway and represents a therapeutic target.

Gallbladder cancer (GBC) is highly aggressive and has poor prognosis, with most patients only diagnosed at an advanced stage. Furthermore, treatment options are limited, and their effect is unsatisfactory. Bromodomain-containing protein (BRD) is an epigenetic regulator that plays a carcinogenic role in several tumors, including squamous cell lung cancer, acute myeloid leukemia, synovial sarcoma, and malignant rhabdomyosarcoma. However, the expression, biological function, and molecular mechanisms of action of BRD9 in GBC are still unknown. Kaplan-Meier analysis, qRT-PCR, and analysis of clinical features were used to assess the clinical significance of BRD9 in GBC. Cell Counting Kit-8 and colony formation assays were performed to determine the effects of BRD9 on cell growth. The functional role of BRD9 in GBC was explored using qRT-PCR, western blotting, siRNA, and CHIP-qPCR. mRNA sequencing was performed to explore the underlying mechanisms of BRD9, and a nude mouse model of GBC was established to explore the anti-tumor effects of the BRD9 inhibitor I-BRD9 in vivo. BRD9 expression was elevated in GBC tissues compared with adjacent non-tumor tissues, and high BRD9 expression was associated with poor prognosis in patients with GBC. BRD9 knockdown by siRNA significantly decreased cell growth. Targeting BRD9 with I-BRD9 inhibited the proliferation of GBC cells without significant toxic effects. Additionally, I-BRD9 treatment suppressed CST1 expression in GBC cell lines, thereby inhibiting the PI3K-AKT pathway. The transcription factor FOXP1 was found to interact with BRD9 to regulate CST1 expression. Collectively, these results suggest that BRD9 may be a promising biomarker and therapeutic target for GBC.

Dissecting and predicting different types of binding sites in nucleic acids based on structural information.

The biological functions of DNA and RNA generally depend on their interactions with other molecules, such as small ligands, proteins and nucleic acids. However, our knowledge of the nucleic acid binding sites for different interaction partners is very limited, and identification of these critical binding regions is not a trivial work. Herein, we performed a comprehensive comparison between binding and nonbinding sites and among different categories of binding sites in these two nucleic acid classes. From the structural perspective, RNA may interact with ligands through forming binding pockets and contact proteins and nucleic acids using protruding surfaces, while DNA may adopt regions closer to the middle of the chain to make contacts with other molecules. Based on structural information, we established a feature-based ensemble learning classifier to identify the binding sites by fully using the interplay among different machine learning algorithms, feature spaces and sample spaces. Meanwhile, we designed a template-based classifier by exploiting structural conservation. The complementarity between the two classifiers motivated us to build an integrative framework for improving prediction performance. Moreover, we utilized a post-processing procedure based on the random walk algorithm to further correct the integrative predictions. Our unified prediction framework yielded promising results for different binding sites and outperformed existing methods.

Longitudinal patient-reported outcomes after minimally invasive McKeown esophagectomy for patients with esophageal squamous cell carcinoma.

PURPOSE: Surgery for esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and high complication rate, resulting in a heavy symptom burden and poor health-related quality of life (QOL). We evaluated longitudinal patient-reported outcomes (PROs) to analyze the correlations between symptoms and QOL and their changing characteristics during postoperative rehabilitation. METHODS: We investigated patients with ESCC who underwent minimally invasive McKeown esophagectomy at Sichuan Cancer Hospital between April 2019 and December 2019. Longitudinal data of the clinical characteristics and PROs were collected. The MD Anderson Symptom Inventory and European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires were used to assess symptoms and QOL and compare the trajectories of PROs during the investigation. RESULTS: A total of 244 patients with ESCC were enrolled in this study. Regarding QOL, role and emotional functions returned to baseline at 1 month after surgery, and cognitive and social functions returned to baseline at 3 months after surgery. However, physical function and global QOL did not return to baseline at 1 year after surgery. At 7 days and 1, 3, 6, and 12 months after surgery, the main symptoms of the patients were negatively correlated with physical, role, emotional, cognitive, and social functions and the overall health status (P < 0.05). CONCLUSION: Patients with ESCC experience reduced health-related QOL and persisting symptoms after minimally invasive McKeown esophagectomy, but a recovery trend was observed within 1 month. The long-term QOL after esophagectomy is acceptable.

Machine Learning Model for Predicting Axillary Lymph Node Metastasis in Clinically Node Positive Breast Cancer Based on Peritumoral Ultrasound Radiomics and SHAP Feature Analysis.

OBJECTIVE: This study seeks to construct a machine learning model that merges clinical characteristics with ultrasound radiomic analysis-encompassing both the intratumoral and peritumoral-to predict the status of axillary lymph nodes in patients with early-stage breast cancer. METHODS: The study employed retrospective methods, collecting clinical information, ultrasound data, and postoperative pathological results from 321 breast cancer patients (including 224 in the training group and 97 in the validation group). Through correlation analysis, univariate analysis, and Lasso regression analysis, independent risk factors related to axillary lymph node metastasis in breast cancer were identified from conventional ultrasound and immunohistochemical indicators, and a clinical feature model was constructed. Additionally, features were extracted from ultrasound images of the intratumoral and its 1-5 mm peritumoral to establish a radiomics feature formula. Furthermore, by combining clinical features and ultrasound radiomics features, six machine learning models (Logistic Regression, Decision Tree, Support Vector Machine, Extreme Gradient Boosting, Random Forest, and K-Nearest Neighbors) were compared for diagnostic efficacy, and constructing a joint prediction model based on the optimal ML algorithm. The use of Shapley Additive Explanations (SHAP) enhanced the visualization and interpretability of the model during the diagnostic process. RESULTS: Among the 321 breast cancer patients, 121 had axillary lymph node metastasis, and 200 did not. The clinical feature model had an AUC of 0.779 and 0.777 in the training and validation groups, respectively. Radiomics model analysis showed that the model including the Intratumor +3 mm peritumor area had the best diagnostic performance, with AUCs of 0.847 and 0.844 in the training and validation groups, respectively. The joint prediction model based on the XGBoost algorithm reached AUCs of 0.917 and 0.905 in the training and validation groups, respectively. SHAP analysis indicated that the Rad Score had the highest weight in the prediction model, playing a significant role in predicting axillary lymph node metastasis in breast cancer. CONCLUSION: The predictive model, which integrates clinical features and radiomic characteristics using the XGBoost algorithm, demonstrates significant diagnostic value for axillary lymph node metastasis in breast cancer. This model can provide significant references for preoperative surgical strategy selection and prognosis evaluation for breast cancer patients, helping to reduce postoperative complications and improve long-term survival rates. Additionally, the utilization of SHAP enhancing the global and local interpretability of the model.

Comparative analysis of GoPro and digital cameras in head and neck flap harvesting surgery video documentation: an innovative and efficient method for surgical education.

BACKGROUND: An urgent need exists for innovative surgical video recording techniques in head and neck reconstructive surgeries, particularly in low- and middle-income countries where a surge in surgical procedures necessitates more skilled surgeons. This demand, significantly intensified by the COVID-19 pandemic, highlights the critical role of surgical videos in medical education. We aimed to identify a straightforward, high-quality approach to recording surgical videos at a low economic cost in the operating room, thereby contributing to enhanced patient care. METHODS: The recording was comprised of six head and neck flap harvesting surgeries using GoPro or two types of digital cameras. Data were extracted from the recorded videos and their subsequent editing process. Some of the participants were subsequently interviewed. RESULTS: Both cameras, set at 4 K resolution and 30 frames per second (fps), produced satisfactory results. The GoPro, worn on the surgeon's head, moves in sync with the surgeon, offering a unique first-person perspective of the operation without needing an additional assistant. Though cost-effective and efficient, it lacks a zoom feature essential for close-up views. In contrast, while requiring occasional repositioning, the digital camera captures finer anatomical details due to its superior image quality and zoom capabilities. CONCLUSION: Merging these two systems could significantly advance the field of surgical video recording. This innovation holds promise for enhancing technical communication and bolstering video-based medical education, potentially addressing the global shortage of specialized surgeons.

Gouty Tophus Erodes Nasal Bone But Presents as Painless Hump.

A 32-year-old male presented with a painless swelling on his nasal dorsum, persisting for over 3 months. He reported a gradual increase in the size of the mass, with no identifiable triggers except occasional skin redness. He denied nosebleeds, rhinorrhea, nasal obstruction, trauma, prior surgery, or spontaneous pain. His medical history revealed gout, managed with colchicine and diclofenac. Despite dietary and pharmaceutical interventions, he continued to have bouts of hyperuricemia, with blood uric acid levels measuring 739 µmol/L. Multiple tophi were evident, especially on the left first metatarsophalangeal joint (Figure 1A). Examination revealed an irregularly shaped, immobile, hard swelling at the nasal radix, measuring 3 cm×2 cm. Computerized tomography (CT) imaging of the nose showed bilateral nasal bone destruction from the lesion. Given its impact on the patient's appearance and his history of gout, the mass was initially diagnosed as unusual gouty tophus. The patient requested surgical removal of the lesion, and the dissection revealed a mass partly encased by a capsule-like connective tissue adherent to the nasal bone. As the lesion damaged the nasal bone, removal of the lesion led to defect of nasal bone. After an extensive rinse of the surgery site, the incision was sutured.

Study on diagnosing thyroid nodules of ACR TI-RADS 4-5 with multimodal ultrasound radiomics technology.

BACKGROUND: Explore the feasibility of using the multimodal ultrasound (US) radiomics technology to diagnose American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) 4-5 thyroid nodules. METHOD: This study prospectively collected the clinical characteristics, conventional, and US elastography images of 100 patients diagnosed with ACR TI-RADS 4-5 nodules from May 2022 to 2023. Independent risk factors for malignant thyroid nodules were extracted and screened using methods such as the least absolute shrinkage and selection operator (LASSO) logistic regression (LR) model, and a multimodal US radiomics combined diagnostic model was established. Using a multifactorial LR analysis and a Rad-score rating, the predictive performance was validated and evaluated, and the final threshold range was determined to assess the clinical net benefit of the model. RESULTS: In the training set, the US radiomics combined predictive model area under curve (AUC = 0.928) had higher diagnostic performance compared with clinical characteristics (AUC = 0.779), conventional US (AUC = 0.794), and US elastography model (AUC = 0.852). In the validation set, the multimodal US radiomics combined diagnostic model (AUC = 0.829) also had higher diagnostic performance compared with clinical characteristics (AUC = 0.799), conventional US (AUC = 0.802), and US elastography model (AUC = 0.718). CONCLUSION: Multi-modal US radiomics technology can effectively diagnose thyroid nodules of ACR TI-RADS 4-5, and the combination of radiomics signature and conventional US features can further improve the diagnostic performance.

Multi-factor early monitoring method based on D-dimer for iliac crest flap loss.

BACKGROUND: In recent years, the utilization of autogenous vascularized iliac crest flap for repairing jaw defects has seen a significant rise. However, the visual monitoring of iliac bone flaps present challenges, frequently leading to delayed detection of flap loss. Consequently, there's a urgent need to develop effective indicators for monitoring postoperative complications in iliac crest flaps. METHODS: A retrospective analysis was conducted on 160 patients who underwent vascularized iliac crest flap transplantation for jawbone reconstruction from January 2020 to December 2022. We investigated the changes in D-dimer levels among patients with or without postoperative complications. Additionally, multivariable logistic regression analysis was performed to explore potential individual risk factors, including surgical duration, age, pathology type, absolute and relative D-dimer levels, and gender, culminating in the development of a nomogram. RESULTS: On the first day following surgery, patients who experienced thrombosis exhibited a substantial increase in plasma D-dimer levels, reaching 3.75 mg/L, 13.84 times higher than the baseline. This difference was statistically significant (P < 0.05) compared to patients without postoperative complications. Furthermore, the nomogram we have developed and validated effectively predicts venous thrombosis, assigning individual risk scores to patients. This predictive tool was assessed in both training and validation cohorts, achieving areas under the curve (AUC) of 0.630 and 0.600, with the 95% confidence intervals of 0.452-0.807 and 0.243-0.957, respectively. CONCLUSIONS: Our study illustrates that postoperative plasma D-dimer levels can serve as a sensitive biomarker for monitoring thrombosis-induced flap loss. Moreover, we have developed a novel prediction model that integrates multiple factors, thereby enhancing the accuracy of early identification of patients at risk of thrombosis-associated flap loss. This advancement contributes to improving the overall management and outcomes of such procedures.

Algorithm for the reconstruction of the parotid region: a single institution experience.

OBJECTIVE: This study aims to discuss the characteristics and treatment methods of malignant tumors in the parotid region, as well as the therapeutic effects of immediate free flap reconstruction of soft tissue for postoperative defects. MATERIALS AND METHODS: A retrospective review was conducted on 11 cases of soft tissue flap reconstruction for postoperative defects following the resection of malignant tumors in the parotid region. Statistical analysis was performed based on clinical data. RESULTS: Among the 11 cases of malignant tumors in the parotid region, there were 2 cases of secretory carcinoma (SC) of the salivary gland, 2 cases of squamous cell carcinoma (SCC), 2 cases of carcinosarcoma, 1 case of mucoepidermoid carcinoma (MEC), 1 case of epithelial-myoepithelial carcinoma (EMC), 1 case of salivary duct carcinoma (SDC), 1 case of basal cell carcinoma (BCC), and 1 case of osteosarcoma. Among these cases, 4 were initial diagnoses and 7 were recurrent tumors. The defect repairs involved: 8 cases with anterolateral thigh free flap (ALTF), 2 cases with pectoralis major muscle flaps, and 1 case with forearm flap. The size of the flaps ranged from approximately 1 cm × 3 cm to 7 cm × 15 cm. The recipient vessels included: 4 cases with the facial artery, 4 cases with the superior thyroid artery, and 1 case with the external carotid artery. The ratio of recipient vein anastomosis was: 57% for branches of the internal jugular vein, 29% for the facial vein, and 14% for the external jugular vein. Among the 8 cases that underwent neck lymph node dissection, one case showed lymph node metastasis on pathological examination. In the initial diagnosis cases, 2 cases received postoperative radiotherapy, and 1 case received 125I seed implantation therapeutic treatment after experiencing two recurrences. Postoperative follow-up revealed that 2 cases underwent reoperation due to local tumor recurrence, and there were 2 cases lost to follow-up. The survival outcomes after treatment included: one case of distant metastasis and one case of death from non-cancerous diseases. CONCLUSION: Immediate soft tissue flap reconstruction is an important and valuable option to address postoperative defects in patients afflicted with malignant tumors in the parotid region.

A Cohort Study on Deficiency of ADA2 from China.

PURPOSE: Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. METHODS: A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. RESULTS: Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. CONCLUSION: To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

N-acetyl-L-cysteine attenuates oxidative stress-induced bone marrow endothelial cells apoptosis by inhibiting BAX/caspase 3 pathway.

Bone marrow endothelial cells (BMECs) play a crucial role in the maintenance of bone homeostasis. The decline in BMECs is associated with abnormal bone development and loss. At present, the mechanism of age-related oxidative stress enhancement in BMEC dysfunction remains unclear. Our experiment explored injury caused by oxidative stress enhancement in BMECs both in vivo and in vitro. The BMECs, indicators of oxidative stress, bone mass, and apoptosis-related proteins were analyzed in different age groups. We also evaluated the ability of N-Acetyl-L-cysteine (NAC) attenuate oxidative stress injury in BMECs. NAC treatment attenuated reactive oxygen species (ROS) overgeneration and apoptosis in BMECs in vitro and alleviated the loss of BMECs and bone mass in vivo. In conclusion, this study could improve our understanding of the mechanism of oxidative stress-induced BMECs injury and whether NAC has therapeutic potential in senile osteoporosis.

ZnTe/rGO Composite as the Fully Zinced Conversion-Type Cathodes for Aqueous Zinc Ion Batteries.

Conversion-type cathodes for aqueous zinc ion batteries (ZIBs) can provide flat plateau slop and stable output potential, compared to general intercalation-type cathodes. The high volumetric capacity and stable output potential of Te make it a promising cathode for ZIBs, but sluggish kinetics and large volume change hinder its further application. To address these issues, we revisit fully zinced ZnTe and construct ZnTe/rGO composites as the new conversion-type cathode. The electrode undergoes a solid-to-solid conversion reaction and shows a stable output potential with ultra-flat discharge plateau slop of 0.09 V (Ah g-1 )-1 . When ZnTe is de-zinced and transformed to Te during charge process, it has a volume shrinkage which generates empty space in graphene matrix for latter volume expansion of Te. The graphene matrix also improves conductivity and reaction kinetics of the cathode. Due to the combination of pre-zincation of ZnTe, graphene matrix and the elimination of "shuttle effects" process, ZnTe/rGO electrode exhibits a high and stable capacity of 186 mAh g-1 at 500 mA g-1 after 300 cycling, with almost no decay after initial 10 cycles.

Engineering Oxygen Vacancies on VO2 Multilayered Structures for Efficient Zn2+ Storage.

Vanadium dioxide (VO2 (B)) is a proper cathode for aqueous zinc-ion batteries (ZIBs) due to its shear structure and high theoretical capacity. However, the sluggish kinetics and structure instability derived from the strong electrostatic interaction between Zn2+ and the VO2 host hinder its further application. Defect engineering is a useful way to circumvent the limitations. Herein, oxygen-defect VO2 (Od -VO2 ) with tunable oxygen vacancy concentration are obtained via a facile one-step hydrothermal method by adjusting ascorbic acid addition. It is proved that oxygen vacancies can provide extra active sites for Zn2+ storage and reduced electrostatic barrier for Zn2+ transportation, but excessive vacancy content would lead to a reverse effect. The Od -VO2 cathode with optimum oxygen vacancy concentration achieves an outstanding performance with a high capacity of 380 mAhg-1 at 0.2 A g-1 , excellent cycle stability with 92.6 % capacity retention after 2000 cycles at 3 A g-1 and a high energy density of 197 Wh kg-1 at the power density of 0.641 kW kg-1 . Therefore, this defect engineering method for Od -VO2 provides an attractive way for high-performance aqueous ZIB cathodes.

Effects of family multi-generational relationship on multimorbidity and healthy life expectancy for second generations: insight from the China Health and Retirement Longitudinal Study.

OBJECTIVE: In the context of aging, Chinese families consisting of more than three generations (grandparents, parents, children) are the norm. The second generation (parents) and other family members may establish a downward (contact only with children) or two-way multi-generational relationship (contact with children and grandparents). These multi-generational relationships may have the potential effect on multimorbidity burden and healthy life expectancy in the second generation, but less is known about the direction and intensity of this effect. This study aims to explore this potential effect. METHODS: We obtained longitudinal data from the China Health and Retirement Longitudinal Study from 2011 to 2018, which included 6,768 people. Cox proportional hazards regression was used to assess the association between multi-generational relationships and the number of multimorbidity. The Markov multi-state transition model was used to analyze the relationship between multi-generational relationships and the severity of multimorbidity. The multistate life table was used to calculate healthy life expectancy for different multi-generational relationships. RESULTS: The risk of multimorbidity in two-way multi-generational relationship was 0.830 (95% CIs: 0.715, 0.963) times higher than that in downward multi-generational relationship. For mild multimorbidity burden, downward and two-way multi-generational relationship may prevent aggravation of burden. For severe multimorbidity burden, two-way multi-generational relationship may aggravate the burden. Compared with two-way multi-generational relationship, the second generations with downward multi-generational relationship has a higher healthy life expectancy at all ages. CONCLUSION: In Chinese families with more than three generations, the second generations with severe multimorbidity burden may aggravate the condition by providing support to elderly grandparents, and the support provided by offspring to the second generations plays a vital positive role in improving the quality of life and narrowing the gap between healthy life expectancy and life expectancy.

Activation of the p62-Keap1-Nrf2 pathway protects against oxidative stress and excessive autophagy in ovarian granulosa cells to attenuate DEHP-induced ovarian impairment in mice.

Di-(2-ethylhexyl) phthalate (DEHP) is widely used in various plastics but has been demonstrated to cause female reproductive toxicity. However, the exact mechanism underlying the ovarian damage induced by DEHP remains unclear. In this study, DEHP was administered orally to 5-week-old female mice for 30 days at doses of 0, 250, 500, and 1000 mg/kg/day. The findings demonstrated that DEHP exposure disrupted ovarian function and follicular development as well as induced oxidative stress and autophagy in ovarian granulosa cells (GCs). Further, 200 µM mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of DEHP in vivo, induced autophagy in both human ovarian granulosa cells line (KGN) and mouse primary GCs within 24 h in vitro. However, it did not affect the p62-dependent autophagy flux. Furthermore, MEHP-induced autophagy was inhibited by the autophagy inhibitor 3-MA and exacerbated by the autophagy activator rapamycin, indicating that MEHP induces excessive autophagy in GCs. Subsequently, we found that MEHP-induced autophagic cell death was primarily attributed to oxidative damage from elevated intracellular ROS levels. Meanwhile, MEHP exposure induced nuclear translocation of erythroid-derived factor 2-related factor (Nrf2), a key regulator of antioxidant activity resulting in activating antioxidant effects. Interestingly, we also found that MEHP-induced increase in p62 competitively binds Keap1, thereby facilitating nuclear translocation of Nrf2 and establishing a positive feedback loop in antioxidant regulation. Therefore, this study demonstrated that inhibition of Nrf2 could aggravate oxidative damage and enhance excessive autophagy caused by MEHP, while activation of Nrf2 could reverse the trend. These findings have also been reinforced in studies of cultured ovaries in vitro. Our study suggests that the p62-Keap1-Nrf2 pathway may serve as a potential protective mechanism against DEHP-induced oxidative stress and excessive autophagy in mouse GCs.

Understanding the Effect of *CO Coverage on C-C Coupling toward CO2 Electroreduction.

Cu-based tandem nanocrystals have been widely applied to produce multicarbon (C2+) products via enhancing CO intermediate (*CO) coverage toward CO2 electroreduction. Nevertheless, it remains ambiguous to understand the intrinsic correlation between *CO coverage and C-C coupling. Herein, we constructed a tandem catalyst via coupling CoPc with the gas diffusion electrode of Cu (GDE of Cu-CoPc). A faradaic efficiency for C2+ products of 82% was achieved over a GDE of Cu-CoPc at an applied current density of 480 mA cm-2 toward CO2 electroreduction, which was 1.8 times as high as that over the GDE of Cu. Based on in situ experiments and density functional theory calculations, we revealed that the high *CO coverage induced by CO-generating CoPc promoted the local enrichment of *CO with the top adsorption mode, thus reducing the energy barrier for the formation of OCCO intermediate. This work provides an in-depth understanding of the surface coverage-dependent mode-specific C-C coupling mechanism toward CO2 electroreduction.

Leveraging Chiral Zr(IV)-Based Metal-Organic Frameworks To Elucidate Catalytically Active Rh Species in Asymmetric Hydrogenation Reactions.

One of the most widely employed strategies to produce chiral molecules involves the asymmetric hydrogenation of functionalized olefins using rhodium catalysts. Despite their excellent performance, the exact identity of the active Rh species is still ambiguous as each site may plausibly feature one or two phosphorus ligands. In this work, we used a sequential postsynthetic modification approach to successfully incorporate single-site Rh species into a zirconium-based metal-organic framework comprised of chiral spinol-based ligands. These Rh species feature one phosphorus ligand per Rh, which contrasts with the molecular analogue that contains two phosphorus ligands per Rh site. Following extensive characterization of the Rh-monophosphorus material using techniques including solid-state NMR and extended X-ray absorption fine-structure (EXAFS) spectroscopy, we studied their catalytic performance in the asymmetric hydrogenations of enamides and α-dehydroamino acid esters and observed excellent yields and enantioselectivities (up to 99.9% ee). Notably, the Rh-monophosphorus catalyst is 5 times more active than the homogeneous Rh-biphosphorus control, which we attributed to the higher activity of the single-site Rh-monophosphorus species and the confined MOF cavities that can enrich reactants. In addition, we observed a unique topology-dependent behavior in which linker expansion leads to the formation of a novel Zr-MOF with a distinct 4,8-connected net that cannot be phosphorylated, presumably due to intense tensile strain and steric repulsion present within this framework. Finally, we demonstrate the utility of this single-site Rh-monophosphorus catalyst in the gram-scale synthesis of (R)-cinacalcet hydrochloride, a first-in-class drug in the therapy of secondary hyperparathyroidism and parathyroid carcinoma, with 99.1% ee.

CT-based radiomics to predict development of macrovascular invasion in hepatocellular carcinoma: A multicenter study.

BACKGROUND: Macrovascular invasion (MaVI) occurs in nearly half of hepatocellular carcinoma (HCC) patients at diagnosis or during follow-up, which causes severe disease deterioration, and limits the possibility of surgical approaches. This study aimed to investigate whether computed tomography (CT)-based radiomics analysis could help predict development of MaVI in HCC. METHODS: A cohort of 226 patients diagnosed with HCC was enrolled from 5 hospitals with complete MaVI and prognosis follow-ups. CT-based radiomics signature was built via multi-strategy machine learning methods. Afterwards, MaVI-related clinical factors and radiomics signature were integrated to construct the final prediction model (CRIM, clinical-radiomics integrated model) via random forest modeling. Cox-regression analysis was used to select independent risk factors to predict the time of MaVI development. Kaplan-Meier analysis was conducted to stratify patients according to the time of MaVI development, progression-free survival (PFS), and overall survival (OS) based on the selected risk factors. RESULTS: The radiomics signature showed significant improvement for MaVI prediction compared with conventional clinical/radiological predictors (P < 0.001). CRIM could predict MaVI with satisfactory areas under the curve (AUC) of 0.986 and 0.979 in the training (n = 154) and external validation (n = 72) datasets, respectively. CRIM presented with excellent generalization with AUC of 0.956, 1.000, and 1.000 in each external cohort that accepted disparate CT scanning protocol/manufactory. Peel9_fos_InterquartileRange [hazard ratio (HR) = 1.98; P < 0.001] was selected as the independent risk factor. The cox-regression model successfully stratified patients into the high-risk and low-risk groups regarding the time of MaVI development (P < 0.001), PFS (P < 0.001) and OS (P = 0.002). CONCLUSIONS: The CT-based quantitative radiomics analysis could enable high accuracy prediction of subsequent MaVI development in HCC with prognostic implications.

In-Situ Generated High-Valent Iron Single-Atom Catalyst for Efficient Oxygen Evolution.

Oxygen evolution reaction (OER) plays an important role in renewable energy supplies as the anodic reaction for electrochemical transformation of various chemicals. Iron-based OER catalysts are potential candidates due to their abundance but suffer from poor activity. Here we demonstrate that a single-atom iron catalyst with in-situ generated Fe4+ centers is highly active toward OER. Only an overpotential of 320 mV was needed to reach 10 mA cm-2. The catalyst exhibited an ultrahigh turnover frequency of 0.62 s-1 at an overpotential of 0.35 V, which is comparable to currently reported transitional-metal based OER catalysts. Experimental and theoretical studies revealed that the valence state of the metal center transferred from Fe3+ to highly active Fe4+ prior to the OER process. This transformation was originated from the strong interaction between atomic Fe and carbon support via C-O-Fe bonding, leading to a lower energy barrier of the rate-limiting *OOH formation.