bluuebunny/crossref_metadata_2025 huggingface dataset:
Plant Protein‐Peptide Supramolecular Polymers with Reliable Tissue Adhesion for Surgical Sealing
Authors: Nie Junlian , Sun Yingchuan , Cheng Xueliang , Wen Guang , Liu Xiaohuan , Cheng Meng , Zhao Jianwu , Li Wen
Published: March 2023

The fusion of protein science and peptide science opens up new frontiers in creating innovative biomaterials. Herein, a new kind of adhesive soft materials based on a natural occurring plant protein and short peptides via a simple co‐assembly route are explored. The hydrophobic zein is supercharged by sodium dodecyl sulfate to form a stable protein colloid, which is intended to interact with charge‐complementary short peptides via multivalent ionic and hydrogen bonds, forming adhesive materials at macroscopic level. The adhesion performance of the resulting soft materials can be fine‐manipulated by customizing the peptide sequences. The adhesive materials can resist over 78 cmH2O of bursting pressure, which is high enough to meet the sealing requirements of dural defect. Dural sealing and repairing capability of the protein‐peptide biomaterials are further identified in rat and rabbit models. In vitro and in vivo assays demonstrate that the protein‐peptide adhesive shows excellent anti‐swelling property, low cell cytotoxicity, hemocompatibility, and inflammation response. In particular, the protein‐peptide supramolecular biomaterials can in vivo dissociate and degrade within two weeks, which can well match with the time‐window of the dural repairing. This work underscores the versatility and availability of the supramolecular toolbox in the easy‐to‐implement fabrication of protein‐peptide biomaterials.
Design, Synthesis and Application of C2‐Symmetric Cycloglycerodiphosphate Catalysts
Authors: Antenucci Achille , Ghigo Giovanni , Cassetta Davide , Alcibiade Marco , Dughera Stefano
Published: March 2023

Chiral phosphoric acids (CPAs) and their salts are the privileged catalysts in a plethora of asymmetric transformations. All of the scaffolds of efficient CPAs rely on C2‐symmetry and axial chirality, while the only examples of punctually chiral CPAs are TADDOL derivatives. Herein, we present the design and the synthesis of C2‐symmetric cycloglycerophosphates (cGPAs) and their application throughout the addition of trimethylsilyl cyanide (TMSCN) to aldehydes and ketones, to obtain the corresponding cyanohydrins in yields between 77 and 99% and ee between 84.2 and 99.5% (27 examples). A DFT computational model is moreover performed to rationalize the reaction mechanism and its stereochemical outcome.

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Design of Lysozyme‐Templated Biocompatible Fluorescent Nanocomposites and Their Potential Applications for Cell Imaging, Hydrogen Peroxide Sensing, and Cancer Therapy
Authors: Das Sourav , Tripathy Sanchita , Sreedhar Bojja , Mukherjee Sudip , Patra Chitta Ranjan
Published: March 2023

Recently, multifunctional metal‐based nanocomposites gained immense importance in various biomedical applications. Here, a simple approach is reported to synthesize fluorescent bimetallic nanocomposites (NCs) of silver‐gold (Ag@Au NC) and silver‐platinum (Ag@Pt NC) by reducing silver nitrate (AgNO3) on gold nanoparticles and platinum nanoparticles (AuNPs, PtNPs), respectively, in the presence of lysozyme that acts as capping agent. Various in vitro (in normal cells including Chinese hamster ovarian and human umbilical vein endothelial cells) and in vivo (in mouse and chicken egg chorioallantoic membrane model) studies reveal the biocompatibility of these nanocomposites. However, these NCs show inhibition of cancer cell proliferation when treated to various cancer cells (MCF‐7, MDA‐MB‐231, and B16F10), indicating their anticancer property. Intraperitoneal administration of these NCs resulted in the regression of melanoma tumor in C57BL/6J mouse model. Further, these NCs displayed green fluorescence inside MCF‐7 cells facilitating in vitro live‐cell imaging and sense hydrogen peroxide (H2O2) in cellular level (B16F10 and MCF‐7) using their fluorescence enhancement property in presence of H2O2.The results (in vitro and in vivo) altogether demonstrate the promising multifunctional applications of bimetallic nanocomposites (NCs) that can be utilized as promising transformative drugs in cancer theranostics applications.
Oleic Acid Dissolves cGAS–DNA Phase Separation to Inhibit Immune Surveillance
Authors: Wang Lina , Liu Qiaoling , Wang Na , Li Siru , Bian Wei , Sun Zhen , Wang Lulu , Wang Li , Liu Caigang , Song Chengli , Liu Quentin , Yang Qingkai
Published: March 2023

Phase separation (PS) is a fundamental principle in diverse life processes including immunosurveillance. Despite numerous studies on PS, little is known about its dissolution. Here, it is shown that oleic acid (OA) dissolves the cyclic GMP–AMP synthase (cGAS)–deoxyribonucleic acid (DNA) PS and inhibits immune surveillance of DNA. As solvent components control PS and metabolites are abundant cellular components, it is speculated that some metabolite(s) may dissolve PS. Metabolite‐screening reveals that the cGAS–DNA condensates formed via PS are markedly dissolved by long‐chain fatty acids, including OA. OA revokes intracellular cGAS–PS and DNA‐induced activation. OA attenuates cGAS‐mediated antiviral and anticancer immunosurveillance. These results link metabolism and immunity by dissolving PS, which may be targeted for therapeutic interventions.
Biomimetic Enzyme Cascade Structural Color Hydrogel Microparticles for Diabetic Wound Healing Management
Authors: Wang Li , Chen Guopu , Fan Lu , Chen Hanxu , Zhao Yuanjin , Lu Ling , Shang Luoran
Published: March 2023

Hard‐healing diabetic wound brings burgeoning physical and mental burdens to patients. Current treatment strategies tend to achieve multistage promotion and real‐time reporting to facilitate wound management. Herein, a biomimetic enzyme cascade inverse opal microparticles system for wound healing, which is intergated with glucose oxidase (GOD) and copper peroxide (CP). Such microparticles are composed of biofriendly hyaluronic acid methacryloyl (HAMA) and pH‐responsive acrylic acid (AA), which provided abundant binding sites and spaces for chemical immobilizing and physical doping of enzymes and metal bioinorganics. When the cascade catalytic system is applied on wound sites, hyperglycemia environment would serve as a hydrogen peroxide (H2O2) generator through GOD catalysis, while acidic environment triggers the decomposition of CP, further catalyzing H2O2 to generate reactive oxygen species (ROS). Additionally, the distinctive structural color of the microparticles can visually reflect the wound pH and intelligently estimate the healing state. It is demonstrated that such microparticle systems exhibit excellent broad‐spectrum antibacterial and angiogenesis‐promoting properties, as well as significant real‐time reporting ability for wound healing. These features indicate that enzyme cascade structural color microparticles possess valuable potential in wound healing and related field.
A Dendrimer Peptide (KK2DP7) Delivery System with Dual Functions of Lymph Node Targeting and Immune Adjuvants as a General Strategy for Cancer Immunotherapy
Authors: Zhang Rui , Tang Lin , Wang Yusi , Tian Yaomei , Wu Siwen , Zhou Bailing , Dong Chunyan , Zhao Binyan , Yang Yuling , Xie Daoyuan , Yang Li
Published: March 2023

The clinical efficacy of personalized cancer vaccines still needs to be improved due to their insufficient immune effect. The development of innovative adjuvants and lymph node‐targeted delivery systems is the key to improving the clinical efficacy of personalized vaccines. However, there is still a lack of an adjuvant delivery system that is simple in preparation and capable of mass production and integrates adjuvant and lymph node targeted delivery functions. Here, this work reports that a simple dendrimer polypeptide (KK2DP7) nanoparticle enhances the immune efficacy of an OVA/neoantigen‐based vaccine. Due to its multiple functions as a delivery vehicle, immune adjuvant, and facilitator of dendritic cell migration, KK2DP7 efficiently increases the efficiency of antigen uptake and cross‐presentation by antigen‐presenting cells (APCs) and delivers antigens to lymph nodes via APCs. Strikingly, the antitumor effect of KK2DP7/OVA is superior to that of commonly used adjuvants such as poly(I:C), CpG, and aluminum adjuvant combined with OVA. Furthermore, KK2DP7/OVA combined with anti‐PD‐1 antibody is able to prevent tumor recurrence in a postoperative recurrent tumor model. Thus, KK2DP7‐based cancer vaccines alone or in combination with immune checkpoint blockade therapies to treat tumors or postoperative tumor recurrence are a powerful strategy to enhance antitumor immunity.
Near‐Sensor Reservoir Computing for Gait Recognition via a Multi‐Gate Electrolyte‐Gated Transistor
Authors: Liu Xuerong , Sun Cui , Guo Zhecheng , Xia Xiangling , Jiang Qian , Ye Xiaoyu , Shang Jie , Zhang Yuejun , Zhu Xiaojian , Li Run‐Wei
Published: March 2023

The recent emergence of various smart wearable electronics has furnished the rapid development of human–computer interaction, medical health monitoring technologies, etc. Unfortunately, processing redundant motion and physiological data acquired by multiple wearable sensors using conventional off‐site digital computers typically result in serious latency and energy consumption problems. In this work, a multi‐gate electrolyte‐gated transistor (EGT)‐based reservoir device for efficient multi‐channel near‐sensor computing is reported. The EGT, exhibiting rich short‐term dynamics under voltage modulation, can implement nonlinear parallel integration of the time‐series signals thus extracting the temporal features such as the synchronization state and collective frequency in the inputs. The flexible EGT integrated with pressure sensors can perform on‐site gait information analysis, enabling the identification of motion behaviors and Parkinson's disease. This near‐sensor reservoir computing system offers a new route for rapid analysis of the motion and physiological signals with significantly improved efficiency and will lead to robust smart flexible wearable electronics.
COVID‐19 through the lens of seasonal agriculture in South Asia
Authors: Kharel Arjun , Mobarak Ahmed Mushfiq , Shenoy Ashish , Vernot Corey
Published: March 2023

75% of the world's poor reside in rural areas where the local economy is tied to agriculture. We interpret new panel data on COVID‐19 from Nepal and Bangladesh in relation to agricultural seasonality. Conditions in April–June 2020 were comparable to a typical lean season even though the pandemic arrived at harvest time. Income losses stem from both depressed local employment as well as lower migration and remittances. We also document indirect adverse health impacts on nutrition and mental health. Findings are specific to the nature of economic activity at harvest, and effective pandemic policy must evolve with the agricultural season.
Impact and effectiveness of a mandatory competency‐based simulation program for pediatric emergency medicine faculty
Authors: Pirie Jonathan , Fayyaz Jabeen , Prinicipi Tania , Kempinska Anna , Gharib Mireille , Simone Laura , Glanfield Carrie , Walsh Catharine M
Published: March 2023

Introduction

Pediatric emergency medicine physicians struggle to maintain their critical procedural and resuscitation skills. Continuing professional development programs incorporating simulation and competency‐based standards may help ensure skill maintenance. Using a logic model framework, we sought to evaluate the effectiveness of a mandatory annual competency‐based medical education (CBME) simulation program.

Methods

The CBME program, evaluated from 2016 to 2018, targeted procedural, point‐of‐care ultrasound (POCUS) and resuscitation skills. Delivery of educational content included a flipped‐classroom website, deliberate practice, mastery‐based learning, and stop‐pause debriefing. Participants' competence was assessed using a 5‐point global rating scale (GRS; 3 = competent, 5 = mastery). Statistical process control charts were used to measure the effect of the CBME program on team performance during in situ simulations (ISS), measured using the Team Emergency Assessment Measure (TEAM) scale. Faculty completed an online program evaluation survey.

Results

Forty physicians and 48 registered nurses completed at least one course over 3 years (physician mean ± SD 2.2 ± 0.92). Physicians achieved competence on 430 of 442 stations (97.3%). Mean ± SD GRS scores for procedural, POCUS, and resuscitation stations were 4.34 ± 0.43, 3.96 ± 0.35, and 4.17 ± 0.27, respectively. ISS TEAM scores for “followed standards and guidelines” improved significantly. No signals of special cause variation emerged for the other 11 TEAM items, indicating skills maintenance. Physicians rated CBME training as highly valuable (mean question scores 4.15–4.85/5). Time commitment and scheduling were identified as barriers to participation.

Conclusions

Our mandatory simulation‐based CBME program had high completion rates and very low station failures. The program was highly rated and faculty improved or maintained their ISS performance across TEAM scale domains.
Associations between dietary patterns and dementia‐related neuroimaging markers
Authors: Samuelsson Jessica , Marseglia Anna , Lindberg Olof , Westman Eric , Pereira Joana B. , Shams Sara , Kern Silke , Ahlner Felicia , Rothenberg Elisabet , Skoog Ingmar , Zettergren Anna
Published: March 2023

BACKGROUND

The exploration of associations between dietary patterns and dementia‐related neuroimaging markers can provide insights on food combinations that may impact brain integrity.

METHODS

Data were derived from the Swedish Gothenburg H70 Birth Cohort Study (n = 610). Three dietary patterns were obtained using principal component analysis. Magnetic resonance imaging markers included cortical thickness, an Alzheimer's disease (AD) signature score, small vessel disease, and white matter microstructural integrity. Adjusted linear/ordinal regression analyses were performed.

RESULTS

A high‐protein and alcohol dietary pattern was negatively associated with cortical thickness in the whole brain (Beta: −0.011; 95% confidence interval [CI]: −0.018 to −0.003), and with an Alzheimer's disease cortical thickness signature score (Beta: −0.013; 95% CI: −0.024 to −0.001). A positive association was found between a Mediterranean‐like dietary pattern and white matter microstructural integrity (Beta: 0.078; 95% CI: 0.002–0.154). No associations were found with a Western‐like dietary pattern.

DISCUSSION

Dietary patterns may impact brain integrity through neurodegenerative and vascular pathways.

Highlights

Certain dietary patterns were associated with dementia‐related neuroimaging markers.

A Mediterranean dietary pattern was positively associated with white matter microstructure.

A high‐protein and alcohol pattern was negatively associated with cortical thickness.
Driving Polymer Brushes from Synthesis to Functioning
Authors: Wang Rui , Wei Qiangbing , Sheng Wenbo , Yu Bo , Zhou Feng , Li Bin
Published: March 2023

The great success of controlled radical polymerizations has encouraged researchers to develop more facile and robust approaches for surface‐initiated polymerizations (SIPs) to fabricate polymer brushes, even for non‐experts. In recent years, external‐stimuli‐mediated radical polymerization methods have come to the fore as SIPs because of their less rigorous synthetic procedures and high controllability, which expand the opportunities for synthesizing macromolecules with desired chemical compositions and structures, as well as tailor‐made polymers and bioconjugates that show broad applicability and physiological compatibility. This review discusses the latest developments in surface‐initiated polymerization methods, in particular, external‐stimuli mediated atom transfer radical polymerization (ATRP), photo‐induced polymerizations, and reversible addition‐fragmentation chain transfer (RAFT) polymerization, as well as other methods and their combination for the application in surface grafting. The implementation of these methods is of great interest due to their unique possibilities to temporally control a polymerization process, fast and straightforward polymerization, and environmentally benign features, which lead to established and emerging applications in biolubrication, antifouling, and biosensing.
Precise Epitope Organization with Self‐adjuvant Framework Nucleic Acid for Efficient COVID‐19 Peptide Vaccine Construction
Authors: Shen Fengyun , Xiong Zijian , Wu Yumin , Peng Rui , Wang Yue , Sun Lele , Fan Chunhai , Liu Zhuang
Published: March 2023

Peptide vaccines have advantages in easy fabrication and high safety, but their effectiveness is hampered by the poor immunogenicity of the epitopes themselves. Herein, we constructed a series of framework nucleic acids (FNAs) with regulated rigidity and size to precisely organize epitopes in order to reveal the influence of epitope spacing and carrier rigidity on the efficiency of peptide vaccines. We found that assembling epitopes on rigid tetrahedral FNAs (tFNAs) with the appropriate size could efficiently enhance their immunogenicity. Further, by integrating epitopes from SARS‐CoV‐2 on preferred tFNAs, we constructed a COVID‐19 peptide vaccine which could induce high titers of IgG against the receptor binding domain (RBD) of SARS‐CoV‐2 spike protein and increase the ratio of memory B and T cells in mice. Considering the good biocompatibility of tFNAs, our research provides a new idea for developing efficient peptide vaccines against viruses and possibly other diseases.
Metal‐Organic Frameworks for Breakthrough Separation of 2‐Butene Isomers with High Dynamic Selectivity and Capacity
Authors: Jiang Shuyi , Sun Hao , Gong Ke , Huang Xin , Zhu Yuhao , Feng Xiao , Xie Jing , Liu Jingyao , Wang Bo
Published: March 2023

Developing porous sorbents represents a potential energy‐efficient way for industrial gas separation. However, a bottleneck for reducing the energy penalty is the trade‐off between dynamic adsorption capacity and selectivity. Herein, we showed this problem can be overcome by modulating the kinetic and thermodynamic separation behaviours in metal–organic frameworks for sieving 2‐butene geometric isomers, which are desired for upgrading the raffinates to higher value‐added end products. We found that the iron‐triazolate framework can realize the selective shape screening of 2‐butene isomers assisted by electrostatic interactions at the pore apertures. Further introducing uncoordinated N binding sites by ligand substitution lowered the gas diffusion barrier and greatly boosted the dynamic separation performance. In breakthrough tests under ambient conditions, trans‐2‐C4H8 can be efficiently separated from cis‐2‐C4H8 with a record capacity of 2.10 mmol g−1 with high dynamic selectivity of 2.39.
Self‐Assembled L–DNA Linkers for Rapid Construction of Multi‐Specific Antibody‐Drug Conjugates Library
Authors: Zhou Liujuan , Yang Fan , Bai Zhaoshuai , Zhou Xiaohui , Zhang Zhihai , Li Zhihang , Gong Junyuan , Yu Junqi , Pan Liqiang , Cao Chan , Chou James J.
Published: March 2023

One of the key challenges of improving clinical outcomes of antibody drug conjugates (ADCs) is overcoming cancer resistance to the antibody and/or drug components of ADCs, and hence the need for ADC platforms with high combinatory flexibility. Here, we introduce the use of self‐assembled left‐handed DNA (L–DNA) oligonucleotides to link combinatory single‐domain antibodies and toxin payloads for tunable and adaptive delivery of ADCs. We demonstrate that the method allows convenient construction of a library of ADCs with multi‐specific targeting, multi‐specific payloads, and exact drug‐antibody ratio. The newly constructed ADCs with L–DNA scaffold showed favorable properties of in vitro cell cytotoxicity and in vivo suppression and eradication of solid tumors. Collectively, our data suggest that the L–DNA based modular ADC (MADC) platform is a viable option for generating therapeutic ADCs and for potentially expanding ADC therapeutic window via multi‐specificity.
Asymmetric Total Synthesis of Naphthospironone A
Authors: Liu Jia‐Xuan , Zhang Shi‐Peng , Sun Feng‐Sen , Li Hui , Gong Ya‐Ling , Lu Shi‐Chao , Xu Shu
Published: March 2023

Naphthospironone A, a polyhydroxy cagelike bioactive natural product, was synthesised for the first time in this study. The spiro[bicyclo[3.2.1]octane‐pyran] core was constructed by an acid‐promoted epoxide‐opening lactonisation and a base‐induced intramolecular aldol‐type cyclisation.
Spin–Phonon Interactions and Anharmonic Lattice Dynamics in Fe3GeTe2
Authors: Cai Qingan , Zhang Yuemei , Luong Diana , Tulk Christopher A. , Fokwa Boniface P.T. , Li Chen
Published: March 2023

Raman scattering is performed on Fe3GeTe2 (FGT) at temperatures from 8 to 300 K and under pressures from the ambient pressure to 9.43 GPa. Temperature‐dependent and pressure‐dependent Raman spectra are reported. The results reveal respective anomalous softening and moderate stiffening of the two Raman active modes as a result of the increase of pressure. The anomalous softening suggests anharmonic phonon dynamics and strong spin–phonon coupling. Pressure‐dependent density functional theory and phonon calculations are conducted and used to study the magnetic properties of FGT and assign the observed Raman modes, and . The calculations proved the strong spin–phonon coupling for the mode. In addition, a synergistic interplay of pressure‐induced reduction of spin exchange interactions and spin–orbit coupling effect accounts for the softening of the mode as pressure increases.
Virtual reality tool to support fluid power curriculum
Authors: Assaf Hassan , Vacca Andrea
Published: March 2023

Remote learning has recently become a crucial need in engineering education. In applied disciplines such as fluid power (FP), hands‐on lab experiences constitute an essential component for educating future engineers at both the graduate and undergraduate levels. Physical hydraulic trainers have been developed over the years to expose students to applications of modern FP technology. However, there is a notable absence of virtual tools that can provide students with a realistic feeling of assembling, troubleshooting, and operating an actual hydraulic circuit. This paper describes the effort made to develop an original virtual trainer that fulfills these needs. This virtual trainer is designed to replicate existing physical trainers that were recently designed and implemented for FP education but on a virtual platform. The virtual trainer is implemented in Unity3D software, using CAD drawings of the components from the actual trainer, and provides the user with an interactive environment that reproduces all the aspects of a real lab experience. The tool allows the students to learn by mistake, as in typical activities with a physical trainer and includes realistic operating noise. The core part of the virtual trainer is the object‐oriented simulation model that is behind every hydraulic component. First successfully used in the Fall of 2020, and subsequently utilized in both Spring and Fall 2021 courses, the simulator represents an alternative for hands‐on experiences, and could be a valid option for distance learning students in the future. Details of the implementation approach and some significant cases are covered in the following work.
Development and validation of a nomogram for predicting survival in patients with malignant myofibroblastic tumor
Authors: Wang Xiaolu , Liu Baorui , Li Rutian
Published: March 2023

Background

Malignant myofibroblastic tumors are a rare group of soft tissue sarcomas, for which a prognosis prediction model is lacking. Based on the Surveillance, Epidemiology, and End Results (SEER) database and cases from Nanjing Drum Tower Hospital, the current study constructed and validated a nomogram to assess overall survival of patients with malignant myofibroblastic tumors.

Methods

Data of patients with myofibroblastic tumors diagnosed between 2000 and 2018 were extracted from the SEER database. Similarly, data of patients with myofibroblastic tumor in Nanjing Drum Tower Hospital between May 2016 and March 2022 were collected. Then, we conducted univariate and multivariate Cox analyses to identify independent prognostic parameters to develop the nomogram. The model was evaluated by concordance index (C‐index), calibration curve, the area under the curve (AUC), decision curve analysis (DCA), Kaplan–Meier analysis, and subgroup analyses.

Results

Seven variables were selected to construct the nomogram. The results of the C‐index (0.783), calibration curve, the AUCs, and subgroup analyses demonstrated the accurate predictive capacity and excellent discriminative ability of the nomogram. The DCA of the model indicated its better clinical net benefit than that of the traditional system.

Conclusion

Evaluation of the predictive performance of the nomogram revealed the superior sensitivity and specificity of the model and the higher prediction accuracy of the outcomes compared with those of the traditional system. The established nomogram may assist patients in consultation and help physicians in clinical decision‐making.
Differences in clinical characteristics and prognosis between breast neuroendocrine carcinoma and breast invasive ductal carcinoma: A multicentre population‐based study from China
Authors: Wang Ding‐yuan , Li Shuo‐feng , Gao Song‐lin , Yuan Peng , Zhang Bai‐lin
Published: March 2023

Aim

We constructed a multicentre cohort in China to analyse the differences in clinical characteristics, treatment strategies and prognoses between breast neuroendocrine carcinoma (NEC) and invasive ductal carcinoma (IDC) of the breast.

Methods

All patients with early‐stage breast cancer who attended three hospitals in Beijing from 2000 to 2018 were included in the study. We used propensity score matching to make a 1:3 match between NEC and IDC.

Results

After propensity score matching, 153 patients with IDC and 51 patients with NEC were analysed. Multivariate Cox regression showed that compared to patients with IDC, patients with NEC had a worse disease‐free survival (HR = 2.94, 95% CI: 1.69–5.12, p < 0.001).

Conclusion

NEC patients have a worse disease‐free survival than IDC patients.
Correlation and efficacy of TACE combined with lenvatinib plus PD‐1 inhibitor in the treatment of hepatocellular carcinoma with portal vein tumor thrombus based on immunological features
Authors: Zou Xinhua , Xu Qingyu , You Ran , Yin Guowen
Published: March 2023

Background

Although the appearance of portal vein tumor thrombus (PVTT) is significantly associated with unfavorable prognosis, there is insufficient evidence to confirm the efficacy and safety of the triple combination of transarterial chemoembolization (TACE), lenvatinib, and programmed cell death‐1 (PD‐1) inhibitor for patients with hepatocellular carcinoma (HCC) and PVTT. Furthermore, it remains unclear which patient type can obtain the best survival benefit from this combination therapy.

Methods

The data of 160 patients with HCC and PVTT treated with TACE combined with lenvatinib plus PD‐1 inhibitor (TACE+LEN + PD‐1 group) or TACE combined with lenvatinib (TACE+LEN group) were retrospectively collected and analyzed. To estimate the efficacy and safety of combination therapy for patients with advanced HCC, tumor response, progression‐free survival (PFS), overall survival (OS), biochemical indices, and adverse events (AEs) were assessed in this study. More importantly, tumor immune‐related cytokines were used to identify biomarkers predicting the therapeutic response of combination therapy.

Results

TACE+LEN + PD‐1 was superior to TACE+LEN in OS (23.5 vs. 18.3 months, p = 0.0002) and PFS (7.5 vs. 4.3 months, p < 0.0001). Moreover, TACE+LEN + PD‐1 achieved more preferable benefits with respect to disease control rate (80.00% vs. 56.67%) and objective response rate (38.57% vs. 24.45%) compared with TACE+LEN in patients with HCC and PVTT (p = 0.025). Multivariate analysis showed that Child–Pugh grade, PVTT classification, treatment option, and interleukin (IL)‐6, IL‐17, interferon (IFN)‐α, and vascular endothelial growth factor (VEGF) levels were independent factors related to OS, whereas PVTT classification, treatment option, and IL‐6 and IFN‐α levels were independent factors related to PFS. Furthermore, the subgroup analysis illustrated that the inflammatory cytokines VEGF, IL‐6, IL‐17, and IFN‐α might be novel biomarkers for predicting the survival prognosis of patients with advanced HCC and PVTT treated with TACE+LEN + PD‐1. The safety in the combination group was acceptable.

Conclusions

Compared with TACE+LEN, the triple combination treatment of TACE+LEN + PD‐1 has more promising clinical outcomes and acceptable safety in patients with HCC and PVTT. Child–Pugh grade, PVTT classification, and IL‐6, IL‐17, IFN‐α, and VEGF levels are independent prognostic factors for survival time.
GRIK5 stimulates colon cancer growth and metastasis through cAMP/PKA/CADM3 signaling
Authors: Xie Zhengyong , Ke Yongli , Li Zehang , Chen Junyong , Lei Deqiao , Chen Guijin , Wang Changzheng , Chen Yuhong , Ding Hongliang , Cheng Liyang
Published: March 2023

Glutamate receptor, ionotropic, kainate 5 (GRIK5) is a member of glutamate receptors participating, and the kainate receptor family has been proved to regulate cell proliferation and transformation. Our study aimed at exploring the role of GRIK5 in colon tumor progression. Three hundred and ninety eight colon cancer patients in The Cancer Genome Atlas Program (TCGA) data set and 26 clinical colon cancer patients were included for GRIK5 expression and prognosis analysis. GRIK5 overexpressed HCT116 and CT26 cell lines were established for cell proliferation and Transwell assay. Western blot analysis and immunostaining assay was conducted to evaluate the activation of activation of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cell adhesion molecular 3 (CADM3) signaling in cell lines and tumor tissues. Subcutaneous CT26‐bearing mice model was established to examine GRIK5‐induced tumor growth and metastasis in vivo. Our study identified GRIK5 to be upregulated in patients with colon cancer, and higher GRIK5 levels correlated with the poor overall survival in patients. In vitro, GRIK5 overexpression markedly enhanced the proliferative properties and aggressive behaviors of colon cancer cells. Mechanistically, GRIK5 induced the activation of cAMP/PKA signaling, proceeded with augmented CADM3 expression, eventually resulting in sustained tumor growth. GRIK5 was a crucial scaffold in enabling colon cancer growth and metastasis, which offered a promising target for therapeutic manipulation of colon cancer.
Colorless to black switching with high contrast ratio via the electrochemical process of a hybrid organic–inorganic perovskite
Authors: Xu Ming , Gu Jianmin , Fang Zixun , Li Yu , Wang Xing , Zhao Xiaoyu , Jiao Tifeng , Wang Wei
Published: March 2023

Colorless‐to‐black switching has attracted widespread attention for smart windows and multifunctional displays because they are more useful to control solar energy. However, it still remains a challenge owing to the tremendous difficulties in the design of completely reverse absorptions in transmissive and colored states. Herein, we report on an electrochemical device that can switch between colorless and black by using the electrochemical process of hybrid organic–inorganic perovskite MAPbBr3, which shows a high integrated contrast ratio of up to 73% from 400 to 800 nm. The perovskite solution can be used as the active layer to assemble the device, showing superior transmittance over the entire visible region in neutral states. By applying an appropriate voltage, the device undergoes reversible switching between colorless and black, which is attributed to the formation of lead and Br2 in the redox reaction induced by the electron transfer process in MAPbBr3. In addition, the contrast ratio can be modulated over the entire visible region by changing the concentration and the applied voltage. These results contribute toward gaining an insightful understanding of the electrochemical process of perovskites and greatly promoting the development of switchable devices.
Linkage Chemistry of S(VI) Fluorides
Authors: Zeng Daming , Deng Wei‐Ping , Jiang Xuefeng
Published: March 2023

Sulfur(VI)‐fluoride exchange linkage as a next generation of click chemistry was introduced by Sharpless and coworkers in 2014. Distinguished from CuAAC, the SuFEx reaction proceeds under metal‐free conditions, and the reactive linkers are variable, enabling access to a diverse class of linkage compounds. Therein, a series of SuFEx linkers emerged has been widely prevalent in diverse fields. The SVI−F bond in comparison to SVI−Cl bond features excellent stability and chemoselectivity. The linkage chemistry primarily involves the formation of S−O and S−N bonds via commercially available phenols and amines, yet less study onC‐SuFEx linkage. This review will focus on three types of linkage for SuFEx linkers comprising S−O, S−N, and S−C bonds, and we hope to provide a practical guidance for SuFEx linkage chemistry.
X‐ray Study of Cembranoids with Flexible Rings from Boswellia papyrifera Resins Allowing Structural Revision of Misleading Structures from the Past 70 Years
Authors: Sura Madhu Babu , Zhu Yan‐Xia , Cheng Yong‐Xian
Published: March 2023

Thirty new, highly oxygenated and stereogenic 14‐membered macrocyclic diterpenoids, papyrifuranols A‐Z (1–26) and AA‐AD (27–30), and eight known analogs have been isolated from Boswellia papyrifera resins. All the structures were characterized by detailed spectral analyses, quantum calculations, X‐ray diffraction, and modified Mosher's methods. Notably, six previously reported structures were revised. Our study points out misleading factors of macrocyclic cembranoid (CB) representation in the past seven decades by analyzing of 25 X‐ray structures, lending a hand for the innately challenging structure identification of such flexible macrocyclic CBs and avoiding following the tracks of an overturned cart during future structure characterization and total synthesis. Biosynthetic conversions of all the isolates are proposed, and wound healing bioassays reveal that papyrifuranols N−P could significantly stimulate the proliferation and differentiation of umbilical cord mesenchymal stem cells.
Modular Principle for Complex Disordered Tetrahedral Frameworks in Quenched High‐Pressure Phases of Phosphorus Oxide Nitrides
Authors: Günther Daniel , Baumann Dominik , Schnick Wolfgang , Oeckler Oliver
Published: March 2023

Invited for the cover of this issue are the groups of Oliver Oeckler at Leipzig University and Wolfgang Schnick at University of Munich (LMU). The image background depicts a diffraction pattern of an intergrown crystal containing P40O31N46 as a night sky. P40O31N46 and P74O59N84 form complex disordered frameworks, a cutout of which symbolizes the earth's surface (which mainly contains silicates with related building blocks). The structures are built up from chain‐like building units, which fall like rain, symbolizing the modular building scheme. Read the full text of the article at 10.1002/chem.202203892.
Mortality across the spectrum of hemoglobin level in patients undergoing surgical coronary revascularization
Authors: Khalaji Amirmohammad , Ajam Ali , Sheikhy Ali , Behnoush Amir Hossein , Fallahzadeh Aida , Bagheri Jamshid , Mansourian Soheil , Momtahen Shahram , Masoudkabir Farzad , Hosseini Kaveh
Published: March 2023

Background

Preoperative hemoglobin (Hb) level is a predictor of in‐hospital and midterm mortality in patients undergoing coronary artery bypass grafting surgery (CABG). However, the debate about the different hazards across Hb levels and sex differences in outcome occurrence is still on the table.

Methods

This is a registry‐based serial cross‐sectional study at Tehran Heart Center. Nonanemic patients who underwent CABG with complete follow‐up data were included. The Restricted Cubic Splines (RCS) in the Cox model was used to calculate the sex‐specific correlation between in‐hospital, 6‐month, and 1‐year mortalities and normal Hb levels using odds ratio for the in‐hospital and hazard ratios for 6‐month and 1‐year mortality, adjusted for all possible confounders.

Results

From 2005 to 2016, a total of 13,557 patients were included, of which 134 had in‐hospital mortality as our primary outcome. Preoperative Hb levels were significantly lower in the deceased. Moreover, dead patients had significantly higher rates of diabetes and hypertension, while lower ejection fraction. Cut‐offs for reference Hb level were higher for males compared with females. The correlation between Hb level and in‐hospital mortality was nearly U‐shaped. Quantitatively, Hb of ≥15.62 and ≤13.25 g/dL for men and that of ≥14.92 and ≤13.4 g/dL for women tended to be associated with higher in‐hospital mortality.

Conclusions

The association between preoperative Hb level and in‐hospital mortality differs in men and women and does not follow a linear correlation among nonanemic patients. Both low and high numbers in the Hb level spectrum are at greater risk.
Hemolysis of red blood cells in blood vessels modeled via computational fluid dynamics
Authors: Jędrzejczak Krystian , Makowski Łukasz , Orciuch Wojciech , Wojtas Krzysztof , Kozłowski Michał
Published: March 2023

The research aims to verify the universal relationship between vessel shape and the risk of hemolysis using a rheological model of blood reflecting the physiological processes related to blood for any blood vessel. Blood is a multi‐component fluid, the rheology of which depends on many factors, such as the concentration of red blood cells and local shear stress, which significantly affect the process of hemolysis. Blood rheology models used so far cannot be used for all flows and geometries. Therefore, a new rheology model has been introduced suitable for modeling hemolytic flows observed in arteries with atherosclerotic lesions in the in vivo environment. The previously presented model also has advantages in modeling local viscosity in stenosis. Geometries of the blood vessels from computed tomography scans and simplified models of the actual arteries observed during medical procedures were used in the calculations. Population Balance Based Rheology model predicts the concentration of single, deagglomerated red blood cells and the concentration and size of red blood cell agglomerates, which affect blood rheology and hemolysis. Based on the simulations carried out, a correlation was found between the shape of the vessel cavity and the risk of hemolysis. Presented results can be used in the future to create a correlation between the shape of the atherosclerotic lesions and the risk of hemolysis in the blood to make an initial risk assessment for a given patient.
Elucidating the N−N and C−N Bond‐breaking Mechanism in the Photoinduced Formation of Nitrile Imine
Authors: Guerra Cristian , Ayarde‐Henríquez Leandro , Rodríguez‐Núñez Yeray A. , Ensuncho Adolfo , Chamorro Eduardo
Published: March 2023

In this study, we revealed the significance of chemical bonding for the photochemically induced mechanism of 2‐phenyl tetrazole derivatives generating nitrile imines. The correlated electron localization function shows that the formation of imine nitrile involves two key bond events: (i) the heterolytic C−N breakage taking place in the T1 state and (ii) the homolytic N−N rupture occurring in the T2 excited state. In particular, a cation‐radical specie results from the C−N cleavage, whereas the N−N rupture creates a biradical resonant form of imine nitrile. Additionally, we noticed that the substantial pair delocalization of the C−C‐N bonded structure could play a significant role in the conversion of the biradical imine nitrile into both the propargylic and allenic forms via the T1→S0 deactivation.
Does mandatory corporate social responsibility expenditure by businesses help their stakeholders?
Authors: Ahamed Naseem , Tripathi Nitya Nand
Published: March 2023

This study examines the role of financial performance and board characteristics on corporate social responsibility expenditure (CSR expenditure hereafter). The study is based on a natural experimental design where the Government of India made it legally mandatory for companies meeting certain criteria to spend at least 2% of their average profits in the preceding three financial years towards corporate social responsibility in the companies Act 2013. It examines the propensity of companies to spend towards corporate social responsibility over and above the legal mandate. This study analyze two different schools of thought in the field of corporate social responsibility varying in their assertions. The first school of thought asserts that firms engaged aggressively in CSR expenditure would be viewed positively by the customers/prospective customers. The second school of thought asserts that CSR expenditure reduces the profit of the firm that could have been used productively for asset acquisition, and business expansion. The first school of thought focuses on the good corporate citizenship hypothesis whereas the second school of thought focuses on the efficient utilization of scarce resources hypothesis. Using a dataset of companies listed on NSE 500 index, we found a positive and statistically significant relationship between CSR expenditure and accounting‐based firm performance but a negative relationship with market based firm performance. Size of the firm has a positive relationship with firm performance, alluding to the presence of “size” effect. Board size, board independence and cumulative attendance in board meetings exhibit mixed results with firm performance. Note: A slightly different version of this paper was presented in the 15th ICBF‐2022 conference held at IBS Hyderabad in the online mode. We would like to extend our heartfelt gratitude to all the reviewers and participants whose suggestions helped improve this article.
Recent advances in the tumor‐penetrating peptide internalizing RGD for cancer treatment and diagnosis
Authors: Qian Jing , Zhou Sheng , Lin Peng , Lei Jin , Zheng Shiqi , Xu Wenmang , Wang Yuanyuan , Gao Ziran , Yang Julun
Published: March 2023

Cancer has become a prominent disease that seriously endangers human health. The complexity of the biological characteristics of the tumor makes it challenging for traditional therapeutic drugs to penetrate tumor tissues and exert their antitumor effects. Internalizing RGD peptide (iRGD) is a novel tumor‐homing peptide that binds to αvβ3 and αvβ5 integrins on the surface of tumor vessels through the C‐end rule (CendR) motif. The CendR motif binds to the neuropilin‐1 (NRP‐1) receptor on tumor cells, initiating NRP‐1‐mediated transcytosis to facilitate drug entry into the tumor tissue. Multiple studies demonstrated that iRGD improved the penetration and targeting of antitumor drugs, thereby enhancing their antitumor efficacy. In this review, we initially described the origins of iRGD and its penetration mechanism. Furthermore, we presented updates on the application of iRGD in cancer chemotherapy, photodynamic therapy, gene therapy, immunotherapy, treatment with antibodies or protein‐based biologics, and tumor imaging.
Severe and fatal COVID‐19 is characterised by increased circulating glucagon like peptide 1 and procalcitonin modulated by type 2 diabetes
Authors: Bloch Olga , Kobi Perl , Ben Shimol Ariel , Rotmensh Assaf , Kagansky Dana , Zelnik‐Yovel Dana , Yehudah Gilad Ben , Cantrell Dror , Rapoport Micha J.
Published: March 2023

Aims

Endotoxemia commonly occurs in severe and fatal COVID‐19, suggesting that concomitant bacterial stimuli may amplify the innate immune response induced by SARS‐CoV‐2. We previously demonstrated that the endogenous glucagon like peptide 1 (GLP‐1) system in conjunction with increased procalcitonin (PCT) is hyperactivated in patients with severe Gram‐negative sepsis and modulated by type 2 diabetes (T2D). We aimed to determine the association of COVID‐19 severity with endogenous GLP‐1 activation upregulated by increased specific pro‐inflammatory innate immune response in patients with and without T2D.

Materials and Methods

Plasma levels of total GLP‐1, IL‐6, and PCT were estimated on admission and during hospitalisation in 61 patients (17 with T2D) with non‐severe and severe COVID‐19.

Results

COVID‐19 patients demonstrated ten‐fold increase of IL‐6 levels regardless of disease severity. Increased admission GLP‐1 levels (p = 0.03) accompanied by two‐fold increased PCT were found in severe as compared with non‐severe patients. Moreover, GLP‐1 and PCT levels were significantly increased in non‐survived as compared with survived patients at admission (p = 0.01 and p = 0.001, respectively) and at 5 to 6 days of hospitalisation (p = 0.05). Both non‐diabetic and T2D patients demonstrated a positive correlation between GLP‐1 and PCT response (r = 0.33, p = 0.03, and r = 0.54, p = 0.03, respectively), but the intensity of this joint pro‐inflammatory/GLP‐1 response was modulated by T2D. In addition, hypoxaemia down‐regulated GLP‐1 response only in T2D patients with bilateral lung damage.

Conclusions

The persistent joint increase of endogenous GLP‐1 and PCT in severe and fatal COVID‐19 suggests a role of concomitant bacterial infection in disease exacerbation. Early elevation of endogenous GLP‐1 may serve as a new biomarker of COVID‐19 severity and fatal outcome.
Description of the mantle lure and novel mimicry of the endangered Cumberlandian Combshell (Epioblasma brevidens) in the Clinch River, eastern United States
Authors: Jones Jess W. , Taylor Zachary , Lane Timothy
Published: March 2023

The Cumberlandian Combshell (Epioblasma brevidens) is an endangered freshwater mussel endemic to the Tennessee and Cumberland River drainages, major tributaries of the Ohio River of the eastern United States. We conducted mask and snorkel surveys in May and June of 2021 and 2022 to locate, observe, photograph, and video female E. brevidens to document their unique mantle lures at sites in the Clinch River in Tennessee and Virginia. The mantle lure is morphologically specialized mantle tissue that mimics prey items of the host fish. The mantle lure of E. brevidens appears to mimic four distinct characteristics of the reproductive anatomy of the underside (ventral) of a gravid female crayfish, to include: (1) the external apertures of the oviducts located on the base of the third pair of walking legs, (2) crayfish larvae still encased in the egg membrane, (3) pleopods or claws, and (4) postembryonic eggs. Surprisingly, we observed males of E. brevidens displaying mantle lures that were anatomically complex and closely resembled the female mantle lure. The male lure similarly mimics oviducts, eggs, and pleopods but is diminutive (2–3 mm smaller in length or diameter) to those same structures in females. We describe for the first time the mantle lure morphology and mimicry of E. brevidens, showing its close resemblance to the reproductive anatomy of a gravid female crayfish, and a novel form of mimicry in males. To our knowledge, mantle lure displays in males have not been previously documented in freshwater mussels.