MNT inhibits lung adenocarcinoma ferroptosis and chemosensitivity by suppressing SAT1.

Ferroptosis, a type of iron-dependent non-apoptotic cell death, plays a vital role in both tumor proliferation and resistance to chemotherapy. Here, our study demonstrates that MAX's Next Tango (MNT), by involving itself in the spermidine/spermine N1-acetyltransferase 1 (SAT1)-related ferroptosis pathway, promotes the proliferation of lung adenocarcinoma (LUAD) cells and diminishes their sensitivity to chemotherapy. Initially, an RNA-sequence screen of LUAD cells treated with ferroptosis inducers (FINs) reveals a significant increase in MNT expression, suggesting a potential link between MNT and ferroptosis. Overexpression of MNT in LUAD cells hinders changes associated with ferroptosis. Moreover, the upregulation of MNT promotes cell proliferation and suppresses chemotherapy sensitivity, while the knockdown of MNT has the opposite effect. Through the intersection of ChIP-Seq and ferroptosis-associated gene sets, and validation by qPCR and western blot, SAT1 is identified as a potential target of MNT. Subsequently, we demonstrate that MNT binds to the promoter sequence of SAT1 and suppresses its transcription by ChIP-qPCR and dual luciferase assays. Restoration of SAT1 levels antagonizes the efficacy of MNT to inhibit ferroptosis and chemosensitivity and promote cell growth in vitro as well as in vivo. In the clinical context, MNT expression is elevated in LUAD and is inversely connected with SAT1 expression. High MNT expression is also associated with poor patient survival. Our research reveals that MNT inhibits ferroptosis, and impairing chemotherapy effectiveness of LUAD.

Anti-BCMA-engineered Exosomes for Bortezomib Targeted Delivery in Multiple Myeloma.

Exosomes have emerged as promising vehicles for delivering therapeutic cargoes to specific cells or tissues, owing to their superior biocompatibility, reduced immunogenicity, and enhanced targeting capabilities compared to conventional drug delivery systems. In this study, we developed a delivery platform utilizing exosomes derived from monocytes, specifically designed for targeted delivery of Bortezomib (Btz) to multiple myeloma (MM) cells. Our approach involved the genetic modification of monocytes to express antibodies targeting B cell maturation antigen (anti-BCMA), as BCMA selectively expresses on myeloma cells. This modified anti-BCMA was then efficiently incorporated into the monocyte-derived exosomes. These adapted exosomes effectively encapsulated Bortezomib, leading to enhanced drug accessibility within MM cells and sustained intracellular accumulation over an extended period. Remarkably, our results demonstrated that anti-BCMA-Exo-Btz outperformed free Btz in vitro, exhibiting a more potent myeloma-suppressive effect. In orthotopic MM xenograft models, anti-BCMA-Exo-Btz exhibited a significant anti-tumor effect compared to free Btz. Furthermore, it demonstrated remarkable specificity in targeting Bortezomib to myeloma cells in vivo. Importantly, we observed no significant histological damage in mice treated with anti-BCMA-Exo-Btz and a slight effect on PBMCs. Additionally, our study highlighted the multifunctional potential of monocyte-exosomes, which induced cell apoptosis, mediated immune responses, and enhanced the osteogenic potential of mesenchymal stromal cells. In conclusion, our study suggests that exosomes modified with targeting ligands hold therapeutic promise for delivering Bortezomib to myelomas, offering substantial potential for clinical applications.

An injectable and antifouling hydrogel prevents the development of abdominal adhesions by inhibiting the CCL2/CCR2 interaction.

Abdominal adhesion, a serious complication of abdominal surgery, often resists mitigation by current drug administration and physical barriers. To address this issue, we developed an injectable, antifouling hydrogel through the free-radical polymerization of methacrylate chondroitin sulfate (CS-GMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC) monomers, dubbed the CGM hydrogel. We systematically analyzed its physicochemical properties, including rheological strength, biocompatibility, and antifouling capabilities. A rat abdominal cecum adhesion model was constructed to assess the effectiveness of CGM hydrogel in preventing postoperative adhesion and recurrent adhesion. In addition, multi-omics analyses identified the relationship between adhesion development and CCL2/CCR2 interaction. Notably, CGM hydrogel can thwart the recruitment and aggregation of fibroblasts and macrophages by inhibiting the CCL2/CCR2 interaction. Moreover, CGM hydrogel significantly dampens the activity of fibrosis-linked cytokines (TGF-ßR1) and recalibrates extracellular matrix deposition-related cytokines (t-PA and PAI-1, Col Ⅰ and MMP-9). Cumulatively, the dual action of CGM hydrogel-as a physical barrier and cytokine regulator-highlights its promising potential in clinical application for abdominal adhesion prevention.

Multi-omic Analysis of Human B-cell Activation Reveals a Key Lysosomal BCAT1 Role in mTOR Hyperactivation by B-cell receptor and TLR9.

B-lymphocytes play major adaptive immune roles, producing antibody and driving T-cell responses. However, how immunometabolism networks support B-cell activation and differentiation in response to distinct receptor stimuli remains incompletely understood. To gain insights, we systematically investigated acute primary human B-cell transcriptional, translational and metabolomic responses to B-cell receptor (BCR), Toll-like receptor 9 (TLR9), CD40-ligand (CD40L), interleukin-4 (IL4) or combinations thereof. T-independent BCR/TLR9 co-stimulation, which drives malignant and autoimmune B-cell states, jointly induced PD-L1 plasma membrane expression, supported by NAD metabolism and oxidative phosphorylation. BCR/TLR9 also highly induced the transaminase BCAT1, which localized to lysosomal membranes to support branched chain amino acid synthesis and mTORC1 hyperactivation. BCAT1 inhibition blunted BCR/TLR9, but not CD40L/IL4-triggered B-cell proliferation, IL10 expression and BCR/TLR pathway-driven lymphoma xenograft outgrowth. These results provide a valuable resource, reveal receptor-mediated immunometabolism remodeling to support key B-cell phenotypes including PD-L1 checkpoint signaling, and identify BCAT1 as a novel B-cell therapeutic target.

Heterologous expression of P9 from Akkermansia muciniphila increases the GLP-1 secretion of intestinal L cells.

Glucagon-like peptide-1(GLP-1) is an incretin hormone secreted primarily from the intestinal L-cells in response to meals. GLP-1 is a key regulator of energy metabolism and food intake. It has been proven that P9 protein from A. muciniphila could increase GLP-1 release and improve glucose homeostasis in HFD-induced mice. To obtain an engineered Lactococcus lactis which produced P9 protein, mature polypeptide chain of P9 was codon-optimized, fused with N-terminal signal peptide Usp45, and expressed in L. lactis NZ9000. Heterologous secretion of P9 by recombinant L. lactis NZP9 were successfully detected by SDS-PAGE and western blotting. Notably, the supernatant of L. lactis NZP9 stimulated GLP-1 production of NCI-H716 cells. The relative expression level of GLP-1 biosynthesis gene GCG and PCSK1 were upregulated by 1.63 and 1.53 folds, respectively. To our knowledge, this is the first report on the secretory expression of carboxyl-terminal processing protease P9 from A. muciniphila in L. lactis. Our results suggest that genetically engineered L. lactis which expressed P9 may have therapeutic potential for the treatment of diabetes, obesity and other metabolic disorders.

pH-responsive bioadhesive with robust and stable wet adhesion for gastric ulcer healing.

Development of bioadhesives that can be facilely delivered by endoscope and exhibit instant and robust adhesion with gastric tissues to promote gastric ulcer healing remains challenging. In this study, an advanced bioadhesive is prepared through free radical polymerization of ionized N-acryloyl phenylalanine (iAPA) and N-[tris (hydroxymethyl) methyl] acrylamide (THMA). The precursory polymer solution exhibits low viscosity with the capability for endoscope delivery, and the hydrophilic-hydrophobic transition of iAPA upon exposure to gastric acid can trigger gelation through phenyl groups assisted multiple hydrogen bonds formation and repel water molecules on tissue surface to establish favorable environment for interfacial interactions between THMA and functional groups on tissues. The in-situ formed hydrogel features excellent stability in acid environment (14 days) and exhibits firm wet adhesion to gastric tissue (33.4 kPa), which can efficiently protect the wound from the stimulation of gastric acid and pepsin. In vivo studies reveal that the bioadhesive can accelerate the healing of ulcers by inhibiting inflammation and promoting capillary formation in the acetic acid-induced gastric ulcer model in rats. Our work may provide an effective solution for the treatment of gastric ulcers clinically.

Reinforcement Effects on Tensile Behavior of Ultra-High-Performance Concrete (UHPC) with Low Steel Fiber Volume Fractions.

Ultra-high-performance concrete (UHPC) with a low steel fiber volume fraction offers lower material costs than UHPC with typical steel fiber volume fractions, and has the potential to mitigate the ductility degradation of rebar-reinforced UHPC (R-UHPC). This study explores the reinforcement effect on the tensile behavior of UHPC with a low fiber volume fraction with the aim of facilitating more cost-efficient UHPC applications. The axial tensile behavior of 30 UHPC specimens with low fiber volume fractions at different reinforcement ratios was tested through direct tensile tests. The findings indicate that adopting UHPC with a low fiber volume fraction can significantly mitigate the ductility deterioration of rebar-reinforced UHPC (R-UHPC), and both increasing the reinforcement ratio and decreasing the fiber volume fraction contribute to the improvement in ductility. The failure modes of R-UHPC are determined by the ratio of reinforcement ratio and fiber volume fraction, rather than a single parameter, which also means that R-UHPC with different parameters may correspond to different methods to predict tensile load-bearing capacity. For UHPC with a fiber volume fraction low to 0.5%, incorporating steel rebars gives superior multi-crack cracking behavior and excellent capacity to restrict the maximum crack width. Increasing the fiber volume fraction from 0.5% to 1.0% at the same reinforcement ratio will yield little benefit other than an increase in tensile load-bearing capacity.

Prediction of Drug-Target Affinity Using Attention Neural Network.

Studying drug-target interactions (DTIs) is the foundational and crucial phase in drug discovery. Biochemical experiments, while being the most reliable method for determining drug-target affinity (DTA), are time-consuming and costly, making it challenging to meet the current demands for swift and efficient drug development. Consequently, computational DTA prediction methods have emerged as indispensable tools for this research. In this article, we propose a novel deep learning algorithm named GRA-DTA, for DTA prediction. Specifically, we introduce Bidirectional Gated Recurrent Unit (BiGRU) combined with a soft attention mechanism to learn target representations. We employ Graph Sample and Aggregate (GraphSAGE) to learn drug representation, especially to distinguish the different features of drug and target representations and their dimensional contributions. We merge drug and target representations by an attention neural network (ANN) to learn drug-target pair representations, which are fed into fully connected layers to yield predictive DTA. The experimental results showed that GRA-DTA achieved mean squared error of 0.142 and 0.225 and concordance index reached 0.897 and 0.890 on the benchmark datasets KIBA and Davis, respectively, surpassing the most state-of-the-art DTA prediction algorithms.

Establishment of Early Blood Perfusion Promotes CXCL12 Expression and Recruits Monocytes/Macrophages in Damaged Adipose Tissue in Mice Model.

BACKGROUND: Blood perfusion in the recipient site is important for adipose tissue repair after fat grafting. It delivers host-derived macrophages derived from monocytes in bone marrow to initiate inflammatory reactions and regenerative responses. According to the ability of CXCL12, a stromal cell-derived factor, to recruit monocytes/macrophages, we studied its effect on adipose tissue repair and regeneration under ischemic and normal conditions. METHODS: Each inguinal fat pad was crushed for 30 seconds with a clamp in mice (n = 35). The left inguinal vessels were divided and cut off (ischemic group), while the right inguinal vessels were kept patent (control group). Seven animals were sacrificed at 1, 3, 7, 14, and 30 days after surgery, and macrophages (Mac2 and CD206) and adipocytes (perilipin) were assessed. Levels of inflammatory factors (interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α) and CXCL12 were measured by quantitative PCR. RESULTS: The number of macrophages was higher in the control group than in the ischemic group at day 3 (10.33 ± 2.40 vs. 1.33 ± 0.33, p = 0.021). The percentage of M2 macrophages was higher in the control group than in the ischemic group at day 7 (p<0.05). The levels of inflammatory factors and CXCL12 were higher in the control group than in the ischemic group at the early stage (p = 0.038). CONCLUSIONS: Established blood perfusion leads to up-regulation of CXCL12 during adipose tissue repair and regeneration, which may increase recruitment of monocytes to damaged adipose tissue. These findings increase understanding of the cellular events involved in fat graft survival after grafting. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Effect of a Bladder Control Self-Management Program Delivered Through a Health Kiosk.

PURPOSE: The purpose of this study was to examine the feasibility of delivering a bladder control self-management program through a multiuser health kiosk and to evaluate the program's effect on urinary incontinence (UI) and incontinence-specific quality of life (QoL). DESIGN: Secondary analysis of data collected during participants' interactions with the Bladder Control Module (BCM) from the parent study. SUBJECTS AND SETTING: One hundred eleven participants from the parent study were eligible to be included in this secondary analysis. Their mean age was 72.8 years, and most were female (n = 95, 85.6%); 81 (75.7%) identified themselves as Caucasian. Each participant could access the BCM at a health kiosk situated at one of several sites: senior centers, subsidized senior housing, retirement communities, and a public library. METHODS: The BCM comprised 6 sessions self-administered at least 1 week apart. The content focused on lifestyle modification, pelvic floor muscle training, and bladder (habit) retraining, with encouragement of behavioral self-monitoring between sessions. The feasibility of delivering the intervention was measured by the proportion of participants completing each session. The effect of the BCM on incontinence episodes and incontinence-specific QoL was measured, respectively, by a 7-day bladder diary and the Incontinence Impact Questionnaire Short Form. RESULTS: Sixty-one of the 111 eligible participants accessed the BCM. Participants recording incontinence episodes in their baseline bladder diary and completing at least 3 BCM sessions experienced significant decreases in median total UI (P = .01), urge UI (P < .001), and stress UI (P = .02) episodes per day. Incontinence-related QoL significantly improved (P = .03). CONCLUSIONS: Our findings support the potential effectiveness of providing community-based, kiosk-enabled access to a conservative behavioral intervention designed to improve incontinence-related outcomes among older adults with UI. Additional research with a larger sample is warranted.

Artificial intelligence for diagnosis and prognosis prediction of natural killer/T cell lymphoma using magnetic resonance imaging.

Accurate diagnosis and prognosis prediction are conducive to early intervention and improvement of medical care for natural killer/T cell lymphoma (NKTCL). Artificial intelligence (AI)-based systems are developed based on nasopharynx magnetic resonance imaging. The diagnostic systems achieve areas under the curve of 0.905-0.960 in detecting malignant nasopharyngeal lesions and distinguishing NKTCL from nasopharyngeal carcinoma in independent validation datasets. In comparison to human radiologists, the diagnostic systems show higher accuracies than resident radiologists and comparable ones to senior radiologists. The prognostic system shows promising performance in predicting survival outcomes of NKTCL and outperforms several clinical models. For patients with early-stage NKTCL, only the high-risk group benefits from early radiotherapy (hazard ratio = 0.414 vs. late radiotherapy; 95% confidence interval, 0.190-0.900, p = 0.022), while progression-free survival does not differ in the low-risk group. In conclusion, AI-based systems show potential in assisting accurate diagnosis and prognosis prediction and may contribute to therapeutic optimization for NKTCL.

Amino acids inhibit the photodynamic inactivation effect by hindering cellular oxidative stress.

Photodynamic inactivation (PDI) could utilize light to activate reactive oxygen species (ROS) produced by photosensitizers to kill bacteria for preservation. To delve into the complex effects arising during the post-harvest PDI processing, we conducted experiments using Pseudomonas reinekei, a food spoilage bacteria extracted from rotten Pakchoi. Through analyzing the metabolomics results, we discovered that methionine (Met) and glutamate (Glu) exhibited significant inhibitory effects during the PDI process. The oxidative stress generated by light treatment resulted in a reduction of 30.31% and 36.37% in the levels of Met and Glu, respectively. The data also showed that exogenous Met and Glu reduced intracellular oxidative stress levels, increased peroxidase activity, and prevented the damage of intracellular material and cell membrane deformation. That amino acids could inhibit the effect of PDI by hindering oxidative stress. Therefore, the amino acid content should be considered when applying PDI to treat Met- or Glu-rich foods.

Multi-granularity learning of explicit geometric constraint and contrast for label-efficient medical image segmentation and differentiable clinical function assessment.

Automated segmentation is a challenging task in medical image analysis that usually requires a large amount of manually labeled data. However, most current supervised learning based algorithms suffer from insufficient manual annotations, posing a significant difficulty for accurate and robust segmentation. In addition, most current semi-supervised methods lack explicit representations of geometric structure and semantic information, restricting segmentation accuracy. In this work, we propose a hybrid framework to learn polygon vertices, region masks, and their boundaries in a weakly/semi-supervised manner that significantly advances geometric and semantic representations. Firstly, we propose multi-granularity learning of explicit geometric structure constraints via polygon vertices (PolyV) and pixel-wise region (PixelR) segmentation masks in a semi-supervised manner. Secondly, we propose eliminating boundary ambiguity by using an explicit contrastive objective to learn a discriminative feature space of boundary contours at the pixel level with limited annotations. Thirdly, we exploit the task-specific clinical domain knowledge to differentiate the clinical function assessment end-to-end. The ground truth of clinical function assessment, on the other hand, can serve as auxiliary weak supervision for PolyV and PixelR learning. We evaluate the proposed framework on two tasks, including optic disc (OD) and cup (OC) segmentation along with vertical cup-to-disc ratio (vCDR) estimation in fundus images; left ventricle (LV) segmentation at end-diastolic and end-systolic frames along with ejection fraction (LVEF) estimation in two-dimensional echocardiography images. Experiments on nine large-scale datasets of the two tasks under different label settings demonstrate our model's superior performance on segmentation and clinical function assessment.

Fast Interfacial Defluorination Kinetics Enables Stable Cycling of Low-Temperature Lithium Metal Batteries.

The development of low-temperature lithium metal batteries (LMBs) encounters significant challenges because of severe dendritic lithium growth during the charging/discharging processes. To date, the precise origin of lithium dendrite formation still remains elusive due to the intricate interplay between the highly reactive lithium metal anode and organic electrolytes. Herein, we unveil the critical role of interfacial defluorination kinetics of localized high-concentration electrolytes (LHCEs) in regulating lithium dendrite formation, thereby determining the performance of low-temperature LMBs. We investigate the impact of solvation structures of LHCEs on low-temperature LMBs by employing tetrahydrofuran (THF) and 2-methyltetrahydrofuran (2-MeTHF) as comparative solvents. The combination of comprehensive characterizations and theoretical simulations reveals that the THF-based LHCE featured with a strong solvation strength exhibits fast interfacial defluorination reaction kinetics, thus leading to the formation of an amorphous and inorganic-rich solid-electrolyte interphase (SEI) that can effectively suppress the growth of lithium dendrites. As a result, the highly reversible Li metal anode achieves an exceptional Coulombic efficiency (CE) of up to ∼99.63% at a low temperature of -30 °C, thereby enabling stable cycling of low-temperature LMB full cells. These findings underscore the crucial role of electrolyte interfacial reaction kinetics in shaping SEI formation and provide valuable insights into the fundamental understanding of electrolyte chemistry in LMBs.

Simultaneous determination of unecritinib (TQ-B3101) and its active metabolite crizotinib in rat plasma by LC-MS/MS：An application to pharmacokinetic studies.

Unecritinib (TQ-B3101) is a selective tyrosine kinase receptor inhibitor. In the study, in vitro metabolic experiments revealed that the hydrolysis of TQ-B3101 was mainly catalyzed by carboxylesterase 2 (CES2), followed by CES1. Next, a sensitive and reliable LC-MS/MS method was established for the simultaneous determination of TQ-B3101 and its metabolite crizotinib in rat plasma. To prevent in vitro hydrolysis of TQ-B3101, sodium fluoride, the CESs inhibitor at a concentration of 2 M, was immediately added after whole blood collection. Plasma samples were extracted by acetonitrile-induced protein precipitation method, and chromatographically separated on a Gemini C18 column (50 mm × 2.0 mm i.d., 5 µm) using gradient elution with a mobile phase of 0.1% formic acid and 5 mmol/L ammonium acetate with 0.1% formic acid. The retention times for TQ-B3101 and crizotinib were 2.61 and 2.38 min, respectively. The analytes were detected with tandem mass spectrometer by positive electrospray ionization, using the ion transitions at m/z 492.3 → 302.3 for TQ-B3101, m/z 450.3 → 260.3 for crizotinib, and m/z 494.0 → 394.3 for imatinib (internal standard). Method validation was conducted in the linear range of 1.00-800 ng/mL for the two analytes. The precision, accuracy and stabilities all met the acceptance criteria. The pharmacokinetic study indicated that TQ-B3101 was rapidly hydrolyzed to crizotinib with the elimination half-life of 1.11 h after a single gavage administration of 27 mg/kg to Sprague-Dawley rats, and the plasma exposure of TQ-B3101 was only 2.98% of that of crizotinib.

Snowflake Cu2S@ZIF-67: A novel heterostructure substrate for enhanced adsorption and sensitive detection in BPA.

Developing semiconductor substrates with superior stability and sensitivity is challenging in surface-enhanced Raman scattering (SERS) research. Here, a snowflake Cu2S@ZIF-67 heterostructure was fabricated using a straightforward method, exhibiting a notable enhancement factor of 9.0 × 109 and a limit of detection (LOD) of 10-14 M for methylene blue (MB). In addition, the Cu2S@ZIF-67 heterostructure substrate demonstrates outstanding homogeneity (relative standard deviation (RSD) = 9.2%) and stability (120 days). Employing Cu2S generates highly sensitive hotspots via an electromagnetic (EM) mechanism, and the growth of ZIF-67 on its surface augments the adsorption capacity and charge transfer capability (chemical mechanism, CM), thereby enhancing the SERS detection sensitivity. Furthermore, the Cu2S@ZIF-67 heterostructure, which was used as a SERS substrate, facilitated the detection of bisphenol A (BPA) with an LOD of 10-11 M. The Cu2S@ZIF-67 heterostructure substrate has excellent selectivity and anti-interference, which is very suitable for BPA detection in complex environment applications. The accuracy of the Cu2S@ZIF-67 heterostructure as a SERS substrate for detecting BPA in real water samples (water bottles, tap water, and pure milk) was confirmed by comparison with high-performance liquid chromatography (HPLC). These results demonstrate that through the rational design of heterostructures can achieve the quantitative and accurate detection of hazardous substances in food and the environment can be achieved.

Design, synthesis, and antitumor activity evaluation of potent fourth-generation EGFR inhibitors for treatment of Osimertinib resistant non-small cell lung cancer (NSCLC).

Epidermal growth factor receptor (EGFR) is one of the most studied drug targets for treating non-small-cell lung cancer (NSCLC). However, there are no approved inhibitors for the C797S resistance mutation caused by the third-generation EGFR inhibitor (Osimertinib). Therefore, the development of fourth-generation EGFR inhibitors is urgent. In this study, we clarified the structure-activity relationship of several synthesized compounds as fourth-generation inhibitors against human triple (Del19/T790M/C797S) mutation. Representative compound 52 showed potent inhibitory activity against EGFRL858R/T790M/C797S with an IC50 of 0.55 nM and significantly inhibited the proliferation of the Ba/F3 cell line harboring EGFRL858R/T790M/C797S with an IC50 of 43.28 nM. Moreover, 52 demonstrated good pharmacokinetic properties and excellent in vivo efficacy. Overall, the compound 52 can be considered a promising candidate for overcoming EGFR C797S-mediated mutations.

Exploration and future trends on spatial correlation of green innovation efficiency in strategic emerging industries under the digital economy: A social network analysis.

With digital technological change and the increasing frequency of interregional innovation links, the spatial correlation and diversity of strategic emerging industries' green innovation efficiency (SEI-GIE) need to be explored in depth. This paper innovatively constructs the SEI-GIE input-output index system under digital economy. The proposed grey model FINGBM(1,1) with ω-order accumulation and weighted initial value optimization realizes effective prediction of 7 input-output indicators of 30 provinces in China from 2021 to 2025. Super-SBM-DEA, gravity model, and social network analysis are applied to explore spatial network structure's dynamic process of SEI-GIE from 12th to 14th Five-Year-Plan period (2011-2025). Empirical results show that (1) Under the effect of digital economy, the SEI-GIE in China generally shows a U-shaped fluctuation trend, in which the growth trend in the central region is obvious, and the western region shows significant fluctuations. (2) The spatial correlation network of SEI-GIE presents a complex and stable center-periphery circle. Particularly, the overall increase in network efficiency highlights the strong small-world characteristics. (3) Beijing, Shanghai, Zhejiang and Jiangsu have always been in the leading core position, with strong influence and control; And Tianjin's core position in the network will decline. Additionally, Guangxi and Chongqing have great potential, but Guangdong needs to strengthen its radiation effect. (4) Block model shows that plate-I (Beijing, Tianjin) receive spatial spillovers from others, while plates-III,IV have significant spillover effects. This study provides theoretical reference for policymakers from a network perspective to promote development of China's SEI-GIE.

Photoinduced Remote C(sp3)-H Phosphonylation of Amides.

The present study reports an unprecedented protocol for the phosphonylation of unactivated C(sp3)-H bonds. By utilizing 1 mol % 4DPAIPN (1,2,3,5-tetrakis(diphenylamino)-4,6-dicyanobenzene) as the catalyst, satisfactory yields of γ-phosphonylated amides are obtained through a visible-light-induced reaction between N-((4-cyanobenzoyl)oxy)alkanamides and 9-fluorenyl o-phenylene phosphite at room temperature. This protocol demonstrates broad substrate scope and wide functional group compatibility.