Evaluation of compressive damage in concrete using ultrasonic nonlinear coda wave interferometry.

This study investigates the feasibility of nonlinear coda wave interferometry (NCWI) for evaluating compressive damage in concrete, with a particular focus on the interference caused by the compressive stress-induced slow dynamics. Slow dynamics refers to a phenomenon in which the stiffness of concrete immediately decreases after moderate mechanical conditioning and then logarithmically evolves back to its initial value over time. A series of experiments were conducted to validate this concept. The experimental findings indicate that slow dynamics following the unloading of concrete specimen significantly interfere with NCWI testing. The changes in dv/v caused by the slow dynamics are opposite to those induced by the pump wave in NCWI. After the slow dynamics have been eliminated, an evaluation indicator, defined as the efficient nonlinear level αdv/v, demonstrates an excellent correlation with compressive damage. The value of the indicator decreases with increasing compressive stress. Furthermore, the coda wave interferometry (CWI) and direct wave interferometry (DWI) are performed as comparisons. In summary, the feasibility and superiority of NCWI are demonstrated in concrete compressive damage evaluation.

Four new phenylpropanoid glycosides from the leaves of Illicium dunnianum and their neuroprotective activities.

Four previously unreported phenylpropanoid glycosides (1-4), together with four known analogues (5-8), were isolated from the leaves of Illicium dunnianum. The structures of these new compounds were elucidated based on spectroscopic analysis (HR-ESI-MS, NMR, IR, UV) and chemical methods. In addition, the neuroprotective activities of all the isolates were evaluated by measuring their cell viability in H2O2-induced OLN-93 cell injury model.

Ten-Year Follow-Up of Mitral Valve Replacement with the Epic Porcine Valve in a Medicare Population.

BACKGROUND: Bioprosthetic surgical mitral valve replacement (SMVR) remains an important treatment option in the era of transcatheter valve interventions. We present 10-year clinical outcomes of Medicare beneficiaries undergoing SMVR with a contemporary low-profile mitral porcine valve. METHODS: This is a single-arm observational study using Medicare fee-for-service claims data. De-identified patients undergoing SMVR with the Epic™ Mitral valve (Abbott, Minnesota, USA) in the United States between 1/1/2008-12/31/2019 were selected by ICD-9/10 procedure codes and then linked to a manufacturer device tracking database. All-cause mortality, heart failure (HF) re-hospitalization, and mitral valve reintervention (surgical or transcatheter valve-in-valve) were evaluated at 10-years using the Kaplan Meier method. RESULTS: Among 75,739 Medicare beneficiaries undergoing SMVR during the study period, 14,015 were implanted with the Epic™ Mitral valve, of which 76.5% (10,720) had underlying HF. Mean age was 74±8 years. Survival at 10-years in patients without preoperative HF was 40.4% (95% CI 37.4%-43.4%) compared to 25.4% (95% CI 23.8%-27.0%) for patients with HF (p < 0.001). The 10-year freedom from HF rehospitalization was 51.3% (95% CI 49.4%-53.1%). Freedom from mitral valve reintervention was 91.4% (95% CI 89.7%-92.7%) at 10 years. CONCLUSIONS: This real-world nationwide study of Medicare beneficiaries receiving the Epic™ Mitral valve demonstrates >90% freedom from all-cause valve reintervention and >50% freedom from HF rehospitalization at 10-years post-implant. Long-term survival and HF rehospitalization in this population with mitral valve disease undergoing SMVR was found to be impacted by underlying HF.

[Preliminary comparative study of spinal robot-assisted pedicle screw placement using different surgical approaches].

Objective: To compare the effectiveness of spinal robot-assisted pedicle screw placement through different surgical approaches and to guide the clinical selection of appropriate robot-assisted surgical approaches. Methods: The clinical data of 14 patients with thoracolumbar vertebral diseases who met the selection criteria between January 2023 and August 2023 were retrospectively analyzed, and all of them underwent pedicle screw placement under assistant of the Mazor X spinal surgery robot through different surgical approaches. The patients were divided into posterior median approach (PMA) group ( n=6) and intermuscular approach (IMA) group ( n=8) according to the surgical approaches, and there was no significant difference in age, gender, body mass index, disease type, and fixed segment between the two groups ( P>0.05). The operation time, intraoperative blood loss, screw-related complications, and reoperation rate were recorded and compared between the two groups; the inclination angle of the screw, the distance between the screw and the midline, and the caudal inclination angle of the screw were measured based on X-ray films at immediate after operation. Results: There was no significant difference in operation time and intraoperative blood loss between the two groups ( P>0.05). There was no screw-related complication such as nerve injury in both groups, and no patients underwent secondary surgery. At immediate after operation, the inclination angle of the screw, the distance between the screw and the midline, and the caudal inclination angle of the screw in the IMA group were significantly greater than those in the PMA group ( P<0.05). Conclusion: There are differences in the position and inclination angle of screws placed with robot-assisted surgery through different surgical approaches, which may be due to the obstruction of the screw path by soft tissues such as skin and muscles. When using spinal robot-assisted surgery, selecting the appropriate surgical approach for different diseases can make the treatment more reasonable and effective.

Multi-transcriptomics analysis of microvascular invasion-related malignant cells and development of a machine learning-based prognostic model in hepatocellular carcinoma.

Background: Microvascular invasion (MVI) stands as a pivotal pathological hallmark of hepatocellular carcinoma (HCC), closely linked to unfavorable prognosis, early recurrence, and metastatic progression. However, the precise mechanistic underpinnings governing its onset and advancement remain elusive. Methods: In this research, we downloaded bulk RNA-seq data from the TCGA and HCCDB repositories, single-cell RNA-seq data from the GEO database, and spatial transcriptomics data from the CNCB database. Leveraging the Scissor algorithm, we delineated prognosis-related cell subpopulations and discerned a distinct MVI-related malignant cell subtype. A comprehensive exploration of these malignant cell subpopulations was undertaken through pseudotime analysis and cell-cell communication scrutiny. Furthermore, we engineered a prognostic model grounded in MVI-related genes, employing 101 algorithm combinations integrated by 10 machine-learning algorithms on the TCGA training set. Rigorous evaluation ensued on internal testing sets and external validation sets, employing C-index, calibration curves, and decision curve analysis (DCA). Results: Pseudotime analysis indicated that malignant cells, showing a positive correlation with MVI, were primarily concentrated in the early to middle stages of differentiation, correlating with an unfavorable prognosis. Importantly, these cells showed significant enrichment in the MYC pathway and were involved in extensive interactions with diverse cell types via the MIF signaling pathway. The association of malignant cells with the MVI phenotype was corroborated through validation in spatial transcriptomics data. The prognostic model we devised demonstrated exceptional sensitivity and specificity, surpassing the performance of most previously published models. Calibration curves and DCA underscored the clinical utility of this model. Conclusions: Through integrated multi-transcriptomics analysis, we delineated MVI-related malignant cells and elucidated their biological functions. This study provided novel insights for managing HCC, with the constructed prognostic model offering valuable support for clinical decision-making.

Pharmacokinetics of trastuzumab and its efficacy and safety in HER2-positive cancer patients.

Trastuzumab is a potent targeted therapy drug for HER2-positive cancer patients. A comprehensive understanding of trastuzumab's mechanism of action, pharmacokinetic (PK) parameters, and steady-state exposure in different treatment regimens and administration routes is essential for a thorough evaluation of the drug's safety and effectiveness. Due to the distinctive pharmacokinetics, indications, and administration methods of trastuzumab, this understanding becomes crucial. Drug exposure can be assessed by measuring trastuzumab's peak concentration, trough concentration, or area under the curve through assays like enzyme-linked immunosorbent assay (ELISA) or liquid chromatography-tandem mass spectrometry (LC-MS/MS). The dose-response (D-R) and exposure-response (E-R) relationships establish the correlation between drug dosage/exposure and the therapeutic effect and safety. Additionally, various covariates such as body weight, aspartate transaminase, and albumin levels can influence drug exposure. This review provides a comprehensive overview of trastuzumab's mechanism of action, data on steady-state concentration and PK parameters under multiple administration routes and indications, discussions on factors influencing PK parameters, and evaluations of the effectiveness and safety of E-R and D-R in diverse HER2-positive cancer patients.

Gubi decoction mitigates knee osteoarthritis via promoting chondrocyte autophagy through METTL3-mediated ATG7 m6A methylation.

Knee osteoarthritis (KOA) is a chronic joint disease that significantly affects the health of the elderly. As an herbal remedy, Gubi decoction (GBD) has been traditionally used for the treatment of osteoarthritis-related syndromes. However, the anti-KOA efficacy and mechanism of GBD remain unclear. This study aimed to experimentally investigate the anti-KOA efficacy and the underlying mechanism of GBD. The medial meniscus (DMM) mice model and IL-1ß-stimulated chondrocytes were, respectively, constructed as in vivo and in vitro models of KOA to evaluate the osteoprotective effect and molecular mechanism of GBD. The UPLC-MS/MS analysis showed that GBD mainly contained pinoresinol diglucoside, rehmannioside D, hesperidin, liquiritin, baohuoside I, glycyrrhizic acid, kaempferol and tangeretin. Animal experiment showed that GBD could alleviate articular cartilage destruction and recover histopathological alterations in DMM mice. In addition, GBD inhibited chondrocyte apoptosis and restored DMM-induced dysregulated autophagy evidenced by the upregulation of ATG7 and LC3 II/LC3 I but decreased P62 level. Mechanistically, METTL3-mediated m6A modification decreased the expression of ATG7 in DMM mice, as it could be significantly attenuated by GBD. METTL3 overexpression significantly counteracted the protective effect of GBD on chondrocyte autophagy. Further research showed that GBD promoted proteasome-mediated ubiquitination degradation of METLL3. Our findings suggest that GBD could act as a protective agent against KOA. The protective effect of GBD may result from its promotion on chondrocyte autophagy by suppressing METTL3-dependent ATG7 m6A methylation.

Water-land-energy efficiency and nexus within global agricultural trade during 1995-2019.

Agricultural product demand driven by population and economic growth poses challenges to water, land, and energy utilization, and this increasing local demand is largely met through trade. However, the efficiency and nexus pattern of the water, land, and energy embodied in agricultural trade are not well understood. This study uses the multi-regional input-output framework to analyze agricultural water, land, and energy utilization efficiency of resource footprints per unit economic output as well as their transfer and nexus pattern in global agricultural trade for 1995-2019. The results show that many international agricultural trade paths are inefficient in the water, land, and energy resource use because the agricultural products in these paths are exported from relatively low- to high-efficiency economies/regions. However, these inefficient transfer paths show an increasing trend over the study period. Regarding the water-land-energy nexus, conflicts are prevalent in land-energy and water-energy couplings. Most trade paths are conducted to alleviate the pressure on a specific resource, inadvertently increasing the pressure on other resources. Although agricultural trade is important for meeting global food demands, it is not consistently beneficial to the local environment when considering agricultural resources use efficiency. This study is expected to improve our understanding of agricultural trade impacts to the agricultural resources and support the sustainable development of global agriculture.

Wireless Online Rotation Monitoring System for UAV Motors Based on a Soft-Contact Triboelectric Nanogenerator.

Real-time monitoring of UAV motor speed is crucial for enhancing control performance and ensuring flight safety. However, this task faces challenges such as difficult sensor installation and high costs. This study introduces a wireless rotational speed sensing system based on a UAV-rotary triboelectric nanogenerator (UR-TENG). By employing a carefully designed structure with soft contact and a freestanding-triboelectric-layer mode, UR-TENG exhibits characteristics like low friction, affordability, ease of production, and self-powering capability. This eliminates the need for an external power source and addresses the complexity of installation in the limited space of UAVs. Experimental findings demonstrate that UR-TENG possesses high sensitivity and stability, maintaining the structural integrity of the UAV. The goodness of fit is notably high at 0.99959, with a maximum error rate of only 0.014 within a range of 6270 rpm. Moreover, UR-TENG integrates with a microcontroller unit (MCU) and external circuitry to form a monitoring system. This system transmits electrical signals to a PC via a Wi-Fi module, facilitating real-time rotational speed sensing and anomaly detection. Finally, a practical application demonstration on a UAV validates the adaptability of UR-TENG to complex operational environments. This study presents a promising approach for online rotation monitoring of UAV motors, with potential for commercialization, and introduces new avenues for TENG application in UAV technology.

Ribbon-Ordered Superlattice Enables Reversible Anion Redox and Stable High-Voltage Na-Ion Battery Cathodes.

High-voltage layered oxide cathodes attract great attention for sodium-ion batteries (SIBs) due to the potential high energy density, but high voltage usually leads to rapid capacity decay. Herein, a stable high-voltage NaLi0.1Ni0.35Mn0.3Ti0.25O2 cathode with a ribbon-ordered superlattice is reported, and the intrinsic coupling mechanism between structure evolution and the anion redox reaction (ARR) is revealed. Li introduction constructs a special Li-O-Na configuration activating reversible nonbonded O 2p (|O2p)-type ARR and regulates the structure evolution way, enabling the reversible Li ions out-of-layer migration instead of the irreversible transition metal ions out-of-layer migration. The reversible structure evolution enhances the reversibility of the bonded O 2p (O2p)-type ARR and inhibits the generation of oxygen dimers, thus suppressing the irreversible molecular oxygen (O2)-type ARR. After the structure regulation, the structure evolution becomes reversible, |O2p-type ARR is activated, O2p-type ARR becomes stable, and O2-type ARR is inhibited, which largely suppresses the capacity degradation and voltage decay. The discharge capacity is increased from 154 to 168 mA h g-1, the capacity retention after 200 cycles significantly increases from 35 to 84%, and the voltage retention increases from 78 to 93%. This study presents some guidance for the design of high-voltage, O3-type oxide cathodes for high-performance SIBs.

Benzo-Extended Heli(aminoborane)s: Inner Rim BN-Doped Helical Molecular Carbons with Remarkable Chiroptical Properties.

Atomically precise synthesis of three-dimensional boron-nitrogen (BN)-based helical structures constitutes an undeveloped field with challenges in synthetic chemistry. Herein, we synthesized and comprehensively characterized a new class of helical molecular carbons, named benzo-extended [n]heli(aminoborane)s ([n]HABs), in which the helical structures consisted of n = 8 and n = 10 ortho-condensed conjugated rings with alternating BN atoms at the inner rims. X-ray crystallographic analysis, photophysical studies, and density functional theory calculations revealed the unique characteristics of this novel [n]HAB system. Owing to the high enantiomerization energy barriers, the optical resolution of [8]HAB and [10]HAB was achieved with chiral high-performance liquid chromatography. The isolated enantiomers of [10]HAB exhibited record absorption and luminescence dissymmetry factors (|gabs|=0.061; |glum|=0.048), and boosted CPL brightness up to 292 M-1 cm-1, surpassing most helicene derivatives, demonstrating that the introduction of BN atoms into the inner positions of helicenes can increase both the |gabs| and |glum| values.

Characteristic brain functional activation and connectivity during actual and imaginary right-handed grasp.

We used 34-channel functional near infrared spectroscopy to investigate and compare changes in oxyhemoglobin concentration of brain networks in bilateral prefrontal cortex, sensorimotor cortex, and occipital lobe of 22 right-handed healthy adults during executive right-handed grasp (motor execution task) and imagined right-handed grasp (motor imagery task). Then calculated lateral index and functional contribution degree, and measured functional connectivity strength between the regions of interest. In the motor executive block task, there was a significant increase in oxyhemoglobin concentration in regions of interest except for right occipital lobe (P<0.05), while in the motor imagery task, all left regions of interest's oxyhemoglobin concentration increased significantly (P<0.05). Except the prefrontal cortex in motor executive task, the left side of the brain was dominant. Left sensorimotor cortex played a major role in these two tasks, followed by right sensorimotor cortex. Among all functional contribution degree, left sensorimotor cortex, right sensorimotor cortex and left occipital lobe ranked top three during these tasks. In continuous acquisition tasks, functional connectivity on during motor imagery task was stronger than that during motor executive task. Brain functions during two tasks of right-hand grasping movement were partially consistent. However, the excitability of brain during motor imagery was lower, and it was more dependent on the participation of left prefrontal cortex, and its synchronous activity of the whole brain was stronger. The trend of functional contribution degree was basically consistent with oxyhemoglobin concentration and lateral index, and can be used as a novel index to evaluate brain function. [ChiCTR2200063792 (2022-09-16)].

Molecular detection, subtyping of Blastocystis sp. in migratory birds from nature reserves in northeastern China.

Migratory birds play an important role in the cross-regional transmission of zoonotic pathogens. Assessing the presence of zoonotic pathogens carried by migratory birds is critical for disease control. However, information about Blastocystis infection in the migratory birds is very limited. Thus, we conducted this study with the aim to explore the occurrence, prevalence and subtyping of Blastocystis in four breeds of migratory birds in northeastern China. From October 2022 to April 2023, a total of 427 fresh fecal samples were obtained from four breeds of migratory birds in five nature reserves in northeastern China, and screened for Blastocystis by PCR amplification. Twenty-one (4.92 %) of the studied samples were confirmed Blastocystis-positive, and two known zoonotic subtypes ST6 and ST7 were founded, with ST7 being the major subtype. Until now, we firstly reported the infection status and subtyping of Blastocystis in the migratory Greater White-Fronted Goose, White Stork, Oriental White Stork and Bean Goose in China. More importantly, these findings present further data on the genetic diversity and transmission routes of Blastocystis and further arouse public health concerns about this organism.

Asymmetric bifunctionalization of allenes with aryl iodides and amino acids enabled by chiral aldehyde/palladium combined catalysis.

Even though catalytic asymmetric bifunctionalization of allenes has been extensively studied, almost all of the reported examples have been achieved in a two-component manner. In this study, we report a highly efficient asymmetric bifunctionalization of allenes with iodohydrocarbons and NH2-unprotected amino acid esters. The adopted chiral aldehyde/palladium combined catalytic system precisely governs the chemoselectivity, regioselectivity, and stereoselectivity of this three-component reaction. A wide range of substituted aryl iodides, allenes and amino acid esters can well participate in this reaction and deliver structurally diverse α,α-disubstituted α-amino acid esters with excellent experimental outcomes. One of the resulting products is utilized for the total synthesis of the molecule (S,R)-VPC01091.

Investigating agricultural water sustainability in arid regions with Bayesian network and water footprint theories.

Water scarcity is a significant constraint in agricultural ecosystems of arid regions, necessitating sustainable development of agricultural water resources. This study innovatively combines Bayesian theory and Water Footprint (WF) to construct a Bayesian Network (BN). Water quantity and quality data were evaluated comprehensively by WF in agricultural production. This evaluation integrates WF and local water resources to establish a sustainability assessment framework. Selected nodes are incorporated into a BN and continuously updated through structural and parameter learning, resulting in a robust model. Results reveal a nearly threefold increase of WF in the arid regions of Northwest China from 1989 to 2019, averaging 189.95 × 108 m3 annually. The region's agricultural scale is expanding, and economic development is rapid, but the unsustainability of agricultural water use is increasing. Blue WF predominates in this region, with cotton having the highest WF among crops. The BN indicates a 70.1 % probability of unsustainable water use. Sensitivity analysis identifies anthropogenic factors as primary drivers influencing water resource sustainability. Scenario analysis underscores the need to reduce WF production and increase agricultural water supply for sustainable development in arid regions. Proposed strategies include improving irrigation methods, implementing integrated water-fertilizer management, and selecting drought-resistant, economically viable crops to optimize crop planting structures and enhance water use efficiency in current agricultural practices in arid regions. This study not only offers insights into water management in arid regions but also provides practical guidance for similar agricultural contexts. The BN model serves as a flexible tool for informed decision-making in dynamic environments.

Mandarin fish von Hippel-Lindau protein regulates the NF-κB signaling pathway via interaction with IκB to promote fish ranavirus replication.

The von Hippel-Lindau tumor suppressor protein (VHL), an E3 ubiquitin ligase, functions as a critical regulator of the oxygen-sensing pathway for targeting hypoxia-inducible factors. Recent evidence suggests that mammalian VHL may also be critical to the NF-κB signaling pathway, although the specific molecular mechanisms remain unclear. Herein, the roles of mandarin fish ( Siniperca chuatsi) VHL ( scVHL) in the NF-κB signaling pathway and mandarin fish ranavirus (MRV) replication were explored. The transcription of scVHL was induced by immune stimulation and MRV infection, indicating a potential role in innate immunity. Dual-luciferase reporter gene assays and reverse transcription quantitative PCR (RT-qPCR) results demonstrated that scVHL evoked and positively regulated the NF-κB signaling pathway. Treatment with NF-κB signaling pathway inhibitors indicated that the role of scVHL may be mediated through scIKKα, scIKKß, scIκBα, or scp65. Co-immunoprecipitation (Co-IP) analysis identified scIκBα as a novel target protein of scVHL. Moreover, scVHL targeted scIκBα to catalyze the formation of K63-linked polyubiquitin chains to activate the NF-κB signaling pathway. Following MRV infection, NF-κB signaling remained activated, which, in turn, promoted MRV replication. These findings suggest that scVHL not only positively regulates NF-κB but also significantly enhances MRV replication. This study reveals a novel function of scVHL in NF-κB signaling and viral infection in fish.

Directional Adaptive Triboelectric Nanogenerator with Wind-Wave Synergy.

To enhance the adaptability and synergy of the triboelectric nanogenerator (TENG) in a wave environment, this paper introduces a directional adaptive triboelectric nanogenerator (DA-TENG) with wind-water synergistic action for wave energy collection. An innovative design combining a wind vane on the top and fan-shaped blade electrodes internally allows the DA-TENG to adjust its swinging direction adaptively to align with the direction of wave motion. The internal multiple power generation units work in coordination, effectively addressing the issues of low efficiency associated with spherical TENGs in capturing multidirectional wave energy. The DA-TENG demonstrates superior performance under various wind speed conditions, showcasing its practical application potential. Experimental results show that the DA-TENG, equipped with a single tail wind vane and a 700 g mass block, can achieve an output voltage, current, and charge of 374.97 V, 84.77 µA, and 622.69 nC under a mild wind environment. Its peak power density reaches 7.51 W m-3, enabling successful data transmission for a wireless temperature and humidity sensor and powering 248 light-emitting diodes (LEDs). This research expands the possibilities of omnidirectional wave energy collection and the collaborative operation of multiple power generation units, offering an effective method for powering low-power maritime devices.

Therapeutic Effect of Stem Cells from Different Sources on Diabetic Foot Ulcers: Systematic Review and Network Meta-Analysis.

AIM: To evaluate the efficacy of stem cell therapy from different sources on the ankle-brachial index, wound closure percentage, and wound closure time in the treatment of diabetic foot ulcers (DFUs). METHODS: A literature search was conducted in PubMed, Embase, Cochrane Library's Central Register of Controlled Trials, and Web of Science, extending through June 29, 2023. Quality evaluation was done using the Cochrane's bias risk assessment tool (RoB 2.0). Employing a Bayesian approach, the statistical computations was executed with the JAGS software, leveraging the gemtc 0.8-2 and rjags 4-10 libraries, within the R environment 4.1.2. The included interventions came from peripheral blood, bone marrow, placenta, umbilical cord blood, adipose tissue, or others. RESULT: A preliminary search identified 2286 articles, of which 23 randomized controlled trials met the inclusion criteria and were ultimately included. The analysis findings indicated that mesenchymal stem cells derived from the umbilical cord (HUCMSCs) led to a notable enhanced the ankle-brachial index in patients with DFUs compared to standard treatment (MD: 0.2; 95% CI [0.01, 0.36]). HUCMSCs were found to be the optimal therapeutic approach for enhancing the ankle-brachial index (SUCRA = 82.7%). Research on the wound closure percentage revealed that compared to platelet-rich plasma (PRP), processed microvascular tissue (PMVT), peripheral blood stem cells (PBSCs), microfragmented adipose tissue (MFAT), autologous bone marrow-derived stem cell therapy (ABMSCT), adipose-derived stem cells (ASCs), and dehydrated human umbilical cord allograft (EpiCord), Huoxue Shengji Decoction (HXSJD) + ABMSCT (H_Group_hematopoietic) significantly increased the wound closure percentage in DFU patients (P < 0.05). According to the SUCRA ranking, HXSJD + ABMSCT was the best therapeutic method to increase the percentage of wound closure (SUCRA = 93.8%). CONCLUSION: This study employed a network meta-analysis method, combining direct and indirect comparisons, to analyze the latest clinical data and concluded that umbilical cord mesenchymal stem cells and the combination of HXSJD + autologous bone marrow hematopoietic stem cell treatment as adjunctive therapies for DFUs may have beneficial effects. Future research needs to focus on this.

Role of N6-methyladenosine in tumor neovascularization.

Tumor neovascularization is essential for the growth, invasion, and metastasis of tumors. Recent studies have highlighted the significant role of N6-methyladenosine (m6A) modification in regulating these processes. This review explores the mechanisms by which m6A influences tumor neovascularization, focusing on its impact on angiogenesis and vasculogenic mimicry (VM). We discuss the roles of m6A writers, erasers, and readers in modulating the stability and translation of angiogenic factors like vascular endothelial growth factor (VEGF), and their involvement in key signaling pathways such as PI3K/AKT, MAPK, and Hippo. Additionally, we outline the role of m6A in vascular-immune crosstalk. Finally, we discuss the current development of m6A inhibitors and their potential applications, along with the contribution of m6A to anti-angiogenic therapy resistance. Highlighting the therapeutic potential of targeting m6A regulators, this review provides novel insights into anti-angiogenic strategies and underscores the need for further research to fully exploit m6A modulation in cancer treatment. By understanding the intricate role of m6A in tumor neovascularization, we can develop more effective therapeutic approaches to inhibit tumor growth and overcome treatment resistance. Targeting m6A offers a novel approach to interfere with the tumor's ability to manipulate its microenvironment, enhancing the efficacy of existing treatments and providing new avenues for combating cancer progression.

Targeted degradation of membrane and extracellular proteins with LYTACs.

Targeted protein degradation technology has gained substantial momentum over the past two decades as a revolutionary strategy for eliminating pathogenic proteins that are otherwise refractory to treatment. Among the various approaches developed to harness the body's innate protein homeostasis mechanisms for this purpose, lysosome targeting chimeras (LYTACs) that exploit the lysosomal degradation pathway by coupling the target proteins with lysosome-trafficking receptors represent the latest innovation. These chimeras are uniquely tailored to degrade proteins that are membrane-bound and extracellular, encompassing approximately 40% of all proteome. Several novel LYTAC formulas have been developed recently, providing valuable insights for the design and development of therapeutic degraders. This review delineates the recent progresses of LYTAC technology, its practical applications, and the factors that dictate target degradation efficiency. The potential and emerging trends of this technology are discussed as well. LYTAC technology offers a promising avenue for targeted protein degradation, potentially revolutionizing the therapeutic landscape for numerous diseases.