Erythrocyte-Membrane-Camouflaged Magnetic Nanocapsules With Photothermal/Magnetothermal Effects for Thrombolysis.

Venous/arterial thrombosis poses significant threats to human health. However, drug-enabled thrombolysis treatment often encounters challenges such as short half-life and low bioavailability. To address these issues, the design of erythrocyte-membrane (EM) camouflaged nanocapsules (USIO/UK@EM) incorporating ultra-small iron oxide (USIO) and urokinase (UK) drug, which exhibits remarkable photothermal/magnetothermal effects and drug delivery ability for venous/arterial thrombolysis, is reported. USIO, UK, and EM are coextruded to fabricate USIO/UK@EM with average sizes of 103.7 nm. As USIO/UK@EM possesses wide photoabsorption and good magnetic properties, its solution demonstrates a temperature increase to 41.8-42.9 °C within 5 min when exposed to an 808 nm laser (0.33 mW cm-2) or alternating magnetic field (AMF). Such photothermal/magnetothermal effect along with UK confers impressive thrombolytic rates of 82.4% and 74.2%, higher than that (≈15%) achieved by UK alone. Further, the EM coating extends the circulating half-life (t1/2 = 3.28 h). When USIO/UK@EM is administered to mice and rabbits, tail vein thrombus in mice and femoral artery thrombus in rabbits can be dissolved by the synergetic effect of thermothrombolysis and UK. Therefore, this study not only offers insights into the rational design of multifunctional biomimetic nanocapsules but also showcases a promising thrombolysis strategy utilizing nanomedicine.

A Functional "Key" Amplified Piezoelectric Effect Modulates ROS Storm with an Open Source for Multimodal Synergistic Cancer Therapy.

Chemodynamic therapy (CDT) is a non-invasive strategy for generating reactive oxygen species (ROS) and is promising for cancer treatment. However, increasing ROS in tumor therapy remains challenging. Therefore, exogenous excitation and inhibition of electron-hole pair recombination are attractive for modulating ROS storms in tumors. Herein, a Ce-doped BiFeO3 (CBFO) piezoelectric sonosensitizer to modulate ROS generation and realize a synergistic mechanism of CDT/sonodynamic therapy and piezodynamic therapy (PzDT) is proposed. The mixed Fe2+ and Ce3+ can implement a circular Fenton/Fenton-like reaction in the tumor microenvironment. Abundant ·OH can be generated by ultrasound (US) stimulation to enhance CDT efficacy. As a typical piezoelectric sonosensitizer, CBFO can produce O2 - owing to the enhanced polarization by the US, resulting in the motion of charge carriers. In addition, CBFO can produce a piezoresponse irradiated upon US, which accelerates the migration rate of electrons/holes in opposite directions and results in energy band bending, further achieving toxic ROS production and realizing PzDT. Density functional theory calculations confirmed that Ce doping shortens the diffusion of electrons and improves the conductivity and catalytic activity of CBFO. This distinct US-enhanced strategy emphasizes the effects of doping engineering and piezoelectric-optimized therapy and shows great potential for the treatment of malignant tumors.

Exploring ALK fusion in colorectal cancer: a case series and comprehensive analysis.

Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients.

High-performance flexible p-type Ce-filled Fe3CoSb12 skutterudite thin film for medium-to-high-temperature applications.

P-type Fe3CoSb12-based skutterudite thin films are successfully fabricated, exhibiting high thermoelectric performance, stability, and flexibility at medium-to-high temperatures, based on preparing custom target materials and employing advanced pulsed laser deposition techniques to address the bonding challenge between the thin films and high-temperature flexible polyimide substrates. Through the optimization of fabrication processing and nominal doping concentration of Ce, the thin films show a power factor of >100 µW m-1 K-2 and a ZT close to 0.6 at 653 K. After >2000 bending cycle tests at a radius of 4 mm, only a 6 % change in resistivity can be observed. Additionally, the assembled p-type Fe3CoSb12-based flexible device exhibits a power density of 135.7 µW cm-2 under a temperature difference of 100 K with the hot side at 623 K. This work fills a gap in the realization of flexible thermoelectric devices in the medium-to-high-temperature range and holds significant practical application value.

Primate Model Carrying LMNA Mutation Develops Dilated Cardiomyopathy.

To solve the clinical transformation dilemma of lamin A/C (LMNA)-mutated dilated cardiomyopathy (LMD), we developed an LMNA-mutated primate model based on the similarity between the phenotype of primates and humans. We screened out patients with LMD and compared the clinical data of LMD with TTN-mutated and mutation-free dilated cardiomyopathy to obtain the unique phenotype. After establishment of the LMNA c.357-2A>G primate model, primates were continuously observed for 48 months, and echocardiographic, electrophysiological, histologic, and transcriptional data were recorded. The LMD primate model was found to highly simulate the phenotype of clinical LMD. In addition, the LMD primate model shared a similar natural history with humans.

Zinc peroxide-based nanotheranostic platform with endogenous hydrogen peroxide/oxygen generation for enhanced photodynamic-chemo therapy of tumors.

Nanotheranostic platforms, which can respond to tumor microenvironments (TME, such as low pH and hypoxia), are immensely appealing for photodynamic therapy (PDT). However, hypoxia in solid tumors harms the treatment outcome of PDT which depends on oxygen molecules to generate cytotoxic singlet oxygen (1O2). Herein, we report the design of TME-responsive smart nanotheranostic platform (DOX/ZnO2@Zr-Ce6/Pt/PEG) which can generate endogenously hydrogen peroxide (H2O2) and oxygen (O2) to alleviate hypoxia for improving photodynamic-chemo combination therapy of tumors. DOX/ZnO2@Zr-Ce6/Pt/PEG nanocomposite was prepared by the synthesis of ZnO2 nanoparticles, in-situ assembly of Zr-Ce6 as typical metal-organic framework (MOF) on ZnO2 surface, in-situ reduction of Pt nanozymes, amphiphilic lipids surface coating and then doxorubicin (DOX) loading. DOX/ZnO2@Zr-Ce6/Pt/PEG nanocomposite exhibits average sizes of ∼78 nm and possesses a good loading capacity (48.8 %) for DOX. When DOX/ZnO2@Zr-Ce6/Pt/PEG dispersions are intratumorally injected into mice, the weak acidic TEM induces the decomposition of ZnO2 core to generate endogenously H2O2, then Pt nanozymes catalyze H2O2 to produce O2 for alleviating tumor hypoxia. Upon laser (630 nm) irradiation, the Zr-Ce6 component in DOX/ZnO2@Zr-Ce6/Pt/PEG can produce cytotoxic 1O2, and 1O2 generation rate can be enhanced by 2.94 times due to the cascaded generation of endogenous H2O2/O2. Furthermore, the generated O2 can suppress the expression of hypoxia-inducible factor α, and further enable tumor cells to become more sensitive to chemotherapy, thereby leading to an increased effectiveness of chemotherapy treatment. The photodynamic-chemo combination therapy from DOX/ZnO2@Zr-Ce6/Pt/PEG nanoplatform exhibits remarkable tumor growth inhibition compared to chemotherapy or PDT. Thus, the present study is a good demonstration of a TME-responsive nanoplatform in a multimodal approach for cancer therapy.

Roles of TRPM channels in glioma.

Gliomas are the most common type of primary brain tumor. Despite advances in treatment, it remains one of the most aggressive and deadly tumor of the central nervous system (CNS). Gliomas are characterized by high malignancy, heterogeneity, invasiveness, and high resistance to radiotherapy and chemotherapy. It is urgent to find potential new molecular targets for glioma. The TRPM channels consist of TRPM1-TPRM8 and play a role in many cellular functions, including proliferation, migration, invasion, angiogenesis, etc. More and more studies have shown that TRPM channels can be used as new therapeutic targets for glioma. In this review, we first introduce the structure, activation patterns, and physiological functions of TRPM channels. Additionally, the pathological mechanism of glioma mediated by TRPM2, 3, 7, and 8 and the related signaling pathways are described. Finally, we discuss the therapeutic potential of targeting TRPM for glioma.

•TRPM channels are widely expressed in the human body and play an important role in gliomas.• Abnormal expression of TRPM2, 3, 7, and 8 channels in gliomas is associated with disease severity and prognosis.•TRPM2, 3, 7, and 8 channels are effective targets in glioma.

Boosting thermoelectric performance of single-walled carbon nanotubes-based films through rational triple treatments.

Single-walled carbon nanotubes (SWCNTs)-based thermoelectric materials, valued for their flexibility, lightweight, and cost-effectiveness, show promise for wearable thermoelectric devices. However, their thermoelectric performance requires significant enhancement for practical applications. To achieve this goal, in this work, we introduce rational "triple treatments" to improve the overall performance of flexible SWCNT-based films, achieving a high power factor of 20.29 µW cm-1 K-2 at room temperature. Ultrasonic dispersion enhances the conductivity, NaBH4 treatment reduces defects and enhances the Seebeck coefficient, and cold pressing significantly densifies the SWCNT films while preserving the high Seebeck coefficient. Also, bending tests confirm structural stability and exceptional flexibility, and a six-legged flexible device demonstrates a maximum power density of 2996 µW cm-2 at a 40 K temperature difference, showing great application potential. This advancement positions SWCNT films as promising flexible thermoelectric materials, providing insights into high-performance carbon-based thermoelectrics.

Silver Copper Chalcogenide Thermoelectrics: Advance, Controversy, and Perspective.

Thermoelectric technology, which enables a direct and pollution-free conversion of heat into electricity, provides a promising path to address the current global energy crisis. Among the broad range of thermoelectric materials, silver copper chalcogenides (AgCuQ, Q = S, Se, Te) have garnered significant attention in thermoelectric community in light of inherently ultralow lattice thermal conductivity, controllable electronic transport properties, excellent thermoelectric performance across various temperature ranges, and a degree of ductility. This review epitomizes the recent progress in AgCuQ-based thermoelectric materials, from the optimization of thermoelectric performance to the rational design of devices, encompassing the fundamental understanding of crystal structures, electronic band structures, mechanical properties, and quasi-liquid behaviors. The correlation between chemical composition, mechanical properties, and thermoelectric performance in this material system is also highlighted. Finally, several key issues and prospects are proposed for further optimizing AgCuQ-based thermoelectric materials.

A mechanical-assisted post-bioprinting strategy for challenging bone defects repair.

Bioprinting that can synchronously deposit cells and biomaterials has lent fresh impetus to the field of tissue regeneration. However, the unavoidable occurrence of cell damage during fabrication process and intrinsically poor mechanical stability of bioprinted cell-laden scaffolds severely restrict their utilization. As such, on basis of heart-inspired hollow hydrogel-based scaffolds (HHSs), a mechanical-assisted post-bioprinting strategy is proposed to load cells into HHSs in a rapid, uniform, precise and friendly manner. HHSs show mechanical responsiveness to load cells within 4 s, a 13-fold increase in cell number, and partitioned loading of two types of cells compared with those under static conditions. As a proof of concept, HHSs with the loading cells show an enhanced regenerative capability in repair of the critical-sized segmental and osteoporotic bone defects in vivo. We expect that this post-bioprinting strategy can provide a universal, efficient, and promising way to promote cell-based regenerative therapy.

Engineering topological interface states in metal-wire waveguides for broadband terahertz signal processing.

Innovative terahertz waveguides are in high demand to serve as a versatile platform for transporting and manipulating terahertz signals for the full deployment of future six-generation (6G) communication systems. Metal-wire waveguides have emerged as promising candidates, offering the crucial advantage of sustaining low-loss and low-dispersion propagation of broadband terahertz pulses. Recent advances have opened up new avenues for implementing signal-processing functionalities within metal-wire waveguides by directly engraving grooves along the wire surfaces. However, the challenge remains to design novel groove structures to unlock unprecedented signal-processing functionalities. In this study, we report a plasmonic signal processor by engineering topological interface states within a terahertz two-wire waveguide. We construct the interface by connecting two multiscale groove structures with distinct topological invariants, i.e., featuring a π-shift difference in the Zak phases. The existence of this topological interface within the waveguide is experimentally validated by investigating the transmission spectrum, revealing a prominent transmission peak in the center of the topological bandgap. Remarkably, we show that this resonance is highly robust against structural disorders, and its quality factor can be flexibly controlled. This unique feature not only facilitates essential functions such as band filtering and isolating but also promises to serve as a linear differential equation solver. Our approach paves the way for the development of new-generation all-optical analog signal processors tailored for future terahertz networks, featuring remarkable structural simplicity, ultrafast processing speeds, as well as highly reliable performance.

Elk1 enhances inflammatory cell infiltration and exacerbates acute lung injury/acute respiratory distress syndrome by suppressing Fcgr2b transcription.

OBJECTIVE: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with significant mortality rates. The role of Fcgr2b in the pathogenesis of ALI/ARDS is not fully elucidated. This study aimed to investigate the functions of Fcgr2b in ALI/ARDS and explore its underlying mechanisms. METHODS: Methods: In this study, rat models of ARDS and pulmonary microvascular endothelial cell (PMVEC) injury models were established through the administration of lipopolysaccharide (LPS). The expression levels of Fcgr2b and Elk1 were quantified in both LPS-induced ARDS rats and PMVECs. Subsequent gain- and loss-of-function experiments were conducted, followed by comprehensive assessments of lung tissue for pathomorphological changes, edema, glycogen storage, fibrosis, and infiltration of inflammatory cells. Additionally, bronchoalveolar lavage fluid was analyzed for T-helper 17 (Th17) cell infiltration, inflammatory response, and microvascular permeability to evaluate lung injury severity in ARDS models. Furthermore, the activity, cytotoxicity, apoptosis, and angiogenic potential of PMVECs were assessed to gauge cell injury. The interaction between Elk1 and Fcgr2b was also examined to confirm their regulatory relationship. RESULTS: In the context of LPS-induced ARDS and PMVEC injury, Fcgr2b expression was markedly reduced, whereas Elk1 expression was elevated. Overexpression of Fcgr2b led to a decrease in Th17 cell infiltration and mitigated lung tissue damage in ARDS models, in addition to reducing LPS-induced injury in PMVECs. Elk1 was found to suppress Fcgr2b transcription through the recruitment of histone 3 lysine 9 trimethylation (H3K9me3). Knockdown of Elk1 diminished Th17 cell infiltration and lung tissue damage in ARDS models, and alleviated LPS-induced injury in PMVECs, effects that were reversed upon Fcgr2b upregulation. CONCLUSION: Elk1 negatively regulates Fcgr2b transcription, thereby augmenting the inflammatory response and exacerbating lung injury in LPS-induced ALI/ARDS.

The efficacy of coaxial percutaneous iodine-125 seed implantation combined with arterial infusion chemotherapy for advanced pancreatic cancer: a randomized clinical trial.

BACKGROUND: This study aimed to evaluate the clinical efficacy of coaxial percutaneous Iodine-125 (125I) seed implantation in combination with arterial infusion chemotherapy for the treatment of advanced pancreatic cancer (PC) through a randomized controlled trial. METHODS: A total of 101 patients with advanced PC were randomized into two groups: control group treated with systemic intravenous chemotherapy and experimental group that received 125I seed implantation in combination with arterial infusion chemotherapy. Outcomes, including tumor control, abdominal pain relief, and survival time were compared between these two groups (Trial Registration No. KYKT2018-65). RESULTS: Pretreatment abdominal pain scores were comparable between the two groups, whereas the abdominal pain scores at 1- and 3-month post-treatment were significantly lower in the control group than those in the experimental group (1-month: 3.74 ± 1.54 vs. 4.48 ± 1.46, p = .015; 3-month: 3.64 ± 2.21 vs. 5.40 ± 1.56, p < .001). At 3-month post-treatment, computed tomography (CT) scan revealed a significantly higher disease control rate in the experimental group than that in the control group (94.0% vs. 74.5%, p = .007). The median survival time in the experimental group was significantly longer than that in the control group (15-month vs. 9-month, p < .001). CONCLUSION: The combination of coaxial percutaneous 125I seed implantation with arterial infusion chemotherapy could significantly alleviate abdominal pain, improve tumor control rates, and prolong survival time in patients with advanced PC.

Changes in Spino-pelvic Sagittal Parameters after Oblique Lateral Lumbar Interbody Fusion and Their Correlation with Clinical Outcome.

Objective: The study aimed to evaluate the impact of OLIF on spinal-pelvic sagittal parameters and its correlation with clinical outcomes in patients with degenerative lumbar spondylolisthesis. Methods: A retrospective analysis of 43 patients (23 males, 20 females) with lumbar 4/5 degenerative spondylolisthesis who underwent OLIF from January 2018 to January 2023 was conducted. Key parameters studied included SP, DH, FH, AS, LL, SS, PT, PI, and LASD. Results: All surgeries were successfully completed according to the original plan, and the minimum follow-up time was greater than 6 months, with a mean operation time of 198.21±51.32 min; the mean intraoperative bleeding volume was 121.00±56.88 ml. The VAS score of lumbar pain and ODI index decreased from the preoperative VAS score, and the ODI index of lower lumbar pain from the preoperative VAS score of 6.50±1.36 and 74.36±6.27 to the postoperative Lumbar pain of 3.20±1.28 and 32.41±8.21, respectively, and the differences were statistically significant (P < .05). 6.27 to 3.20±1.28 and 32.41±8.21 at the final follow-up visit. The differences were statistically significant (P < .05). The results of Pearson correlation analysis showed positive correlation between postoperative LL and FH, SP and AS, VAS (P < .05), and service correlation between SP and SS, LASD (P < .05), and correlation between pre- and post-surgery difference of LL, FH, SP and the improvement rate of ODI and VAS scores (P < .05), with the difference of pre- and post-surgery difference of LL, FH and the ODI, VAS score improvement rate were the strongest correlation. Postoperatively, significant improvements were observed in LL and FH. Pearson correlation analysis indicated a positive correlation between changes in sagittal parameters and clinical outcomes, measured by VAS and ODI scores. Conclusion: The postoperative spine-pelvis sagittal parameters were significantly improved compared with the preoperative ones, and the changes of the spine-pelvis sagittal parameters before and after the operation were correlated with the clinical outcomes, among which the differences of LL and FH had the strongest correlation with the improvement rates of ODI and VAS scores. OLIF effectively improved spinal-pelvic sagittal parameters and clinical outcomes in degenerative lumbar spondylolisthesis, with changes in LL and FH showing the strongest correlation with patient-reported outcome improvements. An oblique lateral interbody fusion can effectively reconstruct spine-pelvis sagittal parameters in patients with degenerative lumbar spondylolisthesis.

Remarkable purification of organic dyes by NiOOH-modified industrial waste residues.

Extracting functional materials from industrial waste residues to absorb organic dyes can maximize waste reuse and minimize water pollution. However, the extraordinarily low purification efficiency still limits the practical application of this strategy. Herein, the lamellar NiOOH is in-situ anchored on the industrial waste red mud surface (ARM/NiOOH) as an adsorbent to purify organic dyes in wastewater. ARM/NiOOH adsorbent with high specific surface area and porosity provides considerable active sites for the congo red (CR), thereby significantly enhancing the removal efficiency of CR. Besides, we fit a reasonable adsorption model for ARM/NiOOH adsorbent and investigate its adsorption kinetics. Resultantly, ARM/NiOOH adsorbent can remarkably adsorb 348.0 mg g-1 CR within 5 min, which is 7.91 times that of raw RM. Our work provides a strategy for reusing industrial waste and purifying sewage pollution, which advances wastewater treatment engineering.

Nonlinear optical response of heme solutions.

Heme is the prosthetic group for cytochrome that exists in nearly all living organisms and serves as a vital component of human red blood cells (RBCs). Tunable optical nonlinearity in suspensions of RBCs has been demonstrated previously, however, the nonlinear optical response of a pure heme (without membrane structure) solution has not been studied to our knowledge. In this work, we show optical nonlinearity in two common kinds of heme (i.e., hemin and hematin) solutions by a series of experiments and numerical simulations. We find that the mechanism of nonlinearity in heme solutions is distinct from that observed in the RBC suspensions where the nonlinearity can be easily tuned through optical power, concentration, and the solution properties. In particular, we observe an unusual phenomenon wherein the heme solution exhibits negative optical nonlinearity and render self-collimation of a focused beam at specific optical powers, enabling shape-preserving propagation of light to long distances. Our results may have potential applications in optical imaging and medical diagnosis through blood.

MOFs-Based Magnetic Nanozyme to Boost Cascade ROS Accumulation for Augmented Tumor Ferroptosis.

The emerging cell death modality of ferroptosis has garnered increasing attention for antitumor treatment but still suffers from low therapeutic efficacy. A metal-organic frameworks (MOFs)-based magnetic nanozyme (PZFH) comprising porphyrin-based Zr-MOF (PCN) on zinc ferrite (ZF) nanoparticles modified with hyaluronic acid, delivering excellent magnetophotonic response for efficient ferroptosis, is reported here. PZFH shows multienzyme-like cascade activity encompassing a photon-triggered oxidase-like catalysis to generate O2 -, which is converted to H2O2 by superoxide dismutase-like activity and subsequent ·OH by magneto-promoted peroxidase (POD) behavior. Newly formed Fe─N coordination and increased Fe2+/Fe3+ levels in the PZFH contribute to the enhanced POD activity, which is further enhanced by accelerated surface electron transfer when exposure to alternated magnetic field. Accumulation of lipid peroxides is eventually accomplished through the conversion of ·OH radicals and singlet oxygen (1O2) produced through laser irradiation. When combined with the depletion of inhibition of glutathione and glutathione peroxidase 4, PZFH exhibits significantly enhanced ferroptosis in tumor-bearing mice, offering insights into nanomedicine for ferroptosis and holding great promise in clinical antitumor therapies.

TGR5-mediated lateral hypothalamus-dCA3-dorsolateral septum circuit regulates depressive-like behavior in male mice.

Although bile acids play a notable role in depression, the pathological significance of the bile acid TGR5 membrane-type receptor in this disorder remains elusive. Using depression models of chronic social defeat stress and chronic restraint stress in male mice, we found that TGR5 in the lateral hypothalamic area (LHA) predominantly decreased in GABAergic neurons, the excitability of which increased in depressive-like mice. Upregulation of TGR5 or inhibition of GABAergic excitability in LHA markedly alleviated depressive-like behavior, whereas down-regulation of TGR5 or enhancement of GABAergic excitability facilitated stress-induced depressive-like behavior. TGR5 also bidirectionally regulated excitability of LHA GABAergic neurons via extracellular regulated protein kinases-dependent Kv4.2 channels. Notably, LHA GABAergic neurons specifically innervated dorsal CA3 (dCA3) CaMKIIα neurons for mediation of depressive-like behavior. LHA GABAergic TGR5 exerted antidepressant-like effects by disinhibiting dCA3 CaMKIIα neurons projecting to the dorsolateral septum (DLS). These findings advance our understanding of TGR5 and the LHAGABA→dCA3CaMKIIα→DLSGABA circuit for the development of potential therapeutic strategies in depression.

Methylated ctDNA predicts early recurrence risk in patients undergoing resection of initially unresectable colorectal cancer liver metastases.

Background: Patients with initially unresectable colorectal cancer liver metastases (IU-CRLM) might benefit from using an effective systemic treatment followed by resection of liver metastases but the curative success rate is quite low. Indeed, nearly one-third of patients exhibit early recurrence within the first 6 months after surgery, and these individuals often have poor overall survival. Objectives: This study aims to clarify the application value of serial circulating tumor DNA (ctDNA) analysis in predicting the clinical outcome of IU-CRLM patients following liver metastasectomy. Design: A retrospective study was conducted on a cohort of patients with IU-CRLM between February 2018 and April 2021. Methods: Plasma samples at different time points during CRLM treatment [baseline (BL), preoperation (PRE), postoperation (POST), end-of-treatment (EOT), and progressive disease (PD)] were retrospectively collected from patients with initially unresectable CRLM enrolled at the Sun Yat-sen University Cancer Center. Dynamic changes of SEPTIN 9 (SEPT9) and Neuropeptide Y (NPY) methylated circulating tumor DNA (MetctDNA) levels in serial plasma samples were detected using droplet-digital PCR (ddPCR). Results: SEPT9 and NPY genes were hypermethylated in colon cancer cell lines and tissues while no difference was observed between primary and metastatic tumors. Patients with MetctDNA positive at POST or EOT had significantly lower recurrence-free survival (RFS) compared to patients with MetctDNA negative at these time points [POST: Hazard ratio (HR) 9.44, 95% confidence interval (CI) 5.15-17.30, p < 0.001; EOT: HR 11.48, 95% CI 3.27-40.31, p < 0.001]. Multivariate analysis demonstrated that POST (OR 33.96, 95% CI 4.03-286.10, p = 0.001) and EOT (OR 18.36, 95% CI 1.14-295.71, p = 0.04) MetctDNA was an independent risk factor for early recurrence. Time-dependent receiver operating characteristic curve (T-ROC) analysis revealed that area under the curve (AUC) value was greatest at the relapse time point of 6 months post-intervention, with POST-AUC and EOT-AUC values of 0.74 (95% CI 0.66-0.81) and 0.73 (95% CI 0.53-0.94), respectively. Serial MetctDNA analysis showed that RFS was significantly lower in patients with no MetctDNA clearance compared with those with MetctDNA clearance (HR 26.05, 95% CI 4.92-137.81, p < 0.001). Conclusion: Our study confirmed that serial ctDNA analysis of NPY and SEPT9 gene methylation could effectively predict early recurrence in IU-CRLM patients, especially at POST and EOT.

Zinc Doping Induces Enhanced Thermoelectric Performance of Solvothermal SnTe.

The creation of hierarchical nanostructures can effectively strengthen phonon scattering to reduce lattice thermal conductivity for improving thermoelectric properties in inorganic solids. Here, we use Zn doping to induce a remarkable reduction in the lattice thermal conductivity in SnTe, approaching the theoretical minimum limit. Microstructure analysis reveals that ZnTe nanoprecipitates can embed within SnTe grains beyond the solubility limit of Zn in the Zn alloyed SnTe. These nanoprecipitates result in a substantial decrease of the lattice thermal conductivity in SnTe, leading to an ultralow lattice thermal conductivity of 0.50 W m-1 K-1 at 773 K and a peak ZT of ~0.48 at 773 K, marking an approximately 45 % enhancement compared to pristine SnTe. This study underscores the effectiveness of incorporating ZnTe nanoprecipitates in boosting the thermoelectric performance of SnTe-based materials.