Gasdermin-E-mediated pyroptosis drives immune checkpoint inhibitor-associated myocarditis via cGAS-STING activation.

Immune checkpoint inhibitor (ICI)-induced myocarditis involves intensive immune/inflammation activation; however, its molecular basis is unclear. Here, we show that gasdermin-E (GSDME), a gasdermin family member, drives ICI-induced myocarditis. Pyroptosis mediated by GSDME, but not the canonical GSDMD, is activated in myocardial tissue of mice and cancer patients with ICI-induced myocarditis. Deficiency of GSDME in male mice alleviates ICI-induced cardiac infiltration of T cells, macrophages, and monocytes, as well as mitochondrial damage and inflammation. Restoration of GSDME expression specifically in cardiomyocytes, rather than myeloid cells, in GSDME-deficient mice reproduces ICI-induced myocarditis. Mechanistically, quantitative proteomics reveal that GSDME-dependent pyroptosis promotes cell death and mitochondrial DNA release, which in turn activates cGAS-STING signaling, triggering a robust interferon response and myocardial immune/inflammation activation. Pharmacological blockade of GSDME attenuates ICI-induced myocarditis and improves long-term survival in mice. Our findings may advance the understanding of ICI-induced myocarditis and suggest that targeting the GSDME-cGAS-STING-interferon axis may help prevent and manage ICI-associated myocarditis.

Advancing flexible thermoelectrics for integrated electronics.

With the increasing demand for energy and the climate challenges caused by the consumption of traditional fuels, there is an urgent need to accelerate the adoption of green and sustainable energy conversion and storage technologies. The integration of flexible thermoelectrics with other various energy conversion technologies plays a crucial role, enabling the conversion of multiple forms of energy such as temperature differentials, solar energy, mechanical force, and humidity into electricity. The development of these technologies lays the foundation for sustainable power solutions and promotes research progress in energy conversion. Given the complexity and rapid development of this field, this review provides a detailed overview of the progress of multifunctional integrated energy conversion and storage technologies based on thermoelectric conversion. The focus is on improving material performance, optimizing the design of integrated device structures, and achieving device flexibility to expand their application scenarios, particularly the integration and multi-functionalization of wearable energy conversion technologies. Additionally, we discuss the current development bottlenecks and future directions to facilitate the continuous advancement of this field.

Electron beam lithography of GeTe through polymorphic phase transformation.

We report two previously undiscovered phases of GeTe including the sphalerite (c-) phase and the hexagonal (h-) phase with interlayer van der Waals gaps. A polymorphic phase transformation from rhombohedral α-GeTe to c- and h-GeTe at near room temperature is first realized via electron beam irradiation. Their underlying thermodynamics and kinetics are illustrated using the in situ heating experiments and molecular dynamics simulations. Density-functional theory calculations indicate that c-GeTe exhibits typical metallic behavior and h-GeTe is a narrow-gap semiconductor with a strong spin-orbital coupling effect. Our findings shed light on a strategy for designing GeTe-based quantum devices compromising nanopillars and heterostructures via an atomic-scale electron beam lithography technique.

Constrained patterning of orientated metal chalcogenide nanowires and their growth mechanism.

One-dimensional metallic transition-metal chalcogenide nanowires (TMC-NWs) hold promise for interconnecting devices built on two-dimensional (2D) transition-metal dichalcogenides, but only isotropic growth has so far been demonstrated. Here we show the direct patterning of highly oriented Mo6Te6 NWs in 2D molybdenum ditelluride (MoTe2) using graphite as confined encapsulation layers under external stimuli. The atomic structural transition is studied through in-situ electrical biasing the fabricated heterostructure in a scanning transmission electron microscope. Atomic resolution high-angle annular dark-field STEM images reveal that the conversion of Mo6Te6 NWs from MoTe2 occurs only along specific directions. Combined with first-principles calculations, we attribute the oriented growth to the local Joule-heating induced by electrical bias near the interface of the graphite-MoTe2 heterostructure and the confinement effect generated by graphite. Using the same strategy, we fabricate oriented NWs confined in graphite as lateral contact electrodes in the 2H-MoTe2 FET, achieving a low Schottky barrier of 11.5 meV, and low contact resistance of 43.7 Ω µm at the metal-NW interface. Our work introduces possible approaches to fabricate oriented NWs for interconnections in flexible 2D nanoelectronics through direct metal phase patterning.

Free-space coupled, large-active-area superconducting microstrip single-photon detector for photon-counting time-of-flight imaging.

Numerous applications at the photon-starved regime require a free-space coupling single-photon detector with a large active area, low dark count rate (DCR), and superior time resolutions. Here, we developed a superconducting microstrip single-photon detector (SMSPD), with a large active area of 260 µm in diameter, a DCR of ∼5k c p s, and a low time jitter of ∼171p s, operated at a near-infrared of 1550 nm and a temperature of ∼2.0K. As a demonstration, we applied the detector to a single-pixel galvanometer scanning system and successfully reconstructed the object information in depth and intensity using a time-correlated photon counting technology.

Primary diffuse large B-cell lymphoma of adrenal gland: A case report.

INTRODUCTION: Most adrenal tumors are benign and primary adrenal malignancies are relatively rare. Primary adrenal lymphoma (PAL) is a very rare and highly aggressive malignant tumor with unknown etiology, atypical clinical symptoms, nonspecific imaging manifestations, difficult disease diagnosis and poor prognosis. CASE REPORT: This case report details a 42-year-old woman who was admitted to the hospital with a 1-year-old bilateral adrenal mass and 1-month-old left upper abdominal pain. Enhanced CT of the abdomen showed a right adrenal nodule and a large occupying lesion in the left adrenal region, with a high probability of pheochromocytoma. Intraoperatively, a huge tumor measuring about 12*12*10 cm was found in the left adrenal region, infiltrating the left kidney, spleen and pancreatic tail. Postoperative pathology: lymphocytes were found in the renal capsule and subcapsule, lymphocytes were found in the pancreas; lymphocytes were found in the spleen. Consider a tumor of the lymphohematopoietic system, possibly lymphoma. CONCLUSION: This case demonstrates that primary adrenal diffuse large B-cell lymphoma (PADLBCL) is highly aggressive, has a poor prognosis, is prone to recurrence, has poor therapeutic outcomes, and is difficult to diagnose. Clinicians should consider the possibility of PADLBCL when encountering huge adrenal-occupying lesions and consider chemotherapy before surgery. Reducing the tumor size before surgery is a more favorable therapeutic approach, thus prolonging the patient life and improving the quality of survival.

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.

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.

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.

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.

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.

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.

Clinical and molecular characteristics of RNF43 mutations as promising prognostic biomarkers in colorectal cancer.

Background: Transmembrane E3 ubiquitin ligase (RNF43) mutations are present in approximately 6-18% of colorectal cancers (CRC) and could enhance Wnt/ß-catenin signaling, which is emerging as a promising therapeutic target. This study aims to investigate the clinical and molecular characteristics and potential heterogeneity of RNF43-mutant CRC. Methods: A total of 78 patients with RNF43-mutant CRC were enrolled from July 2013 to November 2022. Demographic data, clinical characteristics, treatment regimens used, and survival outcomes were collected and analyzed. Results: Our study uncovered that patients with RNF43 mutations in the N-terminal domain (NTD; n = 50) exhibited shorter overall survival (OS; median months, 50.80 versus not reached; p = 0.043) compared to those in the C-terminal domain (CTD; n = 17). Most RNF43 mutations in NTD had positive primary lymph node status, low tumor mutation burden (TMB-L), and correlated with proficient mismatch repair (pMMR)/microsatellite stable (MSS) status. By contrast, RNF43 mutations in CTD were significantly enriched in deficient MMR (dMMR)/microsatellite instability (MSI-H) tumors with high TMB (TMB-H). N-terminal RNF43-mutated tumors harbored a hotspot variant (RNF43 R117fs), which independently predicted a significantly worse outcome in pMMR/MSS CRC with a median OS of 18.9 months. Patients with RNF43 mutations and the BRAF V600E alterations demonstrated sensitivity to BRAF/EGFR inhibitors. Moreover, we observed that pMMR/MSS patients with RNF43 R117fs mutation had a higher incidence of stage IV, ⩾2 metastatic sites, low TMB, and none of them received PD-1/PD-L1 inhibitor therapy. Conclusion: Our findings provide the first evidence that RNF43 mutations in NTD and the R117fs variant correlate with a poorer prognosis in CRC patients, providing strategies for Wnt-targeted therapy to improve clinical efficacy.

Flexible power generators by Ag2Se thin films with record-high thermoelectric performance.

Exploring new near-room-temperature thermoelectric materials is significant for replacing current high-cost Bi2Te3. This study highlights the potential of Ag2Se for wearable thermoelectric electronics, addressing the trade-off between performance and flexibility. A record-high ZT of 1.27 at 363 K is achieved in Ag2Se-based thin films with 3.2 at.% Te doping on Se sites, realized by a new concept of doping-induced orientation engineering. We reveal that Te-doping enhances film uniformity and (00l)-orientation and in turn carrier mobility by reducing the (00l) formation energy, confirmed by solid computational and experimental evidence. The doping simultaneously widens the bandgap, resulting in improved Seebeck coefficients and high power factors, and introduces TeSe point defects to effectively reduce the lattice thermal conductivity. A protective organic-polymer-based composite layer enhances film flexibility, and a rationally designed flexible thermoelectric device achieves an output power density of 1.5 mW cm-2 for wearable power generation under a 20 K temperature difference.

Decoupling Carrier-Phonon Scattering Boosts the Thermoelectric Performance of n-Type GeTe-Based Materials.

The coupled relationship between carrier and phonon scattering severely limits the thermoelectric performance of n-type GeTe materials. Here, we provide an efficient strategy to enlarge grains and induce vacancy clusters for decoupling carrier-phonon scattering through the annealing optimization of n-type GeTe-based materials. Specifically, boundary migration is used to enlarge grains by optimizing the annealing time, while vacancy clusters are induced through the aggregation of Ge vacancies during annealing. Such enlarged grains can weaken carrier scattering, while vacancy clusters can strengthen phonon scattering, leading to decoupled carrier-phonon scattering. As a result, a ratio between carrier mobility and lattice thermal conductivity of ∼492.8 cm3 V-1 s-1 W-1 K and a peak ZT of ∼0.4 at 473 K are achieved in Ge0.67Pb0.13Bi0.2Te. This work reveals the critical roles of enlarged grains and induced vacancy clusters in decoupling carrier-phonon scattering and demonstrates the viability of fabricating high-performance n-type GeTe materials via annealing optimization.

Simultaneously Boosting Thermoelectric and Mechanical Properties of n-Type Mg3Sb1.5Bi0.5-Based Zintls through Energy-Band and Defect Engineering.

Incorporating donor doping into Mg3Sb1.5Bi0.5 to achieve n-type conductivity is one of the crucial strategies for performance enhancement. In pursuit of higher thermoelectric performance, we herein report co-doping with Te and Y to optimize the thermoelectric properties of Mg3Sb1.5Bi0.5, achieving a peak ZT exceeding 1.7 at 703 K in Y0.01Mg3.19Sb1.5Bi0.47Te0.03. Guided by first-principles calculations for compositional design, we find that Te-doping shifts the Fermi level into the conduction band, resulting in n-type semiconductor behavior, while Y-doping further shifts the Fermi level into the conduction band and reduces the bandgap, leading to enhanced thermoelectric performance with a power factor as high as >20 µW cm-1 K-2. Additionally, through detailed micro/nanostructure characterizations, we discover that Te and Y co-doping induces dense crystal and lattice defects, including local lattice distortions and strains caused by point defects, and densely distributed grain boundaries between nanocrystalline domains. These defects efficiently scatter phonons of various wavelengths, resulting in a low thermal conductivity of 0.83 W m-1 K-1 and ultimately achieving a high ZT. Furthermore, the dense lattice defects induced by co-doping can further strengthen the mechanical performance, which is crucial for its service in devices. This work provides guidance for the composition and structure design of thermoelectric materials.

[Correlation analysis of serum MMP-1 and MMP-2 levels with lower extremity deep venous thrombosis after operation for lower limb fracture].

OBJECTIVE: To investigate the relationship between serum matrix metalloproteinase-1(MMP-1) and matrix metalloproteinase-2(MMP-2) and the formation of deep venous thrombosis(LDVT) in lower extremity patients after surgery for lower extremity fracture, and to analyze the value of MMP-1 and MMP-2 in predicting the occurrence of LDVT after lower extremity fracture. METHODS: From June 2018 to December 2021, 352 patients who planned to receive surgical treatment of lower limb fracture in our hospital were selected as the research objects. Venous blood was collected at 1, 2 and 3 days after surgery, respectively, and serum MMP-1 and MMP-2 levels were detected. The incidence of LDVT during hospitalization was analyzed, and the risk factors of postoperative LDVT in patients with lower limb fracture surgery and the predictive value of MMP-1 and MMP-2 for LDVT were analyzed. RESULTS: LDVT occurred in 40 patients (LDVT group), the incidence of LDVT was 11.36%, and 312 patients did not occurred(no occurred group). The serum levels of MMP-1 and MMP-2 in LDVT group increased gradually after surgery; the serum levels of MMP-1 and MMP-2 in the no occurred group increased slightly after surgery at 2 days and then decreased at 3 days after surgery (P<0.01);the serum levels of MMP-1 and MMP-2 in LDVT group were higher than those in the no occurred group at 2 days and 3 days after surgery (P<0.05). Serum levels of MMP-1 and MMP-2 were positively correlated with serum levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor -α (TNF-α) in LDVT patients at 2 days and 3 days postoperatively (P<0.05). Operative time, MMP-1 and MMP-2 postoperative 3 days were related to the occurrence of LDVT after lower limb fracture (P<0.01). The area under the curve(AUC) predicted by MMP-1 and MMP-2 postoperative 3 days for LDVT after lower limb fracture was 0.738 and 0.744 respectively, and the AUC predicted by combined MMP-1 and MMP-2 was 0.910, which was higher than that predicted by single indicator(Z=2.819 and 2.025, P<0.05). CONCLUSION: High levels of MMP-1 and MMP-2 after lower extremity fracture are closely related to the occurrence of LDVT, and 3 d mMP-1 and MMP-2 after surgery maybe used as evaluation indexes for LDVT risk prediction.

High-efficiency broadband fiber-to-chip coupler using a 3D nanoprinting microfiber.

We propose a method for coupling a tapered optical fiber to an inverted tapered SiN waveguide by fabricating a microfiber using 3D nanoprinting lithography. The microfiber consists of three parts: a tapered cladding cap, an S-bend, and a straight part, all composed of high-refractive-index material. Light is adiabatically coupled from the tapered fiber to the printed microfiber through the cladding cap. The light is then transmitted through the S-bend and the straight part with low loss and is finally coupled to the waveguide through the evanescent field. In the simulation, our design can achieve a high coupling efficiency (TE mode) of ∼97% at a wavelength of 1542 nm with a wide bandwidth of ∼768n m at the 1-dB cutoff criterion.