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Since thermoelectric materials have different physical and chemical properties, the design of contact layers requires dedicated efforts, and the welding temperatures are distinctly different. Therefore, a general interface design and connection technology can greatly facilitate the development of thermoelectric devices. Herein, we proposed a screening strategy for the contact materials based on the calculation of phase diagram method, and Mg 2 Ni has been identified as a matched contact layer for n-type Mg 3 Sb 2 -based materials. And this screening strategy can be effectively applied to other thermoelectric materials. By adopting the low-temperature sintering silver nanoparticles technology, the Zintl phase thermoelectric device can be fabricated at low temperature but operate at medium temperature. The single-leg n-type Mg 3.15 Co 0.05 SbBi 0.99 Se 0.01 device achieves an efficiency of ~13.3%, and a high efficiency of ~11% at the temperature difference of 430 K has been realized for the Zintl phase thermoelectric device comprised together with p-type Yb 0.9 Mg 0.9 Zn 1.198 Ag 0.002 Sb 2 . Additionally, the thermal aging and thermal cycle experiments proved the long-term reliability of the Mg 2 Ni/Mg 3.15 Co 0.05 SbBi 0.99 Se 0.01 interface and the nano-silver sintering joints. Our work paves an effective avenue for the development of advanced devices for thermoelectric power generation. Based on the CALPHAD method, authors propose an effective screening strategy for thermoelectric contact materials, realizing a high efficiency of ~11% (at ∆T = 430 K) for the full-Zintl phase thermoelectric device.

Lately, autologous CD19-targeting chimeric antigen receptor (CAR) T cells have shown excellent efficacy in treatment of autoimmune diseases, but with great safety concerns, such as infections. In this study, we aimed to evaluate the safety, tolerability, and efficacy of allogeneic CD19 CAR natural killer (NK)-cell therapy in patients with relapsed or refractory systemic lupus erythematosus (SLE). In this open-label, single-arm, prospective, first-in-human case series, we evaluated allogeneic CD19 CAR NK-cell therapy in adult patients (aged 18–65 years) with relapsed or refractory SLE at one site in China. Patients who had received at least two previous standard systemic therapies and continued to exhibit moderate-to-severe disease activity were eligible for inclusion. This study consisted of schedule escalation and dose escalation, with schedule escalation from 7 days and dose escalation commencing at 0·75 × 109 CAR NK cells on day 0. All patients received a lymphodepleting conditioning regimen with fludarabine (25 mg/m2 per day) and cyclophosphamide (300 mg/m2 per day) administered daily from days –5 to –3, followed by three CAR NK-cell infusions within a single treatment cycle at identical dose levels and inter-infusion intervals. Dose-limiting adverse events were monitored in patients for 28 days. The primary endpoints of this study were safety and tolerability, including the incidence of dose-limiting toxicities and adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. This study was registered with ClinicalTrials.gov (NCT06010472) and follow-up is ongoing. 18 patients with relapsed or refractory SLE with moderate-to-severe disease activity were enrolled between Aug 21, 2023, and June 16, 2024. Of the 18 patients, 17 (94%) were female; the median age was 37·5 years (IQR 32·0–39·8), and the median disease duration was 10·5 years (IQR 4·5–14·8). Patients had received at least two standard systemic therapies, including biological agents (belimumab and telitacicept) in 14 (78%) of 18 patients, and plasmapheresis in one patient. Cytokine release syndrome was reported in one (6%) of 18 patients (grade 1). Neurotoxicity and other CAR NK-cell therapy-related severe adverse events were not observed, and there were no dose-limiting toxicities. Of the nine patients with more than 12 months’ follow-up, six (67%) attained DORIS remission and lupus low disease activity state. This study suggests that allogeneic CAR NK-cell therapy is a potent option for treatment of autoimmune diseases and indicates that such a therapy might address limitations of current autologous CAR T-cell therapy, including manufacturing scale and time, access, safety, and cost. Shanghai Municipal Health Commission, Changhai Hospital Affiliated to Naval Medical University, and National Natural Science Foundation of China. For the Chinese translation of the abstract see Supplementary Materials section.

BackgroundPlant ZIP genes represent an important transporter family involved in metal transport. Evidence has implied that some ZIPs may contribute to plant Cd uptake, but a genome-wide examination of ZIPs’ role in Cd tolerance and uptake has rarely been reported. In this study, a genome-wide bioinformatic screening of candidate ZIP genes in Arabidopsis and rice was performed, followed by a systematic determination of their expression profile in response to Cd stress. Typical up-regulated ZIPs genes were then expressed in yeast cells to examine their effect on hosts’ Cd uptake.ResultsA total of 27 ZIP genes in Arabidopsis and rice were screened out based on sequence similarity. In Arabidopsis, Cd exposure strongly impacted the expression of most ZIPs, among which AtIRT1, AtIRT2, AtIRT4 AtZIP9, AtZIP10 and AtZIP12 were sharply up-regulated and AtIRT3, AtIRT5 were significantly down-regulated in root. In rice, all tested genes in shoot except for OsIRT1 and OsIRT12 were sharply up-regulated, while OsIRT1 and OsZIP1 in root were significantly down-regulated. Interestingly, some genes like AtIRT3, AtZIP5, AtZIP12, OsIRT1 and OsZIP1 showed converse expression regulation when subject to the tested Cd stress. When expressed in yeast cells, three ZIPs, AtIRT1, OsZIP1 and OsZIP3, caused a substantial increase in Cd sensitivity and Cd accumulation of the host cells.ConclusionsIn conclusion, this study revealed a distinct pattern in ZIPs family genes expression between Arabidopsis and rice in response to Cd stress. Arabidopsis mainly up-regulated root ZIPs genes, while rice mainly up-regulated shoot ZIPs genes. Three genes, AtIRT1, OsZIP1 and OsZIP3, conferred an increased Cd accumulation and sensitivity to Cd stress when expressed in yeast cells, further implying their roles in Cd uptake in plants.

ObjectiveThis study aimed to investigate the relationship between endometrial echo and pregnancy outcome in patients undergoing thawed embryo transfer and explore the effect of different endometrial preparation schemes on endometrial echo.MethodsA retrospective analysis was conducted on data from 2910 patients who underwent freeze-thaw embryo transfer (FET)-assisted pregnancy in the reproductive medicine centre of our hospital from January 2019 to March 2024. Based on the endometrial echo on the transplantation day, the patients were divided into two groups: the endometrial echo uniform group and the endometrial echo uneven group. Based on the endometrial preparation protocol, they were divided into the natural cycle (NC) group, hormone replacement cycle (HRT) group, and downregulated combined HRT (GnRHa+HRT) group. The general data, pregnancy outcome and endometrial echo of those undergoing different endometrial preparation protocols were compared.ResultsThe clinical pregnancy rate in the homogeneous endometrial echo group was significantly higher than that in the non-homogeneous endometrial echo group. The equalisation rate of endometrial echo in the NC group and GnRHa+HRT group was significantly higher than that in the HRT group (p<0.05). Binary logistic regression analysis revealed that homogeneous endometrial echo was associated with a significantly improved clinical pregnancy rate of patients with FET. After adjusting for confounding factors, we found that compared with the HRT endometrial preparation protocol, NC and GnRHa+HRT endometrial preparation protocol significantly improved homogeneous endometrial echo.ConclusionNon-homogeneous endometrial echo on the transplantation day was associated with a decreased clinical pregnancy rate of FET. The endometrial preparation protocol of the NC and GnRHa+HRT cycle can improve homogeneous endometrial echo. In FET, clinicians should develop a personalised endometrial preparation protocol based on patients’ situations.

Intrahepatic cholangiocarcinoma (ICC) typically exhibits poor responsiveness to immune checkpoint inhibitors (ICIs) due to its microsatellite-stable (MSS) status and low tumor mutational burden (TMB). Conventional biomarkers like PD-L1 expression show limited predictive value, creating an urgent need for novel therapeutic targets in this aggressive malignancy. We describe a stage IV ICC patient with PD-L1 positivity and a somatic KMT2D mutation (p.R5303C) who attained sustained complete remission after pembrolizumab treatment, despite developing severe multi-organ immune-related adverse events (irAEs) including hepatitis, pneumonitis, and thrombocytopenia. Mechanistic analysis revealed that KMT2D deficiency potentially remodeled the tumor immune microenvironment through epigenetic reprogramming, characterized by enhanced CD8+ T-cell infiltration. Our findings advocate for combinatorial biomarker strategies incorporating epigenetic markers (KMT2D status) with PD-L1 expression to optimize ICI patient selection, while highlighting the need for vigilant toxicity monitoring in this subset.

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections with Candida of the skin, nails, and mucous membrane. It is a rare and severe disease resulting from autoimmune defects or immune dysregulations. Nonetheless, the diagnosis and treatment of CMC still pose significant challenges. Erroneous or delayed diagnoses remain prevalent, while the long-term utility of traditional antifungals often elicits adverse reactions and promotes the development of acquired resistance. Furthermore, disease relapse can occur during treatment with traditional antifungals. In this review, we delineate the advancements in molecular diagnostic and therapeutic approaches to CMC. Genetic and biomolecular analyses are increasingly employed as adjuncts to clinical manifestations and fungal examinations for accurate diagnosis. Simultaneously, a range of therapeutic interventions, including Janus kinase (JAK) inhibitors, hematopoietic stem cell transplantation (HSCT), cytokines therapy, novel antifungal agents, and histone deacetylase (HDAC) inhibitors, have been integrated into clinical practice. We aim to explore insights into early confirmation of CMC as well as novel therapeutic options for these patients.

Malignant tumor, the leading cause of death worldwide, poses a serious threat to human health. For decades, natural product has been proven to be an essential source for novel anticancer drug discovery. Shikonin (SHK), a natural molecule separated from the root of , shows great potential in anticancer therapy. However, its further clinical application is significantly restricted by poor bioavailability, adverse effects, and non-selective toxicity. With the development of nanotechnology, nano drug delivery systems have emerged as promising strategies to improve bioavailability and enhance the therapeutic efficacy of drugs. To overcome the shortcoming of SHK, various nano drug delivery systems such as liposomes, polymeric micelles, nanoparticles, nanogels, and nanoemulsions, were developed to achieve efficient delivery for enhanced antitumor effects. Herein, this review summarizes the anticancer pharmacological activities and pharmacokinetics of SHK. Additionally, the latest progress of SHK nanomedicines in cancer therapy is outlined, focusing on long circulation, tumor targeting ability, tumor microenvironment responsive drug release, and nanosystem-mediated combination therapy. Finally, the challenges and prospects of SHK nanomedicines in the future clinical application are spotlighted.

With the rapid spread of built-in GPS handheld smart devices, the trajectory data from GPS sensors has grown explosively. Trajectory data has spatio-temporal characteristics and rich information. Using trajectory data processing techniques can mine the patterns of human activities and the moving patterns of vehicles in the intelligent transportation systems. A trajectory similarity measure is one of the most important issues in trajectory data mining (clustering, classification, frequent pattern mining, etc.). Unfortunately, the main similarity measure algorithms with the trajectory data have been found to be inaccurate, highly sensitive of sampling methods, and have low robustness for the noise data. To solve the above problems, three distances and their corresponding computation methods are proposed in this paper. The point-segment distance can decrease the sensitivity of the point sampling methods. The prediction distance optimizes the temporal distance with the features of trajectory data. The segment-segment distance introduces the trajectory shape factor into the similarity measurement to improve the accuracy. The three kinds of distance are integrated with the traditional dynamic time warping algorithm (DTW) algorithm to propose a new segment–based dynamic time warping algorithm (SDTW). The experimental results show that the SDTW algorithm can exhibit about 57%, 86%, and 31% better accuracy than the longest common subsequence algorithm (LCSS), and edit distance on real sequence algorithm (EDR) , and DTW, respectively, and that the sensitivity to the noise data is lower than that those algorithms.

Electrochemically constructing C–N and N–C–N bonds provides an economical and sustainable alternative to conventional chemosynthesis. Herein, a hierarchically ordered open superstructure of N-doped carbon isolated with accessible three-coordinated Zn single-atom sites is explored for efficient electrocatalytic N–C–N coupling. Benefiting from the distinctive structural merits, this catalyst enables electrocatalytic preparation of N–C–N bonded compounds from methanol and amines. Notably, the Faradaic efficiency and selectivity of N,N,N’,N’ -tetramethyldiaminomethane reach up to 77% and 96% at 0.8 V, respectively. Further integrating the aminoalkylation reaction, an electro-thermo cascade synthesis is explored with the electrochemically obtained N,N,N’,N’ -tetramethyldiaminomethane serving as a unique reagent, leading to a specific set of organonitrogen compounds with (dimethylamino)methyl substituent, including topotecan hydrochloride, an anti-tumor drug, with a high yield of 95%. Furthermore, the in situ spectroscopic characterization and calculations unveil that the under-coordinated Zn-N 3 sites play a pivotal role in stabilizing the key *CH 2 O intermediate, thereby facilitating subsequent nucleophilic addition with amines. Here, this study report efficient electrocatalytic N–C–N coupling over a hierarchically ordered open superstructure of N-doped carbon isolated with accessible three-coordinated single Zn atoms, achieving sustainable synthesis of organonitrogen compounds.

Mg 3 Sb 2 -based Zintl compounds are considered as promising thermoelectric materials due to their low thermal conductivity and high Seebeck coefficient. In this paper, we studied the thermoelectric properties of p -type lithium (Li)-doped Mg 3 Sb 2 prepared by ball milling and hot pressing. A maximum ZT value ~ 0.6 at about 773 K was achieved in Mg 2.975 Li 0.025 Sb 2 , which was ascribed to the increased carrier concentration by Li doping. Mixed scattering mechanism is dominated at lower temperature, yielding higher carrier mobility. Isoelectronic substitution of Zn on the Mg site further increased the electrical conductivity by narrowing the band gap and decreased the lattice thermal conductivity by double substitution, contributing to an enhanced average ZT in Mg 2.475 Zn 0.5 Li 0.025 Sb 2 .