Development of [177Lu]Lu-LNC1010 for peptide receptor radionuclide therapy of nasopharyngeal carcinoma.

PURPOSE: Somatostatin Receptor 2 (SSTR2)-targeted radiopharmaceutical [68Ga]Ga-DOTATATE has potential advantages in the diagnosis of nasopharyngeal carcinoma (NPC). This study introduces a novel long-lasting SSTR2 analogue, LNC1010, based on DOTATATE, a truncated Evans blue-binding moiety, and a polyethylene-glycol linker. We hypothesised that peptide receptor radionuclide therapy (PRRT) is more effective with [177Lu]Lu-LNC1010 than with [177Lu]Lu-DOTATATE in treating metastatic NPC. METHODS: We assessed binding characteristics of LNC1010 in vitro using C666-1 NPC cells and in-vivo pharmacokinetics of [68Ga]Ga/[177Lu]Lu-LNC1010 in C666-1 NPC xenografts via PET and SPECT imaging, biodistribution studies, and PRRT, and compared them with [68Ga]Ga/[177Lu] Lu-labelled DOTATATE. Furthermore, a proof-of-concept approach for imaging and therapy was conducted in a patient with metastatic NPC. RESULTS: LNC1010 exhibited strong uptake and specific affinity for SSTR2 in C666-1 NPC cells. PET and SPECT imaging demonstrated higher uptake and longer tumour retention of [68Ga]Ga/[177Lu]Lu-LNC1010 than [68Ga]Ga/[177Lu]Lu-DOTATATE in C666-1 NPC xenografts, indicating its suitability for PRRT applications in NPCs. Biodistribution studies confirmed the higher uptake and prolonged retention of [177Lu]Lu-LNC1010 than [177Lu]Lu-DOTATATE. In preclinical PRRT studies, [177Lu]Lu-LNC1010 showed greater inhibition of tumour growth in C666-1 NPC xenografts than [177Lu]Lu-DOTATATE. In a subsequent pilot clinical study, PRRT with [177Lu]Lu-LNC1010 achieved favourable therapeutic and negligible side effects in a patient with metastatic NPC. CONCLUSION: [177Lu]Lu-LNC1010 demonstrated increased tumour uptake and prolonged retention in SSTR2-positive NPCs, with superior anti-tumour efficacy to that of [177Lu]Lu-DOTATATE in preclinical studies. These findings suggest that PRRT with [177Lu]Lu-LNC1010 is a promising treatment for advanced NPC, extending the clinical scope of PRRT beyond neuroendocrine tumours.

Nematic Ising superconductivity with hidden magnetism in few-layer 6R-TaS2.

In van der Waals heterostructures (vdWHs), the manipulation of interlayer stacking/coupling allows for the construction of customizable quantum systems exhibiting exotic physics. An illustrative example is the diverse range of states of matter achieved through varying the proximity coupling between two-dimensional (2D) quantum spin liquid (QSL) and superconductors within the TaS2 family. This study presents a demonstration of the intertwined physics of spontaneous rotational symmetry breaking, hidden magnetism, and Ising superconductivity (SC) in the three-fold rotationally symmetric, non-magnetic natural vdWHs 6R-TaS2. A distinctive phase emerges in 6R-TaS2 below a characteristic temperature (T*) of approximately 30 K, which is characterized by a remarkable set of features, including a giant extrinsic anomalous Hall effect (AHE), Kondo screening, magnetic field-tunable thermal hysteresis, and nematic magneto-resistance. At lower temperatures, a coexistence of nematicity and Kondo screening with Ising superconductivity is observed, providing compelling evidence of hidden magnetism within a superconductor. This research not only sheds light on unexpected emergent physics resulting from the coupling of itinerant electrons and localized/correlated electrons in natural vdWHs but also emphasizes the potential for tailoring exotic quantum states through the manipulation of interlayer interactions.

The H1/H5 domain contributes to OsTRBF2 phase separation and gene repression during rice development.

Transcription factors (TFs) tightly control plant development by regulating gene expression. The phase separation of TFs plays a vital role in gene regulation. Many plant TFs have the potential to form phase-separated protein condensates; however, little is known about which TFs are regulated by phase separation and how it affects their roles in plant development. Here, we report that the rice (Oryza sativa) single Myb TF TELOMERE REPEAT-BINDING FACTOR 2 (TRBF2) is highly expressed in fast-growing tissues at the seedling stage. TRBF2 is a transcriptional repressor that binds to the transcriptional start site of thousands of genes. Mutation of TRBF2 leads to pleiotropic developmental defects and misexpression of many genes. TRBF2 displays characteristics consistent with phase separation in vivo and forms phase-separated condensates in vitro. The H1/H5 domain of TRBF2 plays a crucial role in phase separation, chromatin targeting, and gene repression. Replacing the H1/H5 domain by a phase-separated intrinsically disordered region from Arabidopsis (Arabidopsis thaliana) AtSERRATE partially recovers the function of TRBF2 in gene repression in vitro and in transgenic plants. We also found that TRBF2 is required for trimethylation of histone H3 Lys27 (H3K27me3) deposition at specific genes and genome wide. Our findings reveal that phase separation of TRBF2 facilitates gene repression in rice development.

Three-dimensional hidden phase probed by in-plane magnetotransport in kagome metal CsV3Sb5 thin flakes.

Transition metal compounds with kagome structure have been found to exhibit a variety of exotic structural, electronic, and magnetic orders. These orders are competing with energies very close to each other, resulting in complex phase transitions. Some of the phases are easily observable, such as the charge density wave (CDW) and the superconducting phase, while others are more challenging to identify and characterize. Here we present magneto-transport evidence of a new phase below ~ 35 K in the kagome topological metal CsV3Sb5 (CVS) thin flakes between the CDW and the superconducting transition temperatures. This phase is characterized by six-fold rotational symmetry in the in-plane magnetoresistance (MR) and is connected to the orbital current order in CVS. Furthermore, the phase is characterized by a large in-plane negative magnetoresistance, which suggests the existence of a three-dimensional, magnetic field-tunable orbital current ordered phase. Our results highlight the potential of magneto-transport to reveal the interactions between exotic quantum states of matter and to uncover the symmetry of such hidden phases.

Adipose Kiss1 controls aerobic exercise-related adaptive responses in adipose tissue energy homeostasis.

Kisspeptin signaling regulates energy homeostasis. Adiposity is the principal source and receiver of peripheral Kisspeptin, and adipose Kiss1 metastasis suppressor (Kiss1) gene expression is stimulated by exercise. However, whether the adipose Kiss1 gene regulates energy homeostasis and plays a role in adaptive alterations during prolonged exercise remains unknown. Here, we investigated the role of Kiss1 role in mice and adipose tissues and the adaptive changes it induces after exercise, using adipose-specific Kiss1 knockout (Kiss1adipoq-/-) and adeno-associated virus-induced adipose tissue Kiss1-overexpressing (Kiss1adipoq over) mice. We found that adipose-derived kisspeptin signal regulates lipid and glucose homeostasis to maintain systemic energy homeostasis, but in a sex-dependent manner, with more pronounced metabolic changes in female mice. Kiss1 regulated adaptive alterations of genes and proteins in tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OxPhos) pathways in female gWAT following prolonged aerobic exercise. We could further show that adipose Kiss1 deficiency leads to reduced peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α) protein content of soleus muscle and maximum oxygen uptake (VO2 max) of female mice after prolonged exercise. Therefore, adipose Kisspeptin may be a novel adipokine that increases organ sensitivity to glucose, lipids, and oxygen following exercise.

Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade.

Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor efficacy. Targeted radionuclide therapy delivers radiation directly to tumor sites. LNC1004 is a fibroblast activation protein (FAP)-targeting radiopharmaceutical, conjugated with the albumin binder Evans Blue, which has demonstrated enhanced tumor uptake and retention in previous preclinical and clinical studies. Herein, we demonstrate that 68Ga/177Lu-labeled LNC1004 exhibits increased uptake and prolonged retention in MC38/NIH3T3-FAP and CT26/NIH3T3-FAP tumor xenografts. Radionuclide therapy with 177Lu-LNC1004 induced a transient upregulation of PD-L1 expression in tumor cells. The combination of 177Lu-LNC1004 and anti-PD-L1 immunotherapy led to complete eradication of all tumors in MC38/NIH3T3-FAP tumor-bearing mice, with mice showing 100% tumor rejection upon rechallenge. Immunohistochemistry, single-cell RNA sequencing (scRNA-seq), and TCR sequencing revealed that combination therapy reprogrammed the tumor microenvironment in mice to foster antitumor immunity by suppressing malignant progression and increasing cell-to-cell communication, CD8+ T-cell activation and expansion, M1 macrophage counts, antitumor activity of neutrophils, and T-cell receptor diversity. A preliminary clinical study demonstrated that 177Lu-LNC1004 was well-tolerated and effective in patients with refractory cancers. Further, scRNA-seq of peripheral blood mononuclear cells underscored the importance of addressing immune evasion through immune checkpoint blockade treatment. This was emphasized by the observed increase in antigen processing and presentation juxtaposed with T cell inactivation. In conclusion, our data supported the efficacy of immunotherapy combined with 177Lu-LNC1004 for cancer patients with FAP-positive tumors.

Enhanced Detection of Early Pulmonary Fibrosis Disease Using 68Ga-FAPI-LM3 PET.

Early detection of pulmonary fibrosis is a critical yet insufficiently met clinical necessity. This study evaluated the effectiveness of FAPI-LM3, a 68Ga-radiolabeled heterobivalent molecular probe that targets fibroblast activating protein (FAP) and somatostatin receptor 2 (SSTR2), in the early detection of pulmonary fibrosis, leveraging its potential for early disease identification. A bleomycin-induced early pulmonary fibrosis model was established in C57BL/6 mice for 7 days. FAP and SSTR2 expression levels were quantitatively assessed in human idiopathic pulmonary fibrosis lung tissue samples and bleomycin-treated mouse lung tissues by using western blotting, real-time quantitative PCR (RT-qPCR), and immunofluorescence techniques. The diagnostic performance of FAPI-LM3 was investigated by synthesizing monomeric radiotracers 68Ga-FAPI-46 and 68Ga-DOTA-LM3 alongside the heterobivalent probe 68Ga-FAPI-LM3. These imaging radiopharmaceuticals were used in small-animal PET to compare their uptake in fibrotic and normal lung tissues. Results indicated significant upregulation of FAP and SSTR2 at both RNA and protein levels in fibrotic lung tissues compared with that in normal controls. PET imaging demonstrated significantly enhanced uptake of the 68Ga-FAPI-LM3 probe in fibrotic lung tissues, with superior visual effects compared to monomeric tracers. At 60 min postinjection, early stage fibrotic tissues (day 7) demonstrated low-to-medium uptake of monomeric probes, including 68Ga-DOTA-LM3 (0.45 ± 0.04% ID/g) and 68Ga-FAPI-46 (0.78 ± 0.09% ID/g), whereas the uptake of the heterobivalent probe 68Ga-FAPI-LM3 (1.90 ± 0.10% ID/g) was significantly higher in fibrotic lesions than in normal lung tissue. Blockade experiments confirmed the specificity of 68Ga-FAPI-LM3 uptake, which was attributed to synergistic targeting of FAP and SSTR2. This study demonstrates the potential of 68Ga-FAPI-LM3 for early pulmonary fibrosis detection via molecular imaging, offering significant benefits over monomeric tracers 68Ga-FAPI-46 and 68Ga-DOTA-LM3. This strategy offers new possibilities for noninvasive and precise early detection of pulmonary fibrosis.

Boosted Second Harmonic Generation and Cascaded Sum Frequency Generation from a Surface Crystallized Glass Ceramic Microcavity.

The development of novel materials and structures for efficient second-order nonlinear micro/nano devices remains a significant challenge. In this study, the remarkable enhancement of second-harmonic generation (SHG) and cascaded sum frequency generation in whispering gallery mode microspheres made of surface-crystallized glass with a 6-µm Ba2TiSi2O8 crystal layer are demonstrated. Attributed to the core-shell design, the Ba2TiSi2O8 located on the surface can be efficiently coupled with whispering gallery modes, resulting in a highly efficient micron-scale cavity-enhanced second-order optical nonlinearity. Greatly enhanced SHG of the microcavity is observed, which is up to 80 times stronger than that of a non-resonant sample. Furthermore, owing to the wavelength non-selectivity of random quasi-phase matching, ultra-wideband SHG with a strong response ranging from 860 to 1600 nm and high-contrast polarization characteristics is demonstrated. The glass-ceramic-based microsphere cavity also boosts the cascading optical nonlinearity, manifested by a two-magnitude enhancement of cascaded sum frequency generation. This work delineates an efficient strategy for boosting nonlinear optical response in glass ceramics, which will open up new opportunities for applications in photonics and optical communications.

Short-term resistance training combined with cheese supplementation can optimize body parameters and intestinal microbiota in healthy adults.

Background: Resistance training (RT) and protein supplementation have beneficial effects on the human body. However, it is unknown if RT's health-promoting benefits are enhanced by food-borne protein, such as cheese supplements. This study investigated at how the body composition, lipid profile, muscle strength and intestinal microbiota changed following four weeks of RT combined with cheese supplementation. Methods: Thirty-five male and untrained adults were divided into 4 groups [control group (CON), low-dose group (LG), medium-dose group (MG), and high-dose group (HG)] and underwent a 4-week RT (3 times/week) in combination with cheese supplementation. Participants received 108 g (LG), 216 g (MG), or 324 g (HG) of cheese on the day of RT, and each serving (108 g) of cheese contained 6.7 g of food-borne protein. The RT program was a whole-body program with movements such as chest presses, leg presses, seated rowing, knee extensions and triceps pushdown. The exercise consisted of 3 sets of 8-12 repetitions at 70%RM, with a 120-s break in between. Body parameters (body composition, lipid profile and muscle strength) were assessed at baseline and after the 4 weeks of the intervention. The feces sample was taken every weekend. A two-way (group × time) mixed-design ANOVA was used to examine the body parameters. Independent one-way ANOVA was used to analyze the differences between groups in baseline characteristics and different values of each parameter. Results: HDL-C level was higher in MG than in LG. In comparison to LG, MG had lower levels of total cholesterol, low-density lipoprotein cholesterol, body weight, body mass index, body fat mass and body fat percentage. However, there was no difference in muscle strength between in the four groups. The abundance of Actinobacteria was higher in LG and Erysipelotrichaceae was lower in MG and HG. Conclusion: The findings suggest that cheese could be a readily available food-borne protein supplement to enhance the beneficial effects of RT on health. It may improve body composition and lipid profile by altering the proportion of intestinal microbiota. During the 4-week RT intervention, 13.4 g of foodborne protein in the form of cheese 3 times per week was the ideal dosage.

Design, Preclinical Evaluation, and Clinical Translation of 68Ga-FAPI-LM3, a Heterobivalent Molecule for PET Imaging of Nasopharyngeal Carcinoma.

Extensive research has been conducted on radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) and p-Cl-Phe-cyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH2 (LM3) peptides for imaging of FAP and somatostatin receptor 2 (SSTR2)-positive tumors. In this study, we designed and synthesized a FAPI-LM3 heterobivalent molecule radiolabeled with 68Ga and evaluated its effectiveness in both tumor xenografts and patients with nasopharyngeal carcinoma (NPC). Methods: The synthesis of FAPI-LM3 was based on the structures of FAPI-46 and LM3. After radiolabeling with 68Ga, its dual-receptor-binding affinity was evaluated in vitro and in vivo. Preclinical studies, including small-animal PET and biodistribution evaluation, were conducted on HT-1080-FAP and HT-1080-SSTR2 tumor xenografts. The feasibility of 68Ga-FAPI-LM3 PET/CT in a clinical setting was evaluated in patients with NPC, and the results were compared with those of 18F-FDG. Results: 68Ga-FAPI-LM3 showed high affinity for both FAP and SSTR2. The tumor uptake of 68Ga-FAPI-LM3 was significantly higher than that of 68Ga-FAPI-46 and 68Ga-DOTA-LM3 in HT-1080-FAP-plus-HT-1080-SSTR2 tumor xenografts. In a clinical study involving 6 NPC patients, 68Ga-FAPI-LM3 PET/CT showed significantly higher uptake than did 18F-FDG in primary and metastatic lesions, leading to enhanced lesion detectability and tumor delineation. Conclusion: 68Ga-FAPI-LM3 exhibited FAPI and SSTR2 dual-receptor-targeting properties both in vitro and in vivo, resulting in improved tumor uptake and retention compared with that observed with monomeric 68Ga-FAPI and 68Ga-DOTA-LM3. This study highlights the clinical feasibility of 68Ga-FAPI-LM3 PET/CT for NPC imaging.

Optimizing sludge dewatering efficiency with ultrasonic Treatment: Insights into Parameters, Effects, and microstructural changes.

Sludge dewatering plays a critical role in the efficient and cost-effective management of wastewater treatment plants. Ultrasonic treatment has emerged as a promising technique for improving dewatering processes. This study aims to evaluate the impact of ultrasonic treatment on sludge dewatering characteristics. A series of experiments were conducted to evaluate the dewatering characteristics of sludge under ultrasonic treatment. Experimental data was collected, and the effects of ultrasonic parameters on dewatering efficiency were analyzed. Ultrasound has the capacity to disintegrate sludge flocs, liberate tightly bound water, and enhance sludge dewatering capabilities. The application of ultrasound leads to the breakdown of sludge flocs, which facilitates a substantial amount of organic acids or carbonates. This, in turn, modifies the pH value of the sludge. Additionally, ultrasound induces instantaneous high temperature and pressure within the liquid phase, consequently elevating the temperature of the sludge slurry. Optimum ultrasound energy density and duration of ultrasound treatment exist. For the sludge samples analyzed in this investigation, it was determined that the optimal ultrasonic energy density is 9.8 W, while the optimal duration of ultrasound treatment is 30 s. Excessively escalating the sound energy density or prolonging the duration of ultrasound may yield unfavorable outcomes in terms of sludge dewatering effectiveness. To enhance sludge dewatering, it is crucial to select appropriate ultrasonic energy density and duration of ultrasonic treatment. This study demonstrates the positive impact of ultrasonic treatment on the dewatering characteristics of sludge. The findings provide valuable insights into the potential of ultrasonic technology for enhancing sludge dewatering.

The effects of race and probiotic supplementation on the intestinal microbiota of 10-km open-water swimmers.

This study collected the stools of 10-km open-water swimmers after race and probiotic supplementation, and 16S rRNA sequencing and metabolomic analysis were performed to clarify their intestinal microbiota characteristics. The findings revealed a relatively high proportion of Firmicutes in all the athletes. Firmicutes in female athletes were significantly higher after probiotic supplementation. The intestinal microbiota of athletes was closely associated with the pathways of exercise against cancer, exercise against aging, exercise for improving cognition, sphingolipid metabolism and endocrine resistance. Future research should focus on the relationship between Firmicutes and Proteobacteria with super class metabolites in athletes. This report initially explored the changes in intestinal microbiota involved in metabolic pathways in athletes after race and after probiotic supplementation and provided a theoretical basis for the further improvement of the monitoring of their physical function after race and selection of nutritional strategies during exercise training.

Prominent Josephson tunneling between twisted single copper oxide planes of Bi2Sr2-xLaxCuO6+y.

Josephson tunneling in twisted cuprate junctions provides a litmus test for the pairing symmetry, which is fundamental for understanding the microscopic mechanism of high temperature superconductivity. This issue is rekindled by experimental advances in van der Waals stacking and the proposal of an emergent d+id-wave. So far, all experiments have been carried out on Bi2Sr2CaCu2O8+x (Bi-2212) with double CuO2 planes but show controversial results. Here, we investigate junctions made of Bi2Sr2-xLaxCuO6+y (Bi-2201) with single CuO2 planes. Our on-site cold stacking technique ensures uncompromised crystalline quality and stoichiometry at the interface. Junctions with carefully calibrated twist angles around 45° show strong Josephson tunneling and conventional temperature dependence. Furthermore, we observe standard Fraunhofer diffraction patterns and integer Fiske steps in a junction with a twist angle of 45.0±0.2°. Together, these results pose strong constraints on the d or d+id-wave pairing and suggest an indispensable isotropic pairing component.

Development of FAPI Tetramers to Improve Tumor Uptake and Efficacy of FAPI Radioligand Therapy.

Radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) have shown promise as cancer diagnostic agents; however, the relatively short tumor retention of FAPIs may limit their application in radioligand therapy. In this paper, we report the design, synthesis, and evaluation of a FAPI tetramer. The aim of the study was to evaluate the tumor-targeting characteristics of radiolabeled FAPI multimers in vitro and in vivo, thereby providing information for the design of FAP-targeted radiopharmaceuticals based on the polyvalency principle. Methods: FAPI tetramers were synthesized on the basis of FAPI-46 and radiolabeled with 68Ga, 64Cu, and 177Lu. In vitro FAP-binding characteristics were identified using a competitive cell-binding experiment. To evaluate their pharmacokinetics, small-animal PET, SPECT, and ex vivo biodistribution analyses were performed on HT-1080-FAP and U87MG tumor-bearing mice. In addition, the 2 tumor xenografts received radioligand therapy with 177Lu-DOTA-4P(FAPI)4, and the antitumor efficacy of the 177Lu-FAPI tetramer was evaluated and compared with that of the 177Lu-FAPI dimer and monomer. Results: 68Ga-DOTA-4P(FAPI)4 and 177Lu-DOTA-4P(FAPI)4 were highly stable in phosphate-buffered saline and fetal bovine serum. The FAPI tetramer exhibited high FAP-binding affinity and specificity both in vitro and in vivo. 68Ga-, 64Cu-, and 177Lu-labeled FAPI tetramers exhibited higher tumor uptake, longer tumor retention, and slower clearance than FAPI dimers and FAPI-46 in HT-1080-FAP tumors. The uptake (percentage injected dose per gram) of 177Lu-DOTA-4P(FAPI)4, 177Lu-DOTA-2P(FAPI)2, and 177Lu-FAPI-46 in HT-1080-FAP tumors at 24 h was 21.4 ± 1.7, 17.1 ± 3.9, and 3.4 ± 0.7, respectively. Moreover, 68Ga-DOTA-4P(FAPI)4 uptake in U87MG tumors was approximately 2-fold the uptake of 68Ga-DOTA-2P(FAPI)2 (SUVmean, 0.72 ± 0.02 vs. 0.42 ± 0.03, P < 0.001) and more than 4-fold the uptake of 68Ga-FAPI-46 (0.16 ± 0.01, P < 0.001). In the radioligand therapy study, remarkable tumor suppression was observed with the 177Lu-FAPI tetramer in both HT-1080-FAP and U87MG tumor-bearing mice. Conclusion: The satisfactory FAP-binding affinity and specificity, as well as the favorable in vivo pharmacokinetics of the FAPI tetramer, make it a promising radiopharmaceutical for theranostic applications. Improved tumor uptake and prolonged retention of the 177Lu-FAPI tetramer resulted in excellent characteristics for FAPI imaging and radioligand therapy.

A study on computer vision for facial emotion recognition.

Artificial intelligence has been successfully applied in various fields, one of which is computer vision. In this study, a deep neural network (DNN) was adopted for Facial emotion recognition (FER). One of the objectives in this study is to identify the critical facial features on which the DNN model focuses for FER. In particular, we utilized a convolutional neural network (CNN), the combination of squeeze-and-excitation network and the residual neural network, for the task of FER. We utilized AffectNet and the Real-World Affective Faces Database (RAF-DB) as the facial expression databases that provide learning samples for the CNN. The feature maps were extracted from the residual blocks for further analysis. Our analysis shows that the features around the nose and mouth are critical facial landmarks for the neural networks. Cross-database validations were conducted between the databases. The network model trained on AffectNet achieved 77.37% accuracy when validated on the RAF-DB, while the network model pretrained on AffectNet and then transfer learned on the RAF-DB results in validation accuracy of 83.37%. The outcomes of this study would improve the understanding of neural networks and assist with improving computer vision accuracy.

Evaluation of a community-based integrated care model (CIE) for frail older people in rural Foshan, China: study protocol for a stepped-wedge cluster randomized controlled trial {1}.

BACKGROUND: While community-based eldercare has proven to be effective in qualitative studies, there is limited evidence on the effectiveness of this geriatric care model in rural communities where caring for older people is traditionally the responsibility of family members, but a formal long-term care was recently introduced in China. CIE is a rural community-embedded intervention using multidisciplinary team, to provide evidenced-based integrated care services for frail older people including social care services and allied primary healthcare and community-based rehabilitation services. METHODS: CIE is a prospective stepped-wedge cluster randomized trial conducted at 5 community eldercare centers in rural China. The multifaceted CIE intervention, guided by chronic care model and integrated care model, consists of five components: comprehensive geriatric assessment, individualized care planning, community-based rehabilitation, interdisciplinary case management, and care coordination. The intervention is rolled out in a staggered manner in these clusters of centers at an interval of 1 month. The primary outcomes include functional status, quality of life, and social support. Process evaluation will also be conducted. Generalized linear mixed model is employed for binary outcomes. DISCUSSION: This study is expected to provide important new evidence on clinical effectiveness and implementation process of an integrated care model for frail older people. The CIE model is also unique as the first registered trial implementing a community-based eldercare model using multidisciplinary team to promote individualized social care services integrated with primary healthcare and community-based rehabilitation services for frail older people in rural China, where formal long-term care was recently introduced. TRIAL REGISTRATION {2A}: China Clinical Trials Register ( http://www.chictr.org.cn/historyversionpub.aspx?regno=ChiCTR2200060326 ). May 28th, 2022.

Giant electrically tunable magnon transport anisotropy in a van der Waals antiferromagnetic insulator.

Anisotropy is a manifestation of lowered symmetry in material systems that have profound fundamental and technological implications. For van der Waals magnets, the two-dimensional (2D) nature greatly enhances the effect of in-plane anisotropy. However, electrical manipulation of such anisotropy as well as demonstration of possible applications remains elusive. In particular, in-situ electrical modulation of anisotropy in spin transport, vital for spintronics applications, has yet to be achieved. Here, we realized giant electrically tunable anisotropy in the transport of second harmonic thermal magnons (SHM) in van der Waals anti-ferromagnetic insulator CrPS4 with the application of modest gate current. Theoretical modeling found that 2D anisotropic spin Seebeck effect is the key to the electrical tunability. Making use of such large and tunable anisotropy, we demonstrated multi-bit read-only memories (ROMs) where information is inscribed by the anisotropy of magnon transport in CrPS4. Our result unveils the potential of anisotropic van der Waals magnons for information storage and processing.