Characterization of PANoptosis-related genes and the immune landscape in moyamoya disease.

Moyamoya disease (MMD) is a cerebrovascular narrowing and occlusive condition characterized by progressive stenosis of the terminal portion of the internal carotid artery and the formation of an abnormal network of dilated, fragile perforators at the base of the brain. However, the role of PANoptosis, an apoptotic mechanism associated with vascular disease, has not been elucidated in MMD. In our study, a total of 40 patients' genetic data were included, and a total of 815 MMD-related differential genes were screened, including 215 upregulated genes and 600 downregulated genes. Among them, DNAJA3, ESR1, H19, KRT18 and STK3 were five key genes. These five key genes were associated with a variety of immune cells and immune factors. Moreover, GSEA (gene set enrichment analysis) and GSVA (gene set variation analysis) showed that the different expression levels of the five key genes affected multiple signaling pathways associated with MMD. In addition, they were associated with the expression of MMD-related genes. Then, based on the five key genes, a transcription factor regulatory network was constructed. In addition, targeted therapeutic drugs against MMD-related genes were obtained by the Cmap drug prediction method: MST-312, bisacodyl, indirubin, and tropanyl-3,5-dimethylbenzoate. These results suggest that the PANoptosis-related genes may contribute to the pathogenesis of MMD through multiple mechanisms.

High-throughput sequencing-based analysis of the composition and diversity of the endophyte community in roots of Stellera chamaejasme.

Stellera chamaejasme (S. chamaejasme) is an important medicinal plant with heat-clearing, detoxifying, swelling and anti-inflammatory effects. At the same time, it is also one of the iconic plants of natural grassland degradation in northwest China, playing a key role in the invasion process. Plant endophytes live in healthy plant tissues and can synthesize substances needed for plant growth, induce disease resistance in host plants, and enhance plant resistance to environmental stress. Therefore, studying the root endophytes of S. chamaejasme is of great significance for mining beneficial microbial resources and biological prevention and control of S. chamaejasme. This study used Illumina MiSeq high-throughput sequencing technology to analyze the composition and diversity of endophytes in the roots of S. chamaejasme in different alpine grasslands (BGC, NMC and XGYZ) in Tibet. Research results show that the main phylum of endophytic fungi in the roots of S. chamaejasme in different regions is Ascomycota, and the main phyla of endophytic bacteria are Actinobacteria, Proteobacteria and Firmicutes (Bacteroidota). Overall, the endophyte diversity of the NMC samples was significantly higher than that of the other two sample sites. Principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) results showed significant differences in the composition of endophytic bacterial and fungal communities among BGC, NMC and XGYZ samples. Co-occurrence network analysis of endophytes showed that there were positive correlations between fungi and some negative correlations between bacteria, and the co-occurrence network of bacteria was more complex than that of fungi. In short, this study provides a vital reference for further exploring and utilizing the endophyte resources of S. chamaejasme and an in-depth understanding of the ecological functions of S. chamaejasme endophytes.

Anion/Cation Co-Doping to Improve the Thermoelectric Performance of Sn-Enriched n-Type SnSe Polycrystals with Suppressed Lattice Thermal Conductivity.

Enhancing the thermoelectric performance of n-type polycrystalline SnSe is essential, addressing challenges posed by elevated thermal conductivity and compromised power factor inherent in its intrinsic p-type characteristics. This investigation utilized solid-state reactions and spark plasma sintering techniques for the synthesis of n-type SnSe. A significant improvement in the figure of merit (ZT) is achieved through strategic reduction in Se concentration and optimization of crystal orientation. The co-doping with Br and Ge further improves the material; Br amplifies carrier concentration, enhancing electrical conductivity, while Ge introduces effective phonon scattering centers. In the Br/Ge co-doped SnSe sample, thermal conductivity dropped to 0.38 Wm⁻¹K⁻¹, yielding a remarkable power factor of 662 µW mK- 2 at 773 K, culminating in a ZT of 1.34. This signifies a noteworthy 605% improvement over the pristine sample, underscoring the pivotal role of Ge doping in enhancing n-type material thermoelectric properties. The enhancement is attributed to Br doping introducing additional electronic states near the valence band, and Ge doping modifying the band structure, fostering resonant states near the conduction band. The Br/Ge co-doping further transforms the band structure, influencing electrical conductivity, Seebeck coefficient, and thermal conductivity, advancing the understanding and application of n-type SnSe materials for superior thermoelectric performance.

Delivery of Probiotics with Cellulose-Based Films and Their Food Applications.

Probiotics have attracted great interest from many researchers due to their beneficial effects. Encapsulation of probiotics into biopolymer matrices has led to the development of active food packaging materials as an alternative to traditional ones for controlling food-borne microorganisms, extending food shelf life, improving food safety, and achieving health-promoting effects. The challenges of low survival rates during processing, storage, and delivery to the gut and low intestinal colonization, storage stability, and controllability have greatly limited the use of probiotics in practical food-preservation applications. The encapsulation of probiotics with a protective matrix can increase their resistance to a harsh environment and improve their survival rates, making probiotics appropriate in the food packaging field. Cellulose has attracted extensive attention in food packaging due to its excellent biocompatibility, biodegradability, environmental friendliness, renewability, and excellent mechanical strength. In this review, we provide a brief overview of the main types of cellulose used for probiotic encapsulation, as well as the current advances in different probiotic encapsulating strategies with cellulose, grafted cellulose, and cellulose-derived materials, including electrospinning, cross-linking, in-situ growth, casting strategies, and their combinations. The effect of cellulose encapsulation on the survival rate of probiotics and the patented encapsulated probiotics are also introduced. In addition, applications of cellulose-encapsulated probiotics in the food industry are also briefly discussed. Finally, the future trends toward developing encapsulated probiotics with improved health benefits and advanced features with cellulose-based materials are discussed.

Chelating Coordination Regulated Photochromic Electrospun Nanofibers for Waterproof and Long-Color-Retention Rewritable Wearables.

Photochromic materials with rapid color-switching, long color retention times, and rewritability are crucial for meeting the requirements of future rewritable ink-free media. However, these requirements are challenging to satisfy simultaneously due to the inherent constraints among these features. Herein, a novel photochromic nanofiber nonwoven fabric was designed and constructed based on a conjugated organic-inorganic hybrid structure through electrospinning and hot-pressing techniques. The as-prepared fabric can change color in merely 5 s under UV irradiation and can reach saturation within 2 min. In addition, upon the introduction of a potent metal chelator, its color retention time exceeds 14 days under ambient conditions, significantly longer than that of most rewritable materials recently reported (several hours to 5 days). Moreover, the fabric exhibits high writing resolution and can be photoprinted and heat-erased for over 100 cycles while still retaining 96% of its initial reflectivity. Hydrophobic thermoplastic polyurethane provides the fabric with excellent waterproof and antifouling properties, thus preventing the composite from swelling or collecting graffiti due to moisture or dust. This work exploits a competitive approach for designing flexible, rewritable, and superior functional wearables with practical applications.

Evaluation of cerebrovascular reactivity in moyamoya disease using oxygen-dependent magnetic resonance imaging.

Moyamoya disease (MMD) is a rare cerebrovascular disorder marked by progressive stenosis of the internal carotid arteries. Assessing cerebral hemodynamics, specifically cerebrovascular reactivity (CVR), is vital for MMD management and prognosis. In this study, fMRI was performed in a prospective cohort of 47 patients with MMD and 32 healthy controls to investigate its utility in evaluating CVR and to explore the influence of cerebral posterior circulation compensation on CVR in MMD. The regions where the CVR values of participants with MMD were lower than those of healthy controls were primarily concentrated in the frontal, parietal, and temporal lobes (p < 0.05). In certain regions mainly supplied by posterior circulation, the CVR values of compensatory-normal subgroup tended to exceed those of compensatory-poor subgroup. fMRI can detect a significant decrease in CVR values in patients with MMD compared to healthy controls. Compensation for the posterior cerebral circulation may affect cerebrovascular reactivity.

Zabramski classification in predicting the occurrence of symptomatic intracerebral hemorrhage in sporadic cerebral cavernous malformations.

OBJECTIVE: The authors aimed to investigate the evolutionary characteristics of the Zabramski classification of cerebral cavernous malformations (CCMs) and the value of the Zabramski classification in predicting clinical outcome in patients with sporadic CCM. METHODS: This retrospective study consecutively included cases of sporadic CCM that had been untreated from January 2001 through December 2021. Baseline and follow-up patient information was recorded. The evolution of the Zabramski classification of a sporadic CCM was defined as the initial lesion type changing into another type for the first time on MRI follow-up. The primary outcome was the occurrence of a hemorrhage event, which was defined as a symptomatic event with radiological evidence of overt intracerebral hemorrhage. RESULTS: Among the 255 included cases, 55 (21.6%) were classified as type I CCM, 129 (50.6%) as type II CCM, and 71 (27.8%) as type III CCM, based on initial MRI. During a mean follow-up of 58.8 ± 33.6 months, 51 (20.0%) patients had lesion classification transformation, whereas 204 (80.0%) patients maintained their initial type. Among the 51 transformed lesions, 29 (56.9%) were type I, 11 (21.6%) were type II, and 11 (21.6%) were type III. Based on all follow-up imaging, of the initial 55 type I lesions, 26 (47.3%) remained type I and 27 (49.1%) regressed to type III because of hematoma absorption; 91.5% of type II and 84.5% of type III lesions maintained their initial type during MRI follow-up. The classification change rate of type I lesions was statistically significantly higher than those of type II and III lesions. After a total follow-up of 1157.7 patient-years, new clinical hemorrhage events occurred in 40 (15.7%) patients. The annual cumulative incidence rate for symptomatic hemorrhage in all patients was 3.4 (95% CI 2.5-4.7) per 100 person-years. Kaplan-Meier survival analysis showed that the annual cumulative incidence rate for symptomatic hemorrhage of type I CCM (15.3 per 100 patient-years) was significantly higher than those of type II (0.6 per 100 patient-years) and type III (2.3 per 100 patient-years). CONCLUSIONS: This study suggests that the Zabramski classification is helpful in estimating clinical outcome and can assist with surgical decision-making in patients with sporadic CCM.

Advances in Fiber-Based Wearable Sensors for Personal Digital Health Monitoring.

With the continuous growth of the global economy, an increasing concern has emerged among individuals with regard to personal digital health. Smart fiber-based sensors meet people's demands for wearable devices with the advantages of excellent skin-friendliness and breathability, enabling efficient and prompt monitoring of personal digital health signals in daily life. Furthermore, by integrating machine learning and big data analysis techniques, a closed-loop system can be established for personal digital health, covering data collection, data analysis, as well as medical diagnosis and treatment. Herein, we provide a review of the recent research progress on fiber-based wearable sensors for personal digital health. Firstly, a brief introduction is provided to demonstrate the importance of fiber-based wearable sensors in personal digital health. Then, the monitoring of biophysical signals through fiber-based sensors is described, and they are classified based on different sensing principles in biophysical signal monitoring (resistive, capacitive, piezoelectric, triboelectric, magnetoelastic, and thermoelectric). After that, the fiber-based biochemical signal sensors are described through the classification of monitoring targets (biofluids and respiratory gases). Finally, a summary is presented on the application prospects and the prevailing challenges of fiber-based sensors, aiming to implement their future role in constructing personal digital health networks.

Upregulated Cytoskeletal Proteins Promote Pathological Angiogenesis in Moyamoya Disease.

BACKGROUND: Moyamoya disease (MMD) is a rare progressive vascular disease that leads to intracranial internal carotid artery stenosis and eventual occlusion. However, its pathogenesis remains unclear. The purpose of this study is to explore the role of abnormally expressed proteins in the pathogenesis of MMD. METHODS: Data-independent acquisition mass spectrometry identifies the differentially expressed proteins in MMD serum by detecting the serum from 60 patients with MMD and 20 health controls. The differentially expressed proteins were validated using enzyme linked immunosorbent assays. Immunofluorescence for superficial temporal artery and middle cerebral artery specimens was used to explore the morphological changes of vascular wall in MMD. In vitro experiments were used to explore the changes and mechanisms of differentially expressed proteins on endothelial cells. RESULTS: Proteomic analysis showed that a total of 14 726 peptides and 1555 proteins were quantified by mass spectrometry data. FLNA (filamin A) and ZYX (zyxin) proteins were significantly higher in MMD serum compared with those in health controls (Log2FC >2.9 and >2.8, respectively). Immunofluorescence revealed an intimal hyperplasia in superficial temporal artery and middle cerebral artery specimens of MMD. FLNA and ZYX proteins increased the proportion of endothelial cells in S phase and promoted their proliferation, angiogenesis, and cytoskeleton enlargement. Mechanistic studies revealed that AKT (serine/threonine kinase)/GSK-3ß (glycogen synthase kinase 3ß)/ß-catenin signaling pathway plays a major role in these FLNA- and ZYX-induced changes in endothelial cells. CONCLUSIONS: This study provides proteomic data on a large sample size of MMD. The differential expression of FLNA and ZYX in patient with MMD and following in vitro experiments suggest that these upregulated proteins are related to the pathology of cerebrovascular intimal hyperplasia in MMD and are involved in MMD pathogenesis, with diagnostic and therapeutic ramifications.

High-Performance Thermoelectric Flexible Ag2Se-Based Films with Wave-Shaped Buckling via a Thermal Diffusion Method.

Herein, an n-type Ag2Se thermoelectric flexible thin film has been fabricated on a polyimide (PI) substrate via a novel thermal diffusion method, and the thermoelectric performance is well-optimized by adjusting the pressure and temperature of thermal diffusion. All of the Ag2Se films are beneficial to grow (013) preferred orientations, which is conducive to performing a high Seebeck coefficient. By increasing the thermal diffusion temperature, the electrical conductivity can be rationally regulated while maintaining the independence of the Seebeck coefficient, which is mainly attributed to the increased electric mobility. As a result, the fabricated Ag2Se thin film achieves a high power factor of 18.25 µW cm-1 K-2 at room temperature and a maximum value of 21.7 µW cm-1 K-2 at 393 K. Additionally, the thermal diffusion method has resulted in a wave-shaped buckling, which is further verified as a promising structure to realize a larger temperature difference by the simulation results of finite element analysis (FEA). Additionally, this unique surface morphology of the Ag2Se thin film also exhibits outstanding mechanical properties, for which the elasticity modulus is only 0.42 GPa. Finally, a flexible round-shaped module assembled with Sb2Te3 has demonstrated an output power of 166 nW at a temperature difference of 50 K. This work not only introduces a new method of preparing Ag2Se thin films but also offers a convincing strategy of optimizing the microstructure to enhance low-grade heat utilization efficiency.

Eco-civilization: A complementary pathway rooted in theory and practice for global sustainable development.

Eco-civilization, as a civilizational discourse led by China, implies the next stage of civilization after industrial civilization, the essence of which is to respect, conform to, and protect nature. Although the international community is paying more attention to eco-civilization, the existing literature still lacks a systematic discussion of which theories and practices underpin the construction of eco-civilization. Due to the ambiguity of eco-civilization, some even criticize it as being a form of purely partisan politics in China. By systematically reviewing its theoretical pillars, practical actions, and major achievements, this perspective paper argues that China's eco-civilization is not a partisan politics, but rather a legitimate, imperative pathway to global sustainable development rooted in complementary theory and practice, i.e., theories guide practices, and practices enrich theories. We highlight that the theoretical basis and practical actions of eco-civilization constitute a continual improvement process that permits diverse viewpoints and understanding, and any action exploring how to achieve a harmonious coexistence between humans and nature is consistent with the values of eco-civilization.

Association between DIAPH1 variant and posterior circulation involvement with Moyamoya disease.

Moyamoya disease (MMD) is a chronic and progressive cerebrovascular stenosis or occlusive disease that occurs near Willis blood vessels. The aim of this study was to investigate the mutation of DIAPH1 in Asian population, and to compare the angiographic features of MMD patients with and without the mutation of the DIAPH1 gene. Blood samples of 50 patients with MMD were collected, and DIAPH1 gene mutation was detected. The angiographic involvement of the posterior cerebral artery was compared between the mutant group and the non-mutant group. The independent risk factors of posterior cerebral artery involvement were determined by multivariate logistic regression analysis. DIAPH1 gene mutation was detected in 9 (18%) of 50 patients, including 7 synonymous mutations and 2 missense mutations. However, the incidence of posterior cerebral artery involvement in mutation positive group was very higher than that in mutation negative group (77.8% versus 12%; p = 0.001). There is an association between DIAPH1 mutation and PCA involvement (odds ratio 29.483, 95% confidence interval 3.920-221.736; p = 0.001). DIAPH1 gene mutation is not a major genetic risk gene for Asian patients with moyamoya disease but may play an important role in the involvement of posterior cerebral artery.

Somatic GJA4 mutation in intracranial extra-axial cavernous hemangiomas.

OBJECTIVE: Extra-axial cavernous hemangiomas (ECHs) are sporadic and rare intracranial occupational lesions that usually occur within the cavernous sinus. The aetiology of ECHs remains unknown. METHODS: Whole-exome sequencing was performed on ECH lesions from 12 patients (discovery cohort) and droplet digital polymerase-chain-reaction (ddPCR) was used to confirm the identified mutation in 46 additional cases (validation cohort). Laser capture microdissection (LCM) was carried out to capture and characterise subgroups of tissue cells. Mechanistic and functional investigations were carried out in human umbilical vein endothelial cells and a newly established mouse model. RESULTS: We detected somatic GJA4 mutation (c.121G>T, p.G41C) in 5/12 patients with ECH in the discovery cohort and confirmed the finding in the validation cohort (16/46). LCM followed by ddPCR revealed that the mutation was enriched in lesional endothelium. In vitro experiments in endothelial cells demonstrated that the GJA4 mutation activated SGK-1 signalling that in turn upregulated key genes involved in cell hyperproliferation and the loss of arterial specification. Compared with wild-type littermates, mice overexpressing the GJA4 mutation developed ECH-like pathological morphological characteristics (dilated venous lumen and elevated vascular density) in the retinal superficial vascular plexus at the postnatal 3 weeks, which were reversed by an SGK1 inhibitor, EMD638683. CONCLUSIONS: We identified a somatic GJA4 mutation that presents in over one-third of ECH lesions and proposed that ECHs are vascular malformations due to GJA4-induced activation of the SGK1 signalling pathway in brain endothelial cells.

Endothelial hyperactivation of mutant MAP3K3 induces cerebral cavernous malformation enhanced by PIK3CA GOF mutation.

Cerebral cavernous malformations (CCMs) refer to a common vascular abnormality that affects up to 0.5% of the population. A somatic gain-of-function mutation in MAP3K3 (p.I441M) was recently reported in sporadic CCMs, frequently accompanied by somatic activating PIK3CA mutations in diseased endothelium. However, the molecular mechanisms of these driver genes remain elusive. In this study, we performed whole-exome sequencing and droplet digital polymerase chain reaction to analyze CCM lesions and the matched blood from sporadic patients. 44 of 94 cases harbored mutations in KRIT1/CCM2 or MAP3K3, of which 75% were accompanied by PIK3CA mutations (P = 0.006). AAV-BR1-mediated brain endothelial-specific MAP3K3I441M overexpression induced CCM-like lesions throughout the brain and spinal cord in adolescent mice. Interestingly, over half of lesions disappeared at adulthood. Single-cell RNA sequencing found significant enrichment of the apoptosis pathway in a subset of brain endothelial cells in MAP3K3I441M mice compared to controls. We then demonstrated that MAP3K3I441M overexpression activated p38 signaling that is associated with the apoptosis of endothelial cells in vitro and in vivo. In contrast, the mice simultaneously overexpressing PIK3CA and MAP3K3 mutations had an increased number of CCM-like lesions and maintained these lesions for a longer time compared to those with only MAP3K3I441M. Further in vitro and in vivo experiments showed that activating PI3K signaling increased proliferation and alleviated apoptosis of endothelial cells. By using AAV-BR1, we found that MAP3K3I441M mutation can provoke CCM-like lesions in mice and the activation of PI3K signaling significantly enhances and maintains these lesions, providing a preclinical model for the further mechanistic and therapeutic study of CCMs.

Effects of Si Substrates with Variable Initial Orientations on the Growth and Thermoelectric Properties of Bi-Sb-Te Thin Films.

For thermoelectric thin film, the substrate plays an important role during the growing process and produces effects on its thermoelectric properties. Some special kinds of substrates provide an optimal combination of influences on both the structure and thermoelectric properties. In this work, Bi-Sb-Te films are deposited on Si substrates with different initial orientations by magnetron sputtering in two ways: with and without a pre-coating process. The preferred orientations of the Bi-Sb-Te films are greatly affected by the substrates, in which the thin film tends to deposit on Si substrate with (100) initial orientation and high (015)-texture, while the (00l)-textured Bi-Sb-Te film easily deposits on Si substrate with (110) initial orientation. The experimental and theoretical calculation results indicate that Bi-Sb-Te film with (00l)-texture presents good electrical conductivity and a higher power factor than that of film with (015)-texture.

Exosomal miR-3131 derived from endothelial cells with KRAS mutation promotes EndMT by targeting PICK1 in brain arteriovenous malformations.

AIMS: To explore the underlying mechanism by which low-frequency KRAS mutations result in extensive EndMT occurrence. METHODS: Exosomes derived from primarily cultured brain arteriovenous malformation (bAVMs) and human umbilical vein endothelial cells (HUVECs) transfected with KRASG12D , KRASWT , or KRASNC lentiviruses were isolated, and their effects on HUVECs were identified by western blotting and immunofluorescence staining. The expression levels of exosomal microRNAs (miRNAs) were evaluated by miRNA microarray, followed by functional experiments on miR-3131 and detection of its downstream target, and miR-3131 inhibitor in reversing the EndMT process induced by KRASG12D -transfected HUVECs and bAVM endothelial cells (ECs) were explored. RESULTS: Exosomes derived from KRASG12D bAVM ECs and KRASG12D -transfected HUVECs promoted EndMT in HUVECs. MiR-3131 levels were highest in the exosomes of KRASG12D -transfected HUVECs, and HUVECs transfected with the miR-3131 mimic acquired mesenchymal phenotypes. RNA-seq and dual-luciferase reporter assays revealed that PICK1 is the direct downstream target of miR-3131. Exosomal miR-3131 was highly expressed in KRASG12D bAVMexos compared with non-KRAS-mutant bAVMexos or HUVECexos . Finally, a miR-3131 inhibitor reversed EndMT in HUVECs treated with exosomes or the supernatant of KRASG12D -transfected HUVECs and KRASG12D bAVM ECs. CONCLUSION: Exosomal miR-3131 promotes EndMT in KRAS-mutant bAVMs, and miR-3131 might be a potential biomarker and therapeutic target in KRASG12D -mutant bAVMs.

KRAS mutation-induced EndMT of brain arteriovenous malformation is mediated through the TGF-ß/BMP-SMAD4 pathway.

OBJECTIVE: Somatic KRAS mutations have been identified in the majority of brain arteriovenous malformations (bAVMs), and subsequent in vivo experiments have confirmed that KRAS mutation in endothelial cells (ECs) causes AVMs in mouse and zebrafish models. Our previous study demonstrated that the KRASG12D mutant independently induced the endothelial-mesenchymal transition (EndMT), which was reversed by treatment with the lipid-lowering drug lovastatin. However, the underlying mechanisms of action were unclear. METHODS: We used human umbilical vein ECs (HUVECs) overexpressing the KRASG12D mutant for Western blotting, quantitative real-time PCR, and immunofluorescence and wound healing assays to evaluate the EndMT and determine the activation of downstream pathways. Knockdown of SMAD4 by RNA interference was performed to explore the role of SMAD4 in regulating the EndMT. BAVM ECs expressing the KRASG12D mutant were obtained to verify the SMAD4 function. Finally, we performed a coimmunoprecipitation assay to probe the mechanism by which lovastatin affects SMAD4. RESULTS: HUVECs infected with KRASG12D adenovirus underwent the EndMT. Transforming growth factor beta (TGF-ß) and bone morphogenetic protein (BMP) signalling pathways were activated in the KRASG12D-mutant HUVECs and ECs in bAVM tissue. Knocking down SMAD4 expression in both KRASG12D-mutant HUVECs and ECs in bAVM tissues inhibited the EndMT. Lovastatin attenuated the EndMT by downregulating p-SMAD2/3, p-SMAD1/5 and acetylated SMAD4 expression in KRASG12D-mutant HUVECs. CONCLUSIONS: Our findings suggest that the KRASG12D mutant induces the EndMT by activating the ERK-TGF-ß/BMP-SMAD4 signalling pathway and that lovastatin inhibits the EndMT by suppressing TGF-ß/BMP pathway activation and SMAD4 acetylation.

The community perception of human-water connections is indirectly influenced by the landscape context: A case study in the lower reaches of the Yellow river.

Humans and water are closely connected in large river basins and form social-ecological systems (SESs). However, cross-scale effect in SESs make it difficult to identify the key forces driving human-water connections at the community scale when ignoring the landscape context. Focusing on the incongruous human-water relationships in the lower reaches of the Yellow River, we built local resident perception-based networks linking the agricultural subsystem, environmental subsystem, and cultural subsystem by distributing farmer household questionnaires and extracted 13 indicators from 7 kinds of network metrics to indicate human-water connections. We applied analysis of variance (ANOVA), random forest (RF) and multilevel linear model (MLM) methods to identify the driving forces of perception-based human-water connections among 20 factors at both the community and landscape scales. The results showed that the perception-based network indicators were mainly directly influenced by community-level driving factors, especially the accessibility of information, such as the frequency of going out, the frequency of accessing the Yellow River channel, and the information source for the national policy on the Yellow River. The influences of community-level driving factors on network indicators were affected by landscape-level driving factors, e.g., the nighttime light, population density, gross domestic product and proportion of artificial land, thus indicating indirect influences from the landscape context. These analyses and findings can enrich the methods by which social, ecological and hydrological elements are structurally linked in sociohydrologic research and highlight the cross-scale effect of the landscape context on human-water systems at the community level.