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Abstract Microbiological Rapid On-Site Evaluation (M-ROSE) is based on smear staining and microscopic observation, providing critical references for the diagnosis and treatment of pulmonary infectious disease. Automatic identification of pathogens is the key to improving the quality and speed of M-ROSE. Recent advancements in deep learning have yielded numerous identification algorithms and datasets. However, most studies focus on artificially cultured bacteria and lack clinical data and algorithms. Therefore, we collected Gram-stained bacteria images from lower respiratory tract specimens of patients with lung infections in Chinese PLA General Hospital obtained by M-ROSE from 2018 to 2022 and desensitized images to produce 1705 images (4,912 × 3,684 pixels). A total of 4,833 cocci and 6,991 bacilli were manually labelled and differentiated into negative and positive. In addition, we applied the detection and segmentation networks for benchmark testing. Data and benchmark algorithms we provided that may benefit the study of automated bacterial identification in clinical specimens.

This paper aimed to further introduce the finite element analysis of non-smooth data for semilinear stochastic subdiffusion problems driven by fractionally integrated additive noise. The mild solution of this stochastic model consisted of three different Mittag-Leffler functions. We analyzed the smoothness of the solution and utilized complex integration to approximate the error of the solution operator under non-smooth data. Consequently, optimal convergence estimates were obtained, and we also obtained the continuity conditions of the mild solution. Finally, the influence of the fractional parameters $ \alpha $ and $ \gamma $ on the convergence rates were accurately demonstrated through numerical examples.

Background: STIL is an important cell cycle-regulating protein specifically recruited to the mitotic centrosome to promote the replication of centrioles in dividing cells. However, the potential role of STIL in the regulation of the biological functions of triple-negative breast cancer remains still unclear. Methods: We screened for differentially expressed STIL in the Cancer Genome Atlas database. The expression of STIL protein in 10 pairs of breast cancer tissues and adjacent normal tissues was further assessed by western blotting. Functionally, the knockdown and overexpression of STIL have been used to explore the effects of STIL on breast cancer cell proliferation, migration, and invasion. Mechanistically, RNA-seq, dual-luciferase reporter assay, chromatin immunoprecipitation assay, mass spectrometry, immunoprecipitation assay, and DNA pull-down assay were performed. Results: Breast cancer tissues and cells have higher STIL expression than normal tissues and cells. STIL knockdown impairs breast cancer cell growth, migration, and invasion, whereas STIL overexpression accelerates these processes. STIL promotes breast cancer progression by regulating FANCD2 expression, and exploration of its molecular mechanism demonstrated that STIL interacts with KLF16 to regulate the expression of FANCD2. Conclusions: Collectively, our findings identified STIL as a critical promoter of breast cancer progression that interacts with KLF16 to regulate Fanconi anemia pathway protein FANCD2. In summary, STIL is a potential novel biomarker and therapeutic target for breast cancer.

Abstract Effective targeting of cancer-associated fibroblasts (CAFs) is hindered by the lack of specific biomarkers and a poor understanding of the mechanisms by which different populations of CAFs contribute to cancer progression. While the role of TGFβ in CAFs is well-studied, less attention has been focused on a structurally and functionally similar protein, Activin A (encoded by INHBA). Here, we identified INHBA(+) CAFs as key players in tumor promotion and immunosuppression. Spatiotemporal analyses of patient-matched primary, metastatic, and recurrent ovarian carcinomas revealed that aggressive metastatic tumors enriched in INHBA(+) CAFs were also enriched in regulatory T cells (Tregs). In ovarian cancer mouse models, intraperitoneal injection of the Activin A neutralizing antibody attenuated tumor progression and infiltration with pro-tumorigenic subsets of myofibroblasts and macrophages. Downregulation of INHBA in human ovarian CAFs inhibited pro-tumorigenic CAF functions. Co-culture of human ovarian CAFs and T cells revealed the dependence of Treg differentiation on direct contact with INHBA(+) CAFs. Mechanistically, INHBA/recombinant Activin A in CAFs induced the autocrine expression of PD-L1 through SMAD2-dependent signaling, which promoted Treg differentiation. Collectively, our study identified an INHBA(+) subset of immunomodulatory pro-tumoral CAFs as a potential therapeutic target in advanced ovarian cancers which typically show a poor response to immunotherapy.

Abstract TNF acts as one pathogenic driver for inducing intestinal epithelial cell (IEC) death and substantial intestinal inflammation. How the IEC death is regulated to physiologically prevent intestinal inflammation needs further investigation. Here, we report that EF-hand domain-containing protein D2 (EFHD2), highly expressed in normal intestine tissues but decreased in intestinal biopsy samples of ulcerative colitis patients, protects intestinal epithelium from TNF-induced IEC apoptosis. EFHD2 inhibits TNF-induced apoptosis in primary IECs and intestinal organoids (enteroids). Mice deficient of Efhd2 in IECs exhibit excessive IEC death and exacerbated experimental colitis. Mechanistically, EFHD2 interacts with Cofilin and suppresses Cofilin phosphorylation, thus blocking TNF receptor I (TNFR1) internalization to inhibit IEC apoptosis and consequently protecting intestine from inflammation. Our findings deepen the understanding of EFHD2 as the key regulator of membrane receptor trafficking, providing insight into death receptor signals and autoinflammatory diseases.

Abstract The synovium is an important component of any synovial joint and is the major target tissue of inflammatory arthritis. However, the multi-omics landscape of synovium required for functional inference is absent from large-scale resources. Here we integrate genomics with transcriptomics and chromatin accessibility features of human synovium in up to 245 arthritic patients, to characterize the landscape of genetic regulation on gene expression and the regulatory mechanisms mediating arthritic diseases predisposition. We identify 4765 independent primary and 616 secondary cis-expression quantitative trait loci (cis-eQTLs) in the synovium and find that the eQTLs with multiple independent signals have stronger effects and heritability than single independent eQTLs. Integration of genome-wide association studies (GWASs) and eQTLs identifies 84 arthritis related genes, revealing 38 novel genes which have not been reported by previous studies using eQTL data from the GTEx project or immune cells. We further develop a method called eQTac to identify variants that could affect gene expression by affecting chromatin accessibility and identify 1517 regions with potential regulatory function of chromatin accessibility. Altogether, our study provides a comprehensive synovium multi-omics resource for arthritic diseases and gains new insights into the regulation of gene expression.

Background: Polycystic ovary syndrome (PCOS) is characterized by excess androgens, ovulatory dysfunction, and polycystic ovaries. The mechanisms underlying ovulatory and metabolic disorders in PCOS remain elusive, hampering therapeutic development. Enhanced metabolic health correlates with increased microbiota gene content and microbial diversity. We aimed to explore the impact of gut microbiota and serum steroids on PCOS regulation associated with androgen excess.Methods: The fecal samples of patients with hyperandrogenic PCOS (n = 14) and control group with PCOS (n = 14) were analyzed by 16S rRNA gene sequencing. The peripheral venous blood of all subjects was collected to detect serum hormones. The association between gut microbiota and serum hormones was analyzed with the R language.Results: Our findings reveal that the hyperandrogenic PCOS group exhibits lower richness and diversity of gut microbiota compared to the control group. Characteristic genera in PCOS patients with hyperandrogenism include Bifidobacterium, Enterobacteriaceae_unclassified, Streptococcus, Saccharimonadaceae, Enterococcus, and Eubacterium_nodatum_group. Five hormones, including 5β-androsterone, deoxycorticosterone, corticosterone, 11-dehydrocorticosterone, and cortexolone, emerge as potential serum biomarkers for identifying patients with hyperandrogenic-PCOS (HA-PCOS). Furthermore, a lower vitamin D3 level may act as a susceptibility factor, suggesting that vitamin D3 supplementation could serve as a potential intervention for PCOS with hyperandrogenism.Conclusion: Specific fecal microbiota and serum steroids may be used as characteristic markers for clinical diagnosis of hyperandrogenic-PCOS. This research enhances our understanding of the intricate interplay among hormones, gut microbiota, and hyperandrogenemia in patients with PCOS.

Due to a dramatic increase in livestock, the impact of grazing on animal communities is a global conservation concern, especially in temperate forests. Recognizing the interaction between livestock and wildlife is essential for developing more effective and holistic strategies for wildlife conservation and sustainable livestock management. In this study, we conducted systematic camera trapping at 129 sites within the central portion of the Giant Panda National Park in China to assess the interspecific relationships between livestock and 21 sympatric wild species. Using the joint species distribution model, we fitted a null model and a constrained model to investigate the distinction between the spatial distribution relationship of species (as raw associations) and the interactions between livestock and wildlife (as residual associations). The results of raw associations showed that livestock exhibited a significant positive spatial co-occurrence with Temminck's tragopan, Himalayan porcupine, Chinese serow, Reeves's muntjac, and forest musk-deer (p 0.05), indicating no strong evidence of negative interactions between livestock and wildlife. Since livestock grazing is a source of income for residents, grazing management policies within the Giant Panda National Park should not prohibit all grazing practices.

In order to explore the application potential of aspartic protease (Asp) of Trichoderma sp., the protease gene (asp) was cloned from Trichoderma asperellum by real-time polymerase chain reaction, and was successfully expressed in Pichia Pastoris GS115. The recombinant protease (rAsp) was isolated and purified, and its biochemical properties and its effectiveness in hydrolyzing soy protein isolate (SPI) were studied. The results showed that the protease encoded by the asp gene belonged to the aspartic protease family, and its sequence identity with other members of this family was up to 47.74%. The protease activity of rAsp in the fermentation broth obtained by induced expression in a conical flask was 25.8 U/mL. The optimal reaction pH and temperature of rAsp were 2.5 and 45 ℃, respectively, and rAsp had strong stability in the pH range of 2.0–6.0 and below 45 ℃. The activity of rAsp was promoted by Cu2+ and Mn2+ but inhibited by Fe3+, sodium dodecylsulfate (SDS) and pepstantin. The hydrolysis efficiency of SPI with rAsp was 7.7% higher than that with commercial pepsin. Moreover, the ability of rAsp to reduce the allergenicity of β-conglycinin and glycinin was 1.4 and 1.8 times greater than that of the pepsin, respectively. Therefore, rAsp has potential application in soy protein processing.

Abstract Background The efficacy of anti‐programmed cell death protein 1 (PD‐1) immunotherapy in various cancers, including gastric cancer (GC), needs to be potentiated by more effective targeting to enhance therapeutic efficacy or identifying accurate biomarkers to predict clinical responses. Here, we attempted to identify molecules predicting or/and promoting anti‐PD‐1 therapeutic response in advanced GC (AGC). Methods The transcriptome of AGC tissues from patients with different clinical responses to anti‐PD‐1 immunotherapy and GC cells was analyzed by RNA sequencing. The protein and mRNA levels of the major facilitator superfamily domain containing 2A (MFSD2A) in GC cells were assessed via quantitative real‐time polymerase chain reaction, Western blotting, and immunohistochemistry. Additionally, the regulation of anti‐PD‐1 response by MFSD2A was studied in tumor‐bearing mice. Cytometry by Time‐of‐Flight, multiple immunohistochemistry, and flow cytometry assays were used to explore immunological responses. The effects of MFSD2A on lipid metabolism in mice cancer tissue and GC cells was detected by metabolomics. Results Higher expression of MFSD2A in tumor tissues of AGC patients was associated with better response to anti‐PD‐1 immunotherapy. Moreover, MFSD2A expression was lower in GC tissues compared to adjacent normal tissues, and its expression was inversely correlated with GC stage. The overexpression of MFSD2A in GC cells enhanced the efficacy of anti‐PD‐1 immunotherapy in vivo by reprogramming the tumor microenvironment (TME), characterized by increased CD8+ T cell activation and reduced its exhaustion. MFSD2A inhibited transforming growth factor β1 (TGFβ1) release from GC cells by suppressing cyclooxygenase 2 (COX2)‐prostaglandin synthesis, which consequently reprogrammed TME to promote anti‐tumor T cell activation. Conclusions MFSD2A potentially serves as a predictive biomarker for anti‐PD‐1 immunotherapy response in AGC patients. MFSD2A may be a promising therapeutic target to potentiate the efficacy of anti‐PD‐1 immunotherapy by reprogramming the TME to promote T cells activation.

Abstract Background To develop and validate a multivariable risk prediction model for ketosis‐prone type 2 diabetes mellitus (T2DM) based on clinical characteristics. Methods A total of 964 participants newly diagnosed with T2DM were enrolled in the modeling and validation cohort. Baseline clinical data were collected and analyzed. Multivariable logistic regression analysis was performed to select independent risk factors, develop the prediction model, and construct the nomogram. The model's reliability and validity were checked using the receiver operating characteristic curve and the calibration curve. Results A high morbidity of ketosis‐prone T2DM was observed (20.2%), who presented as lower age and fasting C‐peptide, and higher free fatty acids, glycated hemoglobin A1c and urinary protein. Based on these five independent influence factors, we developed a risk prediction model for ketosis‐prone T2DM and constructed the nomogram. Areas under the curve of the modeling and validation cohorts were 0.806 (95% confidence interval [CI]: 0.760–0.851) and 0.856 (95% CI: 0.803–0.908). The calibration curves that were both internally and externally checked indicated that the projected results were reasonably close to the actual values. Conclusions Our study provided an effective clinical risk prediction model for ketosis‐prone T2DM, which could help for precise classification and management.

Abstracts Phosphorylation of IRF3 is critical to induce type I interferon (IFN-I) production in antiviral innate response. Here we report that lysine methyltransferase SMYD2 inhibits the expressions of IFN-I and proinflammatory cytokines in macrophages upon viral infections. The Smyd2-deficient mice are more resistant to viral infection by producing more IFN-I and proinflammatory cytokines. Mechanistically, SMYD2 inhibits IRF3 phosphorylation in macrophages in response to viral infection independent of its methyltransferase activity. We found that SMYD2 interacts with the DNA-binding domain (DBD) and IRF association domain (IAD) domains of IRF3 by its insertion SET domain (SETi) and could recruit phosphatase PP1α to enhance its interaction with IRF3, which leads to decreased phosphorylation of IRF3 in the antiviral innate response. Our study identifies SMYD2 as a negative regulator of IFN-I production against virus infection. The new way of regulating IRF3 phosphorylation will provide insight into the understanding of IFN-I production in the innate response and possible intervention of the related immune disorders.

Nanotechnology has ushered in significant advancements in drug design, revolutionizing the prevention, diagnosis, and treatment of various diseases. The strategic utilization of nanotechnology to enhance drug loading, delivery, and release has garnered increasing attention, leveraging the enhanced physical and chemical properties offered by these systems. Polyamidoamine (PAMAM) dendrimers have been pivotal in drug delivery, yet there is room for further enhancement. In this study, we conjugated PAMAM dendrimers with chitosan (CS) to augment cellular internalization in tumor cells. Specifically, doxorubicin (DOX) was initially loaded into PAMAM dendrimers to form DOX-loaded PAMAM (DOX@PAMAM) complexes via intermolecular forces. Subsequently, CS was linked onto the DOX-loaded PAMAM dendrimers to yield CS-conjugated PAMAM loaded with DOX (DOX@CS@PAMAM) through glutaraldehyde crosslinking via the Schiff base reaction. The resultant DOX@CS@PAMAM complexes were comprehensively characterized using Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Notably, while the drug release profile of DOX@CS@PAMAM in acidic environments was inferior to that of DOX@PAMAM, DOX@CS@PAMAM demonstrated effective acid-responsive drug release, with a cumulative release of 70% within 25 h attributed to the imine linkage. Most importantly, DOX@CS@PAMAM exhibited significant selective cellular internalization rates and antitumor efficacy compared to DOX@PAMAM, as validated through cell viability assays, fluorescence imaging, and flow cytometry analysis. In summary, DOX@CS@PAMAM demonstrated superior antitumor effects compared to unconjugated PAMAM dendrimers, thereby broadening the scope of dendrimer-based nanomedicines with enhanced therapeutic efficacy and promising applications in cancer therapy.

We introduce a quantum information theory-inspired method to improve the characterization of many-body Hamiltonians on near-term quantum devices. We design a new class of similarity transformations that, when applied as a preprocessing step, can substantially simplify a Hamiltonian for subsequent analysis on quantum hardware. By design, these transformations can be identified and applied efficiently using purely classical resources. In practice, these transformations allow us to shorten requisite physical circuit-depths, overcoming constraints imposed by imperfect near-term hardware. Importantly, the quality of our transformations is $tunable$: we define a 'ladder' of transformations that yields increasingly simple Hamiltonians at the cost of more classical computation. Using quantum chemistry as a benchmark application, we demonstrate that our protocol leads to significant performance improvements for zero and finite temperature free energy calculations on both digital and analog quantum hardware. Specifically, our energy estimates not only outperform traditional Hartree-Fock solutions, but this performance gap also consistently widens as we tune up the quality of our transformations. In short, our quantum information-based approach opens promising new pathways to realizing useful and feasible quantum chemistry algorithms on near-term hardware.

This study aimed to explore the efficacy and potential mechanisms of rechallenge therapy with microtubule-targeting agents (MTAs) in patients with HER2-low metastatic breast cancer (MBC). We performed a systematic review to investigate the rechallenge treatment concept in the field of HER2-low MBC treatment and utilized a series of cases identified in the literature to illustrate the concept. Here we reported two clinical cases of HER2-low MBC patients whose disease progressed after prior treatment with MTAs such as docetaxel and vincristine. When rechallenged with disitamab vedotin ((RC48-antibody-drug conjugate (ADC), a monomethyl auristatin (MMAE) MTA)), both patients achieved a partial response and the final progression-free survival (PFS) was 13.5 and 9 months, respectively. Genomic profiling detected a PIK3CA H1047R mutation in the patients. The patients were treated with everolimus before being rechallenged with RC48, which may lead to a better response. This study further summarizes and analyzes the potential mechanism of the PI3K-AKT signaling pathway in MTA resistance and reveals that the PIK3CA H1047R mutation may be a potential molecular marker for the efficacy prediction of mTOR inhibitors, providing new insights and potential therapeutic strategies for the application of MTAs to MBC patients.

ABSTRACTIt is critical to determine the real-world performance of vaccines against coronavirus disease 2019 (COVID-19) so that appropriate treatments and policies can be implemented. There was a rapid wave of infections by the Omicron variant in Jilin Province (China) during spring 2022. We examined the effectiveness of inactivated vaccines against Omicron using real-world data from this epidemic. This retrospective case-case study of vaccine effectiveness (VE) examined infected patients who were quarantined and treated from April 16 to June 8, 2022 and responded to an electronic questionnaire. Data were analyzed by univariable and multivariable analyses. A total of 2968 cases with SARS-CoV-2 infections (asymptomatic: 1061, mild disease: 1763, pneumonia: 126, severe disease: 18) were enrolled in the study. Multivariable regression indicated that the risk for pneumonia or severe disease was greater in those who were older or had underlying diseases, but was less in those who received COVID-19 vaccines. Relative to no vaccination, VE against the composite of pneumonia and severe disease was significant for those who received 2 doses (60.1%, 95%CI: 40.0%, 73.5%) or 3 doses (68.1%, 95%CI: 44.6%, 81.7%), and VE was similar in the subgroups of males and females. However, VE against the composite of all three classes of symptomatic diseases was not significant overall, nor after stratification by sex. There was no statistical difference in the VE of vaccines from different manufacturers. The inactivated COVID-19 vaccines protected patients against pneumonia and severe disease from Omicron infection, and booster vaccination enhanced this effect.

Abstract Introduction The mortality rate of hospitalized patients with severe hospital-acquired pneumonia (SHAP) remains high. Empirical broad-spectrum antibiotic coverage and the misuse of high-grade antibiotics could lead to the emergence of multi-drug and even pandrug-resistant bacteria. In addition to metagenomic next-generation sequencing (mNGS), microbiological rapid on-site evaluation (M-ROSE) might be a useful technique to identify the pathogens in the early stage; however, the effect of M-ROSE guiding anti-infection treatment on prognostic outcomes of SHAP patients is still unclear. Methods/design This is a multicenter, single-blind, prospective, randomized controlled trial to evaluate the effect of M-ROSE guiding anti-infection treatment in SHAP patients, which will provide new strategies for the prevention and control of clinical multi-drug resistance bacteria. A total of 166 patients with SHAP, aged 18 years and over, will be recruited from seven centers in Beijing and randomly assigned to the intervention group (M-ROSE combined with mNGS) or the control group (mNGS only) in a 1:1 ratio using the central randomization system. Patients in the intervention group will accept M-ROSE and mNGS analysis, and the control group will accept mNGS analysis. Individualized anti-infective treatment and routine treatment will be selected according to the analysis results. The primary outcome is the ICU outcome (mortality). The safety of the intervention measures will be evaluated during the entire trial period. This trial will be the first randomized controlled trial to evaluate the effect of M-ROSE guiding treatment on mortality in patients with SHAP and may change the prevalence of multi-drug resistant bacteria. Ethics and dissemination This trial adheres to the Declaration of Helsinki and guidelines of Good Clinical Practice. Signed informed consent will be obtained from all participants. The trial has been approved by the Chinese PLA General Hospital (Approval Number: 20220322001). Trial registration ClinicalTrials.gov NCT05300776. Registered on 25 March 2022.

Abstract Background Visceral obesity is associated with high cardiovascular events risk in type 2 diabetes mellitus (T2DM). Whether normal-weight visceral obesity will pose a higher atherosclerotic cardiovascular disease (ASCVD) risk than body mass index (BMI)-defined overweight or obese counterparts with or without visceral obesity remains unclear. We aimed to explore the relationship between general obesity and visceral obesity and 10-year ASCVD risk in patients with T2DM. Methods Patients with T2DM (6997) who satisfied the requirements for inclusion were enrolled. Patients were considered to have normal weight when 18.5 kg/m2 ≤ BMI

Summary: The roles of long noncoding RNA (lncRNA) and RNA-binding proteins (RBPs) in antiviral innate response warrant further investigation. Here, we identify an lncRNA, termed lncRNA-BTX (between Tbk1 and Xpot), which is upregulated upon viral infection via an IRF3-type I interferon-independent pathway, promoting viral innate immune escape. Deletion of lncRNA-BTX in cells or mice significantly reduces viral load in vitro or in vivo, respectively. Mechanistically, lncRNA-BTX strengthens the interactions between DHX9 or ILF3 (two RBPs that have opposite functions in regulating the replication of RNA virus) and their respective partner, JMJD6 or ILF2, which regulates intracellular translocations of DHX9 and ILF3 from the nucleus to the cytoplasm. Put simply, lncRNA-BTX facilitates DHX9’s return to the cytoplasm and retains ILF3 within the nucleus, promoting viral replication. This work unveils a strategy developed by the virus to bypass host innate immunity, thus providing a potential target for antiviral therapeutics.

Objective To establish a monitoring system and a standard database system for neonatal hearing screening program and evaluate its effect. Methods The hearing screening data of newborns in Nanjing in 2021 from the neonatal hearing screening information system of Jiangsu Province were selected as the experimental group, and the manual registration data of neonatal hearing screening in Nanjing in 2020 were selected as the control group. The initial screening rate, re-screening rate, referral rate and hearing impairment disease management rate of neonates were compared between two groups. Results The initial screening rate, re-screening rate and referral rate of neonatal hearing screening in the information management system were 99.27%,85.73% and 91.60% respectively, which were significantly higher than those in the manual registration control group (96.94%, 68.36% and 66.20%, P

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. NAFLD starts with hepatic lipid accumulation, which may cause inflammation and ultimately lead to fibrosis in the liver. Studies have shown that intestinal microorganisms and a variety of bioactive substances produced by them interact with host hepatocytes through the portal vein, resulting in the occurrence and development of NAFLD. The bidirectional communication between the intestinal tract and the liver is called the gut-liver axis. In this paper, the mechanism of the occurrence and development of NAFLD mediated by the gut-liver axis is elaborated from the perspectives of intestinal microbial composition, intestinal barrier function, intestinal microbial components and intestinal microbial metabolites, as well as the role of nutritional intervention in ameliorating NAFLD by targeting the gut-liver axis. This article reviews the existing knowledge on the mechanisms of the complex interaction between intestinal disorders and NAFLD in order to provide nutritional strategies for the prevention and improvement of NAFLD.

We develop a strong coupling approach towards quantum magnetism in Mott insulators for Wannier-obstructed bands. Despite the lack of Wannier orbitals, electrons can still singly occupy a set of exponentially localized but nonorthogonal orbitals to minimize the repulsive interaction energy. We develop a systematic method to establish an effective spin model from the electron Hamiltonian using a diagrammatic approach. The nonorthogonality of the Mott basis gives rise to multiple new channels of spin-exchange (or permutation) interactions beyond Hartree–Fock and superexchange terms. We apply this approach to a Kagome lattice model of interacting electrons in Wannier-obstructed bands (including both Chern bands and fragile topological bands). Due to the orbital nonorthogonality, as parameterized by the nearest-neighbor orbital overlap g, this model exhibits stable ferromagnetism up to a finite bandwidth W∼Ug, where U is the interaction strength. This provides an explanation for the experimentally observed robust ferromagnetism in Wannier-obstructed bands. The effective spin model constructed through our approach also opens up the possibility for frustrated quantum magnetism around the ferromagnet-antiferromagnet crossover in Wannier-obstructed bands.