Engineering Strategies to Modulate the Gut Microbiome and Immune System.

The gut microbiota, predominantly residing in the colon, is a complex ecosystem with a pivotal role in the host immune system. Dysbiosis of the gut microbiota has been associated with various diseases, and there is an urgent need to develop new therapeutics that target the microbiome and restore immune functions. This Brief Review discusses emerging therapeutic strategies that focus on oral delivery systems for modulating the gut microbiome. These strategies include genetic engineering of probiotics, probiotic-biomaterial hybrids, dietary fibers, and oral delivery systems for microbial metabolites, antimicrobial peptides, RNA, and antibiotics. Engineered oral formulations have demonstrated promising outcomes in reshaping the gut microbiome and influencing immune responses in preclinical studies. By leveraging these approaches, the interplay between the gut microbiota and the immune system can be harnessed for the development of novel therapeutics against cancer, autoimmune disorders, and allergies.

Split aminoacyl-tRNA synthetases for proximity-induced stop codon suppression.

Synthetic biology tools for regulating gene expression have many useful biotechnology and therapeutic applications. Most tools developed for this purpose control gene expression at the level of transcription, and relatively few methods are available for regulating gene expression at the translational level. Here, we design and engineer split orthogonal aminoacyl-tRNA synthetases (o-aaRS) as unique tools to control gene translation in bacteria and mammalian cells. Using chemically induced dimerization domains, we developed split o-aaRSs that mediate gene expression by conditionally suppressing stop codons in the presence of the small molecules rapamycin and abscisic acid. By activating o-aaRSs, these molecular switches induce stop codon suppression, and in their absence stop codon suppression is turned off. We demonstrate, in Escherichia coli and in human cells, that split o-aaRSs function as genetically encoded AND gates where stop codon suppression is controlled by two distinct molecular inputs. In addition, we show that split o-aaRSs can be used as versatile biosensors to detect therapeutically relevant protein-protein interactions, including those involved in cancer, and those that mediate severe acute respiratory syndrome-coronavirus-2 infection.

Recoding UAG to selenocysteine in Saccharomyces cerevisiae.

Unique chemical and physical properties are introduced by inserting selenocysteine (Sec) at specific sites within proteins. Recombinant and facile production of eukaryotic selenoproteins would benefit from a yeast expression system; however, the selenoprotein biosynthetic pathway was lost in the evolution of the kingdom Fungi as it diverged from its eukaryotic relatives. Based on our previous development of efficient selenoprotein production in bacteria, we designed a novel Sec biosynthesis pathway in Saccharomyces cerevisiae using Aeromonas salmonicida translation components. S. cerevisiae tRNASer was mutated to resemble A. salmonicida tRNASec to allow recognition by S. cerevisiae seryl-tRNA synthetase as well as A. salmonicida selenocysteine synthase (SelA) and selenophosphate synthetase (SelD). Expression of these Sec pathway components was then combined with metabolic engineering of yeast to enable the production of active methionine sulfate reductase enzyme containing genetically encoded Sec. Our report is the first demonstration that yeast is capable of selenoprotein production by site-specific incorporation of Sec.

Inulin-gel-based oral immunotherapy remodels the small intestinal microbiome and suppresses food allergy.

Despite the potential of oral immunotherapy against food allergy, adverse reactions and loss of desensitization hinder its clinical uptake. Dysbiosis of the gut microbiota is implicated in the increasing prevalence of food allergy, which will need to be regulated to enable for an effective oral immunotherapy against food allergy. Here we report an inulin gel formulated with an allergen that normalizes the dysregulated ileal microbiota and metabolites in allergic mice, establishes allergen-specific oral tolerance and achieves robust oral immunotherapy efficacy with sustained unresponsiveness in food allergy models. These positive outcomes are associated with enhanced allergen uptake by antigen-sampling dendritic cells in the small intestine, suppressed pathogenic type 2 immune responses, increased interferon-γ+ and interleukin-10+ regulatory T cell populations, and restored ileal abundances of Eggerthellaceae and Enterorhabdus in allergic mice. Overall, our findings underscore the therapeutic potential of the engineered allergen gel as a suitable microbiome-modulating platform for food allergy and other allergic diseases.

Neoadjuvant camrelizumab plus apatinib for locally advanced microsatellite instability-high or mismatch repair-deficient colorectal cancer (NEOCAP): a single-arm, open-label, phase 2 study.

BACKGROUND: PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer. METHODS: We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18-75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0-1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1-14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing. FINDINGS: Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5-23·5) months. 28 (54%; 95% CI 35-68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39-80) had a pathological complete response. 38 (73%; 95% CI 59-84) of 52 patients had a complete response. Grade 3-5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis. INTERPRETATION: Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach. FUNDING: The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Non-cytotoxic nanomolar concentration of arctigenin protects neuronal cells from chemotherapy-induced ferroptosis by regulating SLC7A11-cystine-cysteine axis.

Neurotoxicity is a common side effect of certain types of therapeutic drugs, posing a major hurdle for their clinical application. Accumulating evidence suggests that ferroptosis is involved in the neurotoxicity induced by these drugs. Therefore, targeting ferroptosis is considered to be a reasonable approach to prevent such side effect. Arctigenin (ATG) is a major bioactive ingredient of Arctium lappa L., a popular medicinal plant in Asia, and has been reported to have multiple bioactivities including neuroprotection. However, the mechanisms underlying the neuroprotection of ATG has not been well elucidated. The purpose of this study was to investigate whether the neuroprotection of ATG was associated with its ability to protect neuronal cells from ferroptosis. Using neuronal cell ferroptosis model induced by either classic ferroptosis induces or therapeutic drugs, we demonstrated for the first time that ATG in the nanomolar concentration range effectively prevented neuronal cell ferroptosis induced by classic ferroptosis inducer sulfasalazine (SAS) and erastin (Era), or therapeutic drug oxaliplatin (OXA) and 5-fluorouracil (5-FU). Mechanistically, we uncovered that the anti-ferroptotic effect of ATG was attributed to its ability to activate SLC7A11-cystine-cysteine axis. The findings of the present study implicate that ATG holds great potential to be developed as a novel agent for preventing SLC7A11 inhibition-mediated neurotoxicity.

Glymphatic abnormality in systemic lupus erythematosus detected by diffusion tensor image analysis along the perivascular space.

OBJECTIVES: This study aimed to evaluate the activity of the glymphatic system in systemic lupus erythematosus (SLE) by a diffusion-based method termed "Diffusion Tensor Image Analysis aLong the Perivascular Space (DTI-ALPS)", and examined its correlations with morphological changes in the brain. METHODS: In this cross-sectional study, forty-five female patients with SLE and thirty healthy controls (HCs) were included. Voxel-based and surface-based morphometric analyses were performed to examine T1 weighted images, and diffusion tensor images were acquired to determine diffusivity along the x-, y-, and z-axes in the plane of the lateral ventricle body. The ALPS-index was calculated. The differences in values between SLE patients and HC group were compared using the independent samples t test or Mann-Whitney U test. For the correlations between the ALPS-index and brain morphological parameters, partial correlation analysis and Pearson's correlation analysis were conducted. RESULTS: SLE patients showed lower values for the ALPS-index in left (1.543 ± 0.141 vs 1.713 ± 0.175, p < 0.001), right (1.428 ± 0.142 vs 1.556 ± 0.139, p < 0.001) and whole (1.486 ± 0.121 vs 1.635 ± 0.139, p < 0.001) brain compared with the HC group. The reduced ALPS-index showed significant positive correlations with gray matter loss. CONCLUSION: The non-invasive ALPS-index could serve as a sensitive and effective neuroimaging biomarker for individually quantifying glymphatic activity in patients with SLE. Glymphatic system abnormality may be involved in the pathophysiologic mechanism underlying central nervous system damage in SLE patients.

Theoretical Study of the Ternary Compound Monolayer CuP2Se for Photocatalytic Water Splitting with Efficient Optical Absorption.

Utilizing photocatalytic method to produce hydrogen by splitting water is an efficient strategy to solve the hotspot issues of energy crisis and environmental pollution. Herein, we systematically investigate the corresponding properties of the reported Cu-bearing ternary compound monolayer CuP2Se by using the first-principle calculations. The monolayer CuP2Se has quite small cleavage energy of 0.51 J/m2, indicating it can be easily produced by the mechanical exfoliation method experimentally. In addition, it is an indirect bandgap semiconductor material which has a moderate value of 1.91 eV. The conduction band minimum (CBM) and valence band maximum (VBM) can perfectly straddle the redox potentials of water when a biaxial strain of -4% to 4% is applied, unveiling the high photocatalytic thermodynamic stability of monolayer CuP2Se in response to the effect of solvent tension. Remarkably, the monolayer CuP2Se also demonstrates significant sunlight capturing ability in the visible region. The outstanding electronic and optical properties suggest that the monolayer CuP2Se is undoubtedly a viable material for photocatalytic water splitting.

The effects of oxaliplatin-based adjuvant chemotherapy in high-risk stage II colon cancer with mismatch repair-deficient: a retrospective study.

BACKGROUND: For high-risk stageIImismatch repair deficient (dMMR) colon cancers, the benefit of adjuvant chemotherapy remains debatable. The principal aim of this study was to evaluate the prognostic value of high-risk factors and the effect of oxaliplatin-based adjuvant chemotherapy among dMMR stageIIcolon cancers. METHODS: Patients with stage II dMMR colon cancers diagnosed between June 2011 and May 2018 were enrolled in the study. Clinicopathological characteristics, treatment, and follow-up data were retrospectively collected. The high-risk group was defined as having one of the following factors: pT4 disease, fewer than twelve lymph nodes harvested (< 12 LNs), poorly differentiated histology, perineural invasion (PNI), lymphatic vascular invasion (LVI), or elevated preoperative carcinoembryonic antigen (CEA). The low-risk group did not have any risk factors above. Factors associated with disease-free survival (DFS) were included in univariate and multivariate Cox analyses. RESULTS: We collected a total of 262 consecutive patients with stage II dMMR colon cancer. 179 patients (68.3%) have at least one high-risk factor. With a median follow-up of 50.1 months, the low-risk group was associated with a tended to have a better 3-year DFS than the high-risk group (96.4% vs 89.4%; P = 0.056). Both elevated preoperative CEA (HR 2.93; 95% CI 1.26-6.82; P = 0.013) and pT4 disease (HR 2.58; 95% CI 1.06-6.25; P = 0.037) were independent risk factors of recurrence. Then, the 3-year DFS was 92.6% for the surgery alone group and 88.1% for the adjuvant chemotherapy group (HR 1.64; 95% CI 0.67-4.02; P = 0.280). Furthermore, no survival benefit from oxaliplatin-based adjuvant chemotherapy was observed in the high-risk group and in the subgroups with pT4 disease or < 12 LNs. CONCLUSIONS: These data suggests that not all high-risk factors have a similar impact on stage II dMMR colon cancers. Elevated preoperative CEA and pT4 tumor stage are associated with increased recurrence risk. However, oxaliplatin-based adjuvant chemotherapy shows no survival benefits in stage II dMMR colon cancers, either with or without high-risk factors.

Long-Term Outcomes of dMMR/MSI-H Rectal Cancer Treated With Anti-PD-1-Based Immunotherapy as Curative-Intent Treatment.

BACKGROUND: Neoadjuvant anti-PD-1 therapy has shown encouraging efficacy in patients with deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC), which suggests its potential as a curative-intent therapy and a promising treatment option for organ preservation. We aimed to investigate the long-term outcomes of patients with dMMR/MSI-H LARC who experienced clinical complete response (cCR) after anti-PD-1 therapy. METHODS: We retrospectively analyzed patients with dMMR/MSI-H LARC who achieved cCR and received nonoperative management following neoadjuvant anti-PD-1-based treatment from 4 Chinese medical centers. Patients were followed up for at least 1 year after they achieved cCR, their clinical data were collected, and survival outcomes were analyzed using the Kaplan-Meier method. RESULTS: A total of 24 patients who achieved cCR and received nonoperative management from March 2018 to May 2022 were included, with a median age of 51.0 years (range, 19.0-77.0 years). The median treatment course to reach cCR was 6.0 (range, 1.0-12.0). Fifteen patients (62.5%) continued their treatments after experiencing cCR, and the median treatment course was 17.0 (range, 3.0-36.0). No local regrowth or distant metastasis was observed in a median follow-up time of 29.1 months (range, 12.6-48.5 months) after cCR. The 3-year disease-free and overall survivals were both 100%. CONCLUSIONS: Patients with dMMR/MSI-H locally advanced or low-lying rectal cancer who achieved cCR following anti-PD-1-based therapy had promising long-term outcomes. A prospective clinical trial with a larger sample size is required to further validate these findings.

A New Dy(III) Complex: Fluorescence Performances, Loading with Resveratrol-Hydrogels Against Skin Aging and Molecular Docking.

In the present research, novel lanthanide coordination compounds [DyL(PhCOO)(CH3OH)](ClO4)2·(CH3OH)2 (1) were characterized by the compression of 2,6-diformyl-4-methyl-phenol (dmp) and 1,3-diamino-2-propanol using benzoate as the secondary ligand, where L indicates the deprotonated macrocyclic ligand. Through the high structural rigidity driven by the coordination of the macrocyclic ligand formed by condensation in methanol solution and sodium benzoate with Dy(ClO4)3·6H2O, compound 1 exhibits outstanding cyan-emitting fluorescence performance and potential applications as a fluorescent material. Additionally, hyaluronic acid (HA)/ carboxymethyl chitosan (CMCS) hydrogels were prepared with loaded resveratrol metal-organic complexes according to the synthetic chemical approach. In biological study, we evaluated the effect of hydrogels on oxidative stress on human dermal fibroblasts. Examined by molecular docking simulation, the results showed that the binding interactions were from the phenol group, the carboxyl group and also the "-N=" group, indicating Dy metal complex has excellent biological capability.

High Curie temperature ferromagnetic monolayer T-CrSH and valley physics of T-CrSH/WS2 heterostructure.

Two-dimensional magnetic materials are attracting widespread attention not only for their excellent applications in spintronic devices but also for their potential to regulate valley splitting, which is crucial for valleytronics. Herein, we design a monolayer Janus ferromagnetic semiconductor T-CrSH by using first-principles calculations. We reveal that monolayer T-CrSH has a magnetic moment of 3µB per unit cell, which is primarily contributed by the 3d orbitals of the Cr atom. Monte Carlo simulations suggest that the Curie temperature of T-CrSH is 193 K, and it can rise to 402 K when a 5% tensile strain is applied. Furthermore, the valley degeneracy of WS2 can be lifted when monolayer T-CrSH is used as a substrate. The obtained valley splitting in the conduction band is 13.7 meV and that in the valence band is 157.5 meV. In addition, the large valley polarization of 12.8 meV in the conduction band makes it easy to achieve an electron-doped valley Hall current and spin Hall current when performing in an in-plane electric field.

Glycyrol Alleviates Acute Kidney Injury by Inhibiting Ferroptsis.

Acute kidney injury (AKI) is a common clinical problem with high morbidity and mortality. The discovery of ferroptosis has provided novel insights into the mechanisms underlying AKI and paves the way for developing ferroptosis-based approaches to treat AKI. Glycyrol (GC) is a representative coumarin compound isolated from licorice that demonstrates various pharmacological activities. However, its potential for a protective effect against kidney injury remains unknown. We hypothesized that GC might be able to protect against AKI via suppression of ferroptosis. This hypothesis was tested in a cell-culture model of RSL3-induced nephrocyte ferroptosis and a mouse model of folic acid-induced AKI. The results showed that GC exerted a significant protective effect against nephrocyte ferroptosis in vitro and was effective against folic acid-induced AKI in vivo, where it was mechanistically associated with suppressing HO-1-mediated heme degradation. Collectively, the findings of the present study support the hypothesis that GC holds considerable potential to be developed as a novel agent for treating ferroptosis-related AKI.

Rigid Phase Formation and Sb3+ Doping of Tin (IV) Halide Hybrids toward Photoluminescence Enhancement and Tuning for Anti-Counterfeiting and Information Encryption.

Multi-excitonic emitting materials in luminescent metal halides are emerging candidates for anti-counterfeiting and information encryption applications. Herein, ATPP2SnCl6 (ATPP=acetonyltriphenylphosphonium) phase was designed and synthesized by rationally choosing emissive organic reagent of ATPPCl and non-toxic stable metal ions of Sn4+, and Sb3+ was further doped into ATPP2SnCl6 to tune the photoluminescence with external self-trapped excitons emission. The derived non-toxic ATPP2SnCl6 shows multi-excitonic luminescent centers verified by optical study and differential charge-density from density functional theory calculations. Incorporation of Sb3+ dopants and the increasing concentrations induce the efficient energy transfer therein, thus enhancing photoluminescence quantum yield from 5.1 % to 73.8 %. The multi-excitonic emission inspires the creation of information encryption and decryption by leveraging the photoluminescence from ATPPCl to ATPP2SnCl6 host and ATPP2SnCl6 : Sb3+. This study facilitates the anti-counterfeiting application by employing solution-processable luminescent metal halides materials with excitation-dependent PL properties.

Ancestral archaea expanded the genetic code with pyrrolysine.

The pyrrolysyl-tRNA synthetase (PylRS) facilitates the cotranslational installation of the 22nd amino acid pyrrolysine. Owing to its tolerance for diverse amino acid substrates, and its orthogonality in multiple organisms, PylRS has emerged as a major route to install noncanonical amino acids into proteins in living cells. Recently, a novel class of PylRS enzymes was identified in a subset of methanogenic archaea. Enzymes within this class (ΔPylSn) lack the N-terminal tRNA-binding domain that is widely conserved amongst PylRS enzymes, yet remain active and orthogonal in bacteria and eukaryotes. In this study, we use biochemical and in vivo UAG-readthrough assays to characterize the aminoacylation efficiency and substrate spectrum of a ΔPylSn class PylRS from the archaeon Candidatus Methanomethylophilus alvus. We show that, compared with the full-length enzyme from Methanosarcina mazei, the Ca. M. alvus PylRS displays reduced aminoacylation efficiency but an expanded amino acid substrate spectrum. To gain insight into the evolution of ΔPylSn enzymes, we performed molecular phylogeny using 156 PylRS and 105 pyrrolysine tRNA (tRNAPyl) sequences from diverse archaea and bacteria. This analysis suggests that the PylRS•tRNAPyl pair diverged before the evolution of the three domains of life, placing an early limit on the evolution of the Pyl-decoding trait. Furthermore, our results document the coevolutionary history of PylRS and tRNAPyl and reveal the emergence of tRNAPyl sequences with unique A73 and U73 discriminator bases. The orthogonality of these tRNAPyl species with the more common G73-containing tRNAPyl will enable future efforts to engineer PylRS systems for further genetic code expansion.

Analysis of the 2p-manifold population distribution in a diode-pumped metastable Ar laser.

The complex excited energy levels in the diode-pumped metastable Ar laser may induce harmful effects in laser cycling. Significantly, the influence of the population distribution in 2p energy levels on the laser performance is unclear yet. In this work, the absolute populations in all the 2p states were measured online by the simultaneous applications of tunable diode laser absorption spectroscopy and optical emission spectroscopy. The results showed that most atoms were populated to the 2p8, 2p9, and 2p10 levels while lasing, and the majority of the 2p9 population was efficiently transferred to the 2p10 level with the aid of helium, which was beneficial for the laser performance.

Ghost imaging based on Fermat spiral laser array designed for remote sensing.

We propose a Fermat spiral laser array as illumination source in ghost imaging. Due to the aperiodic structure, the Fermat spiral laser array generates illuminating light field without spatial periodicity on the normalized second-order intensity correlation function. A single-pixel detector is used to receive the signal light from object for image reconstruction. The effects of laser array parameters on the quality of ghost imaging are analyzed comprehensively. Through experimental demonstration, the Fermat spiral laser array successfully achieves ghost imaging with high quality by combining with the compressive sensing reconstruction algorithm. This method is expected to be applied in remote sensing by combining with phased and collimated fiber laser array equipped with the high emitting power and high-speed modulation frequency.

Fast object imaging and classification based on circular harmonic Fourier moment detection.

Limited by the number of illumination fields and the speed of a spatial light modulator, single-pixel imaging (SPI) cannot realize real-time imaging and fast classification of an object. In this paper, we proposed the circular harmonic Fourier single-pixel imaging (CHF-SPI) for the first time to realize fast imaging and classification of objects. The light field distribution satisfies the circular harmonic Fourier formula, and the light intensity values of the single-pixel detector are equivalent to the circular harmonic Fourier moments. Then the target can be reconstructed under low sampling ratio by inverse transformation. Through simulation and experimental verification, clear imaging can be performed at a sampling ratio of 0.9%. In addition, circular harmonic Fourier moments are used to construct multi-distortion invariant to classify objects with rotation and scale change. The scale change multiples of objects can be calculated and the objects can be classified by using 10 light fields. It is of great significance to classify objects quickly without imaging.

Efficient and noise-resistant single-pixel imaging based on Pseudo-Zernike moments.

An efficient and noise-resistant single-pixel imaging (SPI) technique based on Pseudo-Zernike moments (PZ-SPI) is proposed. In this technique, the illumination light fields are modulated to satisfy the Pseudo-Zernike polynomials. Then the modulated light fields are projected onto the object. And the single-pixel detector is used to measure the reflected light intensities to calculate the Pseudo-Zernike moments. Finally, the object image is reconstructed by iterative summation of the product of the Pseudo-Zernike polynomials and the Pseudo-Zernike moments. Through the numerical simulation and experimental demonstration, PZ-SPI can effectively reconstruct image at low sampling ratios. Besides, comparing with the Fourier-SPI and Zernike-SPI, PZ-SPI has good robustness to background noise in SPI system. These advantages expand the application of PZ-SPI in complex environments.

Disrupted resting-state brain functional network properties in non-neuropsychiatric systemic lupus erythematosus patients.

INTRODUCTION: Previous fMRI studies revealed that the abnormal functional connectivity (FC) was related to cognitive impairment in patients with SLE. However, it remains unclear how the disease severity affects the functional topological organization of the whole-brain network in SLE patients without neuropsychiatric symptoms (non-NPSLE). OBJECTIVE: We aim to examine the impairment of the whole-brain functional network in SLE patients without neuropsychiatric symptoms (non-NPSLE), which may improve the understanding of neural mechanism in SLE. METHODS: We acquired resting-state fMRI data from 32 non-NPSLE patients and 32 healthy controls (HC), constructed their whole-brain functional network, and then estimated the topological properties including global and nodal parameters by using graph theory. Meanwhile, we also investigated the differences in intra- and inter-network FC between the non-NPSLE patients and the HC. RESULTS: The non-NPSLE patients showed significantly lower clustering coefficient, global and local efficiency, but higher characteristic path length than the HC. The non-NPSLE patients had significantly lower nodal strength in two regions, ventromedial prefrontal cortex (vmPFC) and anterior PFC (aPFC) than the HC. We found the non-NPSLE patients had significantly lower intra-network FC within frontal-parietal network (FPN) and within default mode network (DMN), and significantly lower inter-network FC between DMN and FPN than the HC. The intra-network FC within DMN was negatively correlated with systemic lupus erythematosus disease activity index (SLEDAI). CONCLUSION: Abnormal whole-brain functional network properties and abnormal intra- and inter-network FC may be related to cognitive impairment and disease degree in the non-NPSLE patients. Our findings provide a network perspective to understand the neural mechanisms of SLE.