Chemical Logic Gates on Active Colloids.

Recent studies have shown that active colloidal motors using enzymatic reactions for propulsion hold special promise for applications in fields ranging from biology to material science. It will be desirable to have active colloids with capability of computation so that they can act autonomously to sense their surroundings and alter their own dynamics. It is shown how small chemical networks that make use of enzymatic chemical reactions on the colloid surface can be used to construct motor-based chemical logic gates. The basic features of coupled enzymatic reactions that are responsible for propulsion and underlie the construction and function of chemical gates are described using continuum theory and molecular simulation. Examples are given that show how colloids with specific chemical logic gates, can perform simple sensing tasks. Due to the diverse functions of different enzyme gates, operating alone or in circuits, the work presented here supports the suggestion that synthetic motors using such gates could be designed to operate in an autonomous way in order to complete complicated tasks.

L-Type Calcium Channel Modulates Low-Intensity Pulsed Ultrasound-Induced Excitation in Cultured Hippocampal Neurons.

As a noninvasive technique, ultrasound stimulation is known to modulate neuronal activity both in vitro and in vivo. The latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and further impact the electrophysiological properties of targeted neurons. However, the underlying mechanism of low-intensity pulsed ultrasound (LIPUS)-induced neuro-modulation effects is still unclear. Here, we characterize the excitatory effects of LIPUS on spontaneous activity and the intracellular Ca2+ homeostasis in cultured hippocampal neurons. By whole-cell patch clamp recording, we found that 15 min of 1-MHz LIPUS boosts the frequency of both spontaneous action potentials and spontaneous excitatory synaptic currents (sEPSCs) and also increases the amplitude of sEPSCs in hippocampal neurons. This phenomenon lasts for > 10 min after LIPUS exposure. Together with Ca2+ imaging, we clarified that LIPUS increases the [Ca2+]cyto level by facilitating L-type Ca2+ channels (LTCCs). In addition, due to the [Ca2+]cyto elevation by LIPUS exposure, the Ca2+-dependent CaMKII-CREB pathway can be activated within 30 min to further regulate the gene transcription and protein expression. Our work suggests that LIPUS regulates neuronal activity in a Ca2+-dependent manner via LTCCs. This may also explain the multi-activation effects of LIPUS beyond neurons. LIPUS stimulation potentiates spontaneous neuronal activity by increasing Ca2+ influx.

Recent advances in discovery and biosynthesis of natural products from myxobacteria: an overview from 2017 to 2023.

Covering: 2017.01 to 2023.11Natural products biosynthesized by myxobacteria are appealing due to their sophisticated chemical skeletons, remarkable biological activities, and intriguing biosynthetic enzymology. This review aims to systematically summarize the advances in the discovery methods, new structures, and bioactivities of myxobacterial NPs reported in the period of 2017-2023. In addition, the peculiar biosynthetic pathways of several structural families are also highlighted.

A case study on the pitfalls in prenatal ultrasonic detection of butterfly vertebra.

Introduction: Butterfly vertebra is a rare congenital anomaly that is observed both in isolation and also as part of syndromic diseases. In prenatal ultrasonic scans the typical shapes of the two halves for butterfly vertebra are wedge-shaped or triangular. In the case we presented, the 3 dimensional computed tomography (3D CT) showed that the shape was unusual and rare. To improve the prenatal ultrasonic discriminability of this rare form of butterfly vertebra we used multi-directional ultrasonic images, corresponding to postpartum 3D CT images. Case report: A 25-year-old woman was referred to our department for ultrasound screening. The routine fetal back spinal scan yielded findings indicative of an anomaly within the ninth thoracic vertebral body. The affected vertebra was examined by two-dimensional (2D) and three-dimensional (3D) ultrasound while the fetus was prone and supine. The focussed scanning of the fetal spine from the back, anterior and lateral approaches aided us to reach the final prenatal diagnosis of butterfly vertebra with asymmetric halves.The diagnosis of butterfly vertebra was confirmed by the radiologist with 3D CT after the woman chose to terminate the pregnancy due to multiple malformations. In 3D CT, the body of the ninth thoracic vertebra appeared to be two lateral halves of different sizes, and the bigger half was C-shaped. When prenatal ultrasonic images and postnatal CT images were compared, the echoic shape of the affected vertebra scanned from the front right side was very similar to the CT. Conclusion: Due to the variable sizes and shapes of vertebrae affected in butterfly vertebra, prenatal diagnosis can be difficult using ultrasound. When the presence of fetal vertebral abnormalities is suspected, it is imperative for sonographers to adopt a comprehensive approach that extends beyond the conventional spinal examination performed solely from the dorsal aspect of the fetus. Instead, a thorough assessment should involve scanning the fetus from various angles, including anterior and lateral perspectives, in order to obtain a comprehensive and detailed evaluation of the identified vertebra.

Mechanical Enhancement of the Gelatin/Poly(zinc acrylate) Hydrogel Stent in Bile.

Hydrogels with the features of softness, biocompatibility, and modifiability have emerged as excellent materials in the biomedical field. However, the poor mechanical properties of the hydrogels limit their further practical applications. Double-network and metal ion coordination, such as Cu2+ and Zn2+, have achieved a significant reinforcement of the mechanical strength of the hydrogels. Herein, we report a Zn2+-enhanced polyelectrolyte double-network hydrogel stent with a mechanical enhancement phenomenon in bile. The gelatin/poly(zinc acrylate) (PZA) stent was constructed by dip-coating and UV irradiation. Although the mechanical strength of the as-prepared stent was quite weak, it was discovered to be mechanically enhanced by the natural bile. After exploring the effect of different components on the stents according to the components of bile, we found that Ca2+ in bile made a contribution to the mechanical enhancement of the stent. It is envisioned that this bile-enhanced gelatin/PZA stent provides a train of thought for the potential application of hydrogels in the biliary environment.

Regulation of T cells by myeloid-derived suppressor cells: emerging immunosuppressor in lung cancer.

Myeloid-derived suppressor cells (MDSCs), major components maintaining the immune suppressive microenvironment in lung cancer, are relevant to the invasion, metastasis, and poor prognosis of lung cancer, through the regulation of epithelial-mesenchymal transition, remodeling of the immune microenvironment, and regulation of angiogenesis. MDSCs regulate T-cell immune functions by maintaining a strong immunosuppressive microenvironment and promoting tumor invasion. This raises the question of whether reversing the immunosuppressive effect of MDSCs on T cells can improve lung cancer treatment. To understand this further, this review explores the interactions and specific mechanisms of different MDSCs subsets, including regulatory T cells, T helper cells, CD8 + T cells, natural killer T cells, and exhausted T cells, as part of the lung cancer immune microenvironment. Second, it focuses on the guiding significance confirmed via clinical liquid biopsy and tissue biopsy that different MDSC subsets improve the prognosis of lung cancer. Finally, we conclude that targeting MDSCs through action targets or signaling pathways can help regulate T-cell immune functions and suppress T-cell exhaustion. In addition, immune checkpoint inhibitors targeting MDSCs may serve as a new approach for enhancing the efficiency of immunotherapy and targeted therapy for lung cancer in the future, providing better comprehensive options for lung cancer treatment.

Small Extracellular Vesicles Secreted by Peri-urethral Tissues Regulate Fibroblast Function and Contribute to the Pathogenesis of Female Stress Urinary Incontinence.

OBJECTIVE: This study aimed to explore the existence of small extracellular vesicles (sEVs) in peri-urethral tissues and the role of abnormal expression of sEVs in the pathogenesis of female stress urinary incontinence (SUI). METHODS: sEVs were extracted from peri-urethral vaginal wall tissues using differential centrifugation and were observed by transmission electron microscopy (TEM). The number of sEVs and their protein contents were compared between SUI and control groups using nanoparticle tracking analysis (NTA) and bicinchoninic acid (BCA) protein assay. Fibroblasts were cultured separately with SUI (SsEVs group) and normal tissue sEVs (NsEVs group). Proliferation and migration of fibroblasts were compared between groups using CCK-8 and wound healing assays, respectively. Expression levels of collagen I and III were compared among blank control (BC), NsEVs, and SsEVs groups using real-time PCR. Protein mass spectrometry was used to test the differentially expressed proteins contained in sEVs between groups. RESULTS: sEVs were extracted and found under the electron microscope. There were significantly more sEVs extracted from the SUI group compared to the normal group. Fibroblasts showed increased proliferative and decreased migratory abilities, and expressed more collagen in the SsEVs group compared to the NsEVs and BC groups. Protein spectrum analysis demonstrated several differentially expressed targets, including components of microfibrils, elastin polymer, and anti-inflammatory factors. CONCLUSION: sEVs were detected in the peri-urethral tissues. SUI tissues expressed more sEVs than control. The abnormal expression of sEVs and their protein contents may contribute to the pathogenesis and progression of SUI.

A pDNA/rapamycin nanocomposite coating on interventional balloons for inhibiting neointimal hyperplasia.

Drug-coated balloon (DCB) is a therapeutic method that can effectively deliver antiproliferative drugs such as paclitaxel and rapamycin (RAPA) with no permanent implants left behind. However, delayed reendothelialization due to the toxicity of the delivered drugs leads to poor therapeutic effects. Here, we propose a new design of DCB coating, which incorporates both vascular endothelial growth factor (VEGF)-encoding plasmid DNA (pDNA) that can promote endothelial repair and RAPA into protamine sulfate (PrS). We demonstrate that the PrS/pDNA/RAPA coating had stability and good anticoagulation properties in vitro. We further show that the coating exhibited excellent transfer capacity from balloon substrates to vessel walls both in vitro and in vivo. Furthermore, the PrS/pDNA/RAPA coating effectively inhibited neointimal hyperplasia after balloon-induced vascular injuries through the down-regulation of the mammalian target of Rapamycin (mTOR) and promoted endothelium regeneration through increased expression of VEGF in vivo. These data indicate that our nanocomposite coating has great potential for use as a novel coating of DCB to treat neointimal hyperplasia after vascular injuries.

Evaluation of efficacy and safety for compound kushen injection combined with intraperitoneal chemotherapy for patients with malignant ascites: A systematic review and meta-analysis.

Objectives: Compound Kushen injection (CKI) combined with intraperitoneal chemotherapy (IPC) is widely used in the treatment of malignant ascites (MA). However, evidence about its efficacy and safety remains limited. This review aimed to evaluate the efficacy and safety of CKI combined with IPC for the treatment of MA. Methods: Protocol of this review was registered in PROSPERO (CRD42022304259). Randomized controlled trials (RCTs) on the efficacy and safety of IPC with CKI for the treatment of patients with MA were searched through 12 electronic databases and 2 clinical trials registration platforms from inception until 20 January 2023. The Cochrane risk-of-bias tool was used to assess the quality of the included trials through the risk of bias assessment. We included RCTs that compared IPC single used or CKI combined with IPC for patients with MA schedule to start IPC. The primary outcome was identified as an objective response rate (ORR), while the secondary outcomes were identified as the quality of life (QoL), survival time, immune functions, and adverse drug reactions (ADRs). The Revman5.4 and Stata17 software were used to calculate the risk ratio (RR) at 95% confidence intervals (CI) for binary outcomes and the mean difference (MD) at 95% CI for continuous outcomes. The certainty of the evidence was assessed according to the GRADE criteria. Results: A total of 17 RCTs were assessed, which included 1200 patients. The risk of bias assessment of the Cochrane risk-of-bias tool revealed that one study was rated high risk and the remaining as unclear or low risk. Meta-analysis revealed that CKI combined with IPC had an advantage in increasing ORR (RR = 1.31, 95% CI 1.20 to 1.43, p < 0.00001) and QoL (RR = 1.50, 95% CI 1.23 to 1.83, p < 0.0001) when compared with IPC alone. Moreover, the combined treatment group showed a lower incidence of myelosuppression (RR = 0.51, 95%CI 0.40-0.64, p < 0.00001), liver dysfunction (RR = 0.33, 95%CI 0.16 to 0.70, p = 0.004), renal dysfunction (RR = 0.39, 95%CI 0.17 to 0.89, p = 0.02), and fever (RR = 0.51, 95%CI 0.35 to 0.75, p = 0.0007) compared to those of the control group. The quality of evidence assessment through GRADE criteria showed that ORR, myelosuppression, and fever were rated moderate, renal dysfunction and liver dysfunction were rated low, and QoL and abdominal pain were rated very low. Conclusion: The efficacy and safety of CKI combined with IPC were superior to that with IPC alone for the treatment of MA, which indicates the potentiality of the treatment. However, more high-quality RCTs are required to validate this conclusion. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022304259], identifier [PROSPERO 2022 CRD42022304259].

Constructing a Myxobacterial Natural Product Database to Facilitate NMR-Based Metabolomics Bioprospecting of Myxobacteria.

Myxobacteria are fascinating prokaryotes featuring a potent capacity for producing a wealth of bioactive molecules with intricate chemical topology as well as intriguing enzymology, and thus it is critical to developing an efficient pipeline for bioprospecting. Herein, we construct the database MyxoDB, the first public compendium solely dedicated to myxobacteria, which enabled us to provide an overview of the structural diversity and taxonomic distribution of known myxobacterial natural products. Moreover, we demonstrated that the cutting-edge NMR-based metabolomics was effective to differentiate the biosynthetic priority of myxobacteria, whereby MyxoDB could greatly streamline the dereplication of multifarious known compounds and accordingly speed up the discovery of new compounds. This led to the rapid identification of a class of linear di-lipopeptides (archangimins) and a rare rearranged sterol (corasterol) that were endowed with unique chemical architectures and/or biosynthetic enzymology. We also showcased that NMR-based metabolomics, MyxoDB, and genomics can also work concertedly to accelerate the targeted discovery of a polyketidic compound pyxipyrrolone C. All in all, this study sets the stage for the discovery of many more novel natural products from underexplored myxobacterial resources.

Discovery and Biosynthesis of Glycosylated Cycloheximide from a Millipede-Associated Actinomycete.

Chemical redundancy of microbial natural products (NPs) underscores the importance to exploit new resources of microorganisms. Insect-associated microbes are prolific but largely underexplored sources of diverse NPs. Herein, we discovered the new compound α-l-rhamnosyl-actiphenol (1) from a millipede-associated Streptomyces sp. ML6, which is the first glycosylated cycloheximide-class natural product. Interestingly, bioinformatics analysis of the ML6 genome revealed that the biosynthesis of 1 involves a cooperation between two gene clusters (chx and rml) located distantly on the genome of ML6. We also carried out in vitro enzymatic glycosylation of cycloheximide using an exotic promiscuous glycosyltransferase BsGT-1, which resulted in the production of an additional cycloheximide glycoside cycloheximide 7-O-ß-d-glucoside (5). Although the antifungal and cytotoxic activities of the new compounds 1 and 5 were attenuated relative to those of cycloheximide, our work not only enriches the chemical repertoire of the cycloheximide family but also provides new insights into the structure-activity relationship optimization and ecological roles of cycloheximide.

Retrospective Clinical Study on Integrated Chinese and Western Medicine in Treatment of Limited-Stage Small Cell Lung Cancer.

OBJECTIVE: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival (PFS) and overall survival (OS) of limited-stage small cell lung cancer (LS-SCLC) patients after the first-line chemoradiotherapy. METHODS: The data of 67 LS-SCLC patients who received combined treatment of CM and Western medicine (WM) between January 2013 and May 2020 at the outpatient clinic of Guang'anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method (Kaplan-Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time. RESULTS: The median PFS in the CM and WM combination treatment group and the WM group were 19 months (95% CI: 12.357-25.643) vs. 9 months (95% CI: 5.957-12.043), HR=0.43 (95% CI: 0.27-0.69, P<0.001), respectively. The median OS in the CM and WM combination group and the WM group were 34 months (95% CI could not be calculated) vs. 18.63 months (95% CI: 16.425-20.835), HR=0.40 (95% CI: 0.24-0.66, P<0.001), respectively. Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months (P<0.001). CONCLUSION: The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone. (Registration No. ChiCTR2200056616).

[Correlation of sperm HDS with sperm DFI and morphology and its influence on in vitro fertilization in infertile males].

OBJECTIVE: To invest the correlation of sperm high DNA stainability (HDS) with sperm DNA fragmentation index (DFI) and sperm abnormalities and its influence on in vitro fertilization (IVF) in male infertility patients, and assess the clinical value of HDS. METHODS: Using flow cytometry-assisted sperm chromatin structure assay (SCSA), we examined sperm HDS and sperm DFI in 322 male infertility patients undergoing IVF due to female fallopian tube factors only. Based on sperm HDS, we divided the patients into five groups and compared the semen routine parameters, percentage of morphologically abnormal sperm (MAS), sperm DFI, rates of fertilization, cleavage and high-quality embryos, and pregnancy outcomes among different HDS groups. RESULTS: Among the 322 male infertility patients, 119 (36.96%) were found with a sperm HDS of 0 － <5%, 117 (36.34%) of 5% － <10%, 50 (15.53%) of 10% － <15%, 23 (7.14%) of 15% － <20%, and 13 (4.03%) of ≥20%. Sperm concentration, motility and progressive motility were decreased with the increase of sperm HDS, but with no statistically significant difference (P > 0.05), so were the rates of fertilization, high-quality embryos and pregnancy (P > 0.05). Sperm DFI and sperm abnormality were correlated positively with sperm HDS (r = 0.236, r = 0.203). The rate of early abortion was remarkably increased in those with sperm HDS greater than 10%. CONCLUSION: Sperm HDS may be a risk indicator of sperm DFI and sperm abnormality, and can be used as a predictive indicator of early abortion in IVF.

Computed tomography-guided radiofrequency ablation of cervical intervertebral discs for the treatment of refractory cervicogenic headache: A retrospective chart review.

OBJECTIVE: To evaluate the feasibility and efficacy of computed tomography (CT)-guided radiofrequency ablation (RFA) of cervical intervertebral discs for the treatment of discogenic cervicogenic headache (CEH). BACKGROUND: Some patients with CEH experience no obvious therapeutic effect after conventional therapy, particularly patients with refractory CEH originating from abnormal cervical intervertebral discs. Treatment for this type of CEH remains poorly characterized. METHODS: Using a single intervention arm, pretest/posttest design, we retrospectively analyzed the data of patients who underwent CT-guided RFA of cervical intervertebral discs for CEH at the Pain Medicine Center of Zhejiang Provincial People's Hospital from January 2017 to April 2021. If conservative treatment failed in patients with discogenic CEH, we classified the patients as having refractory CEH and performed RFA of cervical intervertebral discs. We used a numeric rating scale (NRS) to assess pain intensity for 6 months. We also compared therapeutic outcome of patients with different characteristics. RESULTS: A total of 44 patients who underwent CT-guided RFA of cervical intervertebral discs were enrolled and 41 of them were analyzed in the present study. The preoperative median (25th, 75th) NRS score was 4 (4, 5), and it was significantly reduced to 1 (0, 4) 6 months after RFA (p < 0.001). The number of patients with ≥50% of their pain relieved after 6 months was 28 of 41 (68%). No serious treatment-related complications occurred in this study. Compared with single-level RFA, multi-level RFA shows greater effects on pain intensity reduction (p = 0.032) and pain relief rate (p = 0.047) of patients. CONCLUSION: In patients who have discogenic CEH, CT-guided RFA of the cervical intervertebral discs appears to be a promising treatment with no serious complications.

[Correlation of sperm DNA fragmentation index and high DNA stainability with teratospermia severity and the patient's age: A study of 1 393 infertile males].

OBJECTIVE: To investigate the correlation of the severity of teratospermia and the age of the patient with sperm DNA fragmentation index (DFI) and high DNA stainability (HDS) in male infertility patients. METHODS: We collected semen samples from 1 393 infertile males from July to December 2021. Based on the WHO Laboratory Manual for the Examination and Processing of Human Semen (5th Ed), we performed sperm morphology analysis, examined perm DFI and HDS by flow cytometry, and analyzed the impacts of the severity of teratospermia and the age of the patients on sperm DFI and HDS. RESULTS: Among the 1 393 male infertility patients, 124 (8.90%) were found with extremely severe, 214 (15.36%) with severe, 235 (16.87%) with moderate, 163 (11.70%) with mild teratospermia, and 657 (47.16%) with morphologically normal sperm (MNS), with statistically significant differences in sperm DFI and HDS among the five groups, and 822 (59.00%) were aged <35 years, 306 (21.97%) 35－<40 years, 223 (16.01%) 40－<45 years and 42 (3.02%) ≥45 years, with statistically significant differences in sperm DFI and HDS among different age groups (P < 0.05). Sperm DFI and HDS were correlated negatively with the percentage of MNS (P > 0.05), but positively with the age of the patients (P < 0.05). CONCLUSION: Increased severity of teratospermia and age of the patient can increase sperm DFI and HDS, and sperm nuclear chromatin integrity and maturity are important indicators of male fertility.

A Pitfall in Prenatal Ultrasonic Detection of Submucous Cleft Palate.

OBJECTIVE: We present a case with prenatal diagnosis of submucous cleft palate (SMCP) which was described using 2- and 3-dimensional (3D) ultrasonography in utero. CASE REPORT: A 25-year-old pregnant woman was referred to our department for fetal ultrasound screening. After the detection of cardiac and spinal malformations of fetal, further detailed examination detected SMCP, which showed a gap within the hard palate on axial transversal view with the soft palate visible on sagittal view. The imaging of a defective hard palate in prenatal 3D ultrasonography is similar to that in postmortem 3D computed tomography reconstruction. CONCLUSION: A gap within the hard palate and verification of the visibility of the soft palate should be key points in the prenatal diagnosis of SMCP. Three-dimensional ultrasonic imaging is helpful for displaying the shape and extent of the bony defect in SMCP.

The characteristics and related factors of insomnia among postoperative patients with gastric cancer: a cross-sectional survey.

PURPOSE: This study aims to explore the characteristics and related factors of insomnia of patients after operation for gastric cancer. METHODS: A cross-sectional survey was carried out and finally 115 patients with insomnia after operation for gastric cancer were included. The general information, gastric cancer-related information, sleep quality, and other symptoms were investigated. RESULTS: ① The Pittsburgh sleep quality index score of most insomnia patients after gastric cancer surgery was 11-15 points, and the sleep quality rating was "poor". ② The sleep quality of patients with insomnia after surgery for gastric cancer is related to the number of chemotherapy cycles, fatigue, and depression. ③ The probability of reduced sleep quality with the number of chemotherapy cycles >6 is 3.640 times that of ≤6. The probability of reduced sleep quality during moderate to severe fatigue was 4.390 times that of patients with no or mild fatigue. CONCLUSION: Attention to related factors may be associated with improvement of sleep quality in patients with gastric cancer after surgery.

Combining NMR-Based Metabolic Profiling and Genome Mining for the Accelerated Discovery of Archangiumide, an Allenic Macrolide from the Myxobacterium Archangium violaceum SDU8.

An unprecedented 19-membered allenic macrolide archangiumide (1) was discovered from the myxobacterium Archangium violaceum SDU8 by integrating NMR-based metabolic profiling and genome mining. Its biosynthesis pathway was proposed based on the architectural analysis of the encoding trans-AT PKS genes and validated by isotope labeling. The methodology of combing 2D NMR-based metabolic profiling and bioinformatics-aided structure prediction, as exemplified by this study, is anticipated to improve discovery efficiency of a broader range of microbial "dark matter".

A Novel Strategy to Fabricate Cation-Cross-linked Graphene Oxide Membrane with High Aqueous Stability and High Separation Performance.

Graphene oxide (GO) membranes have shown enormous promise in desalination and molecular/ionic sieving. However, the instability of GO membranes in aqueous solutions seriously hinders their practical applications. Herein, we report a novel and simple strategy to fabricate stable GO membranes in water-based environments through the insertion of various metal cations from metal foils (e.g., copper (Cu), iron (Fe), nickel (Ni), and zinc (Zn) foils) and natural deposition. Based on the cation-π, coordination, and electrostatic interaction between metal cations and GO nanosheets, the aqueous stability and mechanical strength of the membranes are significantly improved. The permeation rates for acetone, toluene, and p-xylene molecules across the GO membrane cross-linked by copper ions with a deposition time of 24 h are 0.966, 0.074, and 0.100 mol m-2 h-1, respectively. Moreover, this membrane displays excellent separation performance, and the separation factor of K+/Mg2+ is up to 68.8 in mono-/multivalent metal cation sieving, which indicate the effective molecular/ionic sieving performance. Meanwhile, the ionic sieving of the GO membrane cross-linked by copper ions has excellent repeatability and long-term stability. The versatility of this natural deposition strategy to fabricate GO membranes cross-linked by metal cations is investigated by using Fe foil, Zn foil, and Ni foil as well as other porous substrates such as polyvinylidene fluoride (PVDF), polyethersulfone (PES), and nylon membranes and filter paper. This fabrication strategy also enables low-cost preparation of large-area GO membranes. Therefore, GO membranes cross-linked by metal cations and prepared by this simple metal cation incorporation strategy have large potential application for molecular/ionic sieving in various solution systems.