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In recent decades, many reports have been published on the composition and function of the tumor microenvironment (TME), among which cancer-associated fibroblasts (CAFs) have received much attention. CAFs have different degrees of heterogeneity in terms of their origin, phenotype, and function and can be divided into different subpopulations. These subgroups may play different roles in the occurrence and development of tumors. In addition, CAFs are closely associated with tumor immunity and have been found to regulate immune cell activity and to suppress the tumor immune response. In this review, we systematize the heterogeneity and characteristics of CAFs, discuss how specific CAF subgroups contribute to cancer progression by inducing an immunosuppressive microenvironment, and finally, we examine the future clinical applications of CAF subgroups. [ABSTRACT FROM AUTHOR]

Previous studies provide empirical evidence for the connection between air pollution and tourism. However, many of them take the nexus as a linear one. It remains unexplored whether any thresholds are required for the nexus to materialize. This study systematically investigates whether PM2.5 concentrations–an essential indicator of air pollution–affect tourism in China at various tourism development levels. We analyze 284 Chinese cities from 2008 to 2018 using the Unconditional Quantile Regression method. Our statistical results reveal that air pollution positively influences tourism (regarding tourist visits and tourism revenue) in areas with low tourism development levels. However, a complex correlation between air pollution and tourism emerges when tourism development has reached a certain level. The correlation is initially negative, then positive, and finally disappears. But, the overall correlation remains negative. The effects of the interaction between air pollution and tourism resources on tourism are inverted U-shaped, implying that tourism resources can mitigate the negative effects of air pollution on tourism only when tourism development has reached a certain level. Based on the above findings, the associated policy implications are discussed. [ABSTRACT FROM AUTHOR]

In this study, Na-attapulgite was explored as an excipient to prepare domperidone sustained-release tablets and test them in accordance with United States Pharmacopoeia requirements. Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) were employed to explore the compatibility between Na-attapulgite and domperidone. The XRD and DSC show no interaction between the drug and Na-attapulgite. The FTIR spectrum indicates a shift in the absorption of N-H in the drug molecule, which can be explained by the hydrogen bonding interaction between the N-H in the DOM molecule and the -OH on the surface of Na-ATP. The diameter, hardness, friability and drug content of the tablets were measured, and they all met the relevant requirements of the United States Pharmacopoeia. In addition, the tablets with Na-attapulgite as excipient exhibit a better release performance within the release time of 12 h. These results demonstrate that the domperidone sustained-release tablets have been successfully prepared by using Na-attapulgite as an excipient. The doping of Na-ATP in domperidone sustained-release tablets improves the cytocompatibility. Moreover, with the increase of Na-ATP content, cells proliferate remarkably and cell activity is significantly enhanced. [ABSTRACT FROM AUTHOR]

The meiotic G2/M1 transition is mostly regulated by posttranslational modifications, however, the cross-talk between different posttranslational modifications is not well-understood, especially in spermatocytes. Sumoylation has emerged as a critical regulatory event in several developmental processes, including reproduction. In mouse oocytes, inhibition of sumoylation caused various meiotic defects and led to aneuploidy. However, the role of sumoylation in male reproduction has only begun to be elucidated. Given the important role of several SUMO targets (including kinases) in meiosis, in this study, the role of sumoylation was addressed by monitoring the G2/M1 transition in pachytene spermatocytes in vitro upon inhibition of sumoylation. Furthermore, to better understand the cross-talk between sumoylation and phosphorylation, the activity of several kinases implicated in meiotic progression was also assessed upon down-regulation of sumoylation. The results of the analysis demonstrate that inhibition of sumoylation with ginkgolic acid (GA) arrests the G2/M1 transition in mouse spermatocytes preventing chromosome condensation and disassembling of the synaptonemal complex. Our results revealed that the activity of PLK1 and the Aurora kinases increased during the G2/M1 meiotic transition, but was negatively regulated by the inhibition of sumoylation. In the same experiment, the activity of c-Abl, the ERKs, and AKT were not affected or increased after GA treatment. Both the AURKs and PLK1 appear to be “at the right place, at the right time” to at least, in part, explain the meiotic arrest obtained in the spermatocyte culture. [ABSTRACT FROM AUTHOR]

Sumoylation (a covalent modification by Small Ubiquitin-like Modifiers or SUMO proteins) has been implicated in the regulation of various cellular events including cell cycle progression. We have recently identified CDK1, a master regulator of mitosis and meiosis, as a SUMO target both in vivo and in vitro, supporting growing evidence concerning a close cross talk between sumoylation and phosphorylation during cell cycle progression. However, any data regarding the effect of sumoylation upon CDK1 activity have been missing. In this study, we performed a series of in vitro experiments to inhibit sumoylation by three different means (ginkgolic acid, physiological levels of oxidative stress, and using an siRNA approach) and assessed the changes in CDK1 activity using specific antibodies and a kinase assay. We have also tested for an interaction between SUMO and active and/or inactive CDK1 isoforms in addition to having assessed the status of CDK1-interacting sumoylated proteins upon inhibition of sumoylation. Our data suggest that inhibition of sumoylation increases the activity of CDK1 probably through changes in sumoylated status and/or the ability of specific proteins to bind CDK1 and inhibit its activity. [ABSTRACT FROM AUTHOR]

In this study, DNA arrays have been employed to monitor gene expression patterns in testis of mice exposed to tobacco smoke for 24 weeks and compared to control animals. The results of the analysis revealed significant changes in expression of several genes that may have a role in spermatogenesis. Cdk14 was chosen for further characterization because of a suggested role in the testis and in regulation of Wnt signaling. RT-PCR analysis confirmed down regulation of Cdk14 in mice exposed to cigarette smoke (CS). Cdk14 is expressed in all testicular cells; spermatogonia- and Sertoli-derived cell lines treated with cigarette smoke extract (CSE) in vitro showed down-regulation of CDK14 mRNA and protein levels as well as down-regulation of β-catenin levels. CS-induced down-regulation of CDK14 mRNA and protein levels was also observed in several lung epithelium-derived cell lines including primary normal human bronchial epithelial cells (NHBE), suggesting that the effect is not restricted to the testis. Similar to testicular cells, CS-induced down-regulation of CDK14 in lung cells correlated with decreased levels of β-catenin, a finding suggesting impaired Wnt signaling. In the lungs, CDK14 was localized to the alveolar and bronchial epithelium. [ABSTRACT FROM AUTHOR]

Coatings are of great significance for irons and steels in regards to the harsh marine environment. Graphene oxides (GO) have been considered as an ideal filler material of epoxy coating. However, the undesired dispersion in the epoxy together with easy agglomeration and stacking remain great problems for practical application of GO composited epoxy coatings. A method that can effectively solve both self-aggregation and poor dispersion of GO is highly desired. Herein, we present a high dispersion strategy of graphene oxides in epoxy by co-decoration of nano-SiO2 and silane coupling agent. The co-decorated GO filled epoxy coating exhibits high anti-corrosion performance, including high electrochemical impedance, high self-corrosive potential, low self-corrosive current, and superior electrochemical impedance stability for ten days to Q235 carbon steel. This work displays new possibilities for designing novel coating materials with high performance toward practical marine anti-corrosion applications. [ABSTRACT FROM AUTHOR]

A practical protocol for the synthesis of ketones by Pd‐catalyzed cross‐coupling of phenol derivatives with nitroalkanes followed by a Nef‐type reaction has been developed. The readily available nitroalkanes served as alkyl nucleophiles under basic conditions to couple with easy‐to‐handle phenol derivatives derived from naturally abundant phenols. The avoidance of using organometallics and organic halides makes this protocol more sustainable. The reaction was compatible with various functional groups, including nitro, cyano, acetyl, aldehyde, halide, and ester groups. Furthermore, the successful application of our method in drug synthesis exemplified its synthetic potential in pharmaceutical sciences. Preliminary mechanistic investigations strongly suggested the possible involvement of α‐aryl‐substituted nitroalkane intermediates. [ABSTRACT FROM AUTHOR]

A diverse set of SUMO target proteins has been identified. Therefore, there is a growing interest in studying sumoylation and SUMO interactions in cells. When the sumoylation of a protein or a SUMO interaction is suspected, a standard co-immunoprecipitation analysis using anti-SUMO and anti-target protein antibody is usually performed as a first step. However, the identification of endogenous sumoylated proteins is challenging because of the activity of isopeptidases, and often only a small fraction of a target protein is sumoylated at a given time. Here, we briefly summarize several important steps to ensure a successful co-immunoprecipitation analysis to detect possible sumoylation. [ABSTRACT FROM AUTHOR]

To address the ever‐increasing need for higher speed and density of information storage, recent developments in ultrafast optical switching have focused on deterministic control of magnetic properties of materials using femtosecond circularly polarized optical pulses. However, a monolithic high‐speed optical helicity‐dependent switching at room temperature has remained elusive. In recent years, ultra‐thin flat optical structures, known as metasurfaces, have been developed that offer a versatile way to manipulate electromagnetic fields using subwavelength spatial resolution. Here, a monolithic multilayer nanostructure capable of achieving optical helicity‐dependent switching in arbitrary geometries using femtosecond meta‐circularly polarized optical pulses is theoretically described and experimentally demonstrated at room temperature. The proposed monolithic meta‐magnetic platform provides a practical route to reform the current data memory, storage, and information processing technologies in integrated opto‐magnetic systems, holding great promise for cutting‐edge applications in information, spintronics, sensing, and memory storage devices. [ABSTRACT FROM AUTHOR]

Yes-Associated Protein (YAP) and Transcriptional Co-activator with PDZ-binding Motif (TAZ) have both emerged as important drivers of cancer progression and metastasis. YAP and TAZ are often upregulated or nuclear localized in aggressive human cancers. There is abundant experimental evidence demonstrating that YAP or TAZ activation promotes cancer formation, tumor progression, and metastasis. In this review we summarize the evidence linking YAP/TAZ activation to metastasis, and discuss the roles of YAP and TAZ during each step of the metastatic cascade. Collectively, this evidence strongly suggests that inappropriate YAP or TAZ activity plays a causal role in cancer, and that targeting aberrant YAP/TAZ activation is a promising strategy for the treatment of metastatic disease. To this end, we also discuss several potential strategies for inhibiting YAP/TAZ activation in cancer and the challenges each strategy poses. [ABSTRACT FROM AUTHOR]

This study utilizes high-resolution population grid data from 2004 to 2018 to assess the extent of urban polycentricity in 284 Chinese prefecture-level cities. A new method for measuring urban polycentricity is devised using the Clauset-Newman-Moore grey modularity maximization algorithm. Additionally, the Spatial Durbin Model is applied to investigate the effect of urban polycentricity on the mean and spatial variation of PM 2.5 concentrations. Our statistical results show that the increased distance between urban centers and the increased size disparity between the large and small centers effectively reduces air pollution within the city. On the other hand, in cities with a strong clustering of urban centers and significant size disparity between main and sub-centers, the polycentric urban structure cannot help reduce air pollution but merely shift it to other urban centers within the city. Hence, interpreting the severity of urban air pollution solely on the basis of the citywide average of air pollution may be insufficient. It is necessary to consider the possible relocation of air-polluting activities associated with polycentric urban structures. Policymakers should take into account the potential spatial inequality of air pollution driven by urban polycentricity. [Display omitted] • New algorithm for measuring urban polycentricity (distance dispersion and size disparity of urban centers). • New approach for measuring "urban" air pollution. • Suggested method for addressing the spatial spillover effects of air pollution in data analysis. • Polycentric urban structures reduce air pollution but exacerbate the uneven distribution of air pollution. • Benefits and potential drawbacks of urban polycentricity in mitigating air pollution. [ABSTRACT FROM AUTHOR]

3D hosts are promising to extend the cycle life of lithium metal anodes but have rarely been implemented with lean electrolytes thus impacting the practical cell energy density. To overcome this challenge, a 3D host that is lightweight and easy to fabricate with optimum pore size that enables full utilization of its pore volume, essential for lean electrolyte operations, is reported. The host is fabricated by casting a VGCF (vapor‐grown carbon fiber)‐based slurry loaded with a sparingly soluble rubidium nitrate salt as an additive. The network of fibers generates uniform pores of ≈3 µm in diameter with a porosity of 80%, while the nitrate additive enhances lithiophilicity. This 3D host delivers an average coulombic efficiency of 99.36% at 1 mA cm−2 and 1 mAh cm−2 for over 860 cycles in half‐cell tests. Full cells containing an anode with 1.35‐fold excess lithium paired with LiNi0.8Mn0.1Co0.1O2 (NMC811) cathodes exhibit capacity retention of 80% over 176 cycles at C/2 under a lean electrolyte condition of 3 g Ah−1. This work provides a facile and scalable method to advance 3D lithium hosts closer to practical lithium‐metal batteries. [ABSTRACT FROM AUTHOR]

Stochastic resonance can detect weak periodic signals from strong background noise without loss of signal energy. However, the classical bistable stochastic resonance has the inherent output saturation defect, which limits the detection performance of system. And it is more difficult to detect signal with strong background noise. In this article, we constructed improved unsaturated bistable stochastic resonance to overcome this shortcoming. The improved bistable potential function makes the output signal more easily oscillate in two potential wells. To improve the stability and the accuracy of the method, we further propose an adaptive improved unsaturated bistable stochastic resonance (AIUBSR) by constructing a synthetic index (SI). The SI combines zero‐crossing ratio and structural correlation coefficient, which can measure the periodicity of output signal and the accuracy of detective frequency at the same time. Theoretical analysis and numerical simulations show that the proposed AIUBSR can have good weak signal detection capability in strong background noise. [ABSTRACT FROM AUTHOR]

Background: The advent of immune checkpoint inhibitors (ICIs) therapy has resulted in significant survival benefits in patients with non-small-cell lung cancer (NSCLC) without increasing toxicity. However, the utilisation of immunotherapy for small-cell lung cancer (SCLC) remains unclear, with a scarcity of systematic comparisons of therapeutic effects and safety of immunotherapy in these two major lung cancer subtypes. Herein, we aimed to provide a comprehensive landscape of immunotherapy and systematically review its specific efficacy and safety in advanced lung cancer, accounting for histological types.Methods: We identified studies assessing immunotherapy for lung cancer with predefined endpoints, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAE), from PubMed, Embase, Medline, and Cochrane library. A random-effects or fixed-effect model was adopted according to different settings.Results: Overall, 38 trials with 20,173 patients with lung cancer were included in this study. ICI therapy resulted in a significantly prolonged survival in both patients with NSCLC and SCLC when compared with chemotherapy (hazard ratio [HR] = 0.74; 95% confidence interval [CI], 0.70-0.79] and [HR = 0.82; 95% CI, 0.75-0.90], respectively). The magnitude of disease control and survival benefits appeared superior with ICI plus standard of care (SOC) when compared with SOC alone. OS and PFS advantages were observed only when immunotherapy was employed as the first-line treatment in patients with SCLC.Conclusion: ICI therapy is a promising therapeutic option in patients with NSCLC and SCLC. ICI plus SOC can be recommended as the optimal first-line treatment for patients with SCLC, and double-target ICIs combined with SOC are recommended in patients with NSCLC as both the first and subsequent lines of treatment. Additionally, non-first-line immunotherapy is not recommended in patients with SCLC. [ABSTRACT FROM AUTHOR]

The COVID-19 has become a global pandemic that dramatically impacted human lives and economic activities. Due to the high risk of getting affected in high-density population areas and the implementation of national emergency measures under the COVID-19 pandemic, both travel and transportation among cities become difficult for engineers and equipment. Consequently, the costly physical commissioning of a new manufacturing system is greatly hindered. As an emerging technology, digital twins can achieve semi-physical simulation to avoid the vast cost of physical commissioning of the manufacturing system. Therefore, this paper proposes a digital twins-based remote semi-physical commissioning (DT-RSPC) approach for open architecture flow-type smart manufacturing systems. A digital twin system is developed to enable the remote semi-physical commissioning. The proposed approach is validated through a case study of digital twins-based remote semi-physical commissioning of a smartphone assembly line. The results showed that combining the open architecture design paradigm with the proposed digital twins-based approach makes the commissioning of a new flow-type smart manufacturing system more sustainable. [ABSTRACT FROM AUTHOR]

Digital sensor arrays based on ring oscillators are used to monitor the temperature of Field Programmable Gate Array (FPGA) chips, but traditional sensor structures using binary frequency counters consume excessive hardware logic resources. This paper proposed a compact temperature sensor array that used low-decoding-complexity linear feedback shift registers (LFSR) as a frequency counter to efficiently count the ring oscillator frequency. We implemented an experimental system on a Spartan-6 FPGA, and the logic resource consumption of the entire system was 927 Look-Up-Tables (LUTs) with an overhead of only 10%. The single sampling time was approximately 40 μs. The proposed temperature sensor array has good temperature sensing capabilities, and the measured error is ± 0.9 °C (3 σ). [ABSTRACT FROM AUTHOR]

In the article, a new thermal resistance measurement method for GaN high electron mobility transistor (HEMTs) is proposed based on temperature sensitive electrical parameter (TSEP) with the use of MOS switches to connect the drain–source at the beginning of the measurement processes. Compared with traditional methods, the connection of the source and drain reduces the delay caused by the matching circuit. In our experiments, we measured a GaN HEMT at 48 V with a power consumption of 5.28 W. The delay time was less than 2~μs , and the thermal resistance was 9.85 °C/W. We also measured the thermal resistance at the same current-different voltages and different voltages-same power. The results show that the thermal resistance of the GaN HEMT increases with the increase of the power and voltage. Furthermore, the results have been verified by infrared (IR) and simulation methods. Compared with Raman thermography and IR, this method can conveniently measure the thermal resistance of GaN HEMTs without breaking the package, and the temperature accuracy was ±2 °C or better. And the thermal resistance information of each layer of structure, such as the chip-solder-carrier, can be extracted by structural function method to improve the thermal design of GaN HEMTs. [ABSTRACT FROM AUTHOR]

This paper proposes an electrical method for estimation of the vertical junction temperature of silicon carbide bipolar junction transistors (SiC BJTs). This measurement method is based on measurement of the base–collector voltage (VBC) drop at a low current (VBC(low)) during the turn-off process. This voltage shows both good sensitivity and linearity with respect to temperature. The traditional temperature-sensitive electrical parameter VBE(low) (i.e., the base-emitter voltage at a low current) and an infrared camera are used to compare the characteristics of VBC(low). The results show that use of VBC(low) provides more accurate junction temperature and thermal resistance measurement results, which can then be used to extract the vertical junction temperature of the SiC BJT under test. [ABSTRACT FROM AUTHOR]

A low-cost practical technology is urgently needed to minimize cadmium (Cd) pollution in rice in many parts of the world. In the present study, we elucidated the effects and mechanisms of four alkaline compound materials via field experiments in southern China. The results indicated that these two alkaline Si–rich compound materials (AF-SC, alkaline fertilizer compounded with Si–Ca mineral powder; AF-SS, AF compounded with Si–Se mineral powder) could achieve multi-objective gains by simultaneously reducing grain Cd, increasing yield and improving soil quality at a lower cost. The grain Cd content was decreased by an average of about 75% in two field sites, which even ensured safe grain production in areas with medium Cd pollution. The rice yield was increased by a range of 6.7%–21.0% for different varieties and sites. Moreover, the materials abated soil acidification with the increase of 0.36–0.62 pH units, increased the contents of available P and available Si, subsequently reducing available Cd content in soils. Structural equation model and regression analysis showed that the alkaline environment provided by the alkaline components in compound materials effectively inhibited the formation of Fe/Mn plaques on the root surface, reducing the uptake of Cd from the environment. In addition, the decrease in grain Cd was also attributed to the inhibition of Cd translocation from root to stem, mainly caused by the increase of available Si. These findings reveal that the base application of such alkaline Si–rich compound materials is a viable solution for the remediation of Cd-polluted paddy fields in south China. [Display omitted] • Si–rich materials enable effective and low-cost remediation of Cd-polluted soils. • They also have advantages of increasing yield and improving soil quality. • Decrease of available Cd and Fe/Mn plaque caused by raised pH inhibited Cd uptake. • Increased available Si inhibited Cd transport from root to stem, further reducing grain Cd accumulation. [ABSTRACT FROM AUTHOR]

[Display omitted] • SmVO 4 can be dispersed on the surface of H-Mordenite support in the form of nanoparticles with the scale is 17 ∼ 23 nm. The modified nanoscale particles have better photocatalytic properties. • The SmVO 4 /HMOR (70.99 %) has an good degradation activity for rhodamine B in comparison with pure SmVO 4 (33.12 %), The rate constant k (0.50 h−1) was boosted to 2.9 times as much as SmVO 4 monomer (0.17 h−1) under visible light irradiation for 2.5 h. When 3.7 wt% H 2 O 2 (30 %) was added into the photocatalytic system, the photocatalytic degradation rate could reach 93.26 % within 30 min. • The method without any templates and surfactants, realizing the high dispersion of SmVO 4 through simple methods. • HMOR has been proved acted as electron acceptor to accelerate the transfer efficiency of photoelectrons, inhibiting the recombination of charges and improving the photocatalytic efficiency. • The co-action of adsorption and photocatalytic oxidation has important effect on the photodegradation of RhB at ambient temperature. Photocatalytic application is obstructed by the self-aggregation and low specific surface area of nano materials. High dispersion of SmVO 4 nanoparticles on HMOR zeolite (HMOR) were prepared by template-free method. Not only the agglomeration of nanomaterials is restrained, but also the combination of low-cost zeolite and semiconductor to prepare high-performance photocatalyst is conducive to the rational utilization of resources. Sm(NO 3) 3 ·6H 2 O and NH 4 VO 3 were used as precursors, and mixed with HMOR to prepare SmVO 4 /HMOR by precipitation method.. This method does not use any templates and surfactants, realizing the high dispersion of SmVO 4 nanoparticles on the surface of HMOR with the particle size are 17 ∼ 23 nm. The photocatalytic activity of SmVO 4 /HMOR was tested by degradation of rhodamine B (RhB). Compared with the monomer of SmVO 4 , the degradation rate of 29.81 wt% SmVO 4 /HMOR was increased from 33.12 % to 70.99 % under visible light irradiation for 2.5 h. The rate constant k (0.50 h−1) was boosted to 2.9 times as much as SmVO 4 monomer (0.17 h−1). When 3.7 wt% H 2 O 2 (30 %) was added into the photocatalytic system, the photocatalytic degradation rate could reach 93.26 % within 30 min. The synergistic effect of SmVO 4 and HMOR is critical on the improvement of the removal efficiency of RhB. SmVO 4 in the form of nanoparticles on the HMOR support has high photocatalytic activity. In addition, HMOR acted as electron acceptor to accelerate the transfer efficiency of photoelectrons, inhibiting the recombination of charges and improve the photocatalytic efficiency. [ABSTRACT FROM AUTHOR]

This paper presents the synthesis of Ag@PDA/M-ATP/PCN photocatalysts for the removal of heavy metals and organic dyes via the in-situ reduction method. According to the photoluminescence (PL) spectra, time-resolved fluorescence spectra, UV–vis absorption spectra, transient photocurrent response spectra, and the EIS results, the composite of M-ATP, PDA coating, and single-atom Ag doping further promotes the separation of the photogenerated carriers, reduces the band-gap, improves the photocatalytic performance, and promotes the synergistic effect of charge separation and transfer to enhance the photocatalytic performance. The catalysts prepared by this composite strategy exhibit high charge separation efficiency, higher catalytic efficiency, and better stability than the conventional single-method modified polymeric carbon nitride catalysts. • The doping of polymeric carbon nitride with M-ATP increases the specific surface area of the carrier. • Polydopamine (PDA) is used for the reduction of AgNPs, avoiding the use of chemical reducing and stabilizing agents. • M-ATP/PCN have enhanced stability and improved catalytic activity. [ABSTRACT FROM AUTHOR]

Abstract: The Fanconi anaemia (FA) FANCG protein is an integral component of the FA nuclear core complex that is required for monoubiquitylation of FANCD2. FANCG is also part of another protein complex termed D1-D2-G-X3 that contains FANCD2 and the homologous recombination repair proteins BRCA2 (FANCD1) and XRCC3. Formation of the D1-D2-G-X3 complex is mediated by serine-7 phosphorylation of FANCG and occurs independently of the FA core complex and FANCD2 monoubiquitylation. FANCG contains seven tetratricopeptide repeat (TPR) motifs that mediate protein–protein interactions and here we show that mutation of several of the TPR motifs at a conserved consensus residue ablates the in vivo binding activity of FANCG. Expression of mutated TPR1, TPR2, TPR5 and TPR6 in Chinese hamster fancg mutant NM3 fails to functionally complement its hypersensitivities to mitomycin C (MMC) and phleomycin and fails to restore FANCD2 monoubiquitylation. Using co-immunoprecipitation analysis, we demonstrate that these TPR-mutated FANCG proteins fail to interact with BRCA2, XRCC3, FANCA or FANCF. The interactions of other proteins in the D1-D2-G-X3 complex are also absent, including the interaction of BRCA2 with both the monoubiquitylated (FANCD2-L) and non-ubiquitylated (FANCD2-S) isoforms of FANCD2. Interestingly, a mutation of TPR7 (R563E), that complements the MMC and phleomycin hypersensitivity of human FA-G EUFA316 cells, fails to complement NM3, despite the mutated FANCG protein co-precipitating with FANCA, BRCA2 and XRCC3. Whilst interaction of TPR7-mutated FANCG with FANCF does appear to be reduced in NM3, FANCD2 is monoubiquitylated suggesting that sub-optimal interactions of FANCG in the core complex and the D1-D2-G-X3 complex are responsible for the observed MMC- and phleomycin-hypersensitivity, rather than a defect in FANCD2 monoubiquitylation. Our data demonstrate that FANCG functions as a mediator of protein–protein interactions and is vital for the assembly of multi-protein complexes including the FA core complex and the D1-D2-G-X3 complex. [Copyright &y& Elsevier]