TM-Score predicts immunotherapy efficacy and improves the performance of the machine learning prognostic model in gastric cancer.

Immunotherapy is becoming increasingly important, but the overall response rate is relatively low in the treatment of gastric cancer (GC). The application of tumor mutational burden (TMB) in predicting immunotherapy efficacy in GC patients is limited and controversial, emphasizing the importance of optimizing TMB-based patient selection. By combining TMB and major histocompatibility complex (MHC) related hub genes, we established a novel TM-Score. This score showed superior performance for immunotherapeutic selection (AUC = 0.808) compared to TMB, MSI status, and EBV status. Additionally, it predicted the prognosis of GC patients. Subsequently, a machine learning model adjusted by the TM-Score further improved the accuracy of survival prediction (AUC > 0.8). Meanwhile, we found that GC patients with low TM-Score had a higher mutation frequency, higher expression of HLA genes and immune checkpoint genes, and higher infiltration of CD8+ T cells, CD4+ helper T cells, and M1 macrophages. This suggests that TM-Score is significantly associated with tumor immunogenicity and tumor immune environment. Notably, based on the RNA-seq and scRNA-seq, it was found that AKAP5, a key component gene of TM-Score, is involved in anti-tumor immunity by promoting the infiltration of CD4+ T cells, NK cells, and myeloid cells. Additionally, siAKAP5 significantly reduced MHC-II mRNA expression in the GC cell line. In addition, our immunohistochemistry assays confirmed a positive correlation between AKAP5 and human leukocyte antigen (HLA) expression. Furthermore, AKAP5 levels were higher in patients with longer survival and those who responded to immunotherapy in GC, indicating its potential value in predicting prognosis and immunotherapy outcomes. In conclusion, TM-Score, as an optimization of TMB, is a more precise biomarker for predicting the immunotherapy efficacy of the GC population. Additionally, AKAP5 shows promise as a therapeutic target for GC.

Fe-Zn alloy, a new biodegradable material capable of reducing ROS and inhibiting oxidative stress.

Fe-based biodegradable materials have attracted significant attention due to their exceptional mechanical properties and favorable biocompatibility. Currently, research on Fe-based materials mainly focuses on regulating the degradation rate. However, excessive release of Fe ions during material degradation will induce the generation of reactive oxygen species (ROS), leading to oxidative stress and ferroptosis. Therefore, the control of ROS release and the improvement of biocompatibility for Fe-based materials are very important. In this study, new Fe-Zn alloys were prepared by electrodeposition with the intention of using Zn as an antioxidant to reduce oxidative damage during alloy degradation. Initially, the impact of three potential degradation ions (Fe2+, Fe3+, Zn2+) from the Fe-Zn alloy on human endothelial cell (EC) activity and migration ability was investigated. Subsequently, cell adhesion, cell activity, ROS production and DNA damage were assessed at various locations surrounding the alloy. Finally, the influence of different concentrations of Zn2+ in the medium on cell viability and ROS production was evaluated. High levels of ROS exhibited evident toxic effects on ECs and promoted DNA damage. As an antioxidant, Zn2+ effectively reduced ROS production around Fe and improved the cell viability on its surface at a concentration of 0.04 mmol/l. These findings demonstrate that Fe-Zn alloy can attenuate the ROS generated from Fe degradation thereby enhancing cytocompatibility.

The enhancement of mechanical properties and uniform degradation of electrodeposited Fe-Zn alloys by multilayered design for biodegradable stent applications.

Pure Fe is a potential biodegradable stent material due to its better biocompatibility and mechanical properties, but its degradation rate needs to be improved. Alloying with Zn to form Fe-Zn alloy is anticipated to meet the degradation rate requirements while retaining the iron's inherent properties. Therefore, Fe-Zn alloys with monolayered and multilayered structures were prepared by electrodeposition. The alloys' composition, microstructure, mechanical properties, in vitro degradation and biocompatibility were assessed. Results showed that the Zn content ranged from 2.1 wt% to 11.6 wt%. After annealing at 450°C, all the alloys consisted of α(Fe) solid solution and Zn-rich B2 ordered coherent phase, except for the alloy with 11.6 wt% Zn content, in which a Fe3Zn10 phase appeared. The layered structure consisted of alternating columnar-grain and nano-grain layers, which compensated for the intrinsic brittleness of electrodeposited metals and improved the galvanic effect of the alloy, thus increasing the strength and plasticity and changing the corrosion from localized to uniform while augmenting the corrosion rate. The yield strength of the multilayered alloy exceeded 350 MPa, its elongation was more than 20%, and its corrosion rate obtained by immersion test in Hank's solution reached 0.367 mm·y-1. Fe-Zn alloys with lower Zn content had good cytocompatibility with the human umbilical vein endothelial cells and good blood compatibility. The above results verified that the multilayered Fe-Zn alloy prepared by electrodeposition presented enhanced mechanical properties, higher degradation rate, uniform degradation mechanism and good biocompatibility. It should be qualified for the application of biodegradable stents. STATEMENT OF SIGNIFICANCE: A potential biodegradable Fe-Zn alloy, which is difficult to be obtained by the metallurgical method, was prepared by electrodeposition to solve the low degradation rate of iron-based biomaterials. A multilayered microstructure design composed of alternating columnar-grain and nano-grain layers was achieved by changing the electrical parameters. The layered design compensated for the intrinsic poor plasticity of electrodeposited metals. It increased the galvanic effect of the alloy, thus augmenting the corrosion rate and changing the corrosion mode of the alloy from localized to uniform corrosion. The yield strength of multilayered alloy exceeded 350 MPa; its elongation was more than 20%. Moreover, the layered alloy had good cytocompatibility and blood compatibility. It indicates that the alloy is qualified for biodegradable stent application.

Effective oxygen metabolism-based prognostic signature for colorectal cancer.

Backgroud: Oxygen metabolism is an important factor affecting the development of tumors, but its roles and clinical value in Colorectal cancer are not clear. We developed an oxygen metabolism (OM) based prognostic risk model for colorectal cancer and explored the role of OM genes in cancer. Methods: Gene expression and clinical data obtained from The Cancer Genome Atlas, Clinical Proteomic Tumor Analysis Consortium databases were consider as discovery and validation cohort, respectively. The prognostic model based on differently expressed OM genes between tumor and GTEx normal colorectal tissues were constructed in discovery cohort and validated in validation cohort. The Cox proportional hazards analysis was used to test clinical independent. Upstream and downstream regulatory relationships and interaction molecules are used to clarify the roles of prognostic OM genes in colorectal cancer. Results: A total of 72 common differently expressed OM genes were detected in the discovery and validation set. A five-OM gene prognostic model including LRT2, ATP6V0E2, ODC1, SEL1L3 and VDR was established and validated. Risk score determined by the model was an independent prognostic according to routine clinical factors. Besides, the role of prognostic OM genes involves transcriptional regulation of MYC and STAT3, and downstream cell stress and inflammatory response pathways. Conclusions: We developed a five-OM gene prognostic model and study the unique roles of oxygen metabolism in of colorectal cancer.

APOBEC3B and CD274 as Combined Biomarkers for Predicting Response to Immunotherapy in Urothelial Carcinoma of the Bladder.

Immunotherapy has become a promising form of treatment for cancers. There is a need to predict response to immunotherapy accurately. In the UCSC Xena, pan-cancer analysis revealed a positive relationship between APOBEC3B (A3B) and tumor mutational burden (R = 0.28, P < 0.001) and microsatellite instability (R = 0.12, P < 0.05). Naturally, the A3B high expression group had higher tumor mutational burden and microsatellite instability than the low expression group. The bladder cancer (BLCA) cohort in The Cancer Genome Atlas (TCGA) revealed tumor mutational signatures of A3B high and low expression groups. Compared to the low expression group, the high expression group had a higher number of SNPs and mutations. Subsequently, A3B was profiled for immune cell infiltration and immune checkpoints in bladder cancer. The results showed that A3B was positively correlated with most immune cells. Compared with the A3B low expression group, the A3B high expression group had higher expression of immune checkpoints. A3B was positively correlated with CD274 (R = 0.12, P = 0.016). This indicated that the high expression of A3B may have a better response to immunotherapy. Furthermore, data from the IMvigor210 immunotherapy clinical trial was used to confirm the findings of this study. The combined survival analysis of A3B and CD274 showed that the group of patients with high expression of CD274 and A3B was found to have a significantly higher survival rate than the rest of the patient group (P < 0.047). The results demonstrated that A3B has a significant role in immunotherapy. Moreover, the combined biomarkers of A3B and CD274 were more effective in predicting response to immunotherapy in bladder urothelial carcinoma. The findings of this study provide valuable insights for precision medicine.

Biological applications of copper-containing materials.

Copper is an indispensable trace metal element in the human body, which is mainly absorbed in the stomach and small intestine and excreted into the bile. Copper is an important component and catalytic agent of many enzymes and proteins in the body, so it can influence human health through multiple mechanisms. Based on the biological functions and benefits of copper, an increasing number of researchers in the field of biomaterials have focused on developing novel copper-containing biomaterials, which exhibit unique properties in protecting the cardiovascular system, promoting bone fracture healing, and exerting antibacterial effects. Copper can also be used in promoting incisional wounds healing, killing cancer cells, Positron Emission Tomography (PET) imaging, radioimmunological tracing and radiotherapy of cancer. In the present review, the biological functions of copper in the human body are presented, along with an overview of recent progress in our understanding of the biological applications and development of copper-containing materials. Furthermore, this review also provides the prospective on the challenges of those novel biomaterials for future clinical applications.

Roles of sphingosine-1-phosphate signaling in cancer.

The potent pleiotropic lipid mediator sphingosine-1-phosphate (S1P) participates in numerous cellular processes, including angiogenesis and cell survival, proliferation, and migration. It is formed by one of two sphingosine kinases (SphKs), SphK1 and SphK2. These enzymes largely exert their various biological and pathophysiological actions through one of five G protein-coupled receptors (S1PR1-5), with receptor activation setting in motion various signaling cascades. Considerable evidence has been accumulated on S1P signaling and its pathogenic roles in diseases, as well as on novel modulators of S1P signaling, such as SphK inhibitors and S1P agonists and antagonists. S1P and ceramide, composed of sphingosine and a fatty acid, are reciprocal cell fate regulators, and S1P signaling plays essential roles in several diseases, including inflammation, cancer, and autoimmune disorders. Thus, targeting of S1P signaling may be one way to block the pathogenesis and may be a therapeutic target in these conditions. Increasingly strong evidence indicates a role for the S1P signaling pathway in the progression of cancer and its effects. In the present review, we discuss recent progress in our understanding of S1P and its related proteins in cancer progression. Also described is the therapeutic potential of S1P receptors and their downstream signaling cascades as targets for cancer treatment.

Determination of a potential antitumor quassinoid in rat plasma by UPLC-MS/MS and its application in a pharmacokinetic study.

A sensitive UPLC-MS/MS method was developed and validated for the determination of brusatol in rat plasma. Chromatographic separation was carried out on a C18 column using methanol and 10mM ammonium acetate containing 0.1% (v/v) formic acid (55:45, v/v). The lower limit of quantification (LLOQ) was 1.0 ng/mL for brusatol in plasma. The intra- and inter-day precision for the analyte ranged from 3.2% to 9.2% and 1.3% to 7.8%, and the accuracy was between 97.3% and 108.5%. The method was successfully applied in a pharmacokinetic study of brusatol following intravenous injection (0.5, 1.0, and 2.0mg/kg) of brusatol.

Paeoniflorin inhibits proliferation and invasion of breast cancer cells through suppressing Notch-1 signaling pathway.

Paeoniflorin (PF), one of the major active ingredients of Chinese peony, was reported to possess anti-tumor effect. However, the role of PF in breast cancer remains to be clarified. Therefore, in this context, the present study investigated the effects of PF on breast cancer cell proliferation and invasion, as well as the underlying mechanism. Our results found that PF suppressed the proliferation and invasion of breast cancer cells. We further demonstrated that PF down-regulated the expression of Notch-1; in addition, overexpression of Notch-1 reversed PF-inhibited proliferation and invasion, and knockdown of Notch-1 enhanced PF-inhibited proliferation and invasion in breast cancer cells. In conclusion, the present study suggests that PF inhibits proliferation and invasion of breast cancer cells through suppressing Notch-1 signaling pathway. Therefore, PF may represent a chemopreventive and/or therapeutic agent in the prevention of breast cancer.

(2-Hydroxypropyl)-ß-Cyclodextrin Is a New Angiogenic Molecule for Therapeutic Angiogenesis.

BACKGROUND: Peripheral artery disease (PAD), which is caused by atherosclerosis, results in progressive narrowing and occlusion of the peripheral arteries and inhibits blood flow to the lower extremities. Therapeutic angiogenesis is a promising strategy for treating ischemia caused by PAD. Nitric oxide (NO) has been shown to be a key mediator of angiogenesis. It has been demonstrated that ß-cyclodextrincan stimulate vessel growth in rabbit corneas. In this study, we assessed the mechanism of action and therapeutic potential of a new angiogenic molecule, (2-hydroxypropyl)-ß-cyclodextrin (2HP-ß-CD). METHODS AND RESULTS: 2HP-ß-CD significantly increased vascular endothelial growth factor A (VEGF-A) and platelet-derived growth factor BB (PDGF-BB) peptides in human umbilical vein endothelial cells (HUVECs) and also increased basic fibroblast growth factor (bFGF) peptide in human aortic smooth muscle cells (HASMCs). 2HP-ß-CD stimulated both proliferation and migration of HUVECs in an endothelial nitric oxide synthase (eNOS)/NO-dependent manner, whereas NO was found to be involved in proliferation, but not migration, of HASMCs. In a unilateral hindlimb ischemia model in mice, 2HP-ß-CD injections not only promoted blood flow recovery and increased microvessel densities in ischemic muscle, but also promoted coverage of the vessels with smooth muscle cells, thus stabilizing the vessels. Administration of 2HP-ß-CD increased the expression of several angiogenic factors, including VEGF-A, PDGF-BB and transforming growth factor beta-1 (TGF-ß1) in ischemic muscle. Injections of 2HP-ß-CD also stimulated protein kinase B and extracellular regulated protein kinases (ERK), leading to an increase in phosphorylation of eNOS in ischemic muscle. Treatment with the NOS inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), showed that stimulation of blood flow induced by 2HP-ß-CD was partially dependent on NO. CONCLUSIONS: Therapeutic angiogenesis by 2HP-ß-CD may be beneficial to patients with PAD.

MiR-217 Promotes Tumor Proliferation in Breast Cancer via Targeting DACH1.

OBJECTIVE: The expression of DACH1 was frequently lost in human breast cancer, which significantly correlated with poor prognosis. Herein, we aim to investigate its underlying mechanisms. METHODS: The expression of miR-217 was detected by Taqman PCR. The mRNA and protein level of DACH1 were investigated by real time PCR and western blot. The dual-luciferase reporter system was used to determine the direct interaction between miR-217 and DACH1. A series of gain&loss of function assays were performed to measure the affects of miR-217 on tumor proliferation and cell cycle distribution. RESULTS: Compared to that in normal breast samples, the expression of miR-217 was significantly upregulated in breast cancer tissues. High level of miR-217 was notably correlated with highly histological grade, the triple negative subtype and advanced tumor stage. Moreover, the expression of miR-217 was negatively correlated with the expression of DACH1. The results of dual-luciferase reporter assay demonstrated that miR-217 directly targets and inhibits the transcriptive activity of DACH1. In vitro, treatment with miR-217 mimics significantly suppressed the proliferation of MCF-7 cells, induced G1 phase arrest and inhibited the expression of cyclin D1; while these effects were significantly reversed by the restoration of DACH1. In MDA-MB-231 cells, treatment with miR-217 inhibitors enhanced the cellular proliferation, promoted cell cycle progression and upregulated the expression of cyclin D1, which were neutralized by the pre-treatment of siRNA-DACH1. In vivo, inhibition of miR-217 significantly suppressed the xenografts growth and downregulated the expression of cyclin D1. CONCLUSION: We found that miR-217 was commonly overexpressed in breast cancer, which could enhance tumor proliferation via promoting cell cycle progression. Moreover, the DACH1 (the cell fate determination factor) was identified as a novel target of miR-217. Our results proposed inhibiting miR-217 to be a potent therapeutic strategy for breast cancer.

Complex transcriptional regulation of citrate metabolism in Clostridium perfringens.

A Gram-positive, spore-forming bacterium, Clostridium perfringens, possesses genes for citrate metabolism, which might play an important role in the utilization of citrate as a sole carbon source. In this study, we identified a chromosomal citCDEFX-mae-citS operon in C. perfringens strain 13, which is transcribed on three mRNAs of different sizes. Expression of the cit operon was significantly induced when 5 mM extracellular citrate was added to the growth medium. Most interestingly, three regulatory systems were found to be involved in the regulation of the expression of cit genes: 1) the two upstream divergent genes citG and citI; 2) two different two-component regulatory systems, CitA/CitB (TCS6 consisted of CPE0531/CPE0532) and TCS5 (CPE0518/CPE0519); and 3) the global two-component VirR/VirS-VR-RNA regulatory system known to regulate various genes for toxins and degradative enzymes. Our results suggest that in C. perfringens the citrate metabolism might be strictly controlled by a complex regulatory system.

Transcriptional regulation of hemO encoding heme oxygenase in Clostridium perfringens.

A Gram-positive anaerobic pathogen, Clostridium perfringens, causes clostridial myonecrosis or gas gangrene in humans by producing numerous extracellular toxins and enzymes that act in concert to degrade host tissues. The ability of infectious bacteria to acquire sufficient iron during infection is essential for the pathogen to cause disease. In the C. perfringens strain 13 genome, a heme oxygenase gene homologue (CPE0214, hemO) was found and its role was examined. The purified recombinant HemO protein showed heme oxygenase activity that can convert heme to biliverdin. hemO transcription was induced in response to extracellular hemin in a dose-dependent manner. The global two-component VirR/VirS regulatory system and its secondary regulator VR-RNA had positive regulatory effects on the transcription of hemO. These data indicate that heme oxygenase may play important roles in iron acquisition and cellular metabolism, and that the VirR/VirS-VR-RNA system is also involved in the regulation of cellular iron homeostasis, which might be important for the survival of C. perfringens in a human host.

Genetic and biochemical analysis of a class C non-specific acid phosphatase (NSAP) of Clostridium perfringens.

Clostridium perfringens, a Gram-positive anaerobe, is a human pathogen that causes gas gangrene in muscle tissues. Its ability to grow and survive in the host is believed to be due to the production of numerous enzymes that enable the organism to obtain essential nutrients from the host. In this study, CPE0201, a putative acid phosphatase gene deduced by genome analysis, was shown to encode a non-specific acid phosphatase in C. perfringens. Multiple alignments of the amino acid sequence showed that CPE0201 shares two signature motifs that belong to a class C acid phosphatase family. Expression of CPE0201 was shown to be positively regulated by the global VirR/VirS-VR-RNA regulatory cascade at the transcriptional level. To determine the acid phosphatase activity of the CPE0201-encoded protein, cloning, expression, purification and several biochemical characterizations were carried out. The optimum pH for activity of the CPE0201 enzyme was 4.8, and its V(max) and K(m) were 3.08 nmol ml(-1) min(-1) and 2.84 mM, respectively, with p-nitrophenyl phosphate (PNPP) as substrate. A CPE0201 mutant did not grow in a minimal medium containing PNPP, while it showed normal growth when Na(2)HPO(4) was added to the medium. The enzyme appears to be associated with the surface of the cell, where it may function to acquire inorganic phosphate from organic phosphomonoesters in acidic conditions, which could play an important role in the survival and growth of C. perfringens in the host tissue.

Virulence gene regulation by the agr system in Clostridium perfringens.

A gram-positive anaerobic pathogen, Clostridium perfringens, causes clostridial myonecrosis or gas gangrene in humans by producing numerous extracellular toxins and enzymes that act in concert to degrade host tissue. The agr system is known to be important for the regulation of virulence genes in a quorum-sensing manner in Staphylococcus aureus. A homologue for S. aureus agrBD (agrBD(Sa)) was identified in the C. perfringens strain 13 genome, and the role of C. perfringens agrBD (agrBD(Cp)) was examined. The agrBD(Cp) knockout mutant did not express the theta-toxin gene, and transcription of the alpha- and kappa-toxin genes was also significantly decreased in the mutant strain. The mutant strain showed a recovery of toxin production after the addition of the culture supernatant of the wild-type strain, indicating that the agrBD(Cp) mutant lacks a signal molecule in the culture supernatant. An agr-virR double-knockout mutant was constructed to examine the role of the VirR/VirS two-component regulatory system, a key virulence regulator, in agrBD(Cp)-mediated regulation of toxin production. The double-mutant strain could not be stimulated for toxin production with the wild-type culture supernatant. These results indicate that the agrBD(Cp) system plays an important role in virulence regulation and also suggest that VirR/VirS is required for sensing of the extracellular signal and activation of toxin gene transcription in C. perfringens.

Measuring microelastic properties of stratum corneum.

We explore the compression moduli of a thin biological tissue through probe microscopy. The elastic modulus (E') of isolated stratum corneum is measured at varying depths through the use of an atomic force microscope (AFM) as well as a nano-indentor (Hysitron Triboscope). In addition, a nano-DMA is used to measure visco-elastic properties. Measurements on dry and hydrated stratum corneum show an order of magnitude difference in E' and the measured tandelta (E''/E') is seen to increase from approximately 0.1 to 0.25. In addition, extensive validation of the experiments is conducted with different indentation probes at different force ranges to reveal the effects of indentor geometry and indentation depth on the measured elastic modulus. The sensitivity of the measurements is tested with applying known treatments to stratum corneum and exploring their effects on biomechanical parameters.

[Effect of vascular endothelial growth factor antisense oligodeoxynucleotides on angiogenesis in lymphoma of nude mice].

BACKGROUND & OBJECTIVE: It has been reported that vascular endothelial growth factor (VEGF) plays an important role in progression of lymphoma, and lymphoma with high level of VEGF is likely to metastasise at early stage. This study was to explore effects of antisense oligodeoxynucleotides (ASODN) targeting VEGF on angiogenesis of lymphoma through in vitro, and in vivo experiments. METHODS: Human lymphoma cell line Namalwa cells were incubated with VEGF ASODN (final concentrations were 10, 20, and 30 micromol/L, respectively), or scrambled sequence for 24 h or 48 h. VEGF mRNA expression in treated cells was detected by reverse transcriptase-polymerase chain reaction (RT-PCR), and its protein expression was detected by SP immunohistochemistry. After incubation of 30 micromol/L of VEGF ASODN, 30 micromol/L of scrambled sequence, and PBS as negative control, Namalwa cells were injected into nude mice. Diameters of tumors in ASODN group (6 mice), scrambled sequence group (6 mice), and PBS group (4 mice) were measured, microvessel density (MVD) was detected via immunohistochemistry. RESULTS: Expression of VEGF mRNA in cells treated with 10, 20, and 30 micromol/L of ASODN were 1.28, 0.86, and 0.47, respectively; those of PBS-treated cells, and scrambled sequence-treated cells were 1.79, and 1.84. Positive rate of VEGF protein in ASODN-treated cells was significantly lower than those in scrambled sequence-treated cells, and PBS-treated cells (23.3% vs. 46.9%, and 47.8%, P<0.05). MVDs of ASODN group, scrambled sequence group, and PBS group were 12.26+/-0.78, 23.92+/-1.14, and 24.13+/-1.21, respectively. CONCLUSION: VEGF ASODN can down-regulate expression of VEGF, and suppress angiogenesis in lymphoma.

Relationship between apoptosis and E-cadherin expression in bronchial epithelium of smoking mouse.

To investigate whether apoptosis is associated with cell adhesion in bronchial epithelium, and whether it contributes to the kinetics of injury and repair of surface epithelia, this study was performed for E-cadherin expression by using immunohistochemistry technique and for apoptosis by TUNEL method. An animal model of smoking was used for this study. The results showed that epithelial cells with membrane anchored E-cadherin decreased remarkably at several time points during 6 months of exposure to smoke (P < 0.01) and then restored to normal level. This fluctuation was associated exclusively with the alteration in number of apoptotic cells (P < 0.01). There was no significant difference in activation of nuclear transcription factor NF-kappa B among groups (P > 0.05). All these suggested that apoptosis is associated with E-cadherin expression in bronchial epithelium of smoking mouse.

Measurement of mobility of adsorbed colloids by lateral force microscopy.

The surface mobility of colloidal latex particles adsorbed on mica was measured by moving the particles with an AFM tip in the lateral force microscopy mode. The same particle was repeatedly scanned while the normal force was gradually increased, until the particle was displaced from its location on the substrate. The lateral (friction) force curve obtained for that scan was then used to determine the force needed to displace the particle. The data accumulated for approximately 100 particles indicate a wide distribution in the lateral force required. However, the data show that the mean lateral force is proportional to the particle diameter, with the effect of electrostatic interactions on the mobility of adsorbed particles seen to be weak. These results are consistent with classical theories of friction in macroscopic systems.