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.

Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Initial Results of a Phase III Trial.

OBJECTIVE: To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia (MRF). BACKGROUND DATA: nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower-risk LARC patients with uninvolved MRF. METHODS: Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to nCT group with 4 cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported the results of secondary end points: histopathologic response, surgical events, and toxicity. RESULTS: Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathologic complete response rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm ( P =0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm ( P =0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P =0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P =0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a nonsurgical approach. Similar results were observed in subgroup analysis. CONCLUSIONS: nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.

Outcomes of physeal-sparing posterior cruciate ligament reconstruction for adolescents with an open physis.

PURPOSE: The posterior cruciate ligament (PCL) rupture rarely occurs, especially in skeletally immature adolescents, and poses a dilemma in appropriately managing the open physis with its vast growth potential. However, although many epiphyseal-protecting techniques for anterior cruciate ligament (ACL) reconstruction have been reported, a similar problem in PCL reconstruction has received scant attention and needs more relevant research. So, this study aims to evaluate the short-term clinical and imaging results of the arthroscopic physeal-sparing reconstruction program. METHOD: All the 13 patients we reviewed in this study have accepted the arthroscopic physeal-sparing PCL reconstruction from January 2019 to December 2022 in our Department of Orthopedics. Primary demographic data collected include gender (8 males and 5 females), age (11-15 years, average 13.3 years), follow-up period (15-35 months, average 25.2 months), injury mechanism (nine non-contact injuries and four contact injuries), and days following injury (1-10 days, average 5.3 days). The assessment of clinical outcomes included pre- and postoperative physical examination, knee functional scores, and imaging data. RESULT: All patients in this study were followed up with an average 25.2-month (range 15-35 months) follow-up period. All the cases preoperatively had a positive posterior drawer test and turned negative at the final follow-up. The average ROM improved from 103.6° ± 11.4° to 132.6° ± 3.6° at the last follow-up (p < 0.05). The VAS score decreased from 5.8 ± 1.6 to 0.9 ± 0.5 (p < 0.05); the average KT-1000 healthy-side to affected-side difference decreased from 11.3 ± 1.6 to1.8 ± 0.5 mm. The comparison of all the knee functional scores (IKDC, Tegner scores, and Lysholm) at preoperative and last follow-up showed a significant difference (p < 0.05). None of the cases had operation-related complications, and all recovered to sports well. CONCLUSION: The arthroscopic physeal-sparing posterior cruciate ligament reconstruction is a dependable and recommended treatment for posterior cruciate ligament rupture in adolescents with open physis, showing a striking improvement in knee function without growth arrest and angular deformity of the affected limb in the short-term follow-up.

A new mitochondria-targeted fluorescent probe for exogenous and endogenous superoxide anion imaging in living cells and pneumonia tissue.

As a precursor of all reactive oxygen species (ROS), superoxide anions play an important role in organisms. However, excessive superoxide anions can cause various diseases. Thus, it is highly urgent to develop efficient tools for in situ superoxide anion detection. In this work, a novel boric acid-based, mitochondria-targeted fluorescent probe Mito-YX for superoxide anion detection was designed by regulating its intramolecular charge transfer (ICT) effect. The probe exhibited turn-on fluorescence enhancement within 4 min of reaction with the superoxide anion. In addition, Mito-YX also exhibited high selectivity and a low detection limit down to 0.24 µM with good mitochondrial targeting characteristics, which provided a necessary basis for in vivo detection of superoxide anions. What is more, Mito-YX was successfully applied for the in situ monitoring of superoxide anions in living MCF-7 cells, RAW 264.7 cells and a mouse model of lung inflammation stimulated by LPS. This work provided an important and promising tool for rapid in situ diagnosis and research of the progression of pneumonia.

Structural transition and interconversion between the 2D self-assembled structures of pentacene.

The 2D self-assemblies and structural transitions of pentacene on a Cd(0001) surface have been investigated with low temperature scanning tunneling microscopy (STM). With increasing coverage, pentacene molecules show a structural evolution from the initial disordered gas-like phase through the porous network phase to the herringbone phase, and finally to the brickwall phase at the full monolayer. In particular, orientational frustration and cooperative rotation of pentacene molecules take place in the herringbone phase. Furthermore, successive STM scanning leads to structural interconversions between the porous network phase, herringbone phase, and brickwall phase, indicating the metastability of the 2D assembled structures of pentacene on Cd(0001). These structural transitions and interconversion can be attributed to the interplay between the repulsive electrostatic forces resulting from the charge transfer from the substrate to pentacene and the attractive effects originating from dipole-dipole interactions and intermolecular van der Waals forces.

Spontaneous chiral resolution of pentahelicene molecules on Cd(0001).

Chiral resolution is of fundamental importance to conglomerate or racemate crystallization. Here we demonstrate that the spontaneous chiral resolution of pentahelicene racemates occurred in the monolayer domains. When deposited on a Cd(0001) surface, pentahelicene molecules crystallize into a commensurate (6 × 6)R0° structure built mainly from homochiral trimers. Spontaneous chirality separation takes place in the form of opposite mirror domains, where 2D enantiomorphism is not expressed by the oblique adlattice, but by the supramolecular chirality of the pentahelicene trimers. Furthermore, annealing the sample or extreme close-packing lead to the presence of lattice handedness through the formation of a porous network structure or an edge-on phase. These results provide valuable insight for 2D conglomerate crystallization and stereochemical recognition.

Perspective on optimal strategies of building cluster expansion models for configurationally disordered materials.

Cluster expansion (CE) provides a general framework for first-principles-based theoretical modeling of multicomponent materials with configurational disorder, which has achieved remarkable success in the theoretical study of a variety of material properties and systems of different nature. On the other hand, there remains a lack of consensus regarding what is the optimal strategy to build CE models efficiently that can deliver accurate and robust prediction for both ground state energetic properties and statistical thermodynamic properties at finite temperature. There have been continuous efforts to develop more effective approaches to CE model building, which are further promoted by recent tremendous interest of applying machine learning techniques in materials research. In this Perspective, we present a critical review of recent methodological developments in building CE models for multicomponent materials, with particular focus on different approaches and strategies proposed to address cluster selection and training data generation. We comment on the pros and cons of different methods in a general formalism and present some personal views on the prospects of theoretical approaches to multicomponent materials.

Relationship of HER2 Alteration and Microsatellite Instability Status in Colorectal Adenocarcinoma.

BACKGROUND: The impact of HER2 somatic mutations in colorectal carcinoma (CRC) has not been well studied and its relationship with microsatellite instability-high (MSI-H) is yet to be fully elucidated. MATERIALS AND METHODS: From February 2017 to February 2020, the data of patients with CRC who underwent next-generation sequencing and had detailed record of clinicopathological information were investigated. HER2 alteration and its relationship with MSI-H were analyzed. RESULTS: Among 731 patients who underwent sequencing, 55 patients (7.5%) had HER2 alteration, including 29 (4.0%) with HER2 somatic mutations, 24 (3.3%) with HER2 gene amplification, and 2 patients (0.2%) with both HER2 mutations and amplification. R678Q was the most common mutated kinase domain, and no HER2 kinase domain in-frame insertions/deletions were found in HER2 mutated cases. MSI-H was found in 5.2% of our cohort and 36.8% of MSI-H patients had HER2 mutation. For HER2 mutated cases, 48.3% were MSI-H, whereas none of the HER2 amplification cases were MSI-H. MSI-H patients with HER2 mutation had significantly worse median progression-free survival for programmed death-1 (PD-1) antibody than those without HER2 alteration (p = .036). CONCLUSION: High MSI-H rate was found in HER2 mutated cases, but no MSI-H was found in HER2 amplification cases. MSI-H patients with HER2 mutated had worse progression-free survival for PD-1 antibody than those without. IMPLICATIONS FOR PRACTICE: This study highlights the high microsatellite instability-high (MSI-H) rate in HER2 mutated cases but no MSI-H in HER2 amplification cases. Moreover MSI-H patients with HER2 mutated had worse progression-free survival for programmed death-1 antibody than those without. Further research to explore the internal relationship between HER2 alteration and MSI-H is needed.

Effect of oxygen concentrations and branched-chain amino acids on the growth and development of sub-seafloor fungus, Schizophyllum commune 20R-7-F01.

Fungi have been reported to be the dominant eukaryotic group in anoxic sub-seafloor sediments, but how fungi subsist in the anoxic sub-marine sedimental environment is rarely understood. Our previous study demonstrated that the fungus, Schizophyllum commune 20R-7-F01 isolated from a ~2 km sediment below the seafloor, can grow and produce primordia in the complete absence of oxygen with enhanced production of branched-chain amino acids (BCAAs), but the primordia cannot be developed into fruit bodies without oxygen. Here, we present the individual and synergistic effects of oxygen and BCAAs on the fruit-body development of this strain. It was found that the fungus required a minimum oxygen concentration of 0.5% pO2 to generate primordia and 1% pO2 to convert primordia into mature fruit body. However, if BCAAs (20 mM) were added to the medium, the primordium could be developed into fruit body at a lower oxygen concentration up to 0.5% pO2 where genes fst4 and c2h2 playing an important role in compensating oxygen deficiency. Moreover, under hypoxic conditions, the fungus showed an increase in mitochondrial number and initiation of auto-phagocytosis. These findings suggest that the fruit-body formation of S. commune may have multiple mechanisms, including energy and amino acid metabolism in response to oxygen concentrations.

Homochiral to heterochiral transition in a pentahelicene monolayer on Bi(111).

We report the nucleation and two dimensional (2D) crystallization of the helical aromatic hydrocarbon pentahelicene ([5]H) on the semimetallic Bi(111) surface studied via low-temperature scanning tunneling microscopy. Individual homochiral dimers and heterochiral trimers appear on the substrate at a low coverage. With an increase in the coverage, a chiral phase transition takes place from the 2D conglomerate of [5]H dimers to the 2D racemate of [5]H trimers. The heterochiral [5]H trimers reveal a wavy arrangement due to the swing of 5[H] trimer rows after every second or third trimers. The swing mechanism of the trimer rows can be attributed to the steric repulsion between the adjacent trimers with same handedness.

Comparison of Immune Microenvironment Between Colon and Liver Metastatic Tissue in Colon Cancer Patients with Liver Metastasis.

BACKGROUND: Liver metastasis is an indicator of unfavorable responses to immunotherapy in colorectal cancer patients. However, the difference of immune microenvironment between primary tumors and liver metastases has not been well understood. PATIENTS AND METHODS: Fifty-four colon cancer with liver metastasis patients who received resection of both primary and metastasis lesions have been analyzed. The immune score is based on the density of infiltrating immune cells (CD3+ cell, CD8+ cell, CD11b+ cell, CD11c+ cell, and CD33+ cell) in the center and margin of the tumor. The expression of immune markers between the primary tumor and hepatic metastases was analyzed using Wilcoxon's signed rank test. RESULTS: All the five markers had higher expression in tumor margins than center tumor in both primary tumor and hepatic metastases lesions. The expression of CD11c and CD11b had no difference between metastatic lesions and primary tumor. In tumor margins, except CD11b, all the other 4 markers expressed significantly higher in hepatic metastases than in primary tumor. Intra-tumor, CD3 had higher expression in primary tumor than in hepatic metastases, while CD33 had higher expression in hepatic metastases than in primary tumor. CD8+ CD3+ cells of the total CD8+ cell population in primary tumor was significantly higher than in hepatic metastases (36.42% vs. 24.88%, p = 0.0069). CONCLUSIONS: The immune microenvironment between primary tumor and hepatic metastasis is different. More immunosuppressing cells in liver may partially explain why immunotherapy in colon cancer is less effective with liver metastatic disease.

Clinical and Cancer-Related Predictors for Venous Thromboembolism in Cancer Patients Presenting to the Emergency Department.

BACKGROUND: The accurate detection of cancer-associated venous thromboembolism (VTE) can avoid unnecessary diagnostic imaging or laboratory tests. OBJECTIVE: We sought to determine clinical and cancer-related risk factors of VTE that can be used as predictors for oncology patients presenting to the emergency department (ED) with suspected VTE. METHODS: We retrospectively analyzed all consecutive patients who presented with suspicion of VTE to The University of Texas MD Anderson Cancer Center ED between January 1, 2009, and January 1, 2013. Logistic regression models were used to identify risk factors that were associated with VTE. The ability of these factors to predict VTE was externally validated using a second cohort of patients who presented to King Hussein Cancer Center ED between January 1, 2009, and January 1, 2016. RESULTS: Cancer-related covariates associated with the occurrence of VTE were high-risk cancer type (odds ratio [OR] 3.64 [95% confidence interval {CI} 2.37-5.60], p < 0.001), presentation within 6 months of the cancer diagnosis (OR 1.92 [95% CI 1.62-2.28], p < 0.001), active cancer (OR 1.35 [95% CI 1.10-1.65], p = 0.003), advanced stage (OR 1.40 [95% CI 1.01-1.94], p = 0.044), and the presence of brain metastasis (OR 1.73 [95% CI 1.32-2.27], p < 0.001). When combined, these factors along with other clinical factors showed high prediction performance for VTE in the external validation cohort. CONCLUSIONS: Cancer risk group, presentation within 6 months of cancer diagnosis, active and advanced cancer, and the presence of brain metastases along with other related clinical factors can be used to predict VTE in patients with cancer presenting to the ED.

Hexagonal Monolayer Ice without Shared Edges.

When adsorbed on solids, water molecules are usually arranged into a honeycomb hydrogen-bond network. Here we report the discovery of a novel monolayer ice built exclusively from water hexamers but without shared edges, distinct from all conventional ice phases. Water grown on graphite crystalizes into a robust monolayer ice after annealing, attaining an exceedingly high density of 0.134 Å^{-2}. Unlike chemisorbed ice on metal surfaces, the ice monolayer can translate and rotate on graphite terraces and grow across steps, confirming its two-dimensional nature. First-principles calculations identify the monolayer ice structure as a robust self-assembly of closely packed water hexamers without edge sharing, whose stability is maintained by maximizing the number of intralayer hydrogen bonds on inert surfaces.

Chirality switching of the self-assembled CuPc domains induced by electric field.

Chiral switching of the self-assembled domains of CuPc molecules on the Cd(0001) surface has been investigated by means of a low temperature scanning tunneling microscopy (STM). With the coverage increasing, the CuPc molecules show the structural evolutions from an initial gas-like state to a network phase, a square phase, and finally to a compact phase at full monolayer. In the network and square phases, the achiral CuPc molecules reveal both the point chirality and chiral domains. In particular, the chirality of network domain can be switched from one enantiomer to another driven by the electric filed from a STM tip, which can also lead to the lattice rotation of network phase. These results demonstrate that (i) there is strong interaction between the CuPc molecules and STM tip; (ii) the adsorbed CuPc molecules carry considerable net charge or polarizability due to the charge transfer; (iii) the network phase has a low barrier for the interconversion between right- and left-handed domains. Our findings are significant for the understanding and control of the domain's chirality in the self-assembled structures.

Identification, cloning and expression analysis of an alpha-CGTase produced by stain Y112.

Cyclodextrin glycosyltransferase (CGTase) is an enzyme able to convert starch and other substrates into cyclodextrins (CDs). A marine strain Y112 producing α-CGTase was identified as Bacillus agaradhaerens Y112 by physiological and biochemical characterization, and 16S rDNA analysis. The gene coding for α-CGTase was cloned, sequenced and expressed in Escherichia coli BL21 (DE3) cells. Recombinant α-CGTase was purified in one-step chromatographic separation and its purity evaluated by SDS-PAGE, showing the presence of one band with a molecular mass of about 92 kDa. Additionally, enzymatic capability was analyzed by measuring the starch conversion, and resulted in about 45% of CDs obtained after 6 h of cyclodextrin reaction. Of these CDs, mainly α-CD was produced (70% of the total CDs yield), suggesting the potential of this CGTase for industrial applications.

Off-Center Rotation of CuPc Molecular Rotor on a Bi(111) Surface and the Chiral Feature.

Molecular rotors with an off-center axis and the chiral feature of achiral CuPc molecules on a semi-metallic Bi(111) surface have been investigated by means of a scanning tunneling microscopy (STM) at liquid nitrogen (LN2) temperature. The rotation axis of each CuPc molecular rotor is located at the end of a phthalocyanine group. As molecular coverage increases, the CuPc molecules are self-assembled into various nanoclusters and finally into two-dimensional (2D) domains, in which each CuPc molecule exhibits an apparent chiral feature. Such chiral features of the CuPc molecules can be attributed to the combined effect of asymmetric charge transfer between the CuPc and Bi(111) substrate, and the intermolecular van der Waals interactions.

Warm temperatures induce transgenerational epigenetic release of RNA silencing by inhibiting siRNA biogenesis in Arabidopsis.

Owing to their sessile nature, plants have evolved sophisticated genetic and epigenetic regulatory systems to respond quickly and reversibly to daily and seasonal temperature changes. However, our knowledge of how plants sense and respond to warming ambient temperatures is rather limited. Here we show that an increase in growth temperature from 22 °C to 30 °C effectively inhibited transgene-induced posttranscriptional gene silencing (PTGS) in Arabidopsis. Interestingly, warmth-induced PTGS release exhibited transgenerational epigenetic inheritance. We discovered that the warmth-induced PTGS release occurred during a critical step that leads to the formation of double-stranded RNA (dsRNA) for producing small interfering RNAs (siRNAs). Deep sequencing of small RNAs and RNA blot analysis indicated that the 22-30 °C increase resulted in a significant reduction in the abundance of many trans-acting siRNAs that require dsRNA for biogenesis. We discovered that the temperature increase reduced the protein abundance of SUPPRESSOR OF GENE SILENCING 3, as a consequence, attenuating the formation of stable dsRNAs required for siRNA biogenesis. Importantly, SUPPRESSOR OF GENE SILENCING 3 overexpression released the warmth-triggered inhibition of siRNA biogenesis and reduced the transgenerational epigenetic memory. Thus, our study reveals a previously undescribed association between warming temperatures, an epigenetic system, and siRNA biogenesis.

Research Advances in Bacteria-based Microrobot.

The concept of bacteria-based microrobot has been well recognized. It has shown great advantages and potentials for the early diagnosis and early treatment of malignant tumor and in reducing chemotherapy toxicities. In this article we review the concept,structure,and potential clinical applications of bacteria-based microrobot.

Absolute configuration and chiral self-assembly of rubrene on Bi(111).

We investigated the chiral self-assembly of rubrene molecules on a semi-metallic Bi(111) surface using low-temperature scanning tunneling microscopy. The absolute configuration of isolated rubrene enantiomers was identified from high-resolution images. Two types of homochiral domains of rubrene monomers and hexamers were observed, respectively. For rubrene monomers, chiral separation was spontaneous with each chiral monomer appearing in their respective domain. For rubrene hexamers, two levels of organization chirality were recorded: one is six heterochiral rubrene molecules arranged alternatively in a rubrene hexamer; and the other is a homochiral arrangement of individual hexamers. After annealing at 350 K, a large area of supramolecular self-assembled L- and R-type triangular heterochiral hexamers was obtained at the narrow terrace of Bi(111). Moreover, a molecular chiral inversion from the L-(R-) type to the R-(L-) type occurs during the formation of the hexamer domain structure and can be attributed to the enhanced intermolecular interactions governed by the intensive intermolecular extrusion at the narrow terrace.

MAE-FMD: multi-agent evolutionary method for functional module detection in protein-protein interaction networks.

BACKGROUND: Studies of functional modules in a Protein-Protein Interaction (PPI) network contribute greatly to the understanding of biological mechanisms. With the development of computing science, computational approaches have played an important role in detecting functional modules. RESULTS: We present a new approach using multi-agent evolution for detection of functional modules in PPI networks. The proposed approach consists of two stages: the solution construction for agents in a population and the evolutionary process of computational agents in a lattice environment, where each agent corresponds to a candidate solution to the detection problem of functional modules in a PPI network. First, the approach utilizes a connection-based encoding scheme to model an agent, and employs a random-walk behavior merged topological characteristics with functional information to construct a solution. Next, it applies several evolutionary operators, i.e., competition, crossover, and mutation, to realize information exchange among agents as well as solution evolution. Systematic experiments have been conducted on three benchmark testing sets of yeast networks. Experimental results show that the approach is more effective compared to several other existing algorithms. CONCLUSIONS: The algorithm has the characteristics of outstanding recall, F-measure, sensitivity and accuracy while keeping other competitive performances, so it can be applied to the biological study which requires high accuracy.