The current status and global trends of clinical trials related to robotic surgery: a bibliometric and visualized study.

Conducting clinical trials can evaluate the effectiveness and safety of surgical robots. To promote the advancement of academic robotic programs in surgery, this study captures the development trend and research hotspots of clinical trials related to surgical robots by bibliometric analysis. Bibliometrix package in R software was used to analyze the publication year, authors, countries, institutes, and journals. The visualization maps of keywords were formed using VOSviewer. The keywords with the strongest citation bursts and the institutional collaboration map were created by CiteSpace. Urology dominates with 31.3% of publications and the controlled clinical trials in urology and orthopedic accounted for the highest proportion, reaching 73%. North America, the USA, and Seoul National University lead in productivity. The most productive country, region and institution are North America, USA and Seoul National University, respectively. The trend of collaboration is regional instead of international. Keyword and burst keyword analysis revealed a primary focus in clinical research on robotic surgery: evaluating process improvements, comparing robotic and traditional surgery, and assessing feasibility. Long-term clinical trials assess surgical robots not only intraoperative performance but also postoperative complications and overall surgical outcomes. The development in the field is unbalanced between regions and countries. To promote multi-center clinical trials, governments can streamline review procedures and establish international consensus review standards, while academic institutions can form academic alliances. Also, the study offers recommendations for the development of academic robotic programs and regional collaboration units in robotic surgery, which may provide researchers with a strong reference for future research.

Effect of Cosolvent on the Vesicle Formation Pathways under Solvent Exchange Process: A Dissipative Particle Dynamics Simulation.

The effective control over the vesicle formation pathways is vital for tuning its function. Recently, a liquid-liquid phase-separated intermediate (LLPS) is observed before a vesicular structure during the solvent exchange self-assembly of block copolymers. Though the understanding of polymer structures and chemical compositions on the competition between LLPS and micellization has made some progress, little is known about the role of cosolvent on it. In this study, the influence of cosolvent on the vesicle formation pathways is investigated by using dissipative particle dynamics. The results show that the range of water fraction within which the LLPS is favored will be highly dependent on the affinity difference of cosolvent to water and to polymer repeat units. The change of the cosolvent-water interaction and the water fraction impact the distribution of cosolvent in the polymer domain, the miscibility between the components in the system as well as the chain conformations, which finally induce different self-assembly behaviors. Our findings would be helpful for understanding the LLPS and controlling the morphologies of diblock polymers in solutions for further applications.

A DOPO-Based Compound Containing Aminophenyl Silicone Oil for Reducing Fire Hazards of Polycarbonate.

A novel P/N/Si-containing flame retardant (marked as DASO) was synthesized through an Atherton-Todd reaction between 9,10-dihydro-9-oxa-10-phospha-phenanthrene-10-oxide and aminophenyl silicone oil, and further used for reducing fire hazards of polycarbonate (PC). The chemical structure of DASO was verified via FTIR, 1H, and 31P NMR. Upon the incorporation of 2 wt% DASO, the FRPC composite achieved a high limiting oxygen index (LOI) of 32.2% and a desired UL-94 V-0 rating. In this case, the peak heat release rate (PHRR) and total smoke production (TSP) were reduced by 26% and 44% as compared with the pure PC, respectively. The improved fire safety contributed to the flame retardant roles of DASO in both the condensed phase and gas phase. The presence of DASO promoted the formation of dense and highly graphited char layer in the condensed phase, and released non-combustible gases and phosphorus-containing radicals in the gas phase. Furthermore, the FRPC composites displayed comparable elongation at break but a slightly reduced tensile and impact strength.

A Nitrogen-Rich DOPO-Based Derivate for Increasing Fire Resistance of Epoxy Resin with Comparable Transparency.

To endow synergistically epoxy resin (EP) with excellent fire resistance and high optical transparency, a nitrogen-rich DOPO-based derivate (named as FATP) was synthesized and incorporated into EP. It showed that the incorporation of the FATP reduced the fire hazard of the EP, as demonstrated by the fact that the EP/4% FATP blends gained a UL-94 V-0 rating and an LOI value of 35%, with the lowest values of the THR (86.7 MJ/m2), the PHRR (1059.3 kW/m2), and the TSP (89.6 MJ/m2). The presence of the FATP also reduced the thermal stability and the crosslinking density whilst improving the curing reaction and the storage modulus of the EP/FATP blends. The TG-FTIR spectra showed that •HPO/•PO free radicals and some nonflammable gases (HN3 and NH3) were produced during the pyrolysis, and the characterization (SEM, Raman spectroscopy, and XPS) of char residues confirmed that the FATP facilitated the formation of continuous and compact carbon layers of greater graphitization degree. It was thus concluded that the FATP played the flame-retardant roles in both the gas and condensed phases. Furthermore, the FREPs kept almost identical transparency as the pristine EP, and mechanical properties were also slightly enhanced. The FREPs presented in this work show promising applications in the fields of advanced optical technology.

Linc-UROD stabilizes ENO1 and PKM to strengthen glycolysis, proliferation and migration of pancreatic cancer cells.

Pancreatic cancer (PC) is a fatal malignancy, threatening human health in worldwide. Long non-coding RNAs (lncRNAs) have been acknowledged to be essential regulators in various biological processes of human cancers. However, the role of some novel lncRNAs in PC remain to be explored. In this study, we focused on the function and molecular mechanism of a novel lncRNA linc-UROD (also named TCONS_00002016 or XLOC_000166) in PC. The expression of linc-UROD was found to be upregulated in PC cells. The results of loss-of-function assays demonstrated that linc-UROD knockdown suppressed cell proliferation and migration, induced cell cycle G0/G1 arrest, and accelerated apoptosis of PC cells. Through mechanistic experiments, we found that IGF2BP3 stabilized linc-UROD through METTL3-mediated m6A modification. In addition, linc-UROD enhances the stability of ENO1 and PKM through interacting with them to inhibit ubiquitination. Detection on glucose consumption, pyruvate kinase activity and lactate production indicated that linc-UROD accelerated glycolysis of PC cells through PKM/ENO1-mediated pathway. To summarize, linc-UROD stabilized by IGF2BP3/METTL3 contributes to glycolysis and malignant phenotype of PC cells by stabilizing ENO1 and PKM. The findings suggest that linc-UROD may be a novel therapeutic target for PC patients.

CD155 Cooperates with PD-1/PD-L1 to Promote Proliferation of Esophageal Squamous Cancer Cells via PI3K/Akt and MAPK Signaling Pathways.

BACKGROUND: Esophageal cancer is still a leading cause of death among all tumors in males, with unsatisfactory responses to novel immunotherapies such as anti-PD-1 agents. Herein, we explored the role of CD155 in esophageal squamous cell cancer (ESCA) and its underlying molecular mechanisms. METHODS: Publicly available datasets were used for differential gene expression and immune infiltration analyses, and their correlation with patient survival. A total of 322 ESCA and 161 paracancer samples were collected and evaluated by performing immunohistochemistry and the H score was obtained by performing semiquantitative analysis. In vitro transfection of ESCA cell lines with lentivirus vectors targeting CD155 was performed to knockdown the protein. These cells were analyzed by conducting RNA sequencing, and the effects of CD155 knockdown on cell cycle and apoptosis were verified with flow cytometry and Western blotting. In addition, in vivo experiments using these engineered cell lines were performed to determine the role of CD155 in tumor formation. A small interfering RNA-mediated knockdown of Nectin3 was used to determine whether it phenocopied the profile of CD155 knockdown. RESULTS: CD155 is highly expressed in ESCA tissues and is positively associated with PD1, PDL1, CD4, IL2RA, and S100A9 expression. Furthermore, CD155 knockdown inhibited ESCA cells' proliferation by impairing the cell cycle and inducing cell apoptosis. Bioinformatics analysis of the gene expression profile of these engineered cells showed that CD155 mainly contributed to the regulation of PI3K/Akt and MAPK signals. The downregulation of Nectin3 expression phenocopied the profile of CD155 knockdown. DISCUSSION: CD155 may cooperate with PD-1/PD-L1 to support ESCA proliferation in ways other than regulating its underlying immune mechanisms. Indeed, CD155 downregulation can impair ESCA cell pro-cancerous behavior via the inhibition of the PI3K/Akt and MAPK signaling pathways. Moreover, Nectin3 may be a ligand of CD155 and participate in the regulation of ESCA cells' proliferation. Hence, the inhibition of CD155 may enhance the therapeutic effect of anti-PD-1 immunotherapies in ESCA.

The Proliferative Role of Immune Checkpoints in Tumors: Double Regulation.

Cancer remains a serious social health problem, and immunotherapy has become the major treatments in tumor treatment. Additionally, improving the efficiency and safety of treatment is necessary. Further, more therapy targets are warranted for future tumor treatments. In this review, in addition to examining the currently recognized role of immune regulation, we focus on the proliferative role of 15 immune checkpoints in various tumors, including PD1, PD-L1, FGL1, CD155, CD47, SIRPα, CD276, IDO1, SIGLEC-15, TIM3, Galectin-9, CD70, CD27, 4-1BBL, and HVEM. We managed to conclude that various immune checkpoints such as PD1/PD-L1, FGL1, CD155, CD47/SIRPα, CD276, and SIGLEC-15 all regulate the cell cycle, and specifically through Cyclin D1 regulation. Furthermore, a variety of signal pathways engage in proliferation regulation, such as P13K, AKT, mTOR, and NK-κB, which are also the most common pathways involved in the regulation of immune checkpoint proliferation. Currently, only PD1/PD-L1, CD47/SIRPα, TIM3/Galectin-9, and CD70/CD27 checkpoints have been shown to interact with each other to regulate tumor proliferation in pairs. However, for other immune checkpoints, the role of their receptors or ligands in tumor proliferation regulation is still unknown, and we consider the enormous potential in this area. An increasing number of studies have validated the various role of immune checkpoints in tumors, and based on this literature review, we found that most of the immune checkpoints play a dual regulatory role in immunity and proliferation. Therefore, the related pathways in proliferation regulation can served the role of therapy targets in tumor therapy. Further, great potential is displayed by IDO1, SIGLEC-15, 4-1BBL, and HVEM in tumor proliferation regulation, which may become novel therapy targets in tumor treatment.

Facile Preparation of a Novel Vanillin-Containing DOPO Derivate as a Flame Retardant for Epoxy Resins.

A novel bio-based flame retardant designated AVD has been synthesized in a one-pot process via the reaction of 9,10-dihydro-9-oxa-10-phospha-phenanthrene-10-oxide (DOPO), vanillin (VN), and 2- aminobenzothiazole (ABT). The structure of AVD was confirmed using Fourier transform infrared spectroscopy (FTIR), and 1H and 31P nuclear magnetic resonance spectroscopy (NMR). The curing process, thermal stability, flame retardancy, and mechanical properties of the epoxy resin (EP) modified with AVD have been investigated comprehensively. The extent of curing, the glass transition temperature and the crosslinking density of the blend decreased gradually with increasing AVD content. The thermogravimetric analysis (TGA) was used to demonstrate that the presence of AVD reduced the thermal decomposition rate for EP and enhanced the formation of carbon residue during resin decomposition. A blend of 7.5 wt% AVD (0.52% phosphorus) displays a UL-94V-0 rating and a LOI of 31.1%. Reduction of the peak heat release rate, total heat release rate and total smoke production was 41.26%, 35.70%, and 24.03%, respectively, as compared to the values for pure EP. The improved flame retardancy of the flame retardant epoxy (FREP) may be attributed to the formation of a compact and continuous protective char layer into the condensed phase as well as the release of non-combustible gases and phosphorus-containing radicals from the decomposition of AVD in the gas phase. AVD is a new and efficient biobased flame retardant for epoxy with great prospects for industrial applications.

Preparation of Mn2+ Doped Piperazine Phosphate as a Char-Forming Agent for Improving the Fire Safety of Polypropylene/Ammonium Polyphosphate Composites.

A piperazine phosphate doped with Mn2+ (HP-Mn), as a new char-forming agent for intumescent flame retardant systems (IFR), was designed and synthesized using 1-hydroxy ethylidene-1,1-diphosphonic acid, piperazine, and manganese acetate tetrahydrate as raw materials. The effect of HP-Mn and ammonium polyphosphate (APP) on the fire safety and thermal stability of polypropylene (PP) was investigated. The results showed that the combined incorporation of 25 wt.% APP/HP-Mn at a ratio of 1:1 endowed the flame retardant PP (PP6) composite with the limiting oxygen index (LOI) of 30.7% and UL-94 V-0 rating. In comparison with the pure PP, the peak heat release rate (PHRR), the total heat release (THR), and the smoke production rate (PSPR) of the PP6 were reduced by 74%, 30%, and 70%, respectively. SEM and Raman analysis of the char residues demonstrated that the Mn2+ displayed a catalytic cross-linking charring ability to form a continuous and compact carbon layer with a high degree of graphitization, which can effectively improve the flame retardancy of PP/APP composites. A possible flame-retardant mechanism was proposed to reveal the synergistic effect between APP and HP-Mn.

PD-L1 expression and immune cells infiltration in primary tracheobronchial neoplasm.

BACKGROUND: Primary tracheobronchial neoplasm is rare yet poses a serious threat to life. Due to its low incidence, the immune microenvironment of such tumors remained unclear. This study aimed to clarify the expression of programmed death-ligand 1 (PD-L1) and infiltration of immune cells in primary tracheobronchial neoplasm, which might be useful for guiding treatment and evaluating clinical outcome. METHODS: We assessed retrospectively the expression of PD-L1 and infiltration in cells expressing CD8, CD16, CD68, CD163 and FOXP3 in 21 patients with primary tracheobronchial neoplasm who underwent surgery in Tangdu Hospital from January 2016 to July 2021. The expression of PD-L1 was assessed based on the tumor proportion score system. The density of immune cells was analyzed by automatic image analysis software. RESULTS: In this study, all of 16 participants with adenoid cystic carcinoma (ACC) had no expression of PD-L1, whereas 4/5 (80%) of those with squamous cell carcinomas (SCC) were positive for PD-L1 expression. Compared with ACC, the density of FOXP3+ cells in both the intratumoral region and peritumoral region was higher in SCC (P<0.01). The density of FOXP3+ cells was significantly higher than that of CD8+, CD16+, and CD163+ cells in SCC in the intratumoral region (P<0.01). In contrast, the density of FOXP3+ cells was significantly lower than that of CD8+, CD16+, and CD68+ cells in ACC in both the intratumoral region and peritumoral regions. The density of CD68+ cells was significantly higher than that of CD8+ cells (P<0.05) and CD163+ cells (P<0.01) in ACC in the intratumoral region. Furthermore, the tumors of patients with metastasis more commonly of immune-excluded status, in which the CD8+ cells accumulated in peritumoral region. CONCLUSIONS: This study demonstrated that the expression of PD-L1 in primary tracheobronchial neoplasm was mainly concentrated in patients with SCC. In the immune microenvironment of SCC, FOXP3+ cells were the dominant immune cells, while in the immune microenvironment of ACC, CD68+ cells were the main immune cells. Therefore, the immune microenvironment was significantly different in primary tracheobronchial neoplasm according to histology.

Cross-Linking Modification of Ammonium Polyphosphate via Ionic Exchange and Self-Assembly for Enhancing the Fire Safety Properties of Polypropylene.

Modified ammonium polyphosphate (MAPP) was prepared as a novel mono-component intumescent flame retardant (IFR) via the ionic exchange between ammonium polyphosphate (APP) and piperazine sulfonate, which is synthesized by self-assembly using 1-(2-aminoethyl) piperazine (AEP) and p-aminobenzene sulfonic acid (ASC) as raw materials. This all-in-one IFR integrating three functional elements (carbon, acid, and gas source) showed more efficient flame retardancy and excellent smoke suppression as well as better mechanical properties than the conventional APP. The incorporation of 22.5 wt.% MAPP into polypropylene (PP) eliminated the melt dripping phenomenon and passed the UL-94 V-0 rating. The results of the cone calorimetry test (CCT) revealed that the release of heat, smoke, and CO is significantly decreased, demonstrating that this novel IFR endows PP with excellent fire safety more effectively. For PP/MAPP composites, a possible IFR mechanism was proposed based on the analysis of the pyrolysis gas and char residues.

One-Step Synthesis of Highly Efficient Oligo(phenylphosphonic Dihydroxypropyl Silicone Oil) Flame Retardant for Polycarbonate.

A highly efficient flame retardant and smoke suppression oligomer, oligo(phenylphosphonic dihydroxypropyl silicone oil) (PPSO), was synthesized by a one-step reaction. The chemical structure of PPSO was confirmed by Fourier transform infrared (FTIR), 31P nuclear magnetic resonance (31P NMR), and 29Si nuclear magnetic resonance (29Si NMR). The flame-retardant effect of PPSO on the polycarbonate (PC) matrix was investigated by limiting oxygen index, UL-94 vertical burning test, and cone calorimetry, respectively. The results showed that PC/PPSO composites passed UL-94 V-0 rate testing with only 1.3 wt. % PPSO. Furthermore, the incorporation of PPSO can suppress the release of smoke. The flame-retardant mechanism was also investigated via thermogravimetric analysis-fourier transform infrared spectroscopy (TG-FTIR), field-emission scanning electronic microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy. From the result of pyrolysis gas and char residue, PPSO played a synergistic flame-retardant mechanism including the gas phase and the condensed phase.

Design and Application of Highly Efficient Flame Retardants for Polycarbonate Combining the Advantages of Cyclotriphosphazene and Silicone Oil.

A novel flame retardant (HSPCTP) was successfully designed and incorporated into a polycarbonate (PC) matrix. Combining the advantages of cyclotriphosphazene and silicone oil, PC/HSPCTP composites passed UL-94 V-0 rating testing with only 3 wt% HSPCTP, and their LOI value increased from 25.0% to 28.4%. The findings showed that HSPCTP exhibits both gas-phase and solid-phase flame-retardant effects. Furthermore, the incorporation of HSPCTP into PC could suppress the release of smoke. Finally, the flame-retardant mechanism is discussed in depth.

Fabrication of a superhydrophobic mesh based on PDMS/SiO2 nanoparticles/PVDF microparticles/KH-550 by one-step dip-coating method.

In this study, a facile one-step dip-coating approach was reported for fabrication of superhydrophobic copper mesh by using PDMS, SiO2 nanoparticles, PVDF microparticles and a couple agent 3-aminopropyltriethoxysilane (KH-550). It is found that undesirable SiO2 agglomeration was obviously reduced by introducing KH-550 and PVDF microparticles. The KH-550 acts as the bridge-linker and binds SiO2, PVDF and PDMS together. The as-prepared superhydrophobic mesh exhibited a promising water contact angle of 160.1° and a small sliding angle of 2.5°. The coating displayed excellent resistance to various pollutants and retained its superhydrophobicity after abrasions (sandpaper abrasion or adhesive tape tear). The strong chemical stability was also observed when the mesh was immersed in various solutions, especially in neutral and alkaline solutions. The applications of the superhydrophobic mesh for quantitative water droplet manipulation and oil spill cleanup were also illustrated. The method is facile and economic, and could be used for large-scale fabrications for industrial applications.

A glucose modified filter paper for effective oil/water separation.

Efficient and low-cost oil/water separation remains a great challenge for industries. Natural cellulose-based filter paper, because of its abundance, low cost, biodegradability and excellent chemical stability, has been developed as an oil/water separator in recent years. In the present study, a superhydrophilic and underwater superoleophobic filter paper is successfully prepared by an aldol condensation reaction to crosslink glucose molecules with filter paper. The prepared filter paper is characterized by IR-spectroscopy, SEM spectroscopy and wettability measurements, and it has high underwater oil contact angles of over 162° for hexane, toluene and petroleum ether. It is shown that the modified filter paper has high water recovery from various oil/water mixtures, not only in a gentle environment but also in acidic, alkaline, and salty environments and at different temperatures. Moreover, the glucose modified filter paper shows excellent oil/water emulsion separation efficiency (>99%) and good recycling performance. The preparation is economic and could be easily scaled up, suggesting its great potential for large-scale industrial applications.

Self-assembly of amphiphilic peptide (AF)6H5K15: coarse-grained molecular dynamics simulation.

Amphiphilic peptides are receiving considerable interest for drug delivery because of their self-assembly nature. A molecular dynamics simulation study is reported here to investigate the self-assembly of FA32 peptide composed of 32 amino acid (AF)6H5K15. The peptide, as well as water and counterions, are represented by the MARTINI coarse-grained model. Within 5 µs simulation duration, the peptide is observed to form micelles. Ala and Phe stay in the hydrophobic core, Lys in the hydrophilic shell, and amphiphilic His at the interface. The assembly process and microscopic structures are analyzed in terms of the number of clusters, the radii of micelle, core and shell, and the density profiles of residues. A three-step process is proposed for the assembly: small clusters are initially aggregated and then merged into large clusters, eventually micelles are formed. The effects of simulation box size and peptide concentration are examined in detail. It is found that the micellar structures and microscopic properties are essentially independent of box size. With increasing concentration, quasi-spherical micelles change to elongated shape and micelle size generally increases. The simulation study provides microscopic insight into the assembly process of FA32 peptide and the microscopic structures.

CO2 capture in poly(ionic liquid) membranes: atomistic insight into the role of anions.

We report the first atomistic simulation study to characterize poly(ionic liquid) (PIL) membranes and examine their capability for post-combustion CO(2) capture. Four PILs based on 1-vinyl-3-butylimidazolium ([VBIM](+)) are examined with four different anions, namely bis(trifluoromethylsulfonyl)imide ([TF(2)N](-)), thiocyanate ([SCN](-)), hexafluorophosphate ([PF(6)](-)) and chloride ([Cl](-)). Gas molecules (CO(2) and N(2)) in [VBIM](+)-based PILs interact with polycations more strongly than with anions. Therefore, the role of anions in gas solubility is insignificant, which is in remarkable contrast to monomeric ILs. The solubilities predicted in the four PILs are close and in good agreement with available experimental data. The sorption, diffusion and permeation selectivities of CO(2)/N(2) predicted from simulation are consistent with experiment. Particularly, the diffusion selectivities are approximately equal to one, implying that CO(2)/N(2) separation is governed by sorption. This study provides atomistic insight into the mechanisms of gas sorption, diffusion and permeation in [VBIM](+)-based PILs and reveals that polycations play a dominant role in determining gas-membrane interaction and separation.

pH-sensitive drug loading/releasing in amphiphilic copolymer PAE-PEG: integrating molecular dynamics and dissipative particle dynamics simulations.

Molecular dynamics (MD) and dissipative particle dynamics (DPD) simulations are integrated to investigate the loading/releasing of anti-cancer drug camptothecin (CPT) in pH-sensitive amphiphilic copolymer, composed of hydrophobic poly(ß-amino ester) (PAE) and hydrophilic methyl ether-capped poly(ethylene glycol) (PEG). MD simulation is used to estimate the Flory-Huggins interaction parameters and miscibility of binary components. On this basis, DPD simulation is applied to examine the micellization of PAE-PEG, CPT loading in PAE-PEG, and CPT releasing in PAEH-PEG. With increasing concentration, PAE-PEG forms spherical then disk-like micelles and finally vesicles, as a competitive counterbalance of free energies for the formation of shell, interface and core. CPT loading in PAE-PEG micelles/vesicles is governed by adsorption-growth-micellization mechanism, and CPT is loaded into both hydrophobic core and interface of hydrophobic core/hydrophilic shell. The predicted loading efficiency is close to experimental value. Similar to literature reports, the loading of high concentration of CPT is observed to cause morphology transition from micelles to vesicles. Upon protonation, CPT is released from micelles/vesicles by swelling-demicellization-releasing mechanism. This multi-scale simulation study provides microscopic insight into the mechanisms of drug loading and releasing, and might be useful for the design of new materials for high-efficacy drug delivery.

Folding mechanisms of individual beta-hairpins in a Go model of Pin1 WW domain by all-atom molecular dynamics simulations.

This paper examines the folding mechanism of an individual beta-hairpin in the presence of other hairpins by using an off-lattice model of a small triple-stranded antiparallel beta-sheet protein, Pin1 WW domain. The turn zipper model and the hydrophobic collapse model originally developed for a single beta-hairpin in literature is confirmed to be useful in describing beta-hairpins in model Pin1 WW domain. We find that the mechanism for folding a specific hairpin is independent of whether it folds first or second, but the formation process are significantly dependent on temperature. More specifically, beta1-beta2 hairpin folds via the turn zipper model at a low temperature and the hydrophobic collapse model at a high temperature, while the folding of beta2-beta3 hairpin follows the turn zipper model at both temperatures. The change in folding mechanisms is interpreted by the interplay between contact stability (enthalpy) and loop lengths (entropy), the effect of which is temperature dependent.

Temperature-dependent folding pathways of Pin1 WW domain: an all-atom molecular dynamics simulation of a Go model.

We study the folding thermodynamics and kinetics of the Pin1 WW domain, a three-stranded beta-sheet protein, by using all-atom (except nonpolar hydrogens) discontinuous molecular dynamics simulations at various temperatures with a Go model. The protein exhibits a two-state folding kinetics near the folding transition temperature. A good agreement between our simulations and the experimental measurements by the Gruebele group has been found, and the simulation sheds new insights into the structure of transition state, which is hard to be straightforwardly captured in experiments. The simulation also reveals that the folding pathways at approximately the transition temperature and at low temperatures are much different, and an intermediate state at a low temperature is predicted. The transition state of this small beta-protein at its folding transition temperature has a well-established hairpin 1 made of beta1 and beta2 strands while its low-temperature kinetic intermediate has a formed hairpin 2 composed of beta2 and beta3 strands. Theoretical results are compared with other simulation results as well as available experimental data. This study confirms that specific side-chain packing in an all-atom Go model can yield a reasonable prediction of specific folding kinetics for a given protein. Different folding behaviors at different temperatures are interpreted in terms of the interplay of entropy and enthalpy in folding process.