Three-Dimensional Printing Conformal Cooling with Structural Lattices for Plastic Injection Molding

The design of three-dimensional printing based conformal cooling channels(CCCs)in injection molding holds great significance.Compared to CCCs,conformal cooling(CC)cavity solutions show promise in delivering enhanced cooling performance for plastic products,although they have been underexplored.In this research,CC cavity is designed within the mold geometry,reinforced by body-centered cubic(BCC)lattice structures to enhance mechanical strength.Three distinct BCC lattice variations have been integrated into the CC cavity:the BCC structure,BCC with cubes,and BCC with pillars.The thermal performances of the BCC lattice-added CC cavity are assessed numerically after experimental validation.To provide feasible solutions from viewpoints of thermal performances,various BCC lattice structure thicknesses are analyzed in the range of 0.8–1.2mm.Thermal simulation outcomes reveal that thicker lattice structures enhance mechanical strength but simultaneously lead to an increase in cooling time.Upon examining all the proposed CC cavity solutions supported by BCC,the cooling times range from 2.2 to 4 s,resulting in a reduction of 38.6%to 66.1%when compared to conventional straightdrilled channels.In contrast to CCCs,CC cavities have the potential to decrease the maximum temperature nonuniformity from 8.5 to 6 K.Nevertheless,the presence of lattice structures in CC cavity solutions results in an elevated pressure drop,reaching 2.8MPa,whereas the results for CCCs remain below2.1MPa.

Three-dimensional conformal intensity-modulated radiation therapy of left femur foci does not damage the sciatic nerve

During radiotherapy to kill femoral hydatid tapeworms, the sciatic nerve surrounding the focus can be easily damaged by the treatment. Thus, it is very important to evaluate the effects of ra- diotherapy on the surrounding nervous tissue. In the present study, we used three-dimensional, conformal, intensity-modulated radiation therapy to treat bilateral femoral hydatid disease in Meriones meridiani. The focus of the hydatid disease on the left femur was subiected to radio- therapy （40 Gy） for 14 days, and the right femur received sham irradiation. Hematoxylin-eosin staining, electron microscopy, and terminal deoxynucleotidyl transferase-dUTP nick end labeling assays on the left femurs showed that the left sciatic nerve cell structure was normal, with no ob- vious apoptosis after radiation. Trypan blue staining demonstrated that the overall protoscolex structure in bone parasitized with Echinococcus granulosus disappeared in the left femur of the animals after treatment. The mortality of the protoscolex was higher in the left side than in the right side. The succinate dehydrogenase activity in the protoscolex in bone parasitized with Echi- nococcus granulosus was lower in the left femur than in the right femur. These results suggest that three-dimensional conformal intensity-modulated radiation therapy achieves good therapeutic effects on the secondary bone in hydatid disease in Meriones meridiani without damaging the morphology or function of the sciatic nerve.

Clinical observation of gemcitabine and concomitant three-dimensional conformal radiotherapy in the treatment of locally advanced non-small cell lung cancer

Objective： To evaluate the clinical effect of gemcitabine and concurrent three-dimensional conformal radiation therapy （3D-CRT） for locally advanced non-small cell lung cancer （NSCLC）. Methods： From April 2002 to June 2005, 38 patients with inoperable stage Ⅲ NSCLC were treated with gemcitabine and 3D-CRT simultaneously. Chemotherapy consisted of intravenously gemcitabine 350 mg/m^2 on days 1, 8, 15, 22, 29, 36.3D-CRT was delivered up to a total dose of 60-64 Gy with a 2.0 Gy dose fraction per day, 5 days per week. Results： The overall response rates of primary tumor and mediastinum metastatic node were 86.8% （33/38） and 90.6% （29/32） respectively, and 91.7% （22/24） and 78.6% （11/14） for squamous cell carcinoma and adenocarcinoma respectively. The acute side effects of patients were mostly myelosuppression, nausea, vomiting, radiation-induced esophagitis and pneumonitis （RTOG 1/11）, however, all of them were cured. Conclusion： Concurrent application of gemcitabine and 3D-CRT can improve the overall response rate for locally advanced NSCLC without aggravating the side effects.

A theory for three-dimensional response of micropolar plates

Through combined applications of the transfer-matrix method and asymptotic expansion technique,we formulate a theory to predict the three-dimensional response of micropolar plates.No ad hoc assumptions regarding through-thickness assumptions of the field variables are made,and the governing equations are two-dimensional,with the displacements and microrotations of the mid-plane as the unknowns.Once the deformation of the mid-plane is solved,a three-dimensional micropolar elastic field within the plate is generated,which is exact up to the second order except in the boundary region close to the plate edge.As an illustrative example,the bending of a clamped infinitely long plate caused by a uniformly distributed transverse force is analyzed and discussed in detail.

Three-dimensional visualization technology for guiding one-step percutaneous transhepatic cholangioscopic lithotripsy for the treatment of complex hepatolithiasis

BACKGROUND Biliary stone disease is a highly prevalent condition and a leading cause of hospitalization worldwide.Hepatolithiasis with associated strictures has high residual and recurrence rates after traditional multisession percutaneous transhepatic cholangioscopic lithotripsy(PTCSL).AIM To study one-step PTCSL using the percutaneous transhepatic one-step biliary fistulation(PTOBF)technique guided by three-dimensional(3D)visualization.METHODS This was a retrospective,single-center study analyzing,140 patients who,between October 2016 and October 2023,underwent one-step PTCSL for hepatolithiasis.The patients were divided into two groups:The 3D-PTOBF group and the PTOBF group.Stone clearance on choledochoscopy,complications,and long-term clearance and recurrence rates were assessed.RESULTS Age,total bilirubin,direct bilirubin,Child-Pugh class,and stone location were similar between the 2 groups,but there was a significant difference in bile duct strictures,with biliary strictures more common in the 3D-PTOBF group(P=0.001).The median follow-up time was 55.0(55.0,512.0)days.The immediate stone clearance ratio(88.6%vs 27.1%,P=0.000)and stricture resolution ratio(97.1%vs 78.6%,P=0.001)in the 3D-PTOBF group were significantly greater than those in the PTOBF group.Postoperative complication(8.6%vs 41.4%,P=0.000)and stone recurrence rates(7.1%vs 38.6%,P=0.000)were significantly lower in the 3D-PTOBF group.CONCLUSION Three-dimensional visualization helps make one-step PTCSL a safe,effective,and promising treatment for patients with complicated primary hepatolithiasis.The perioperative and long-term outcomes are satisfactory for patients with complicated primary hepatolithiasis.This minimally invasive method has the potential to be used as a substitute for hepatobiliary surgery.

Oxygen tension modulates cell function in an in vitro three-dimensional glioblastoma tumor model

Hypoxia is a typical feature of the tumor microenvironment,one of the most critical factors affecting cell behavior and tumor progression.However,the lack of tumor models able to precisely emulate natural brain tumor tissue has impeded the study of the effects of hypoxia on the progression and growth of tumor cells.This study reports a three-dimensional(3D)brain tumor model obtained by encapsulating U87MG(U87)cells in a hydrogel containing type I collagen.It also documents the effect of various oxygen concentrations(1%,7%,and 21%)in the culture environment on U87 cell morphology,proliferation,viability,cell cycle,apoptosis rate,and migration.Finally,it compares two-dimensional(2D)and 3D cultures.For comparison purposes,cells cultured in flat culture dishes were used as the control(2D model).Cells cultured in the 3D model proliferated more slowly but had a higher apoptosis rate and proportion of cells in the resting phase(G0 phase)/gap I phase(G1 phase)than those cultured in the 2D model.Besides,the two models yielded significantly different cell morphologies.Finally,hypoxia(e.g.,1%O2)affected cell morphology,slowed cell growth,reduced cell viability,and increased the apoptosis rate in the 3D model.These results indicate that the constructed 3D model is effective for investigating the effects of biological and chemical factors on cell morphology and function,and can be more representative of the tumor microenvironment than 2D culture systems.The developed 3D glioblastoma tumor model is equally applicable to other studies in pharmacology and pathology.

Three-dimensional cell-based strategies for liver regeneration

Liver regeneration and the development of effective therapies for liver failure remain formidable challenges in modern medicine.In recent years,the utilization of 3D cell-based strategies has emerged as a promising approach for addressing these urgent clinical requirements.This review provides a thorough analysis of the application of 3D cell-based approaches to liver regeneration and their potential impact on patients with end-stage liver failure.Here,we discuss various 3D culture models that incorporate hepatocytes and stem cells to restore liver function and ameliorate the consequences of liver failure.Furthermore,we explored the challenges in transitioning these innovative strategies from preclinical studies to clinical applications.The collective insights presented herein highlight the significance of 3D cell-based strategies as a transformative paradigm for liver regeneration and improved patient care.

Late course three-dimensional conformal radiotherapy for esophageal carcinoma

Objective： The aim of our study was to evaluate the clinical results and acute side effects of late course three-dimensional conformal radiotherapy （3DCRT） for esophageal carcinoma. Methods： From January 2004 to October 2006, 70 patients with esophageal carcinoma received late course 3DCRT. Their clinical data were analyzed retrospectively. The short-term clinical results, acute side effects, local control rates and survival rates were evaluated. Results： The complete response rate was 62.9%, partial response rate was 35.7%, and the overall response rate was 98.6%. The 1-, 2-and 3-year local control rates were 77.1%, 51.4% and 45.7%, respectively. The 1-, 2-and 3-year overall survival rates were 75.7%, 54.3% and 38.6%, respectively. The median survival time was 26 months. Conclusion： The technique of late course 3DCRT is an effective treatment for esophageal carcinoma and tend to improve the overall survival rate.

Three-dimensional stability calculation method for high and large composite slopes formed by mining stope and inner dump in adjacent open pits

The 2D limit equilibrium method is widely used for slope stability analysis.However,with the advancement of dump engineering,composite slopes often exhibit significant 3D mechanical effects.Consequently,it is of significant importance to develop an effective 3D stability calculation method for composite slopes to enhance the design and stability control of open-pit slope engineering.Using the composite slope formed by the mining stope and inner dump in Baiyinhua No.1 and No.2 open-pit coal mine as a case study,this research investigates the failure mode of composite slopes and establishes spatial shape equations for the sliding mass.By integrating the shear resistance and sliding force of each row of microstrip columns onto the bottom surface of the strip corresponding to the main sliding surface,a novel 2D equivalent physical and mechanical parameters analysis method for the strips on the main sliding surface of 3D sliding masses is proposed.Subsequently,a comprehensive 3D stability calculation method for composite slopes is developed,and the quantitative relationship between the coordinated development distance and its 3D stability coefficients is examined.The analysis reveals that the failure mode of the composite slope is characterized by cutting-bedding sliding,with the arc serving as the side interface and the weak layer as the bottom interface,while the destabilization mechanism primarily involves shear failure.The spatial form equation of the sliding mass comprises an ellipsoid and weak plane equation.The analysis revealed that when the coordinated development distance is 1500 m,the error rate between the 3D stability calculation result and the 2D stability calculation result of the composite slope is less than 8%,thereby verifying the proposed analytical method of equivalent physical and mechanical parameters and the 3D stability calculation method for composite slopes.Furthermore,the3D stability coefficient of the composite slope exhibits an exponential correlation with the coordinated development distance,with the coefficient gradually decreasing as the coordinated development distance increases.These findings provide a theoretical guideline for designing similar slope shape parameters and conducting stability analysis.

The combined application of stem cells and three-dimensional bioprinting scaffolds for the repair of spinal cord injury

Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality.Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord.Consequently,there is a critical need to develop new treatments to promote functional repair after spinal cord injury.Over recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord injury.Alongside significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures.This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization.These three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal cord.In this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting scaffolds.In particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.

Three-Dimensional Conformal Radiotherapy for Rectal Cancer and the Changes in Cancer Multi-biomarkers

OBJECTIVE To investigate the clinical efficacy of three-dimensional conformal radiotherapy （3D-CRT） for locally advanced or postoperatively relapsed rectal cancer, and to examine the changes in cancer multi-biomarkers. METHODS Sixty patients with locally advanced or postoperatively relapsed rectal cancer were randomly divided into two groups after 40 Gy external radiation, namely a late-course 3D-CRT group and a conventional radiotherapy group that served as the control. There were 30 patients in each group. For patients in the 3D-CRT group, multi-biomarkers were measured before and after radiotherapy and after relapse. RESULTS Response rates in the 3D-CRT and the control groups were 86.7% （26/30） and 70% （21/30） respectively, without a significant difference （P〉0.05）. The 1-, 2- and 3-year survival rates were 80%, 53.3% and 36.7% in the 3D-CRT group; in the control group the rates were 56.7%, 40% and 13.3% respectively, with a significant difference （P=0.0213）. CEA, CA19-9, CA242 and FER decreased after radiotherapy in the 3D-CRT group, P〈0.01, indicating a significant difference. The values after relapse were higher than those without relapse, P〈0.01, indicating a significant difference. CONCLUSION Conventional radiotherapy with a 3D-CRT boost gives better therapeutic effect to patients with locally advanced or postoperatively locally relapsed rectal cancer. A multi-biomarker protein chip diagnosis system can be utilized as an effective tool to determine the therapeutic effect and prognosis.

Application of three-dimensional speckle tracking technique in measuring left ventricular myocardial function in patients with diabetes

BACKGROUND Diabetic cardiomyopathy is considered as a chronic complication of diabetes mellitus(DM).Therefore,early detection of left ventricular systolic function(LVSF)damage in DM is essential.AIM To explore the use of the three-dimensional speckle tracking technique(3D-STI)for measuring LVSF in DM patients via meta-analysis.METHODS The electronic databases were retrieved from the initial accessible time to 29 April 2023.The current study involved 9 studies,including 970 subjects.We carried out this meta-analysis to estimate myocardial function in DM compared with controls according to myocardial strain attained by 3D-STI.RESULTS Night articles including 970 subjects were included.No significant difference was detected in the left ventricular ejection fraction between the control and the diabetic group(P>0.05),while differences in global longitudinal strain,global circumferential strain,global radial strain,and global area strain were markedly different between the controls and DM patients(all P<0.05).CONCLUSION The 3D-STI could be applied to accurately measure early LVSF damage in patients with DM.

Dosimetric study of five-field intensity-modulated radiotherapy compared with conventional three-dimensional conformal radiotherapy for rectal cancer

Objective： The aim of the study was to compare the difference of dose distribution in clinical target volume and organ at risk （OAR） between five-field intensity-modulated radiotherapy （IMRT） and conventional three-dimensional conformal radiotherapy （3DCRT） in the radiotherapy of rectal cancer. Methods： Fifteen patients with rectal cancer treated with radio- therapy （RT） were retrospectively analyzed. Among the patients, seven received RT preoperatively and 8 postoperatively. The target volume and the OARs such as the small bowel, bladder and femoral heads were contoured for each patient. 3DCRT-plan and IMRT-plan were performed for each patient respectively, with the prescribed dose covering at least 95% of the planning target volume （PTV）. The conformity index （CI） and homogeneity index （HI） were used for evaluation of the dose distribution in the target volume, and the Dx% （the lowest dose to the x% volume of the OARs that received the highest dose of irradiation） and the mean dose were used for evaluation of the dose to OARs. Paired-T test was used for companson of the difference between the two plans. Results： In the IMRT-plan and 3DCRT-plan, the CI were 0.94 and 0.87 （P = 0.000） and the HI were 1.13 and 1.17, respectively （P = 0.001）. For small bowel, the D30%, D50% and the mean dose were 19.67 Gy, 15.13 Gy and 18.81 Gy in the IMRT-plan and 25.20 Gy, 22.20 Gy and 22.89 Gy in the 3DCRT-plan, respectively （P 〈 0.001 for all pairs of parameters）. For bladder, the D30%, D50%, and the mean dose were 24.80 Gy, 34.20 Gy and 28.70 Gy in the IMRT- plan, and 35.07 Gy, 44.67 Gy and 35.68 Gy in the 3DCRT-plan, respectively （P 〈 0.001 for all pairs of parameters）. For femoral heads, the D5% in the IMRT-plan and 3DCRT-plan were 40.6 Gy and 40.47 Gy, respectively （P = 0.936）, and the mean dose were 30.14 Gy and 25.57 Gy, respectively （P = 0.001）. Conclusion： Five-field IMRT-plan is better than 3DCRT-plan in the conformity and the dose homogeneity within target volume and also better in sparing the small bowel and bladder.

Evaluation of whole-course three-dimensional conformal radiotherapy combined with late-course accelerated hyperfractionated radiotherapy for esophageal carcinoma patients

Objective： The aim of the study was to evaluate the therapeutic effect and safety of whole-course three-dimensional conformal radiotherapy （3DCRT） combined with late-course accelerated hyperfractionated radiotherapy （LCAFR） on patients with esophageal carcinoma. Methods： one hundred and one patients with esophageal carcinoma were divided into two groups. Observing group （49 cases） were treated by whole-course 3DCRT. Patients in control group （52 cases） were treated by conventional radiotherapy. Clinical efficiencies and radiation toxicities were compared between two groups. Results： The side effects including radiation esophagitis （63.2%） and tracheitis （49.0%） decreased in observing group, but there was no significant difference between two groups （69.2% and 55.7% in controls）. The 1-, 2-and 3-year tumor local control rates and overall survival rates in the observing group were significantly improved compared with the control group, being respectively 87.8%, 75.5%, 63.3% vs 71.2%, 55.8%, 42.3% and 85.7%, 71.4%, 46.7% vs 69.2%, 51.9%, 26.9% （all P 0.05）. Conclusion： The therapeutic effect of whole-course 3DCRT combined with LCAFR for esophageal carcinomas is superior to conventional radiotherapy.

Influences of Motion Artifacts on Three-Dimensional Reconstruction Volume and Conformal Radiotherapy Planning

Objective ：To investigate the influences of motion artifacts on three-dimensional （3D） reconstruction volume and conformal radiotherapy planning. Methods： A phantom which can mimic the clip motion of lung tumor along the cranial-caudal direction is constructed by step motor, small ball of polyethylene and potato. Ten different scan protocols were set and CT data of the phantom were acquired by using a commercial GE LightSpeedl6 CT scanner. The 3D reconstruction of the CT data was implemented by adopting volume-rendering technology of GE AdvantageSim 6.0 system. The reconstructed volumes of each target in different scan protocols were measured through 3D measuring tools. Thus, relative deviations of the reconstruction volumes between moving targets and static ones were determined. The three-dimensional conformal radiation therapy （3D- CRT） plans and conformal fields were created and compared for a static/moving target with the WiMRT treatment planning system （TPS）. Results：For a static target, there was no obvious difference among the 3D reconstruction volumes when the CT data were acquired with different pitches and slices. The appearance of 3D reconstruction volume and 3D conformal field of a moving target was quite different from that of static one. The maximum relative deviation is nearly 90% for a moving target scanned with different scan protocols. The relative deviations are variable among the different targets, about from -39.8% to 89.5% for a smaller target and from - 18.4% to 20.5% for a larger one. Conclusion ：The motion artifacts have great effects on 3 D-CRT planning and reconstruction volume, which will greatly induce distorted conformal radiation fields and false DVHs for a moving target.

High-speed autopolarization synchronization modulation three-dimensional structured illumination microscopy

In recent years,notable progress has been achieved in both the hardware and algorithms of structured illumination microscopy(SIM).Nevertheless,the advancement of three-dimensional structured illumination microscopy(3DSIM)has been impeded by challenges arising from the speed and intricacy of polarization modulation.We introduce a high-speed modulation 3DSIM system,leveraging the polarizationmaintaining and modulation capabilities of a digital micromirror device(DMD)in conjunction with an electrooptic modulator.The DMD-3DSIM system yields a twofold enhancement in both lateral(133 nm)and axial(300 nm)resolution compared to wide-field imaging and can acquire a data set comprising 29 sections of 1024 pixels×1024 pixels,with 15 ms exposure time and 6.75 s per volume.The versatility of the DMD-3DSIM approach was exemplified through the imaging of various specimens,including fluorescent beads,nuclear pores,microtubules,actin filaments,and mitochondria within cells,as well as plant and animal tissues.Notably,polarized 3DSIM elucidated the orientation of actin filaments.Furthermore,the implementation of diverse deconvolution algorithms further enhances 3D resolution.The DMD-based 3DSIM system presents a rapid and reliable methodology for investigating biomedical phenomena,boasting capabilities encompassing 3D superresolution,fast temporal resolution,and polarization imaging.

Laccase/caffeic acid-catalyzed crosslinking coupled with galactomannan alters the conformational structure of ovalbumin and alleviates Th2-mediated allergic asthma

Ovalbumin(OVA)is the major allergenic protein that can induce T helper 2(Th2)-allergic reactions,for which current treatment options are inadequate.In this study,we developed a polymerized hypoallergenic OVA product via laccase/caffeic acid(Lac/CA)-catalyzed crosslinking in conjunction with galactomannan(Man).The formation of high molecular weight crosslinked polymers and the Ig G-binding were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western blotting.The study indicated that Lac/CA-catalyzed crosslinking plus Man conjugation substantially altered secondary and tertiary structures of OVA along with the variation in surface hydrophobicity.Gastrointestinal digestion stability assay indicated that crosslinked OVA exhibited less resistance in simulated gastric fluid(SGF)and simulated intestinal fluid(SIF).Mouse model study indicated that Lac-Man/OVA ameliorated eosinophilic airway inflammatory response and efficiently downregulated the expression of Th2-related cytokines(interleukin(IL)-4,IL-5,and IL-13),and upregulated IFN-γand IL-10 expression.Stimulation of bone marrow-derived dendritic cells with Lac-Man/OVA suppressed the expression of phenotypic maturation markers(CD80 and CD86)and MHC class II molecules,and suppressed the expression levels of proinflammatory cytokines.The knowledge obtained in the present study offers an effective way to acquire a hypoallergenic OVA product that can have a therapeutic effect in alleviating OVA-induced allergic asthma.

Illuminating β-arrestin conformational dynamics by fluorine NMR

In a recent paper, solution-state ^(19)F NMR spectroscopy was used to probe the conformational dynamics of β-arrestin-1, an essential adaptor and signaling component of the G-protein couple receptor (GPCR) signaling pathway. This work reveals a highly complex conformational energy landscape of β-arrestin-1, and illuminates the molecular mechanism of the membrane phosphoinositide PIP2-induced β-arrestin-1 activation at residue level.(https://doi.org/10.1038/s41467-023-43694-1).

Development of a toroidal soft x-ray imaging system and application for investigating three-dimensional plasma on J-TEXT

A toroidal soft x-ray imaging(T-SXRI)system has been developed to investigate threedimensional(3D)plasma physics on J-TEXT.This T-SXRI system consists of three sets of SXR arrays.Two sets are newly developed and located on the vacuum chamber wall at toroidal positionsφof 126.4°and 272.6°,respectively,while one set was established previously atφ=65.50.Each set of SXR arrays consists of three arrays viewing the plasma poloidally,and hence can be used separately to obtain SXR images via the tomographic method.The sawtooth precursor oscillations are measured by T-SXRI,and the corresponding images of perturbative SXR signals are successfully reconstructed at these three toroidal positions,hence providing measurement of the 3D structure of precursor oscillations.The observed 3D structure is consistent with the helical structure of the m/n=1/1 mode.The experimental observation confirms that the T-SXRI system is able to observe 3D structures in the J-TEXT plasma.

Recent advances in protein conformation sampling by combining machine learning with molecular simulation

The rapid advancement and broad application of machine learning(ML)have driven a groundbreaking revolution in computational biology.One of the most cutting-edge and important applications of ML is its integration with molecular simulations to improve the sampling efficiency of the vast conformational space of large biomolecules.This review focuses on recent studies that utilize ML-based techniques in the exploration of protein conformational landscape.We first highlight the recent development of ML-aided enhanced sampling methods,including heuristic algorithms and neural networks that are designed to refine the selection of reaction coordinates for the construction of bias potential,or facilitate the exploration of the unsampled region of the energy landscape.Further,we review the development of autoencoder based methods that combine molecular simulations and deep learning to expand the search for protein conformations.Lastly,we discuss the cutting-edge methodologies for the one-shot generation of protein conformations with precise Boltzmann weights.Collectively,this review demonstrates the promising potential of machine learning in revolutionizing our insight into the complex conformational ensembles of proteins.