Integrated profiling identifies DXS253E as a potential prognostic marker in colorectal cancer.

BACKGROUND: Increasing evidence suggests that DXS253E is critical for cancer development and progression, but the function and potential mechanism of DXS253E in colorectal cancer (CRC) remain largely unknown. In this study, we evaluated the clinical significance and explored the underlying mechanism of DXS253E in CRC. METHODS: DXS253E expression in cancer tissues was investigated using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Kaplan-Meier plot was used to assess the prognosis of DXS253E. The cBioPortal, MethSurv, and Tumor Immune Estimation Resource (TIMER) databases were employed to analyze the mutation profile, methylation, and immune infiltration associated with DXS253E. The biological functions of DXS253E in CRC cells were determined by CCK-8 assay, plate cloning assay, Transwell assay, flow cytometry, lactate assay, western blot, and qRT-PCR. RESULTS: DXS253E was upregulated in CRC tissues and high DXS253E expression levels were correlated with poor survival in CRC patients. Our bioinformatics analyses showed that high DXS253E gene methylation levels were associated with the favorable prognosis of CRC patients. Furthermore, DXS253E levels were linked to the expression levels of several immunomodulatory genes and an abundance of immune cells. Mechanistically, the overexpression of DXS253E enhanced proliferation, migration, invasion, and the aerobic glycolysis of CRC cells through the AKT/mTOR pathway. CONCLUSIONS: We demonstrated that DXS253E functions as a potential role in CRC progression and may serve as an indicator of outcomes and a therapeutic target for regulating the AKT/mTOR pathway in CRC.

TNKS1BP1 mediates AECII senescence and radiation induced lung injury through suppressing EEF2 degradation.

BACKGROUND: Although recent studies provide mechanistic understanding to the pathogenesis of radiation induced lung injury (RILI), rare therapeutics show definitive promise for treating this disease. Type II alveolar epithelial cells (AECII) injury in various manner results in an inflammation response to initiate RILI. RESULTS: Here, we reported that radiation (IR) up-regulated the TNKS1BP1, causing progressive accumulation of the cellular senescence by up-regulating EEF2 in AECII and lung tissue of RILI mice. Senescent AECII induced Senescence-Associated Secretory Phenotype (SASP), consequently activating fibroblasts and macrophages to promote RILI development. In response to IR, elevated TNKS1BP1 interacted with and decreased CNOT4 to suppress EEF2 degradation. Ectopic expression of EEF2 accelerated AECII senescence. Using a model system of TNKS1BP1 knockout (KO) mice, we demonstrated that TNKS1BP1 KO prevents IR-induced lung tissue senescence and RILI. CONCLUSIONS: Notably, this study suggested that a regulatory mechanism of the TNKS1BP1/CNOT4/EEF2 axis in AECII senescence may be a potential strategy for RILI.

Surprising Dynamics Phenomena in the Diels-Alder Reaction of C60 Uncovered with AI.

We performed an extensive artificial intelligence-accelerated quasi-classical molecular dynamics investigation of the time-resolved mechanism of the Diels-Alder reaction of fullerene C60 with 2,3-dimethyl-1,3-butadiene. In a substantial fraction (10%) of reactive trajectories, the larger C60 noncovalently attracts the 2,3-dimethyl-1,3-butadiene long before the barrier so that the diene undergoes the series of complex motions including roaming, somersaults, twisting, and twisting somersaults around the fullerene until it aligns itself to pass over the barrier. These complicated processes could be easily missed in typically performed quantum chemical simulations with shorter and fewer trajectories. After the barrier is passed, the bonds take longer to form compared to the simplest prototypical Diels-Alder reaction of ethene with 1,3-butadiene despite high similarities in transition states and barrier widths evaluated with intrinsic reaction coordinate (IRC) calculations. C60 is mainly responsible for these differences as its reaction with 1,3-butadiene is similar to the reaction with 2,3-dimethyl-1,3-butadiene: the only substantial difference being that the extra methyl groups double the probability of the prolonged alignment phase in dynamics. These additional calculations of C60 with 1,3-butadiene could be performed via active learning more easily by reusing the data generated for the other two reactions, showing the potential for larger-scale exploration of the effects of different substrates in the same types of reactions.

Sensor Network Attack Synthesis against Fault Diagnosis of Discrete Event Systems.

This paper investigates the problem of synthesizing network attacks against fault diagnosis in the context of discrete event systems (DESs). It is assumed that the sensor observations sent to the operator that monitors a system are tampered with by an active attacker. We first formulate the process of online fault diagnosis under attack. Then, from the attack viewpoint, we define a sensor network attacker as successful if it can degrade the fault diagnosis in the case of maintaining itself as undiscovered by the operator. To verify such an attacker, an information structure called a joint diagnoser (JD) is proposed, which describes all possible attacks in a given attack scenario. Based on the refined JD, i.e., stealthy joint diagnoser (SJD), we present an algorithmic procedure for synthesizing a successful attacker if it exists.

Investigating the impact of sebum secretion on liquid makeup foundation darkening and its solution.

OBJECTIVES: Darkening has been an issue of concern for foundation products. The secretion of sebum plays a significant role in the process of foundation darkening, but the underlying mechanisms and solutions have been rarely reported. The aim of this study was to explore the relationship between sebum secretion and liquid foundation darkening and to provide possible solutions for reducing sebum-induced darkening in liquid foundation. METHODS: Artificial sebum in different concentrations was added to a basic liquid foundation to simulate different stages of sebum secretion. The colour of the mixture was then measured by a spectrophotometer on the standard opacity chart. Potential technical solutions for anti-darkening were applied to a basic liquid foundation, and its ability to anti-darkening was further verified in vivo. RESULTS: (1) The influences of sebum addition on liquid foundation darkening had a significant positive correlation with the increase in transmissivities (R2 = 0.852, p < 0.01). (2) A certain range of sebum addition can reduce the darkening of volatile foundations. (3) The liquid foundations using pigments with high dispersibility in sebum were less influenced by sebum. (4) The replacement of pigments with oil-fixing ability could effectively reduce the darkening of liquid foundations induced by sebum (p < 0.01). CONCLUSION: The effect of sebum on the darkening of liquid foundation was accompanied by a greater transmissivity as its pigment concentration decreased. Balanced volatility, the addition of powders with higher sebum dispersibility and the replacement of oil-fixing powders could reduce the darkening of the liquid foundation caused by sebum secretion.

OBJECTIFS: L'assombrissement a été un problème de préoccupation pour les produits de fond de teint. La sécrétion de sébum joue un rôle significatif dans le processus d'assombrissement du fond de teint, mais les mécanismes sous-jacents et les solutions ont été rarement rapportés. L'objectif de cette étude était d'explorer la relation entre la sécrétion de sébum et l'assombrissement du fond de teint liquide, et de fournir des solutions possibles pour réduire l'assombrissement induit par le sébum dans le fond de teint liquide. MÉTHODES: Du sébum artificiel à différentes concentrations a été ajouté à un fond de teint liquide de base pour simuler différents stades de sécrétion de sébum. La couleur du mélange a ensuite été mesurée par un spectrophotomètre sur le tableau standard d'opacité. Des solutions techniques potentielles pour l'anti-assombrissement ont été appliquées à un fond de teint liquide de base et leur capacité à prévenir l'assombrissement a été vérifiée in vivo. RÉSULTATS: (1) Les influences de l'ajout de sébum sur l'assombrissement du fond de teint liquide avaient une corrélation significativement positive avec l'augmentation des transmissivités (R2 = 0.852 p < 0.01). (2) Une certaine plage de concentration de sebum peut réduire l'assombrissement des fondations volatiles. (3) Les fonds de teint liquides utilisant des pigments à haute dispersibilité dans le sébum étaient moins influencés par le sébum. (4) Le remplacement des pigments par des poudres à capacité de fixation d'huile pouvait efficacement réduire l'assombrissement des fonds de teint liquides induit par le sébum (p < 0.01). CONCLUSION: L'effet du sébum sur l'assombrissement du fond de teint liquide était accompagné d'une plus grande transmissivité à mesure que la concentration de son pigment diminuait. La volatilité équilibrée, l'ajout de poudres à plus grande dispersibilité de sébum et le remplacement de poudres à capacité de fixation d'huile pourraient réduire l'assombrissement du fond de teint liquide causé par la sécrétion de sébum.

Energy-conserving molecular dynamics is not energy conserving.

Molecular dynamics (MD) is a widely-used tool for simulating molecular and materials properties. It is common wisdom that molecular dynamics simulations should obey physical laws and, hence, lots of effort is put into ensuring that molecular dynamics simulations are energy conserving. The emergence of machine learning (ML) potentials for MD leads to a growing realization that monitoring conservation of energy during simulations is of low utility because the dynamics is often unphysically dissociative. Other ML methods for MD are not based on a potential and provide only forces or trajectories which are reasonable but not necessarily energy-conserving. Here we propose to clearly distinguish between the simulation-energy and true-energy conservation and highlight that the simulations should focus on decreasing the degree of true-energy non-conservation. We introduce very simple, new criteria for evaluating the quality of molecular dynamics by estimating the degree of true-energy non-conservation and we demonstrate their practical utility on an example of infrared spectra simulations. These criteria are more important and intuitive than simply evaluating the quality of the ML potential energies and forces as is commonly done and can be applied universally, e.g., even for trajectories with unknown or discontinuous potential energy. Such an approach introduces new standards for evaluating MD by focusing on the true-energy conservation and can help in developing more accurate methods for simulating molecular and materials properties.

Influence of landscape patterns on nitrate and particulate organic nitrogen inputs to urban stormwater runoff.

This study investigated the effect of the landscape pattern of permeable/impermeable patches on NO3--N and particulate organic nitrogen (PON) concentrations during stormwater runoff transport and their source contributions. Six landscape pattern indices, namely, mean proximity index (MPI), largest patch index (LPI), mean shape index (MSI), landscape shape index (LSI), connect index (CONNECT), and splitting index (SPLIT), were selected to reflect the fragmentation, complexity, and connectivity of permeable patches in urban catchments. The results show that lower fragmentation, higher complexity, and greater connectivity can reduce NO3--N concentrations in road runoff and drainage flow (i.e., the flow in the stormwater drainage network), as well as PON concentrations in road runoff. Further, the above landscape pattern is effective for mitigating the contributions of NO3--N and PON from road runoff. Low impact development (LID) can be incorporated with the landscape pattern of permeable/impermeable patches to mitigate nitrogen pollution in urban stormwater at the catchment scale by optimizing the spatial arrangement.

[sEMG Wireless Acquisition System Based on CC3200 and ADS1299].

A multi-channel surface electromyography wireless acquisition system is designed, which is mainly composed of ADS1299 integrated analog front-end chip and CC3200 wireless MCU of TI company. The key indicators of hardware are measured according to the industry standard, and the results are better than the industry standard, which can meet the continuous use of multi-scene tasks. This system has the advantages of high performance, low power consumption and small size. It has been applied to the detection of surface EMG signal in motion gesture recognition and has a good application value.

Screening and identification of a specific peptide binding to breast cancer cells from a phage-displayed peptide library.

OBJECTIVES: Breast cancer is a popular fatal malignant tumor for women with high of rates incidence and mortality. Development of the new approaches for breast cancer targeted diagnosis and chemotherapy is emergently needed by the current clinical practice, the important first step is finding a breast cancer specifically binding molecule or fragment as early clinical indicators. RESULTS: By a phage-displayed peptide library, a 12-mer peptide, CSB1 was screened out using MCF-7 cells as the target. The consequently results under immunofluorescence and laser scanning confocal microscope (LSCM) indicated that CSB1 bound MCF-7 cells and breast cancer tissues specifically and sensitively with high affinity. Bioinformatics analysis suggested that the peptide CSB1 targets the 5-Lipoxygenase-Activating Protein (FLAP), which has been implicated in breast cancer progression and prognosis. CONCLUSIONS: The peptide, CSB1 is of the potential as a candidate to be used for developing the new approaches of molecular imaging detection and targeting chemotherapy of breast cancer in the future.

Rhodococcus oryzae sp. nov., a novel actinobacterium isolated from rhizosphere soil of rice (Oryza sativa L.).

A Gram-stain-positive, non-motile, creamy-white actinobacterium, which has an elementary branching rod-coccus life cycle was isolated from the rhizosphere soil of rice (Oryza sativa L.) collected from Northeast Agricultural University in Harbin, Heilongjiang province, north-east PR China, and its taxonomic status was examined by using a polyphasic approach. Results from the 16S rRNA gene sequence study showed that the isolate, designated strain NEAU-CX67T, belonged to the genus Rhodococcus and formed a cluster with Rhodococcus maanshanensis DSM 44675T, Rhodococcus kronopolitis NEAU-ML12T and Rhodococcus tukisamuensis JCM 11308T (98.3, 98.1 and 97.7% gene sequence similarity, respectively). The major fatty acids were C16 : 0, 10-methyl C18 : 0, C18 : 1 ω9c and C16 : 1 ω7c. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The major isoprenoid quinone was MK-8(H2). Whole-cell hydrolysates contained meso-diaminopimelic acid. Arabinose, galactose and ribose were detected as diagnostic sugars from whole-cell hydrolysates. Mycolic acids were detected. The genomic DNA G+C content of strain NEAU-CX67T was 64.6 mol%. Strain NEAU-CX67T exhibited low average nucleotide identity and digital DNA-DNA hybridization values with R. maanshanensis DSM 44675T (92.1 and 45.4 %) and R. tukisamuensis JCM 11308T (81.9 and 24.4 %). On the basis of results of phylogenetic, genotypic, physiological and chemotaxonomic analysis, strain NEAU-CX67T is considered to represent a novel species of the genus Rhodococcus for which the name Rhodococcus oryzae sp. nov. is proposed. The type strain is NEAU-CX67T (=DSM 107701T=CCTCC AB 2018233T).

Development of a novel drug targeting delivery system for cervical cancer therapy.

'Targeting peptides' have demonstrated their value in diagnostic imaging and therapy and novel peptide probes specific to cervical cancer were developed. In the M13KE phage dodecapeptide (12-mer) peptide library, the phage clone S7 showed the best binding to the cancer cells as confirmed by immunofluorescence and flow cytometry assays, and was selected for continued studies. Its binding peptide, CSP3, was synthesized from the sequence of S7's 12-mer at the N-terminus of the minor coat protein pIII of this M13KE phage vector. The peptide's binding was analyzed by the same assays used for S7. It was also assessed using competitive inhibition and binding to a tissue chip. The results demonstrated that the CSP3 peptide bound to cervical carcinoma cells with high sensitivity and specificity. The positive results indicated that the peptide CSP3, conjugated with nanomaterials and chemotherapeutics, may be developed as a targeting vehicle for therapeutic drug delivery against cervical cancer, especially cervical cancer with multiple drug resistance. For this aim, we prepared a CSP3 conjugated liposome drug delivery system containing doxorubicin (DOX) and microRNA101 (miR101) expression plasmids (CSP3-Lipo-DOX-miR101), and the primary result showed that the system demonstrated significantly enhanced cytotoxicity to SiHa cells and DOX resistant SiHa cells, SiHa/ADR. Our results showed that CSP3 is a cervical cancer targeting 12aa peptide with high specificity and sensitivity, and the CSP3 conjugated drug delivery system, CSP3-Lipo-DOX-miR101 has promising potential for development as an efficient drug system for the therapy of cervical cancer.

Annexin A2 Enhances the Progression of Colorectal Cancer and Hepatocarcinoma via Cytoskeleton Structural Rearrangements.

Annexin A2 (ANXA2) is reported to be associated with cancer development. To investigate the roles ANXA2 plays during the development of cancer, the RNAi method was used to inhibit the ANXA2 expression in caco2 (human colorectal cancer cell line) and SMMC7721 (human hepatocarcinoma cell line) cells. The results showed that when the expression of ANXA2 was efficiently inhibited, the growth and motility of both cell lines were significantly decreased, and the development of the motility relevant microstructures, such as pseudopodia, filopodia, and the polymerization of microfilaments and microtubules were obviously inhibited. The cancer cell apoptosis was enhanced without obvious significance. The possible regulating pathway in the process was also predicted and discussed. Our results suggested that ANXA2 plays important roles in maintaining the malignancy of colorectal and hepatic cancer by enhancing the cell proliferation, motility, and development of the motility associated microstructures of cancer cells based on a possible complicated signal pathway.

Microbial analysis of MAP pot-stewed duck wings under different conditions during 15 °C storage.

This study was to investigate the changes of microbial community and counts of MAP pot-stewed duck wing (PSDW) under different packaging films and spices ratio during 15 °C storage, using the traditional bacterial cultivation and PCR-DGGE. Results of microbial counting showed that the shelf-life of PDSW during 15 °C storage for recommendation was within six days, and the packaging films and spices ratio didn't affect the change of microbial numbers in PSDW during storage. PCR-DGGE analysis revealed that Staphylococcus equorum, Weissella sp., Leuconostoc mesenteroides became the dominating bacteria of PSDW at the end of storage, and high barrier cover film, general barrier base film and spice ratio 1:1, had a better inhibition effect on bacteria in PSDW products, which could be used as the condition for PSDW storage. This study will help PSDW processing enterprises visualize the biodiversity of PSDW during storage, and choose the best condition for the subsequent processing.

Scalable parameterized quantum circuits classifier.

As a generalized quantum machine learning model, parameterized quantum circuits (PQC) have been found to perform poorly in terms of classification accuracy and model scalability for multi-category classification tasks. To address this issue, we propose a scalable parameterized quantum circuits classifier (SPQCC), which performs per-channel PQC and combines the measurements as the output of the trainable parameters of the classifier. By minimizing the cross-entropy loss through optimizing the trainable parameters of PQC, SPQCC leads to a fast convergence of the classifier. The parallel execution of identical PQCs on different quantum machines with the same structure and scale reduces the complexity of classifier design. Classification simulations performed on the MNIST Dataset show that the accuracy of our proposed classifier far exceeds that of other quantum classification algorithms, achieving the state-of-the-art simulation result and surpassing/reaching classical classifiers with a considerable number of trainable parameters. Our classifier demonstrates excellent scalability and classification performance.

Physics-Informed Active Learning for Accelerating Quantum Chemical Simulations.

Quantum chemical simulations can be greatly accelerated by constructing machine learning potentials, which is often done using active learning (AL). The usefulness of the constructed potentials is often limited by the high effort required and their insufficient robustness in the simulations. Here, we introduce the end-to-end AL for constructing robust data-efficient potentials with affordable investment of time and resources and minimum human interference. Our AL protocol is based on the physics-informed sampling of training points, automatic selection of initial data, uncertainty quantification, and convergence monitoring. The versatility of this protocol is shown in our implementation of quasi-classical molecular dynamics for simulating vibrational spectra, conformer search of a key biochemical molecule, and time-resolved mechanism of the Diels-Alder reaction. These investigations took us days instead of weeks of pure quantum chemical calculations on a high-performance computing cluster.

SimPLE, a visuotactile method learned in simulation to precisely pick, localize, regrasp, and place objects.

Existing robotic systems have a tension between generality and precision. Deployed solutions for robotic manipulation tend to fall into the paradigm of one robot solving a single task, lacking "precise generalization," or the ability to solve many tasks without compromising on precision. This paper explores solutions for precise and general pick and place. In precise pick and place, or kitting, the robot transforms an unstructured arrangement of objects into an organized arrangement, which can facilitate further manipulation. We propose SimPLE (Simulation to Pick Localize and placE) as a solution to precise pick and place. SimPLE learns to pick, regrasp, and place objects given the object's computer-aided design model and no prior experience. We developed three main components: task-aware grasping, visuotactile perception, and regrasp planning. Task-aware grasping computes affordances of grasps that are stable, observable, and favorable to placing. The visuotactile perception model relies on matching real observations against a set of simulated ones through supervised learning to estimate a distribution of likely object poses. Last, we computed a multistep pick-and-place plan by solving a shortest-path problem on a graph of hand-to-hand regrasps. On a dual-arm robot equipped with visuotactile sensing, SimPLE demonstrated pick and place of 15 diverse objects. The objects spanned a wide range of shapes, and SimPLE achieved successful placements into structured arrangements with 1-mm clearance more than 90% of the time for six objects and more than 80% of the time for 11 objects.

Quantification of agricultural plastic debris loss through soil erosion and associated phthalic acid esters emissions into the aquatic environment.

Terrestrial agricultural plastic film (APF) residue migration triggered by soil erosion constitutes a primary disruption in the plastic waste cycle. However, the migration mechanisms of APF residue and phthalate acid esters (PAEs) emissions from APF debris into China's aquatic environment remain inadequately understood. This study assessed APF residue loss induced by soil erosion and the associated PAEs emissions from 14 crop categories across China for 1998-2020, employing an integrated estimation framework and high-resolution agricultural activity data. Our findings indicate that the APF residue loss ranged in 968.95-2081.76 tons yr-1 during the study period, peaking in 2016. Areas with high APF residue losses were concentrated in southwestern, central, northwestern, northeastern, northern, and eastern China. Moreover, PAEs emitted from APF debris ranged in 29.57-59.42 kg yr-1 over the same period, with emission hotspots identified in northwestern, southwestern, and eastern China. The APF application, meteorological factors, and soil properties collectively accounted for 33.82 %, 33.33 %, and 13.66 % of the total variance, respectively. Finally, the potential ecological risk posed by PAEs to the aquatic environment was found to be low. Overall, our findings offer crucial insights into the dynamics of plastic contamination and provide foundational knowledge for safeguarding aquatic environments in China.

Combination therapies with Wnt signaling inhibition: A better choice for prostate cancer treatment.

The intractability and high mortality rate of castration-resistant prostate cancer (CRPC) remain the most challenging problems in the field of prostate cancer (PCa). Emerging evidence has shown that the dysregulation of Wnt signaling pathways, which are highly conserved cascades that regulate embryonic development and maintain tissue homeostasis, is involved in various stages of PCa occurrence and progression. In this review, we systemically discuss the mechanisms by which the androgen receptor (AR) signaling pathway and Wnt signaling pathways participate in the occurrence of PCa and its progression to CRPC. Specifically, we elaborate on how Wnt signaling pathways induce the malignant transformation of prostate cells, promote the malignant progression of PCa and establish an immunosuppressive prostate tumor microenvironment through interaction with the AR pathway or in an AR-independent manner. We also discuss how Wnt signaling pathways enhances the stemness characteristics of prostate cancer stem cells (PCSCs) to induce the occurrence and metastasis of CPPC. Additionally, we discuss the latest progress in the use of different types of drugs that inhibit the Wnt signaling pathways in the treatment of PCa. We believe that the combination of Wnt signaling-based drugs with endocrine and other therapies is necessary and may enhance the clinical efficacy in the treatment of all types of PCa.

Wnt signaling: Modulating tumor-associated macrophages and related immunotherapeutic insights.

Wnt signaling pathways are highly conserved cascades that mediate multiple biological processes through canonical or noncanonical pathways, from embryonic development to tissue maintenance, but they also contribute to the pathogenesis of numerous cancers. Recent studies have revealed that Wnt signaling pathways critically control the interplay between cancer cells and tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) and potentially impact the efficacy of cancer immunotherapy. In this review, we summarize the evidence that Wnt signaling pathways boost the maturation and infiltration of macrophages for immune surveillance in the steady state but also polarize TAMs toward immunosuppressive M2-like phenotypes for immune escape in the TME. Both cancer cells and TAMs utilize Wnt signaling to transmit signals, and this interaction is crucial for the carcinogenesis and progression of common solid cancers, such as colorectal, gastric, hepatocellular, breast, thyroid, prostate, kidney, and lung cancers; osteosarcoma; and glioma. Specifically, compared with those in solid cancers, Wnt signaling pathways play a distinct role in the pathogenesis of leukemia. Efforts to develop Wnt-based drugs for cancer treatment are still ongoing, and some indeed enhance the anticancer immune response. We believe that the combination of Wnt signaling-based therapy with conventional or immune therapies is a promising therapeutic approach and can facilitate personalized treatment for most cancers.

Emerging Diabetes Therapies: Regenerating Pancreatic ß Cells.

The incidence of diabetes mellitus (DM) is steadily increasing annually, with 537 million diabetic patients as of 2021. Restoring diminished ß cell mass or impaired islet function is crucial in treating DM, particularly type 1 DM. However, the regenerative capacity of islet ß cells, which primarily produce insulin, is severely limited, and natural regeneration is only observed in young rodents or children. Hence, there is an urgent need to develop advanced therapeutic approaches that can regenerate endogenous ß cells or replace them with stem cell (SC)-derived or engineered ß-like cells. Current strategies for treating insulin-dependent DM mainly include promoting the self-replication of endogenous ß cells, inducing SC differentiation, reprogramming non-ß cells into ß-like cells, and generating pancreatic-like organoids through cell-based intervention. In this Review, we discuss the current state of the art in these approaches, describe associated challenges, propose potential solutions, and highlight ongoing efforts to optimize ß cell or islet transplantation and related clinical trials. These effective cell-based therapies will generate a sustainable source of functional ß cells for transplantation and lay strong foundations for future curative treatments for DM.