COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas.

A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.

TRPML3/BK complex promotes autophagy and bacterial clearance by providing a positive feedback regulation of mTOR via PI3P.

TRPML3 is a Ca2+/Na+ release channel residing in both phagophores and endolysosomal membranes. It is activated by PI3P and PI3,5P2. Its activity can be enhanced by high luminal pH and by replacing luminal Na+ with K+. Here, we report that big-conductance Ca2+-activated potassium (BK) channels form a positive feedback loop with TRPML3. Ca2+ release via TRPML3 activates BK, which in turn facilitates TRPML3-mediated Ca2+ release, potentially through removing luminal Na+ inhibition. We further show that TRPML3/BK and mammalian target of rapamycin (mTOR) form another positive feedback loop to facilitate autophagy induction in response to nutrient starvation, i.e., mTOR inhibition upon nutrient starvation activates TRPML3/BK, and this further reduces mTOR activity, thereby increasing autophagy induction. Mechanistically, the feedback regulation between TRPML3/BK and mTOR is mediated by PI3P, an endogenous TRPML3 activator that is enriched in phagophores and is up-regulated by mTOR reduction. Importantly, bacterial infection activates TRPML3 in a BK-dependent manner, and both TRPML3 and BK are required for mTOR suppression and autophagy induction responding to bacterial infection. Suppressing either TRPML3 or BK helps bacteria survival whereas increasing either TRPML3 or BK favors bacterial clearance. Considering that TRPML3/BK is inhibited by low luminal pH but activated by high luminal pH and PI3P in phagophores, we suggest that TRPML3/BK and mTOR form a positive feedback loop via PI3P to ensure efficient autophagy induction in response to nutrient deprivation and bacterial infection. Our study reveals a role of TRPML3-BK coupling in controlling cellular homeostasis and intracellular bacterial clearance via regulating mTOR signaling.

An interpretable single-cell RNA sequencing data clustering method based on latent Dirichlet allocation.

Single-cell RNA sequencing (scRNA-seq) detects whole transcriptome signals for large amounts of individual cells and is powerful for determining cell-to-cell differences and investigating the functional characteristics of various cell types. scRNA-seq datasets are usually sparse and highly noisy. Many steps in the scRNA-seq analysis workflow, including reasonable gene selection, cell clustering and annotation, as well as discovering the underlying biological mechanisms from such datasets, are difficult. In this study, we proposed an scRNA-seq analysis method based on the latent Dirichlet allocation (LDA) model. The LDA model estimates a series of latent variables, i.e. putative functions (PFs), from the input raw cell-gene data. Thus, we incorporated the 'cell-function-gene' three-layer framework into scRNA-seq analysis, as this framework is capable of discovering latent and complex gene expression patterns via a built-in model approach and obtaining biologically meaningful results through a data-driven functional interpretation process. We compared our method with four classic methods on seven benchmark scRNA-seq datasets. The LDA-based method performed best in the cell clustering test in terms of both accuracy and purity. By analysing three complex public datasets, we demonstrated that our method could distinguish cell types with multiple levels of functional specialization, and precisely reconstruct cell development trajectories. Moreover, the LDA-based method accurately identified the representative PFs and the representative genes for the cell types/cell stages, enabling data-driven cell cluster annotation and functional interpretation. According to the literature, most of the previously reported marker/functionally relevant genes were recognized.

Acetyl-CoA Carboxylase1 Influences ECERIFERUM2 Activity to Mediate the Synthesis of Very-Long-Chain Fatty Acid Past C28.

Cuticular wax is a protective layer on the aerial surfaces of land plants. In Arabidopsis (Arabidopsis thaliana), cuticular wax is mainly constituted of compounds derived from very-long-chain fatty acids (VLCFAs) with chain lengths longer than C28. CER2-LIKE (ECERIFERUM2-LIKE) proteins interact with CER6/KCS6 (ECERIFERUM6/ß-Ketoacyl-CoA Synthase6), the key enzyme of the fatty acid elongase complex, to modify its substrate specificity for VLCFA elongation past C28. However, the molecular regulatory mechanism of CER2-LIKE proteins remains unclear. Arabidopsis eceriferum19 (cer19) mutants display wax-deficient stems caused by loss of waxes longer than C28, indicating that CER19 may participate in the CER2-LIKE-mediated VLCFA elongation past C28. Using positional cloning and genetic complementation, we showed that CER19 encodes Acetyl-CoA Carboxylase1 (ACC1), which catalyzes the synthesis of malonyl-CoA, the essential substrate for the CER6/KCS6-mediated condensation reaction in VLCFA synthesis. We demonstrated that ACC1 physically interacts with CER2-LIKE proteins via split-ubiquitin yeast two-hybrid (SUY2H) and firefly luciferase complementation imaging (LCI) analysis. Additionally, heterologous expression in yeast and genetic analysis in Arabidopsis revealed that ACC1 affects CER2 activity to influence VLCFA elongation past C28. These findings imply that CER2-LIKE proteins might function as a link between ACC1 and CER6/KCS6 and subsequently enhance CER6/KCS6 binding to malonyl-CoA for further utilization in VLCFA elongation past C28. This information deepens our understanding of the complex mechanism of cuticular wax biosynthesis.

Tolerogenic CD11c+dendritic cells regulate CD4+Tregs in replacing delayed ischemic preconditioning to alleviate ischemia-reperfusion acute kidney injury.

Ischemia-reperfusion injury (IRI) is one of the primary clinical causes of acute kidney injury (AKI). The key to IRI lies in immune-inflammatory damage, where dendritic cells (DCs) play a central role in eliciting immune responses within the context of inflammation induced by ischemia-reperfusion. Our previous study has confirmed that delayed ischemic preconditioning (DIPC) can reduce the kidney injury by mediating DCs to regulate T-cells. However, the clinical feasibility of DIPC is limited, as pre-clamping of the renal artery is not applicable for the prevention and treatment of ischemia-reperfusion acute kidney injury (I/R-AKI) in clinical patients. Therefore, the infusion of DCs as a substitute for DIPC presents a more viable strategy for preventing renal IRI. In this study, we further evaluated the impact and mechanism of infused tolerogenic CD11c+DCs on the kidneys following IRI by isolating bone marrow-derived dendritic cells and establishing an I/R-AKI model after pre-infusion of DCs. Renal function was significantly improved in the I/R-AKI mouse model after pre-infused with CD11c+DCs. The pro-inflammatory response and oxidative damage were reduced, and the levels of T helper 2 (Th2) cells and related anti-inflammatory cytokines were increased, which was associated with the reduction of autologous DCs maturation mediated by CD11c+DCs and the increase of regulatory T-cells (Tregs). Next, knocking out CD11c+DCs, we found that the reduced immune protection of tolerogenic CD11c+DCs reinfusion was related to the absence of own DCs. Together, pre-infusion of tolerogenic CD11c+DCs can replace the regulatory of DIPC on DCs and T-cells to alleviate I/R-AKI. DC vaccine is expected to be a novel avenue to prevent and treat I/R-AKI.

Impact of mutations in SARS-COV-2 spike on viral infectivity and antigenicity.

Since the outbreak of SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, the viral genome has acquired numerous mutations with the potential to alter the viral infectivity and antigenicity. Part of mutations in SARS-CoV-2 spike protein has conferred virus the ability to spread more quickly and escape from the immune response caused by the monoclonal neutralizing antibody or vaccination. Herein, we summarize the spatiotemporal distribution of mutations in spike protein, and present recent efforts and progress in investigating the impacts of those mutations on viral infectivity and antigenicity. As mutations continue to emerge in SARS-CoV-2, we strive to provide systematic evaluation of mutations in spike protein, which is vitally important for the subsequent improvement of vaccine and therapeutic neutralizing antibody strategies.

Identification of alternative splicing-derived cancer neoantigens for mRNA vaccine development.

Messenger RNA (mRNA) vaccines have shown great potential for anti-tumor therapy due to the advantages in safety, efficacy and industrial production. However, it remains a challenge to identify suitable cancer neoantigens that can be targeted for mRNA vaccines. Abnormal alternative splicing occurs in a variety of tumors, which may result in the translation of abnormal transcripts into tumor-specific proteins. High-throughput technologies make it possible for systematic characterization of alternative splicing as a source of suitable target neoantigens for mRNA vaccine development. Here, we summarized difficulties and challenges for identifying alternative splicing-derived cancer neoantigens from RNA-seq data and proposed a conceptual framework for designing personalized mRNA vaccines based on alternative splicing-derived cancer neoantigens. In addition, several points were presented to spark further discussion toward improving the identification of alternative splicing-derived cancer neoantigens.

DeepCCI: a deep learning framework for identifying cell-cell interactions from single-cell RNA sequencing data.

MOTIVATION: Cell-cell interactions (CCIs) play critical roles in many biological processes such as cellular differentiation, tissue homeostasis, and immune response. With the rapid development of high throughput single-cell RNA sequencing (scRNA-seq) technologies, it is of high importance to identify CCIs from the ever-increasing scRNA-seq data. However, limited by the algorithmic constraints, current computational methods based on statistical strategies ignore some key latent information contained in scRNA-seq data with high sparsity and heterogeneity. RESULTS: Here, we developed a deep learning framework named DeepCCI to identify meaningful CCIs from scRNA-seq data. Applications of DeepCCI to a wide range of publicly available datasets from diverse technologies and platforms demonstrate its ability to predict significant CCIs accurately and effectively. Powered by the flexible and easy-to-use software, DeepCCI can provide the one-stop solution to discover meaningful intercellular interactions and build CCI networks from scRNA-seq data. AVAILABILITY AND IMPLEMENTATION: The source code of DeepCCI is available online at https://github.com/JiangBioLab/DeepCCI.

Targeted inhibition of DHODH is synergistic with BCL2 blockade in HGBCL with concurrent MYC and BCL2 rearrangement.

High-grade B-cell lymphoma (HGBCL), the subtype of non-Hodgkin lymphoma, to be relapsed or refractory in patients after initial therapy or salvage chemotherapy. Dual dysregulation of MYC and BCL2 is one of the important pathogenic mechanisms. Thus, combined targeting of MYC and BCL2 appears to be a promising strategy. Dihydroorotate dehydrogenase (DHODH) is the fourth rate-limiting enzyme for the de novo biosynthesis of pyrimidine. It has been shown to be a potential therapeutic target for multiple diseases. In this study, the DHODH inhibitor brequinar exhibited growth inhibition, cell cycle blockade, and apoptosis promotion in HGBCL cell lines with MYC and BCL2 rearrangements. The combination of brequinar and BCL2 inhibitors venetoclax had a synergistic inhibitory effect on the survival of DHL cells through different pathways. Venetoclax could upregulate MCL-1 and MYC expression, which has been reported as a resistance mechanism of BCL2 inhibitors. Brequinar downregulated MCL-1 and MYC, which could potentially overcome drug resistance to venetoclax in HGBCL cells. Furthermore, brequinar could downregulate a broad range of genes, including ribosome biosynthesis genes, which might contribute to its anti-tumor effects. In vivo studies demonstrated synergetic tumor growth inhibition in xenograft models with brequinar and venetoclax combination treatment. These results provide preliminary evidence for the rational combination of DHODH and BCL2 blockade in HGBCL with abnormal MYC and BCL2.

Achieving Dual Emission of Fluorescence and Phosphorescence from Anti-Kasha's Metal-Organic Halides for Information Encryption.

Luminescent materials typically emit their fluorescence or phosphorescence at a specific wavelength with different excitation energies via the so-called Kasha's rule. If fluorescence or phosphorescence emission via anti-Kasha's rule could be achieved, it will hold great promise for applications in many fields. In this work, we report the synthesis and characterization of new metal-organic halide materials with dual emission of efficient room-temperature phosphorescence and fluorescence, which obey anti-Kasha's rule. Here, three emitting metal-organic halides with formula [ZnX2(bidpe)] (X = Cl for 1, X = Br for 2, X = I for 3, bidpe = 4,4'-bis(imidazol-1-yl)diphenyl ether) were prepared and their photophysical properties were investigated. The complexes exhibit dual emission of fluorescence and phosphorescence via anti-Kasha's rule, and their RTP properties of resultant products are modulated by halide substitution synthesis. DFT calculations indicate that the singlet states exhibit a halide-ligand charge transfer (XLCT) character while the triplet states are dominated by the intraligand π-π* transitions. Furthermore, the multilevel information encryption and anticounterfeiting applications are developed by virtue of anti-Kasha's rule emission.

Suppressing the Thermal Quenching Effect via a Cluster Conformer in Copper(I)-Iodide Coordination Polymeric Phosphors for High-Power White LED Lighting.

High-power LED lighting is a crucial challenge due to the notorious thermal quenching (TQ) effect of traditional phosphors at high operating currents, which would result in poor device performance and hamper practical optoelectronic application. Herein, we demonstrate ligand engineering of a cubane- versus staircase-like [Cu4I4] conformer as a node in coordination polymers, which remarkably suppresses the TQ effect of cluster-based photoluminescence. For complex 1 (the formula [Cu4I4(bbimb)2]n) with the cubane-like [Cu4I4] conformer as a node, the metallophilicity interaction enables ultrabright triplet emission with a photoluminescence quantum yield over 82%, and the phonon-assisted detrapping process of excitons effectively suppresses the TQ effect in the wide temperature range. In contrast, the staircase-like [Cu4I4] conformer as a node in complex 2 (the formula [Cu4I4(bbtmb)2]n) exhibits a serious TQ effect over the investigated temperature. Phosphor-converted white LEDs (pc-wLEDs) were fabricated by integrating the cluster-based coordination polymers as a color converter, and their electroluminescence performances were investigated under high bias currents. The prototype pc-wLED device by incorporating the phosphor with the suppressed TQ effect exhibits a continuous rise in brightness under a high bias current of 300 mA. The results demonstrate that ligand engineering of the cluster conformer via suppressing the TQ effect proves efficient in designing an ideal color converter for high-power pc-wLED lighting.

Long- and Intermediate-Term Ambient Particulate Pollution Is Associated with Increased Osteoarthritis Risk: A Population-Based Prospective Analysis.

Recent studies found the intrusion and retention of exogenous fine particles into joints, but epidemiological data for long- and intermediate-term exposure associations are scare. Here, all urban working, retired employee, and rural residents (16.78 million) in Beijing from January 1, 2011 to December 31, 2019 were included to investigate the effects of long- and intermediate-term ambient particulate exposure on development of osteoarthritis. We identified 1,742,067 participants as first-visit patients with osteoarthritis. For each interquartile range increase in annual PM2.5 (23.32 µg/m3) and PM10 (23.92 µg/m3) exposure concentration, the pooled hazard ratios were respectively 1.238 (95% CI: 1.228, 1.249) and 1.178 (95% CI: 1.168, 1.189) for first osteoarthritis outpatient visits. Moreover, age at first osteoarthritis outpatient visits significantly decreased by 4.52 (95% CI: 3.45 to 5.40) days per µg/m3 for annual PM2.5 exposure at below 67.85 µg/m3. Finally, among the six constituents analyzed, black carbon appears to be the most important component associated with the association between PM2.5 exposure and the three osteoarthritis-related outcomes.

The global patent landscape of emerging infectious disease monkeypox.

BACKGROUND: Monkeypox is an emerging infectious disease with confirmed cases and deaths in several parts of the world. In light of this crisis, this study aims to analyze the global knowledge pattern of monkeypox-related patents and explore current trends and future technical directions in the medical development of monkeypox to inform research and policy. METHODS: A comprehensive study of 1,791 monkeypox-related patents worldwide was conducted using the Derwent patent database by descriptive statistics, social network method and linear regression analysis. RESULTS: Since the 21st century, the number of monkeypox-related patents has increased rapidly, accompanied by increases in collaboration between commercial and academic patentees. Enterprises contributed the most in patent quantity, whereas the initial milestone patent was filed by academia. The core developments of technology related to the monkeypox include biological and chemical medicine. The innovations of vaccines and virus testing lack sufficient patent support in portfolios. CONCLUSIONS: Monkeypox-related therapeutic innovation is geographically limited with strong international intellectual property right barriers though it has increased rapidly in recent years. The transparent licensing of patent knowledge is driven by the merger and acquisition model, and the venture capital, intellectual property and contract research organization model. Currently, the patent thicket phenomenon in the monkeypox field may slow the progress of efforts to combat monkeypox. Enterprises should pay more attention to the sharing of technical knowledge, make full use of drug repurposing strategies, and promote innovation of monkeypox-related technology in hotspots of antivirals (such as tecovirimat, cidofovir, brincidofovir), vaccines (JYNNEOS, ACAM2000), herbal medicine and gene therapy.

DeepST: identifying spatial domains in spatial transcriptomics by deep learning.

Recent advances in spatial transcriptomics (ST) have brought unprecedented opportunities to understand tissue organization and function in spatial context. However, it is still challenging to precisely dissect spatial domains with similar gene expression and histology in situ. Here, we present DeepST, an accurate and universal deep learning framework to identify spatial domains, which performs better than the existing state-of-the-art methods on benchmarking datasets of the human dorsolateral prefrontal cortex. Further testing on a breast cancer ST dataset, we showed that DeepST can dissect spatial domains in cancer tissue at a finer scale. Moreover, DeepST can achieve not only effective batch integration of ST data generated from multiple batches or different technologies, but also expandable capabilities for processing other spatial omics data. Together, our results demonstrate that DeepST has the exceptional capacity for identifying spatial domains, making it a desirable tool to gain novel insights from ST studies.

Renal outcomes after contrast exposure in patients with diabetes who use sodium-glucose cotransporter 2 inhibitors.

BACKGROUND: Contrast-induced nephropathy has become increasingly prevalent as the age and prevalence of comorbidities in the general population have increased. Most cases of contrast-induced nephropathy are reversible; however, some may progress to acute kidney disease, and subsequently, to chronic kidney disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are known for their renoprotective effects. However, whether the use of these inhibitors affects the risk of contrast-induced kidney injury remains unclear. METHODS: Data were collected from the Taipei Medical University Clinical Research Database. We included patients with diabetes who had contrast exposure between 2016 and 2020 because of computed tomography or coronary angiography. The primary outcome was the risk of a major adverse kidney event (MAKE), which encompassed acute kidney disease, chronic kidney disease progression, and the need for renal replacement therapy. Overlap weighting was performed to reduce the effects of potential confounders. RESULTS: This study included 12 421 patients, who were divided into two groups: SGLT2i users (n = 920) and nonusers (n = 11 501). The follow-up period after contrast exposure was 6 months. The risk of a MAKE was lower in SGLT2i users than in nonusers (incidence, 36.9 vs. 49.9 per 1000 person-months, respectively; P = .0011). Furthermore, the incidence of acute kidney disease or chronic kidney disease progression was significantly lower in the SGLT2i users than in nonusers. However, no significant between-group difference was noted in the incidence of other MAKEs. CONCLUSIONS: SGLT2i may be safely used in diabetic patients needing contrast exposure. The risk of a MAKE may be lower in SGLT2i users than in nonusers.

Analysis of genetic diversity and structure of endangered Dengchuan cattle population using a single-nucleotide polymorphism chip.

This study aimed to evaluate the genetic diversity and structure within the Dengchuan cattle population and effectively protect and utilize their germplasm resources. Herein, the single-nucleotide polymorphisms (SNPs) of 100 Dengchuan cattle (46 bulls and 54 cows) were determined using the GGP Bovine 100K SNP Beadchip. The results showed that among the Dengchuan cattle, a total of 101,220 SNPs were detected, and there were 83,534 SNPs that passed quality control, of which 85.7% were polymorphic. The average genetic distance based on identity-by-state (IBS) within the conservation population of Dengchuan cattle was 0.26 ± 0.02. A total of 3,999 genome-length runs of homozygosity (ROHs) were detected in the Dengchuan cattle, with ROH lengths primarily concentrated in the range of 1-5 Mb, accounting for 87.02% of the total. The average inbreeding coefficient based on ROHs was 4.6%, within the conservation population of Dengchuan cattle, whereas it was 4.9% for bulls, and the Wright inbreeding coefficient (FIS) value was 2.4%, demonstrating a low level of inbreeding within the Dengchuan cattle population. Based on neighbor-joining tree analysis, the Dengchuan cattle could be divided into 16 families. In summary, the conservation population of Dengchuan cattle displays relatively abundant diversity and a moderate genetic relationship. Inbreeding was observed among a few individuals, but the overall inbreeding level of the population remained low. It is important to maintain this low level of inbreeding when introducing purebred bloodlines to expand the core group. This approach will ensure the long-term conservation of Dengchuan cattle germplasm resources and prevent loss of genetic diversity.

Potential pathological mechanisms and pharmacological interventions for cadmium-induced miscarriage.

The prevalence of cadmium (Cd) contamination has emerged as a significant global concern. Exposure to Cd during pregnancy is associated with adverse pregnancy outcomes, including miscarriage. However, there is currently a lack of comprehensive summaries on Cd-induced miscarriage. Therefore, it is imperative to further strengthen research into in vivo studies, clinical status, pathological mechanisms, and pharmacological interventions for Cd-induced miscarriage. This study systematically presents the current knowledge on animal models and clinical trials investigating Cd exposure-induced miscarriage. The underlying mechanisms involving oxidative stress, inflammation, endocrine disruption, and placental dysfunction caused by Cd-induced miscarriage are also extensively discussed. Additionally, potential drug interventions such as melatonin, vitamin C, and vitamin E are highlighted for their pharmacological role in mitigating adverse pregnancy outcomes induced by Cd.

Assessing the impact of Chlorantraniliprole (CAP) pesticide stress on oilseed rape (Brassia campestris L.): Residue dynamics, enzyme activities, and metabolite profiling.

This study investigates the effects of chlorantraniliprole (CAP) pesticide stress on oilseed rape through comprehensive pot experiments. Assessing CAP residue variations in soil and oilseed rape (Brassia campestris L.), enzyme activities (POD, CPR, GST), and differential metabolites, we unveil significant findings. The average CAP residue levels were 18.38-13.70 mg/kg in unplanted soil, 9.94-6.30 mg/kg in planted soil, and 0-4.18 mg/kg in oilseed rape samples, respectively. Soil microbial influences and systemic pesticide translocation into oilseed rape contribute to CAP residue variations. Under the influence of CAP stress, oilseed rape displays escalated enzyme activities (POD, CPR, GST) and manifests 57 differential metabolites. Among these, 32 demonstrate considerable downregulation, mainly impacting amino acids and phenolic compounds, while 25 exhibit noteworthy overexpression, primarily affecting flavonoid compounds. This impact extends to 24 metabolic pathways, notably influencing amide biosynthesis, as well as arginine and proline metabolism. These findings underscore the discernible effects of CAP pesticide stress on oilseed rape.

An intelligent grasper to provide real-time force feedback to shorten the learning curve in laparoscopic training.

BACKGROUND: A lack of force feedback in laparoscopic surgery often leads to a steep learning curve to the novices and traditional training system equipped with force feedback need a high educational cost. This study aimed to use a laparoscopic grasper providing force feedback in laparoscopic training which can assist in controlling of gripping forces and improve the learning processing of the novices. METHODS: Firstly, we conducted a pre-experiment to verify the role of force feedback in gripping operations and establish the safe gripping force threshold for the tasks. Following this, we proceeded with a four-week training program. Unlike the novices without feedback (Group A2), the novices receiving feedback (Group B2) underwent training that included force feedback. Finally, we completed a follow-up period without providing force feedback to assess the training effect under different conditions. Real-time force parameters were recorded and compared. RESULTS: In the pre-experiment, we set the gripping force threshold for the tasks based on the experienced surgeons' performance. This is reasonable as the experienced surgeons have obtained adequate skill of handling grasper. The thresholds for task 1, 2, and 3 were set as 0.731 N, 1.203 N and 0.938 N, respectively. With force feedback, the gripping force applied by the novices with feedback (Group B1) was lower than that of the novices without feedback (Group A1) (p < 0.005). During the training period, the Group B2 takes 6 trails to achieve gripping force of 0.635 N, which is lower than the threshold line, whereas the Group A2 needs 11 trails, meaning that the learning curve of Group B2 was significantly shorter than that of Group A2. Additionally, during the follow-up period, there was no significant decline in force learning, and Group B2 demonstrated better control of gripping operations. The training with force feedback received positive evaluations. CONCLUSION: Our study shows that using a grasper providing force feedback in laparoscopic training can help to control the gripping force and shorten the learning curve. It is anticipated that the laparoscopic grasper equipped with FBG sensor is promising to provide force feedback during laparoscopic training, which ultimately shows great potential in laparoscopic surgery.