BACKGROUND: Telesurgery has the potential to overcome spatial limitations for surgeons, which depends on surgical robot and the quality of network communication. However, the influence of network latency and bandwidth on telesurgery is not well understood. METHODS: A telesurgery system capable of dynamically adjusting image compression ratios in response to bandwidth changes was established between Beijing and Sanya (Hainan province), covering a distance of 3000 km. In total, 108 animal operations, including 12 surgical procedures, were performed. Total latency ranging from 170 ms to 320 ms and bandwidth from 15-20 Mbps to less than 1 Mbps were explored using designed surgical tasks and hemostasis models for renal vein and internal iliac artery rupture bleeding. Network latency, jitter, frame loss, and bit rate code were systemically measured during these operations. National Aeronautics and Space Administration Task Load Index (NASA-TLX) and a self-designed scale measured the workload and subjective perception of surgeons. RESULTS: All 108 animal telesurgeries, conducted from January 2023 to June 2023, were performed effectively over a total duration of 3866 min. The operations were completed with latency up to 320 ms and bandwidths as low as 1-5 Mbps. Hemostasis for vein and artery rupture bleeding models was effectively achieved under these low bandwidth conditions. The NASA-TLX results indicated that latency significantly impacted surgical performance more than bandwidth and image clarity reductions. CONCLUSIONS This telesurgery system demonstrated safety and reliability. A total of 320 ms latency is acceptable for telesurgery operations. Reducing image clarity can effectively mitigate the potential latency increase caused by decreased bandwidth, offering a new method to reduce the impact of latency on telesurgery.
Animals ; Robotic Surgical Procedures/methods* ; Laparoscopy/methods*

This paper realized a portable brain-computer interface (BCI) system tailored for smart healthcare. Through the decoding of steady-state visual evoked potential (SSVEP), this system can rapidly and accurately identify the intentions of subjects, thereby meeting the practical demands of daily medical scenarios. Firstly, an SSVEP stimulation interface and an electroencephalogram (EEG) signal acquisition software were designed, which enable the system to execute multi-target and multi-task operations while also incorporating data visualization functionality. Secondly, the EEG signals recorded from the occipital region were decomposed into eight sub-frequency bands using filter bank canonical correlation analysis (FBCCA). Subsequently, the similarity between each sub-band signal and the reference signals was computed to achieve efficient SSVEP decoding. Finally, 15 subjects were recruited to participate in the online evaluation of the system. The experimental results indicated that in real-world scenarios, the system achieved an average accuracy of 85.19% in identifying the intentions of the subjects, and an information transfer rate (ITR) of 37.52 bit/min. This system was awarded third prize in the Visual BCI Innovation Application Development competition at the 2024 World Robot Contest, validating its effectiveness. In conclusion, this study has developed a portable, multifunctional SSVEP online decoding system, providing an effective approach for human-computer interaction in smart healthcare.
Brain-Computer Interfaces ; Humans ; Evoked Potentials, Visual/physiology* ; Electroencephalography ; Signal Processing, Computer-Assisted ; Software ; Adult ; Male

OBJECTIVE To establish a rapid nondestructive detection method for the sporoderm-broken rate of Ganoderma lucidum spore powder by hyperspectral technology combined with chemometrics. METHODS Hyperspectral images of Ganoderma lucidum spore powder samples with different sporoderm-broken rates were collected, and spectral data in the visible-shortwave near-infrared band(397−1 004 nm) range of each sample were calculated after selecting the region of interest. Compared 6 spectral preprocessing methods[standard normal variable transformation, multivariate scattering correction, Savitsky-Golay(SG) smoothing, wavelet transform, SG smoothing+standard normal variable transformation, and SG smoothing+multivariate scattering correction], 5 characteristic band extraction methods(competitive adaptive reweighting, successive projections algorithm, uninformative variables elimination, least angle regression, and genetic algorithm), and 5 algorithms(partial least squares regression, support vector regression, extreme learning machine, multilayer perceptron, and LightGBM) for constructing quantitative correction models to predicts performance. RESULTS The optimal combination was SG smoothing+competitive adaptive reweighted feature band selection+partial least squares. The quantitative correction model established based on the algorithm combination achieved a prediction set coefficient of 0.868 2, and a root mean square error of 0.011 7 for Ganoderma lucidum spore powder samples with a sporoderm-broken rate range of 90%−100%. The selected optimal algorithm combination was applied to construct a quantitative correction model with a sporoderm-broken rate range of 0−100%, the coefficient of determination for the test set was 0.973 1 and the root mean square error was 0.049 3, showing good generalization ability. CONCLUSION The established quantitative detection model can realize the rapid and non-destructive detection of the sporoderm-broken rate of Ganoderma lucidum spore powder, which provides technical support for the quality control of Ganoderma lucidum spore powder and its products.

Objective To construct hepatocyte-specific silence information regulator 3(Sirt3)gene knockout(Sirt3 Δhep)mice by Cre-loxP technique,and to provide an important animal model for further studying the biological function of the hepatocyte Sirt3 gene in diseases.Methods LoxP-labeled Sirt3flox/flox mice were mated with Alb-Cre homozygous(Alb-Cre+/+)mice,and the F1 generation Sirt3flox/-/Alb-Cre+/-mice were then mated with Sirt3flox/flox mice,and the F2 genotype of Sirt3flox/flox/Alb-Cre+/-mice were the Sirt3 Δhep mice constructed in this ex-periment.Sirt3flox/flox/Alb-Cre-/-(Sirt3flox/flox)mice were the control mice.Mouse tail genome DNA was extracted and PCR was used to identify the genotypes of the offspring mice.Immunofluorescence was used to detect Sirt3 ex-pression in mouse hepatocytes.Primary hepatocytes and tissue proteins of Sirt3 Δhep mice were extracted,and the ex-pression of Sirt3 in mouse hepatocytes and other tissues was verified by Western blot.HE staining was used to ob-serve mice's liver,heart,spleen,and lung tissue structure.Results Sirt3 Δhep mice were successfully identified.Immunofluorescence and Western blot results demonstrated a significant decrease in the expression of Sirt3 in the hepatocytes of these mice compared to the control group(P<0.01).At the same time,there was no significant difference in the expression of Sirt3 in the heart,spleen,kidney,and lung tissues of Sirt3 Δhep mice compared with the control group(P>0.05).The results of HE staining showed that the histological characteristics of the liver,heart,spleen,lungs,kidneys,and other major organs of Sirt3 Δhep mice were not significantly different from those of the control group mice.Conclusion Hepatocyte-specific Sirt3 gene knockout mice are successfully constructed,which provides an animal model to explore further the role and molecular mechanism of the hepatocyte Sirt3 gene in diseases.

Human induced pluripotent stem cells (hiPSCs) are promising in regenerative medicine. However, the pluripotent stem cells (PSCs) may form clumps of cancerous tissue, which is a major safety concern in PSCs therapies. Rapamycin is a safe and widely used immunosuppressive pharmaceutical that acts through heterodimerization of the FKBP12 and FRB fragment. Here, we aimed to insert a rapamycin inducible caspase 9 (riC9) gene in a safe harbor AAVS1 site to safeguard hiPSCs therapy by drug induced homodimerization. The donor vector containing an EF1α promoter, a FRB-FKBP-Caspase 9 (CARD domain) fusion protein and a puromycin resistant gene was constructed and co-transfected with sgRNA/Cas9 vector into hiPSCs. After one to two weeks screening with puromycin, single clones were collected for genotype and phenotype analysis. Finally, rapamycin was used to induce the homodimerization of caspase 9 to activate the apoptosis of the engineered cells. After transfection of hiPSCs followed by puromycin screening, five cell clones were collected. Genome amplification and sequencing showed that the donor DNA has been precisely knocked out at the endogenous AAVS1 site. The engineered hiPSCs showed normal pluripotency and proliferative capacity. Rapamycin induced caspase 9 activation, which led to the apoptosis of all engineered hiPSCs and its differentiated cells with different sensitivity to drugs. In conclusion, we generated a rapamycin-controllable hiPSCs survival by homodimerization of caspase 9 to turn on cell apoptosis. It provides a new strategy to guarantee the safety of the hiPSCs therapy.
Humans ; Induced Pluripotent Stem Cells ; Sirolimus/metabolism* ; Caspase 9/metabolism* ; RNA, Guide, CRISPR-Cas Systems ; Pluripotent Stem Cells/metabolism* ; Cell Differentiation ; Puromycin/metabolism*

In the digital transformation of Chinese pharmaceutical industry, how to efficiently govern and analyze industrial data and excavate the valuable information contained therein to guide the production of drug products has always been a research hotspot and application difficulty. Generally, the Chinese pharmaceutical technique is relatively extensive, and the consistency of drug quality needs to be improved. To address this problem, we proposed an optimization method combining advanced calculation tools(e.g., Bayesian network, convolutional neural network, and Pareto multi-objective optimization algorithm) with lean six sigma tools(e.g., Shewhart control chart and process performance index) to dig deeply into historical industrial data and guide the continuous improvement of pharmaceutical processes. Further, we employed this strategy to optimize the manufacturing process of sporoderm-removal Ganoderma lucidum spore powder. After optimization, we preliminarily obtained the possible interval combination of critical parameters to ensure the P_(pk) values of the critical quality properties including moisture, fineness, crude polysaccharide, and total triterpenes of the sporoderm-removal G. lucidum spore powder to be no less than 1.33. The results indicate that the proposed strategy has an industrial application value.
Bayes Theorem ; Data Mining ; Drug Industry ; Powders ; Reishi ; Spores, Fungal

Five new flavonoid derivatives, cajavolubones A-E (1-5), along with six known analogues (6-11) were isolated from Cajanus volubilis, and their structures were elucidated by spectroscopic analysis and quantum chemical calculations. Cajavolubones A and B (1 and 2) were identified as two geranylated chalcones. Cajavolubone C (3) was a prenylated flavone, while cajavolubones D and E (4 and 5) were two prenylated isoflavanones. Compounds 3, 8, 9 and 11 displayed cytotoxicity against HCT-116 cancer cell line.
Flavonoids/chemistry* ; Cajanus ; Molecular Structure ; Chalcones/chemistry*

Five new terpenoids, including two vibsane-type diterpenoids (1, 2) and three iridoid allosides (3-5), together with eight known ones, were isolated from the leaves and twigs of Viburnum odoratissimum var.sessiliflorum. Their planar structures and relative configurations were determined by spectroscopic methods, especially 2D NMR techniques. The sugar moieties of the iridoids were confirmed as β-D-allose by GC analysis after acid hydrolysis and acetylation. The absolute configurations of neovibsanin Q (1) and dehydrovibsanol B (2) were determined by quantum chemical calculation of their theoretical electronic circular dichroism (ECD) spectra and Rh₂(OCOCF₃)₄-induced ECD analysis. The anti-inflammatory activities of compounds 1, 3, 4, and 5 were evaluated using an LPS-induced RAW264.7 cell model. Compounds 3suppressed the release of NO in a dose-dependent manner, with an IC₅₀ value of 55.64 μmol·L^-1. The cytotoxicities of compounds 1-5 on HCT-116 cells were assessed and the results showed that compounds 2 and 3 exhibited moderate inhibitory activities with IC₅₀ values of 13.8 and 12.3 μmol·L^-1, respectively.
Terpenes/pharmacology* ; Viburnum/chemistry* ; Molecular Structure ; Diterpenes/chemistry* ; Plant Leaves/chemistry*

OBJECTIVE To investigate the anti-tumor effects of the components of Ganoderma lucidum(Gc) based on the two-dimensional(2D) and three-dimensional(3D) culture of colorectal cancer HCT116 cells. METHODS The chemical compositional of the three components was identified by UPLC-Q-TOF-MS. An in vitro 3D culture model of HCT116 cells was established by using Matrigel as the matrix material, and the effects of Gc1, Gc2, Gc3, and 5-fluorouracil(5-FU) on the proliferation of HCT116 cells in 2D and 3D culture models were evaluated, and the effects of Gc3 on cell-cycle, apoptosis, drug resistance, lipid metabolism, and 5-FU's anti-tumor activity were evaluated. Cell viability was detected by CCK-8 assay. mRNA expression level of the cells was analyzed by Real-time PCR. Proteins expression level of the cells was analyzed by Western blotting. HPLC was used to detect the content of 5-FU in cells. RESULTS A total of 76, 69, and 17 compounds were identified from Gc1, Gc2, and Gc3, respectively. Compared with 2D culture, the proliferation rate of HCT116 cells was decreased in the 3D culture model, and the expression of cell cycle-promoters CDK2, CDK4, CDK6, and fatty acid synthesizer FASN, SREBP1 were significantly down-regulated. On the contrary, the expression of cell cycle-suppressor p21, p27, and lipid droplet breakdown proteins ATGL and drug resistance gene ITGB1, CDH1, ABCB1, and ABCC1 mRNA were significantly up-regulated. Gc1, Gc2, Gc3 and 5-FU inhibited the proliferation of both 2D and 3D cultured HCT116 cells in a dose dependent manner after incubation for 48 h, and the inhibitory effect of Gc3 was significantly stronger than Gc1 and Gc2. Gc3 could not only reduce the expression of CDK2, CDK4, Bcl-xl, ATGL, and LC3B proteins, but also increase the expression of p21, p27, Bax, Cleaved caspase-3, and Cleaved PARP1 proteins, and overexpression of LC3B or ATGL attenuated Gc3-induced cytotoxicity in 3D cultured HCT116 cells. In addition, Gc3 significantly inhibited the expression of ITGB1, CDH1, ABCB1, and ABCC1 mRNA, and increased the intracellular 5-FU content, and enhanced the anti-tumor activity. CONCLUSION Gc3 significantly inhibit the proliferation of 3D-cultured HCT116 cells by inhibiting cell autophagy and lipid droplet breakdown, and enhance the anti-cancer activity of 5-FU by inhibiting the expression of ITGB1, CDH1, ABCB1, and ABCC1 mRNA.

Objective:To establish the Ultra-High Performance Liquid Chromatography (UPLC) characteristic chromatogram of different parts of Alpinia oxyphylla Miq., and to compare different parts of the chemical components based on multivariate statistical analysis. Methods:The UPLC was used to establish the fingerprint of Alpinia oxyphylla Miq. . The chromatograms were matched to generate the UPLC charactersistic chromatogram of different parts. Based on the variance analysis of single factor, combined with the Principal Component Analysis (PCA) ,Cluster Analysis (CA) and the Partial Orthogonal Least Square Discriminant Analysis (OPLS-DA) to analyze the differences of different medicinal parts of Alpinia oxyphylla Miq.. Results:16 common peaks of Alpinia oxyphylla Miq. were demarcated in crude drugs, compared with the medicinal materials of Alpinia oxyphylla Miq., the peak 13 (tectochhrysin) was lost in the decoction pieces, and the shell were missing peak 5 and peak 6. The results of PCA and CA showed that 15 batches of different medicinal parts of Alpinia oxyphylla Miq. can be broadly divided into 3 categories. The OPLS-DA result showed that the value of the peak area of peaks 14 (Nootkatone), 4, 7 and 12 were the main factors affecting the chemical composition of different parts of Alpinia oxyphylla Miq. .Conclusion:The fingerprint determination method established in this study is stable and controllable, which could distinguish the different parts of Alpinia oxyphylla Miq. .