Triacylglycerol lipase, OsSG34, plays an important role in grain shape and appearance quality in rice.

Optimal grain-appearance quality is largely determined by grain size. To date, dozens of grain size-related genes have been identified. However, the regulatory mechanism of slender grain formation is not fully clear. We identified the OsSG34 gene by map-based cloning. A 9-bp deletion on 5'-untranslated region of OsSG34, which resulted in the expression difference between the wild-type and sg34 mutant, led to the slender grains and good transparency in sg34 mutant. OsSG34 as an α/ß fold triacylglycerol lipase affected the triglyceride content directly, and the components of cell wall indirectly, especially the lignin between the inner and outer lemmas in rice grains, which could affect the change in grain size by altering cell proliferation and expansion, while the change in starch content and starch granule arrangement in endosperm could affect the grain-appearance quality. Moreover, the OsERF71 was identified to directly bind to cis-element on the mutant site, thereby regulating the OsSG34 expression. Knockout of three OsSG34 homologous genes resulted in slender grains as well. The study demonstrated OsSG34, involved in lipid metabolism, affected grain size and quality. Our findings suggest that the OsSG34 gene could be used in rice breeding for high yield and good grain-appearance quality via marker-assisted selection and gene-editing approaches.

Cavitation-on-a-Chip Enabled Size-Specific Liposomal Drugs for Selective Pharmacokinetics and Pharmacodynamics.

The size of liposomal drugs has been demonstrated to strongly correlate with their pharmacokinetics and pharmacodynamics. While the microfluidic method successfully achieves the production of liposomes with well-controlled sizes across various buffer/lipid flow rate ratio (FRR) settings, any adjustments to the FRR inevitably influence the concentration, encapsulation efficiency (EE), and stability of liposomal drugs. Here we describe a controllable cavitation-on-a-chip (CCC) strategy that facilitates the precise regulation of liposomal drug size at any desired FRR. The CCC-enabled size-specific liposomes exhibited striking differences in uptake and biodistribution behaviors, thereby demonstrating distinct antitumor efficacy in both tumor-bearing animal and melanoma patient-derived organoid (PDO) models. Intriguingly, as the liposome size decreased to approximately 80 nm, the preferential accumulation of liposomal drugs in the liver transitioned to a predominant enrichment in the kidneys. These findings underscore the considerable potential of our CCC approach in influencing the pharmacokinetics and pharmacodynamics of liposomal nanomedicines.

GMOIT: a tool for effective screening of genetically modified crops.

BACKGROUND: Advancement in agricultural biotechnology has resulted in increasing numbers of commercial varieties of genetically modified (GM) crops worldwide. Though several databases on GM crops are available, these databases generally focus on collecting and providing information on transgenic crops rather than on screening strategies. To overcome this, we constructed a novel tool named, Genetically Modified Organisms Identification Tool (GMOIT), designed to integrate basic and genetic information on genetic modification events and detection methods. RESULTS: At present, data for each element from 118 independent genetic modification events in soybean, maize, canola, and rice were included in the database. Particularly, GMOIT allows users to customize assay ranges and thus obtain the corresponding optimized screening strategies using common elements or specific locations as the detection targets with high flexibility. Using the 118 genetic modification events currently included in GMOIT as the range and algorithm selection results, a "6 + 4" protocol (six exogenous elements and four endogenous reference genes as the detection targets) covering 108 events for the four crops was established. Plasmids pGMOIT-1 and pGMOIT-2 were constructed as positive controls or calibrators in qualitative and quantitative transgene detection. CONCLUSIONS: Our study provides a simple, practical tool for selecting, detecting, and screening strategies for a sustainable and efficient application of genetic modification.

Mimicking Tumor Metastasis Using a Transwell-Integrated Organoids-On-a-Chip Platform.

The mortality rate among cancer patients is primarily attributed to tumor metastasis. The evaluation of metastasis potential provides a powerful framework for personalized therapies. However, little work has so far been undertaken to precisely model tumor metastasis in vitro, hindering the development of preventive and therapeutic interventions. In this work, a tumor-metastasis-mimicked Transwell-integrated organoids-on-a-chip platform (TOP) for precisely evaluating tumor metastatic potential is developed. Unlike the conventional Transwell device for detecting cell migration, the engineered device facilitates the assessment of metastasis in patient-derived organoids (PDO). Furthermore, a novel Transwell chamber with a hexagon-shaped structure is developed to mimic the migration of tumor cells into surrounding tissues, allowing for the evaluation of tumor metastasis in a horizontal direction. As a proof-of-concept demonstration, tumor organoids and metastatic clusters are further evaluated at the protein, genetic, and phenotypic levels. In addition, preliminary drug screening is undertaken to highlight the potential for using the device to combat cancers. In summary, the tumor-metastasis-mimicked TOP offers unique capabilities for evaluating the metastasis potential of tumor organoids and contributes to the development of personalized cancer therapies.

Catalyst-Free Synthesis of Thiosulfonates and 3-Sulfenylindoles from Sodium Sulfinates in Water.

This paper presents a green and efficient aqueous-phase method for the synthesis of thiosulfonates, which has the benefits of no need for catalysts or redox reagents and a short reaction time, providing a method with great economic value for synthesizing thiosulfonates. Furthermore, 3-Sulfenylindoles can be easily synthesized using this method, which expands the potential applications of this reaction.

Lanthanide/B(C6F5)3-Promoted Hydroboration Reduction of Indoles and Quinolines with Pinacolborane.

We have developed a lanthanide/B(C6F5)3-promoted hydroboration reduction of indoles and quinolines with pinacolborane (HBpin). This reaction provides streamlined access to a range of nitrogen-containing compounds in moderate to excellent yields. Large-scale synthesis and further transformations to bioactive compounds indicate that the method has potential practical applications. Preliminary mechanistic studies suggest that amine additives promote the formation of indole-borane intermediates, and the lanthanide/B(C6F5)3-promoted hydroboration reduction proceeds via hydroboration of indole-borane intermediates with HBpin and in situ-formed BH3 species, followed by the protodeborylation process.

Microbial degradation mechanism and pathway of the insecticide thiamethoxam by isolated Bacillus Cereus from activated sludge.

The high water solubility and ecotoxicity of thiamethoxam (TMX) is a potential hazard to ecosystems and human health. Here, a strain of Bacillus cereus with high TMX degradation activity was isolated from the sediment of the A2O process in the wastewater treatment plant and was able to utilize TMX as its sole carbon source. Under different environmental conditions, the degradation efficiency of TMX by Bacillus cereus-S1 (strain S1) ranged from 41.0% to 68.9% after 216 h. The optimum degradation conditions were DO = 3.5 mg/L and pH 9.0. The addition of an appropriate carbon-to-nitrogen ratio could accelerate the degradation of TMX. A plausible biodegradation pathway has been proposed based on the identified metabolites and their corresponding degradation pathways. TMX can be directly converted into Clothianidin (CLO), TMX-dm-hydroxyl and TMX-Urea by a series of reactions such as demethylation, oxadiazine ring cleavage and C=N substitution by hydroxy group. The main products were TMX-dm-hydroxyl and TMX-Urea, the amount of CLO production is relatively small. This study aims to provide a new approach for efficient degradation of TMX; furthermore, strain S1 is a promising biological source for in situ remediation of TMX contamination.

Skill assessment based on clutch use in cross-platform robot-assisted surgery.

BACKGROUND: Many studies have investigated the transfer of skills between laparoscopic and robot-assisted surgery (RAS). These studies have considered time, error, and clinical outcomes in the assessment of skill transfer. However, little is known about the specific operations of the surgeon. Clutch control use is an important skill in RAS. Therefore, the present study aimed to propose a novel objective algorithm based on computer vision that can automatically evaluate a surgeon's clutch use. Additionally, the study aimed to evaluate the correlation between clutch metrics and surgical skill on different surgical robot platforms. METHODS: The robotic surgery training center of Wuhan University trained 30 laparoscopic surgeons as the study group between 2023 and 2024. Laparoscopic surgeons were trained by combining robotic simulator exercises and RAS animal experiments. During the training, video and hand movement data were collected. Hand movements identified by a skin-color model were combined with labeling information to classify clutch use. The metrics were validated on different robotic platforms (dv-Trainer, EDGE MP1000, Toumai™ MT1000, and DaVinci Xi system) and among surgeons with different surgical skill levels. RESULTS: On the robotic simulator, clutch accuracy in the expert group was significantly higher than in the study group for all tasks. No significant differences were observed in the number of clutches between the expert and study groups. In the RAS experiment, the number of clutches decreased significantly for both study and expert groups. The accuracy was maintained at a high level in the expert group but decreased rapidly in the study group. CONCLUSIONS: We proposed a new objective assessment of surgical skills, clutch use metrics, in cross-platform RAS. Additionally, we verified that the metrics significantly correlated with the surgical skill levels of the surgeons.

Sleep Quality in Patients With Ocular Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation.

OBJECTIVES: To investigate the sleep quality in patients with ocular graft-versus-host disease (oGVHD) compared with patients without oGVHD after allogeneic hematopoietic stem cell transplantation (alloHCT) and healthy controls. METHODS: This cross-sectional study analyzed 142 patients after alloHCT including 94 patients with oGVHD and 48 without. Fifty healthy controls were also enrolled. oGVHD was diagnosed according to International Chronic Ocular GVHD Consensus Group (ICOGCG) criteria. Sleep quality was assessed by the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI). Poor sleep quality was defined as CPQSI score greater than 6. RESULTS: Patients after alloHCT demonstrated a significantly higher CPQSI score than those of controls {7.0 [interquartile range (IQR) 5.0-10.0] vs. 5.5 [IQR 4.8-7.0], P =0.002}, especially in the oGVHD subgroup (7.5 [IQR 5.0-11.0] vs. 6.0 [IQR 5.0-8.0], P =0.04) with nearly double prevalence of poor sleep quality (58 [62%] vs. 18 [37%], P =0.006). Poor sleep quality was strikingly correlated with oGVHD diagnosis (adjusted odds ratio [OR]=2.55, 95% confidence interval [CI]: 1.02-6.34, P =0.04) and systemic immunosuppressants (adjusted OR=2.61, 95% CI: 1.32-5.71, P =0.02). Among the ocular parameters, poor sleep quality was significantly associated with higher ICOGCG score (adjusted OR=1.20, 95% CI: 1.03-1.39, P =0.02) and lower tear film break-up time (adjusted OR=0.85, 95% CI: 0.74-0.99, P =0.05). CONCLUSIONS: Poor sleep quality was associated with an increased severity of oGVHD and tear film instability in the long-term alloHCT survivorship.

Application of the Five-Step Phase-Shifting Method in Reflective Ghost Imaging for Efficient Phase Reconstruction.

The conventional approach to phase reconstruction in Reflective Ghost Imaging (RGI) typically involves the introduction of three reference screens into the reference path, deeming the Fourier transform step indispensable. However, this method introduces complexity to the system and raises concerns regarding potential errors in phase retrieval. In response to these challenges, we advocate for adopting the Five-Step Phase-Shifting (FSPS) method in the RGI system. This method presents two key advantages over traditional approaches: (1) It streamlines the phase reconstruction process by eliminating the requirement for a Fourier inverse transform. (2) It avoids the need to insert objects into the reference optical path, simplifying the computation of reference optical path intensity and enabling seamless application to Computational Ghost Imaging (CGI), overcoming the constraints of Dual-Arm Ghost Imaging (DAGI). We substantiate the theoretical proposition through numerical simulations involving two intricate objects. Furthermore, our discussion delves into exploring the influence of varying reflective angles on the phase reconstruction performance.

[Application of the cigarette purchase tasks in achieving China' s tobacco control goals].

OBJECTIVE: To assess cigarette demand among Chinese smokers through a cigarette purchase task (CPT) and to evaluate cigarette prices under different hypothetical scenarios in order to meet the goals of smoking prevalence reduction in China. METHODS: In the study, 447 participants completed a hypothetical CPT at baseline assessments of a trial, thus, cigarette demand curves were individually fitted for each participant using an exponentiated version of the exponential demand model. Typically, five demand indices were derived, intensity (consumption when free), breakpoint (first price at which consumption is suppressed to 0), maximum output (Omax), maximum price (Pmax, price at which Omax occurred), and elasticity (the ratio of the change in quantity demanded to the change in price). A one-way analysis of variance was used to explore the correlations between the cigarette purchase task indices and socio-demographic and smoking characteristics. The one-way decay model was employed to simulate the smoking cessation rates and determine optimal cigarette prices in a series of scenarios for achieving 20% smoking prevalence. RESULTS: The price elasticity drawn from CPT was 0.54, indicating that a 10% price increase could reduce smoking by 5.4% in the participated smokers. Smokers with higher income were less sensitive to cigarette prices (elasticity=-2.31, P=0.028). Cigarette purchase task indices varied significantly among the smokers with different prices of commonly used cigarettes, tobacco dependence, and smoking volume. The smokers who consumed cigarettes of higher prices reported higher breakpoint, Omax and Pmax, but lower intensity (P=0.001). The smokers who were moderately or highly nicotine dependent reported higher intensity, breakpoint, Omax and Pmax, and they had lower intensity (P=0.001). The smokers who had a higher volume of cigarettes reported higher intensity and Omax, and lower intensity (P < 0.001). To achieve the goal of reducing smoking prevalence to 20% in mainland China, we estimated the desired increase on smoking cessation rate and prices accordingly in a series of scenarios, considering the gender variance and reduced smoking initiation. In scenario (a), to achieve a smoking prevalence goal of 20%, it would be necessary for 24.81% of the current smokers to quit smoking when there were no new smokers. Our fitting model yielded a corresponding value of 59.64 yuan (95%CI 53.13-67.24). Given the assumption in scenario (b) that only males quitted smoking, the desired cessation rates would be 25.82%, with a higher corresponding price of 62.15 yuan (95%CI 55.40-70.06) to induce desired cessation rates. In the proposed scenario (c) where 40 percent of the reduction in smoking prevalence came from reduced smoking initiation, and females and males equally quitted smoking due to increased cigarette prices, the price of a pack of cigarettes would be at least 37.36 yuan (95%CI 32.32-42.69) (equals to $ 5.20) per pack to achieve the cessation rate of 14.89 percent. In scenario (d) where only males quitted smoking due to increased cigarette prices considering the reduced smoking initiation, the respective smoking cessation rates should be 15.49% with the desired prices of 38.60 yuan (95%CI 33.53-44.02). After adjusting for education levels and income levels in scenario (c), the price of cigarettes would be at least 37.37 yuan/pack (equals to $ 5.20) (95%CI 30.73-44.94) and 37.84 yuan/pack (equals to $ 5.26) (95%CI 31.94-44.53), respectively. CONCLUSION: Cigarette purchase task indices are significantly associated with income levels and prices of commonly used cigarettes, levels of tobacco dependence, and smoking volume, which is inspiring in studying price factors that influence smoking behavior. It is suggested that higher cigarette prices, surpassing the current actual market level, is imperative in mainland China. Stronger policy stra-tegies should be taken to increase tobacco taxes and retail cigarette prices to achieve the Healthy China 2030 goal of reducing smoking prevalence to 20%.

Polymorphonuclear myeloid-derived suppressor cells play a proinflammatory role via TNF-α+ B cells through BAFF/BTK/NF-κB signalling pathway in the pathogenesis of collagen-induced arthritis mice.

Although various studies have been performed on the function of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in RA, the results were conflicting. Here we were trying to clarify the role of PMN-MDSCs in the pathogenesis of RA and its specific mechanisms. We detected the frequencies and counts of PMN-MDSCs, TNF-α+ B cells and Ki67+ B cells in spleen and inflamed joints of collagen-induced arthritis (CIA) mice using flow cytometry. The pathological role of PMN-MDSCs was examined by anti-Ly6G neutralizing antibodies against PMN-MDSCs or adoptive transfer of PMN-MDSCs. And the modulation of PMN-MDSCs on B cells was conducted by coculture assays, RNA-Seq, RT-qPCR, and so on. The mechanism of BAFF regulating B cells was verified through western blot and flow cytometry. PMN-MDSCs accumulated in the spleen and joints of CIA mice. PMN-MDSCs depletion could alleviate the arthritis severity, which was accompanied by decreased TNF-α secretion and proliferation of B cells. And its adoptive transfer also facilitated disease progress. Furthermore, PMN-MDSCs from CIA mice had higher expression level of BAFF, which regulated TNF-α expression, proliferation and apoptosis of B cells in vitro. What's more, BAFF promoted phosphorylation of BTK/NF-κB signalling pathway. And Ibrutinib (BTK inhibitor) could reverse the effect of BAFF on TNF-α expression of B cells. Our study suggested that PMN-MDSCs enhanced disease severity of CIA and manipulated TNF-α expression, proliferation and apoptosis of B cells via BAFF, furthermore, BAFF promoted TNF-α expression through BTK/NF-κB signalling pathway, which demonstrated a novel pathogenesis of PMN-MDSCs in CIA.

One-Step Formation of Targeted Liposomes in a Versatile Microfluidic Mixing Device.

Targeted liposomes, as a promising carrier, have received tremendous attention in COVID-19 vaccines, molecular imaging, and cancer treatment, due to their enhanced cellular uptake and payload accumulation at target sites. However, the conventional methods for preparing targeted liposomes still suffer from limitations, including complex operation, time-consuming, and poor reproducibility. Herein, a facile and scalable strategy is developed for one-step construction of targeted liposomes using a versatile microfluidic mixing device (MMD). The engineered MMD provides an advanced synthesis platform for multifunctional liposome with high production rate and controllability. To validate the method, a programmed death-ligand 1 (PD-L1)-targeting aptamer modified indocyanine green (ICG)-liposome (Apt-ICG@Lip) is successfully constructed via the MMD. ICG and the PD-L1-targeting aptamer are used as model drug and targeting moiety, respectively. The Apt-ICG@Lip has high encapsulation efficiency (89.9 ± 1.4%) and small mean diameter (129.16 ± 5.48 nm). In vivo studies (PD-L1-expressing tumor models) show that Apt-ICG@Lip can realize PD-L1 targeted photoacoustic imaging, fluorescence imaging, and photothermal therapy. To verify the versatility of this approach, various targeted liposomes with different functions are further prepared and investigated. These experimental results demonstrate that this method is concise, efficient, and scalable to prepare multifunctional targeted liposomal nanoplatforms for molecular imaging and disease theranostics.

Microbial cell factories using Paenibacillus: status and perspectives.

Considered a "Generally Recognized As Safe" (GRAS) bacterium, the plant growth-promoting rhizobacterium Paenibacillus has been widely applied in: agriculture, medicine, industry, and environmental remediation. Paenibacillus species not only accelerate plant growth and degrade toxic substances in wastewater and soil but also produce industrially-relevant enzymes and antimicrobial peptides. Due to a lack of genetic manipulation tools and methods, exploitation of the bioresources of naturally isolated Paenibacillus species has long been limited. Genetic manipulation tools and methods continue to improve in Paenibacillus, such as shuttle plasmids, promoters, and genetic tools of CRISPR. Furthermore, genetic transformation systems develop gradually, including: penicillin-mediated transformation, electroporation, and magnesium amino acid-mediated transformation. As genetic manipulation methods of homologous recombination and CRISPR-mediated editing system have developed gradually, Paenibacillus has come to be regarded as a promising microbial chassis for biomanufacturing, expanding its application scope, such as: industrial enzymes, bioremediation and bioadsorption, surfactants, and antibacterial agents. In this review, we describe the applications of Paenibacillus bioproducts, and then discuss recent advances and future challenges in the development of genetic manipulation systems in this genus. This work highlights the potential of Paenibacillus as a new microbial chassis for mining bioresources.

Interleukin-13 reduces bone erosion in rheumatoid arthritis by up-regulating osteoprotegerin expression in fibroblast-like synoviocytes : an in vitro and in vivo study.

OBJECTIVES: Bone erosion in rheumatoid arthritis (RA) is partly caused by excessive activation of osteoclasts. Osteoclasts can be derived from RA synovium and their differentiation can be inhibited by osteoprotegerin (OPG), a decoy receptor of the osteoclastogenesis-promoting cytokine receptor activator of nuclear factor κB ligand (RANKL). Fibroblast-like synoviocytes (FLSs) are the main stromal cells in the synovium that can secret OPG. The OPG secretion of FLSs can be modulated by various cytokines. Interleukin (IL)-13 can alleviate bone erosion in RA mouse models, but the mechanisms remain unclear. Therefore, we aimed to investigate whether IL-13 can induce OPG secretion by RA-FLSs, thus ameliorating bone destruction in RA by inhibiting osteoclast differentiation. METHODS: OPG, RANKL, and IL-13 receptors expression by RA-FLSs were evaluated by RT-qPCR. OPG secretion was determined by ELISA. Western blot was performed to analyse OPG expression and the activation of the STAT6 pathway. IL-13 and (or) OPG siRNA pre-treated RA-FLSs conditioned medium were used in osteoclast induction to test if IL-13 can inhibit osteoclastogenesis by up-regulating OPG in RA-FLSs. Micro-CT and immunofluorescence were performed to determine if IL-13 can induce OPG expression and alleviate bone erosion in vivo. RESULTS: IL-13 can promote OPG expression of RA-FLSs, and the promotion can be overcome by IL-13Rα1 or IL-13Rα2 siRNA transfection, or STAT6 inhibitor. Osteoclast differentiation can be inhibited by IL-13 pre-treated RA-FLSs conditioned medium. The inhibition can be reversed by OPG siRNA transfection. IL-13 injection can increase OPG expression in the joints while reducing bone destruction in collagen-induced arthritis mice. CONCLUSIONS: IL-13 can inhibit osteoclastogenesis by up-regulating OPG in RA-FLSs through IL-13 receptors via the STAT6 pathway, thus may ameliorate bone erosion in RA.

Remote teaching system for robotic surgery and its validation: results of a randomized controlled study.

BACKGROUND: Currently, only a limited number of remote assistance modalities are utilized in the basic phase of robotic surgery training to facilitate the rapid acquisition of robotic surgery skills by surgeons. This study aimed to investigate the benefits of real-time remote surgical robotic skill training based on a multi-channel video recording and playback system. METHODS: We randomly divided 40 medical students without prior expertise in the use of surgical robots into two groups to assess the performance of trainees on a robotic simulator (Mimic dV-Trainer). The remote group received remote training, while the control group received live one-on-one guidance. We compared the learning curves of the two groups based on simulator scores. Furthermore, the NASA task load index (NASA-TLX) scale was used to measure the fatigue load of the trainers. RESULTS: We observed no significant differences in the demographics or initial baseline skill levels between the two groups. Participants in the remote group achieved higher total scores in the Match Board 2 and Thread the Rings 1 exercises compared to the control group. In addition, trainers in the remote group reported lower subjective fatigue load than in the control group. CONCLUSIONS: The remote approach to surgical robotics skills training based on the Remote Teaching System for Robotic Surgery (ReTeRoS) is both feasible and has the potential for large-scale training.

Phase Retrieval Based on Shaped Incoherent Sources.

Current ghost imaging phase reconstruction schemes require either complex optical systems, iterative algorithms, Fourier transform steps, or entangled photon pairs. These factors may increase the difficulty of system design, lead to phase retrieval errors, or result in excessive time consumption. To tackle this challenge, we propose a five-step phase-shifting method that eliminates the need for complex optical systems, Fourier transform steps, entangled photon pairs, or iterative algorithms. Using five specifically designed incoherent sources, we can generate five distinct ghost imaging patterns. Subsequently, the phase information of the object can be calculated from these five speckle patterns. Additionally, we offer a detailed theoretical explanation for choosing the five-step phase-shifting method over the more commonly used three-step or four-step phase-shifting methods. We demonstrate the applicability of this theoretical proposal through numerical simulations involving two types of complicated objects. The results illustrate that the phase information of the complex object can be successfully and quantitatively reconstructed.

Synchronous Dual Electrolyte Additive Sustains Zn Metal Anode with 5600†h Lifespan.

Despite conspicuous merits of Zn metal anodes, the commercialization is still handicapped by rampant dendrite formation and notorious side reaction. Manipulating the nucleation mode and deposition orientation of Zn is a key to rendering stabilized Zn anodes. Here, a dual electrolyte additive strategy is put forward via the direct cooperation of xylitol (XY) and graphene oxide (GO) species into typical zinc sulfate electrolyte. As verified by molecular dynamics simulations, the incorporated XY molecules could regulate the solvation structure of Zn2+ , thus inhibiting hydrogen evolution and side reactions. The self-assembled GO layer is in favor of facilitating the desolvation process to accelerate reaction kinetics. Progressive nucleation and orientational deposition can be realized under the synergistic modulation, enabling a dense and uniform Zn deposition. Consequently, symmetric cell based on dual additives harvests a highly reversible cycling of 5600 h at 1.0 mA cm-2 /1.0 mAh cm-2 .

CAFs-derived SCUBE1 promotes malignancy and stemness through the Shh/Gli1 pathway in hepatocellular carcinoma.

BACKGROUND: The tumour microenvironment and cirrhotic liver are excellent sources of cancer-associated fibroblasts (CAFs), which participate in carcinogenesis. Thus, it is important to clarify the crosstalk between CAFs and HCC cells and the related mechanism in regulating carcinogenesis. METHODS: Human hepatocellular carcinoma (HCC) tissues and matched adjacent normal tissues were obtained from HCC patients. Immunohistochemistry, Western blotting (WB) and RT-qPCR were performed to detect the expression of SCUBE1. The roles of SCUBE1 in inducing stemness features in HCC cells were explored and investigated in vitro and in vivo. Student's t tests or Mann-Whitney U tests were used to compare continuous variables, while chi-square tests or Fisher's exact tests were used to compare categorical variables between two groups. RESULTS: SCUBE1 was confirmed to be highly expressed in CAFs in HCC and had a strong connection with stemness and a poor prognosis. In addition, CAFs were found to secrete SCUBE1 to enhance the malignancy of HCC cells and increase the proportion of CD133-positive cells. Silencing SCUBE1 expression had the opposite effect. The Shh pathway was activated by SCUBE1 stimulation. Inhibition of cyclopamine partially reversed the stimulating effect of SCUBE1 both in vivo and in vitro. Moreover, based on the RT-qPCR, ELISA and WB results, a high SCUBE1 expression level was found in HCC tissue and serum. CONCLUSION: This study revealed that CAFs-derived SCUBE1 can enhance the malignancy and stemness of HCC cells through the Shh pathway. This study aims to provide new perspectives for future HCC studies and provide new strategies for HCC treatment.

3D-Printed Integrated Ultrasonic Microneedle Array for Rapid Transdermal Drug Delivery.

Transdermal drug delivery (TDD) is an attractive alternative to oral and hypodermic injection drug administration, and is poised to increase its impact on medicine and pharmaceutical design. Microneedles (MNs) are a new minimally invasive TDD method widely used in medicine and cosmetology. MNs create a microscale channel from the stratum corneum to the dermis and enable drug delivery of hydrophilic and macromolecular into the skin. Although MNs allow different drugs to penetrate the stratum corneum, they cannot provide an extra driving force for drug transport in tissue. To overcome this limitation and achieve fast, controllable drug delivery, an integrated 3D-printed ultrasonic MN array (USMA) device consisting of hollow MNs and an ultrasonic transducer is proposed. The hollow MNs enable drug to penetrate the stratum corneum, and the ultrasound transmitted through the MNs provides the driving force for drug transportation in tissue. Using methylene blue and bovine serum albumin as model drugs, we tested the drug delivery performance of USMA on porcine skin; the results show that USMA significantly enhanced the delivery efficiency of model drugs. Besides, USMA obviously reduced MNs insertion force and tissue damage, which were well-tolerated and gentle. This study suggests that the integrated ultrasonic MN array has great potential for clinical drug delivery with high efficiency and lessening the suffering of patients.