Skin-integrated wireless haptic interfaces for virtual and augmented reality.

Traditional technologies for virtual reality (VR) and augmented reality (AR) create human experiences through visual and auditory stimuli that replicate sensations associated with the physical world. The most widespread VR and AR systems use head-mounted displays, accelerometers and loudspeakers as the basis for three-dimensional, computer-generated environments that can exist in isolation or as overlays on actual scenery. In comparison to the eyes and the ears, the skin is a relatively underexplored sensory interface for VR and AR technology that could, nevertheless, greatly enhance experiences at a qualitative level, with direct relevance in areas such as communications, entertainment and medicine1,2. Here we present a wireless, battery-free platform of electronic systems and haptic (that is, touch-based) interfaces capable of softly laminating onto the curved surfaces of the skin to communicate information via spatio-temporally programmable patterns of localized mechanical vibrations. We describe the materials, device structures, power delivery strategies and communication schemes that serve as the foundations for such platforms. The resulting technology creates many opportunities for use where the skin provides an electronically programmable communication and sensory input channel to the body, as demonstrated through applications in social media and personal engagement, prosthetic control and feedback, and gaming and entertainment.

Laser-Ignited Lipid Peroxidation Nanoamplifiers for Strengthening Tumor Photodynamic Therapy Through Aggravating Ferroptotic Propagation and Sustainable High Immunogenicity.

Photodynamic therapy (PDT) is extensively investigated for tumor therapy in the clinic. However, the efficacy of PDT is severely limited by the tissue penetrability of light, short effective half-life and radius of reactive oxygen species (ROS), and the weak immunostimulatory effect. In this study, a glutathione (GSH)-activatable nano-photosensitizer is developed to load with arachidonic acid (AA) and camouflage by erythrocyte membrane, which serves as a laser-ignited lipid peroxidation nanoamplifier (MAR). The photosensitive effect of MAR is recovered accompanied by the degradation in the tumor microenvironment and triggers the peroxidation of AA upon laser excitation. Interestingly, it aggravates the propagation of ferroptosis among cancer cells by driving the continuous lipid peroxidation chain reactions with the participation of the degradation products, ferrous ions (Fe2+), and AA. Consequently, even the deep-seated tumor cells without illumination also undergo ferroptosis owing to the propagation of ferroptotic signal. Moreover, the residual tumor cells undergoing ferroptosis still maintain high immunogenicity after PDT, thus continuously triggering sufficient tumor-associated antigens (TAAs) release to remarkably promote the anti-tumor immune response. Therefore, this study will provide a novel "all-in-one" nano-photosensitizer that not only amplifies the damaging effect and expands the effective range of PDT but also improves the immunostimulatory effect after PDT.

Total Synthesis of Yuzurine-type Alkaloid Daphgraciline.

The first total synthesis of daphgraciline has been achieved, which also represents the first example of the synthesis of Daphniphyllum yuzurine-type alkaloids (∼50 members). The unique bridged azabicyclo[4.3.1] ring system in the yuzurine-type subfamily was efficiently and diastereoselectively assembled via a mild type II [5+2] cycloaddition for the first time. The compact tetracyclic [6-7-5-5] skeleton was installed efficiently via an intramolecular Diels-Alder reaction, followed by a benzilic acid-type rearrangement. The synthetically challenging spiro tetrahydropyran moiety in the final product was installed diastereoselectively via a TiIII-mediated reductive epoxide coupling reaction. Potential access to enantioenriched daphgraciline is presented.

Sex-Related Differences on Chemical Composition, Anatomy, Histochemistry, and Biological Activities of Juniperus rigida.

Sex-related differences on phenolic profiles, chemical composition of essential oils, anatomy, histochemistry and biological activities (antioxidant and antibacterial activities) of Juniperus rigida needles collected from Yijun and Fugu region were first studied. In two regions, female and male had similar contents of total phenolic and total flavonoid. 10 phenolic compounds were analyzed by RP-HPLC, amentoflavone content was significantly higher in female than male in Yijun, and chlorogenic acid content was significantly higher in female than male in Fugu. 30 compounds (over 0.5 %) were detected in the essential oils, and the total contents of female were lower than male in Yijun. This difference mainly comes from Germacrene D, which was about twice as high in male as in female. Male needles had significantly larger mechanical tissue and phloem in Yijun. Histochemical analysis indicated that the phenols were stored in epidermal cells, sponge tissue, endodermis cells, edge of resin duct, stomatal bands, and the flavonoids were stored in epidermal cells, endodermis cells, edge of resin duct, stomatal bands. No sex-related differences were found in histochemical analysis, antioxidant activities (ABTS, FRAP) and antibacterial activities (9 strains). This preliminary study provided a reference for production practice and theoretical research of J. rigida.

Juniperus sabina L. as a Source of Podophyllotoxins: Extraction Optimization and Anticholinesterase Activities.

Juniperus sabina L. (J. sabina) has been an important plant in traditional medicine since ancient times. Its needles are rich in podophyllotoxin, a precursor compound to anti-tumor drugs. However, no systematic research has been done on J. sabina as a source of podophyllotoxins or their biological action. Hence, extracts of podophyllotoxin and deoxypodophyllotoxin were the main optimization targets using the Box-Behnken design (BBD) and response surface methodology (RSM). The total phenol content and antioxidant activity of J. sabina needle extract were also optimized. Under the optimal process conditions (ratio of material to liquid (RLM) 1:40, 90% methanol, and ultrasonic time 7 min), the podophyllotoxin extraction rate was 7.51 mg/g DW, the highest level reported for Juniperus spp. distributed in China. To evaluate its biological potential, the neuroprotective acetyl- and butyrylcholinease (AChE and BChE) inhibitory abilities were tested. The needle extract exhibited significant anti-butyrylcholinesterase activity (520.15 mg GALE/g extract), which correlated well with the high levels of podophyllotoxin and deoxypodophyllotoxin. This study shows the potential medicinal value of J. sabina needles.

Combinatory glycoengineering of monoclonal antibodies and its application in cancer therapy: a narrative review.

Background and Objective: The application of immunotherapy, especially in terms of recombinant monoclonal antibodies (mAbs), is a revolution in the pharmaceutical industry field. Glycosylation plays an essential role in the structures and functions of mAbs, which must be carefully monitored and designed throughout their entire lifespan to ensure safety and efficacy. This review aimed to summarize the current status of the glycoengineering of mAbs for providing reference for the pharmaceutical industry. The application of glycoengineering of mAbs in cancer therapy will also be discussed in this article. Methods: We searched the PubMed/MEDLINE database to identify studies published between 1970 and 2023 that investigated glycoengineering of recombinant mAbs and its applications. The major findings of these studies were summarized. Key Content and Findings: This article reviews the relationship between glycosylation profiles and antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), shelf-life, and other properties of mAbs. Furthermore, the rational design of glycosylation profiles provides solutions to the unmet needs of new drug development and biosimilar manufacturers. This review also emphatically describes various feasible strategies to optimize the glycosylation pattern in biomanufacturing reported in recent years, especially the approaches of combinatory glycoengineering explored in this field. Finally, we share examples of glycoengineering of mAbs applied in cancer therapy. Conclusions: Glycan modifications have been achieved through genetic and metabolic glycoengineering. A better understanding of the interplay between cells and the exogenous environment help the combinatorial strategy for glycoengineering in precise control mode. Furthermore, new high-tech approaches for glycoengineering are leading biological engineering and biotherapeutics to a new stage.

Ten-step asymmetric total syntheses of potent antibiotics anthracimycin and anthracimycin B.

The increase in antibiotic resistance calls for the development of novel antibiotics with new molecular structures and new modes of action. However, in the past few decades only a few novel antibiotics have been discovered and progressed into clinically used drugs. The discovery of a potent anthracimycin antibiotic represents a major advance in the field of antibiotics. Anthracimycin is a structurally novel macrolide natural product with an excellent biological activity profile: (i) potent in vitro antibacterial activity (MIC 0.03-1.0 µg mL-1) against many methicillin-resistant Staphylococcus aureus (MRSA) strains, Bacillus anthracis (anthrax), and Mycobacterium tuberculosis; (ii) low toxicity to human cells (IC50 > 30 µM); (iii) a novel mechanism of action (inhibiting DNA/RNA synthesis). While the first total synthesis of anthracimycin was elegantly accomplished by Brimble et al. with 20 steps, we report a 10-step asymmetric total synthesis of anthracimycin and anthracimycin B (first total synthesis). Our convergent strategy features (i) one-pot sequential Mukaiyama vinylogous aldol/intramolecular Diels-Alder reaction to construct trans-decalin with high yield and excellent endo/exo selectivity and (ii) Z-selective ring-closing metathesis to forge the 14-membered ring. In vitro antibacterial evaluation suggested that our synthetic samples exhibited similar antibacterial potency to the naturally occurring anthracimycins against Gram-positive strains. Our short and reliable synthetic route provides a supply of anthracimycins for further in-depth studies and allows medicinal chemists to prepare a library of analogues for establishing structure-activity relationships.

A Covalently Crosslinked Ink for Multimaterials Drop-on-Demand 3D Bioprinting of 3D Cell Cultures.

In vitro 3D cell models have been accepted to better recapitulate aspects of in vivo organ environment than 2D cell culture. Currently, the production of these complex in vitro 3D cell models with multiple cell types and microenvironments remains challenging and prone to human error. Here, a versatile ink comprising a 4-arm poly(ethylene glycol) (PEG)-based polymer with distal maleimide derivatives as the main ink component and a bis-thiol species as the activator that crosslinks the polymer to form the hydrogel in less than a second is reported. The rapid gelation makes the polymer system compatible with 3D bioprinting. The ink is combined with a novel drop-on-demand 3D bioprinting platform, designed specifically for producing 3D cell cultures, consisting of eight independently addressable nozzles and high-throughput printing logic for creating complex 3D cell culture models. The combination of multiple nozzles and fast printing logic enables the rapid preparation of many complex 3D cell cultures comprising multiple hydrogel environments in one structure in a standard 96-well plate format. The platform's compatibility for biological applications is validated using pancreatic ductal adenocarcinoma cancer (PDAC) and human dermal fibroblast cells with their phenotypic responses controlled by tuning the hydrogel microenvironment.

Synthesis of the Core Structure of Daphnimacropodines.

Daphniphyllum alkaloids daphnimacropodines A-C possess a highly congested ring system and share a common tetracyclic ring skeleton. To access the challenging chemical structure of daphnimacropodines, a divergent synthetic approach toward their total synthesis is described. A stereoselective synthesis of the core structure of daphnimacropodines has been achieved from a simple diketone building block. Our approach features an intramolecular carbamate aza-Michael addition and a hydropyrrole synthesis via a Au-catalyzed alkyne hydration followed by an aldol condensation, whereas all the other attempts failed.

Evaluation of sterilisation methods for bio-ink components: gelatin, gelatin methacryloyl, hyaluronic acid and hyaluronic acid methacryloyl.

Reliable and scalable sterilisation of hydrogels is critical to the clinical translation of many biofabrication approaches, such as extrusion-based 3D bioprinting of cell-laden bio-inks. However sterilisation methods can be destructive, and may have detrimental effects on the naturally-derived hydrogels that constitute much of the bio-ink palette. Determining effective sterilisation methods requires detailed analysis of the effects of sterilisation on relevant properties such as viscosity, printability and cytocompatibility. Yet there have been no studies specifically exploring the effects of sterilisation on bio-inks to date. In this work, we explored the effects of various sterilisation techniques on four of the most widely used bio-ink components: gelatin, gelatin methacryloyl, hyaluronic acid, and hyaluronic acid methacrylate. Autoclaving was the most destructive sterilisation method, producing large reductions in viscosity and in mechanical properties following crosslinking. Filter sterilisation caused some reduction in rheological properties of GelMA due to removal of higher molecular weight components, but did not affect photocrosslinking. Ethylene oxide (EtO) was the least destructive sterilisation method in terms of rheological properties for all materials, had no detrimental effect on the photocrosslinkable methacrylate/methacrylamide groups, and so was chosen for more detailed examination. In biological analyses, we found that EtO treatment successfully eradicated a bacterial challenge of E. coli, caused no decrease in viability of human mesenchyman stem cells (hMSCs), and had no effect on their rate of proliferation. Finally, we found that EtO-treated hydrogels supported encapsulated hMSCs to differentiate towards the chondrogenic lineage, and to produce new cartilage matrix. Our results bring to light various effects that sterilisation can have on bio-inks, as well as highlighting EtO sterilisation as a method which minimises degradation of properties, while still promoting biological function.

Needle-shaped ultrathin piezoelectric microsystem for guided tissue targeting via mechanical sensing.

Needles for percutaneous biopsies of tumour tissue can be guided by ultrasound or computed tomography. However, despite best imaging practices and operator experience, high rates of inadequate tissue sampling, especially for small lesions, are common. Here, we introduce a needle-shaped ultrathin piezoelectric microsystem that can be injected or mounted directly onto conventional biopsy needles and used to distinguish abnormal tissue during the capture of biopsy samples, through quantitative real-time measurements of variations in tissue modulus. Using well-characterized synthetic soft materials, explanted tissues and animal models, we establish experimentally and theoretically the fundamental operating principles of the microsystem, as well as key considerations in materials choices and device designs. Through systematic tests on human livers with cancerous lesions, we demonstrate that the piezoelectric microsystem provides quantitative agreement with magnetic resonance elastography, the clinical gold standard for the measurement of tissue modulus. The piezoelectric microsystem provides a foundation for the design of tools for the rapid, modulus-based characterization of tissues.

[Comparison of endoscopic ultrasonography with computer-assisted tomography in the determination of preoperative stage and resectability of pancreatic and ampullary cancers].

OBJECTIVE: To study and compare the accuracy and sensitivity of endoscopic ultrasonography (EUS) and CT scaning in determination of preoperative stage and vascular invasion by pancreatic and ampullary cancers. METHODS: Fourty-two pancreatic cancer patients and 18 ampullary cancer patients were studied. With patients prepared according to conventional endoscopy, Olympus EUM-30 scope 1 set with a side view and 360 degrees rotate and switchable scanning probe [ultrasound frequency (7.5/12 MHz)], was introduced to the descending duodenum through the esophagus. Gas within the duodenum and stomach was aspirated. Then, in order to to facilitate ultrasound transmission, 200 ml deaerated water was injected into the duodenum and 500 ml into the stomach to distend it. The structures of each part of pancreatic head and ampullary together with surrounding vessels were scanned. Then, the scope was withdrawn to the gastric antrum, body and fundus gradually, while the pancreatic body and tail were scanned. RESULTS: Between Apr. 1996 to May 2004, a total of 42 pancreatic cancer patients and 18 ampullary cancer patients were examined by EUS. Meanwhile, all these 58 patients received preoperative CT scaning. The results of stage and vascular invasion determined by EUS in this series were as following; pancreatic cancer group (n = 42): accuracy in T2-4 stage was 100.0% (5/5), 75.0% (9/12) and 48.0% (12/25), respectively; ampullary cancer group (n = 18): T1-4 stage was 75.0% (3/4), 66.7% (2/3), 75.0% (6/8) and 33.3% (1/3), respectively; the accuracy in N stage: P-group: 80.0% in N1 (4/5), 90.0% in N0 (9/10); A-group: 50.0% in N1 (3/6), 91.0% in N0 (10/11). The sensitivity, specificity of vascular invasion, resectability and unresectablilty determined by EUS and CT as compared with surgical findings during operation was 52.9% (9/17), 93.1% (27/29), 77.1% (27/35) and 81.8% (9/11) for EUS (n = 60), respectively; and 11.8% (2/17), 92.6% (25/27), 62.5% (25/40) and 50.0% (2/4) for CT (n = 58), respectively. CONCLUSION: Endoscopic ultrosonography being one of the best image examinations to determine the stage and vascular invasion for pancreatic and ampullary cancer paitients is able to detect small pancreatic or ampullary cancer less than 2.0 cm in diameter due to its high resolution; but can not detect the secondary multiple distal metastases such as spread into the liver, peritonium or hepatoduodenal ligament, etc. due to its ultrasound depth limitation.

[Comparative study of endoluminal ultrasonography and spiral computed tomography in preoperative staging of rectal carcinoma].

OBJECTIVE: To compare the efficacy of endoluminal ultrasonography (EUS) and spiral computed tomography (SCT) in preoperative staging of rectal carcinoma. METHODS: Both EUS and SCT were performed prior to surgery in 68 patients with rectal carcinoma. After radical surgery, the preoperative findings were compared with histologic findings of the operative specimens, and the efficacy of EUS and SCT in staging the rectal carcinoma were evaluated. RESULTS: For T stage, EUS accuracy was 86.8%, while SCT was 70.6%. The difference was significant (P<0.05). For N stage, EUS accuracy was 67.6% and SCT was 63.2%. The difference was not significant (P>0.05). CONCLUSION: EUS is superior to SCT for the judgement of tumor infiltration depth, but neither is able to provide satisfactory assessment of lymph node metastases.