Competing C and N as Reactive Centers for Microsolvated Ambident Nucleophiles CN-(H2O)n=0-3: A Theoretical Study of E2/SN2 Reactions with CH3CH2X (X = Cl, Br, I).

As an ambident nucleophile, CN- has both C and N atoms that can act as the reactive center to facilitate substitution reactions. We investigate in detail the potential energy profiles of CN-(H2O)0-3 with CH3CH2X (X = Cl, Br, I) to explore the influence of solvent molecules on competition between the different nucleophilic atoms C and N involving the SN2 and E2 pathways. The energy barrier sequence for the transition states follows C@inv-SN2 < N@inv-SN2 < C@anti-E2 < N@anti-E2. When two different atoms act as nucleophilic atoms, the SN2 reaction is always preferred over the E2 reaction, and this preference increases with microsolvation. For the ambident nucleophiles CN-(H2O)0-3, C as the reactive center always has stronger nucleophilicity and basicity than N acting as the reactive center. Regarding the leaving group, the height of the energy barrier is positively correlated with the acidity of the CH3CH2X substrate for the E2 pathway and with X-heterolysis for the SN2 pathway. Furthermore, we found that in the gas phase, the energy barrier for different leaving group systems decreases gradually in the order Cl > Br > I, while in the SMD solution, the energy barrier and product energy increase slightly in the system from X = Cl to Br; this change may be due to the significantly weakened transition-state interaction for the X = Br system. Our activation strain, quantitative molecular orbital, and charge analyses reveal the physical mechanisms underlying the various computed trends. In addition, we also demonstrate the two points recently proposed by Vermeeren, P. . Chem. Eur. J. 2020, 26, 15538-15548.

All Resistive Pressure-Temperature Bimodal Sensing E-Skin for Object Classification.

Electronic skin (E-skin) with multimodal sensing ability demonstrates huge prospects in object classification by intelligent robots. However, realizing the object classification capability of E-skin faces severe challenges in multiple types of output signals. Herein, a hierarchical pressure-temperature bimodal sensing E-skin based on all resistive output signals is developed for accurate object classification, which consists of laser-induced graphene/silicone rubber (LIG/SR) pressure sensing layer and NiO temperature sensing layer. The highly conductive LIG is employed as pressure-sensitive material as well as the interdigital electrode. Benefiting from high conductivity of LIG, pressure perception exhibits an excellent sensitivity of -34.15 kPa-1 . Meanwhile, a high temperature coefficient of resistance of -3.84%°C-1 is obtained in the range of 24-40 °C. More importantly, based on only electrical resistance as the output signal, the bimodal sensing E-skin with negligible crosstalk can simultaneously achieve pressure and temperature perception. Furthermore, a smart glove based on this E-skin enables classifying various objects with different shapes, sizes, and surface temperatures, which achieves over 92% accuracy under assistance of deep learning. Consequently, the hierarchical pressure-temperature bimodal sensing E-skin demonstrates potential application in human-machine interfaces, intelligent robots, and smart prosthetics.

Blockade of IL-11 Trans-Signaling or JAK2/STAT3 Signaling Ameliorates the Profibrotic Effect of IL-11.

OBJECTIVES: Systemic sclerosis (SSc) is a rare rheumatic disease characterized by vascular damage, dysregulated immune response, and fibrosis. Interleukin-11 (IL-11) is upregulated in SSc. This study aimed to investigate the pathological and therapeutic role of the IL-11 trans-signaling pathway in SSc. METHODS: Plasma IL-11 level was evaluated in 32 patients with SSc and 15 healthy controls, while the expression levels of ADAM10, ADAM17, IL-11, IL-11 Rα, or IL-11 co-stained with CD3 or CD163 in the skin of SSc patients and healthy controls were analyzed. Fibroblasts were treated with IL-11 and ionomycin to evaluate the profibrotic effect of IL-11 trans-signaling pathway. TJ301 (sgp130Fc) and WP1066 (a JAK2/STAT3 inhibitor) intervention groups were set up to investigate the antifibrotic effect of targeting IL-11. RESULTS: Levels of plasma IL-11 were extremely low in most SSc patients and healthy controls. In contrast, levels of IL-11, IL-11 Rα, and ADAM10, but not ADAM17, were significantly elevated in the skin of SSc patients. Moreover, the numbers of IL-11+ CD3+ cells and IL-11+ CD163+ cells were increased in the skin of SSc patients. Besides, IL-11 and ADAM10 were also elevated in the skin and pulmonary of bleomycin-induced SSc mouse. Fibroblasts co-stimulated with IL-11 and ionomycin showed increased expression of COL3 and phosphorylation of STAT3, which could be inhibited by TJ301 or WP1066. TJ301 also ameliorated skin and lung fibrosis in BLM-induced SSc mouse. CONCLUSIONS: IL-11 induces fibrosis in SSc by regulating the trans-signaling pathway. Blockage of sgp130Fc or inhibition of the JAK2/STAT3 pathway could ameliorate the profibrotic effect of IL-11.

Competition between Elimination and Substitution for Ambident Nucleophiles CN- and Iodoethane Reactions in Gaseous and Aqueous Medium.

Nucleophilic substitution (SN2) and elimination (E2) reactions between ambident nucleophiles have long been considered as typical reactions in organic chemistry, and exploring the competition between the two reactions is of great importance in chemical synthesis. As a nucleophile, CN- can use its C and N atoms as the reactive centers to undergo E2 and SN2 reactions, but related research is currently limited. This study uses the CCSD(T)/pp/t//MP2/ECP/d electronic structure method to perform detailed investigations on the potential energy profiles for SN2 and E2 reactions between CN- and CH3CH2I in gaseous and aqueous media. The potential energy profiles reveal that the energy barriers for SN2 and E2 reactions with the C atom as the reactive center are consistently lower than those with the N atom, indicating that the C atom has a stronger nucleophilic ability and stronger basicity. Furthermore, the potential energy profiles in both gas and aqueous environments show that the barriers of SN2 reactions are lower than those for E2 reactions with both C and N as the attacking atom. By using the frontier molecular orbital and activation strain models to explain the interesting phenomenon, the transition from the gas phase to solution was investigated, specifically in the gas-microsolvation-water transition. The results show that water molecules reduce the nucleophilicity and basicity of CN-, while strain energy (ΔEstrain) causes a greater increase in the energy barrier for E2 reactions. This study provides new insights and perspectives on the understanding of CN- as a nucleophile in SN2 reactions and serves as theoretical guidance for organic synthesis.

Effect of Induction Therapy With Olamkicept vs Placebo on Clinical Response in Patients With Active Ulcerative Colitis: A Randomized Clinical Trial.

Importance: Olamkicept, a soluble gp130-Fc-fusion-protein, selectively inhibits interleukin 6 (IL-6) trans-signaling by binding the soluble IL-6 receptor/IL-6 complex. It has anti-inflammatory activities in inflammatory murine models without immune suppression. Objective: To assess the effect of olamkicept as induction therapy in patients with active ulcerative colitis. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled phase 2 trial of olamkicept in 91 adults with active ulcerative colitis (full Mayo score ≥5, rectal bleeding score ≥1, endoscopy score ≥2) and an inadequate response to conventional therapy. The study was conducted at 22 clinical study sites in East Asia. Patients were recruited beginning in February 2018. Final follow-up occurred in December 2020. Interventions: Eligible patients were randomized 1:1:1 to receive a biweekly intravenous infusion of olamkicept 600 mg (n = 30) or 300 mg (n = 31) or placebo (n = 30) for 12 weeks. Main Outcomes and Measures: The primary end point was clinical response at week 12 (defined as ≥3 and ≥30% decrease from baseline total Mayo score; range, 0-12 [worst] with ≥1 decrease and ≤1 in rectal bleeding [range, 0-3 {worst}]). There were 25 secondary efficacy outcomes, including clinical remission and mucosal healing at week 12. Results: Ninety-one patients (mean age, 41 years; 25 women [27.5%]) were randomized; 79 (86.8%) completed the trial. At week 12, more patients receiving olamkicept 600 mg (17/29 [58.6%]) or 300 mg (13/30 [43.3%]) achieved clinical response than placebo (10/29 [34.5%]), with adjusted difference vs placebo of 26.6% (90% CI, 6.2% to 47.1%; P = .03) for 600 mg and 8.3% (90% CI, -12.6% to 29.1%; P = .52) for 300 mg. Among patients randomized to receive 600 mg olamkicept, 16 of 25 secondary outcomes were statistically significant compared with placebo. Among patients randomized to receive 300 mg, 6 of 25 secondary outcomes were statistically significant compared with placebo. Treatment-related adverse events occurred in 53.3% (16/30) of patients receiving 600 mg olamkicept, 58.1% (18/31) receiving 300 mg olamkicept, and 50% (15/30) receiving placebo. The most common drug-related adverse events were bilirubin presence in the urine, hyperuricemia, and increased aspartate aminotransferase levels, and all were more common in the olamkicept groups compared with placebo. Conclusions and Relevance: Among patients with active ulcerative colitis, biweekly infusion of olamkicept 600 mg, but not 300 mg, resulted in a greater likelihood of clinical response at 12 weeks compared with placebo. Further research is needed for replication and to assess longer-term efficacy and safety. Trial Registration: ClinicalTrials.gov Identifier: NCT03235752.

Enhanced Acoustic Droplet Vaporization through the Active Magnetic Accumulation of Drug-Loaded Magnetic Particle-Encapsulated Nanodroplets (MPE-NDs) in Cancer Therapy.

The application of drug-loaded nanodroplets is still limited by their insufficient accumulation owing to the enhanced permeability and retention (EPR) effect failure in cancer therapy. To overcome these limitations, we propose an alternative magnetic particle-encapsulated nanodroplet (MPE-ND) with outstanding biosafety and magnetic targeting by encapsulating fluorinated Fe3O4-SiO2 nanoparticles inside the liquid core of the nanodroplets. Meanwhile, doxorubicin (DOX) can be stably loaded into the shell through both electrostatic and hydrophobic interactions to obtain drug-loaded MPE-NDs. Both in vitro and in vivo experiments have consistently demonstrated that drug-loaded MPE-NDs can significantly increase the local drug concentration and enhance the damage of tumor tissues through acoustic droplet vaporization under a static magnetic field (eADV therapy). Histological examination reveals that eADV therapy efficiently suppresses tumor proliferation by inducing apoptosis, destroying supply vessels, and inhibiting neovascularization. Drug-loaded MPE-NDs can be expected to open a new gateway for ultrasound-triggered drug delivery and cancer treatment.

Arterial Labeling Ultrasound Subtraction Angiography (ALUSA) Based on Acoustic Phase-Change Nanodroplets.

Biomedical imaging technology (like digital subtraction angiography (DSA)) based on contrast agents has been widely employed in the diagnosis of vascular-related diseases. While the DSA achieves the high-resolution observation of specified vessels and their downstream perfusion at the cost of invasive, radioactive operation and hepatorenal toxicity. To address those problems, this study develops arterial labeling ultrasound (US) subtraction angiography (ALUSA) based on a new perfluorobutane (PFB) nanodroplets with a lower vaporization threshold through spontaneous nucleation. The nanodroplets can be selectively vaporized to microbubbles, indicating a highly echogenic signal at B-mode images only using a diagnostic transducer. By labeling a single blood vessel for nanodroplets vaporization and tracking its downstream blood perfusion in segmental renal arteries at a frame rate of 500 Hz. The results demonstrate the color-coded super-resolution ALUSA image, exhibiting the downstream arcuate and interlobular arteries of each segmental renal artery with a resolution of 36 µm in a rabbit kidney. Furthermore, ALUSA could offer the vascular structures, blood flow velocity, and direction of their primary supply vessels in the mouse breast tumor. ALUSA fills the gap of noninvasive labeling angiography in US and opens a broad vista in the diagnosis and treatment of tumor and vascular-related diseases.

MiR-1247-3p protects rat cardiomyocytes against hypoxia/reoxygenation-induced injury via targeting BCL2L11 and caspase-2.

Acute myocardial infarction (AMI) represents a severe coronary heart disease with relatively high rate of mortality and usually can lead to the damage of the myocardial tissues. Reperfusion of the ischemic myocardial tissues can minimize AMI-induced damage. As far as we know, the molecular mechanisms underlying ischemia/reperfusion (I/R)-induced injury remains elusive. This study was undertaken to explore the role of miR-1247-3p in regulating myocardial I/R injury. The hypoxia/reoxygenation (H/R)-treated H9c2 cells showed a decreased cell viability and mitochondrial membrane potential with an increase in the apoptosis; furthermore, miR-1247-3p was down-regulated in these cells. MiR-1247-3p overexpression attenuated H/R-induced H9c2 cell injury; while miR-1247-3p knockdown in H9c2 cells exhibited similar effects being observed in H/R-treated cells. The bioinformatics prediction revealed Bcl-2-like protein 11 (BCL2L11) and caspase-2 were two potential targets for miR-1247-3p, and functional assays confirmed that miR-1247-3p targeted both BCL2L11 and caspase-2 3' untranslated regions, which lead to the repressed expression of these genes. Silencing of BCL2L11 and caspase-2 both, respectively, counteracted the H9c2 cell injury caused by H/R treatment. Moreover, BCL2L11 and caspase-2 overexpression, respectively, impaired the protective effects of miR-1247-3p overexpression on H/R-treated H9c2 cells. The data in the present investigation revealed that miR-1247-3p restoration exhibited protective effects on H/R-induced cardiomyocyte injury through targeting BCL2L11 and caspase-2, implying that miR-1247-3p along with caspase-2/BCL2L11 signaling may provide novel sight for a better understating of I/R-induced myocardial damage. The role of miR-1247-3p might be further confirmed in animal models and clinical studies.

MXene-based ultra-thin film for terahertz radiation shielding.

We have successfully fabricated Ti-based MXenes flakes, Ti3C2Tx, by chemical etching, then prepared it as an organic dispersion and finally spin-coated it on polyimide plastic substrate for terahertz wave shielding. The shielding effectivity of the 12 µm ultra-thin film can reach up to 17 dB measured by the terahertz time-domain spectra. We can attribute the excellent phenomenon to the intrinsic absorption of triple-layered Ti3C2, due to the similar double-peak type refraction curves, which have been respectively observed from the experimental samples and the simulation ones. High conductivity and strong THz absorption indicate the Ti3C2Tx MXene is the absorptive electromagnetic shielding material. Comparing with other kinds of THz shielding materials, the Ti-based MXenes might be a potential candidate for the next generation of ultra-thin and lightweight THz shielding.

The strain effect on the electronic properties of the MoSSe/WSSe van der Waals heterostructure: a first-principles study.

The structural, mechanical and electronic properties of the MoSSe/WSSe van der Waals (vdW) heterostructure under various degrees of horizontal and vertical strain are systematically investigated based on first-principles methods. It is found that the MoSSe/WSSe vdW heterostructure of the most stable AB stacking is a direct band gap semiconductor and exhibits a type-II band alignment, which demonstrates an effective separation of photogenerated electron-hole pairs and increases their lifetime accordingly. The high angle-dependent Young's modulus and normal Poisson's ratios show the mechanical stability and anisotropy. It is found that the band gap of the heterostructure can be modulated effectively by applying strain, exhibiting a decreasing trend with increasing strain, and even lead to an intriguing semiconductor-metal transition under a certain large tensile strain. In particular, a negative correlation between the band gap and structure pressure provides a theoretical basis for experimentally regulating the electronic properties. Moreover, different strains can induce two different conditions of direct-indirect transition or can maintain the characteristics of the direct-band-gap. All these interesting results provide a detailed understanding of the MoSSe/WSSe vdW heterostructure under strain and indicate that it is a good candidate for low-dimensional electronic, nano-electronic and optoelectronic devices.

Retrospective analysis of 98 cases of maxillary sinus squamous cell carcinoma and therapeutic exploration.

BACKGROUND: Maxillary sinus squamous cell carcinoma (MSSCC) is a relatively rare head and neck cancer with poorly defined prognosis, and the present study aimed to investigate the outcomes for MSSCC according to different treatments. METHODS: Tianjin Medical University Cancer Institute and Hospital pathology database was reviewed from 2007 to 2017, and 98 patients with pathologically confirmed MSSCC were enrolled. Retrospective analysis and follow-up were performed for each patient. Multivariate analysis of prognostic factors was performed using Cox's regression model. RESULTS: For all the 98 cases of MSSCC, the 5-year overall survival (OS) and disease-free survival (DFS) rates were 31.0% and 29.3%, respectively. Among 98 patient, 33 patients were treated with systemic treatment (NON-SUR), 19 patients underwent neoadjuvant chemotherapy and/or radiotherapy followed by surgery (CT/RT+SUR), 38 patients received surgery followed by chemotherapy and/or radiotherapy (SUR+RT/CT), and 8 patients were performed surgery alone (SUR).The OS rate for each group was 27.3%, 57.9%, 30.6% and 37.5%, respectively, while the DFS was 21.2%, 36.8%, 31.6% and 25.0%, respectively. The OS rate of CT/RT+SUR was significantly higher than that of NON-SUR and SUR+CT/RT groups (P < 0.05). Multivariate analysis revealed that smoking, low differentiation, and advanced T stage were independent risk factors for OS, while low differentiation and advanced N stage for DFS. CONCLUSIONS: Surgery-based treatment is still the first-line therapeutic strategy for MSSCC. And neoadjuvant chemoradiotherapy followed by surgery is highly recommended for MSSCC patients, especially those with advanced tumors or requesting high quality of life.

[A case with a novel weak D type].

OBJECTIVE: To report on a novel weak D type identified in a Chinese individual. METHODS: Peripheral blood sample was collected for a voluntary blood donor with weakened expression of D antigen. Routine serological testing was carried out to determine the D, C, c, E and e antigens of the Rh blood group. A D-screening kit was used to analyze the RhD epitopes. The 10 exons and flanking intronic regions of the RHD gene were sequenced. The zygosity of RHD was determined with a sequence-specific primer PCR method. RESULTS: A novel RHD allele, RHD (1022T>A), was found in the subject with a weak D phenotype. Serological testing of the RhD epitopes has coined with the weak D phenotype. CONCLUSION: A novel weak D allele has been identified in Chinese population.

[Identification of a novel FUT1 allele of para-Bombay phenotype].

OBJECTIVE: To explore the molecular basis for an individual with para-Bombay phenotype of the H blood group. METHODS: Intron 5 to 3'-UTR of the ABO gene and exon 4 of the FUT1 gene were amplified with PCR and subjected to direct sequencing. Mutations of the FUT1 gene were identified by TOPO cloning sequencing. RESULTS: Direct sequencing showed that her ABO genotype was B101/O01. TOPO cloning sequencing found that this individual had three mutations of the FUT1 gene, including an heterozygous AG deletion (CAGAGAG→CAGAG) at position 547 to 552, and two C→T mutations at positions 35 (C35T) and 293 (C293T) on the other homologous chromosome. The two alleles comprised a new recombination of mutations c.35T>C and c.293C>T, and the sequence has been submitted to NCBI (No. MG597611). CONCLUSION: A novel combination of FUT1 alleles with c.35 C>T and c.293C>T has been identified in an individual with para-Bombay phenotype.

[Identification of a novel Ax allele of the ABO blood group].

OBJECTIVE: To explore the molecular basis for an individual with Ax28 phenotype of the ABO subtype. METHODS: The ABO group antigens on red blood cells of the proband were identified by monoclonal antibodies. The ABO antibody in serum was detected by standard A, B, O cells. Exons 1 to 7 of the ABO gene were respectively amplified by PCR and directly sequenced. Amplicons for exons 5 to 7 were also sequenced after cloning. RESULTS: Weakened A antigen was detected on red blood cells from the proband. Both anti-A and anti-B antibodies were detected in the serum. Heterozygous 261G/del was detected in exon 6, while heterozygous 467C/T and 830T/C were detected in exon 7 by direct DNA sequencing. After cloning and sequencing, two alleles (O01 and Ax28) were obtained. Compared with A102, the sequence of Ax28 contained one nucleotide changes (T to C) at position 830, which resulted in amino acid change (Val to Ala) at position 277. CONCLUSION: The novel mutation c.830T>C of the galactosaminyltransferase gene may give rise to the Ax28 phenotype.

IGF-binding protein 2 is a candidate target of therapeutic potential in cancer.

Insulin-like growth factor (IGF)-binding protein 2(IGFBP2), a key member of IGF family, has been reported as a notable oncogene in most human epithelium cancers. Increasing evidences suggested that IGFBP2 might be a candidate target of therapuetic potential by regulating key cancer metastasis and invasion-associated signaling networks, but there is still confusion about the mechanism on how IGFBP2 takes part in these processes. In this review, we summarized the current points of view that IGFBP2 functions in signaling pathways during tumorigenesis and tumor progression and discussed its potential clinical applications as a therapeutic target.

Targeting STAT3/miR-21 axis inhibits epithelial-mesenchymal transition via regulating CDK5 in head and neck squamous cell carcinoma.

BACKGROUND: Abnormal activation of STAT3 and miR-21 plays a vital role in progression and invasion of solid tumors. The cyclin-dependent kinase 5 (CDK5) is reported to contribute to cancer metastasis by regulating epithelial-mesenchymal transition (EMT). However, the role of STAT3/miR-21 axis and CDK5 in head and neck squamous cell carcinoma remains unclear. METHODS: We measured the expression of miR-21, CDK5 and EMT markers in 60 HNSCC tumor samples. We used Immunohistochemistry and in situ hybridization assay to examine the role of STAT3/miR-21 axis and CDK5 activation in the invasiveness of HNSCC. The clinical survival relevance was analyzed by Kaplan-Meier analysis and univariate/multivariate COX regression model. Multiple approaches including scratch, transwell chamber assay and other molecular biology techniques were used to validate the anti-invasion effect of targeting miR-21 in Tca8113 and Hep-2 cell lines in vitro. Furthermore, whether miR-21 depletion inhibits HNSCC invasion in vivo was confirmed in Tca8113 xenograft tumor model. RESULTS: The expression of miR-21 and CDK5 were significantly correlated with lymph node metastasis in HNSCC. Hep-2 and Tca8113 cell lines showed co-overexpression of miR-21 and CDK5. WP1066 or asON-miR-21 treatment depleted miR-21 and CDK5 expression and significantly inhibited migration or invasion in Hep-2 and Tca8113 cells. The expression levels of CDK5/p35, N-cadherin, vimentin, ß-catenin were inhibited while E-cadherin level was increased by miR-21 depletion in vitro and in vivo. Conversely, ectopic CDK5 overexpression significantly induced tumor cell motility and EMT. Moreover, ectopic CDK5 overexpression in Hep-2 and Tca8113 cells rescued the observed phenotype after miR-21 silencing or WP1066 treatment. CONCLUSIONS: miR-21 cooperates with CDK5 to promote EMT and invasion in HNSCC. This finding suggests that CDK5 may be an important cofactor for targeting when designing metastasis-blocking therapy by targeting STAT3/miR-21 axis with STAT3 inhibitor or miR-21 antisense oligonucleotide. This is the first demonstration of the novel role of STAT3/miR-21 axis and CDK5/CDK5R1 (p35) in metastasis of HNSCC.

[Study of molecular mechanism and antigen expression of CisAB01 blood group].

OBJECTIVE: To explore the molecular mechanism of CisAB01 subtype in the ABO blood group system, and to investigate the expression of A and B antigens in red blood cells (RBCs). METHODS: For 5 unrelated individuals with the CisAB phenotype, the molecular basis for the blood type was studied with serological assay, DNA sequencing and haplotype analysis. Bioinformatics analysis was carried out to investigate the changes in structure and function of relevant enzymes. Expression of A and B antigens in RBCs of CisAB01 was detected by flow cytometry. RESULTS: All of the 5 samples were found to have a CisAB01 subtype. The underlying mutations, 467C>T and 803G>C in exon 7, have resulted in replacement of amino acid P156L and G268A. The mean fluorescence intensity (MFI) of A antigen in CisAB01 cases was 135, while the control group was 172. The B antigens in CisAB01 cases (MFI=38) showed significant decrease in MFI compared with the control group (MFI=164). CONCLUSION: 803G>C mutation of the ABO gene probably underlies the CisAB01 subtype. Fluorescence intensity of A antigens in CisAB01 subtype cases is slightly lower than the normal type, while the B antigen was significantly lower.

Transparent Self-Healing Anti-Freezing Ionogel for Monolayered Triboelectric Nanogenerator and Electromagnetic Energy-Based Touch Panel.

The advent of Internet of Things and artificial intelligence era necessitates the advancement of self-powered electronics. However, prevalent multifunctional electronics still face great challenges in rigid electrodes, stacked layers, and external power sources to restrict the development in flexible electronics. Here, a transparent, self-healing, anti-freezing (TSA) ionogel composed of fluorine-rich ionic liquid and fluorocarbon elastomer, which is engineered for monolayered triboelectric nanogenerators (M-TENG) and electromagnetic energy-based touch panels is developed. Notably, the TSA-ionogel exhibits remarkable features including outstanding transparency (90%), anti-freezing robustness (253 K), impressive stretchability (600%), and repetitive self-healing capacity. The resultant M-TENG achieves a significant output power density (200 mW m-2 ) and sustains operational stability beyond 1 year. Leveraging this remarkable performance, the M-TENG is adeptly harnessed for biomechanical energy harvesting, self-powered control interface, electroluminescent devices, and enabling wireless control over electrical appliances. Furthermore, harnessing Faraday's induction law and exploiting human body's intrinsic antenna properties, the TSA-ionogel seamlessly transforms into an autonomous multifunctional epidermal touch panel. This touch panel offers impeccable input capabilities through word inscription and participation in the Chinese game of Go. Consequently, the TSA-ionogel's innovation holds the potential to reshape the trajectory of next-generation electronics and profoundly revolutionize the paradigm of human-machine interaction.

Programmable ultrasound imaging guided theranostic nanodroplet destruction for precision therapy of breast cancer.

Ultrasound-stimulated contrast agents have gained significant attention in the field of tumor treatment as drug delivery systems. However, their limited drug-loading efficiency and the issue of bulky, imprecise release have resulted in inadequate drug concentrations at targeted tissues. Herein, we developed a highly efficient approach for doxorubicin (DOX) precise release at tumor site and real-time feedback via an integrated strategy of "programmable ultrasonic imaging guided accurate nanodroplet destruction for drug release" (PND). We synthesized DOX-loaded nanodroplets (DOX-NDs) with improved loading efficiency (15 %) and smaller size (mean particle size: 358 nm). These DOX-NDs exhibited lower ultrasound activation thresholds (2.46 MPa). By utilizing a single diagnostic transducer for both ultrasound stimulation and imaging guidance, we successfully vaporized the DOX-NDs and released the drug at the tumor site in 4 T1 tumor-bearing mice. Remarkably, the PND group achieved similar tumor remission effects with less than half the dose of DOX required in conventional treatment. Furthermore, the ultrasound-mediated vaporization of DOX-NDs induced tumor cell apoptosis with minimal damage to surrounding normal tissues. In summary, our PND strategy offers a precise and programmable approach for drug delivery and therapy, combining ultrasound imaging guidance. This approach shows great potential in enhancing tumor treatment efficacy while minimizing harm to healthy tissues.