A crossover study to evaluate the pharmacokinetics and bioequivalence of hydroxychloroquine tablets in healthy Chinese subjects.

AIMS: Hydroxychloroquine (HCQ) has a high variability and a long half-life in the human body. The purpose of this study was to evaluate the bioequivalence of a generic HCQ tablet (test preparation) versus a brand HCQ tablet (reference preparation) under fasting and fed conditions in a crossover design. MATERIALS AND METHODS: This was an open-label, two-period randomized, single-dose, crossover study in 47 healthy Chinese subjects who were sequentially and randomly allocated either to the fed group (high-fat meal; n = 23) or the fasting group (n = 24). Participants in each group were randomized to the two arms to receive either a single 200-mg dose of the test preparation or a 200-mg dose of the reference preparation. The application of the two preparations in each patient was separated by a 28-day washout period, regarded as sufficiently long to avoid significant interference from residual drug in the body. Whole blood samples were collected over 72 hours after drug administration. RESULTS: A total of 23 subjects completed both the fed and the fasting parts of the trial. There were no significant differences in Cmax, AUC0-72h, and T1/2 between the test and reference preparation (p < 0.05). Food had no significant effect on Cmax and T1/2 (p < 0.05), but AUC0-72h values were significantly reduced under fed condition compared to fasting condition (p < 0.05). The 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of Cmax and AUC0-72h were 0.84 - 1.05 and 0.89 - 0.98 in the fed study, and 0.97 - 1.07 and 0.97 - 1.05 in the fasting study, respectively. The carryover effect due to non-zero blood concentrations resulted in higher AUC0-72h values in the second period for both test and reference formulations and had no effect on the statistical results. No serious adverse events were reported. CONCLUSION: The investigation demonstrated that the test and reference preparations are bioequivalent and well tolerated under both fasting and fed conditions in healthy Chinese subjects.

SKLB-14b, a novel oral microtubule-destabilizing agent based on hydroxamic acid with potent anti-tumor and anti-multidrug resistance activities.

A hydroxamic acid based microtubule-destabilizing agent (MDA) SKLB-14b was discovered in this study, which was derived from shortening the linker length of the HDAC6 and microtubule dual-target inhibitor SKLB-23bb. SKLB-14b exhibited low nanomolar IC50 values on a wide spectrum of human cancer cell lines including both sensitive and multidrug-resistant cell lines. Surprisingly, its anti-proliferative activity relied on the presence of the hydroxamic acid group but lost inhibitory activity against HDACs. SKLB-14b bound to the colchicine site of tubulin and could inhibit tubulin polymerization. It exhibited good metabolic stability in liver microsomes, no inhibitory effect on CYP450 isoenzymes and high oral bioavailability. In vivo experiments revealed that SKLB-14b was potent in both sensitive (A2780S, HCT116) and resistant (A2780/T) xenograft mice models. Furthermore, in the patient-derived tumor xenograft (PDX) models of osimertinib resistant non-small cell lung cancer (NSCLC), 50 mg/kg of SKLB-14b administered every twodays inhibited tumor growth by 70.6% without obvious toxicity, better than the 59.7% inhibition rate of paclitaxel. Mechanistically, we found that SKLB-14b exerted anti-tumor and anti-multidrug resistance effects in vitro and in vivo through cell cycle arrest and pro-apoptotic activities, as well as vascular disrupting activities. Therefore, we discovered that SKLB-14b, as a novel MDA based on hydroxamic acid, could serve as a potential drug candidate for cancer therapy which deserves further investigation.

Large-Area Integrated Triboelectric Sensor Array for Wireless Static and Dynamic Pressure Detection and Mapping.

Large-area flexible pressure sensors are of paramount importance for various future applications, such as electronic skin, human-machine interfacing, and health-monitoring devices. Here, a self-powered and large-area integrated triboelectric sensor array (ITSA) based on coupling a triboelectric sensor array and an array chip of CD4066 through a traditional connection is reported. Enabled by a simple and cost-effective fabrication process, the size of the ITSA can be scaled up to 38 × 38 cm2 . In addition, unlike previously proposed triboelectric sensors arrays, which can only react to the dynamic interaction, this ITSA is able to detect static and dynamic pressure. Moreover, through integrating the ITSA with a signal processing circuit, a complete wireless sensing system is present. Diverse applications of the system are demonstrated in detail, including detecting pressure, identifying position, tracking trajectory, and recognizing the profile of external contact objects. Thus, the ITSA in this work opens a new route in the direction of large-area, self-powered, and wireless triboelectric sensing systems.

Flavonoids with Inhibitory Effects on NLRP3 Inflammasome Activation from Millettia velutina.

Eight new flavonoids, including two ß-hydroxy/methoxychalcones, velutones A and B (1 and 2), two 1,3-diarylpropan-1-ols, velutols C and D (3 and 4), a dihydroxychalcone, velutone E (5), a chalcone, velutone F (6), a furanoflavanone, velutone G (7), and a furanoflavonol, velutone H (8), and 14 known compounds were isolated from Millettia velutina. Their structures were determined by high-resolution electrospray ionisation mass spectrometry (HR-ESIMS) and spectroscopic data analyses and time-dependent density functional theory electronic circular dichroism (TD-DFT-ECD) calculations. Among the isolated constituents, compound 6 exhibited the most potent inhibitory effect (IC50: 1.3 µM) against nigericin-induced IL-1ß release in THP-1 cells. The initial mechanism of action study revealed that compound 6 suppressed NLRP3 inflammasome activation via blocking ASC oligomerization without affecting the priming step, which subsequently inhibited caspase-1 activation and IL-1ß secretion. Most importantly, compound 6 exerted potent protective effects in the LPS-induced septic shock mice model by improving the survival rate of mice and suppressing serum IL-1ß release. These results demonstrated that compound 6 had the potential to be developed as a broad-spectrum NLRP3 inflammasome inhibitor for the treatment of NLRP3-related disease.

Modulation of LPS-induced inflammation in RAW264.7 murine cells by novel isoflavonoids from Millettia pulchra.

Millettia pulchra is a renowned anti-inflammatory herbal medicine in southeast provinces of China. However, the underlying anti-inflammation mechanism remained incompletely understood. Herein, four new isoflavones, pulvones A-D and eleven reported constituents were isolated from the stems of Millettia pulchra with their structures being elucidated by HRMS and NMR analysis. The anti-inflammatory activities of pulvones A and C were further evaluated due to the better inhibitory activity on nitric oxide production in LPS-stimulated RAW264.7 cells and no obvious cytotoxicity to RAW264.7 cells. Western blot showed that pulvones A significantly decreased the levels of iNOS and COX-2 proteins and pulvones C only decreased the level of iNOS protein. ELISA analysis demonstrated that pulvones A inhibited the production of both interleukin-6 (IL-6) and IL-1ß while pulvones C showed better suppression effect on IL-1ß production in LPS-stimulated RAW264.7 cells. Then, their potential inhibitory effects on NF-κB pathway were tested in LPS-stimulated RAW264.7 cells. Immunofluorescence and western blot assay showed that pulvones A and C reduced the nuclear translocation of NF-κB(p65) and interrupted IκB phosphorylation. The ADP-Glo™ kinase assay showed pulvones A and C could directedly inhibit the IKKß kinase activity with the inhibitory rate of 40%, which were also verified by docking study. Collectively, these results suggested that pulvones A and C's anti-inflammatory effects were relevant to the interruption of NF-κB activation by inhibiting IKKß kinase.

Nanofiber-Reinforced Silver Nanowires Network as a Robust, Ultrathin, and Conformable Epidermal Electrode for Ambulatory Monitoring of Physiological Signals.

Extremely soft and thin electrodes with high skin conformability have potential applications in wearable devices for personal healthcare. Here, a submicrometer thick, highly robust, and conformable nanonetwork epidermal electrode (NEE) is reported. Electrospinning of polyamide nanofibers and electrospraying of silver nanowires are simultaneously performed to form a homogeneously convoluted network in a nonwoven way. For a 125 nm thick NEE, a low sheet resistance of ≈4 Ω sq-1 with an optical transmittance of ≈82% is achieved. Due to the nanofiber-based scaffold that undertakes most of the stress during deformation, the electric resistance of the NEE shows very little variation; less than 1.2% after 50 000 bending cycles. The NEE can form a fully conformal contact to human skin without additional adhesives, and the NEE shows a contact impedance that is over 50% lower than what is found in commercial gel electrodes. Due to conformal contact even under deformation, the NEE proves to be a stable, robust, and comfortable approach for measuring electrocardiogram signals, especially when a subject is in motion. These features make the NEE promising for use in the ambulatory measurement of physiological signals for healthcare applications.

Folate-receptor-targeted co-self-assembly carrier-free gemcitabine nanoparticles loading indocyanine green for chemo-photothermal therapy.

The carrier-free chemo-photothermal therapy has become a promising strategy to improve anti-cancer therapeutic efficacy owing to the combination of chemotherapy and photothermal therapy, with improved chemotherapy drug pharmacodynamics and pharmacokinetics, high drug loading, and reduced toxicity. We designed a novel carrier-free targeting nanoparticles, co-self-assembled amphiphilic prodrugs 3',5'-dioleoyl gemcitabine (DOG), and tumor-targeted γ-octadecyl folate (MOFA), with encapsulated US Food and Drug Administration (FDA)-approved photosensitizer indocyanine green (ICG) for synergistic chemo-photothermal therapy. The DOG linking oleic acid to the sugar moiety of gemcitabine (GEM) showed better self-assembly ability among GEM amphiphilic prodrugs linking different fatty acids. The readily available and highly reproducible 3',5'-dioleoyl gemcitabine/γ-octadecyl folate/indocyanine green (DOG/MOFA/ICG) nanoparticles were prepared by reprecipitation and showed nano-scale structure with mono-dispersity, great encapsulation efficiency of ICG (approximately 74%), acid- and laser irradiation-triggered GEM release in vitro and sustained GEM release in vivo after intravenous administration as well as excellent temperature conversion (57.0°C) with near-infrared laser irradiation. The combinational DOG/MOFA/ICG nanoparticles with near-infrared laser irradiation showed better anti-tumor efficacy than individual chemotherapy or photothermal therapy, with very low hemolysis and inappreciable toxicity for L929 cells. This co-self-assembly of the ICG and the chemotherapy drug (GEM) provides a novel tactic for the rational design of multifunctional nanosystems for targeting drug delivery and theranostics.

Bright fluorescent purine analogues as promising probes.

Modified bright fluorescent nucleosides that respond to the microenvironment have great potential as probes. A series of novel 8-(phenylethynyl)phenylated 2-amino-2'-deoxyadenosine and 2'-deoxyisoguanosine derivatives have been synthesized by Sonogashira-type coupling reaction and Suzuki reaction. The maximum emission of the new compounds is in the visible region, with strong solvatochromicity and pH-dependent fluorescent properties. Furthermore, some of them exhibit bright fluorescence emissions in various solvents (ε × Φ = 4000-39,000 cm-1 M-1). These consequences indicate that purine analogues could respond to the microenvironment and serve as promising fluorescent probes.Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2021.2004418 .

Discovery of a Series of Hydroxamic Acid-Based Microtubule Destabilizing Agents with Potent Antitumor Activity.

Hydroxamic acid group is one of the characteristic pharmacophores of histone deacetylase (HDAC) inhibitors. But here, we discovered a series of hydroxamic acid-based microtubule destabilizing agents (MDAs), which were derived from shortening the length of the linker in HDAC6 inhibitor SKLB-23bb. Interestingly, the low nanomolar antiproliferative activity of these MDAs depended on the presence of hydroxamic acid groups, but their inhibitory effects on HDAC were lost. Among them, 12b showed favorable metabolism stability, high bioavailability, and potent antitumor activity in multidrug-resistant cell lines and A2780/T xenograft model. More importantly, in the patient-derived xenograft models of triple-negative breast cancer and osimertinib-resistant non-small-cell lung cancer, both 20 mg/kg oral and 10 mg/kg intravenous administration of 12b could induce more than 70% tumor inhibition without obvious toxicity. Overall, we discovered that 12b, as a novel MDA based on hydroxamic acid, could serve as a potential MDA for further investigation.

Identification and optimization of piperine analogues as neuroprotective agents for the treatment of Parkinson's disease via the activation of Nrf2/keap1 pathway.

Parkinson's disease (PD) is a slowly progressive and complex neurodegenerative disorder. Up to date, there are no approved drugs that could slow or reverse the neurodegenerative process of PD. Here, we reported the synthesis of series of piperine analogues and the evaluation of their neuroprotective effects against hydrogen peroxide (H2O2) induced damage in the neuron-like PC12 cells. Among these analogues, 3b exhibited the most potent protection effect and its underlying mechanism was further investigated. Further results indicated that the ROS scavenging and cytoprotection effect of 3b might be related to the Nrf2 activation and upregulation of related phase II antioxidant enzymes, such as HO-1 and NQO1. In in vivo study, oral administration (100 mg/kg) of 3b significantly attenuated PD-associated behavioral deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD and protected tyrosine hydroxylase-immunopositive dopaminergic neurons. Our results provided evidence that 3b might be a promising candidate for Parkinson's disease treatment.

Alkaloids from Black Pepper (Piper nigrum L.) Exhibit Anti-Inflammatory Activity in Murine Macrophages by Inhibiting Activation of NF-κB Pathway.

Black pepper (Piper nigrum L.) has been commonly utilized in food preparation and traditional medicine in several countries. Seven new amide alkaloids, pipernigramides A-G (3, 10, 38, and 41-44), a new piperic ester, pipernigrester A (48), along with 47 known compounds were isolated from the EtOH extract of P. nigrum. The inhibitory effects on nitric oxide (NO) of all compounds were then evaluated. Among the tested compounds, three of them (42-44) significantly inhibited inducible nitric oxide synthase (iNOS)-mediated NO (IC50 = 4.74 ± 0.18, 4.08 ± 0.19, and 3.71 ± 0.32 µM, respectively), and IL-1ß, IL-6, TNF-α, and PGE2 release in RAW 264.7 cells stimulated by lipopolysaccharide. Moreover, 42-44 suppressed IκB degradation and further inhibited the cytosol-nucleus translocation of the p65 subunit by targeting IKK-ß. In the carrageenan-induced paw edema test, 42-44 demonstrated anti-inflammatory effects as well. These results indicate that all three compounds from P.nigrum have the potential anti-inflammatory effects.

Curcumin inhibits cellular cholesterol accumulation by regulating SREBP-1/caveolin-1 signaling pathway in vascular smooth muscle cells.

AIM: To investigate the protective effect and the possible mechanism of curcumin on anti-atherosclerosis. METHODS: Morphological changes of atherosclerotic lesions taken from apoE knockout (apoE-/-) mice were determined by hematoxylin- eosin staining. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC. The protein expression of caveolin-1 was quantified by Western blotting. Translocation and the expression of sterol response element-binding protein-1 (SREBP-1) were indirectly detected by an immunofluorescence analysis. RESULTS: The administration of 20 mg. kg(-1 ). d(-1 )curcumin to apoE-/- mice for 4 months induced a 50% reduction of atherosclerotic lesions and yielded a 5- fold increase in the caveolin-1 expression level as compared to the model group. Rat vascular smooth muscle cells (VSMC) pretreated with 50 mg/L ox-lipid density lipoprotein(ox-LDL) for 48 h increased cellular lipid contents, and stimulated SREBP-1 translocation, but decreased the caveolin-1 expression level. Lipid-loaded cells exposed to curcumin at various concentrations (12.5, 25, and 50 micromol/L) for different durations (0, 6, 12, 24, and 48 h) significantly diminished the number and area of cellular lipid droplets, total cholesterol, cholesterol ester, and free cholesterol accompanying the elevation of the caveolin-1 expression level (approximately 3-fold); the translocation of SREBP-1 from the cytoplasm to the nucleus was inhibited compared with the models. Lipid-loaded VSMC exposed to N-acetyl- Leu-Leu-norleucinal, a SREBP-1 protease inhibitor, showed increased nuclear translocation of SREBP-1, reduced caveolin-1 expression level, and upregulated cellular lipid levels. CONCLUSION: Curcumin inhibits ox-LDL-induced cholesterol accumulation in cultured VSMC through increasing the caveolin-1 expression via the inhibition of nuclear translocation of SREBP-1.

Triboelectrification-Enabled Self-Powered Data Storage.

Data storage by any means usually requires an electric driving power for writing or reading. A novel approach for self-powered, triboelectrification-enabled data storage (TEDS) is presented. Data are incorporated into a set of metal-based surface patterns. As a probe slides across the patterned surface, triboelectrification between the scanning probe and the patterns produces alternatively varying voltage signal in quasi-square wave. The trough and crest of the quasi-square wave signal are coded as binary bits of "0" and "1," respectively, while the time span of the trough and the crest is associated with the number of bits. The storage of letters and sentences is demonstrated through either square-shaped or disc-shaped surface patterns. Based on experimental data and numerical calculation, the theoretically predicted maximum data storage density could reach as high as 38.2 Gbit in-2. Demonstration of real-time data retrieval is realized with the assistance of software interface. For the TEDS reported in this work, the measured voltage signal is self-generated as a result of triboelectrification without the reliance on an external power source. This feature brings about not only low power consumption but also a much more simplified structure. Therefore, this work paves a new path to a unique approach of high-density data storage that may have widespread applications.

Highly Adaptive Solid-Liquid Interfacing Triboelectric Nanogenerator for Harvesting Diverse Water Wave Energy.

Harvesting water wave energy presents a significantly practical route to energy supply for self-powered wireless sensing networks. Here we report a networked integrated triboelectric nanogenerator (NI-TENG) as a highly adaptive means of harvesting energy from interfacing interactions with various types of water waves. Having an arrayed networking structure, the NI-TENG can accommodate diverse water wave motions and generate stable electric output regardless of how random the water wave is. Nanoscaled surface morphology consisting of dense nanowire arrays is the key for obtaining high electric output. A NI-TENG having an area of 100 × 70 mm2 can produce a stable short-circuit current of 13.5 µA and corresponding electric power of 1.03 mW at a water wave height of 12 cm. This merit promises practical applications of the NI-TENG in real circumstances, where water waves are highly variable and unpredictable. After energy storage, the generated electric energy can drive wireless sensing by autonomously transmitting data at a period less than 1 min. This work proposes a viable solution for powering individual standalone nodes in a wireless sensor network. Potential applications include but are not limited to long-term environment monitoring, marine surveillance, and off-shore navigation.

In Situ Active Poling of Nanofiber Networks for Gigantically Enhanced Particulate Filtration.

Enhancing the filtration efficiency of air filtering material without increasing its airflow resistance is a major challenge and of great significance. In this work, we report a type of active-poled nanofiber onto which in situ active poling is applied. It results in significantly enhanced filtration efficiency as well as dust holding capacity while keeping the airflow resistance constant. Owing to the in situ applied electric field, the nanofibers as well as the particulates are polarized. As a result, at a poling voltage of 2 kV, the removal efficiency and the quality factor for PM2.5 are enhanced by 17% and 130%, respectively. More importantly, the dust holding capacity represents a 3.5-fold enhancement over normal nanofibers. The approach reported in this work has the potential of being practically utilized in air purification purposes because it can bring about not only promoted filtration performance but also lowered noise and reduced power consumption.

Highly Robust, Transparent, and Breathable Epidermal Electrode.

Recently emerged electronic skins with applications in on-body sensing and human-machine interfaces call for the development of high-performance skin-like electrodes. In this work, we report a highly robust, transparent, and breathable epidermal electrode composed of a scaffold-reinforced conductive nanonetwork (SRCN). Solution-dispersed Ag nanowires, through facile vacuum filtration, are embedded into a scaffold made of polyamide nanofibers. Optical transmittance of 84.9% at 550 nm wavelength is achieved at a significantly low sheet resistance of 8.2 Ω sq-1. The resistance of the SRCN only slightly increases by less than 0.1% after being bent for 3000 cycles at the maximum curvature of 300 m-1 and by less than 1.5% after being dipped in saline solution for 2500 cycles. The excellent robustness is attributed to the reinforcement from the nanofiber-based scaffold as a backbone that maintains the connections among the Ag nanowires by undertaking most of the loaded stress. The SRCN not only forms tight and conformal bonding with the target surface but also allows the evaporation of perspiration, making it suitable as an epidermal electrode for long-time use. Furthermore, fine and clean-cut circuit patterns with a line width on the micrometer scale can be readily prepared, paving the way for fabricating sophisticated functional electronic skins.

Triboelectrification-Induced Self-Assembly of Macro-Sized Polymer Beads on a Nanostructured Surface for Self-Powered Patterning.

Here we report an electrostatic-templated self-assembly (ETSA) method for arbitrarily patterning millimeter-sized polymer beads on a nanostructured surface without using an extra voltage source. A patterned electrode underneath an electrification layer generates "potential wells" of the corresponding pattern at predefined window sites, which capture and anchor the beads within the window sites by electrostatic force. Analytical calculation is combined with numerical modeling to derive the electrostatic force acting on the beads, which is in great agreement with experimentally measured values. The generated pattern is solely determined by the predefined underlying electrode, making it arbitrarily switchable by using different electrode patterns. By transferring the assembled beads into an elastomer matrix, possible applications of the ETSA in fabricating optical and flexible displays are demonstrated.

Natural products berberine and curcumin exhibited better ameliorative effects on rats with non-alcohol fatty liver disease than lovastatin.

Studies have shown that satins and herbal products have potential to treat non-alcohol fatty liver disease (NAFLD) in clinic. However, no study has compared their effects, and their mechanisms remain unresolved. Here, we choose lovastatin and two herbal products including berberine and curcumin to compare their effects in treating NAFLD. NAFLD model was established by high fat food, and rats were administrated with lovastatin, berberine, curcumin, berberine + curcumin at the dosage of 100, 100, 100, 50 + 50 mg/kg bw, respectively. The body weight, visceral fat gain, histological inspection and serum parameters were studied to exam the curative effects. In addition, mediators including SREBP-1c, caveolin-1, pERK, NF-κB, TNF-α, and pJNK were studied. Results showed that berberine + curcumin group exhibited lower body and fat weigh compared with lovastatin group. Biochemical assays showed that LDL-c, ALT, AST, ALP, MDA, LSP level were lower in berberine + curcumin group compared with lovastatin group. Lower expression of SREBP-1c, pERK, TNF-α, and pJNK were also observed in berberine + curcumin group. We conclude that combination of curcumin and berberine exhibited better ameliorative effects in treating NAFLD than lovastatin, and this enhanced effect is associated with oxidative stress, hepatic inflammation and lipid metabolism.

Acceleration to death from liver cancer in people with hepatitis B viral mutations detected in plasma by mass spectrometry.

Liver cancer is the leading cause of cancer death in many regions of the world. With the goal to discover biomarkers that reflect subsets of high-risk individuals and their prognosis, we nested our study in a male cohort of 5,581 hepatitis B surface antigen carriers in Qidong, People's Republic of China, who were recruited starting in 1989. By December 2003, 667 liver cancer cases were diagnosed in this group and plasma samples collected at the initial screening at enrollment were available in 515 cases who had succumbed to liver cancer. Hepatitis B virus (HBV) DNA could be isolated in 355 (69%) of these samples. In 14%, 15%, 19%, 31%, and 22%, screening took place at < or = 1.5, 1.51 to 3, 3.01 to 5, 5.01 to 9, and > 9 years before death, respectively; and 39% died at age below 45 years. The relation between mutations in HBV and time to death were determined by logistic regression for the odds of mutation and by survival analyses methods with age as the time scale. In 279 (79%) of these individuals, the samples contained a two-nucleotide 1762T/1764A HBV mutation. Sixteen samples lacking the 1762T/1764A mutation had novel mutations elsewhere in the 1761 to 1767 region of the HBV genome. There was a statistically significant difference (P = 0.012) for the high prevalence of the HBV mutations in the men who died from hepatocellular carcinoma under the age of 45 years relative to those who died after 55 years of age and HBV mutations accelerated death (relative hazard, 1.40; 95% confidence interval, 1.06-1.85) and that the effect was attenuated by age from 2.04 for age 35 years to 1.0 for age 65 years with the 90% confidence band being above 1 for ages < 50 years. These findings provide a conceptual framework to explain the acceleration of mortality in individuals infected with HBV.

Stretchable Porous Carbon Nanotube-Elastomer Hybrid Nanocomposite for Harvesting Mechanical Energy.

A stretchable porous nanocomposite (PNC) is reported based on a hybrid of a multiwalled carbon nanotubes network and a poly(dimethylsiloxane) matrix for harvesting energy from mechanical interactions. The deformation-enabled energy-generating process makes the PNC applicable to various mechanical interactions, including pressing, stretching, bending, and twisting. It can be potentially used as an energy solution for wearable electronics.