Disruption of DNA-PKcs-mediated cGAS retention on damaged chromatin potentiates DNA damage-inducing agent-induced anti-multiple myeloma activity.

BACKGROUND: Targeting DNA damage repair factors, such as DNA-dependent protein kinase catalytic subunit (DNA-PKcs), may offer an opportunity for effective treatment of multiple myeloma (MM). In combination with DNA damage-inducing agents, this strategy has been shown to improve chemotherapies partially via activation of cGAS-STING pathway by an elevated level of cytosolic DNA. However, as cGAS is primarily sequestered by chromatin in the nucleus, it remains unclear how cGAS is released from chromatin and translocated into the cytoplasm upon DNA damage, leading to cGAS-STING activation. METHODS: We examined the role of DNA-PKcs inhibition on cGAS-STING-mediated MM chemosensitivity by performing mass spectrometry and mechanism study. RESULTS: Here, we found DNA-PKcs inhibition potentiated DNA damage-inducing agent doxorubicin-induced anti-MM effect by activating cGAS-STING signaling. The cGAS-STING activation in MM cells caused cell death partly via IRF3-NOXA-BAK axis and induced M1 polarization of macrophages. Moreover, this activation was not caused by defective classical non-homologous end joining (c-NHEJ). Instead, upon DNA damage induced by doxorubicin, inhibition of DNA-PKcs promoted cGAS release from cytoplasmic chromatin fragments and increased the amount of cytosolic cGAS and DNA, activating cGAS-STING. CONCLUSIONS: Inhibition of DNA-PKcs could improve the efficacy of doxorubicin in treatment of MM by de-sequestrating cGAS in damaged chromatin.

Advances in the Treatment of Neuropathic Pain by Sympathetic Regulation.

PURPOSE OF REVIEW: To explore the mechanism and therapeutic effect of sympathetic nerve regulation on neuropathic pain. RECENT FINDINGS: A comprehensive search was conducted in the PubMed and CNKI libraries, using the following keywords: stele ganglion block, neuropathic pain, sympathetic nerve block, sympathetic chemical destruction, and sympathetic radiofrequency thermocoagulation. We selected and critically reviewed research articles published in English that were related to sympathetic modulation in the treatment of neuropathic pain. The collected literature will be classified according to content and reviewed in combination with experimental results and clinical cases. Neuropathic pain was effectively treated with sympathetic regulation technology. Its mechanism includes the inhibition of sympathetic nerve activity, regulation of the inflammatory response, and inhibition of pain transmission, which greatly alleviates neuropathic pain in patients. Stellate ganglion blocks, thoracic and lumbar sympathectomies, chemical destruction, and radiofrequency thermocoagulation have been widely used to treat neuropathic pain. Sympathetic regulation can effectively relieve pain symptoms and improve the patient's quality of life by inhibiting sympathetic nerve activity, reducing the production and release of pain-related mediators, and inhibiting pain transmission. CT-guided radiofrequency thermocoagulation of the thoracic and lumbar sympathetic nerves is effective and durable, with few complications, and is recommended as a treatment for intractable neuropathic pain.

Time-Aware Dual LSTM Neural Network with Similarity Graph Learning for Remote Sensing Service Recommendation.

Technological progress has led to significant advancements in Earth observation and satellite systems. However, some services associated with remote sensing face issues related to timeliness and relevance, which affect the application of remote sensing resources in various fields and disciplines. The challenge now is to help end-users make precise decisions and recommendations for relevant resources that meet the demands of their specific domains from the vast array of remote sensing resources available. In this study, we propose a remote sensing resource service recommendation model that incorporates a time-aware dual LSTM neural network with similarity graph learning. We further use the stream push technology to enhance the model. We first construct interaction history behavior sequences based on users' resource search history. Then, we establish a category similarity relationship graph structure based on the cosine similarity matrix between remote sensing resource categories. Next, we use LSTM to represent historical sequences and Graph Convolutional Networks (GCN) to represent graph structures. We construct similarity relationship sequences by combining historical sequences to explore exact similarity relationships using LSTM. We embed user IDs to model users' unique characteristics. By implementing three modeling approaches, we can achieve precise recommendations for remote sensing services. Finally, we conduct experiments to evaluate our methods using three datasets, and the experimental results show that our method outperforms the state-of-the-art algorithms.

Antidepressant polyprenylated acylphloroglucinols from Hypericum ascyron.

Phytochemical investigation on the 90% EtOH extract of the air-dried aerial parts of Hypericum ascyron resulted in the isolation of three new polycyclic polyprenylated derivatives ascyronines A-C (1-3). Structural elucidation of all the compounds was performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy. All the polycyclic polyprenylated acylphloroglucinols were evaluated for their antidepressant activity by inhibiting the reuptake of tritiated serotonin ([3H]-5-HT) and noradrenalinet ([3H]-NE) in rat brain synaptosomes. Compounds 2 and 3 exhibited weak antidepressant activities in the [3H]-5-HT mode.

Identifying the causal effects of long-term exposure to PM2.5 and ground surface ozone on individual medical costs in China-evidence from a representative longitudinal nationwide cohort.

BACKGROUND: There is little evidence on whether PM2.5 and ground surface ozone have consistent effects on increased individual medical costs, and there is a lack of evidence on causality in developing countries. METHODS: This study utilized balanced panel data from 2014, 2016, and 2018 waves of the Chinese Family Panel Study. The Tobit model was developed within a counterfactual causal inference framework, combined with a correlated random effects and control function approach (Tobit-CRE-CF), to explore the causal relationship between long-term exposure to air pollution and medical costs. We also explored whether different air pollutants exhibit comparable effects. RESULTS: This study encompassed 8928 participants and assessed various benchmark models, highlighting the potential biases from failing to account for air pollution endogeneity or overlooking respondents without medical costs. Using the Tobit-CRE-CF model, significant effects of air pollutants on increased individual medical costs were identified. Specifically, margin effects for PM2.5 and ground-level ozone signifying that a unit increase in PM2.5 and ground-level ozone results in increased total medical costs of 199.144 and 75.145 RMB for individuals who incurred fees in the previous year, respectively. CONCLUSIONS: The results imply that long-term exposure to air pollutants contributes to increased medical costs for individuals, offering valuable insights for policymakers aiming to mitigate air pollution's consequences.

A Novel Pathway for Porcine Epidemic Diarrhea Virus Transmission from Sows to Neonatal Piglets Mediated by Colostrum.

The mechanisms of colostrum-mediated virus transmission are difficult to elucidate because of the absence of experimental animal models and the difficulties in tissue sample collection from mothers in the peripartum period. Porcine epidemic diarrhea virus (PEDV) is a reemerging enteropathogenic coronavirus that has catastrophic impacts on the global pig industry. PEDV primarily infects neonatal piglets by multiple routes, especially 1- to 2-day-old neonatal piglets. Here, our epidemiological investigation and animal challenge experiments revealed that PEDV could be vertically transmitted from sows to neonatal piglets via colostrum, and CD3+ T cells in the colostrum play an important role in this process. The results showed that PEDV colonizing the intestinal epithelial cells (IECs) of orally immunized infected sows could be transferred to CD3+ T cells located just beneath the IECs. Next, PEDV-carrying CD3+ T cells, with the expression of integrin α4ß7 and CCR10, migrate from the intestine to the mammary gland through blood circulation. Arriving in the mammary gland, PEDV-carrying CD3+ T cells could be transported across mammary epithelial cells (MECs) into the lumen (colostrum), as illustrated by an autotransfusion assay and an MECs/T coculture system. The PEDV-carrying CD3+ T cells in colostrum could be interspersed between IECs of neonatal piglets, causing intestinal infection via cell-to-cell contact. Our study demonstrates for the first time that colostrum-derived CD3+ T cells comprise a potential route for the vertical transmission of PEDV. IMPORTANCE The colostrum represents an important infection route for many viruses. Here, we demonstrate the vertical transmission of porcine epidemic diarrhea virus (PEDV) from sows to neonatal piglets via colostrum. PEDV colonizing the intestinal epithelial cells could transfer the virus to CD3+ T cells located in the sow intestine. The PEDV-carrying CD3+ T cells in the sow intestine, with the expression of integrin α4ß7 and CCR10, arrive at the mammary gland through blood circulation and are transported across mammary epithelial cells into the lumen, finally leading to intestinal infection via cell-to-cell contact in neonatal piglets. Our study not only demonstrates an alternative route of PEDV infection but also provides an animal model of vertical transmission of human infectious disease.

Many Roads Lead to Rome: Differential Learning Processes for the Same Perceptual Improvement.

Repeatedly exercising a perceptual ability usually leads to improvement, yet it is unclear whether the mechanisms supporting the same perceptual learning could be flexibly adjusted according to the training settings. Here, we trained adult observers in an orientation-discrimination task at either a single (focused) retinal location or multiple (distributed) retinal locations. We examined the observers' discriminability (N = 52) and bias (N = 20) in orientation perception at the trained and untrained locations. The focused and distributed training enhanced orientation discriminability by the same amount and induced a bias in perceived orientation at the trained locations. Nevertheless, the distributed training promoted location generalization of both practice effects, whereas the focused training resulted in specificity. The two training tactics also differed in long-term retention of the training effects. Our results suggest that, depending on the training settings of the same task, the same discrimination learning could differentially engage location-specific and location-invariant representations of the learned stimulus feature.

Causal effects of maternal exposure to PM2.5 during pregnancy on depression symptoms in adolescence: Identifying vulnerable windows and subpopulations in a national cohort study.

Few studies have examined the causal relationship between chronic exposure to air pollutants during pregnancy and depression in adolescent offspring. In addition, it has not been investigated whether exposure is most harmful to adolescents in certain populations and at certain stages of pregnancy. A total of 1975 adolescents from 1632 families from the China Family Panel Study, a representative national longitudinal cohort, were included in this study. We used high-resolution satellite retrieval data to assess the PM2.5 exposure of mothers during pregnancy. Specifically, we employed a two-stage instrumental variable model (IV-2SLS) within the counterfactual causal inference framework, and selected and validated appropriate instruments, thereby mitigating potentially biased results arising from bi-direction between dependent and independent variables. This approach allowed us to explore the causal relationship between maternal PM2.5 exposure during pregnancy and adolescent depression symptoms. The endogeneity of air pollution during pregnancy and the need for a causal model were suggested by the results of the model comparisons. Using the IV-2SLS model, we found that maternal exposure to PM2.5 during pregnancy exacerbates depressive symptoms in the offspring during adolescence (ß = 0.2, 95% CI: 0.05-0.34). We also found that exposure during the first trimester may cause greater harm. Adolescents with low household income, being male, irregular exercise habits, living in rural areas, and having mothers with poorer mental status may be more vulnerable. The findings suggest that maternal exposure to PM2.5 during pregnancy may have a negative impact on the depression symptoms of offspring in adolescence and that more attention should be paid to vulnerable populations and the window of vulnerability.

Causal effects of air pollution on mental health among Adults--An exploration of susceptible populations and the role of physical activity based on a longitudinal nationwide cohort in China.

Long-term exposure to air pollutants is likely to be associated with mental disorders, but relevant studies remain limited and inconsistent, and evidence to assess causality is particularly lacking, especially in developing countries. In addition, there are few studies on the role of physical activity in this relationship. We investigated the causal relationship between air pollutant exposure and mental health among Chinese adults and whether physical activity could play a positive role in this relationship. Using the balanced panel data for 2014 and 2016 from the China Family Panel Study, a representative Chinese national cohort study, we selected and validated appropriate instrumental variable to explore the causal relationship between air pollution and mental health and explored the moderating effect of physical activity using an instrumental variable fixed effects model (IVFE) in a counterfactual causal inference framework. PM2.5 and ground surface ozone were selected as proxies for different types of air pollutants and extended the interpretability by studying them for populations with different characteristics. A total of 21,944 participants were included in this study. In the IVFE model, we found that both PM2.5 and ground surface ozone significantly negatively affected mental health, and that habitual physical activity counteracted this negative effect regardless of different types of air pollution. We also found that the findings held for adults with different characteristics. The findings suggest that habitual physical activity may offset the deterioration of mental health in adults in developing countries due to air pollution, regardless of age, gender, income, and the presence of chronic diseases.

"Parenchyma transection-first" strategy is superior to "tunnel-first" strategy in robotic spleen-preserving distal pancreatectomy with conservation of splenic vessels.

BACKGROUND: Creating a tunnel between the pancreas and splenic vessels followed by pancreatic parenchyma transection ("tunnel-first" strategy) has long been used in spleen-preserving distal pancreatectomy (SPDP) with splenic vessel preservation (Kimura's procedure). However, the operation space is limited in the tunnel, leading to the risks of bleeding and difficulties in suturing. We adopted the pancreatic "parenchyma transection-first" strategy to optimize Kimura's procedure. METHODS: The clinical data of consecutive patients who underwent robotic SPDP with Kimura's procedure between January 2017 and September 2022 at our center were retrieved. The cohort was classified into a "parenchyma transection-first" strategy (P-F) group and a "tunnel-first" strategy (T-F) group and analyzed. RESULTS: A total of 91 patients were enrolled in this cohort, with 49 in the T-F group and 42 in the P-F group. Compared with the T-F group, the P-F group had significantly shorter operative time (146.1 ± 39.2 min vs. 174.9 ± 46.6 min, P < 0.01) and lower estimated blood loss [40.0 (20.0-55.0) mL vs. 50.0 (20.0-100.0) mL, P = 0.03]. Failure of splenic vessel preservation occurred in 10.2% patients in the T-F group and 2.4% in the P-F group (P = 0.14). The grade 3/4 complications were similar between the two groups (P = 0.57). No differences in postoperative pancreatic fistula, abdominal infection or hemorrhage were observed between the two groups. CONCLUSIONS: The pancreatic "parenchyma transection-first" strategy is safe and feasible compared with traditional "tunnel-first strategy" in SPDP with Kimura's procedure.

Colorimetric Sensors for Chemical and Biological Sensing Applications.

Colorimetric sensors have been widely used to detect numerous analytes due to their cost-effectiveness, high sensitivity and specificity, and clear visibility, even with the naked eye. In recent years, the emergence of advanced nanomaterials has greatly improved the development of colorimetric sensors. This review focuses on the recent (from the years 2015 to 2022) advances in the design, fabrication, and applications of colorimetric sensors. First, the classification and sensing mechanisms of colorimetric sensors are briefly described, and the design of colorimetric sensors based on several typical nanomaterials, including graphene and its derivatives, metal and metal oxide nanoparticles, DNA nanomaterials, quantum dots, and some other materials are discussed. Then the applications, especially for the detection of metallic and non-metallic ions, proteins, small molecules, gas, virus and bacteria, and DNA/RNA are summarized. Finally, the remaining challenges and future trends in the development of colorimetric sensors are also discussed.

Nitrogen allocation for CO2 fixation promotes nitrogen use in the photosynthetic compensation of soybean under heterogeneous light after a pre-shading.

The spatial and temporal distribution of sunlight around plants is constantly changing in natural and farmland environments. Previous studies showed that the photosynthesis of crops responds significantly to heterogeneous light conditions in fields. However, the underlying mechanisms remain unclear. In the present study, soybean plants were treated by heterogeneous light after a pre-shading (SH-HL) to simulate the light condition in relay strip intercropping. Gas exchange and nitrogen (N) of leaves were measured to evaluate the photosynthetic performance, as well as photosynthetic N- and water-use efficiency (PNUE and PWUE). Chlorophylls (Chl) and Rubisco were analyzed as representative photosynthetic N components. Results suggest that SH-HL treated soybean exhibited evident photosynthetic compensation as the net photosynthetic rate (Pn) increased significantly in unshaded leaves, from which the export of photosynthates was enhanced. Under SH-HL, leaf N concentration remained relatively stable in unshaded leaves. While Chl concentration decreased but Rubisco concentration increased in unshaded leaves, indicating preferential allocation of leaf N for CO2 fixation. Results also showed that PNUE increased and PWUE decreased in unshaded leaves under SH-HL. Therefore, we suggest that within-leaf N allocation for CO2 fixation in unshaded leaves rather than within-plant N distribution to unshaded leaves drives the photosynthetic compensation under heterogeneous light after a pre-shading. However, enhanced water loss from unshaded leaves is a cost for efficient N-use under these conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01392-8.

General Design Concepts for CAPodes as Ionologic Devices.

Capacitive analogues of semiconductor diodes (CAPodes) present a new avenue for energy-efficient and nature-inspired next-generation computing devices. Here, we disclose the generalized concept for bias-direction-adjustable n- and p-CAPodes based on selective ion sieving. Controllable-unidirectional ion flux is realized by blocking electrolyte ions from entering sub-nanometer pores. The resulting CAPodes exhibit charge-storage characteristics with a high rectification ratio (96.29 %). The enhancement of capacitance is attributed to the high surface area and porosity of an omnisorbing carbon as counter electrode. Furthermore, we demonstrate the use of an integrated device in a logic gate circuit architecture to implement logic operations ('OR', 'AND'). This work demonstrates CAPodes as a generalized concept to achieve p-n and n-p analogue junctions based on selective ion electrosorption, provides a comprehensive understanding and highlights applications of ion-based diodes in ionologic architectures.

Unraveling the Capacitive Charge Storage Mechanism of Nitrogen-Doped Porous Carbons by EQCM and ssNMR.

Fundamental understanding of ion electroadsorption processes in porous electrodes on a molecular level provides important guidelines for next-generation energy storage devices like electric double layer capacitors (EDLCs). Porous carbons functionalized by heteroatoms show enhanced capacitive performance, but the underlying mechanism is still elusive, due to the lack of reliable tools to precisely identify multiple N species and establish clear structure property relations. Here, we use advanced analytical techniques such as low-temperature solid-state NMR (ssNMR) and electrochemical quartz crystal microbalance (EQCM) to relate the complex nitrogen functionalities to the charging mechanisms and capacitive performance. For the first time, it is demonstrated at a molecular level that N-doping strongly influences the electroadsorption mechanism in EDLCs. Without N-doping, anion (SO42-) adsorption-desorption dominates the charging mechanism, whereas after doping, Li+ electroadsorption plays a key role. With the help of EQCM, it is demonstrated that SO42- is strongly immobilized on the N-doped surface, leaving Li+ as the main charge carrier. The smaller size and higher concentration of Li+ compared to SO42- benefit a higher capacitance. Amine/amide N is responsible for high capacitance, but surprisingly the pyridinic, pyrrolic, and graphitic N groups have no significant influence. 2D 1H-15N NMR spectroscopy indicates that the conversion from pyridinium to pyrrolic N gives rise to a slightly decreased capacitance. This work not only demonstrates ssNMR as a powerful tool for surface chemistry characterization of electrode materials but also uncovers the related charging mechanism by EQCM, paving the way toward a comprehensive picture of EDLC chemistry.

Radiation-hardened silicon photonic passive devices on a 3 µm waveguide platform under gamma and proton irradiation.

Silicon photonics is considered to be an ideal solution as optical interconnect in radiation environments. Our previous study has demonstrated experimentally that radiation responses of device are related to waveguide size, and devices with thick top silicon waveguide layers are expected to be less sensitive to irradiation. Here, we design radiation-resistant arrayed waveguide gratings and Mach-Zehnder interferometers based on silicon-on-insulator with 3 µm-thick silicon optical waveguide platform. The devices are exposed to 60Co γ-ray irradiation up to 41 Mrad(Si) and 170-keV proton irradiation with total fluences from 1×1013 to 1×1016 p/cm2 to evaluate performance after irradiation. The results show that these devices can function well and have potential application in harsh radiation environments.

Suppression of JNK/ERK dependent autophagy enhances Jaspine B derivative-induced gastric cancer cell death via attenuation of p62/Keap1/Nrf2 pathways.

Gastric cancer is one of the most common cancers with few effective treatments, a new treatment agent is desperately needed. C-2, a Jaspine B derivative, has shown anti-cancer efficacy in gastric cancer cells. The anti-cancer mechanism, however, remains unknown. As a result, we investigate the anti-cancer effect and the underlying mechanism of C-2 in gastric cancer cells. The results showed that C-2 selectively reduced the proliferation of gastric cancer cells when compared to normal epithelial gastric cells. Western blotting and flow cytometry further demonstrated that Caspase9 is involved in causing cell death. Meanwhile, C-2 triggered autophagy in gastric cancer cells, inhibition of which with LY294002 can enhance the anti-proliferative activity of C-2. Next, we found that C-2 triggered autophagy through activating JNK/ERK, and that inhibitors of these proteins exacerbated C-2 induced cell death. Mechanically, enhanced phosphorylation of JNK/ERK elevated Beclin-1 by disturbing Beclin-1/Bcl-xL or Beclin-1/Bcl-2 complexes, resulting in autophagy and up-regulation of p62. Finally, p62 binds Keap1 competitively to release Nrf2, boosting Nrf2 translocation from the cytoplasm to the nucleus and triggering expression of Nrf2 target genes, so enhancing survival. C-2 inhibited the growth of gastric cancer cells, while JNK/ERK dependent autophagy antagonized C-2 induced cell growth inhibition through p62/Keap1/Nrf2 pathway.

Structural characteristics of Heparan sulfate required for the binding with the virus processing Enzyme Furin.

Furin is one of the nine-member proprotein convertase family. Furin cleaves proteins with polybasic residues, which includes many viral glycoproteins such as SARS-Cov-2 spike protein. The cleavage is required for the activation of the proteins. Currently, the mechanisms that regulate Furin activity remain largely unknown. Here we demonstrated that Furin is a novel heparin/heparan sulfate binding protein by the use of biochemical and genetic assays. The KD is 9.78 nM based on the biolayer interferometry assay. Moreover, we found that sulfation degree, site-specific sulfation (N-sulfation and 3-O-sulfation), and iduronic acid are the major structural determinants for the binding. Furthermore, we found that heparin inhibits the enzymatic activity of Furin when pre-mixes heparin with either Furin or Furin substrate. We also found that the Furin binds with cells of different origin and the binding with the cells of lung origin is the strongest one. These data could advance our understanding of the working mechanism of Furin and will benefit the Furin based drug discovery such as inhibitors targeting the interaction between heparan sulfate and Furin for inhibition of viral infection.

Construction of Confined Bifunctional 2D Material for Efficient Sulfur Resource Recovery and Hg2+ Adsorption in Desulfurization.

Substantial energy penalty of valuable sulfate recovery restricts the efficiency of wet desulfurization and increases the risk of Hg0 reemission. Although the enhanced sulfite oxidation rate with cobalt-based materials can increase the energy efficiency, inactivation and poisoning of catalyst due to the competition of reactant must be addressed. Here we obtained a superwetting two-dimensional cobalt-nitrogen-doped carbon (2D Co-N-C) nanosheet featuring confined catalysis/adsorption sites for the energy-efficient sulfite oxidation and Hg2+ adsorption. The designed structure exhibits enhanced surface polarity, availability and short reactant diffusion path, thus enabling the significant catalytic TOF value of 0.085 s-1 and simultaneous mercury removal ability of 143.26 mg·g-1. The catalyst nanosheets present regenerating stabilities to improve cost-efficiency. By deployment of the Co-N-C catalysts, a marked reduction of heat penalty up to 69% can be achieved, which makes this catalytic pathway for sulfur resource recovery economically feasible in real industry scenario.

STMN1 as a novel prognostic biomarker in HCC correlating with immune infiltrates and methylation.

BACKGROUND: Upregulation of Stathmin 1 (STMN1), a cytoplasmic phosphoprotein that controls the dynamics of cellular microtubules, is linked to malignant behavior and poor prognosis in a range of malignancies. However, little research has been done on STMN1's potential role in HCC as a single factor in DNA methylation, m6A, or immunological modulation. RESULTS: STMN1 is overexpressed in hepatocellular carcinoma, where it is related to clinicopathological parameters and affects the prognosis of HCC patients. STMN1 overexpression plays an important role in the diagnosis and prognosis of hepatocellular carcinoma. Meanwhile, methylation of 7 CpG sites of STMN1 in HCC was correlated with prognosis, and STMN1 expression was closely related to m6A modification. In addition, STMN1 expression is associated with immune cell infiltration, immune molecules, and immune checkpoints in HCC. CONCLUSION: STMN1 has a significant role in hepatocellular carcinoma diagnosis and prediction. STMN1 is implicated not just in the onset and course but also in the immunological modulation of the disease. DNA methylation and m6A are both linked to STMN1. Therefore, STMN1 could be used as a diagnostic and prognostic biomarker for HCC, as well as a target for immunotherapy.

Bioactive Ion-Based Switchable Supercapacitors.

Switchable supercapacitors (SCs) enable a reversible electrically-driven uptake/release of bioactive ions by polarizing porous carbon electrodes. Herein we demonstrate the first example of a bioactive ion-based switchable supercapacitor. Based on choline chloride and porous carbons we unravel the mechanism of physisorption vs. electrosorption by nuclear magnetic resonance, Raman, and impedance spectroscopy. Weak physisorption facilitates electrically-driven electrolyte depletion enabling the controllable uptake/release of electrolyte ions. A new 4-terminal device is proposed, with a main capacitor and a detective capacitor for monitoring bioactive ion adsorption in situ. Ion-concentration control in printed choline-based switchable SCs realizes switching down to 8.3 % residual capacitance. The exploration of adsorption mechanisms in printable microdevices will open an avenue of manipulating bioactive ions for the application of drug delivery, neuromodulation, or neuromorphic devices.