Condensable Gases Capture with Ionic Liquids.

Condensable gases are the sum of condensable and volatile steam or organic compounds, including water vapor, which are discharged into the atmosphere in gaseous form at atmospheric pressure and room temperature. Condensable toxic and harmful gases emitted from petrochemical, chemical, packaging and printing, industrial coatings, and mineral mining activities seriously pollute the atmospheric environment and endanger human health. Meanwhile, these gases are necessary chemical raw materials; therefore, developing green and efficient capture technology is significant for efficiently utilizing condensed gas resources. To overcome the problems of pollution and corrosion existing in traditional organic solvent and alkali absorption methods, ionic liquids (ILs), known as "liquid molecular sieves", have received unprecedented attention thanks to their excellent separation and regeneration performance and have gradually become green solvents used by scholars to replace traditional absorbents. This work reviews the research progress of ILs in separating condensate gas. As the basis of chemical engineering, this review first provides a detailed discussion of the origin of predictive molecular thermodynamics and its broad application in theory and industry. Afterward, this review focuses on the latest research results of ILs in the capture of several important typical condensable gases, including water vapor, aromatic VOCs (i.e., BTEX), chlorinated VOC, fluorinated refrigerant gas, low-carbon alcohols, ketones, ethers, ester vapors, etc. Using pure IL, mixed ILs, and IL + organic solvent mixtures as absorbents also briefly expanded the related reports of porous materials loaded with an IL as adsorbents. Finally, future development and research directions in this exciting field are remarked.

CD1d protects against hepatocyte apoptosis in non-alcoholic steatohepatitis.

BACKGROUND & AIMS: Hepatocyte apoptosis, a well-defined form of cell death in non-alcoholic steatohepatitis (NASH), is considered the primary cause of liver inflammation and fibrosis. However, the mechanisms underlying the regulation of hepatocyte apoptosis in NASH remain largely unclear. We explored the anti-apoptotic effect of hepatocyte CD1d in NASH. METHODS: Hepatocyte CD1d expression was analyzed in patients with NASH and mouse models. Hepatocyte-specific gene overexpression or knockdown and anti-CD1d crosslinking were used to investigate the anti-apoptotic effect of hepatocyte CD1d on lipotoxicity-, Fas-, and concanavalin (ConA)-mediated liver injuries. A high-fat diet, a methionine-choline-deficient diet, a Fas agonist, and ConA were used to induce lipotoxic and/or apoptotic liver injuries. Palmitic acid was used to mimic lipotoxicity-induced apoptosis in vitro. RESULTS: We identified a dramatic decrease in CD1d expression in hepatocytes of patients with NASH and mouse models. Hepatocyte-specific CD1d overexpression and knockdown experiments collectively demonstrated that hepatocyte CD1d protected against hepatocyte apoptosis and alleviated hepatic inflammation and injuries in NASH mice. Furthermore, decreased JAK2-STAT3 signaling was observed in NASH patient livers. Mechanistically, anti-CD1d crosslinking on hepatocytes induced tyrosine phosphorylation of the CD1d cytoplasmic tail, leading to the recruitment and phosphorylation of JAK2. Phosphorylated JAK2 activated STAT3 and subsequently reduced apoptosis in hepatocytes, which was associated with an increase in anti-apoptotic effectors (Bcl-xL and Mcl-1) and a decrease in pro-apoptotic effectors (cleaved-caspase 3/7). Moreover, anti-CD1d crosslinking effectively protected against Fas- or ConA-mediated hepatocyte apoptosis and liver injury in mice. CONCLUSIONS: Our study uncovered a previously unrecognized anti-apoptotic CD1d-JAK2-STAT3 axis in hepatocytes that conferred hepatoprotection and highlighted the potential of hepatocyte CD1d-directed therapy for liver injury and fibrosis in NASH, as well as in other liver diseases associated with hepatocyte apoptosis. IMPACT AND IMPLICATIONS: Excessive and/or sustained hepatocyte apoptosis is critical in driving liver inflammation and injury. The mechanisms underlying the regulation of hepatocyte apoptosis in non-alcoholic steatohepatitis (NASH) remain largely unclear. Here, we found that CD1d expression in hepatocytes substantially decreases and negatively correlates with the severity of liver injury in patients with NASH. We further revealed a previously unrecognized anti-apoptotic CD1d-JAK2-STAT3 signaling axis in hepatocytes, which confers significant protection against liver injury in NASH and acute liver diseases. Thus, hepatocyte CD1d-targeted therapy could be a promising strategy to manipulate liver injury in both NASH and other hepatocyte apoptosis-related liver diseases.

Hepatocyte CD1d protects against liver immunopathology in mice with schistosomiasis japonica.

Schistosomiasis is a neglected tropical disease with over 250 million people infected worldwide. The main clinically important species Schistosoma mansoni (S. mansoni) and Schistosoma japonicum (S. japonicum) cause inflammatory responses against tissue-trapped eggs, resulting in formation of granulomas mainly in host liver. Persistent granulomatous response results in severe fibrosis in the liver, leading to irreversible impairment of the liver and even death of the host. CD1d, a highly conserved MHC class I-like molecule, is expressed by both haematopoietic and non-haematopoietic cells. CD1d on antigen-presenting cells (APCs) of haematopoietic origin presents pathogen-derived lipid antigens to natural killer T (NKT) cells, which enables them to rapidly produce large amounts of various cytokines and facilitate CD4+ T helper (Th) cell differentiation upon invading pathogens. Noteworthy, hepatocytes of non-haematopoietic origin have recently been shown to be involved in maintaining liver NKT cell homeostasis through a CD1d-dependent manner. However, whether hepatocyte CD1d-dependent regulation of NKT cell homeostasis also modulates CD4+ Th cell responses and liver immunopathology in murine schistosomiasis remains to be addressed. Here, we show in mice that CD1d expression on hepatocytes was decreased dramatically upon S. japonicum infection, accompanied by increased NKT cells, as well as upregulated Th1 and Th2 responses. Overexpression of CD1d in hepatocytes significantly decreased local NKT numbers and cytokines (IFN-γ, IL-4, IL-13), concomitantly with downregulation of both Th1 and Th2 responses and alleviation in pathological damage in livers of S. japonicum-infected mice. These findings highlight the potential of hepatocyte CD1d-targeted therapies for liver immunopathology control in schistosomiasis.

Ionic Liquids in Selective Oxidation: Catalysts and Solvents.

Selective oxidation has an important role in environmental and green chemistry (e.g., oxidative desulfurization of fuels and oxidative removal of mercury) as well as chemicals and intermediates chemistry to obtain high-value-added special products (e.g., organic sulfoxides and sulfones, aldehydes, ketones, carboxylic acids, epoxides, esters, and lactones). Due to their unique physical properties such as the nonvolatility, thermal stability, nonexplosion, high polarity, and temperature-dependent miscibility with water, ionic liquids (ILs) have attracted considerable attention as reaction solvents and media for selective oxidations and are considered as green alternatives to volatile organic solvents. Moreover, for easy separation and recyclable utilization, IL catalysts have attracted unprecedented attention as "biphasic catalyst" or "immobilized catalyst" by immobilizing metal- or nonmetal-containing ILs onto mineral or polymer supports to combine the unique properties of ILs (chemical and thermal stability, capacity for extraction of polar substrates and reaction products) with the extended surface of the supports. This review highlights the most recent outcomes on ILs in several important typical oxidation reactions. The contents are arranged in the series of oxidation of sulfides, oxidation of alcohols, epoxidation of alkenes, Baeyer-Villiger oxidation reaction, oxidation of alkanes, and oxidation of other compounds step by step involving ILs as solvents, catalysts, reagents, or their combinations.

Selective Transformation of Various Nitrogen-Containing Exhaust Gases toward N2 over Zeolite Catalysts.

In this review we focus on the catalytic removal of a series of N-containing exhaust gases with various valences, including nitriles (HCN, CH3CN, and C2H3CN), ammonia (NH3), nitrous oxide (N2O), and nitric oxides (NO(x)), which can cause some serious environmental problems, such as acid rain, haze weather, global warming, and even death. The zeolite catalysts with high internal surface areas, uniform pore systems, considerable ion-exchange capabilities, and satisfactory thermal stabilities are herein addressed for the corresponding depollution processes. The sources and toxicities of these pollutants are introduced. The important physicochemical properties of zeolite catalysts, including shape selectivity, surface area, acidity, and redox ability, are described in detail. The catalytic combustion of nitriles and ammonia, the direct catalytic decomposition of N2O, and the selective catalytic reduction and direct catalytic decomposition of NO are systematically discussed, involving the catalytic behaviors as well as mechanism studies based on spectroscopic and kinetic approaches and molecular simulations. Finally, concluding remarks and perspectives are given. In the present work, emphasis is placed on the structure-performance relationship with an aim to design an ideal zeolite-based catalyst for the effective elimination of harmful N-containing compounds.

Reduced expression of IA channels is associated with postischemic seizures in hyperglycemic rats.

Poststroke seizures are considered to be the major cause of epilepsy in the elderly. The mechanisms of poststroke seizures remain unclear. A history of diabetes mellitus has been identified as an independent predictor of acute poststroke seizures in stroke patients. The present study sought to reveal the mechanisms for the development of postischemic seizures under hyperglycemic conditions. Transient forebrain ischemia was produced in adult Wistar rats by using the four-vessel occlusion method. At the normal blood glucose level, seizures occurred in ∼50% of rats after 25 min of ischemia. However, in rats with hyperglycemia, the incidence rate of postischemic seizures was significantly increased to 100%. The occurrence of postischemic seizures was not correlated with the severity of brain damage in hyperglycemic rats. Mannitol, an osmotic diuretic agent, could neither prevent postischemic seizures nor alleviate the exacerbated brain damage in the presence of hyperglycemia. K(+) channels play a critical role in controlling neuronal excitability. The expression of A-type K(+) channel subunit Kv4.2 in the hippocampus and the cortex was significantly reduced in hyperglycemic rats with seizures compared with those without seizures. These results suggest that the reduction of Kv4.2 expression could contribute to the development of postischemic seizures in hyperglycemia.

Catalytic bubble-free hydrogenation reduction of azo dye by porous membranes loaded with palladium nanoparticles.

Catalytic bubble-free hydrogenation reduction of azo dye by porous membranes loaded with palladium (Pd) nanoparticles was studied for the first time. The effects of Pd loading, dye concentration and reuse repetitions of membranes were investigated. In reduction, the dye concentration decreased whereas the pH rose gradually. An optimal Pd loading was found. The catalytic membranes were able to be reused more than 3 times.

[Application effect and influencing factors of early awake prone position in patients with mild-to-moderate acute respiratory distress syndrome].

OBJECTIVE: To investigate the application effect of early awake prone position in mild-to-moderate acute respiratory distress syndrome (ARDS) patients, and analyze the related factors affecting the prone position outcome. METHODS: A prospective cohort study was conducted. The mild-to-moderate ARDS patients admitted to the emergency department of Yingshang County People's Hospital from January 2020 to June 2023 were enrolled as the research subjects. According to the results of prone tolerance test, the patients were divided into awake prone position group and non-prone position group. All patients were given high flow nasal cannula (HFNC) according to the standard procedures. The patients in the awake prone position group received prone position treatment within 12 hours after admission, in addition to the standard treatment. This could be performed in several times, at least once a day, and at least 2 hours each time. In order to prolong the prone position as much as possible, the patients were allowed to move or keep a small angle side prone. The changes of oxygenation index (PaO2/FiO2) at 0, 24, 48, and 72 hours after admission, the rate of intensive care unit (ICU) transfer, the use rate and use time of non-invasive ventilation (NIV), the total hospital stay, and the daily prone position time and 2-hour ROX index [ratio of pulse oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) and respiratory rate (RR)] of prone position patients were recorded. The successful termination of HFNC was defined as the successful prone position, and the failure of prone position was defined as switching to NIV or transferring to ICU. Subgroup analysis was performed, and the binary multivariate Logistic regression analysis was used to screen the influencing factors of the early awake prone position outcome. RESULTS: A total of 107 patients were finally enrolled, with 61 in the awake prone position group and 46 in the non-prone position group. Both groups showed a gradual increase in PaO2/FiO2 with prolonged admission time. The PaO2/FiO2 at 24 hours after admission in the awake prone position group was significantly higher than that at 0 hour [mmHg (1 mmHg ≈ 0.133 kPa): 191.94±17.86 vs. 179.24±29.27, P < 0.05], while the difference in the non-prone position group was only statistically significant at 72 hours (mmHg: 198.24±17.99 vs. 181.24±16.62, P < 0.05). Furthermore, the PaO2/FiO2 at 48 hours and 72 hours after admission in the awake prone position group was significantly higher than that in the non-prone position group. The use rate of NIV in the awake prone position group was significantly lower than that in the non-prone position group [36.1% (22/61) vs. 56.5% (26/46), P < 0.05]; Kaplan-Meier curve analysis further confirmed that the patients in the awake prone position group used NIV later, and the cumulative rate of NIV usage was significantly lower than that in the non-prone position group (Log-Rank test: χ 2 = 5.402, P = 0.020). Compared with the non-prone position group, the ICU transfer rate in the awake prone position group was significantly lowered [11.5% (7/61) vs. 28.3% (13/46), P < 0.05], and the HFNC time, NIV time, and total hospital stay were significantly shortened [HFNC time (days): 5.71±1.45 vs. 7.24±3.36, NIV time (days): 3.27±1.28 vs. 4.40±1.47, total hospital stay (days): 11 (7, 13) vs. 14 (10, 19), all P < 0.05]. Of the 61 patients who underwent awake prone positioning, 39 were successful, and 22 failed. Compared with the successful group, the patients in the failure group had a higher body mass index [BMI (kg/m2): 26.61±4.70 vs. 22.91±5.50, P < 0.05], lower PaO2/FiO2, proportion of asymptomatic hypoxemia and 2-hour ROX index of prone position [PaO2/FiO2 (mmHg): 163.73±24.73 vs. 185.69±28.87, asymptomatic hypoxemia proportion: 18.2% (4/22) vs. 46.2% (18/39), 2-hour ROX index of prone position: 5.75±1.18 vs. 7.21±1.45, all P < 0.05], and shorter daily prone positioning time (hours: 5.87±2.85 vs. 8.05±1.99, P < 0.05). Binary multivariate Logistic regression analysis showed that all these factors were influencing factors for the outcome of awake prone positioning (all P < 0.05), among which BMI [odds ratio (OR) = 1.447, 95% confidence interval (95%CI) was 1.105-2.063] and non-asymptomatic hypoxemia (OR = 13.274, 95%CI was 1.548-117.390) were risk factors for failure of prone position, while PaO2/FiO2 (OR = 0.831, 95%CI was 0.770-0.907), daily prone positioning time (OR = 0.482, 95%CI was 0.236-0.924), and 2-hour ROX index of prone position (OR = 0.381, 95%CI was 0.169-0.861) were protective factors. CONCLUSIONS: Early awake prone positioning in patients with mild-to-moderate ARDS supported by HFNC is safe and feasible, reducing the use rate and duration of NIV, lowering the ICU transfer rate, and shortening the hospital stay. High BMI and non-asymptomatic hypoxemia are risk factors for failed prone position, while higher PaO2/FiO2 and the ROX index within 2 hours of prone position (the patient's good response to prone position), and prolonged daily prone position can improve the success rate of prone position.

TGF-ß1 induces PD-1 expression in macrophages through SMAD3/STAT3 cooperative signaling in chronic inflammation.

Programmed cell death protein 1 (PD-1), a coinhibitory T cell checkpoint, is also expressed on macrophages in pathogen- or tumor-driven chronic inflammation. Increasing evidence underscores the importance of PD-1 on macrophages for dampening immune responses. However, the mechanism governing PD-1 expression in macrophages in chronic inflammation remains largely unknown. TGF-ß1 is abundant within chronic inflammatory microenvironments. Here, based on public databases, significantly positive correlations between PDCD1 and TGFB1 gene expression were observed in most human tumors. Of note, among immune infiltrates, macrophages as the predominant infiltrate expressed higher PDCD1 and TGFBR1/TGFBR2 genes. MC38 colon cancer and Schistosoma japonicum infection were used as experimental models for chronic inflammation. PD-1hi macrophages from chronic inflammatory tissues displayed an immunoregulatory pattern and expressed a higher level of TGF-ß receptors. Either TGF-ß1-neutralizing antibody administration or macrophage-specific Tgfbr1 knockdown largely reduced PD-1 expression on macrophages in animal models. We further demonstrated that TGF-ß1 directly induced PD-1 expression on macrophages. Mechanistically, TGF-ß1-induced PD-1 expression on macrophages was dependent on SMAD3 and STAT3, which formed a complex at the Pdcd1 promoter. Collectively, our study shows that macrophages adapt to chronic inflammation through TGF-ß1-triggered cooperative SMAD3/STAT3 signaling that induces PD-1 expression and modulates macrophage function.

Organoboron/iodide-catalyzed photoredox N-functionalization of NH-sulfoximines/sulfonimidamides.

An aminoquinolate diarylboron (AQDAB) and tetrabutylammonium iodide (TBAI) co-catalyzed photoredox process for N-functionalization of NH-sulfoximines/sulfonimidamides has been successfully developed. This protocol can afford the corresponding N-sulfenylated and N-phosphonylated products in good to excellent yields under conditions without metallic (photo)catalysts, external oxidants, or acidic/basic additives. A wide range of functional groups are tolerated, and the N-phosphonylated products of NH-sulfonimidamides have been reported for the first time.

Multi-Wavelength Photoacoustic Temperature Feedback Based Photothermal Therapy Method and System.

Photothermal therapy (PTT) is a new type of tumor treatment technology that is noninvasive, repeatable, and does not involve radiation. Owing to the lack of real-time and accurate noninvasive temperature measurement technology in current PTT surgical procedures, empirical and open-loop treatment laser power control mode inevitably leads to overtreatment. Thermal radiation causes irreversible damage to normal tissue around cancer tissue and seriously affects the therapeutic effect of PTT and other therapies conducted at the same time. Therefore, real-time measurement and control of the temperature and thermal damage of the therapeutic target are critical to the success of PTT. To improve the accuracy and safety of PTT, we propose a multi-wavelength photoacoustic (PA) temperature feedback based PTT method and system. PA thermometry information at different wavelengths is mutually corrected, and the therapeutic light dose is regulated in real time to accurately control the treatment temperature. The experimental results on the swine blood sample confirm that the proposed method can realize real-time temperature measurement and control of the target area with an accuracy of 0.56 °C and 0.68 °C, demonstrating its good prospects for application.

Rapid Construction of Green Nanopesticide Delivery Systems Using Sophorolipids as Surfactants by Flash Nanoprecipitation.

Green delivery carriers of nanopesticides, like sophorolipid biosurfactants, are of great significance to reduce environmental pollution and promote sustainable agricultural development. However, the molecular diversity of an unisolated sophorolipid mixture with almost unpredictable self-assembly properties has limited the in-depth study of its structure-activity relationship and hindered the development of green pesticide delivery systems. In this work, the acidic and lactonic sophorolipids were successfully separated from the sophorolipid mixture through silica gel column chromatography. A series of cost-effective green nanopesticides loaded with lambda-cyhalothrin (LC) were rapidly fabricated based on a combination of the acidic and lactonic sophorolipids as surfactants by flash nanoprecipitation. The effects of the acidic-to-lactonic ratio on particle size, drug loading capacity, and biological activity against Hyphantria cunea of LC-loaded nanoparticles were systematically investigated. The resultant nanopesticides exhibited a better insecticidal efficacy than a commercial emulsifiable concentrate formulation. This work opens up a novel strategy to construct scalable, cost-effective, and environmentally friendly nanopesticide systems.

IL-33 induces thymic involution-associated naive T cell aging and impairs host control of severe infection.

Severe infection commonly results in immunosuppression, which leads to impaired pathogen clearance or increased secondary infection in both humans and animals. However, the exact mechanisms remain poorly understood. Here, we demonstrate that IL-33 results in immunosuppression by inducing thymic involution-associated naive T cell dysfunction with aberrant expression of aging-associated genes and impairs host control of infection in mouse disease models of schistosomiasis or sepsis. Furthermore, we illustrate that IL-33 triggers the excessive generation of medullary thymic epithelial cell (mTEC) IV (thymic tuft cells) in a Pou2f3-dependent manner, as a consequence, disturbs mTEC/cortical TEC (cTEC) compartment and causes thymic involution during severe infection. More importantly, IL-33 deficiency, the anti-IL-33 neutralizing antibody treatment, or IL-33 receptor ST2 deficient thymus transplantation rescues T cell immunity to better control infection in mice. Our findings not only uncover a link between severe infection-induced IL-33 and thymic involution-mediated naive T cell aging, but also suggest that targeting IL-33 or ST2 is a promising strategy to rejuvenate T cell immunity to better control severe infection.

Optimization of internals for Selective Catalytic Reduction (SCR) for NO removal.

This work tried to identify the relationship between the internals of selective catalytic reduction (SCR) system and mixing performance for controlling ammonia (NH(3)) slip. In the SCR flow section, arranging the flow-guided internals can improve the uniformity of velocity distribution but is unfavorable for the uniformity of NH(3) concentration distribution. The ammonia injection grids (AIG) with four kinds of nozzle diameters (i.e., 1.0 mm, 1.5 mm, 2.0 mm, and mixed diameters) were investigated, and it was found that the AIG with mixed nozzle diameters in which A3, A4, B3, and B4 nozzles' diameters are 1.0 mm and other nozzles' diameters are 1.5 mm is the most favorable for the uniformity of NH(3) concentration distribution. In the SCR reactor section, the appropriate space length between two catalyst layers, which serves as gas mixing in order to prevent maldistribution of gas concentrations into the second catalyst layer, under the investigated conditions is about 100, 1000, and 12 mm for honeycomb-like cordierite catalyst, plate-type catalysts with parallel channel arrangement, and with cross channel arrangement, respectively. Therefore, the cross channel arrangement is superior to the parallel channel arrangement in saving the SCR reactor volume.

Increased GAD expression in the striatum after transient cerebral ischemia.

Striatum is one of the brain regions that are highly sensitive to transient cerebral ischemia. Most of the striatal neurons die shortly after ischemia but interneurons including large aspiny (LA) neurons survive the same insult. Previous studies have shown that inhibitory synaptic transmission is enhanced in LA neurons after ischemia. The present study is aimed at revealing the mechanisms underlying this phenomenon. Immunohistochemical studies and Western blotting were performed to examine the expression of glutamic decarboxylase (GAD), the key enzyme in the synthesis of GABA, in the striatum. GAD65 expression and the number of GAD67-positive cells were increased after ischemia. GAD67-positive cells in the striatum co-expressed GAD65 after ischemia. The increase of GAD67-positive cells did not result from neurogenesis. Double-labeling of GAD67 and SOM indicates that some of the GAD67-positive cells are from the phenotypic shift of pre-existing somatostatin (SOM)-containing GABAergic interneurons after ischemia. Facilitation of inhibitory synaptic transmission by muscimol, a specific GABA(A) receptor agonist, increased the number of survived cells in the striatum after ischemia. Altogether, these data suggest that GAD expression is increased in the striatum after ischemia, which might contribute to the facilitated inhibitory synaptic transmission and the consequent survival of LA neurons.

Highly efficient capture of odorous sulfur-based VOCs by ionic liquids.

This study proposes the capture of dimethyl sulfide (DMS) and dimethyl disulfide (DMDS) from waste gas using an ionic liquid (IL), namely, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM][Tf2N]), and examines the process from a molecular level to the laboratory scale, which is then scaled up to the industrial level. The binding energy and weak interactions between DMS/DMDS and the anion/cation in [EMIM][Tf2N] were investigated using quantum chemistry calculations to identify the capture mechanism at the molecular scale. A thermodynamic model (UNIFAC-Lei) was established by the vapor-liquid equilibrium data of the [EMIM][Tf2N] + DMS/DMDS systems measured at the laboratory scale. The equilibrium and continuous absorption experiments were performed, and the results demonstrated that [EMIM][Tf2N] exhibits a highly efficient capture performance at atmospheric conditions, particularly, absorption capacities (AC) for DMS and DMDS are 189.72 and 212.94 mg g-1, respectively, and partial coefficients (PC) as more reasonable evaluation metrics for those are 0.509 × 10-4 and 6.977 × 10-4 mol kg-1 Pa-1, respectively, at the 100 % breakthrough. Finally, a mathematical model of the strict equilibrium stage was established for process simulations, and the absorption process was conceptually designed at the industrial scale, which could provide a decision-making basis for chemical engineers and designers.

BACH2 inhibition reverses ß cell failure in type 2 diabetes models.

Type 2 diabetes (T2D) is associated with defective insulin secretion and reduced ß cell mass. Available treatments provide a temporary reprieve, but secondary failure rates are high, making insulin supplementation necessary. Reversibility of ß cell failure is a key translational question. Here, we reverse engineered and interrogated pancreatic islet-specific regulatory networks to discover T2D-specific subpopulations characterized by metabolic inflexibility and endocrine progenitor/stem cell features. Single-cell gain- and loss-of-function and glucose-induced Ca2+ flux analyses of top candidate master regulatory (MR) proteins in islet cells validated transcription factor BACH2 and associated epigenetic effectors as key drivers of T2D cell states. BACH2 knockout in T2D islets reversed cellular features of the disease, restoring a nondiabetic phenotype. BACH2-immunoreactive islet cells increased approximately 4-fold in diabetic patients, confirming the algorithmic prediction of clinically relevant subpopulations. Treatment with a BACH inhibitor lowered glycemia and increased plasma insulin levels in diabetic mice, and restored insulin secretion in diabetic mice and human islets. The findings suggest that T2D-specific populations of failing ß cells can be reversed and indicate pathways for pharmacological intervention, including via BACH2 inhibition.