Dynamic Kinetic Resolution of ß-Substituted α-Diketones via Asymmetric Transfer Hydrogenation.

Developing innovative dynamic kinetic resolution (DKR) modes and achieving the highly regio- and enantioselective semihydrogenation of unsymmetrical α-diketones are two formidable challenges in the field of contemporary asymmetric (transfer) hydrogenation. In this work, we report the highly regio- and stereoselective asymmetric semi-transfer hydrogenation of unsymmetrical α-diketones through a unique DKR mode, which features the reduction of the carbonyl group distal from the labile stereocenter, while the proximal carbonyl remains untouched. Moreover, the protocol affords a variety of enantioenriched acyclic ketones with α-hydroxy-α'-C(sp2)-functional groups, which represent a new product class that has not been furnished in known arts. The utilities of the products have been demonstrated in a series of further transformations including the rapid synthesis of drug molecules. Density functional theory calculations and plenty of control experiments have also been conducted to gain more mechanistic insights into the highly selective semihydrogenation.

Converting Nafion into Li+ -Conductive Nanoporous Materials.

Sulfonated polymers have long been used as proton-conducting materials in fuel cells, and their ionic transport features are highly attractive for electrolytes in lithium-ion/metal batteries (LIBs/LMBs). However, most studies are still based on a preconceived notion of using them directly as polymeric ionic carriers, which precludes exploring them as nanoporous media to construct efficient lithium ions (Li+ ) transport network. Here, effective Li+ -conducting channels realized by swelling nanofibrous Nafion is demonstrated, which is a classical sulfonated polymer in fuel cells. The sulfonic acid groups, interact with LIBs liquid electrolytes to form porous ionic matrix of Nafion and assist partial desolvation of Li+ -solvates to further enhance Li+ transport. Li-symmetric cells and Li-metal full cells (Li4 Ti5 O12 or high-voltage LiNi0.6 Co0.2 Mn0.2 O2 as a cathode) with such membrane show excellent cycling performance and stabilized Li-metal anode. The finding provides a strategy to convert the vast sulfonated polymer family into efficient Li+ electrolyte, promoting the development of high-energy-density LMBs.

NR1H4-mediated circRHOBTB3 modulates the proliferation, metastasis, and Warburg effects of cervical cancer through interacting with IGF2BP3.

Globally, cervical cancer (CC) ranks as the fourth most common cancer and the most lethal malignancy among females of reproductive age. The incidence of CC is increasing in low-income countries, with unsatisfactory outcomes and long-term survival for CC patients. Circular RNAs (CircRNAs) are promising therapeutics that target multiple cancers. In this study, we investigated the tumorigenic role of circRHOBTB3 in CC, showing that circRHOBTB3 is highly expressed in CC cells and circRHOBTB3 knockdown also repressed CC proliferation, migration, invasion, and the Warburg effects. CircRHOBTB3 interacted with the RNA-binding protein, IGF2BP3, to stabilize its expression in CC cells and is putatively transcriptionally regulated by NR1H4. In conclusion, this novel NR1H4/circRHOBTB3/IGF2BP3 axis may provide new insights into CC pathogenesis.

The metabolic score for insulin resistance as a predictor of clinical outcome in stroke patients treated by intravenous thrombolysis.

BACKGROUND AND PURPOSE: Insulin resistance is associated with clinical outcomes among patients with ischemic stroke. We aimed to investigate the association between metabolic score for insulin resistance (METS-IR) and clinical outcomes in stroke patients treated by intravenous thrombolysis (IVT). METHODS: We recruited participants treated with IVT from a prospective registry including 3 stroke centers. Poor outcome was defined as a modified Rankin scale score ≥ 3 points at 90 days after the index stroke. We performed logistic regression models to investigate the association between METS-IR and the risk of poor outcome. We used the receiver operative characteristic to assess the discriminative ability and the restricted cubic spline to explore the relationship between METS-IR and the poor outcome. RESULTS: This study enrolled a total of 1074 patients (median age, 68; 63.8% male). Three hundred sixty (33.5%) patients had poor outcome after IVT. METS-IR was associated with the risk of the poor outcome with the increase of confounding factors in models (odds ratio [OR], 1.078; 95% confidence interval [CI], 1.058-1.099; P < 0.001). The area under the curve for METS-IR for predicting the poor outcome was 0.790 (95% CI, 0.761-0.819). The restricted cubic spline revealed an increasing and non-linear association between METS-IR and the poor outcome (P for non-linearity < 0.001). CONCLUSION: Our study found that METS-IR was associated with an increased risk of poor outcome after IVT. Further studies are warranted to investigate the efficacy of anti-diabetic agents regarding IR on clinical outcomes after IVT.

Effect of platelet-rich plasma vs standard management for the treatment of diabetic foot ulcer wounds: A meta-analysis.

We performed a meta-analysis to evaluate the effect of platelet-rich plasma vs standard management for the treatment of diabetic foot ulcer wounds. A systematic literature search up to March 2022 was performed and 1435 subjects with diabetic foot ulcer wounds at the baseline of the studies; 723 of them were treated with platelet-rich plasma, and 712 used control. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated to assess the effect of platelet-rich plasma vs standard management for the treatment of diabetic foot ulcer wounds using the dichotomous method with a random or fixed-effect model. The use of autologous platelet-rich plasma resulted in significantly higher complete-healed diabetic foot ulcer wounds compared with control (OR, 1.95; 95% CI, 1.49-2.56, P < 0.001). The use of allogeneic platelet-rich plasma resulted in significantly higher complete-healed diabetic foot ulcer wounds compared with control (OR, 6.19; 95% CI, 2.32-16.56, P < 0.001). The use of autologous and allogeneic platelet-rich plasma resulted in significantly higher complete-healed diabetic foot ulcer wounds compared with control. Though, the analysis of outcomes should be with caution because of the low number of studies in certain comparisons, for example, allogeneic platelet-rich plasma compared with control.

Adenosine A3 Receptor Mediates ERK1/2- and JNK-Dependent TNF-α Production in Toxoplasma gondii-Infected HTR8/SVneo Human Extravillous Trophoblast Cells.

Toxoplasma gondii is an intracellular parasite that causes severe disease when the infection occurs during pregnancy. Adenosine is a purine nucleoside involved in numerous physiological processes; however, the role of adenosine receptors in T. gondii-induced trophoblast cell function has not been investigated until now. The goal of the present study was to evaluate the intracellular signaling pathways regulated by adenosine receptors using a HTR-8/SVneo trophoblast cell model of T. gondii infection. HTR8/SVneo human extravillous trophoblast cells were infected with or without T. gondii and then evaluated for cell morphology, intracellular proliferation of the parasite, adenosine receptor expression, TNF-α production and mitogen-activated protein (MAP) kinase signaling pathways triggered by adenosine A3 receptor (A3AR). HTR8/SVneo cells infected with T. gondii exhibited an altered cytoskeletal changes, an increased infection rate and reduced viability in an infection time-dependent manner. T. gondii significantly promoted increased TNF-α production, A3AR protein levels and p38, ERK1/2 and JNK phosphorylation compared to those observed in uninfected control cells. Moreover, the inhibition of A3AR by A3AR siRNA transfection apparently suppressed the T. gondii infection-mediated upregulation of TNF-α, A3AR production and MAPK activation. In addition, T. gondii-promoted TNF-α secretion was dramatically attenuated by pretreatment with PD098059 or SP600125. These results indicate that A3AR-mediated activation of ERK1/2 and JNK positively regulates TNF-α secretion in T. gondii-infected HTR8/SVneo cells.

On building a diabetes centric knowledge base via mining the web.

BACKGROUND: Diabetes has become one of the hot topics in life science researches. To support the analytical procedures, researchers and analysts expend a mass of labor cost to collect experimental data, which is also error-prone. To reduce the cost and to ensure the data quality, there is a growing trend of extracting clinical events in form of knowledge from electronic medical records (EMRs). To do so, we first need a high-coverage knowledge base (KB) of a specific disease to support the above extraction tasks called KB-based Extraction. METHODS: We propose an approach to build a diabetes-centric knowledge base (a.k.a. DKB) via mining the Web. In particular, we first extract knowledge from semi-structured contents of vertical portals, fuse individual knowledge from each site, and further map them to a unified KB. The target DKB is then extracted from the overall KB based on a distance-based Expectation-Maximization (EM) algorithm. RESULTS: During the experiments, we selected eight popular vertical portals in China as data sources to construct DKB. There are 7703 instances and 96,041 edges in the final diabetes KB covering diseases, symptoms, western medicines, traditional Chinese medicines, examinations, departments, and body structures. The accuracy of DKB is 95.91%. Besides the quality assessment of extracted knowledge from vertical portals, we also carried out detailed experiments for evaluating the knowledge fusion performance as well as the convergence of the distance-based EM algorithm with positive results. CONCLUSIONS: In this paper, we introduced an approach to constructing DKB. A knowledge extraction and fusion pipeline was first used to extract semi-structured data from vertical portals and individual KBs were further fused into a unified knowledge base. After that, we develop a distance based Expectation Maximization algorithm to extract a subset from the overall knowledge base forming the target DKB. Experiments showed that the data in DKB are rich and of high-quality.

Room-Temperature Single-Photon Detector Based on Single Nanowire.

Single-photon detectors that can resolve photon number play a key role in advanced quantum information technologies. Despite significant progress in improving conventional photon-counting detectors and developing novel device concepts, single-photon detectors that are capable of distinguishing incident photon number at room temperature are still very limited. We demonstrate a room-temperature photon-number-resolving detector by integrating a field-effect transistor configuration with core/shell-like nanowires. The shell serves as a photosensitive gate, shielding negative back-gated voltage, and leads to a persistent photocurrent. At room temperature, our detector is demonstrated to identify 1, 2, and 3 photon-number states with a confidence of >82%. The detection efficiency is determined to be 23%, and the dark count rate is 1.87 × 10-3 Hz. Importantly, benefiting from the anisotropic nature of 1D nanowires, the detector shows an intrinsic photon-polarization selection, which distinguishes itself from existing intensity single-photon detectors. The unique performance for the single-photon detectors based on single nanowire demonstrates the great potential for future single-photon detection applications.

A Colloidal-Quantum-Dot Infrared Photodiode with High Photoconductive Gain.

The photodiode is a prevailing architecture for photodetection with the merits of fast response and low dark current. However, an ideal photodiode is also desired for both high responsivity and high external quantum efficiency (EQE), which may facilitate more applications. Here the photoconducting effect in a photodiode is discussed and an Au-PbS colloidal quantum dot (CQD)-indium tin oxide Schottky junction photodiode is fabricated. The long carrier lifetime and improved carrier mobility in tetrabutylammonium iodide-modified PbS CQDs cooperating with the proper band structure and an ultrashort channel in the diode enable the photodiode with high photoconductive gain, realizing an EQE of ≈400% and a responsivity (R) of 5.15 A W-1 while simultaneously achieving a response time of 110 µs and a specific detectivity of 1.96 × 1010 Jones under 1550 nm illumination. In addition, this CQD-based photodiode is stable, low cost, and compatible with complementary metal oxide semiconductor technology. All of these promise this device great potential in applications.

Analysis of the influence and mechanism of sulfur passivation on the dark current of a single GaAs nanowire photodetector.

Nanowire photodetectors, which have the advantages of fast response and high photoelectric conversion efficiency, can be widely applied in various industries. However, the rich surface states result in large dark current and can hinder the development of high-performance nanowire photodetectors. In this paper, the influence and mechanism of sulfur surface passivation on the dark current of a single GaAs nanowire photodetector have been studied. The dark current is significantly reduced by about 30 times after surface passivation. We confirm that the origin of the reduction of dark current is the decrease in the surface state density. As a result, a single GaAs nanowire photodetector with low dark current of 7.18 × 10-2 pA and high detectivity of 9.04 × 1012 cmHz0.5W-1 has been achieved. A simple and convenient way to realize high-performance GaAs-based photodetectors has been proposed.

The ambipolar evolution of a high-performance WSe2 transistor assisted by a ferroelectric polymer.

In recent years, the electrical characteristics of WSe2 field-effect transistors (FETs) have been widely investigated with various dielectrics. Among them, being able to perfectly tune the polarity of WSe2 is meaningful and promising work. In this work, we systematically study the electrical properties of bilayer WSe2 FETs modulated by ferroelectric polymer poly(vinylidenefluoride-co-trifluoroethylene) (P(VDF-TrFE)). Compared to traditional gate dielectric SiO2, the P(VDF-TrFE) can not only tune both electron and hole concentrations to the same high level, but also improve the hole mobility of bilayer WSe2 to 265.96 cm2 V-1 s-1 under SiO2 gating. Its drain current on/off ratio is also improved to 2 × 105 for p-type and 4 × 105 for n-type driven by P(VDF-TrFE). More importantly, the ambipolar behaviors of bilayer WSe2 are effectively achieved and maintained because of the remnant polarization field of P(VDF-TrFE). This work indicates that WSe2 FETs with P(VDF-TrFE) gating have huge potential for complementary logic transistor applications, and paves an effective way to achieve in-plane p-n junctions.

Visible to near-infrared photodetectors based on MoS2 vertical Schottky junctions.

Over the past few years, two-dimensional (2D) nanomaterials, such as MoS2, have been widely considered as the promising channel materials for next-generation high-performance phototransistors. However, their device performances still mostly suffer from slow photoresponse (e.g. with the time constant in the order of milliseconds) due to the relatively long channel length and the substantial surface defect induced carrier trapping, as well as the insufficient detectivity owing to the relatively large dark current. In this work, a simple multilayer MoS2 based photodetector employing vertical Schottky junctions of Au-MoS2-ITO is demonstrated. This unique device structure can significantly suppress the dark current down to 10-12 A and enable the fast photoresponse of 64 µs, together with the stable responsivity of ∼1 A W-1 and the high photocurrent to dark current ratio of ∼106 at room temperature. This vertical-Schottky photodetector can also exhibit a wide detection range from visible to 1000 nm. All these results demonstrate clearly that the vertical Schottky structure is an effective configuration for achieving high-performance optoelectronic devices based on 2D materials.

When Nanowires Meet Ultrahigh Ferroelectric Field-High-Performance Full-Depleted Nanowire Photodetectors.

One-dimensional semiconductor nanowires (NWs) have been widely applied in photodetector due to their excellent optoelectronic characteristics. However, intrinsic carrier concentration at certain level results in appreciable dark current, which limits the detectivity of the devices. Here, we fabricated a novel type of ferroelectric-enhanced side-gated NW photodetectors. The intrinsic carriers in the NW channel can be fully depleted by the ultrahigh electrostatic field from polarization of P(VDF-TrFE) ferroelectric polymer. In this scenario, the dark current is significantly reduced and thus the sensitivity of the photodetector is increased even when the gate voltage is removed. Particularly, a single InP NW photodetector exhibits high-photoconductive gain of 4.2 × 10(5), responsivity of 2.8 × 10(5) A W(-1), and specific detectivity (D*) of 9.1 × 10(15) Jones at λ = 830 nm. To further demonstrate the universality of the configuration we also demonstrate ferroelectric polymer side-gated single CdS NW photodetectors with ultrahigh photoconductive gain of 1.2 × 10(7), responsivity of 5.2 × 10(6) A W(-1) and D* up to 1.7 × 10(18) Jones at λ = 520 nm. Overall, our work demonstrates a new approach to fabricate a controllable, full-depleted, and high-performance NW photodetector. This can inspire novel device structure design of high-performance optoelectronic devices based on semiconductor NWs.

Visible Light-Assisted High-Performance Mid-Infrared Photodetectors Based on Single InAs Nanowire.

One-dimensional InAs nanowires (NWs) have been widely researched in recent years. Features of high mobility and narrow bandgap reveal its great potential of optoelectronic applications. However, most reported work about InAs NW-based photodetectors is limited to the visible waveband. Although some work shows certain response for near-infrared light, the problems of large dark current and small light on/off ratio are unsolved, thus significantly restricting the detectivity. Here in this work, a novel "visible light-assisted dark-current suppressing method" is proposed for the first time to reduce the dark current and enhance the infrared photodetection of single InAs NW photodetectors. This method effectively increases the barrier height of the metal-semiconductor contact, thus significantly making the device a metal-semiconductor-metal (MSM) photodiode. These MSM photodiodes demonstrate broadband detection from less than 1 µm to more than 3 µm and a fast response of tens of microseconds. A high detectivity of ∼1012 Jones has been achieved for the wavelength of 2000 nm at a low bias voltage of 0.1 V with corresponding responsivity of as much as 40 A/W. Even for the incident wavelength of 3113 nm, a detectivity of ∼1010 Jones and a responsivity of 0.6 A/W have been obtained. Our work has achieved an extended detection waveband for single InAs NW photodetector from visible and near-infrared to mid-infrared. The excellent performance for infrared detection demonstrated the great potential of narrow bandgap NWs for future infrared optoelectronic applications.

Aurora kinase A activates the vacuolar H+-ATPase (V-ATPase) in kidney carcinoma cells.

Extracellular proton-secreting transport systems that contribute to extracellular pH include the vacuolar H(+)-ATPase (V-ATPase). This pump, which mediates ATP-driven transport of H(+) across membranes, is involved in metastasis. We previously showed (Alzamora R, Thali RF, Gong F, Smolak C, Li H, Baty CJ, Bertrand CA, Auchli Y, Brunisholz RA, Neumann D, Hallows KR, Pastor-Soler NM. J Biol Chem 285: 24676-24685, 2010) that V-ATPase A subunit phosphorylation at Ser-175 is important for PKA-induced V-ATPase activity at the membrane of kidney intercalated cells. However, Ser-175 is also located within a larger phosphorylation consensus sequence for Aurora kinases, which are known to phosphorylate proteins that contribute to the pathogenesis of metastatic carcinomas. We thus hypothesized that Aurora kinase A (AURKA), overexpressed in aggressive carcinomas, regulates the V-ATPase in human kidney carcinoma cells (Caki-2) via Ser-175 phosphorylation. We found that AURKA is abnormally expressed in Caki-2 cells, where it binds the V-ATPase A subunit in an AURKA phosphorylation-dependent manner. Treatment with the AURKA activator anacardic acid increased V-ATPase expression and activity at the plasma membrane of Caki-2 cells. In addition, AURKA phosphorylates the V-ATPase A subunit at Ser-175 in vitro and in Caki-2 cells. Immunolabeling revealed that anacardic acid induced marked membrane accumulation of the V-ATPase A subunit in transfected Caki-2 cells. However, anacardic acid failed to induce membrane accumulation of a phosphorylation-deficient Ser-175-to-Ala (S175A) A subunit mutant. Finally, S175A-expressing cells had decreased migration in a wound-healing assay compared with cells expressing wild-type or a phospho-mimetic Ser-175-to-Asp (S175D) mutant A subunit. We conclude that AURKA activates the V-ATPase in kidney carcinoma cells via phosphorylation of Ser-175 in the V-ATPase A subunit. This regulation contributes to kidney carcinoma V-ATPase-mediated extracellular acidification and cell migration.

Activation of the metabolic sensor AMP-activated protein kinase inhibits aquaporin-2 function in kidney principal cells.

Aquaporin-2 (AQP2) is essential to maintain body water homeostasis. AQP2 traffics from intracellular vesicles to the apical membrane of kidney collecting duct principal cells in response to vasopressin [arginine vasopressin (AVP)], a hormone released with low intravascular volume, which causes decreased kidney perfusion. Decreased kidney perfusion activates AMP-activated kinase (AMPK), a metabolic sensor that inhibits the activity of several transport proteins. We hypothesized that AMPK activation also inhibits AQP2 function. These putative AMPK effects could protect interstitial ionic gradients required for urinary concentration during metabolic stress when low intravascular volume induces AVP release. Here we found that short-term AMPK activation by treatment with 5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside (AICAR; 75 min) in kidney tissue prevented baseline AQP2 apical accumulation in principal cells, but did not prevent AQP2 apical accumulation in response to the AVP analog desmopressin (dDAVP). Prolonged AMPK activation prevented AQP2 cell membrane accumulation in response to forskolin in mouse collecting duct mpkCCDc14 cells. Moreover, AMPK inhibition accelerated hypotonic lysis of Xenopus oocytes expressing AQP2. We performed phosphorylation assays to elucidate the mechanism by which AMPK regulates AQP2. Although AMPK weakly phosphorylated immunoprecipitated AQP2 in vitro, no direct AMPK phosphorylation of the AQP2 COOH-terminus was detected by mass spectrometry. AMPK promoted Ser-261 phosphorylation and antagonized dDAVP-dependent phosphorylation of other AQP2 COOH-terminal sites in cells. Our findings suggest an increasing, time-dependent antagonism of AMPK on AQP2 regulation with AICAR-dependent inhibition of cAMP-dependent apical accumulation and AVP-dependent phosphorylation of AQP2. This inhibition likely occurs via a mechanism that does not involve direct AQP2 phosphorylation by AMPK.

Highly sensitive visible to infrared MoTe2 photodetectors enhanced by the photogating effect.

Two-dimensional materials are promising candidates for electronic and optoelectronic applications. MoTe2 has an appropriate bandgap for both visible and infrared light photodetection. Here we fabricate a high-performance photodetector based on few-layer MoTe2. Raman spectral properties have been studied for different thicknesses of MoTe2. The photodetector based on few-layer MoTe2 exhibits broad spectral range photodetection (0.6-1.55 µm) and a stable and fast photoresponse. The detectivity is calculated to be 3.1 × 10(9) cm Hz(1/2) W(-1) for 637 nm light and 1.3 × 10(9) cm Hz(1/2) W(-1) for 1060 nm light at a backgate voltage of 10 V. The mechanisms of photocurrent generation have been analyzed in detail, and it is considered that a photogating effect plays an important role in photodetection. The appreciable performance and detection over a broad spectral range make it a promising material for high-performance photodetectors.

Cytotoxicity and apoptosis induced by silver nanoparticles in human liver HepG2 cells in different dispersion media.

Silver nanoparticles (Ag NPs) have been widely used in medical and healthcare products owing to their unique antibacterial activities. However, their safety for humans and the environment has not yet been established. This study evaluated the cellular proliferation and apoptosis of Ag NPs suspended in different solvents using human liver HepG2 cells. The ionization of Ag NPs in different dispersion media [deionized water, phosphate-buffered saline (PBS), saline and cell culture] was measured using an Ag ion selective electrode. The MTT assay was used to examine the cell proliferation activities. The effects of Ag NPs on cell cycle, induction of apoptosis, production of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were analyzed using flow cytometry. The degree of Ag NPs ionization differed with dispersion media, with the concentrations of silver ions in deionized water being the highest in all suspensions. Ag NPs could inhibit the viability of HepG2 cells in a time- and concentration-dependent manner. Ag NPs (40, 80 and 160 µg ml(-1)) exposure could cause cell-cycle arrest in the G2/M phase, significantly increasing the apoptosis rate and ROS generation, and decreasing the MMP in HepG2 cells more sensitive to deionized water than in cell culture. These results suggested that the cellular toxicological mechanism of Ag NPs might be related to the oxidative stress of cells by the generation of ROS, leading to mitochondria injury and induction of apoptosis. It also implies that it is important to assess the physicochemical properties of NPs in the media where the biological toxicity tests are performed.

Leaf-induced gibberellin signaling is essential for internode elongation, cambial activity, and fiber differentiation in tobacco stems.

The gibberellins (GAs) are a group of endogenous compounds that promote the growth of most plant organs, including stem internodes. We show that in tobacco (Nicotiana tabacum) the presence of leaves is essential for the accumulation of bioactive GAs and their immediate precursors in the stem and consequently for normal stem elongation, cambial proliferation, and xylem fiber differentiation. These processes do not occur in the absence of maturing leaves but can be restored by application of C(19)-GAs, identifying the presence of leaves as a requirement for GA signaling in stems and revealing the fundamental role of GAs in secondary growth regulation. The use of reporter genes for GA activity and GA-directed DELLA protein degradation in Arabidopsis thaliana confirms the presence of a mobile signal from leaves to the stem that induces GA signaling.

Regulation of proximal tubule vacuolar H(+)-ATPase by PKA and AMP-activated protein kinase.

The vacuolar H(+)-ATPase (V-ATPase) mediates ATP-driven H(+) transport across membranes. This pump is present at the apical membrane of kidney proximal tubule cells and intercalated cells. Defects in the V-ATPase and in proximal tubule function can cause renal tubular acidosis. We examined the role of protein kinase A (PKA) and AMP-activated protein kinase (AMPK) in the regulation of the V-ATPase in the proximal tubule as these two kinases coregulate the V-ATPase in the collecting duct. As the proximal tubule V-ATPases have different subunit compositions from other nephron segments, we postulated that V-ATPase regulation in the proximal tubule could differ from other kidney tubule segments. Immunofluorescence labeling of rat ex vivo kidney slices revealed that the V-ATPase was present in the proximal tubule both at the apical pole, colocalizing with the brush-border marker wheat germ agglutinin, and in the cytosol when slices were incubated in buffer alone. When slices were incubated with a cAMP analog and a phosphodiesterase inhibitor, the V-ATPase accumulated at the apical pole of S3 segment cells. These PKA activators also increased V-ATPase apical membrane expression as well as the rate of V-ATPase-dependent extracellular acidification in S3 cell monolayers relative to untreated cells. However, the AMPK activator AICAR decreased PKA-induced V-ATPase apical accumulation in proximal tubules of kidney slices and decreased V-ATPase activity in S3 cell monolayers. Our results suggest that in proximal tubule the V-ATPase subcellular localization and activity are acutely coregulated via PKA downstream of hormonal signals and via AMPK downstream of metabolic stress.