A2AR antagonists triggered the AMPK/m-TOR autophagic pathway to reverse the calcium-dependent cell damage in 6-OHDA induced model of PD.

Calcium dyshomeostasis, oxidative stress, autophagy and apoptosis are the pathogenesis of selective dopaminergic neuronal loss in Parkinson's disease (PD). Earlier, we reported that A2A R modulates IP3-dependent intracellular Ca2+ signalling via PKA. Moreover, A2A R antagonist has been reported to reduce oxidative stress and apoptosis in PD models, however intracellular Ca2+ ([Ca2+]i) dependent autophagy regulation in the 6-OHDA model of PD has not been explored. In the present study, we investigated the A2A R antagonists mediated neuroprotective effects in 6-OHDA-induced primary midbrain neuronal (PMN) cells and unilateral lesioned rat model of PD. 6-OHDA-induced oxidative stress (ROS and superoxide) and [Ca2+]i was measured using Fluo4AM, DCFDA and DHE dye respectively. Furthermore, autophagy was assessed by Western blot of p-m-TOR/mTOR, p-AMPK/AMPK, LC3I/II, Beclin and ß-actin. Apoptosis was measured by Annexin V-APC-PI detection and Western blot of Bcl2, Bax, caspase3 and ß-actin. Dopamine levels were measured by Dopamine ELISA kit and Western blot of tyrosine hydroxylase. Our results suggest that 6-OHDA-induced PMN cell death occurred due to the interruption of [Ca2+]i homeostasis, accompanied by activation of autophagy and apoptosis. A2A R antagonists prevented 6-OHDA-induced neuronal cell death by decreasing [Ca2+]i overload and oxidative stress. In addition, we found that A2A R antagonists upregulated mTOR phosphorylation and downregulated AMPK phosphorylation thereby reducing autophagy and apoptosis both in 6-OHDA induced PMN cells and 6-OHDA unilateral lesioned rat model. In conclusion, A2A R antagonists alleviated 6-OHDA toxicity by modulating [Ca2+]i signalling to inhibit autophagy mediated by the AMPK/mTOR pathway.

Association between alcohol-associated cirrhosis and inpatient complications among COVID-19 patients: A propensity-matched analysis from the United States.

BACKGROUND: Alcohol-associated cirrhosis (AC) contributes to significant liver-related mortality in the United States. It is known to cause immune dysfunction and coagulation abnormalities. Patients with comorbid conditions like AC are at risk of worse clinical outcomes from coronavirus disease 2019 (COVID-19). The specific association between AC and COVID-19 mortality remains inconclusive, given the lack of robust clinical evidence from prior studies. AIM: To study the predictors of mortality and the outcomes of AC in patients hospitalized with COVID-19 in the United States. METHODS: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) database 2020. Patients were identified with primary COVID-19 hospitalizations based on an underlying diagnosis of AC. A matched comparison cohort of COVID-19 patients without AC was identified after 1:N propensity score matching based on baseline sociodemographic characteristics and Elixhauser comorbidities. Primary outcomes included median length of stay, median inpatient charges, and in-hospital mortality. Secondary outcomes included a prevalence of systemic complications. RESULTS: A total of 1325 COVID-19 patients with AC were matched to 1135 patients without AC. There was no difference in median length of stay and hospital charges in COVID-19 patients with AC compared to non-AC (P > 0.05). There was an increased prevalence of septic shock (5.7% vs 4.1%), ventricular fibrillation/ventricular flutter (0.4% vs 0%), atrial fibrillation (13.2% vs 8.8%), atrial flutter (8.7% vs 4.4%), first-degree atrioventricular nodal block (0.8% vs 0%), upper extremity venous thromboembolism (1.5% vs 0%), and variceal bleeding (3.8% vs 0%) in the AC cohort compared to the non-AC cohort (P < 0.05). There was no difference in inpatient mortality in COVID-19 patients with non-AC compared to AC, with an odds ratio of 0.97 (95% confidence interval: 0.78-1.22, P = 0.85). Predictors of mortality included advanced age, cardiac arrhythmias, coagulopathy, protein-calorie malnutrition, fluid and electrolyte disorders, septic shock, and upper extremity venous thromboembolism. CONCLUSION: AC does not increase mortality in patients hospitalized with COVID-19. There is an increased association between inpatient complications among COVID-19 patients with AC compared to non-AC.

The Role of Automation for Early Diagnosis of Non-fermenter Superbugs in Critically Ill Septicemic Hospitalized Patients.

Introduction Non-fermenting Gram-negative bacilli (NFGNB) are emerging superbugs of bloodstream infections (BSI), causing increased mortality in hospitalized patients. NFGNB are challenging to identify using conventional identification techniques. Hence, automation is beneficial for accurate and fast diagnosis; it also facilitates rapid treatment and recovery of patients. This study aims to isolate/identify NFGNB from BSI and determine its antimicrobial susceptibility pattern. Material and methods This study was conducted in the Department of Microbiology, LLRMMC, Meerut, for a period of six months (June to November 2022). The samples were processed using automated blood culture (BD BACTEC) and an identification/sensitivity testing system (BD Phoenix). Results Out of 1340 blood cultures, 347 (25.7%) were flagged positive for microbial growth. A total of 103 (7.6%) NFGNB were isolated, showing their strong association with BSI. The NFGNB isolates were Pseudomonas species 23 (22.3%), Acinetobacter baumannii 19 (18.4%), Salmonella spp. 19 (18.4%), Sphingomonas paucimobilis 17 (16.5%), Aeromonas hydrophila 5 (4.8%), Rhizobium radiobacter sp. 4 (3.8%), Stenotrophomonas maltophila 3 (2.9%), Burkholderia cepacian 3 (2.9%), Proteus mirabilis 2 (1.9%), Achromobacter xylosoxidans 2 (1.9%), Elizabethkingia meningoseptica 2 (1.9%), Ochromobacter anthropic 2 (1.9%), Cuprivadus pauculus 1 (0.9%), and Ralstonia mannitolilytica 1 (0.9%). Conclusions Automation helps in the prompt reporting of NFGNB and their antibiogram pattern by microbiology laboratories, facilitating the early and accurate management of patients with BSI.

Measuring circularity of a manufacturing organization by using sustainable balanced scorecard.

In recent years, circular economy has become a matter of great importance because of its ability to contribute toward economic, environmental, and social aspects of the sustainability. The circular economy approaches help in resource conservation by reducing, reusing, and recycling products/parts/components/materials. On the other hand, Industry 4.0 is coupled with emerging technologies, which support the firms in efficient resource utilization. These innovative technologies can transform the present manufacturing organizations by reducing resource extraction, CO2 emissions, environmental damage, and power consumption and improve it into a more sustainable manufacturing organization. Industry 4.0 along with circular economy concepts greatly improves the circularity performance. However, there is no framework found for measuring the circularity performance of the firm. Therefore, the current study aims to develop a framework for measuring performance in terms of circularity percentage. In this work, graph theory and matrix approach are employed for measuring the performance based on a sustainable balanced scorecard such as internal process, learning and growth, customer and financial with environmental and social perspectives. A case of an Indian barrel manufacturing organization is discussed for the illustration of proposed methodology. Based on "circularity index" of the organization and the maximum possible circularity index, the circularity was found to be 5.10%. It indicates that there is a huge potential for the improvement in the circularity of the organization. An in-depth sensitivity analysis and comparison are also performed to validate the findings. There are very few studies on measuring the circularity. The study developed the approach for measuring circularity, which may be utilized by industrialists and practitioners for improving the circularity.

Survival analysis of extrahepatic cholangiocarcinoma based on surveillance, epidemiology, and end results database.

Backgrounds/Aims: Cholangiocarcinoma (CCA) can be classified as intrahepatic CCA or extrahepatic CCA (eCCA). We intended to analyze and reports the survival outcomes for eCCA. Methods: Surveillance, epidemiology, and end results (SEER) registry, site recode C24.0, was used to select cases of eCCA from 2000 to 2018. Patients with incomplete data or ages <18 years were excluded. Results: Male (52.69%) and White race (77.99%) predominated. Compared with 2000-2006, survival increased in 2013 (adjusted hazard ratio [HRadj]: 0.68, 95% confidence interval [CI] 0.58-0.70; p < 0.01). Surgery with chemoradiotherapy (HRadj: 0.69, 95% CI 0.60-0.7; p < 0.01) and surgery with chemotherapy (HRadj: 0.72, 95% CI 0.62-0.83; p < 0.01) improved survival over surgery alone. Compared with surgery without lymph node (LN) removal, surgery of four or more regional LN reduced the risk of death by 58% (HRadj: 0.42, 95% CI 0.36-0.51; p < 0.01). Compared with patients without surgery, patients who underwent bile duct excision (HRadj: 0.82, 95% CI 0.72-0.94; p < 0.01), simple or extended lobectomy (HRadj: 0.85, 95% CI 0.75-0.95; p = 0.009), and hepatectomy (HRadj: 0.80, 95% CI 0.72-0.88; p < 0.01) significantly improved survival. Patients with distal CCA had a 17% higher survival than perihilar CCA (HRadj: 0.83, 95% CI 0.74-0.92; p < 0.01) and LN dissection was equally beneficial for both subgroups (p < 0.01). Conclusions: Surgery with chemoradiotherapy has a proven increase in the 5-year survival of the eCCA. LN resection, bile duct excision, lobectomy, and hepatectomy have better outcomes.

Design and synthesis of benzo[d]thiazol-2-yl-methyl-4-(substituted)-piperazine-1-carbothioamide as novel neuronal nitric oxide inhibitors and evaluation of their neuroprotecting effect in 6-OHDA-induced unilateral lesioned rat model of Parkinson's disease.

Neuronal nitric oxide synthase (nNOS) is an enzyme constitutively expressed in the mammalian brain and skeletal muscles. The excessive activation of nNOS in the neurons results in oxidative and nitrosative stress associated with neuronal loss in various neurological disorders. Several nNOS inhibitors have been reported to limit the excessive activation of nNOS. In the present work, we have designed and carried the synthesis of benzo[d]thiazol-2-yl-methyl-4-(substituted)-piperazine-1-carbothioamide as novel neuronal nitric oxide inhibitors (5-28, twenty-four compounds). Stably transfected HEK 293 cells expressing NOS isoforms treated with the compounds (5-28) showed that the eight compounds exhibited > 95% cell survival in the MTT assay. nNOS inhibition assay of the eight compounds illustrated that the compound 18 was most selective for nNOS (nNOS=66.73 ± 1.51; eNOS=28.70 ± 1.39; iNOS =13.26 ± 1.01) in HEK 293 cells expressing NOS isoforms. 6-OHDA-induced unilaterally lesioned rats treated with the compound 18 showed the improvement in motor and non-motor functions. Furthermore, the compound 18 showed the increased levels of dopamine and decreased levels of glutamate and nitrite ions in the isolated rat brain. In the docking analysis, the compound 18 showed the significant binding affinity with the nNOS binding site (the ∆G value = - 9.0 kcal/mol). Overall results demonstrated that the N-(benzo[d]thiazol-2-ylmethyl)-4-(4-nitrophenyl) piperazine-1-carbothioamide (the compound 18) possessed significant nNOS inhibiting activity and neuroprotecting potential in 6-OHDA-induced unilaterally lesioned rat model of PD and more work will be required to establish the role of the compound 18 in the therapy of PD and other neurodegenerative disorders.

Spectrum of signs, symptoms, and treatment in amphotericin B-resistant Trichosporon endophthalmitis: A series of ten cases of post-cataract surgery cluster endophthalmitis.

Purpose: The aim of this study was to present the signs, symptoms, management, and outcome of a series of cases of cluster endophthalmitis caused by a multi-drug resistant fungus, Trichosporon. Methods: This was a retrospective, non-randomized, consecutive interventional case series. Ten cases of postoperative endophthalmitis operated by a surgeon on three consecutive operation theater (OT) days presented 3-5 months after their surgery. All cases were microbiologically confirmed. The pathogen was found to be resistant to most antifungals, including amphotericin B. The cases had a latent period of around 45 days. Management of endophthalmitis included intravitreal injections, anterior chamber (AC) lavage, Pars Plana vitrectomy (PPV), posterior capsulotomy, IOL, and capsular bag removal. Multiple intravitreal injections were required due to recurrence of infections after initial improvement with voriconazole injections. Results: Structural integrity was maintained and infection-free status was achieved in all the eyes. The presenting vision ranged from 6/60 to PL (perception of light). Seven out of 10 had improvement in their final vision over the presenting vision. Final outcome of four patients had vision of 6/24 or better, 4 patients had vision in the range of 2/60 to 6/36 and 2 patients had PL. Conclusion: Trichosporon can cause devasting infections even in the immunocompetent, especially in association with implants and catheters. Triazoles form the mainstay of treatment of Trichosporon infection due to the high susceptibility of the organism in vitro. A regimen including voriconazole and amphotericin B may prove to be the most effective. This is the first report of an outbreak of cluster endophthalmitis caused by Trichosporon.

Augmented sequence features and subcellular localization for functional characterization of unknown protein sequences.

Advances in high-throughput techniques lead to evolving a large number of unknown protein sequences (UPS). Functional characterization of UPS is significant for the investigation of disease symptoms and drug repositioning. Protein subcellular localization is imperative for the functional characterization of protein sequences. Diverse techniques are used on protein sequences for feature extraction. However, many times a single feature extraction technique leads to poor prediction performance. In this paper, two feature augmentations are described through sequence induced, physicochemical, and evolutionary information of the amino acid residues. While augmented features preserve the sequence-order-information and protein-residue-properties. Two bacterial protein datasets Gram-Positive (G +) and Gram-Negative (G-) are utilized for the experimental work. After performing essential preprocessing on protein datasets, two sets of feature vectors are obtained. These feature vectors are used separately to train the different individual and ensembles such as decision tree (C 4.5), k-nearest neighbor (k-NN), multi-layer perceptron (MLP), Naïve Bayes (NB), support vector machine (SVM), AdaBoost, gradient boosting machine (GBM), and random forest (RF) with fivefold cross-validation. Prediction results of the model demonstrate that overall accuracy reported by C4.5 is highest 99.57% on G + and 97.47% on G- datasets with known protein sequences. Similarly, for the UPS overall accuracy of G + is 85.17% with SVM and 82.45% with G- dataset using MLP.

Critical Role of Protons for Emission Quenching of Indoline Dyes in Solution and on Semiconductor Surfaces.

By combining time-correlated single photon counting (TCSPC) measurements, density functional theory (DFT), and time-dependent DFT (TD-DFT) calculations, we herein investigate the role of protons, in solutions and on semiconductor surfaces, for the emission quenching of indoline dyes. We show that the rhodanine acceptor moieties, and in particular the carbonyl oxygens, undergo protonation, leading to nonradiative excited-state deactivation. The presence of the carboxylic acid anchoring group, close to the rhodanine moiety, further facilitates the emission quenching, by establishing stable H-bond complexes with carboxylic acid quenchers, with high association constants, in both ground and excited states. This complexation favors the proton transfer process, at a low quencher concentration, in two ways: bringing close to the rhodanine unit the quencher and assisting the proton release from the acid by a partial-concerted proton donation from the close-by carboxylic group to the deprotonated acid. Esterification of the carboxylic group, indeed, inhibits the ground-state complex formation with carboxylic acids and thus the quenching at a low quencher concentration. However, the rhodanine moiety in the ester form can still be the source of emission quenching through dynamic quenching mechanism with higher concentrations of protic solvents or carboxylic acids. Investigating this quenching process on mesoporous ZrO2, for solar cell applications, also reveals the sensitivity of the adsorbed excited rhodanine dyes toward adsorbed protons on surfaces. This has been confirmed by using an organic base to remove surface protons and utilizing cynao-acrylic dye as a reference dye. Our study highlights the impact of selecting such acceptor group in the structural design of organic dyes for solar cell applications and the overlooked role of protons to quench the excited state for such chemical structures.

A reliable fluorimetric method to screen the nitric oxide synthase inhibitors in 96 well plate.

In general, 4 amino-5-methylamino-2',7'-difluorescein diacetate (DAF-FM-DA) dye is used to detect nitric oxide in biological systems through cell imaging. In this study, we have used 96 well plate format to quantify nitric oxide using DAF-FM-DA through a multimode reader (or independently using fluorospectrometer) and could be visualized in a fluorescence microscope. Similar study otherwise will require a high-end instrument. The method has been validated to screen NOS inhibitors in the HEK 293T cell lines over-expressing the NOS isoforms. We observed that the method is very simple to use, adaptive, sensitive and most importantly it saves time. REAGENTS/TOOLS: Ethanol (70% [v/v] in distilled water), Nω-Nitro-l-arginine (l-NAME), 7-Nitro-Indazole (7-NI) (Sigma, St. Louis, MO), HEK 293T cell lines (National Centre for Cell Science (NCCS), Pune, India), DMEM (Himedia laboratories Pvt), Fetal Bovine Serum (FBS) (Invitrogen, Carlsbad, CA), 100 U/mL penicillin, and 0.1 mg/mL streptomycin in a 5% CO2 atmosphere. Hank's Balanced Salt Solution (HBSS) without Phenol Red of pH 7.4 was prepared with the following composition: NaCl, 8.0g, KCl, 0.4g, CaCl2, 0.14g, MgSO4⋅7H2O, 0.1g, MgCl2·6H2O, 0.1g, Na2HPO4·2H2O, 0.06g, KH2PO4, 0.06g, glucose, 1.0g, NaHCO3, 0.35g, H2O, to 1000 ml, Sterilized and refrigerated, Calcium Ionophore A23187 (Sigma Aldrich 52665-69-7) DAF-FM Di Acetate (Molecular Probes Life Technologies), and DAF-FM Di Aceatate was prepared as a stock solution (5 mM) in DMSO, divided into aliquots and stored at -20 °C, followed by dilution to the required concentration in HBSS buffer before use. EQUIPMENT: Neubauer chamber, Microtube centrifuges (1.5 mL), Micropipettors,10,100, and 1000 mL with corresponding tips, multimode reader (Tecan, Synergy-HT), inverted fluorescence microscope (Nikon, eclipse Ti-S), black flat bottom Microplates (96-well) (Corning 3603).

Neuroprotective effect of IDPU (1-(7-imino-3-propyl-2,3-dihydrothiazolo [4,5-d]pyrimidin-6(7H)-yl)urea) in 6-OHDA induced rodent model of hemiparkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative motor disorder characterized by the degeneration of dopaminergic nigrostriatal neurons. Levodopa (l-DOPA) is the most effective therapy for PD, however, PD progression continues with significant side effects in long term, thus necessitating the search for effective therapy that impedes PD progression. PD therapy through non-dopaminergic pathways offers treatment without the risk of extrapyramidal effects. In this regard, earlier, we had reported, a novel compound IDPU with potential adenosine A2A receptor antagonist effect in haloperidol (chronic treatment) induced Parkinson model. In the present study, we extended our investigation towards i) evaluation of IDPU in well-established 6-OHDA induced Parkinson rat model to establish its role in the therapy of PD ii) its function in alleviating the neuronal loss. We carried the IDPU administration (i.p.) in rats for two weeks after establishing 6-OHDA induced unilateral lesions. The behavioral activity, neurochemical alteration, oxidative stress marker and tyrosine hydroxylase positive neurons in substantia nigra were analyzed. The results showed that IDPU significantly reduced motor and non-motor deficits induced by 6-OHDA in the behavioral tasks such as apomorphine, rota rod and force swim test. Furthermore, the results of oxidative stress biomarkers revealed that IDPU successfully modulated oxidative stress associated biomarkers such as MDA, catalase, superoxide dismutase, nitric oxide and reduced glutathione level. Additionally, IDPU significantly elevated intracellular dopamine, decreased glutamate and calcium levels in brain as compared to 6-OHDA alone treated animals which is evocative of its neuroprotective behavior. Thus, the investigations clearly validated IDPU as a potent anti-parkinsonian agent which showed immense capability to protect neurodegeneration.

Pharmacological assessments of potent A2A receptor antagonist IDPU (1-(7-imino-3-propyl-2,3-dihydrothiazolo[4,5-d]pyrimidin-6(7H)-yl)urea) in rodent model of haloperidol induced Parkinson like symptoms.

A2A receptor antagonists emerged as potential candidate for management of Parkinson's disease. Earlier we had reported the therapeutic potential of 1-(7-imino-3-propyl-2,3-dihydrothiazolo[4,5-d]pyrimidin-6(7H)-yl) urea (IDPU) as A2A receptor antagonist. Herein, we have investigated the effect of IDPU in attenuation of haloperidol induced Parkinson like symptoms in rats. It has successfully restored hypo-locomotion induced by haloperidol and NECA. IDPU also displayed protective effect against oxidative stress induced by chronic haloperidol treatment in rats. The antidepressant activity of IDPU was determined in mice showed that it imperatively reduced depression like symptoms in well-established depression models viz. TST and FST. Additionally, IDPU was found to be a safe and non-toxic chemical entity in acute, sub-acute and neurotoxicity studies. In silico study of IDPU showed acceptable physicochemical parameters and in vitro screening exhibited satisfactory metabolic stability. This study clearly indicates that A2A receptor antagonist IDPU is able to ameliorate Parkinsonian symptoms without exerting any significant toxicity.

Template Synthesis of Decaphyrin without Meso-Bridges: Cyclo[10]pyrrole.

An acenaphthylene-fused cyclo[10]pyrrole 1b was selectively synthesized via an oxidative coupling reaction of the corresponding 2,2'-bipyrrole with the appropriate dianion template, croconate anion. The structure of 1b as the isolated largest cyclo[n]pyrrole was elucidated by X-ray crystallographic analysis. The absorption spectrum exhibited a markedly red-shifted, intensified L band at 1982 nm, which was interpreted by application of Michl's perimeter and Gouterman's 4-orbital models, supported by magnetic circular dichroism (MCD) data and theoretical calculations.

Clinico-Pathological Profile and Surgical Outcome of Patients of Gastrointestinal Tuberculosis Undergoing Laparotomy.

Tuberculosis is one of the earliest diseases affecting the mankind. Abdominal tuberculosis constitutes a common public health issue in developing countries like ours. Gastrointestinal tuberculosis often involves the ileocecal region. Surgery in case of abdominal tuberculosis is required to overcome the deleterious effects of the disease like tissue disorganization, obstruction and perforatio. AIMS AND OBJECTIVES: 1. To study the various clinical profiles of gastrointestinal tuberculosis in patients undergoing laparotomy; 2. To study the surgical pathology of gastrointestinal tuberculosis; 3. To study the various surgical treatment modalities based upon the intraoperative findings and its outcome. Results: This is a prospective study over 12 months at Himalayan Institute of Medical Sciences, SRHU, Swami Ram Nagar, Dehradun. This study was done to study the clinic-pathological profile of gastrointestinal tuberculosis undergoing laparotomy. Incidence of gastro intestinal tuberculosis was seen highest in age group 15 to 25 years with male predominance. Most commonly presentation being intestinal obstruction with ileo-caecal as the most common area involved and right hemicolectomy as the commonest procedure done. Common surgical pathologies were ileo-caecal mass and ileal perforation and this also has relation to pulmonary tuberculosis. CONCLUSION: Inspite of specific antituberculous drugs and vast measures against the disease, including chemoprophylaxis and pasteurisation abdominal tuberculosis remains a fairly common disease even today. Gastrointestinal tuberculosis has an indolent course and the common mode of presentation is usually sub acute or chronic. Prompt surgical exploration, vigilant postoperative care and administration of ATD helped to treat the patients successfully with their complete cure and rehabilitation.

Structural and electronic properties of photoexcited TiO2 nanoparticles from first principles.

The structure and energetics of excitons and individual electron and hole polarons in a model anatase TiO2 nanoparticle (NP) are investigated by means of Density Functional Theory (DFT) and Time Dependent (TD)-DFT calculations. The effect of the Hartree-Fock exchange (HF-exc) contribution in the description of TiO2 NPs with unpaired electrons is examined by comparing the results from semilocal and hybrid DFT functionals with different HF-exc percentages, including a long-range corrected hybrid functional. The performances of TD-DFT and ground state (SCF) DFT approaches in the description of the photoexcited polaron states in TiO2 NPs are also analyzed. Our results confirm that the HF-exc contribution is essential to properly describe the self-trapping of the charge carriers. They also suggest that long-range corrected functionals are needed to properly describe excited state relaxation in TiO2 NPs. TD-DFT geometry optimization of the lowest excited singlet and triplet states deliver photoluminescence values in close agreement with the experimental data.

JNK pathway signaling: a novel and smarter therapeutic targets for various biological diseases.

JNK pathway regulates various physiological processes including inflammatory responses, cell differentiation, cell proliferation, cell death, cell survival and expression of proteins. Deregulation of JNK is linked with various diseases including neurodegenerative disease, autoimmune disease, diabetes, cancer, cardiac hypertrophy and asthma. Three distinct genes JNK1, JNK2 and JNK3 have been identified as regulator of JNK pathway. JNK1 and JNK2 have broad tissue distribution and play a potential role in insulin resistance, inflammation and cell signaling. JNK3 is predominantly found in the CNS neurons, making it an attractive target for neurodegenerative disorders. In this review, we summarize the evidence supporting JNK as a potent therapeutic target, and small molecules from various chemical classes as JNK inhibitors.

Enhanced Charge Separation Efficiency in Pyridine-Anchored Phthalocyanine-Sensitized Solar Cells by Linker Elongation.

A series of zinc phthalocyanine sensitizers (PcS22-24) having a pyridine anchoring group are designed and synthesized to investigate the structural dependence on performance in dye-sensitized solar cells. The pyridine-anchor zinc phthalocyanine sensitizer PcS23 shows 79 % incident-photon to current-conversion efficiency (IPCE) and 6.1 % energy conversion efficiency, which are comparable with similar phthalocyanine dyes having a carboxylic acid anchoring group. Based on DFT calculations, the high IPCE is attributed with the mixture of an excited-state molecular orbital of the sensitizer and the orbitals of TiO2 . Between pyridine and carboxylic acid anchor dyes, opposite trends are observed in the linker-length dependence of the IPCE. The red-absorbing PcS23 is applied for co-sensitization with a carboxyl-anchor organic dye D131 that has a complementary spectral response. The site-selective adsorption of PcS23 and D131 on the TiO2 surface results in a panchromatic photocurrent response for the whole visible-light region of sun light.