Age-related genes affecting the immune cell infiltration in ulcerative colitis revealed by weighted correlation network analysis and machine learning.

OBJECTIVE: The crosstalk between age and immunity in the context of ulcerative colitis (UC) remains incompletely understood. Our objective is to elucidate the specific age-associated genetic factors that modulate immune cell infiltration in UC, with the aim of identifying innovative therapeutic targets for the treatment of this disease. MATERIALS AND METHODS: Potential batch effects between samples were removed by R package "inSilicoMerging". Unsupervised clustering analysis via the "ConsensusClusterPlus" R package was utilized to perform consensus molecular subtyping of immune subtypes in UC. The construction of a heat map was accomplished through the utilization of the R package "pheatmap", while functional enrichment analysis was executed by means of the Metascape database. The identification of the age-related gene module was achieved by performing weighted gene co-expression network analysis (WGCNA) analysis using the R package "WGCNA". The support vector machine (SVM), least absolute shrinkage and selector operation (LASSO), and random forest algorithms were performed via the "e1071", "glmnet" and "randomForest" packages in R, respectively. The diagnostic performance of the parameter was assessed using the receiver operating characteristic (ROC) curve. Correlation analysis was performed by Spearman correlation. The "XSum" package in R was employed to identify potential small-molecule drugs for UC utilizing the Connectivity Map (CMap) database. Molecular docking was performed with Autodock Vina molecular docking software. RESULTS: A significantly greater frequency of UC patients aged below 40 years was observed in the group with extensive disease extent as compared to those with non-extensive disease extent (70% vs. 47%; Chi-square test, p = 0.02). The application of unsupervised clustering analysis allowed for the stratification of UC patients into two distinct immune subtypes, namely cluster C1 and cluster C2. The distribution of immune subtypes was significantly different between different age categories (Chi-square test,  p = 0.00219). The UC samples that were grouped under cluster C1 were distinguished by a higher abundance of macrophages and an elevated number of neutrophils relative to those in cluster C2. Based on both WGCNA and Limma analysis, 146 age-related genes were identified, which exhibited a predominant enrichment in the biological process of cellular senescence. Two age-related genes (MIDN, and PLD6) affecting the immune cell infiltration in UC were identified based on machine learning algorithms (SVM, LASSO, and random forest). The diagnostic performance of MIDN (AUC = 0.93) and PLD6 (AUC = 0.90) in discerning UC patients belonging to cluster C1 was found to be satisfactory, as demonstrated by ROC curve analysis. MIDN demonstrated a positive correlation (r = 0.50,  p < 0.0001) with Neutrophil, while PLD6 exhibited a negative correlation (r = -0.52, p < 0.0001) with Neutrophil levels. The "XSum" algorithm revealed that Entinostat has therapeutic potential for UC. The docking glide score between Entinostat and MIDN, and PLD6 protein was -8.9 kcal/mol and -6.8 kcal/mol, respectively. CONCLUSIONS: We have identified two age-related genes, MIDN and PLD6, that are involved in immune cell infiltration in patients with ulcerative colitis. Furthermore, a small molecule drug (Entinostat) with potential therapeutic effects for UC was screened out. This study presented new perspectives on personalized clinical management and therapy research for UC.

Fabrication of infrared linear arrays of InAs planar avalanche photodiodes.

We report a, to the best of our knowledge, new device fabrication process for 128-pixel linear arrays of InAs planar avalanche photodiodes, utilizing selective area implantation of Beryllium ions into epitaxially-grown InAs wafers. The pixels exhibited uniform avalanche gain and responsivity. Room temperature responsivity values at 1550 and 2004 nm wavelengths are 0.49 ± 0.017 and 0.89 ± 0.024 A/W, respectively. Reverse dark current-voltage and avalanche gain measurements were carried out at different temperatures (from room temperature to 150 K). At 200 K at -15 V reverse bias, the pixels exhibited an avalanche gain of 22.5 ± 1.18 and dark current density of 0.68 ± 0.48 A/cm2.

Simulation of Al0.85Ga0.15As0.56Sb0.44 avalanche photodiodes.

Al0.85Ga0.15As0.56Sb0.44 is a promising avalanche material for near infrared avalanche photodiodes (APDs) because they exhibit very low excess noise factors. However electric field dependence of ionization coefficients in this material have not been reported. We report a Simple Monte Carlo model for Al0.85Ga0.15As0.56Sb0.44, which was validated using reported experimental results of capacitance-voltage, avalanche multiplication and excess noise factors from five APDs. The model was used to produce effective ionization coefficients and threshold energies between 400-1200 kV.cm-1 at room temperature, which are suitable for use with less complex APD simulation models.

[Clinical features and prognostic factors of primary gastric neuroendocrine neoplasms].

Objective: To study the clinical characteristics and classification of gastric neuroendocrine neoplasm(NEN) and prognostic factors of mixed adenoneuroendocrine carcinoma (MANEC) and gastric neuroendocrine carcinoma(NEC). Methods: A total of 148 gastric NENs were divided into type Ⅰ, type Ⅱ and type Ⅲ based on the classification of European Neuroendocrine Tumor Society (ENETS). Kaplan-Meier test and Cox regression model were used in univariate and multivariate survival analysis in 108 cases with pathological G3 gastric NEN. Results: In this study, the percentages of type Ⅰ, type Ⅱ and type Ⅲ were 25.0%(37), 3.4%(5) and 71.6%(106) respectively. Among type Ⅰ patients, 28(75.7%) lesions were located in gastric fundus or body, 29(78.4%) had bumps. Lymph node involvement was found in 4 (10.8%) patients. Twenty-six (70.3%) patients received endoscopic treatment and 11 (29.7%) with surgery. All 5 type Ⅱ patients presented lesions in gastric fundus or body, including 4 with ulcers, who were all treated by endoscope. Three type Ⅱ patients had gastrinoma, and 2 combined with multiple endocrine neoplasmⅠ. In type Ⅲ patients, 56(52.8%) showed ulcerative lesions. The majority of patients (102, 96.2%) had a single lesion, 94(88.7%) with lymph node or other organ metastasis. In this study, no deaths were reported in gastric NEN with a pathological grade of G1 or G2. The mortality rate was 38.9%(42/108) in patients with G3 NEN. Survival analysis suggested that age, metastasis of tumor were associated with poor prognosis (P=0.041, 0.025). Conclusions: Patients with gastric NEN have heterogenous clinical presentations according to gender, age, endoscopic features, infiltration and metastasis, and pathological grade. Aging and metastasis are negative prognostic factors of G3 gastric NEN.

Predicting early recurrence of hepatocellular carcinoma with texture analysis of preoperative MRI: a radiomics study.

AIM: To investigate the feasibility of using texture analysis in preoperative magnetic resonance imaging (MRI) to predict early recurrence (ER) in hepatocellular carcinoma (HCC) post-curative surgery. MATERIAL AND METHODS: Institutional review board was obtained. A retrospective review of all patients who underwent hepatectomy between 1 January 2007 and 31 December 2015 was performed. Inclusion criteria included preoperative MRI, tumour size ≥1 cm, new cases of HCC. Exclusion criteria included loss to follow-up, ruptured HCCs, movement artefacts, and previous hepatectomy or interval adjuvant therapy. Patients were divided into ER and late or no recurrence (LNR) groups. ER was defined as new foci of HCC within 730 days of curative surgery. Radiomics feature extraction was performed on T2, diffusion-weighted imaging (DWI), T1 arterial, and T1 portovenous acquisitions on MATLAB (Mathworks, Matick, MA, USA). The MaZda software was used to analyse 290 texture parameters and PRTools was used for feature selection. RESULTS: Fifty patients (43 male, mean age 67 years) were divided into ER (n=20) and LNR (n=30) groups. Serum alpha-fetoprotein level (p=0.026), serum É£-glutamyltranspeptidase (p=0.014), Child-Pugh score (p=0.02) and the presence of vascular invasion (gross and/or microvascular, p=0.025) were found to be statistically significant different between the two groups. Parameters S(4,0)SumVarnc, S(0,3)SumOfSqs, and S(1,1)DifVarnc of the equilibrium phase were most accurate, achieving 84%, 82%, and 78% accuracy, respectively. CONCLUSION: Texture analysis of preoperative MRI has the potential to predict ER of HCC with up to 84% accuracy using an appropriate, single texture analysis parameter. Future studies are needed to validate these findings.

Analysis of Bi Distribution in Epitaxial GaAsBi by Aberration-Corrected HAADF-STEM.

The Bi content in GaAs/GaAs1 - xBi x /GaAs heterostructures grown by molecular beam epitaxy at a substrate temperature close to 340 °C is investigated by aberration-corrected high-angle annular dark-field techniques. The analysis at low magnification of high-angle annular dark-field scanning transmission electron microscopy images, corroborated by EDX analysis, revealed planar defect-free layers and a non-homogeneous Bi distribution at the interfaces and within the GaAsBi layer. At high magnification, the qHAADF analysis confirmed the inhomogeneous distribution and Bi segregation at the GaAsBi/GaAs interface at low Bi flux and distorted dumbbell shape in areas with higher Bi content. At higher Bi flux, the size of the Bi gathering increases leading to roughly equiaxial Bi-rich particles faceted along zinc blende {111} and uniformly dispersed around the matrix and interfaces. FFT analysis checks the coexistence of two phases in some clusters: a rhombohedral pure Bi (rh-Bi) one surrounded by a zinc blende GaAs1 - xBi x matrix. Clusters may be affecting to the local lattice relaxation and leading to a partially relaxed GaAsBi/GaAs system, in good agreement with XRD analysis.

Mesoscopic Energy Minimization Drives Pseudomonas aeruginosa Biofilm Morphologies and Consequent Stratification of Antibiotic Activity Based on Cell Metabolism.

Segregation of bacteria based on their metabolic activities in biofilms plays an important role in the development of antibiotic resistance. Mushroom-shaped biofilm structures, which are reported for many bacteria, exhibit topographically varying levels of multiple drug resistance from the cap of the mushroom to its stalk. Understanding the dynamics behind the formation of such structures can aid in design of drug delivery systems, antibiotics, or physical systems for removal of biofilms. We explored the development of metabolically heterogeneous Pseudomonas aeruginosa biofilms using numerical models and laboratory knockout experiments on wild-type and chemotaxis-deficient mutants. We show that chemotactic processes dominate the transformation of slender and hemispherical structures into mushroom structures with a signature cap. Cellular Potts model simulation and experimental data provide evidence that accelerated movement of bacteria along the periphery of the biofilm, due to nutrient cues, results in the formation of mushroom structures and bacterial segregation. Multidrug resistance of bacteria is one of the most threatening dangers to public health. Understanding the mechanisms of the development of mushroom-shaped biofilms helps to identify the multidrug-resistant regions. We decoded the dynamics of the structural evolution of bacterial biofilms and the physics behind the formation of biofilm structures as well as the biological triggers that produce them. Combining in vitro gene knockout experiments with in silico models showed that chemotactic motility is one of the main driving forces for the formation of stalks and caps. Our results provide physicists and biologists with a new perspective on biofilm removal and eradication strategies.

Validity of estimating muscle and fat volume from a single MRI section in older adults with sarcopenia and sarcopenic obesity.

AIM: To determine if there is a correlation between the cross-sectional areas (CSAs) in a single section and the volumes of muscles and fat in the thigh of sarcopenic and sarcopenic obesity (SO) populations using magnetic resonance imaging (MRI), and to assess the correlation between thigh MRI data and patient health status, i.e., normal, obese, sarcopenia, and SO. MATERIALS AND METHODS: One hundred and ninety community-dwelling older adults were recruited and categorised into four subgroups based on Asian established criteria: normal, obese, sarcopenia, and SO. MRI images were acquired and muscles, subcutaneous fat (SF), and intermuscular fat (IMF) were automatically segmented in the thighs. Volumes of muscles and fat were calculated for the middle third of the thigh, while CSAs were assessed using a single section at 50% femur length. RESULTS: Correlation between CSA and volume were significantly high (p<0.001) for all components of muscle (0.907), SF (0.963), and IMF (0.939). Thigh CSA and volume both correlated significantly with a clinical diagnosis of normal, obesity, sarcopenia, and SO (p<0.03). CONCLUSIONS: A single CSA at 50% of femur length yields good estimation of muscle and fat volume in the thighs of older adults and correlates closely with the clinical criteria for sarcopenia and SO. This has the potential to greatly reduce costs, scan time, and post-processing time in clinical practice for the prediction of these conditions.

Prescribing Pattern of Antidepressants in Children and Adolescents: Findings from the Research on Asia Psychotropic Prescription Pattern.

OBJECTIVE: Pharmacotherapy of depression in children and adolescents is complex. In the absence of research into the efficacy and safety of antidepressants in this group of patients, their off-label prescription is common. This paper aimed to illustrate the prescription pattern of antidepressants in children and adolescents from major psychiatric centres in Asia. METHODS: The Research on Asia Psychotropic Prescription Pattern on Antidepressants worked collaboratively in 2013 to study the prescription pattern of antidepressants in Asia using a unified research protocol and questionnaire. Forty psychiatric centres from 10 Asian countries / regions participated and 2321 antidepressant prescriptions were analysed. RESULTS: A total of 4.7% antidepressant prescriptions were for children and adolescents. Fluoxetine, sertraline, and escitalopram were the most common antidepressants prescribed for children and adolescents. Almost one-third (30.3%) of prescriptions were for diagnoses other than depressive and anxiety disorders. There was less antidepressant polypharmacy and concomitant use of benzodiazepine, but more concomitant use of antipsychotics in children and adolescents compared with adults. CONCLUSION: Off-label use of antidepressants in children and adolescents was reported by 40 Asian psychiatric institutions that participated in the study. In-service education and regulatory mechanisms should be reinforced to ensure efficacy and safety of antidepressants in children and adolescents.

Water as neutral oral contrast agent in abdominopelvic CT: comparing effectiveness with Gastrografin in the same patient.

INTRODUCTION: Positive oral contrast is no longer deemed necessary for abdominopelvic computed tomography (CT) scans. Studies have shown water to be an equally effective oral contrast agent. However, to our knowledge no study has compared effectiveness between gastrografin and water in the same patient, which will provide a more objective evaluation of the two oral contrast agents. We aim to make a head-to-head comparison of water as neutral oral contrast (OC) against gastrografin as positive OC for abdominopelvic CT scans in the same patient. METHODS: A retrospective review of 206 abdominopelvic CT scans of 103 patients was performed. The scans were reviewed in consensus by two blinded radiologists. The ability to visualise each abdominopelvic organ, contrastassociated artefacts and small bowel wall delineation, was qualitatively scored on a 5-point scale. Each patient had two sets of scores, one with water and another with gastrografin as OC. Paired scores from the two OCs were evaluated by Wilcoxon signed rank test to determine any significant difference in performance between the two OCs for visualisation of abdominopelvic anatomy on CT. RESULTS: There was significantly better delineation of duodenal wall (p<0.001) and overall visualisation of the duodenum (p=0.011) using water as OC compared to gastrografin. No statistically significant differences were demonstrated between water and gastrografin for visualisation of the rest of the abdominopelvic organs, walldelineation of the rest small bowel and contrast-associated artefacts. CONCLUSIONS: Water can be used in place of gastrografin as oral contrast in abdominopelvic CT without compromising visualization of abdominopelvic organs.

Doxycycline-induced hypoglycaemia.

Tetracyclines, including doxycycline, are widely used drugs that form an integral part of daily prescribing, and serious adverse reactions (SARs) are rarely reported. The frequency of hypoglycaemia complicating tetracycline treatment remains unknown, and is not a recognized complication. We describe an 80-year-old man with a history of insulin-dependent diabetes who was recruited into a large research study, and subsequently experienced the unexpected SAR of hypoglycaemia following treatment with doxycycline.

Sex-specific differences in risk factors for sarcopenia amongst community-dwelling older adults.

With considerable variation including potential sex-specific differential rate of skeletal muscle loss, identifying modifiable factors for sarcopenia will be pivotal to guide targeted interventions. This study seeks to identify clinical and biological correlates of sarcopenia in community-dwelling older adults, with emphasis on the role of anabolic and catabolic stimuli, and special reference to gender specificity. In this cross-sectional study involving 200 community-dwelling and functionally independent older adults aged ≥50 years, sarcopenia was defined using the Asian Working Group for Sarcopenia criteria. Comorbidities, cognitive and functional performance, physical activity and nutritional status were routinely assessed. Biochemical parameters included haematological indices, lipid panel, vitamin D level, anabolic hormones [insulin-like growth factor-1 (IGF-1), free testosterone (males only)] and catabolic markers [inflammatory markers (interleukin-6, C-reactive protein) and myostatin]. Multiple logistic regression was performed to identify independent predictors for sarcopenia. Age was associated with sarcopenia in both genders. Malnutrition conferred significantly higher odds for sarcopenia in women (OR = 5.71, 95% CI 1.13-28.84.44, p = 0.035) while higher but acceptable range serum triglyceride was protective in men (OR = 0.05, 95% CI 0.00-0.52, p = 0.012). Higher serum myostatin independently associated with higher odds for sarcopenia in men (OR = 1.11, 95% CI 1.00-1.24, p = 0.041). Serum IGF-1 was significantly lower amongst female sarcopenic subjects, with demonstrable trend for protective effect against sarcopenia in multiple regression models, such that each 1 ng/ml increase in IGF-1 was associated with 1% decline in odds of sarcopenia in women (p = 0.095). Our findings support differential pathophysiological mechanisms for sarcopenia that, if corroborated, may have clinical utility in guiding sex-specific targeted interventions for community-dwelling older adults.

Antidepressant Prescription Pattern in the Presence of Medical Co-morbidity: REAP-AD 2013 Study.

OBJECTIVE: To evaluate the prescription pattern of antidepressants in patients with medical co-morbidity from major psychiatric centres in Asia. METHODS: The Research on Asian Psychotropic Prescription Pattern for Antidepressants (REAP-AD 2013) collected data from 42 psychiatric centres in 10 Asian countries and regions. Antidepressant prescriptions of 2320 patients with various psychiatric disorders were evaluated. Of these, 370 patients who had specified medical co-morbidities formed the study cohort. RESULTS: Escitalopram (20%) and mirtazapine (20%) were the most commonly prescribed antidepressants in patients with medical co-morbidity followed by sertraline (16%), trazodone (15%), and paroxetine (12%). Overall, more than half (52%; 247/476) of prescriptions comprised selective serotonin reuptake inhibitors. Slightly less than two-thirds (63%; n = 233) of patients received at least 1 selective serotonin reuptake inhibitor. In addition, 79% of patients were prescribed only 1 antidepressant. The mean number of antidepressants used per patient was 1.25 (standard deviation, 0.56). There were subtle differences in the most preferred antidepressant across medical illnesses such as diabetes mellitus, liver dysfunction, acid peptic disease, and cerebrovascular disease. Differences were also seen in prescription patterns across different countries. CONCLUSION: Although selective serotonin reuptake inhibitors formed the bulk of antidepressant prescriptions in the presence of medical co-morbidity, mirtazapine was also commonly used in the presence of medical co-morbidities. Specified medical morbidities do influence the selection of antidepressants.

A hybrid approach for fusing 4D-MRI temporal information with 3D-CT for the study of lung and lung tumor motion.

PURPOSE: Accurate visualization of lung motion is important in many clinical applications, such as radiotherapy of lung cancer. Advancement in imaging modalities [e.g., computed tomography (CT) and MRI] has allowed dynamic imaging of lung and lung tumor motion. However, each imaging modality has its advantages and disadvantages. The study presented in this paper aims at generating synthetic 4D-CT dataset for lung cancer patients by combining both continuous three-dimensional (3D) motion captured by 4D-MRI and the high spatial resolution captured by CT using the authors' proposed approach. METHODS: A novel hybrid approach based on deformable image registration (DIR) and finite element method simulation was developed to fuse a static 3D-CT volume (acquired under breath-hold) and the 3D motion information extracted from 4D-MRI dataset, creating a synthetic 4D-CT dataset. RESULTS: The study focuses on imaging of lung and lung tumor. Comparing the synthetic 4D-CT dataset with the acquired 4D-CT dataset of six lung cancer patients based on 420 landmarks, accurate results (average error <2 mm) were achieved using the authors' proposed approach. Their hybrid approach achieved a 40% error reduction (based on landmarks assessment) over using only DIR techniques. CONCLUSIONS: The synthetic 4D-CT dataset generated has high spatial resolution, has excellent lung details, and is able to show movement of lung and lung tumor over multiple breathing cycles.

Low efficacy of delthamethrin-treated net against Singapore Aedes aegypti is associated with kdr-type resistance.

There has been a worldwide surge in the number and severity of dengue in the past decades. In Singapore, relentless vector control efforts have been put in to control the disease since the 1960's. Space spraying, fogging, chemical treatment and source reduction are some commonly used methodologies for controlling its vectors, particularly Aedes aegypti. Here, as we explored the use of a commercially available delthamethrin-treated net as an alternative strategy and the efficacy of the treated net was found to be limited. Through bioassays and molecular studies, the failure of the treated net to render high mortality rate was found to be associated with the knockdown resistance (kdr) mutation. This is the first report of kdr- mutations in Singapore's Ae. aegypti. At least one point mutation, either homozygous or heterozygous, at amino acid residue V1016G of DIIS6 or F1269C of DIIIS6 was detected in 93% of field strains of Ae. aegypti. Various permutations of wild type and mutant amino acids of the four alleles were found to result in varying degree of survival rate among local field Ae. aegypti when exposed to the deltamethrin treated net. Together with the association of higher survival rate with the presence of both V1016G and F1269C, the data suggest the role of these mutations in the resistance to the deltamethrin. The high prevalence of these mutations were confirmed in a country wide survey where 70% and 72% of the 201 Ae. aegypti analysed possessed the mutations at residues 1016 and 1269 respectively. The highest mutated frequency combination was found to be heterozygous alleles (VG/FC) at both residues 1016 and 1269 (37.8%), followed by homozygous mutation at allele 1269 (24.4%) and homozygous mutation at allele 1016 (22.9%). The kdr- type of resistance among the vector is likely to undermine the effectiveness of pyrethroids treated materials against these mosquitoes.

Low efficacy of delthamethrin-treated net against Singapore Aedes aegypti is associated with kdr-type resistance

There has been a worldwide surge in the number and severity of dengue in the past decades. In Singapore, relentless vector control efforts have been put in to control the disease since the 1960’s. Space spraying, fogging, chemical treatment and source reduction are some commonly used methodologies for controlling its vectors, particularly Aedes aegypti. Here, as we explored the use of a commercially available delthamethrin-treated net as an alternative strategy and the efficacy of the treated net was found to be limited. Through bioassays and molecular studies, the failure of the treated net to render high mortality rate was found to be associated with the knockdown resistance (kdr) mutation. This is the first report of kdr- mutations in Singapore’s Ae. aegypti. At least one point mutation, either homozygous or heterozygous, at amino acid residue V1016G of DIIS6 or F1269C of DIIIS6 was detected in 93% of field strains of Ae. aegypti. Various permutations of wild type and mutant amino acids of the four alleles were found to result in varying degree of survival rate among local field Ae. aegypti when exposed to the deltamethrin treated net. Together with the association of higher survival rate with the presence of both V1016G and F1269C, the data suggest the role of these mutations in the resistance to the deltamethrin. The high prevalence of these mutations were confirmed in a country wide survey where 70% and 72% of the 201 Ae. aegypti analysed possessed the mutations at residues 1016 and 1269 respectively. The highest mutated frequency combination was found to be heterozygous alleles (VG/FC) at both residues 1016 and 1269 (37.8%), followed by homozygous mutation at allele 1269 (24.4%) and homozygous mutation at allele 1016 (22.9%). The kdr- type of resistance among the vector is likely to undermine the effectiveness of pyrethroids treated materials against these mosquitoes.

CT volumetry of the liver: where does it stand in clinical practice?

Imaging-based volumetry has been increasingly utilised in current clinical practice to obtain accurate measurements of the liver volume. This is particularly useful prior to major hepatic resection and living donor liver transplantation where the size of the remnant liver and liver graft, respectively, affects procedural success and postoperative mortality and morbidity. The use of imaging-based volumetry, with emphasis on computed tomography, will be reviewed. We will explore the various technical factors that contribute to accurate volumetric measurements, and demonstrate how the accuracies of these techniques are influenced by their methodologies. The strengths and limitations of using anatomical imaging to estimate liver volume will be discussed, in relation to laboratory and functional imaging methods of assessment.

Utilizing hydrogen sulfide as a novel anti-cancer agent by targeting cancer glycolysis and pH imbalance.

BACKGROUND AND PURPOSE: Many disparate studies have reported the ambiguous role of hydrogen sulfide (H2 S) in cell survival. The present study investigated the effect of H2 S on the viability of cancer and non-cancer cells. EXPERIMENTAL APPROACH: Cancer and non-cancer cells were exposed to H2 S [using sodium hydrosulfide (NaHS) and GYY4137] and cell viability was examined by crystal violet assay. We then examined cancer cellular glycolysis by in vitro enzymatic assays and pH regulator activity. Lastly, intracellular pH (pHi ) was determined by ratiometric pHi measurement using BCECF staining. KEY RESULTS: Continuous, but not a single, exposure to H2 S decreased cell survival more effectively in cancer cells, as compared to non-cancer cells. Slow H2 S-releasing donor, GYY4137, significantly increased glycolysis, leading to overproduction of lactate. H2 S also decreased anion exchanger and sodium/proton exchanger activity. The combination of increased metabolic acid production and defective pH regulation resulted in an uncontrolled intracellular acidification, leading to cancer cell death. In contrast, no significant intracellular acidification or cell death was observed in non-cancer cells. CONCLUSIONS AND IMPLICATIONS: Low and continuous exposure to H2 S targets metabolic processes and pH homeostasis in cancer cells, potentially serving as a novel and selective anti-cancer strategy.