Characterization of carbonaceous particles by single particle aerosol mass spectrometer in the urban area of Chengdu, China.

Carbonaceous particles are an important chemical component of atmospheric fine particles. In this study, a single particle aerosol mass spectrometer was used to continuously measure the carbonaceous particles in Chengdu, one of the megacities most affected by haze in China, from January 22 to March 3, 2021. During the observation period, the average mass concentration of PM2.5 was 62.3 ± 37.2 µg m-3, and the emissions from mobile sources were more prominent. Carbonaceous particles accounted for 68.6% of the total particles and could be classified into 10 categories, with elemental carbon (EC) mixed with sulfate (EC-S) particles making the highest contribution (33.1%). EC particles rich in secondary components and organic carbon (OC) particles rich in secondary component exhibited different diurnal variations, suggesting different sources and mixing mechanisms. From "excellent" to "polluted" days, the contributions of EC-S, EC mixed with sulfate and nitrate (EC-SN) and OC mixed with EC (OC-EC) particles increased by 9.8%, 4.5% and 6.6%, respectively, and thus these particles are key targets for future pollution control. The potential source contribution of the southwest area was stronger than that of other areas, and the potential contribution of regional transport to EC-related particles was stronger than to OC-related particles. Most particles were highly mixed with sulfate or nitrate, and the level of secondary mixing further enhanced as pollution worsened.

Improving combination therapies: targeting A2B-adenosine receptor to modulate metabolic tumor microenvironment and immunosuppression.

BACKGROUND: We investigated the role of A2B-adenosine receptor in regulating immunosuppressive metabolic stress in the tumor microenvironment. Novel A2B-adenosine receptor antagonist PBF-1129 was tested for antitumor activity in mice and evaluated for safety and immunologic efficacy in a phase I clinical trial of patients with non-small cell lung cancer. METHODS: The antitumor efficacy of A2B-adenosine receptor antagonists and their impact on the metabolic and immune tumor microenvironment were evaluated in lung, melanoma, colon, breast, and epidermal growth factor receptor-inducible transgenic cancer models. Employing electron paramagnetic resonance, we assessed changes in tumor microenvironment metabolic parameters, including pO2, pH, and inorganic phosphate, during tumor growth and evaluated the immunologic effects of PBF-1129, including its pharmacokinetics, safety, and toxicity, in patients with non-small cell lung cancer. RESULTS: Levels of metabolic stress correlated with tumor growth, metastasis, and immunosuppression. Tumor interstitial inorganic phosphate emerged as a correlative and cumulative measure of tumor microenvironment stress and immunosuppression. A2B-adenosine receptor inhibition alleviated metabolic stress, downregulated expression of adenosine-generating ectonucleotidases, increased expression of adenosine deaminase, decreased tumor growth and metastasis, increased interferon γ production, and enhanced the efficacy of antitumor therapies following combination regimens in animal models (anti-programmed cell death 1 protein vs anti-programmed cell death 1 protein plus PBF-1129 treatment hazard ratio = 11.74 [95% confidence interval = 3.35 to 41.13], n = 10, P < .001, 2-sided F test). In patients with non-small cell lung cancer, PBF-1129 was well tolerated, with no dose-limiting toxicities; demonstrated pharmacologic efficacy; modulated the adenosine generation system; and improved antitumor immunity. CONCLUSIONS: Data identify A2B-adenosine receptor as a valuable therapeutic target to modify metabolic and immune tumor microenvironment to reduce immunosuppression, enhance the efficacy of immunotherapies, and support clinical application of PBF-1129 in combination therapies.

Chinese Herbal Medicine for Idiopathic Pulmonary Fibrosis: An Overview of Systematic Review.

Objective: To summarize the use of Chinese Herbal Medicines (CHMs) for Idiopathic Pulmonary Fibrosis (IPF) and provide high-level evidence for clinical decisions. Methods: We analyzed systematic reviews (SRs). Two English-language and three Chinese-language electronic databases were searched from inception to July 1, 2019. Published SRs and meta-analyses evaluating CHM use in IPF and reporting clinically-relevant outcomes such as lung function, PO2, and quality of life were eligible for inclusion in this overview. The methodological qualities of the included SRs were assessed by AMSTAR and ROBIS tools. Results: All reviews were published from 2008 to 2019. 15SRs were published in Chinese-language while 2 were in English. A total of 15550 participants were included. All intervention arms received CHM with or without conventional treatment and were compared with control arms with conventional treatment alone, or hormone therapy. Twelve SRs were assessed with low risk of bias while five were assessed high risk by ROBIS. The quality of evidence was assessed to be "moderate" or "low" or "very low" using GRADE. Conclusions: CHM has potential benefits for patients with IPF especially in improving lung function (forced vital capacity (FVC), total lung capacity (TLC), and diffusing capacity of the lungs for carbon monoxide (DLCO)), PO2 level, and the quality of life of patients. Due to the low methodological quality of reviews, our findings should be interpreted with caution.

Fabrication of carboxymethyl chitosan/oxidized carboxymethyl cellulose composite film and its assessment for coating preservation of strawberry.

In the current study, a novel chitosan-based composite, carboxymethyl chitosan (CMCHS)/oxidized carboxymethyl cellulose (OCMC) was fabricated and characterized. The composite film (CMCHS 1.5%w/v + OCMC 0.8%w/v) was more uniform and had better tensile properties, UV blocking, water vapor permeability, and antifungal properties than pure CMCHS film. Preservation experiments showed that the CMCHS/OCMC film was more efficient for retaining the quality decrease of strawberry during storage. By the end of 7 days' storage, the hardness, contents of organic acid, soluble solids, and reducing sugar of coated strawberries were increased by 35.1%, 38.5%, 14.1%, and 3.5%, respectively, compared to the control group; and the decay rate of strawberries in CMCHS/OCMC group also dropped to 36%, about 42% decrease than that in control, suggesting the promising application of CMCHS/OCMC composite in coating preservation.

Combined effects of lipase and Lactiplantibacillus plantarum 1-24-LJ on physicochemical property, microbial succession and volatile compounds formation in fermented fish product.

BACKGROUND: Studies have shown that either the addition of starter culture or enzyme can improve fermentation in fish or other products. However, little research has been carried out on the effects of coupling starter cultures with lipase on the microbial community and product quality. Suanzhayu is a Chinese fermented fish product that mainly relies on spontaneous fermentation, resulting in an unstable flavor and quality. The present study investigated the impact of lipase and Lactiplantibacillus plantarum 1-24-LJ on the quality of Suanzhayu. RESULTS: Inoculation decreased pH and 2-thiobarbituric acid reactive substances (TBARS) values, and also helped the dominance of the strain in the ecosystem, whereas lipase addition raised TBARS values and had little effect on pH, water activity (aw ) and microbiota. The addition of lipase and/or Lpb. plantarum increased the content of alcohols, aldehydes, ketones, esters and umami amino acids. The co-additions with the most significant effect and the total contents of volatile compounds (VCs) and free amino acids (FAAs) were 1801.92 g per 100 g and 21 357.05 mg per 100 g, respectively. Former-Lactobacillus was negatively correlated with pH, aw and Prevotella, but positively with VCs (ethyl ester of heptanoic acid, ethyl ester of octanoic acid) and FAAs (Tyr, Phe). Furthermore, adding Lpb. plantarum 1-24-LJ alone or in combination with lipase shortened the fermentation process. CONCLUSION: The present study provides a recommended Suanzhayu process approach for improving product quality and flavor, as well as shortening fermentation time, by adding Lpb. plantarum 1-24-LJ with or without lipase. © 2023 Society of Chemical Industry.

Transitioning Economic Statuses of Appalachian Counties during COVID-19.

In the past decade, the Appalachian economy in the United States was scarcely discussed in the literature. No studies were devoted to local economic development after the outbreak of the Coronavirus Disease in 2019. This paper fills the literature gap by empirically examining how the Appalachian economy transitioned under the influence of the pandemic. Using county-level data from the Appalachian Regional Commission between 2019 and 2022, the study investigates how the Appalachian economy regressed during the pandemic. Transitioning economy indices were calculated for 420 local counties by comparing their composite index values before and after the outbreak of the pandemic. Regressions were run to estimate the influences of the unemployment rate, per capita income, and the poverty rate. During the pandemic, the unemployment rate consistently had the largest impact on the Appalachian counties' composite index value and the least effect on the poverty rate. The results suggest that the most effective strategy is for the government to reduce the local unemployment rate to improve the economic ranking. Supplementary Information: The online version contains supplementary material available at 10.1007/s11293-022-09749-2.

COVID-19's impacts on business activities and female workers: Empirical evidence from global developing economies.

This paper empirically examines the economic impacts of COVID-19 on firms' business activities and female workers in 10 developing economies around the world. Based on a survey conducted by the World Bank, we constructed a firm-level panel dataset and investigated how firms' production and finances have developed during COVID-19. We also investigated female workers' employment situations and how they were affected by firm performance. COVID-19 indeed casted seriously adverse impacts in the developing world. As time passes, firms' production has been recovering, but their finances are worsening, and the female workers are facing worse situations in forms of higher probabilities of losing jobs and getting furloughed. Other variables such as workforce, capacity utilisation, and exports also play important roles in this process.

Metabolic reprogramming by adenosine antagonism and implications in non-small cell lung cancer therapy.

Non-small cell lung cancer (NSCLC) is a heterogeneous disease with genetic and environmental parameters that influence cell metabolism. Because of the complex interplay of environmental factors within the tumor microenvironment (TME) and the profound impact of these factors on the metabolic activities of tumor and immune cells, there is an emerging interest to advance the understanding of these diverse metabolic phenotypes in the TME. High levels of adenosine are characteristic of the TME, and adenosine can have a significant impact on both tumor cell growth and the immune response. Consistent with this, we showed in NSCLC data from TCGA that high expression of the A2BR leads to worse outcome and that expression of A2BR may be different for different mutation backgrounds. We then investigated the metabolic reprogramming of tumor cells and immune cells (T and dendritic cells) by adenosine. We used A2AR and A2BR antagonism or agonism as well as receptor knockout animals to explore whether these treatments altered specific immune compartments or conferred specific therapeutic vulnerabilities. Using the seahorse assay, we found that an A2BR antagonist modulates oxidative stress homeostasis in NSCLC cell lines. In addition, we found distinct metabolic roles of A2AR and A2BR receptors in T cell activation and dendritic cell maturation. These data suggest potential mechanisms and therapeutic benefits of A2 receptor antagonist therapy in NSCLC.

A Simple and Robust Protocol for in vitro Differentiation of Mouse Non-pathogenic T Helper 17 Cells from CD4+ T Cells.

Functional and mechanistic studies of CD4+ T cell lineages rely on robust methods of in vitro T cell polarization. Here, we report an optimized protocol for in vitro differentiation of a mouse non-pathogenic T helper 17 (TH17) cell lineage. Most of the previously established protocols require irradiated splenocytes as artificial antigen presenting cells (APC) for TCR activation. The protocol described here employs plate-bound antibodies and a TH17-polarizing cytokine cocktail to activate and differentiate naïve CD4+ T (Tnai) cells, reflecting a simple and robust protocol for in vitro TH17n differentiation. Using T cells that are genetically engineered with an IL-17 reporter, this protocol may enable the rapid production of a pure population of IL17-expressing CD4+ T cells for system biology studies and high-throughput functional screening.

Geostatistical model of the spatial distribution of arsenic in groundwaters in Gujarat State, India.

Geogenic arsenic contamination in groundwaters poses a severe health risk to hundreds of millions of people globally. Notwithstanding the particular risks to exposed populations in the Indian sub-continent, at the time of writing, there was a paucity of geostatistically based models of the spatial distribution of groundwater hazard in India. In this study, we used logistic regression models of secondary groundwater arsenic data with research-informed secondary soil, climate and topographic variables as principal predictors generate hazard and risk maps of groundwater arsenic at a resolution of 1 km across Gujarat State. By combining models based on different arsenic concentrations, we have generated a pseudo-contour map of groundwater arsenic concentrations, which indicates greater arsenic hazard (> 10 µg/L) in the northwest, northeast and south-east parts of Kachchh District as well as northwest and southwest Banas Kantha District. The total number of people living in areas in Gujarat with groundwater arsenic concentration exceeding 10 µg/L is estimated to be around 122,000, of which we estimate approximately 49,000 people consume groundwater exceeding 10 µg/L. Using simple previously published dose-response relationships, this is estimated to have given rise to 700 (prevalence) cases of skin cancer and around 10 cases of premature avoidable mortality/annum from internal (lung, liver, bladder) cancers-that latter value is on the order of just 0.001% of internal cancers in Gujarat, reflecting the relative low groundwater arsenic hazard in Gujarat State.

De novo synthesis and salvage pathway coordinately regulate polyamine homeostasis and determine T cell proliferation and function.

Robust and effective T cell-mediated immune responses require proper allocation of metabolic resources through metabolic pathways to sustain the energetically costly immune response. As an essential class of polycationic metabolites ubiquitously present in all living organisms, the polyamine pool is tightly regulated by biosynthesis and salvage pathway. We demonstrated that arginine is a major carbon donor and glutamine is a minor carbon donor for polyamine biosynthesis in T cells. Accordingly, the dependence of T cells can be partially relieved by replenishing the polyamine pool. In response to the blockage of biosynthesis, T cells can rapidly restore the polyamine pool through a compensatory increase in extracellular polyamine uptake, indicating a layer of metabolic plasticity. Simultaneously blocking synthesis and uptake depletes the intracellular polyamine pool, inhibits T cell proliferation, and suppresses T cell inflammation, indicating the potential therapeutic value of targeting the polyamine pool for managing inflammatory and autoimmune diseases.

Groundwater Arsenic Distribution in India by Machine Learning Geospatial Modeling.

Groundwater is a critical resource in India for the supply of drinking water and for irrigation. Its usage is limited not only by its quantity but also by its quality. Among the most important contaminants of groundwater in India is arsenic, which naturally accumulates in some aquifers. In this study we create a random forest model with over 145,000 arsenic concentration measurements and over two dozen predictor variables of surface environmental parameters to produce hazard and exposure maps of the areas and populations potentially exposed to high arsenic concentrations (>10 µg/L) in groundwater. Statistical relationships found between the predictor variables and arsenic measurements are broadly consistent with major geochemical processes known to mobilize arsenic in aquifers. In addition to known high arsenic areas, such as along the Ganges and Brahmaputra rivers, we have identified several other areas around the country that have hitherto not been identified as potential arsenic hotspots. Based on recent reported rates of household groundwater use for rural and urban areas, we estimate that between about 18-30 million people in India are currently at risk of high exposure to arsenic through their drinking water supply. The hazard models here can be used to inform prioritization of groundwater quality testing and environmental public health tracking programs.

Correction: Andrographis paniculata (Chuan Xin Lián) for symptomatic relief of acute respiratory tract infections in adults and children: A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0181780.].

Glutathione de novo synthesis but not recycling process coordinates with glutamine catabolism to control redox homeostasis and directs murine T cell differentiation.

Upon antigen stimulation, T lymphocytes undergo dramatic changes in metabolism to fulfill the bioenergetic, biosynthetic and redox demands of proliferation and differentiation. Glutathione (GSH) plays an essential role in controlling redox balance and cell fate. While GSH can be recycled from Glutathione disulfide (GSSG), the inhibition of this recycling pathway does not impact GSH content and murine T cell fate. By contrast, the inhibition of the de novo synthesis of GSH, by deleting either the catalytic (Gclc) or the modifier (Gclm) subunit of glutamate-cysteine ligase (Gcl), dampens intracellular GSH, increases ROS, and impact T cell differentiation. Moreover, the inhibition of GSH de novo synthesis dampened the pathological progression of experimental autoimmune encephalomyelitis (EAE). We further reveal that glutamine provides essential precursors for GSH biosynthesis. Our findings suggest that glutamine catabolism fuels de novo synthesis of GSH and directs the lineage choice in T cells.

Yinzhihuang oral liquid combined with phototherapy for neonatal jaundice: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Neonatal jaundice affects at least 481,000 newborns every year. Phototherapy is recommended but it's effects are limited and adverse reactions can occur. In China, phototherapy combined with Yinzhihuang oral liquid is also used for this condition. This systematic review evaluated the effectiveness and safety of combination therapy with Yinzhihuang oral liquid and phototherapy compared to phototherapy alone for treating neonatal jaundice. METHOD: A comprehensive literature search was performed in four Chinese databases, two English language databases and two trial registries from inception to June 2017. Two authors independently screened the citations and retrieved full publications for randomized trials on Yinzhihuang oral liquid combined with phototherapy for neonatal jaundice. The methodological quality of the trials was assessed according to the Cochrane Collaboration's tool for assessing risk of bias. Data were analyzed using RevMan 5.3. RESULT: Totally 17 trials (involving 2561 neonates) were included in this review. Fourteen of them had a high risk of bias. Significant differences were detected between combination therapy and phototherapy alone for serum bilirubin level (MD - 50.25 µmol/L, 95% CI -64.01 to - 36.50, I2 = 98%; 7 trials, post-hoc decision choosing random effects model), failure of jaundice resolution (RR 0.21, 95% CI 0.14 to 0.32, I2 = 0%; 11 trials, fixed effects model), and time to jaundice resolution (MD - 2.17 days, 95%CI -2.96 to - 1.38, I2 = 98%; 6 trials, random effects model). Adverse events were reported in eight trials but none were serious. Trial sequential analysis for serum bilirubin level suggested that the cumulative Z-curve (which represents 1478 participants) reached the required information size (DARIS = 1301 participants). CONCLUSION: Based on trials with low methodological quality, Yinzhihuang oral liquid combined with phototherapy seemed to be safe and superior to phototherapy alone for reducing serum bilirubin in neonatal jaundice. These potential benefits need to be confirmed in future trials using rigorous methodology. TRIAL REGISTRATION: Systematic review registration: [PROSPERO registration: CRD42016037691 ].

Sub-lethal effects of six neonicotinoids on avoidance behavior and reproduction of earthworms (Eisenia fetida).

Avoidance behavior of earthworms (Eisenia fetida) against six neonicotinoids (NEOs) (acetamiprid, dinotefuram, clothianidin, thiacloprid, nitenpyram, imidacloprid) was studied following the protocol of ISO. The results showed obvious avoidance behavior of E. fetida against the tested insecticides, and the medium effective concentration for avoidance behavior (EC50) of the six pesticides was 0.14, 0.55, 0.91, 7.87, 1.32 and 0.77 mg/kg, respectively. Compared to the acute toxicity, avoidance behavior was more sensitive as an indicator of soil contamination with NEOs. Chronic toxicity of above six NEOs to E. fetida was also evaluated; cocoon production, hatchability, cocoon weight and adult weight were all affected in the test. Cocoon production and hatchability were more sensitive than cocoon weight and adult weight. The reproduction of earthworms were significantly reduced with a 56 d half-maximal effective hatchability concentration (EC50) of 0.37, 0.74, 1.30, 3.57, 1.20 and 0.70 mg/kg (acetamiprid, dinotefuram, clothianidin, thiacloprid, nitenpyram, imidacloprid), respectively. Most of the tested NEOs were highly toxic to E. fetida. Avoidance behavior and reproduction damage of E. fetida was observed at very low concentrations. The existing levels of pollution with NEOs in soil frequently exceed the lowest observed adverse effect concentrations, which are likely to have negative biological and ecological impacts on earthworms.

Metabolic Reprogramming in Modulating T Cell Reactive Oxygen Species Generation and Antioxidant Capacity.

A robust adaptive immune response requires a phase of proliferative burst which is followed by the polarization of T cells into relevant functional subsets. Both processes are associated with dramatically increased bioenergetics demands, biosynthetic demands, and redox demands. T cells meet these demands by rewiring their central metabolic pathways that generate energy and biosynthetic precursors by catabolizing and oxidizing nutrients into carbon dioxide. Simultaneously, oxidative metabolism also produces reactive oxygen species (ROS), which are tightly controlled by antioxidants and plays important role in regulating T cell functions. In this review, we discuss how metabolic rewiring during T cell activation influence ROS production and antioxidant capacity.

Andrographis paniculata (Chuan Xin Lián) for symptomatic relief of acute respiratory tract infections in adults and children: A systematic review and meta-analysis.

INTRODUCTION: Antimicrobial resistance (AMR) is a substantial threat to public health. Safe and effective alternatives are required to reduce unnecessary antibiotic prescribing. Andrographis Paniculata (A. Paniculata, Chuan Xin Lián) has traditionally been used in Indian and Chinese herbal medicine for cough, cold and influenza, suggesting a role in respiratory tract infections (RTIs). This systematic review aimed to evaluate the clinical effectiveness and safety of A. Paniculata for symptoms of acute RTIs (ARTIs). MATERIALS AND METHODS: English and Chinese databases were searched from their inception to March 2016 for randomised controlled trials (RCTs) evaluating oral A. Paniculata without language barriers (Protocol ID: CRD42016035679). The primary outcomes were improvement in ARTI symptoms and adverse events (AEs). A random effects model was used to pool the mean differences and risk ratio with 95% CI reported. Methodological quality was evaluated using the Cochrane risk of bias tool; two reviewers independently screened eligibility and extracted data. RESULTS: Thirty-three RCTs (7175 patients) were included. Most trials evaluated A. Paniculata (as a monotherapy and as a herbal mixture) provided commercially but seldom reported manufacturing or quality control details. A. Paniculata improved cough (n = 596, standardised mean difference SMD: -0.39, 95% confidence interval CI [-0.67, -0.10]) and sore throat (n = 314, SMD: -1.13, 95% CI [-1.37, -0.89]) when compared with placebo. A. Paniculata (alone or plus usual care) has a statistically significant effect in improving overall symptoms of ARTIs when compared to placebo, usual care, and other herbal therapies. Evidence also suggested that A. Paniculata (alone or plus usual care) shortened the duration of cough, sore throat and sick leave/time to resolution when compared versus usual care. No major AEs were reported and minor AEs were mainly gastrointestinal. The methodological quality of included trials was overall poor. CONCLUSIONS: A. Paniculata appears beneficial and safe for relieving ARTI symptoms and shortening time to symptom resolution. However, these findings should be interpreted cautiously owing to poor study quality and heterogeneity. Well-designed trials evaluating the effectiveness and potential to reduce antibiotic use of A. Paniculata are warranted.

Oral administration of Chinese herbal medicine during gestation period for preventing hemolytic disease of the newborn due to ABO incompatibility: A systematic review of randomized controlled trials.

BACKGROUND: About 85.3% of hemolytic disease of the newborn (HDN) is caused by maternal-fetal ABO blood group incompatibility. However, there is currently no recommended "best" therapy for ABO incompatibility during pregnancy. OBJECTIVES: To systematically assess the safety and effectiveness of oral Chinese herbal medicine (CHM) for preventing HDN due to ABO incompatibility. METHODS: The protocol of this review was registered on the PROSPERO website (No. CRD42016038637).Six databases were searched from inception to April 2016. Randomized controlled trials (RCTs) of CHM for maternal-fetal ABO incompatibility were included. The primary outcome was incidence of HDN. The Cochrane risk of bias tool was used to assess the methodological quality of included trials. Risk ratios (RR) and mean differences with 95% confidence interval were used as effect measures. Meta-analyses using Revman 5.3 software were conducted if there were sufficient trials without obvious clinical or statistical heterogeneity available. RESULTS: Totally 28 RCTs involving3413 women were included in the review. The majority of the trials had unclear or high risk of bias. Our study found that the rate of HDN and the incidence of neonatal jaundice might be 70% lower in the herbal medicine group compared with the usual care group (RR from 0.25 to 0.30).After treatment with herbal medicine, women were twice as likely to have antibody titers lower than 1:64 compared with women who received usual care(RR from 2.15 to 3.14) and the umbilical cord blood bilirubin level in the herbal medicine group was 4umol/L lower than in those receiving usual care. There was no difference in Apgar scores or birthweights between the two groups. CONCLUSIONS: This review found very low-quality evidence that CHM prevented HDN caused by maternal-fetal ABO incompatibility. No firm conclusions can be drawn regarding the effectiveness or safety of CHM for this condition.

The Antiproliferative and Colony-suppressive Activities of STAT3 Inhibitors in Human Cancer Cells Is Compromised Under Hypoxic Conditions.

Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been indicated as a novel cancer drug target, since it plays an important role in diverse oncogenic processes including survival, cell proliferation and migration. Emerging STAT3 inhibitors have demonstrated efficacy in cancer cells and animal tumor models. It is well known that most solid tumors are characterized by hypoxia, but it is not clear if hypoxic conditions affect activity of STAT3 inhibitors. To examine this, two STAT3 inhibitors were tested to investigate their inhibitory efficacy in cancer cells grown under hypoxic conditions compared with those without hypoxia. Cell proliferation, colony formation and western blot assays were performed to examine the differences in the cell viability, proliferation and proteins in the STAT3 pathway. Under hypoxic conditions, the half-maximal inhibitory concentration values for both STAT3 inhibitors were increased compared to normoxic conditions in human pancreatic cancer, medulloblastoma and sarcoma cell lines. In addition, the ability of both STAT3 inhibitors to inhibit colony formation in pancreatic cancer, medulloblastoma and sarcoma cell lines was reduced under hypoxic conditions when compared to cells under normoxic conditions. Furthermore, there was an increase in phosphorylated STAT3 levels in cancer cells under hypoxic conditions, suggesting this may be one of the mechanisms of resistance. In summary, the results presented here provide a novel finding of STAT3 inhibitor activity under hypoxic conditions and indicate that under such low oxygen conditions, the anticancer efficacy of STAT3 inhibitors was indeed hampered. These results highlight the need to develop new therapeutic strategies to overcome the resistance of cancer cells to STAT3 inhibitors under hypoxic conditions.