Palladium-Catalyzed Electrochemical Iodination of 1-Arylpyridine N-Oxides.

The palladium-catalyzed C-H iodination of 1-arylpyridine N-oxides proceeded under electrochemical oxidation conditions using I2 as an iodine source. The reaction of isoquinoline N-oxides possessing various para- or meta-substituted aryl groups at the 1-position proceeded to give the corresponding iodination products. Electron-donating groups on the aryl group facilitated the reaction to give relatively high yields of the product. The reaction was also found to be applicable to 2-aryl-3-picoline N-oxides.

Photochromism and Photomagnetism in Two Ni(II) Complexes Based on a Photoactive 2,4,6-Tris-2-Pyridyl-1,3,5-Triazine Ligand.

It is still challenging to construct novel photochromic and photomagnetic materials in the field of molecular materials. Herein, the 2,4,6-tris-2-pyridyl-1,3,5-triazine (TPTz) molecule was found to display photochromic properties under room temperature light irradiation. Two mononuclear structures, [Ni(H2O)(TPTz)(C2O4)]·2H2O (1; C2O42- = oxalate) [Ni(H2O)(TPTz)(C2O4)]·0.5H2O (2), and one chain compound [Ni(TPTz)(H2-HEDP)]·2H2O (3; HEDP = hydroxyethylidene diphosphonate) were obtained by assembling TPTz with polydentate O-ligands (oxalate and phosphonate) and the paramagnetic Ni2+ ions. The electron-transfer (ET)-dominated photochromism was observable in 1 and 2 after light irradiation with the photogeneration of relatively stable radicals, and the resultant photochromism was demonstrated via UV-vis, photoluminescence, X-ray photoelectron spectra, electron paramagnetic resonance spectra, and molecular orbital calculations. Due to the denser stacking interactions between the adjacent organic molecules, 2 exhibited a faster photochromic rate than 1. Compared with 1 and 2, compound 3 did not show photochromic behavior, which was deciphered by the theoretical calculations for all of the compounds. Importantly, the magnetic couplings appeared between photogenerated radicals and paramagnetic Ni2+ ions, resulting in a scarcely photomagnetic phenomenon of 1 and 2 in the Ni-based electron transfer photochromic materials. This work enriches the available kind of ligands for the design of ET photochromic materials, putting forward a method to tune the electron transfer photochromic efficiency in the molecular materials.

Development and characterization of anti-galectin-9 antibodies that protect T cells from galectin-9-induced cell death.

Antibodies that target immune checkpoint proteins such as programmed cell death protein 1, programmed death ligand 1, and cytotoxic T-lymphocyte-associated antigen 4 in human cancers have achieved impressive clinical success; however, a significant proportion of patients fail to respond to these treatments. Galectin-9 (Gal-9), a ß-galactoside-binding protein, has been shown to induce T-cell death and facilitate immunosuppression in the tumor microenvironment by binding to immunomodulatory receptors such as T-cell immunoglobulin and mucin domain-containing molecule 3 and the innate immune receptor dectin-1, suggesting that it may have potential as a target for cancer immunotherapy. Here, we report the development of two novel Gal-9-neutralizing antibodies that specifically react with the N-carbohydrate-recognition domain of human Gal-9 with high affinity. We also show using cell-based functional assays that these antibodies efficiently protected human T cells from Gal-9-induced cell death. Notably, in a T-cell/tumor cell coculture assay of cytotoxicity, these antibodies significantly promoted T cell-mediated killing of tumor cells. Taken together, our findings demonstrate potent inhibition of human Gal-9 by neutralizing antibodies, which may open new avenues for cancer immunotherapy.

Sequential condensation and double desulfonylative cyclopropanation of 1,2-bis(sulfonylmethyl)arenes with 3-arylacroleins: access to biscyclopropane-fused tetralins.

Efficient tBuOK-mediated sequential condensation and double desulfonylative cyclopropanation of readily accessible 1,2-bis(sulfonylmethyl)arenes with 3-arylacroleins is described. This high-yielding, single-step strategy provides a variety of polysubstituted biscyclopropane-fused tetralins with six contiguous stereogenic centers via the construction of five carbon-carbon single bonds. A plausible mechanism is proposed and discussed. In the overall reaction process, water and sulfinic acid salts were generated as the byproducts.

ß-arrestin2 deficiency ameliorates S-100-induced autoimmune hepatitis in mice by inhibiting infiltration of monocyte-derived macrophage and attenuating hepatocyte apoptosis.

Autoimmune hepatitis (AIH) is a progressive hepatitis syndrome characterized by high transaminase levels, interface hepatitis, hypergammaglobulinemia, and the presence of autoantibodies. Misdiagnosis or delayed treatment of AIH can lead to cirrhosis or liver failure, which poses a major risk to human health. ß-Arrestin2, a key scaffold protein for intracellular signaling pathways, has been found to be involved in many autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. However, whether ß-arrestin2 plays a role in AIH remains unknown. In the present study, S-100-induced AIH was established in both wild-type mice and ß-arrestin2 knockout (Arrb2 KO) mice, and the experiments identified that liver ß-arrestin2 expression was gradually increased, and positively correlated to serum ANA, ALT and AST levels during AIH progression. Furthermore, ß-arrestin2 deficiency ameliorated hepatic pathological damage, decreased serum autoantibody and inflammatory cytokine levels. ß-arrestin2 deficiency also inhibited hepatocyte apoptosis and prevented the infiltration of monocyte-derived macrophages into the damaged liver. In vitro experiments revealed that ß-arrestin2 knockdown suppressed the migration and differentiation of THP-1 cells, whereas ß-arrestin2 overexpression promoted the migration of THP-1 cells, which was regulated by the activation of the ERK and p38 MAPK pathways. In addition, ß-arrestin2 deficiency attenuated TNF-α-induced primary hepatocyte apoptosis by activating the Akt/GSK-3ß pathway. These results suggest that ß-arrestin2 deficiency ameliorates AIH by inhibiting the migration and differentiation of monocytes, decreasing the infiltration of monocyte-derived macrophages into the liver, thereby reducing inflammatory cytokines-induced hepatocytes apoptosis. Therefore, ß-arrestin2 may act as an effective therapeutic target for AIH.

Incorporating field-based research into remote learning: An assessment of soil lead pollution in different land-use types in Los Angeles.

A research-based course was developed to investigate the legacy of soil lead (Pb) pollution in Los Angeles, California. During the course, undergraduate and graduate students collected a total of 270 soil samples for analyses of metal (loid) concentrations in different land-use types (residential, park, and school). Residential soils had significantly higher Pb concentrations than other land uses (p < 0.01) exceeding the California recommended safety level for soil Pb (80 mg/kg) at the highest frequency (64% of samples), followed by schools (42%) and parks (6.0%). Soil Pb from all 87 census block groups was correlated with battery recycling plant and railroad proximity as geospatial indicators of childhood Pb exposure risk. Meanwhile, census block groups with higher Pb levels were correlated with higher percentages of the following population: those without health insurance, without college degrees, with a lower median household income and income below the poverty line, and ethnic and racial minorities (r = -0.46 to 0.59, p < 0.05). Principal component regression models significantly improved soil Pb estimation over correlation analysis by incorporating sociodemographic, economic, and geospatial risk factors for Pb exposure (R2 = 0.58, p < 0.05). This work provides new insights into how topsoil Pb prevails in various land-use types and their co-occurring sociodemographic, economic, and geospatial risk factors, indicating the need for multi-scalar assessment across urban land uses.

RNA methyltransferase BmMettl3 and BmMettl14 in silkworm (Bombyx mori) and the regulation of silkworm embryonic development.

N6-methyladenosine (m6A) is a ubiquitous reversible epigenetic RNA modification that plays an important role in regulating many biological processes, especially embryonic development. However, regulation of m6A methylation during silkworm embryonic development and diapause remains to be investigated. In this study, we analyzed the phylogeny of subunits of methyltransferases BmMettl3 and BmMettl14, and detected the expression patterns of BmMettl3 and BmMettl14 in different tissues and at different developmental stages in silkworm. To investigate the function of m6A on the development of silkworm embryo, we analyzed the m6A/A ratio in diapause and diapause termination eggs. The results showed that BmMettl3 and BmMettl14 were highly expressed in gonads and eggs. Moreover, the expression of BmMettl3 and BmMettl14 and the m6A/A ratio were significantly increased in diapause termination eggs compared with diapause eggs in the early stage of silkworm embryonic development. Furthermore, in BmN cell cycle experiments, the percentage of cells in the S phase increased when lacking BmMettl3 or BmMettl14. This work contributes to understanding the role of m6A methylation during insect embryogenesis and gametogenesis. It also provides a research orientation to further analyze the role of m6A methylation in diapause initiation and termination during insect embryonic development.

Effects of Mindfulness-Based Elder Care (MBEC) on symptoms of depression and anxiety and spiritual well-being of institutionalized seniors with disabilities: a randomized controlled trial.

BACKGROUND: Despite the need to incorporate seniors from various settings into mindfulness-based empirical research, issues of geriatric frailties and non-compliance remain. This study aimed to evaluate the effects of a mindfulness-based elder care (MBEC) program on mental health and spiritual well-being among seniors with disabilities in long-term care residential settings. METHODS: This single-blind, randomized controlled trial (RCT) randomly assigned seventy-seven participants into an MBEC group or control group of an eight-week MBEC program. Participants were assessed every four weeks at baseline (T0), mid-intervention (T1), post-intervention (T2) and follow-up (T3) using the Geriatric Depression Scale Short Form (GDS-SF), the State-Trait Anxiety Inventory (STAI) and the Spiritual Well-Being Scale (SWBS), respectively. RESULTS: Linear mixed model (LMM) showed that MBEC participants' mental health improved significantly after completing the intervention; compared with controls, the MBEC group exhibited significantly lower anxiety (state-anxiety at T2; trait-anxiety at T2 and T3) and fewer depressive symptoms. Spiritual well-being was also significantly enhanced compared to that in the control group. CONCLUSIONS: MBEC has positive effects on both mental health and spiritual well-being outcomes among seniors with disabilities. In long-term care facilities, seniors with abilities have the potential to adhere to and engage in activities of a mindfulness-based intervention. This low risk, easily accessible, and effective 8-week program is recommended to be integrated into regular long-term care institutional routines. TRIAL REGISTRATION: This study was registered with Clinical Trial Registry (ClinicalTrials.gov - U.S. National Library of Medicine #NCT05123261. Retrospectively registered on 07/04/2021.). The CONSORT 2010 guidelines were used in this study for properly reporting how the randomized trial was conducted.

COVID-related dysphonia and persistent long-COVID voice sequelae: A systematic review and meta-analysis.

PURPOSE: Dysphonia is a common symptom due to the coronavirus disease of the 2019 (COVID-19) infection. Nonetheless, it is often underestimated for its impact on human's health. We conducted this first study to investigate the global prevalence of COVID-related dysphonia as well as related clinical factors during acute COVID-19 infection, and after a mid- to long-term follow-up following the recovery. METHODS: Five electronic databases including PubMed, Embase, ScienceDirect, the Cochrane Library, and Web of Science were systematically searched for relevant articles until Dec, 2022, and the reference of the enrolled studies were also reviewed. Dysphonia prevalence during and after COVID-19 infection, and voice-related clinical factors were analyzed; the random-effects model was adopted for meta-analysis. The one-study-removal method was used for sensitivity analysis. Publication bias was determined with funnel plots and Egger's tests. RESULTS: Twenty-one articles comprising 13,948 patients were identified. The weighted prevalence of COVID-related dysphonia during infection was 25.1 % (95 % CI: 14.9 to 39.0 %), and male was significantly associated with lower dysphonia prevalence (coefficients: -0.116, 95 % CI: -0.196 to -0.036; P = .004) during this period. Besides, after recovery, the weighted prevalence of COVID-related dysphonia declined to 17.1 % (95 % CI: 11.0 to 25.8 %). 20.1 % (95 % CI: 8.6 to 40.2 %) of the total patients experienced long-COVID dysphonia. CONCLUSIONS: A quarter of the COVID-19 patients, especially female, suffered from voice impairment during infection, and approximately 70 % of these dysphonic patients kept experiencing long-lasting voice sequelae, which should be noticed by global physicians.

Minimally invasive, single-stage, multilevel surgery for obstructive sleep apnoea: A systematic review and meta-analysis.

OBJECTIVES: Minimally invasive, single-staged multilevel surgery (MISS MLS) could be an optimal treatment for selected patients with obstructive sleep apnea (OSA). We aim to systematically review the efficacy of MISS MLS for patients with OSA, as well as the clinical outcomes and possible complications in OSA patients before and after MISS MLS. DESIGN AND SETTING: Systematic review and meta-analysis. Six databases were searched, and the PRISMA guideline was followed. PARTICIPANTS: Patients with OSA receiving MISS MLS. MAIN OUTCOME MEASURES: The random-effects model was adopted for the statistical synthesis. The percentage and 95% confidence interval (CI) were adopted as the effect measurements of MISS MLS for OSA. Subgroup analyses and sensitivity analyses were also performed to identify the heterogeneity among the studies. RESULTS: There were initially 154 articles for identification. Eventually, six studies with a total of 848 OSA patients completely met the inclusion criteria and were further enrolled for analysis. The pooled analysis showed statistically significant lower AHI (apnea/hypopnea index, /hr.; mean difference: -8.931, 95% CI: -11.591 to -6.271, I2 = 87.4%), ESS (mean difference: -2.947, 95% CI: -4.465 to -1.429, I2 = 94.9%), and snoring severity with 0-10 visual analog scale after surgery (mean difference: -4.966, 95% CI: -5.804 to -4.128, I2 = 96.4%). The success rate was 46% in mild/moderate OSA; however, 18% in severe OSA. There were no major complications occurred. CONCLUSIONS: The acceptable surgical outcomes, esp. in mild/moderate OSA, and rare complications are the major advantages of MISS MLS. The evidence of this study could aid the decision making in selecting suitable treatment programs for OSA patients.

Buckling-induced wavy optical fiber attenuator.

An optical attenuator is an optical device that can modulate the power level of an optical signal. Based on the macro-bending loss of optical fibers, we present a wavy fiber attenuator where the attenuation level can be controlled by a mechanical-induced buckling of the fiber. By bonding a fiber to a prestretched substrate and then releasing the prestrain, the fiber flexes into a sinusoidal wavy curve due to the constraints of the substrate. The level of the light attenuation can simply be controlled by stretching the substrate. The maximum attenuation of the proposed wavy optical fiber attenuator is -87.3 dB.

Environmentally benign cinchonain IIa from Uncaria laevigata for corrosion inhibition of Q235 steel in HCl corrosive medium: Experimental and theoretical investigation.

Traditional corrosion inhibitors make great contribution to metal protection, but also cause environmental pollution. To solve the problem, plant extracts as green corrosion inhibitors have attracted much attention in recent years. Plants are good raw materials for corrosion inhibitors and also meet the requirements of industry. However, they have not been successfully applied in industry due to the unknown composition of the effective corrosion inhibitors and large dosage thereof. Therefore, cinchonain IIa was separated from Uncaria laevigata with abundant sources and low cost from nature in this work. Here we hypothesized that cinchonain IIa could show good corrosion inhibition performance for Q235 steel in the acidic medium. Through experiments and theoretical calculation, we studied the corrosion inhibition effect of cinchonain IIa on Q235 in 1 M HCl solution at 298 K for 48 h. Electrochemical experiments revealed that the inhibition efficiency of 200 mg/L cinchonain IIa in 1 M HCl for Q235 steel was 94.08% for 48 h. It even showed over 93% corrosion inhibition efficiency and durable protection performance to 28 d. Surface observations indicated that cinchonain IIa were firmly attached to the steel surface by forming a protective film. Moreover, quantum chemical calculation and molecular dynamics simulation revealed the inhibition mechanism at molecular and atomic level. Compared with some plant extracts, here we demonstrate that the outstanding advantages of cinchonain IIa include sustained protective effect, small dosage, and low toxicity. Accordingly, it may be used as a green industrial corrosion inhibitor with great potential in oilfield acidification and acid pickling.

Fe3O4-Mg(OH)2 nanocomposite as a scavenger for silver nanoparticles: Rational design, facile synthesis, and enhanced performance.

Silver nanoparticles (AgNPs) are considered as emerging contaminants because of their high toxicity and increasing environmental impact. Removal of discharged AgNPs from water is crucial for mitigating the health and environmental risks. However, developing facile, economical, and environment-friendly approaches remains challenging. Herein, an Fe3O4-Mg(OH)2 nanocomposite, as a novel magnetic scavenger for AgNPs, was prepared by loading Fe3O4 nanoparticles on Mg(OH)2 nanoplates in a one-pot synthesis. Batch removal experiments revealed that the maximum removal capacities for the two model AgNPs (citrate- or polyvinylpyrrolidone-coated AgNPs) were 476 and 442 mg/g, respectively, corresponding to partition coefficients 8.03 and 4.89 mg/g/µM. Removal feasibilities over a wide pH range of 5-11 and in real water matrices and scavenger reusability with five cycles were also confirmed. Both Fe3O4 and Mg(OH)2 components contributed to the removal; however, their nanocomposites exhibited an enhanced performance because of the high specific surface area and pore volume. Chemical adsorption and electrostatic attraction between the coatings on the AgNPs and the two components in the nanocomposite was considered to be responsible for the removal. Overall, the facile synthesis, convenient magnetic separation, and high removal performance highlight the great potential of the Fe3O4-Mg(OH)2 nanocomposite for practical applications.

miR-144-3p ameliorates the progression of osteoarthritis by targeting IL-1ß: Potential therapeutic implications.

The pro-inflammatory cytokine interleukin 1 beta (IL-1ß) plays a critical role in osteoarthritis (OA) disease pathogenesis. MicroRNA (miRNA) activity is related to inflammation in OA and some miRNAs specifically regulate IL-mediated degradation of cartilage type II collagen. Previous studies have indicated that miR-144-3p is a useful target in the regulation of pro-inflammatory cytokines in different diseases. However, the role of miR-144-3p in OA is unclear. In this study, we observed a negative correlation between miR-144-3p and IL-1ß expression in OA. miR-144-3p mimic transfection of OA synovial fibroblasts downregulated levels of IL-1ß expression, while blocking the MAPK, PI3K/Akt, and NF-κB signaling pathways relating to IL-1ß production, and effectively increased miR-144-3p expression in OASFs. Findings from an anterior cruciate ligament transection rat model revealed that administration of miR-144-3p mimic effectively ameliorated OA progression and reduced the numbers of IL-1ß-positive cells in synovial tissue. This study suggests that miR-144-3p is a useful therapeutic target in OA disease.

Spectral shaping of fiber Bragg gratings based on non-rigid origami.

We present a spectrum-tunable fiber Bragg grating (FBG) based on a unique compress-twist deformation mode of non-rigid origami. By applying axial displacement on the FBG-bonded Kresling-ori, a non-uniform strain field emerges. The mechanics-induced non-uniform strain can shift the wavelength of an apodized unchirped FBG and/or transform an apodized unchirped FBG to a chirped one. For the spectrum-shaping mode, the bandwidth of the FBG was tuned from 0.32 nm up to 2.9 nm, measured at the -6dB level. For the wavelength-shift mode, a maximum wavelength shift of 0.6 nm can be achieved.

H2O2 induces nuclear transport of the receptor tyrosine kinase c-MET in breast cancer cells via a membrane-bound retrograde trafficking mechanism.

Reactive oxygen species (ROS) are cellular by-products produced from metabolism and also anticancer agents, such as ionizing irradiation and chemotherapy drugs. The ROS H2O2 has high rates of production in cancer cells because of their rapid proliferation. ROS oxidize DNA, protein, and lipids, causing oxidative stress in cancer cells and making them vulnerable to other stresses. Therefore, cancer cell survival relies on maintaining ROS-induced stress at tolerable levels. Hepatocyte growth factor receptor (c-MET) is a receptor tyrosine kinase overexpressed in malignant cancer types, including breast cancer. Full-length c-MET triggers a signal transduction cascade from the plasma membrane that, through downstream signaling proteins, up-regulates cell proliferation and migration. Recently, c-MET was shown to interact and phosphorylate poly(ADP-ribose) polymerase 1 in the nucleus and to induce poly(ADP-ribose) polymerase inhibitor resistance. However, it remains unclear how c-MET moves from the cell membrane to the nucleus. Here, we demonstrate that H2O2 induces retrograde transport of membrane-associated full-length c-MET into the nucleus of human MCF10A and MCF12A or primary breast cancer cells. We further show that knocking down either coatomer protein complex subunit γ1 (COPG1) or Sec61 translocon ß subunit (SEC61ß) attenuates the accumulation of full-length nuclear c-MET. However, a c-MET kinase inhibitor did not block nuclear c-MET transport. Moreover, nuclear c-MET interacted with KU proteins in breast cancer cells, suggesting a role of full-length nuclear c-MET in ROS-induced DNA damage repair. We conclude that a membrane-bound retrograde vesicle transport mechanism facilitates membrane-to-nucleus transport of c-MET in breast cancer cells.

Pan-cancer analysis of iron metabolic landscape across the Cancer Genome Atlas.

Iron is an essential metal ion in the human body and usually dysregulated in cancers. However, a comprehensive overview of the iron-related genes and their clinical relevance in cancer is lacking. In this study, we utilized the expression profiling, proteomics, and epigenetics from the Cancer Genome Atlas database to systematically characterized the alterations of iron-related genes. There were multiple iron-related genes with dysregulation across 14 cancers and some of these ectopic changes may be associated with aberrant DNA methylation. Meanwhile, a variety of genes were significantly associated with patient survival, especially in kidney renal clear cell carcinoma. Then differentially expressed genes were validated in clinical samples. Finally, we found deferoxamine and erastin could inhibit proliferation in various tumor cells and influence the expression of several iron-related genes. Overall, our study provides a comprehensive analysis of iron metabolism across cancers and highlights the potential treatment of iron targeted therapies for cancers.

SMAD3 Hypomethylation as a Biomarker for Early Prediction of Colorectal Cancer.

The incidence and mortality rates of colorectal cancer (CRC) have been high in recent years. Prevention and early detection are crucial for decreasing the death rate. Therefore, this study aims to characterize the alteration patterns of mothers against decapentaplegic homolog 3 (SMAD3) in patients with CRC and its applications in early detection by using a genome-wide methylation array to identify an aberrant hypomethylation site in the intron position of the SMAD3 gene. Quantitative methylation-specific polymerase chain reaction showed that hypomethylated SMAD3 occurred in 91.4% (501/548) of Taiwanese CRC tissues and 66.6% of benign tubular adenoma polyps. In addition, SMAD3 hypomethylation was observed in 94.7% of patients with CRC from The Cancer Genome Atlas dataset. A decrease in circulating cell-free methylation SMAD3 was detected in 70% of CRC patients but in only 20% of healthy individuals. SMAD3 mRNA expression was low in 42.9% of Taiwanese CRC tumor tissues but high in 29.4% of tumors compared with paired adjacent normal tissues. Hypomethylated SMAD3 was found in cancers of the digestive system, such as liver cancer, gastric cancer, and colorectal cancer, but not in breast cancer, endometrial cancer, and lung cancer. In conclusion, SMAD3 hypomethylation is a potential diagnostic marker for CRC in Western and Asian populations.

Mysm1 epigenetically regulates the immunomodulatory function of adipose-derived stem cells in part by targeting miR-150.

Adipose-derived stem cells (ASCs) are highly attractive for cell-based therapies in tissue repair and regeneration because they have multilineage differentiation capacity and are immunosuppressive. However, the detailed epigenetic mechanisms of their immunoregulatory capacity are not fully defined. In this study, we found that Mysm1 was induced in ASCs treated with inflammatory cytokines. Adipose-derived stem cells with Mysm1 knockdown exhibited attenuated immunosuppressive capacity, evidenced by less inhibition of T cell proliferation, more pro-inflammatory factor secretion and less nitric oxide (NO) production in vitro. Mysm1-deficient ASCs exacerbated inflammatory bowel diseases but inhibited tumour growth in vivo. Mysm1-deficient ASCs also showed depressed miR-150 expression. When transduced with Mysm1 overexpression lentivirus, ASCs exhibited enhanced miR-150 expression. Furthermore, Mysm1-deficient cells transduced with lentivirus containing miR-150 mimics produced less pro-inflammatory factors and more NO. Our study reveals a new role of Mysm1 in regulating the immunomodulatory activities of ASCs by targeting miR-150. These novel insights into the mechanisms through which ASCs regulate immune reactions may lead to better clinical utility of these cells.

Comprehensive analysis of microRNA-messenger RNA regulatory network in gemcitabine-resistant bladder cancer cells.

Chemotherapy is still a standard treatment of unresectable bladder cancer or distant metastases. The chemotherapy resistance always occurs after a period of treatment indicating poor prognosis. The current study aimed to explore the molecular mechanism of chemoresistance in bladder cancer cells. The gene expression profiles of GSE77883, including three untreated T24 cells samples and three gemcitabine-resistant T24 cells samples, was downloaded from Gene Expression Omnibus database. The screening of differentially expressed genes (DEGs), gene function analysis, and interaction prediction between microRNAs (miRNAs) and DEGs were performed by R software. The protein-protein interaction (PPI) and miRNA-DEGs networks were constructed and visualized by Cytoscape software. Then, the small molecules, with potential synergistic or antagonistic effects to gemcitabine resistance, were identified using the Connectivity Map database. Finally, gemcitabine-resistant T24 cell line was established and key genes were validated by quantitative real-time polymerase chain reaction (qRT-PCR). In total, 536 upregulated and 513 downregulated genes were screened and mainly enriched in oxidative stress response and signaling pathways related to extracellular matrix-receptor interaction and focal adhesion. PPI network showed interleukin 6, tumor necrosis factor, kinesin family member 11, and BUB1 mitotic checkpoint serine/threonine kinase B were key genes. The miRNA-DEGs regulatory networks included 18 miRNAs and 185 DEGs, including miR-182-5p, miR-590-3p, miR-320a and serum- and glucocorticoid-regulated kinase 1 (SGK1). Then, the related key genes and miRNAs were confirmed by qRT-PCR. Furthermore, 81 small molecules with antagonistic or synergistic effect to GEM were screened. We have investigated the molecular mechanisms driving GEM-resistance in bladder cancer cells that would contribute to the development of chemotherapy for advanced bladder cancer.