Publications by authors named "Xiang Qin"

215 Publications

Liposomal valinomycin mediated cellular K leak promoting apoptosis of liver cancer cells.

J Control Release 2021 Jul 24;337:317-328. Epub 2021 Jul 24.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China. Electronic address:

Most cancer therapies are suffering from side effects to varying degrees, which might compromise the body functions and long-term health of patients. Balancing treatment efficacy and side effects has become a priority. Inspired by the concept that cellular ion homeostasis can lead to apoptosis, we developed a novel therapeutic strategy by incorporating the K transporter valinomycin into liposomes (Lipo-VM). Valinomycin is a naturally occurring polypeptide showing good biodegradation in vivo with reduced long-term side effects. Lipo-VM facilitates the K efflux of cells and triggers a caspase-dependent pathway of apoptosis by causing the collapse of mitochondrial membrane potential. With the help of a liposome-based nano-delivery system, Lipo-VM shows enhanced cell uptake and accumulation at the tumor site, which results in significant inhibition of tumor growth in a liver cancer model. The proposed valinomycin-anchored liposome provides an efficient and safe approach for cancer therapy.
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http://dx.doi.org/10.1016/j.jconrel.2021.07.037DOI Listing
July 2021

Cancer cells escape p53's tumor suppression through ablation of ZDHHC1-mediated p53 palmitoylation.

Oncogene 2021 Jul 19. Epub 2021 Jul 19.

Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

The inactivation of tumor-suppressor genes contributes heavily to oncogenesis. The mutation of TP53 has been well-studied and recognized as a major factor in the development of tumors. Yet other means of p53 inactivation has not been well-elucidated. We previously identified a hypermethylated gene ZDHHC1 that suppresses tumor growth when the expression was restored, but the specific mechanism was yet to be found. The protein product of ZDHHC1 is an S-palmitoyltransferase and we have identified p53 as a substrate for ZDHHC1-mediated palmitoylation, specifically at the C135, C176, and C275 residues. The novel form of post-translational modification of p53 is required for the nuclear translocation of the tumor suppressor. p53 recruited DNMT3A to ZDHHC1 promoter and is responsible for the hypermethylation of ZDHHC1. The epigenetic feedback loop formed by ZDHHC1 and p53 sheds light on the inactivation of p53 without the presence of genetic mutations.
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http://dx.doi.org/10.1038/s41388-021-01949-5DOI Listing
July 2021

Transmission event of SARS-CoV-2 Delta variant reveals multiple vaccine breakthrough infections.

medRxiv 2021 Jul 12. Epub 2021 Jul 12.

Importance: Vaccine breakthrough by an emergent SARS-CoV-2 variant poses a great risk to global public health.

Objective: To determine the SARS-CoV-2 variant responsible for 6 cases of vaccine breakthrough.

Design: Nasopharyngeal swabs from suspected vaccine breakthrough cases were tested for SARS-CoV-2 by qPCR for Wuhan-Hu1 and Alpha variant. Positive samples were then sequenced by Swift Normalase Amplicon Panels to determine the causal variant.

Setting: Transmission event occurred at events surrounding a wedding outside of Houston, TX. Two patients from India, likely transmitted the Delta variant to other guests.

Participants: Following a positive SARS-CoV-2 qPCR test at a third-party site, six fully vaccinated patients were investigated. Three males and three females ranged from 53 to 69 years old. One patient suffered from diabetes while three others were classified as overweight. No significant other comorbidities were identified. None of the patients had a history of failed vaccination.

Key Points: Which SARS-CoV-2 variant is responsible for 6 cases of vaccine breakthrough, one interventional monoclonal antibody treatment, and one death? Viral sequencing revealed 6 vaccinated patients were infected with the Delta SARS-CoV-2 variant. With no histories of vaccine breakthrough, this suggests Delta variant may possess immune evasion in patients that received the Pfizer BNT162b2, Moderna mRNA-1273, and Covaxin BBV152. Delta variant may pose the highest risk out of any currently circulating SARS-CoV-2 variants, with increased transmissibility over Alpha variant and possible vaccine breakthrough.
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http://dx.doi.org/10.1101/2021.06.28.21258780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282118PMC
July 2021

A variant in the 3'-untranslated region of the MC2R gene decreases the risk of schizophrenia in a female Han Chinese population.

J Int Med Res 2021 Jul;49(7):3000605211029504

Department of Basic Biology, Changsha Medical College, Changsha, China.

Objective: Schizophrenia is a complex mental disorder with high heritability. The hypothalamic-pituitary-adrenal (HPA) axis, which is the stress system of the neuroendocrine system, is considered to impact psychotic disorders. We hypothesized that polymorphisms of HPA axis genes might be involved in the development of schizophrenia.

Methods: A case-control study comprising 234 patients with schizophrenia and 399 matched healthy controls was conducted to investigate the association between the human melanocortin 2 receptor (MC2R) gene and schizophrenia risk. Seven tag single nucleotide polymorphisms (SNPs) (rs16941303, rs16941314, rs2186944, rs28926188, rs7230126, rs948322, and rs948331) of MC2R were genotyped by direct sequencing.

Results: No significant associations were observed between any of the alleles, genotypes, or haplotypes examined within the MC2R gene and the risk of schizophrenia in the total group or in subgroups stratified by smoking or alcoholism. However, a subgroup analysis stratified by sex revealed that under the additive model, the C allele of the MC2R rs948331 SNP significantly decreased the risk of schizophrenia in females (odds ratio=0.18).

Conclusion: The C allele of the MC2R rs948331 locus may be a protective factor, reducing the risk of schizophrenia in the female Han Chinese population.
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http://dx.doi.org/10.1177/03000605211029504DOI Listing
July 2021

Protective autophagy attenuates soft substrate-induced apoptosis through ROS/JNK signaling pathway in breast cancer cells.

Free Radic Biol Med 2021 Jul 6;172:590-603. Epub 2021 Jul 6.

Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 610054, Sichuan, PR China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072, Sichuan, PR China. Electronic address:

Tumor microenvironments are characterized not only in terms of chemical composition, but also by physical properties such as stiffness, which influences morphology, proliferation, and fate of tumor cells. However, the underlying mechanisms between matrix stiffness and the apoptosis-autophagy balance remain largely unexplored. In this study, we cultured human breast cancer MDA-MB-231 cells on rigid (57 kPa), stiff (38 kPa) or soft (10 kPa) substrates and demonstrated that increasing autophagy levels and autophagic flux in the cells cultured on soft substrates partly attenuated soft substrate-induced apoptosis. Mechanistically, this protective autophagy is regulated by intracellular reactive oxygen species (ROS) accumulation, which triggers the downstream signals of JNK, Bcl-2 and Beclin-1. More importantly, soft substrate-induced activation of ROS/JNK signaling promotes cell apoptosis through the mitochondrial pathway, whereas it increases protective autophagy by suppressing the interaction of Bcl-2 and Beclin-1. Taken together, our data suggest that JNK is the mediator of soft substrate-induced breast cancer cell apoptosis and autophagy which is likely to be the mechanism that partly attenuates mitochondrial apoptosis. This study provides new insights into the molecular mechanism by which autophagy plays a protective role against soft substrate-induced apoptosis in human breast cancer cells.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.07.005DOI Listing
July 2021

Hf-Nd-Sr Isotopic Composition of the Tibetan Plateau Dust as a Fingerprint for Regional to Hemispherical Transport.

Environ Sci Technol 2021 Jul 6;55(14):10121-10132. Epub 2021 Jul 6.

State Key Laboratory of Cryosphere Sciences, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou 730000, China.

Large areas of arid regions in the Tibetan Plateau (TP) are undergoing desertification and subsequent aeolian emission and transport. The contribution of TP soils to the atmospheric aerosol burden in Asia and elsewhere is not known. Here, we use Hf, Nd, and Sr isotopes to distinguish the TP from other Asian dust-producing regions and compare the signatures to sediments in major dust sink regions. We found that the Hf-Nd-Sr isotopes of TP soils showed unique spatial signatures. From north to south, Sr/Sr ratios gradually increased, while ε and ε values gradually decreased; from west to east, Sr/Sr and ε gradually increased, while ε changed indistinctly. The Hf-Nd-Sr isotopic compositions of TP soils were controlled by four geographic isotope regions: the northern, southern, western, and eastern TP. Compared with Asian large deserts, the TP showed a unique isotopic composition, which together exhibited a significant spatial change across Asia. Compared to dust isotopes in prominent sink areas, we found that the TP is an important dust source to eastern TP glaciers, the Chinese Loess Plateau, South China Sea, Japan, and Greenland. This study provides clear isotopic evidence that the TP is a major aeolian contributor in the Northern Hemisphere and may have important implications for the global aeolian cycle.
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http://dx.doi.org/10.1021/acs.est.0c04929DOI Listing
July 2021

Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis.

N Engl J Med 2021 07;385(1):46-58

From the Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens (E.K., M.A.D.); the Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, and the Department of Molecular Medicine, University of Pavia, Pavia, Italy (G.P., G.M.); the Department of Hematology, University Medical Center Utrecht, University Utrecht, Utrecht (M.C.M.), the Amyloidosis Center of Expertise, University of Groningen, University Medical Center Groningen, Groningen (W.R.), and Janssen Research and Development, Leiden (B.T., J. Vermeulen) - all in the Netherlands; University College London, London (A.D.W.); Centre Hospitalier Universitaire (CHU) and Reference Center for AL Amyloidosis, Limoges (A.J.), Département de Néphrologie et Transplantation d'Organes, Centre de Référence des Maladies Rénales Rares, Hôpital Rangueil, CHU de Toulouse, Toulouse (A.H.), and the Department of Hematology, CHU Lille, University of Lille, Lille (S.M.) - all in France; the Department of Lymphoma and Myeloma, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston (H.C.L.); the Amyloidosis Center, Boston University School of Medicine and Boston Medical Center (V.S.), and the Division of Hematology/Oncology, John C. Davis Myeloma and Amyloid Program, Tufts Medical Center (R.L.C.) - both in Boston; the Victorian and Tasmanian Amyloidosis Service, Department of Haematology, Monash University Eastern Health Clinical School, Melbourne, VIC (S.G.), the Department of Haematology, Princess Alexandra Hospital and University of Queensland Medical School, Brisbane (P.M.), and the Department of Clinical Haematology, Westmead Hospital, Westmead, NSW (F.K.) - all in Australia; Cross Cancer Institute, University of Alberta, Edmonton (C.P.V.), the Division of Hematology, London Health Sciences Centre, London Regional Cancer Program, Western University, London, ON (S.L.), and the Division of Hematology, Vancouver General Hospital, BC Cancer, University of British Columbia, Vancouver (K. Song) - all in Canada; Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Collaborative Innovation Center of Hematology, Beijing (J.L.); Medical Department V (Hematology/Oncology/Rheumatology), Amyloidosis Center, Heidelberg University Hospital, Heidelberg (S.S.), and Hämatologisch-Onkologische Praxis Altona, Hamburg (T.H.) - both in Germany; the Department of Hematology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem (M.E.G.); the Department of Hematology, Japanese Red Cross Medical Center, Tokyo (K. Suzuki), and the Department of Hematology, Japan Community Health Care Organization Kyoto Kuramaguchi Medical Center, Kyoto (C.S.) - both in Japan; the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine (K.K.), and the Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine (J.-S.K.) - both in Seoul, South Korea; the Amyloidosis and Myeloma Unit, Hospital Clinic of Barcelona, August Pi i Sunyer Biomedical Research Institute, Barcelona (M.T.C.); the Department of Hematology, Ankara University, Ankara, Turkey (M.B.); the Division of Medical Oncology, Department of Medicine, University of Washington, Seattle (E.L.); the Department of Hematology and Medical Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland (J. Valent), and the Division of Hematology, Ohio State University Comprehensive Cancer Center, Columbus (N.B.) - both in Ohio; Clínica São Germano, São Paulo (V.H.), and Clinica CEHON, Rede D'Or Oncologia, Salvador (E.C.) - both in Brazil; the Department of Medicine, University of California, San Francisco, San Francisco (S.W.W.), the Department of Hematology and Hematopoietic Cell Transplantation, Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope, Duarte (M.R.), and Janssen Research and Development, Los Angeles (N.T.) - all in California; the Department of Internal Medicine, Division of Hematology/Oncology, Columbia University Medical Center, New York (D.B.); the Penn Amyloidosis Program, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia (A.J.W.), and Janssen Research and Development, Spring House (X.Q., S.Y.V., B.M.W.) - both in Pennsylvania; Vanderbilt University Medical Center and Veterans Affairs Tennessee Valley Healthcare System, Nashville (S.A.G.); the Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit (J.A.Z.); the Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland (K.J.); and Genmab US, Princeton (T.A.), and Janssen Research and Development, Raritan (J.M.S., S.H.Z.) - both in New Jersey.

Background: Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease.

Methods: We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response.

Results: A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P<0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P = 0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.9%, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7.8% and 4.3%, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%). Systemic administration-related reactions to daratumumab occurred in 7.3% of the patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy.

Conclusions: Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression. (Funded by Janssen Research and Development; ANDROMEDA ClinicalTrials.gov number, NCT03201965.).
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http://dx.doi.org/10.1056/NEJMoa2028631DOI Listing
July 2021

Multistage-responsive nanovehicle to improve tumor penetration for dual-modality imaging-guided photodynamic-immunotherapy.

Biomaterials 2021 Aug 24;275:120990. Epub 2021 Jun 24.

Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 610054, Sichuan, PR China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072, Sichuan, PR China. Electronic address:

The exploration of an intelligent multifunctional imaging-guided therapeutic platform is of great significance because of its ideal delivery efficiency and controlled release. In this work, a tumor microenvironment (TME)-responsive nanocarrier (denoted as [email protected]) is designed for on-demand, sequentially release of a short D-peptide antagonist of programmed cell death-ligand 1 (named as PPPA-1) and a photosensitizer methylene blue (MB). FeO-Au located in the core of [email protected] is used as a magnetic resonance imaging and micro-computed tomography imaging contrast agent for noninvasive diagnosis of solid tumors and simultaneous monitoring of drug delivery. The PPPA-1 coated on [email protected] can be shed due to the cleavage of the peptide substrate by matrix metalloproteinase-2 (MMP-2) that is highly expressed in the tumor stroma, and disulfide bonding is further broken when it encounters high levels of glutathione (GSH) in TME, which finally leads to significant size reduction and charge-reversal. These transitions facilitate penetration and uptake of nanocarriers against tumors. Noticeably, the released PPPA-1 can block the immune checkpoint to create an environment that favors the activation of cytotoxic T lymphocytes and augment the antitumor immune response elicited by photodynamic therapy, thus significantly improving therapeutic outcomes. Studies of the underlying mechanisms suggest that the designed MMP-2 and GSH-sensitive delivery system not only induce apoptosis of tumor cells but also modulate the immunosuppressive tumor microenvironment to eventually augment the suppression tumor metastasis effect of CD8 cytotoxic T cells. Overall, the visualization of the therapeutic processes with comprehensive information renders [email protected] an intriguing platform to realize the combined treatment of metastatic tumors.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120990DOI Listing
August 2021

Construction of wood-based cellulose micro-framework composite form-stable multifunctional materials with thermal and electrical response via incorporating erythritol-urea (thiourea)-carbon nanotubes.

Int J Biol Macromol 2021 Aug 24;184:538-550. Epub 2021 Jun 24.

State Key Laboratory of Featured Metal Resources and Advanced Materials, Guangxi University, Nanning 530004, China; Guangxi Key Laboratory of Processing for Non-ferrous Metals and Featured Materials, Guangxi University, Nanning 530004, China; School of Resources, Environment and Materials, Guangxi University, Nanning 530004, China. Electronic address:

In this study, two kinds of form-stable multifunctional materials with thermal and electrical response (FPCMs: DP-E7U3-CNT, DP-E7T3-CNT) are composed of wood-based honeycomb-like celluloses micro-framework (DP), carbon nanotubes (CNT), erythritol-urea (E7U3) or erythritol-thiourea (E7T3). In FPCMs, DP acts as a skeleton structure to seal E7U3 and E7T3 and provide more pathways for heat conduction. The CNT acts as an extended surface to further improve thermal conductivity. FE-SEM showed that the honeycomb-like pore structure of DP was completely filled with E7U3, E7T3 and CNT. FTIR and XRD analysis show that there is only a combination of physical interactions between the components of FPCMs. DSC curves and thermal conductivity analysis results show that DP-E7U3-1.5CNT and DP-E7T3-1.5CNT with the mass fraction of carbon nanotubes (1.5 wt%) have the highest latent heat values (230.3 J/g, 272.2 J/g) and thermal conductivity (0.9832 W/(m·K), 0.9363 W/(m·K)). Both DP-E7U3-1.5CNT and DP-E7T3-1.5CNT exhibit high latent heat retention and thermal stability after 100 heating-cooling cycles. In addition, DP-E7U3-1.5CNT and DP-E7T3-1.5CNT show excellent performance in light-heat energy conversion-storage, actual latent heat storage and release, thermal and electrical response performance, which make it has great potential to be multifunctional materials with thermal storage sand electrical response.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.150DOI Listing
August 2021

Shear stress triggered circular dorsal ruffles formation to facilitate cancer cell migration.

Arch Biochem Biophys 2021 Sep 22;709:108967. Epub 2021 Jun 22.

Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 610054, Sichuan, PR China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072, Sichuan, PR China. Electronic address:

Circular dorsal ruffles (CDRs) are a kind of special ring-shaped membrane structure rich in F-actin, it is highly involved in the invasion-metastasis of tumor. Shear stress is one of the biophysical elements that affects the fate of tumor cells. However, how shear stress contributes to the CDRs formation is still unclear. In this study, we found that shear stress stimulated the formation of CDRs and promoted the migration of human breast MDA-MB-231 carcinoma cells. Integrin-linked kinase (ILK) mediated the recruiting of ADP-ribosylation factors (ARAP1/Arf1) to CDRs. Meanwhile, the transfection of ARAP1 or Arf1 mutant decreased the number of cells with CDRs, the CDRs areas and perimeters, thus blocked the cancer cell migration. This indicated that the ARAP1/Arf1 were necessary for the CDRs formation and cancer cell migration. Further study revealed that shear stress could stimulate the formation of intracellular macropinocytosis (MPS) thus promoted the ARAP1/Arf1 transportation to early endosome to regulate cancer cell migration after the depolymerization of CDRs. Our study elucidates that the CDRs formation is essential in shear stress-induced breast cancer cell migration, which provides a new research target for exploring the cytoskeletal mechanisms of breast cancer malignance.
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http://dx.doi.org/10.1016/j.abb.2021.108967DOI Listing
September 2021

SWIM domain protein ZSWIM4 is required for JAK2 inhibition resistance in breast cancer.

Life Sci 2021 Aug 5;279:119696. Epub 2021 Jun 5.

Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China; Department of Pathology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, Guangdong, China; Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou 510282, Guangdong, China. Electronic address:

Aims: Janus kinase 2 (JAK2)/signal transducer and activator of transcription (STAT) signaling plays a critical role in the progression of breast cancer. However, a small part of tumor cells survived from the killing effect of JAK2 inhibitor. We aimed to find out the mechanism of drug resistance in breast cancer cells and develop new therapeutic strategies.

Materials And Methods: The anti-tumor effect of TG101209 in breast cancer cells was confirmed by cell counting kit 8 and flow cytometry. Western blotting was used to determine the up-regulation of zinc finger SWIM-type containing 4 (ZSWIM4) induced by TG101209. In vitro and in vivo experiments were performed to evaluate the role of ZSWIM4 in the resistance of breast cancer cells to TG101209. Through the determination and analysis of 50% inhibiting concentration (IC) curves, the effect of combination therapy was confirmed.

Key Findings: Our data indicate that the elevated expression of ZSWIM4 contributes to JAK2 inhibition resistance, as knockdown of ZSWIM4 significantly enhances the sensitivity of breast cancer cells to TG101209 and over-expression of this gene mitigates the killing effect. Furthermore, the expression of vitamin D receptor (VDR) and utilization of 1α,25-(OH)2VD3 is decreased in ZSWIM4-knockdown breast cancer cells. VDR-silencing or GW0742-mediated blockade of VDR activity can partially reverse the JAK2 inhibition resistance.

Significance: Our data implicated that ZSWIM4 might be an inducible resistance gene of JAK2 inhibition in breast cancer cells. The combination of JAK2 inhibitor and VDR inhibitor may achieve better coordinated therapeutic effect in breast cancer.
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http://dx.doi.org/10.1016/j.lfs.2021.119696DOI Listing
August 2021

Black carbon and dust in the Third Pole glaciers: Revaluated concentrations, mass absorption cross-sections and contributions to glacier ablation.

Sci Total Environ 2021 Oct 21;789:147746. Epub 2021 May 21.

Institute of International Rivers and Eco-security, Yunnan University, Kunming, Yunnan 650091, China; Yunnan Key Laboratory of International Rivers and Transboundary Eco-security, Yunnan University, Kunming 650091, China.

In snow and ice, light-absorbing particles (LAPs), such as black carbon (BC) and dust, accelerate the melting of Third Pole glaciers (TPGs). In this study, we revaluated LAP concentrations in the snow pits of TPGs (SP-TPGs), measured LAP mass absorption cross-sections (MACs), and simulated their effects on glacier darkening and melting based on the Spectral Albedo Model for Dirty Snow and a surface energy and mass balance model. The results indicated that because of their short distances to emission sources, the average BC concentrations measured in snow pits in the periphery of Third Pole were much higher than those measured in the inland Tibetan Plateau, and the average dust concentrations generally decreased from north to south. The average MACs of BC in the SP-TPGs varied from 3.1 to 7.7 m g at 550 nm, most of the average spectral values were comparable in the visible and near-infrared bands to those calculated by Mie theory, except those in Urumqi Glacier No. 1 (UR), Syek Zapadniy Glacier (SZ), and Laohugou Glacier No.12 (LH), while the average spectral MACs of dust in the SP-TPGs were considerably smaller in magnitude than most of the variations measured in other regions. Compared with the pure snow surfaces, BC and dust played comparable roles in reducing albedo in UR, SZ, LH, and Renlongba Glacier, whereas BC was the most prominent absorber in the other glaciers. The combined effect of BC and dust accelerated melting by 30.4-345.9 mm w.e. (19.7-45.3% of the total mass balance) through surface albedo darkening (0.06-0.17) and increased radiation absorption (25.8-65.7 W m) within one month of the ablation season. This study provides a new data set of LAP concentrations and MACs and helps to clarify the roles of these factors in the cryospheric environment of the Third Pole.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147746DOI Listing
October 2021

Hirsutanol A inhibits T-acute lymphocytic leukemia Jurkat cell viability through cell cycle arrest and p53-dependent induction of apoptosis.

Exp Ther Med 2021 Jul 11;22(1):741. Epub 2021 May 11.

State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, Macau SAR, P.R. China.

Acute lymphocytic leukemia (ALL) is a type of childhood leukemia with the highest incidence; T-acute lymphocytic leukemia (T-ALL) is far more difficult to treat than B-acute lymphocytic leukemia (B-ALL) and has a poor long-term prognosis. Therefore, there is an urgent requirement to develop effective drugs for the treatment of T-ALL. Hirsutanol A is a natural sesquiterpenoid compound. The aim of the present study was to evaluate the anticancer activity of hirsutanol A against T-acute lymphocytic leukemia Jurkat cells and investigate the mechanism of action. A Cell Counting Kit-8 assay demonstrated that hirsutanol A inhibited the viability of Jurkat cells in a dose- and time-dependent manner. In addition, hirsutanol A induced cell cycle arrest at the G phase as determined via flow cytometry. Furthermore, Hoechst staining, Annexin V-FITC/propidium iodide double staining, mitochondrial membrane potential detection using JC-1 and western blot analysis of apoptotic proteins indicated that the inhibitory effect of hirsutanol A on Jurkat cells was associated with the induction of apoptosis. Of note, hirsutanol A induced the expression of the tumor suppressor p53, whereas simultaneous treatment with pifithrin-α, an inhibitor of p53, significantly reduced Jurkat cell apoptosis induced by hirsutanol A. In summary, the present study suggested that hirsutanol A inhibited Jurkat cell viability through induction of cell cycle arrest and p53-dependent initiation of apoptosis, thus hirsutanol may serve as a promising compound for the treatment of T-ALL.
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http://dx.doi.org/10.3892/etm.2021.10173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138276PMC
July 2021

The Effect of Oral Vitamin A Supplementation on Chalazion in Young Children with Vitamin A Deficiency: A Pilot Study.

J Ocul Pharmacol Ther 2021 Jul-Aug;37(6):354-359. Epub 2021 May 27.

Department of Ophthalmology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Basis of Child Development and Critical Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing, China.

Many researchers have reported that vitamin A (VA) deficiency is related to chalazion. The purpose of this article is to clarify the effects of VA supplementation on chalazion in young children with VA deficiency. Forty-eight young children with VA deficiency suffering from chalazia were enrolled from our previous studies and were followed continuously for 1 year. Serum VA levels and recurrence of chalazion were observed. The mean serum VA levels increased after supplementation ( = 2.17E-15). The mean serum VA levels of subjects who experienced recurrence were lower than those without recurrence ( = 0.015). The recurrence rate and the mean recurrent frequency after supplementation were lower than before supplementation ( = 0.01,  = 6E-6); the mean time to the first recurrence of subjects without recurrence was longer after supplementation than before supplementation ( < 0.01). Oral VA supplementation could reduce the recurrence of chalazion in young children with preexisting VA deficiency.
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http://dx.doi.org/10.1089/jop.2020.0115DOI Listing
May 2021

lncRNA-Associated Competitive Endogenous RNA Regulatory Network in an Aβ-Induced AD Mouse Model Treated with Tripterygium Glycoside.

Neuropsychiatr Dis Treat 2021 19;17:1531-1541. Epub 2021 May 19.

Department of Basic Biology, Changsha Medical College, Changsha, People's Republic of China.

Background: Tripterygium glycoside (TG) has been suggested to have protective effects on the diseases of the central nervous system including Alzheimer's disease (AD). The mechanisms involving lncRNA-associated competing endogenous RNAs (ceRNAs) were shown to play important roles in the development of AD. However, the ceRNA mechanism of TG in treating AD is still unknown. Thus, we aimed to explore the ceRNA mechanism in the treatment of AD with TG.

Methods: A total of 32 C57BL/6J mice were administered 3 µL of Aβ (dual side, 1 mg/mL) by a single stereotactic injection in the brain to conduct AD mouse model. AD mouse models were randomly selected and divided into the AD+normal saline (NS) group (n=16) and the AD+TG group (n=16). The expression data of lncRNAs, mRNAs, and miRNAs in the hippocampus of mice from AD+NS group (n=3) and the AD+TG group (n=3) were obtained by microarray analysis. The MuTaME method was used to predict the ceRNA regulatory network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the DAVID database. A protein-protein interaction (PPI) network was constructed by using STRING software.

Results: TG can significantly improve spatial memory and inhibit the production of p-tau in an Aβ-induced AD mouse model. A total of 661 differentially expressed lncRNAs, 503 mRNAs, and 13 miRNAs were identified. A ceRNA network involving the top 200 mRNA-miRNA-lncRNA pairs with 16 lncRNAs, 11 miRNAs, and 52 mRNAs was visualized. And a PPI network complex filtered 26 gene nodes in DEGs was predicted.

Conclusion: We have identified 503 DEGs, 661 DElncRNAs, and 13 DEmiRNAs during treatment with TG in Aβ-induced AD mouse model. A ceRNA network based on the DElncRNAs, DEmRNAs, and DEmiRNAs was conducted, which provided new insight into the lncRNA-mediated ceRNA regulatory mechanisms underlying the effects of TG in the treatment of AD.
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http://dx.doi.org/10.2147/NDT.S310271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141406PMC
May 2021

Isomeric Dibenzoheptazethrenes for Air-Stable Organic Field-Effect Transistors.

Angew Chem Int Ed Engl 2021 Jul 15;60(29):16230-16236. Epub 2021 Jun 15.

Institute of Molecular Plus, Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Tianjin university, 92 Weijin Road, Tianjin, 300072, China.

Singlet diradicaloids hold great potential as semiconductors for organic field-effect transistors (OFETs). However, their relative low material and device stabilities impede the practical applications. Here, to achieve balanced stability and performance, two isomeric dibenzoheptazethrene derivatives with singlet diradical character were synthesized in a concise manner. Benefitting from the aromatic stabilization, both compounds display a small diradical character and large singlet-triplet gap, as corroborated by variable-temperature electron paramagnetic resonance spectra, single-crystal analysis, and theoretical calculations. OFET devices based on single crystals showed a high hole mobility of 0.15 cm  V  s , which is the highest for zethrene-based semiconductors. Both isomers exhibited remarkable material stability in air-saturated solutions as well as excellent bias-stress and storage stability in device under ambient air.
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http://dx.doi.org/10.1002/anie.202105872DOI Listing
July 2021

Mercury sources and physicochemical characteristics in ice, snow, and meltwater of the Laohugou Glacier Basin, China.

Environ Sci Pollut Res Int 2021 May 13. Epub 2021 May 13.

Institute of Research and Development, Duy Tan University, Da Nang, 550000, Vietnam.

In this work, samples of surface snow, surface ice, snow pit and meltwater from the Laohugou Glacier No. 12 on the northern edge of Tibetan Plateau (TP) were collected during the summer of 2015. The average concentration of Hg in surface snow/ice was 22.41 ng L, while the percentage of dissolved mercury (Hg) was observed to be around 26%. An altitudinal magnification of Hg was not observed for surface snow; however, in contrast, a significant positive magnification of Hg with altitude was observed in the surface ice. A higher concentration of Hg corresponded with the dust layer of the snow pit. It was observed that about 42% of Hg was lost from the surface snow when the glacier was exposed to sunlight within the first 24 h indicating some Hg was emitted back to the atmosphere while some were percolated downwards. The result from the principal component analysis (PCA) showed that the sources of Hg in Laohugou Glacier No. 12 were from crustal and biomass burning. Finally, it was estimated that total export of Hg from the outlet river of Laohugou glacier No. 12 in the year 2015 was about 1439.46 g yr with yield of 22.77 μg m yr. This study provides valuable insights for understanding the behavior of Hg in the glacier of the northern Tibetan Plateau.
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http://dx.doi.org/10.1007/s11356-021-14334-2DOI Listing
May 2021

Salidroside overcomes dexamethasone resistance in T-acute lymphoblastic leukemia cells.

Exp Ther Med 2021 Jun 15;21(6):636. Epub 2021 Apr 15.

Department of Pediatric Hematology, The Affiliated Hospital of Southwest Medical University and Birth Defects Clinical Medical Research Center of Sichuan Province, Luzhou, Sichuan 646000, P.R. China.

The aim of the present study was to analyze whether the use of salidroside (SAL) could overcome dexamethasone (DEX) resistance in T-acute lymphocytic leukemia cells. The human T-ALL DEX-resistant cell line, CEM-C1 and the DEX-sensitive cell line, CEM-C7 were used in the current study. The proliferation inhibition rates in these cells, treated with SAL and DEX alone, and in combination were detected using a Cell Counting Kit-8 assay, while the morphological changes of the cells were observed using an inverted microscope. Reverse transcription-quantitative PCR was used to detect the mRNA expression levels of the c-Myc and LC3 genes, while flow cytometry was used to detect the cell cycle distribution and the rate of apoptosis. In addition, western blot analysis was used to detect the protein expression levels of c-Myc, BCL-2, Bax, cleaved PARP and LC3. and acridine orange staining was used to detect the changes in acidic autophagy vesicles. It was found that SAL could effectively inhibit cell proliferation and induce apoptosis in the CEM-C1 and CEM-C7 cells. In addition, SAL promoted the induction of autophagy. The protein expression levels of c-Myc in the CEM-C1 cells were significantly higher compared with that in the CEM-C7 cells. SAL downregulated the mRNA expression levels of the c-Myc gene and protein in a dose-dependent manner. This suggested that SAL could inhibit the proliferation of the CEM-C1 and CEM-C7 cells, induce apoptosis and autophagy and overcome DEX resistance in the CEM-C1 cells. The mechanism may be associated with the downregulation of c-Myc.
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http://dx.doi.org/10.3892/etm.2021.10068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097222PMC
June 2021

Synthesis of an organic-inorganic hybrid with short organic molecular chains by sol-gel chemistry.

J Mech Behav Biomed Mater 2021 08 29;120:104567. Epub 2021 Apr 29.

College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, 225002, China. Electronic address:

An oligomer with short organic molecular chains was successfully synthesized with KH550 and KH560. This oligomer was combined with tetraethyl orthosilicate and calcium chloride to prepare an organic-inorganic hybrid biological material (OI-BM) by sol-gel chemistry. The hybrid was fully characterized by a series of instrumental characterizations including nuclear magnetic resonance spectrometry, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray energy spectroscopy and inductively coupled plasma spectrometry. OI-BM presented elastic deformation under compression. The elastic modulus and ultimate stress of OI-BM were 0.4 ± 0.1 GPa and 23.0 ± 4.0 MPa, respectively, lower than those of 45S5 bioactive glass (45S5-BG), whereas the strain at failure and modulus of toughness of OI-BM was about 4.5 times and 4 times higher. The hybrid is easy to form due to the improved mechanical property, suggesting excellent machining properties. The hybrid OI-BM produced hydroxyapatite in 1 h in simulated body fluid due to its excellent bioactivity. CCK-8 assay further demonstrated the desirable cytocompatibility of the hybrid. Thus, the hybrid can be a potential material for satisfying the mechanical property requirement of an implant.
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http://dx.doi.org/10.1016/j.jmbbm.2021.104567DOI Listing
August 2021

ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis.

J Exp Clin Cancer Res 2021 Apr 30;40(1):150. Epub 2021 Apr 30.

Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing, 400016, Yuzhong District, China.

Background: Among the common preventable cancers of women, cervical cancer has the highest morbidity. It is curable if detected at an early stage. However, reliable diagnostic and prognostic markers, which relate to physiologic and pathologic regulation of cervical cancer, are not available. In this study, one such potential marker, ZBTB28, was evaluated for its potential usefulness in cervical cancer assessment.

Methods: Public database analysis, reverse-transcription polymerase chain reaction (PCR), and methylation-specific PCR were employed to analyze ZBTB28 expression and promoter methylation. The importance of ZBTB28 in cervical cancer cells was assessed by cellular and molecular analysis in vitro and in vivo.

Results: This study assessed the anti-tumor effects of the transcription factor, ZBTB28, which is often silenced in cervical cancer due to CpG methylation of its promoter. We found ZBTB28 to directly affect cervical cancer cell proliferation, apoptosis, autophagy, and tumorigenesis. Also, it increased cancer cell chemosensitivity to Paclitaxel, Cisplatin, and 5-fluorouracil. Ectopic ZBTB28 expression inhibited the growth of cervical cancer xenografts in nude mice. Furthermore, electron microscopy demonstrated ZBTB28 to induce autophagosomes in cervical cancer cells. ZBTB28 induced cellular autophagy by the degradation of Bcl-XL, reduction of the Bcl-XL-BECN1 complex, and by interaction with the autophagy-related gene FIP200. ZBTB28-induced autophagy of cervical cancer cells was shown to mediate cellular apoptosis through the regulation of FIP200.

Conclusion: These findings identify ZBTB28 as a tumor suppressor gene that can induce autophagy-related apoptosis in cervical cancer cells. As such, ZBTB28 may be a target for the treatment of uterine-cervical carcinoma. Further, ZBTB28 promoter methylation analysis may offer a new objective strategy for cervical cancer screening.
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http://dx.doi.org/10.1186/s13046-021-01948-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086320PMC
April 2021

Tumor suppressor DRD2 facilitates M1 macrophages and restricts NF-κB signaling to trigger pyroptosis in breast cancer.

Theranostics 2021 5;11(11):5214-5231. Epub 2021 Mar 5.

Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Breast cancer (BrCa) is the most common cancer worldwide, and the 5-year relative survival rate has declined in patients diagnosed at stage IV. Advanced BrCa is considered as incurable, which still lack effective treatment strategies. Identifying and characterizing new tumor suppression genes is important to establish effective prognostic biomarkers or therapeutic targets for late-stage BrCa. RNA-seq was applied in BrCa tissues and normal breast tissues. Through analyzing differentially expressed genes, DRD2 was selected for further analysis. And expression and promoter methylation status of DRD2 were also determined. DRD2 functions were analyzed by various cell biology assays . Subcutaneous tumor model was used to explore DRD2 effects . A co-cultivated system was constructed to investigate interactions of DRD2 and macrophages . WB, IHC, IF, TUNEL, qRT-PCR, Co-IP, Antibody Array, and Mass Spectrum analysis were further applied to determine the detailed mechanism. In BrCa, DRD2 was found to be downregulated due to promoter methylation. Higher expression of DRD2 positively correlated with longer survival times especially in HER2-positive patients. DRD2 also promoted BrCa cells sensitivity to Paclitaxel. Ectopic expression of DRD2 significantly inhibited BrCa tumorigenesis. DRD2 also induced apoptosis as well as necroptosis and . DRD2 restricted NF-κB signaling pathway activation through interacting with β-arrestin2, DDX5 and eEF1A2. Interestingly, DRD2 also regulated microenvironment as it facilitated M1 polarization of macrophages, and triggered GSDME-executed pyroptosis. Collectively, this study novelly manifests the role of DRD2 in suppressing BrCa tumorigenesis, predicting prognosis and treatment response. And this study further reveals the critical role of DRD2 in educating M1 macrophages, restricting NF-κB signaling pathway and triggering different processes of programmed cell death in BrCa. Taking together, those findings represent a predictive and therapeutic target for BrCa.
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http://dx.doi.org/10.7150/thno.58322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039962PMC
July 2021

Health-related quality of life in patients with relapsed or refractory multiple myeloma: treatment with daratumumab, lenalidomide, and dexamethasone in the phase 3 POLLUX trial.

Br J Haematol 2021 Jul 6;194(1):132-139. Epub 2021 Apr 6.

Janssen Global Services, Raritan, NJ, USA.

In the phase 3 POLLUX trial, daratumumab in combination with lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival in patients with relapsed/refractory multiple myeloma (RRMM) compared with lenalidomide and dexamethasone (Rd) alone. Here, we present patient-reported outcomes (PROs) from POLLUX, assessed using the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EuroQol 5-dimensional descriptive system (EQ-5D-5L) questionnaires. Changes from baseline are presented as least-squares mean changes with 95% confidence intervals (CIs) derived from a mixed-effects model. PRO assessment compliance rates were high and similar in both D-Rd and Rd groups through cycle 40 (week 156). In this on-treatment analysis, mean changes from baseline were significantly greater in EORTC QLQ-C30 global health status, physical functioning, and pain scores in the D-Rd group versus the Rd group at multiple time points; however, magnitude of changes was low, suggesting no meaningful impact on health-related quality of life (HRQoL). Subgroup results were similar to those in the overall population. In the POLLUX study, baseline HRQoL was maintained with prolonged D-Rd treatment. These findings complement the sustained and significant improvement in progression-free survival observed with D-Rd and supports its use in patients with RRMM. Clinical trial registration: NCT02076009.
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http://dx.doi.org/10.1111/bjh.17435DOI Listing
July 2021

Unveiling the Hidden σ-Dimerization of a Kinetically Protected Olympicenyl Radical.

Chemistry 2021 Jun 14;27(31):8203-8213. Epub 2021 May 14.

Institute of Molecular Plus, Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Tianjin University, 92 Weijin Road, Tianjin, 300072, P. R. China.

The σ-dimer of a kinetically protected olympicenyl radical, which evaded the experimental detection, was revealed by conversion into biolympicenylidene with E-configuration in a regioselective manner. The complicated stereochemistry and energetics of the σ-dimers derived from C symmetry and uneven spin distribution of the olympicenyl radical were revealed by the theoretical calculations, and the energetic preference of π-dimer over σ-dimer by a minute gap was disclosed. The E-biolympicenylidene, a polycyclic ene structure previously considered as reactive intermediate in the phenalenyl radical system, exhibited exceptional stability, which allowed for a detailed investigation on its singlet diradical character and physical properties by means of X-ray crystallography, UV-vis-NIR absorption/emission spectroscopy and cyclic voltammetry, and assisted by theoretical calculations. The E-biolympicenylidene showed high resistance towards both thermal and photochemical ring-cyclization reactions, which was attributed to high activation energies for the rate-determining electrocyclization operated on both disrotatory and conrotatory mode, as well as a small spin density at the bonding sites for the radical-radical coupling process.
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http://dx.doi.org/10.1002/chem.202100631DOI Listing
June 2021

Electrofluorochromic Imaging Analysis of Glycan Expression on Living Single Cell with Bipolar Electrode Arrays.

Anal Chem 2021 03 21;93(12):5114-5122. Epub 2021 Mar 21.

Jiangsu Engineering Laboratory of Smart Carbon-Rich Materials and Device, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.

The in situ glycan profiling of a single tumor cell plays an important role in personalized cancer treatment. Herein, an integrated microfluidic system was designed for living single-cell trapping and real-time monitoring of galactosyl expression on the surface, combining closed bipolar electrode (BPE) arrays and electrofluorochromic (EFC) imaging. Galactosyl groups on human liver cancer HepG2 cells were used as the model analysts, galactose oxidase (GAO) could selectively oxidize hydroxyl sites of galactosyl groups on the cell surface to aldehydes, and then biotin hydrazide (BH) was used to label the aldehydes by aniline-catalyzed hydrazone ligation. With the biotin-avidin system, nanoprobes were finally introduced to the galactosyl groups on the cell surface with avidin as a bridge, which was prepared by simultaneously assembling ferrocene-DNA (Fc-DNA) and biotin-DNA (Bio-DNA) on gold nanoparticles (AuNPs) due to their large surface area and excellent electrical conductivity. After a labeled single cell was captured in the anodic microchannel, the Fc groups attached on the cell surface were oxidized under suitable potential, and the nonfluorescent resazurin on the cathode was correspondingly reduced to produce highly fluorescent resorufin, collected by fluorescence confocal microscope. The combination of EFC imaging and BPE realized monitoring galactosyl group expression of 5.0 × 10 molecules per cell. Furthermore, the proposed platform had the ability to distinguish a single cancer cell from a normal cell according to the expression level of galactosyl groups and to dynamically monitor the galactosyl group variation on the cell surface, providing a simple and accessible method for the single-cell analysis.
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http://dx.doi.org/10.1021/acs.analchem.0c04785DOI Listing
March 2021

Association among multimorbidity, physical disability and depression trajectories: a study of urban-rural differences in China.

Qual Life Res 2021 Aug 6;30(8):2149-2160. Epub 2021 Mar 6.

Department of Health Management, School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.

Purpose: The purpose of this study was to analyse the trajectories of depression in urban and rural areas, and to analyse the relationship among multimorbidity, disability and other variables and trajectories.

Methods: Data from the China Health and Retirement Longitudinal Study were used. A latent class growth model was used to characterise the trajectories of urban and rural depression symptoms. Chi-square test was used to test the differences in respondents' characteristics among depression trajectories groups within urban and rural areas. The relationships among multimorbidity, disability and depression symptom trajectories were analysed via multinomial logistic regression.

Results: Urban and rural depression trajectories were divided into three categories. Respondents in urban areas were divided into rising, remaining-low and declining group, and those in rural areas were divided into rising, remaining-low and remaining-high group. The depression scores of respondents with multimorbidity were more likely to rise, and this result was similar for the disabled respondents. Respondents who need help on activities of daily living and instrumental activities of daily living in urban areas were more likely to decline in depression scores. In rural areas, however, the values were consistently high. In urban and rural areas, the relationships among marital status, education and age and depression trajectories were different.

Conclusions: The depression trajectories are different in urban and rural China. Improving the quality of medical services, promoting the distribution of rural social resources and implementing more recreational activities could be beneficial for the promotion of mental health in rural areas.
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http://dx.doi.org/10.1007/s11136-021-02807-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298219PMC
August 2021

Autophagy inhibitors increase the susceptibility of KRAS-mutant human colorectal cancer cells to a combined treatment of 2-deoxy-D-glucose and lovastatin.

Acta Pharmacol Sin 2021 Feb 19. Epub 2021 Feb 19.

State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.

RAS-driven colorectal cancer relies on glucose metabolism to support uncontrolled growth. However, monotherapy with glycolysis inhibitors like 2-deoxy-D-glucose causes limited effectiveness. Recent studies suggest that anti-tumor effects of glycolysis inhibition could be improved by combination treatment with inhibitors of oxidative phosphorylation. In this study we investigated the effect of a combination of 2-deoxy-D-glucose with lovastatin (a known inhibitor of mevalonate pathway and oxidative phosphorylation) on growth of KRAS-mutant human colorectal cancer cell lines HCT116 and LoVo. A combination of lovastatin (>3.75 μM) and 2-deoxy-D-glucose (>1.25 mM) synergistically reduced cell viability, arrested cells in the G/M phase, and induced apoptosis. The combined treatment also reduced cellular oxygen consumption and extracellular acidification rate, resulting in decreased production of ATP and lower steady-state ATP levels. Energy depletion markedly activated AMPK, inhibited mTOR and RAS signaling pathways, eventually inducing autophagy, the cellular pro-survival process under metabolic stress, whereas inhibition of autophagy by chloroquine (6.25 μM) enhanced the cytotoxic effect of the combination of lovastatin and 2-deoxy-D-glucose. These in vitro experiment results were reproduced in a nude mouse xenograft model of HCT116 cells. Our findings suggest that concurrently targeting glycolysis, oxidative phosphorylation, and autophagy may be a promising regimen for the management of RAS-driven colorectal cancers.
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http://dx.doi.org/10.1038/s41401-021-00612-9DOI Listing
February 2021

Subcutaneous daratumumab in Asian patients with heavily pretreated multiple myeloma: subgroup analyses of the noninferiority, phase 3 COLUMBA study.

Ann Hematol 2021 Apr 18;100(4):1065-1077. Epub 2021 Feb 18.

Division of Hematology and Oncology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Iwate, Japan.

The phase 3 COLUMBA study demonstrated noninferiority of subcutaneous daratumumab (DARA SC) to intravenous daratumumab (DARA IV) in relapsed or refractory multiple myeloma. We present a subgroup analysis of Asian patients from COLUMBA. Eligible patients had ≥ 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or were double refractory. Co-primary endpoints were overall response rate (ORR) and maximum trough concentration (C). Secondary endpoints included rates of infusion-related reactions, progression-free survival, and patient-reported satisfaction with therapy. Sixty-seven Asian patients (DARA SC, n = 30; DARA IV, n = 37) were randomized, including 42 Japanese patients (DARA SC, n = 18; DARA IV, n = 24). Comparable ORRs for DARA SC versus DARA IV were seen in the Asian cohort (66.7% vs 43.2%) and Japanese-only cohort (61.1% vs 54.2%), including patients weighing ≤ 65 kg. Similarity of C was seen in both Asian and Japanese-only cohorts; the ratio of the geometric mean of the C concentrations for DARA SC/DARA IV was 143.96% (90% confidence interval (CI), 112.03-185.00%) and 148.02% (90% CI, 113.32-193.34%), respectively. The Asian cohort (both treatment groups) and Japanese-only cohort (DARA SC group) experienced higher rates of grade 3/4 cytopenias compared with the global COLUMBA population, occurring predominantly in patients of low bodyweight; no patients discontinued treatment due to cytopenias. The Cancer Therapy Satisfaction Questionnaire results generally favored DARA SC. In the Asian and Japanese-only cohorts, DARA SC was comparable to DARA IV. The efficacy, pharmacokinetic, safety, and satisfaction results were generally consistent with the global COLUMBA population regardless of patient bodyweight. ClinicalTrials.gov Identifier: NCT03277105.
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http://dx.doi.org/10.1007/s00277-021-04405-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960612PMC
April 2021

C2orf40 inhibits hepatocellular carcinoma through interaction with UBR5.

J Gastroenterol Hepatol 2021 Feb 12. Epub 2021 Feb 12.

Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background And Aim: Hepatocellular carcinoma (HCC) urgently needs a marker for early diagnosis and targeted treatment. C2orf40 has been identified as a tumor suppressor gene in many cancers. However, the precise role and regulatory mechanism by C2orf40 contribute to HCC remain elusive and merit exploration.

Methods: Reverse-transcription PCR, quantitative real-time PCR, and methylation-specific PCR were used to detect expression and methylation of C2orf40 in HCC cell lines or tissues. The effects of C2orf40 in liver cancer cells were examined via colony formation, CCK8, transwell, and flow cytometric assays. The effect of C2orf40 on tumorigenesis in vivo was determined by xenografts and immunohistochemical analysis. Western blot, indirect immunofluorescence, Co-IP, and cycloheximide (CHX) were used to further investigate the potential mechanism of C2orf40.

Results: The down-regulation of C2orf40 in hepatocellular cancer tissue samples is often related to the degree of methylation of its promoter CpG. The recovery of C2orf40 expression in HCC cell lines can induce G0/G1 phase arrest and apoptosis and also inhibit cell migration and invasion by reversing the epithelial-mesenchymal transition (EMT) process, both in vivo and in vitro. In addition, C2orf40 can increase the expression of p21 through interaction with UBR5.

Conclusions: Low expression levels of C2orf40 are related to the hypermethylation of its promoter. C2orf40 can inhibit HCC through UBR5-dependent or p53-independent mechanisms. C2orf40 may be a diagnostic biomarker and a potential therapeutic target in HCC.
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http://dx.doi.org/10.1111/jgh.15441DOI Listing
February 2021

Health-related quality of life maintained over time in patients with relapsed or refractory multiple myeloma treated with daratumumab in combination with bortezomib and dexamethasone: results from the phase III CASTOR trial.

Br J Haematol 2021 May 8;193(3):561-569. Epub 2021 Feb 8.

Janssen Research & Development, LLC, Raritan, NJ, USA.

In the phase III CASTOR trial, daratumumab, bortezomib and dexamethasone (D-Vd) significantly extended progression-free survival compared with bortezomib and dexamethasone (Vd) alone in patients with relapsed/refractory multiple myeloma (RRMM). Here, we present patient-reported outcomes (PROs) from the CASTOR trial. PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EuroQol 5-dimensional descriptive system questionnaire. Treatment effects through Cycle 8 were measured by a repeated measures mixed-effects model. After Cycle 8, PROs were only collected for patients in the D-Vd group who continued on daratumumab monotherapy. Compliance rates for PRO assessments were high and similar between treatment groups. Mean changes from baseline were generally similar between treatment groups for EORTC QLQ-C30 global health status (GHS), functioning and symptoms, and did not exceed 10 points for either treatment group. Subgroup analyses were consistent with the results observed in the overall population. There was no change in patients' health-related quality of life for the first eight cycles of therapy; thereafter, patients treated with daratumumab over the long-term reported improvements in GHS and pain. These results complement the significant clinical benefits observed with D-Vd in patients with RRMM and support its use in this patient population.
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http://dx.doi.org/10.1111/bjh.17321DOI Listing
May 2021

Phosphite translocation in soybean and mechanisms of Phytophthora sojae inhibition.

Pestic Biochem Physiol 2021 Feb 13;172:104757. Epub 2020 Dec 13.

Fujian Key Laboratory for Monitoring and Integrated Management of Crop Pests, Institute of Plant Protection, Fujian Academy of Agricultural Sciences, Fuzhou 350003, China; Key Laboratory of Green Prevention and Control of Tropical Plant Diseases and Pests, Ministry of Education, College of Plant Protection, Hainan University, Haikou 570228, China. Electronic address:

Although phosphite (Phi)-based fertilizers are used in large quantities in agriculture, the use of Phi-based fungicides against soybean root rot caused by Phytophthora sojae are limited. While, their low toxicity are of high ecological and economic focus. Limited attention has been paid to Phi translocation efficiency in soybeans and the efficacy of Phi as a fungicide against P. sojae. In this study, we evaluated the efficiency of Phi translocation in the Williams soybean cultivar by determining the Phi concentrations in roots, stems, and leaves using high-performance ion chromatography after the application of Phi to the roots. Phi was translocated from roots to leaves within 1 h and its concentration increased significantly in leaves within 36 h after Phi application. Results of an in vitro growth inhibition assay and an in vivo infection assay showed that Phi inhibited P. sojae. Additionally, we examined the activation of the salicylic acid (SA) and ethylene (ET) defense pathways by Phi. The expression of SA and ET pathway-related genes was upregulated in most soybean tissues after Phi application. Our results provide evidence that Phi translocation suppresses root rot caused by P. sojae in soybean.
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http://dx.doi.org/10.1016/j.pestbp.2020.104757DOI Listing
February 2021
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