Iguratimod Inhibits the Aggressiveness of Rheumatoid Fibroblast-Like Synoviocytes by Jin Lin, Ye Yu, Xuanwei Wang, Yini Ke, Chuanyin Sun, Lihuan Yue, Guanhua Xu, Bei Xu, Liqin Xu, Heng Cao, Danyi Xu, Nancy Olsen, Weiqian Chen

“…Iguratimod, a novel disease-modifying anti-rheumatic drug for the treatment of rheumatoid arthritis, has been approved in China and Japan. Here, we aimed to find whether iguratimod can inhibit the aggressive behavior and promote apoptosis of rheumatoid fibroblast-like synoviocytes (RA-FLSs). …”
Get full text

Rational Design of Biocompatible Ir(III) Photosensitizer to Overcome Drug‐Resistant Cancer via Oxidative Autophagy Inhibition by Mingyu Park, Jung Seung Nam, Taehyun Kim, Gwangsu Yoon, Seoyoon Kim, Chaiheon Lee, Chae Gyu Lee, Sungjin Park, Kochan S. Bejoymohandas, Jihyeon Yang, Yoon Hee Kwon, Yoo Jin Lee, Jeong Kon Seo, Duyoung Min, Taiho Park, Tae‐Hyuk Kwon

“…Downregulation of autophagy through oxidative stress is a clinically promising strategy to counteract drug resistance, yet precise control of oxidative stress in autophagic proteins remains challenging. Here, a molecular design strategy of biocompatible neutral Ir(III) photosensitizers is demonstrated, B2 and B4, for precise reactive oxygen species (ROS) control at lysosomes to inhibit autophagy. …”
Get full text

METTL16 is Required for Meiotic Sex Chromosome Inactivation and DSB Formation and Recombination during Male Meiosis by Lisha Yin, Nan Jiang, Wenjing Xiong, Shiyu Yang, Jin Zhang, Mengneng Xiong, Kuan Liu, Yuting Zhang, Xinxin Xiong, Yiqian Gui, Huihui Gao, Tao Li, Yi Li, Xiaoli Wang, Youzhi Zhang, Fengli Wang, Shuiqiao Yuan

“…However, the key regulators involved in this process and the underlying molecular mechanisms remain unclear. Here, we report an essential role of the m6A methyltransferase METTL16 in meiotic sex chromosome inactivation (MSCI), double‐strand break (DSB) formation, homologous recombination and SYCP1 deposition during male meiosis. …”
Get full text

Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma by Yamhilette Licón-Muñoz, Vanessa Avalos, Suganya Subramanian, Bryan Granger, Frank Martinez, Leopoldo A. García-Montaño, Samantha Varela, Drew Moore, Eddie Perkins, Michael Kogan, Stefano Berto, Muhammad O. Chohan, Christian A. Bowers, Sara G.M. Piccirillo

“…We previously showed that in 65% of patients with glioblastoma (GBM), the SVZ is a reservoir of cancer stem-like cells that contribute to treatment resistance and the emergence of recurrence. Here, we build a single-nucleus RNA-sequencing-based microenvironment landscape of the tumor mass and the SVZ of 15 patients and two histologically normal SVZ samples as controls. …”
Get full text

ERK activation waves coordinate mechanical cell competition leading to collective elimination via extrusion of bacterially infected cells by Lara Hundsdorfer, Marie Muenkel, Raul Aparicio-Yuste, Julio Cesar Sanchez-Rendon, Maria Jose Gomez-Benito, Aylin Balmes, Tilman E. Schäffer, Ana Velic, Yi-Ting Yeh, Iordania Constantinou, Kathryn Wright, Gizem Özbaykal Güler, Dominik Brokatzky, Boris Maček, Serge Mostowy, Effie E. Bastounis

“…However, the underlying biochemical pathways remain elusive. Here, using in vitro (epithelial monolayers) and in vivo (zebrafish larvae) models of infection with L. monocytogenes or Shigella flexneri, we explored the role of extracellular-signal-regulated kinase (ERK) activity waves in coordinating the mechanical battle between infected and surrounder uninfected cells that leads to CICE. …”
Get full text

Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines by Anton Wellstein, Thomas Seufferlein, Alexander Kleger, Tim Eiseler, Anton Lahusen, Nora Minhöfer, Kim-André Lohse, Christine Blechner, Jessica Lindenmayer, Sabine Windhorst, Yuan-Na Lin

“…PDAC is described as a “cold” tumor type with poor infiltration by T cells and factors leading to intratumoral T cell suppression have thus received less attention. Here, we identify a cancer cell-intrinsic mechanism that contributes to a T cell-resistant phenotype and describes potential combinatorial therapy.Methods We used an unbiased screening approach of T cell resistant and sensitive murine KPC (KrasLSL-G12D/+; Trp53fl/fl; Ptf1aCre/+) PDAC cells in a three-dimensional co-culture platform with syngeneic antigen-educated T cells to identify potential cell-intrinsic drivers of T cell suppression in PDAC. …”
Get full text

On the substrate turnover rate of NBCe1 and AE1 SLC4 transporters: structure-function considerations by Alexander Pushkin, Liyo Kao, Hristina R. Zhekova, Rustam Azimov, Natalia Abuladze, Xuesi M. Shao, D. Peter Tieleman, Ira Kurtz, Ira Kurtz

“…Whether other SLC4 family members have similar TOR values is currently unknown. Here we report TOR measurements of the electrogenic Na+-CO32− cotransporter NBCe1-A (SLC4A4) and the kidney specific AE1 splice variant, kAE1, that play important roles in renal bicarbonate absorption and are mutated in proximal and distal renal tubular acidosis respectively. …”
Get full text

Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option? by Daniele Fanale, Giuseppe Bronte, Francesco Passiglia, Valentina Calò, Marta Castiglia, Florinda Di Piazza, Nadia Barraco, Antonina Cangemi, Maria Teresa Catarella, Lavinia Insalaco, Angela Listì, Rossella Maragliano, Daniela Massihnia, Alessandro Perez, Francesca Toia, Giuseppe Cicero, Viviana Bazan

“…Clinical application of earlier microtubule inhibitors, however, unfortunately showed several limits, such as neurological and bone marrow toxicity and the emergence of drug-resistant tumor cells. Here we review several natural and synthetic microtubule-targeting agents, which showed antitumor activity and increased efficacy in comparison to traditional drugs in various preclinical and clinical studies. …”
Get full text

Boosting the durability of RuO2 via confinement effect for proton exchange membrane water electrolyzer by Wen-Xing Zheng, Xuan-Xuan Cheng, Ping-Ping Chen, Lin-Lin Wang, Ying Duan, Guo-Jin Feng, Xiao-Ran Wang, Jing-Jing Li, Chao Zhang, Zi-You Yu, Tong-Bu Lu

“…However, the over-oxidation of RuO2 into soluble H2RuO5 species results in a poor durability, which hinders the practical application of RuO2 in proton exchange membrane water electrolysis. Here, we report a confinement strategy by enriching a high local concentration of in-situ formed H2RuO5 species, which can effectively suppress the RuO2 degradation by shifting the redox equilibrium away from the RuO2 over-oxidation, greatly boosting its durability during acidic oxygen evolution. …”
Get full text

Schwann Cell‐Specific Ablation of Beclin 1 Impairs Myelination and Leads to Motor and Sensory Neuropathy in Mice by Lisa Gambarotto, Loris Russo, Silvia Bresolin, Luca Persano, Rachele D'Amore, Giulia Ronchi, Federica Zen, Luisa Muratori, Alice Cani, Samuele Negro, Aram Megighian, Sonia Calabrò, Paola Braghetta, Dario Bizzotto, Matilde Cescon

“…By knocking out Beclin 1 in SCs here a novel mouse model (Becn1 cKO) is generated, developing a severe and progressive neuropathy, accompanied by involuntary tremors, body weight loss, and premature death. …”
Get full text

MicroRNA-122 protects against interferon-α-induced hepatic inflammatory response via the Janus kinase–signal transducer and activator of transcription pathway by Fanwei Liu, Bowen Liu, Shanshan Xu, Yinhua Ni, Xiaoli Liu

“…However, the underlying mechanism of IFN-α in hepatic inflammation remains to be fully elucidated. Here, we utilized LO2 cells treated with the recombinant IFN-α protein and conducted microRNA (miR) sequencing. …”
Get full text

Effects of polymethylmethacrylate nanoplastics on the swimming behaviour and gut microbiome of the freshwater amphipod Gammarus pulex by Sareh Yaripour, Mandar Bandekar, Jiri Vihavainen, Kuldeep More, Aslak Eronen, Manuela Faria Durão, Mikhail Daneliya, Tuure Houni, Tia Halonen, Jari T.T. Leskinen, Jaakko Haverinen, Hannu Huuskonen, Ulrika Candolin, Jukka Kekäläinen, Raine Kortet

“…Aquatic animals are increasingly exposed to NPs but their effects on many aquatic invertebrates remain inadequately known. Here, we assessed the effects of 25 nm polymethylmethacrylate NPs on the swimming behaviour and gut microbiome composition of juveniles of an ecologically important detritivore, the Gammarus pulex (Crustacea: Amphipoda: Gammaridae), during a 10-day exposure period at two different concentrations (2 mg/L and 20 mg/L). …”
Get full text

SARS-CoV-2 transmission dynamics in Mozambique and Zimbabwe during the first 3 years of the pandemic by Roselyn F. Kaondera-Shava, Marta Galanti, Matteo Perini, Jiyeon Suh, Shannon M. Farley, Sergio Chicumbe, Ilesh Jani, Annette Cassy, Ivalda Macicame, Naisa Manafe, Wafaa El-Sadr, Jeffrey Shaman

“…Characterization of the transmission dynamics is critical for understanding how SARS-CoV-2 spreads and the true scale of the pandemic. Here, to better understand SARS-CoV-2 transmission dynamics in two southern African countries, Mozambique and Zimbabwe, we developed a dynamic model-Bayesian inference system to estimate key epidemiological parameters, namely the transmission and ascertainment rates. …”
Get full text

Automated and virus variant-programmable surrogate test qualitatively compares to the gold standard SARS-CoV-2 neutralization assay by Danielle W. Ali, Maggie L. Bartlett, Christopher D. Heger, Francisco Ramirez, Linwood Johnson, Kevin L. Schully, Eric D. Laing, Wei Wang, Carol D. Weiss, Emilie Goguet, Christopher C. Broder, Stephanie A. Richard, Nusrat J. Epsi, Brian Agan, David Tribble, Mark P. Simons, Timothy H. Burgess, Edward Mitre, Simon Pollett, Darci R. Smith

“…To circumvent the challenges of cell-based assays, SARS-CoV-2 surrogate virus neutralization tests (sVNTs) measure inhibition of the binding of the spike (S) protein receptor binding domain (RBD) to its receptor, human angiotensin-converting enzyme 2 (hACE2) by neutralizing antibodies. Here we tested a prototype automated microfluidic cartridge-based sVNT platform using SARS-CoV-2 wild-type (WT) and B.1.617.2 (Delta) variant RBDs. …”
Get full text

Inhibition of the invasive plant Ambrosia trifida by Sigesbeckia glabrescens extracts by Lijuan Yin, Guangzhong Zhang, Haoyu Zhao, Yuxin Zhang, Jiaozi Wangchen, Fanghao Wan, Bo Liu, Wanqiang Qian

“…However, how to control A. trifida through interspecific competition and the underlying mechanisms are unclear. Here, we found that extracts from both the roots and leaves of the medicinal plant Sigesbeckia glabrescens suppressed the growth of A. trifida by reducing the plant height and biomass. …”
Get full text

Construct validity and responsiveness of clinical upper limb measures and sensor-based arm use within the first year after stroke: a longitudinal cohort study by Johannes Pohl, Geert Verheyden, Jeremia Philipp Oskar Held, Andreas Ruediger Luft, Chris Easthope Awai, Janne Marieke Veerbeek

“…Defining sensor-based AU metrics for intentional upper limb movements could be crucial in mitigating bias from walking-related activities. Here, we investigate the measurement properties of a comprehensive set of clinical measures and sensor-based AU metrics when gait and non-functional upper limb movements are excluded. …”
Get full text

ONC213: a novel strategy to resensitize resistant AML cells to venetoclax through induction of mitochondrial stress by Jenna L. Carter, Yongwei Su, Eman T. Al-Antary, Jianlei Zhao, Xinan Qiao, Guan Wang, Holly Edwards, Lisa Polin, Juiwanna Kushner, Sijana H. Dzinic, Kathryn White, Steven A. Buck, Maik Hüttemann, Joshua E. Allen, Varun V. Prabhu, Jay Yang, Jeffrey W. Taub, Yubin Ge

“…We previously reported that ONC213 disrupts oxidative phosphorylation and decreases Mcl-1 protein, which play a key role in venetoclax resistance. Here we investigated the antileukemic activity and underlying molecular mechanism of the combination of ONC213 + venetoclax against AML cells. …”
Get full text

TDP43 augments astrocyte inflammatory activity through mtDNA-cGAS-STING axis in NMOSD by Zhuhe Liu, Yunmeng Bai, Bingtian Xu, Haixia Wen, Kechun Chen, Jingfang Lin, Yuanyuan Wang, Jiangping Xu, Haitao Wang, Fudong Shi, Jigang Wang, Honghao Wang

“…However, the role of TDP43 in neuromyelitis optica spectrum disorder (NMOSD) remains unknown. Here, our observations demonstrate an upregulation of TDP43 in both in vitro and in vivo models of NMOSD, as well as in biological samples from NMOSD patients. …”
Get full text

High trophic similarity between non-native common carp and gibel carp in Turkish freshwaters: Implications for management by Sadi Aksu, Özgür Emiroğlu, Paride Balzani, J. Robert Britton, Esengül Köse, Irmak Kurtul, Sercan Başkurt, Oğuzcan Mol, Emre Çınar, Phillip J. Haubrock, Pinar Oztopcu-Vatan, Ali Serhan Tarkan

“…These stockings, however, increase the risk of accidental introductions and have led to introductions and subsequent invasions of gibel carp Carassius gibelio, a globally invasive and highly detrimental fish species. Here, we assessed the growth types, body conditions and trophic interactions via bulk carbon and nitrogen stable isotope analysis of common and gibel carp in both natural and artificial water bodies in Turkey. …”
Get full text

iRGD-Targeted Biosynthetic Nanobubbles for Ultrasound Molecular Imaging of Osteosarcoma by Liu T, Liang X, Liu W, Yang S, Cui T, Yan F, Li Z

“…However, there is a lack of effective means for early diagnosis due to the heterogeneity of tumors and the complexity of tumor microenvironment. αvβ 3 integrin, a crucial role in the growth and spread of tumors, is not only an effective biomarker for cancer angiogenesis, but also highly expressed in many tumor cells. Here, we selected it as the imaging target and fabricated iRGD-sGVs acoustic probe for the early-stage diagnosis of osteosarcoma.Materials and Methods: Biological nanoscale gas vesicles (sGVs) were extracted from Serratia 39006. …”
Get full text