bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the effects of tDCS on depressive and anxiety symptoms from a transdiagnostic perspective: a systematic review and meta-analysis of randomized controlled trials
Authors: Zheng Esther Zhiwei , Wong Nichol M. L. , Yang Angela S. Y. , Lee Tatia M. C. 
Published: July 2024

AbstractDepressive and anxiety symptoms are prevalent among patients with various clinical conditions, resulting in diminished emotional well-being and impaired daily functioning. The neural mechanisms underlying these symptoms, particularly across different disorders, remain unclear, limiting the effectiveness of conventional treatments. Therefore, it is crucial to elucidate the neural underpinnings of depressive and anxiety symptoms and investigate novel, effective treatments across clinical conditions. Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that can help understand the neural underpinnings of symptoms and facilitate the development of interventions, addressing the two research gaps at both neural and clinical levels. Thus, this systematic review and meta-analysis aims to evaluate the existing evidence regarding the therapeutic efficacy of tDCS in reducing depressive and anxiety symptoms among individuals with diverse clinical diagnoses. This review evaluated evidence from fifty-six randomized, sham-controlled trials that administered repeated tDCS sessions with a parallel design, applying a three-level meta-analytic model. tDCS targeting the left dorsolateral prefrontal cortex (DLPFC) at 2-mA intensity demonstrates moderate efficacy in alleviating depressive symptoms, identifying the left DLPFC as a transdiagnostic neural mechanism of depressive symptoms across clinical conditions. In comparison, the findings on anxiety symptoms demonstrate greater heterogeneity. tDCS over the left DLPFC is effective in reducing depressive symptoms and shows promising effects in alleviating anxiety symptoms among individuals with diverse diagnoses. These findings enhance our understanding of the neuropsychological basis of depressive and anxiety symptoms, laying the groundwork for the development of more effective tDCS interventions applicable across clinical conditions.
MAZ-mediated up-regulation of BCKDK reprograms glucose metabolism and promotes growth by regulating glucose-6-phosphate dehydrogenase stability in triple-negative breast cancer
Authors: Li Yan , Lin Yuxiang , Tang Yali , Jiang Meichen , Chen Xiaobin , Chen Hanxi , Nie Qian , Wu Jinqiao , Tong Xin , Li Jing , Yu Liuwen , Hou Jialin , Guo Wenhui , Chen Lili , Chen Minyan , Zhang Jie , Lin Shuhai , Fu Fangmeng , Wang Chuan 
Published: July 2024

AbstractTumour metabolic reprogramming is pivotal for tumour survival and proliferation. Investigating potential molecular mechanisms within the heterogeneous and clinically aggressive triple-negative breast cancer (TNBC) subtype is essential to identifying novel therapeutic targets. Accordingly, we investigated the role of branched-chain α-keto acid dehydrogenase kinase (BCKDK) in promoting tumorigenesis in TNBC. We analysed The Cancer Genome Atlas dataset and immunohistochemically stained surgical specimens to investigate BCKDK expression and its prognostic implications in TNBC. The effects of BCKDK on tumorigenesis were assessed using cell viability, colony formation, apoptosis, and cell cycle assays, and subsequently validated in vivo. Metabolomic screening was performed via isotope tracer studies. The downstream target was confirmed using mass spectrometry and a co-immunoprecipitation experiment coupled with immunofluorescence analysis. Upstream transcription factors were also examined using chromatin immunoprecipitation and luciferase assays. BCKDK was upregulated in TNBC tumour tissues and associated with poor prognosis. BCKDK depletion led to reduced cell proliferation both in vitro and vivo. MYC-associated zinc finger protein (MAZ) was confirmed as the major transcription factor directly regulating BCKDK expression in TNBC. Mechanistically, BCKDK interacted with glucose-6-phosphate dehydrogenase (G6PD), leading to increased flux in the pentose phosphate pathway for macromolecule synthesis and detoxification of reactive oxygen species. Forced expression of G6PD rescued the growth defect in BCKDK-deficient cells. Notably, the small-molecule inhibitor of BCKDK, 3,6-dichlorobenzo(b)thiophene-2-carboxylic acid, exhibited anti-tumour effects in a patient-derived tumour xenograft model. Our findings hold significant promise for developing targeted therapies aimed at disrupting the MAZ/BCKDK/G6PD signalling pathway, offering potential advancements in treating TNBC through metabolic reprogramming.
LILRB4 regulates multiple myeloma development through STAT3-PFKFB1 pathway
Authors: Xie Li , Chen Chiqi , Zhang Tinghua , Yang Wenqian , Zheng Denghao , Cao Liyuan , Yuan Jin , Xu Yilu , Zhang Yaping , Liu Ligen , Liang Aibin , Yu Zhuo , Zheng Junke 
Published: July 2024

AbstractAlthough multiple myeloma (MM) responds well to immunotherapeutic treatment, certain portions of MM are still unresponsive or relapse after immunotherapy. Other immune molecules are needed for the immunotherapy of MM. Here, we revealed that leukocyte immunoglobulin-like receptor B4 (LILRB4) was highly expressed in multiple myeloma cell lines and patient samples and that the expression of LILRB4 was adversely correlated with the overall survival of MM patients. Knockdown of LILRB4 efficiently delayed the growth of MM cells both in vitro and in vivo. Mechanistically, IKZF1 transactivated LILRB4 expression to trigger the downstream of STAT3-PFKFB1 pathways to support MM cell proliferation. Blockade of LILRB4 signaling by blocking antibodies can effectively inhibit MM progression. Our data show that targeting LILRB4 is potentially an additional therapeutic strategy for the immunotherapeutic treatment of MM.
The PP2A regulator IER5L supports prostate cancer progression
Authors: Crespo Jana R. , Martín-Martín Natalia , Garcia-Longarte Saioa , Corres-Mendizabal Jon , Carlevaris Onintza , Astobiza Ianire , Zabala-Letona Amaia , Guiu Marc , Azkargorta Mikel , Gonzalez-Lopez Monika , Macías-Cámara Nuria , Doan Phuong , Elortza Félix , Mendizabal Isabel , Westermack Jukka , Gomis Roger R. , Ercilla Amaia , Carracedo Arkaitz 
Published: July 2024

AbstractProstate cancer exhibits high prevalence and accounts for a high number of cancer-related deaths. The discovery and characterization of molecular determinants of aggressive prostate cancer represents an active area of research. The Immediate Early Response (IER) family of genes, which regulate Protein Phosphatase 2A (PP2A) activity, has emerged among the factors that influence cancer biology. Here, we show that the less studied member of this family, Immediate Early Response 5 like (IER5L), is upregulated in aggressive prostate cancer. Interestingly, the upregulation of IER5L expression exhibits a robust association with metastatic disease in prostate and is recapitulated in other cancer types. In line with this observation, IER5L silencing reduces foci formation, migration and invasion ability in a variety of human and murine prostate cancer cell lines. In vivo, using zebrafish and immunocompromised mouse models, we demonstrate that IER5L-silencing reduces prostate cancer tumor growth, dissemination, and metastasis. Mechanistically, we characterize the transcriptomic and proteomic landscapes of IER5L-silenced cells. This approach allowed us to identify DNA replication and monomeric G protein regulators as downstream programs of IER5L through a pathway that is consistent with the regulation of PP2A. In sum, we report the alteration of IER5L in prostate cancer and beyond and provide biological and molecular evidence of its contribution to tumor aggressiveness.
Experimental evidence of climate change extinction risk in Neotropical montane epiphytes
Authors: Hollenbeck Emily C. , Sax Dov F. 
Published: July 2024

AbstractClimate change is conjectured to endanger tropical species, particularly in biodiverse montane regions, but accurate estimates of extinction risk are limited by a lack of empirical data demonstrating tropical species’ sensitivity to climate. To fill this gap, studies could match high-quality distribution data with multi-year transplant experiments. Here, we conduct field surveys of epiphyte distributions on three mountains in Central America and perform reciprocal transplant experiments on one mountain across sites that varied in elevation, temperature and aridity. We find that most species are unable to survive outside of their narrow elevational distributions. Additionally, our findings suggest starkly different outcomes from temperature conditions expected by 2100 under different climate change scenarios. Under temperatures associated with low-emission scenarios, most tropical montane epiphyte species will survive, but under emission scenarios that are moderately high, 5-36% of our study species may go extinct and 10-55% of populations may be lost. Using a test of tropical species’ climate tolerances from a large field experiment, paired with detailed species distribution data across multiple mountains, our work strengthens earlier conjecture about risks of wide-spread extinctions from climate change in tropical montane ecosystems.
An ancestral fold reveals the evolutionary link between RNA polymerase and ribosomal proteins
Authors: Yagi Sota , Tagami Shunsuke 
Published: July 2024

Abstract
Numerous molecular machines are required to drive the central dogma of molecular biology. However, the means by which these numerous proteins emerged in the early evolutionary stage of life remains enigmatic. Many of them possess small β-barrel folds with different topologies, represented by double-psi β-barrels (DPBBs) conserved in DNA and RNA polymerases, and similar but topologically distinct six-stranded β-barrel RIFT or five-stranded β-barrel folds such as OB and SH3 in ribosomal proteins. Here, we discover that the previously reconstructed ancient DPBB sequence could also adopt a β-barrel fold named Double-Zeta β-barrel (DZBB), as a metamorphic protein. The DZBB fold is not found in any modern protein, although its structure shares similarities with RIFT and OB. Indeed, DZBB could be transformed into them through simple engineering experiments. Furthermore, the OB designs could be further converted into SH3 by circular-permutation as previously predicted. These results indicate that these β-barrels diversified quickly from a common ancestor at the beginning of the central dogma evolution.
Large-scale photonic network with squeezed vacuum states for molecular vibronic spectroscopy
Authors: Zhu Hui Hui , Sen Chen Hao , Chen Tian , Li Yuan , Luo Shao Bo , Karim Muhammad Faeyz , Luo Xian Shu , Gao Feng , Li Qiang , Cai Hong , Chin Lip Ket , Kwek Leong Chuan , Nordén Bengt , Zhang Xiang Dong , Liu Ai Qun 
Published: July 2024

AbstractAlthough molecular vibronic spectra generation is pivotal for chemical analysis, tackling such exponentially complex tasks on classical computers remains inefficient. Quantum simulation, though theoretically promising, faces technological challenges in experimentally extracting vibronic spectra for molecules with multiple modes. Here, we propose a nontrivial algorithm to generate the vibronic spectra using states with zero displacements (squeezed vacuum states) coupled to a linear optical network, offering ease of experimental implementation. We also fabricate an integrated quantum photonic microprocessor chip as a versatile simulation platform containing 16 modes of single-mode squeezed vacuum states and a fully programmable interferometer network. Molecular vibronic spectra of formic acid and thymine under the Condon approximation are simulated using the quantum microprocessor chip with high reconstructed fidelity ( > 92%). Furthermore, vibronic spectra of naphthalene, phenanthrene, and benzene under the non-Condon approximation are also experimentally simulated. Such demonstrations could pave the way for solving complicated quantum chemistry problems involving vibronic spectra and computational tasks beyond the reach of classical computers.
An intranasal nanoparticle STING agonist protects against respiratory viruses in animal models
Authors: Leekha Ankita , Saeedi Arash , Kumar Monish , Sefat K. M. Samiur Rahman , Martinez-Paniagua Melisa , Meng Hui , Fathi Mohsen , Kulkarni Rohan , Reichel Kate , Biswas Sujit , Tsitoura Daphne , Liu Xinli , Cooper Laurence J. N. , Sands Courtney M. , Das Vallabh E. , Sebastian Manu , Hurst Brett L. , Varadarajan Navin 
Published: July 2024

AbstractRespiratory viral infections cause morbidity and mortality worldwide. Despite the success of vaccines, vaccination efficacy is weakened by the rapid emergence of viral variants with immunoevasive properties. The development of an off-the-shelf, effective, and safe therapy against respiratory viral infections is thus desirable. Here, we develop NanoSTING, a nanoparticle formulation of the endogenous STING agonist, 2′−3′ cGAMP, to function as an immune activator and demonstrate its safety in mice and rats. A single intranasal dose of NanoSTING protects against pathogenic strains of SARS-CoV-2 (alpha and delta VOC) in hamsters. In transmission experiments, NanoSTING reduces the transmission of SARS-CoV-2 Omicron VOC to naïve hamsters. NanoSTING also protects against oseltamivir-sensitive and oseltamivir-resistant strains of influenza in mice. Mechanistically, NanoSTING upregulates locoregional interferon-dependent and interferon-independent pathways in mice, hamsters, as well as non-human primates. Our results thus implicate NanoSTING as a broad-spectrum immune activator for controlling respiratory virus infection.
Regioselective hydroamination of unactivated olefins with diazirines as a diversifiable nitrogen source
Authors: Xing Qingyu , Chandrachud Preeti P. , Tillett Khalilia , Lopchuk Justin M. 
Published: July 2024

AbstractNitrogen-containing compounds, such as amines, hydrazines, and heterocycles, play an indispensable role in medicine, agriculture, and materials. Alkylated derivatives of these compounds, especially in sterically congested environments, remain a challenge to prepare. Here we report a versatile method for the regioselective hydroamination of readily available unactivated olefins with diazirines. Over fifty examples are reported, including the protecting group-free amination of fourteen different natural products. A broad functional group tolerance includes alcohols, ketones, aldehydes, and epoxides. The proximate products of these reactions are diaziridines, which, under mild conditions, are converted to primary amines, hydrazines, and heterocycles. Five target- and diversity-oriented syntheses of pharmaceutical compounds are shown, along with the preparation of a bis-15N diazirine validated in the late-stage isotopic labeling of an RNA splicing modulator candidate. In this work, we report using diazirine (1) as an electrophilic nitrogen source in a regioselective hydroamination reaction, and the diversification of the resulting diaziridines.
Wide-energy programmable microwave plasma-ionization for high-coverage mass spectrometry analysis
Authors: Chu Fengjian , Zhao Gaosheng , Wei Wei , Shuaibu Nazifi Sani , Feng Hongru , Pan Yuanjiang , Wang Xiaozhi 
Published: July 2024

AbstractAlthough numerous ambient ionization mass spectroscopy technologies have been developed over the past 20 years to address diverse analytical circumstances, a single-ion source technique that can handle all analyte types is still lacking. Here, a wide-energy programmable microwave plasma-ionization mass spectrometry (WPMPI-MS) system is presented, through which MS analysis can achieve high coverage of substances with various characteristics by digitally regulating the microwave energy. In addition, ionization energy can be rapidly scanned using programmable waveforms, enabling the simultaneous detection of biomolecules, heavy metals, non-polar molecules, etc., in seconds. WPMPI-MS performs well in analyzing real samples, rapidly analyzing nine toxicological standards in one drop of serum, and demonstrating good quantification and liquid chromatography coupling capability. The WPMPI-MS has also been used to detect soil extracts, solid pharmaceuticals, and landfill leachate, further demonstrating its robust analytical capabilities for real samples. The prospective uses of the technology in biological and chemical analysis are extensive, and it is anticipated to emerge as a viable alternative to commercially available ion sources.
Upland Yedoma taliks are an unpredicted source of atmospheric methane
Authors: Walter Anthony K. M. , Anthony P. , Hasson N. , Edgar C. , Sivan O. , Eliani-Russak E. , Bergman O. , Minsley B. J. , James S. R. , Pastick N. J. , Kholodov A. , Zimov S. , Euskirchen E. , Bret-Harte M. S. , Grosse G. , Langer M. , Nitzbon J. 
Published: July 2024

AbstractLandscape drying associated with permafrost thaw is expected to enhance microbial methane oxidation in arctic soils. Here we show that ice-rich, Yedoma permafrost deposits, comprising a disproportionately large fraction of pan-arctic soil carbon, present an alternate trajectory. Field and laboratory observations indicate that talik (perennially thawed soils in permafrost) development in unsaturated Yedoma uplands leads to unexpectedly large methane emissions (35–78 mg m−2 d−1 summer, 150–180 mg m−2 d−1 winter). Upland Yedoma talik emissions were nearly three times higher annually than northern-wetland emissions on an areal basis. Approximately 70% emissions occurred in winter, when surface-soil freezing abated methanotrophy, enhancing methane escape from the talik. Remote sensing and numerical modeling indicate the potential for widespread upland talik formation across the pan-arctic Yedoma domain during the 21st and 22nd centuries. Contrary to current climate model predictions, these findings imply a positive and much larger permafrost-methane-climate feedback for upland Yedoma.
Total syntheses of (–)-macrocalyxoformins A and B and (–)-ludongnin C
Authors: Cao Zichen , Sun Wenxuan , Zhang Jingfu , Zhuo Junming , Yang Shaoqiang , Song Xiaocui , Ma Yan , Lu Panrui , Han Ting , Li Chao 
Published: July 2024

AbstractThe complex and diverse molecular architectures along with broad biological activities of ent-kauranoids natural products make them an excellent testing ground for the invention of synthetic methods and strategies. Recent efforts notwithstanding, synthetic access to the highly oxidized enmein-type ent-kauranoids still presents considerable challenges to synthetic chemists. Here, we report the enantioselective total syntheses of C-19 oxygenated enmein-type ent-kauranoids, including (–)-macrocalyxoformins A and B and (–)-ludongnin C, along with discussion and study of synthetic strategies. The enabling feature in our synthesis is a devised Ni-catalyzed decarboxylative cyclization/radical-polar crossover/C-acylation cascade that forges a THF ring concomitantly with the β-keto ester group. Mechanistic studies reveal that the C-acylation process in this cascade reaction is achieved through a carboxylation followed by an in situ esterification. Biological evaluation of these synthetic natural products reveals the indispensable role of the ketone on the D ring in their anti-tumor efficacy.
Cell-selective proteomics reveal novel effectors secreted by an obligate intracellular bacterial pathogen
Authors: Sanderlin Allen G. , Kurka Margolis Hannah , Meyer Abigail F. , Lamason Rebecca L. 
Published: July 2024

AbstractPathogenic bacteria secrete protein effectors to hijack host machinery and remodel their infectious niche. Rickettsia spp. are obligate intracellular bacteria that can cause life-threatening disease, but their absolute dependence on the host cell has impeded discovery of rickettsial effectors and their host targets. We implemented bioorthogonal non-canonical amino acid tagging (BONCAT) during R. parkeri infection to selectively label, isolate, and identify effectors delivered into the host cell. As the first use of BONCAT in an obligate intracellular bacterium, our screen more than doubles the number of experimentally validated effectors for the genus. The seven novel secreted rickettsial factors (Srfs) we identified include Rickettsia-specific proteins of unknown function that localize to the host cytoplasm, mitochondria, and ER. We further show that one such effector, SrfD, interacts with the host Sec61 translocon. Altogether, our work uncovers a diverse set of previously uncharacterized rickettsial effectors and lays the foundation for a deeper exploration of the host-pathogen interface.
Rejuvenation of leukocyte trafficking in aged mice through PEPITEM intervention
Authors: Hopkin Sophie J. , Nathan Poppy , Pezhman Laleh , Begum Jenefa , Manning Julia E. , Quinn Lauren M. , Rainger G. Ed , McGettrick Helen M. , Iqbal Asif J. , Chimen Myriam 
Published: July 2024

AbstractInflammageing leads to uncontrolled leukocyte trafficking in response to inflammatory insults. Here, we used a zymosan-induced peritonitis mouse model on inflammation to investigate the role of the PEPITEM pathway on leukocyte migration in ageing. We then analysed whether PEPITEM could modulate leukocyte migration in older adults. We observed a loss of functionality in the PEPITEM pathway, which normally controls leukocyte trafficking in response to inflammation, in older adults and aged mice and show that this can be rescued by supplementation with PEPITEM. Thus, leading to the exciting possibility that PEPITEM supplementation may represent a potential pre-habilitation geroprotective agent to rejuvenate immune functions.
Topical prebiotic nitrate: optimizing the ‘hang-time’, source and dose for specific oral or systemic effects
Authors: Rosier Bob T. , Mira Alex 
Published: July 2024

AbstractIn our opinion, the ‘hang-time’ of nitrate-containing products discussed in the letter by Green and Green is an interesting variable that should be considered when nitrate-based treatment or prevention strategies are designed. However, due to direct nitrate recycling after nitrate intake, products with a long ‘hang-time’ (e.g., chewing gum) may not always have an advantage compared to products with a short ‘hang-time’ (e.g., vegetable juices). We argue that extending the ‘hang-time’ is especially relevant and potentially beneficial for different applications, such as using a low nitrate dose to stimulate the oral effects, reaching oral tissues that may otherwise not be exposed to dietary nitrate (e.g., periodontal pockets), and providing a longer nitrate exposure in individuals with an impaired salivary flow. Apart from the ‘hang-time’, other important variables are the nitrate dose and source (e.g., different salts and vegetable extracts), as well as the desired effect (e.g., an oral effect versus systemic effects). Finally, we believe that the alterations in salivary microbiota observed before and after chewing three nitrate-rich gums over a period of ~5 h, as reported by Green and Green, could be considered beneficial. However, the oral microbiota composition is affected by the circadian rhythm and the effect of gum mastication should be evaluated. These results should thus be confirmed by a placebo-controlled study, where these confounding factors can be accounted for.