bluuebunny/crossref_metadata_2025 huggingface dataset:
Simplified algorithm for genetic subtyping in diffuse large B-cell lymphoma
Authors: Shen Rong , Fu Di , Dong Lei , Zhang Mu-Chen , Shi Qing , Shi Zi-Yang , Cheng Shu , Wang Li , Xu Peng-Peng , Zhao Wei-Li
Published: April 2023

Genetic classification helps to disclose molecular heterogeneity and therapeutic implications in diffuse large B-cell lymphoma (DLBCL). Using whole exome/genome sequencing, RNA-sequencing, and fluorescence in situ hybridization in 337 newly diagnosed DLBCL patients, we established a simplified 38-gene algorithm (termed ‘LymphPlex’) based on the information on mutations of 35 genes and rearrangements of three genes (BCL2, BCL6, and MYC), identifying seven distinct genetic subtypes: TP53Mut (TP53 mutations), MCD-like (MYD88, CD79B, PIM1, MPEG1, BTG1, TBL1XR1, PRDM1, IRF4 mutations), BN2-like (BCL6 fusion, NOTCH2, CD70, DTX1, BTG2, TNFAIP3, CCND3 mutations), N1-like (NOTCH1 mutations), EZB-like (BCL2 fusion, EZH2, TNFRSF14, KMT2D, B2M, FAS, CREBBP, ARID1A, EP300, CIITA, STAT6, GNA13 mutations, with or without MYC rearrangement), and ST2-like (SGK1, TET2, SOCS1, DDX3X, ZFP36L1, DUSP2, STAT3, IRF8 mutations). Extended validation of 1001 DLBCL patients revealed clinical relevance and biological signature of each genetic subtype. TP53Mut subtype showed poor prognosis, characterized by p53 signaling dysregulation, immune deficiency, and PI3K activation. MCD-like subtype was associated with poor prognosis, activated B-cell (ABC) origin, BCL2/MYC double-expression, and NF-κB activation. BN2-like subtype showed favorable outcome within ABC-DLBCL and featured with NF-κB activation. N1-like and EZB-like subtypes were predominated by ABC-DLBCL and germinal center B-cell (GCB)-DLBCL, respectively. EZB-like-MYC+ subtype was characterized by an immunosuppressive tumor microenvironment, while EZB-like-MYC- subtype by NOTCH activation. ST2-like subtype showed favorable outcome within GCB-DLBCL and featured with stromal-1 modulation. Genetic subtype-guided targeted agents achieved encouraging clinical response when combined with immunochemotherapy. Collectively, LymphPlex provided high efficacy and feasibility, representing a step forward to the mechanism-based targeted therapy in DLBCL.
Effect of schizophrenia common variants on infant brain volumes: cross-sectional study in 207 term neonates in developing Human Connectome Project
Authors: Le Hai , Dimitrakopoulou Konstantina , Patel Hamel , Curtis Charles , Cordero-Grande Lucilio , Edwards A. David , Hajnal Joseph , Tournier Jacques-Donald , Deprez Maria , Cullen Harriet
Published: April 2023

Increasing lines of evidence suggest deviations from the normal early developmental trajectory could give rise to the onset of schizophrenia during adolescence and young adulthood, but few studies have investigated brain imaging changes associated with schizophrenia common variants in neonates. This study compared the brain volumes of both grey and white matter regions with schizophrenia polygenic risk scores (PRS) for 207 healthy term-born infants of European ancestry. Linear regression was used to estimate the relationship between PRS and brain volumes, with gestational age at birth, postmenstrual age at scan, ancestral principal components, sex and intracranial volumes as covariates. The schizophrenia PRS were negatively associated with the grey (β = −0.08, p = 4.2 × 10−3) and white (β = −0.13, p = 9.4 × 10−3) matter superior temporal gyrus volumes, white frontal lobe volume (β = −0.09, p = 1.5 × 10−3) and the total white matter volume (β = −0.062, p = 1.66 × 10−2). This result also remained robust when incorporating individuals of Asian ancestry. Explorative functional analysis of the schizophrenia risk variants associated with the right frontal lobe white matter volume found enrichment in neurodevelopmental pathways. This preliminary result suggests possible involvement of schizophrenia risk genes in early brain growth, and potential early life structural alterations long before the average age of onset of the disease.
The contribution of penguin guano to the Southern Ocean iron pool
Authors: Belyaev Oleg , Sparaventi Erica , Navarro Gabriel , Rodríguez-Romero Araceli , Tovar-Sánchez Antonio
Published: April 2023

Iron plays a crucial role in the high-nutrient, low-chlorophyll Southern Ocean regions, promoting phytoplankton growth and enhancing atmospheric carbon sequestration. In this area, iron-rich Antarctic krill (Euphausia superba) and baleen whale species, which are among their main predators, play a large role in the recycling of iron. However, penguins have received limited attention despite their representing the largest seabird biomass in the southern polar region. Here, we use breeding site guano volumes estimated from drone images, deep learning-powered penguin census, and guano chemical composition to assess the iron export to the Antarctic waters from one of the most abundant penguin species, the Chinstrap penguin (Pygoscelis antarcticus). Our results show that these seabirds are a relevant contributor to the iron remobilization pool in the Southern Ocean. With an average guano concentration of 3 mg iron g−1, we estimate that the Chinstrap penguin population is recycling 521 tonnes iron yr−1, representing the current iron contribution half of the amount these penguins were able to recycle four decades ago, as they have declined by more than 50% since then.
O2 partitioning of sulfur oxidizing bacteria drives acidity and thiosulfate distributions in mining waters
Authors: Whaley-Martin Kelly J. , Chen Lin-Xing , Nelson Tara Colenbrander , Gordon Jennifer , Kantor Rose , Twible Lauren E. , Marshall Stephanie , McGarry Sam , Rossi Laura , Bessette Benoit , Baron Christian , Apte Simon , Banfield Jillian F. , Warren Lesley A.
Published: April 2023

The acidification of water in mining areas is a global environmental issue primarily catalyzed by sulfur-oxidizing bacteria (SOB). Little is known about microbial sulfur cycling in circumneutral pH mine tailing impoundment waters. Here we investigate biological sulfur oxidation over four years in a mine tailings impoundment water cap, integrating aqueous sulfur geochemistry, genome-resolved metagenomics and metatranscriptomics. The microbial community is consistently dominated by neutrophilic, chemolithoautotrophic SOB (relative abundances of ~76% in 2015, ~55% in 2016/2017 and ~60% in 2018). Results reveal two SOB strategies alternately dominate across the four years, influencing acid generation and sulfur speciation. Under oxic conditions, novel Halothiobacillus drive lower pH conditions (as low as 4.3) and lower [S2O32−] via the complete Sox pathway coupled to O2. Under anoxic conditions, Thiobacillus spp. dominate in activity, via the incomplete Sox and rDSR pathways coupled to NO3−, resulting in higher [S2O32−] and no net significant acidity generation. This study provides genomic evidence explaining acidity generation and thiosulfate accumulation patterns in a circumneutral mine tailing impoundment and has significant environmental applications in preventing the discharge of sulfur compounds that can impact downstream environments. These insights illuminate opportunities for in situ biotreatment of reduced sulfur compounds and prediction of acidification events using gene-based monitoring and in situ RNA detection.
Enhancer hijacking at the ARHGAP36 locus is associated with connective tissue to bone transformation
Authors: Melo Uirá Souto , Jatzlau Jerome , Prada-Medina Cesar A. , Flex Elisabetta , Hartmann Sunhild , Ali Salaheddine , Schöpflin Robert , Bernardini Laura , Ciolfi Andrea , Moeinzadeh M-Hossein , Klever Marius-Konstantin , Altay Aybuge , Vallecillo-García Pedro , Carpentieri Giovanna , Delledonne Massimo , Ort Melanie-Jasmin , Schwestka Marko , Ferrero Giovanni Battista , Tartaglia Marco , Brusco Alfredo , Gossen Manfred , Strunk Dirk , Geißler Sven , Mundlos Stefan , Stricker Sigmar , Knaus Petra , Giorgio Elisa , Spielmann Malte
Published: April 2023

Heterotopic ossification is a disorder caused by abnormal mineralization of soft tissues in which signaling pathways such as BMP, TGFβ and WNT are known key players in driving ectopic bone formation. Identifying novel genes and pathways related to the mineralization process are important steps for future gene therapy in bone disorders. In this study, we detect an inter-chromosomal insertional duplication in a female proband disrupting a topologically associating domain and causing an ultra-rare progressive form of heterotopic ossification. This structural variant lead to enhancer hijacking and misexpression of ARHGAP36 in fibroblasts, validated here by orthogonal in vitro studies. In addition, ARHGAP36 overexpression inhibits TGFβ, and activates hedgehog signaling and genes/proteins related to extracellular matrix production. Our work on the genetic cause of this heterotopic ossification case has revealed that ARHGAP36 plays a role in bone formation and metabolism, outlining first details of this gene contributing to bone-formation and -disease.
Total escape of SARS-CoV-2 from dual monoclonal antibody therapy in an immunocompromised patient
Authors: Jaki Lena , Weigang Sebastian , Kern Lisa , Kramme Stefanie , Wrobel Antoni G. , Grawitz Andrea B. , Nawrath Philipp , Martin Stephen R. , Dähne Theo , Beer Julius , Disch Miriam , Kolb Philipp , Gutbrod Lisa , Reuter Sandra , Warnatz Klaus , Schwemmle Martin , Gamblin Steven J. , Neumann-Haefelin Elke , Schnepf Daniel , Welte Thomas , Kochs Georg , Huzly Daniela , Panning Marcus , Fuchs Jonas
Published: April 2023

Monoclonal antibodies (mAbs) directed against the spike of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective therapeutic options to combat infections in high-risk patients. Here, we report the adaptation of SARS-CoV-2 to the mAb cocktail REGN-COV in a kidney transplant patient with hypogammaglobulinemia. Following mAb treatment, the patient did not clear the infection. During viral persistence, SARS-CoV-2 acquired three novel spike mutations. Neutralization and mouse protection analyses demonstrate a complete viral escape from REGN-COV at the expense of ACE-2 binding. Final clearance of the virus occurred upon reduction of the immunosuppressive regimen and total IgG substitution. Serology suggests that the development of highly neutralizing IgM rather than IgG substitution aids clearance. Our findings emphasise that selection pressure by mAbs on SARS-CoV-2 can lead to development of escape variants in immunocompromised patients. Thus, modification of immunosuppressive therapy, if possible, might be preferable to control and clearance of the viral infection.
Active site recovery and N-N bond breakage during hydrazine oxidation boosting the electrochemical hydrogen production
Authors: Zhu Libo , Huang Jian , Meng Ge , Wu Tiantian , Chen Chang , Tian Han , Chen Yafeng , Kong Fantao , Chang Ziwei , Cui Xiangzhi , Shi Jianlin
Published: April 2023

Substituting hydrazine oxidation reaction for oxygen evolution reaction can result in greatly reduced energy consumption for hydrogen production, however, the mechanism and the electrochemical utilization rate of hydrazine oxidation reaction remain ambiguous. Herein, a bimetallic and hetero-structured phosphide catalyst has been fabricated to catalyze both hydrazine oxidation and hydrogen evolution reactions, and a new reaction path of nitrogen-nitrogen single bond breakage has been proposed and confirmed in hydrazine oxidation reaction. The high electro-catalytic performance is attributed to the instantaneous recovery of metal phosphide active site by hydrazine and the lowered energy barrier, which enable the constructed electrolyzer using bimetallic phosphide catalyst at both sides to reach 500 mA cm−2 for hydrogen production at 0.498 V, and offer an enhanced hydrazine electrochemical utilization rate of 93%. Such an electrolyzer can be powered by a bimetallic phosphide anode-equipped direct hydrazine fuel cell, achieving self-powered hydrogen production at a rate of 19.6 mol h−1 m−2.
Acceleration of U.S. Southeast and Gulf coast sea-level rise amplified by internal climate variability
Authors: Dangendorf Sönke , Hendricks Noah , Sun Qiang , Klinck John , Ezer Tal , Frederikse Thomas , Calafat Francisco M. , Wahl Thomas , Törnqvist Torbjörn E.
Published: April 2023

While there is evidence for an acceleration in global mean sea level (MSL) since the 1960s, its detection at local levels has been hampered by the considerable influence of natural variability on the rate of MSL change. Here we report a MSL acceleration in tide gauge records along the U.S. Southeast and Gulf coasts that has led to rates (>10 mm yr−1 since 2010) that are unprecedented in at least 120 years. We show that this acceleration is primarily induced by an ocean dynamic signal exceeding the externally forced response from historical climate model simulations. However, when the simulated forced response is removed from observations, the residuals are neither historically unprecedented nor inconsistent with internal variability in simulations. A large fraction of the residuals is consistent with wind driven Rossby waves in the tropical North Atlantic. This indicates that this ongoing acceleration represents the compounding effects of external forcing and internal climate variability.
Effectiveness of inactivated COVID-19 vaccines among older adults in Shanghai: retrospective cohort study
Authors: Huang Zhuoying , Xu Shuangfei , Liu Jiechen , Wu Linlin , Qiu Jing , Wang Nan , Ren Jia , Li Zhi , Guo Xiang , Tao Fangfang , Chen Jian , Lu Donglei , Wang Yuheng , Li Juan , Sun Xiaodong , Wang Weibing
Published: April 2023

We conducted a matched retrospective cohort study of two cohorts to estimate inactivated vaccine effectiveness (VE) and its comparative effectiveness of booster dose among older people in Shanghai. Cohort 1 consisted of a vaccinated group (≥1 dose) and an unvaccinated group (3,317,475 pairs), and cohort 2 consisted of a booster vaccinated group and a fully vaccinated group (2,084,721 pairs). The Kaplan–Meier method and Cox regression models were used to estimate risk and hazard ratios (HRs) study outcomes. For cohort 1, the overall estimated VEs of ≥1 dose of inactivated vaccine against SARS-CoV-2 infection, severe/critical Covid-19, and Covid-19 related death were 24.7% (95%CI 23.7%−25.7%), 86.6% (83.1%−89.4%), and 93.2% (88.0%−96.1%), respectively. Subset analysis showed that the booster vaccination provided greatest protection. For cohort 2, compared with full vaccination, relative VEs of booster dose against corresponding outcome were 16.3% (14.4%−17.9%), 60.5% (37.8%−74.9%), and 81.7% (17.5%−95.9%). Here we show, although under the scenario of persistent dynamic zero-Covid policy and non-pharmaceutical interventions, promoting high uptake of the full vaccination series and booster dose among older adults is critically important. Timely vaccination with the booster dose provided effective protection against Covid-19 outcomes.
The role of oxygen-vacancy in bifunctional indium oxyhydroxide catalysts for electrochemical coupling of biomass valorization with CO2 conversion
Authors: Ye Fenghui , Zhang Shishi , Cheng Qingqing , Long Yongde , Liu Dong , Paul Rajib , Fang Yunming , Su Yaqiong , Qu Liangti , Dai Liming , Hu Chuangang
Published: April 2023

Electrochemical coupling of biomass valorization with carbon dioxide (CO2) conversion provides a promising approach to generate value-added chemicals on both sides of the electrolyzer. Herein, oxygen-vacancy-rich indium oxyhydroxide (InOOH-OV) is developed as a bifunctional catalyst for CO2reduction to formate and 5-hydroxymethylfurfural electrooxidation to 2,5-furandicarboxylic acid with faradaic efficiencies for both over 90.0% at optimized potentials. Atomic-scale electron microscopy images and density functional theory calculations reveal that the introduction of oxygen vacancy sites causes lattice distortion and charge redistribution. Operando Raman spectra indicate oxygen vacancies could protect the InOOH-OVfrom being further reduced during CO2conversion and increase the adsorption competitiveness for 5-hydroxymethylfurfural over hydroxide ions in alkaline electrolytes, making InOOH-OVa main-group p-block metal oxide electrocatalyst with bifunctional activities. Based on the catalytic performance of InOOH-OV, a pH-asymmetric integrated cell is fabricated by combining the CO2reduction and 5-hydroxymethylfurfural oxidation together in a single electrochemical cell to produce 2,5-furandicarboxylic acid and formate with high yields (both around 90.0%), providing a promising approach to generate valuable commodity chemicals simultaneously on both electrodes.
Stereodefined polymetalloid alkenes synthesis via stereoselective boron-masking of polyborylated alkenes
Authors: Eghbarieh Nadim , Hanania Nicole , Masarwa Ahmad
Published: April 2023

Polyborylated-alkenes are valuable polymetalloid reagents in modern organic synthesis, providing access to a wide array of transformations, including the construction of multiple C–C and C–heteroatom bonds. However, because they contain similar boryl groups, many times their transformation faces the main challenge in controlling the chemo-, regio- and stereoselectivity. One way to overcome these limitations is by installing different boron groups that can provide an opportunity to tune their reactivity toward better chemo-, regio- and stereoselectivity. Yet, the preparation of polyborylated-alkenes containing different boryl groups has been rare. Herein we report concise, highly site-selective, and stereoselective boron-masking strategies of polyborylated alkenes. This is achieved by designed stereoselective trifluorination and MIDA-ation reactions of readily available starting polyborylated alkenes. Additionally, the trifluoroborylated-alkenes undergo a stereospecific interconversion to Bdan-alkenes. These transition-metal free reactions provide a general and efficient method for the conversion of polyborylated alkenes to access 1,1-di-, 1,2-di-, 1,1,2-tris-(borylated) alkenes containing BF3M, Bdan, and BMIDA, a family of compounds that currently lack efficient synthetic access. Moreover, tetraborylethene undergoes the metal-free MIDA-ation reaction to provide the mono BMIDA tetraboryl alkene selectively. The mixed polyborylalkenes are then demonstrated to be useful in selective C–C and C–heteroatom bond-forming reactions. Given its simplicity and versatility, these stereoselective boron-masking approaches hold great promise for organoboron synthesis and will result in more transformations.
Migrating mule deer compensate en route for phenological mismatches
Authors: Ortega Anna C. , Aikens Ellen O. , Merkle Jerod A. , Monteith Kevin L. , Kauffman Matthew J.
Published: April 2023

Billions of animals migrate to track seasonal pulses in resources. Optimally timing migration is a key strategy, yet the ability of animals to compensate for phenological mismatches en route is largely unknown. Using GPS movement data collected from 72 adult female deer over a 10-year duration, we study a population of mule deer (Odocoileus hemionus) in Wyoming that lack reliable cues on their desert winter range, causing them to start migration 70 days ahead to 52 days behind the wave of spring green-up. We show that individual deer arrive at their summer range within an average 6-day window by adjusting movement speed and stopover use. Late migrants move 2.5 times faster and spend 72% less time on stopovers than early migrants, which allows them to catch the green wave. Our findings suggest that ungulates, and potentially other migratory species, possess cognitive abilities to recognize where they are in space and time relative to key resources. Such behavioral capacity may allow migratory taxa to maintain foraging benefits amid rapidly changing phenology.
Oxynitrides enabled photoelectrochemical water splitting with over 3,000 hrs stable operation in practical two-electrode configuration
Authors: Xiao Yixin , Kong Xianghua , Vanka Srinivas , Dong Wan Jae , Zeng Guosong , Ye Zhengwei , Sun Kai , Navid Ishtiaque Ahmed , Zhou Baowen , Toma Francesca M. , Guo Hong , Mi Zetian
Published: April 2023

Solar photoelectrochemical reactions have been considered one of the most promising paths for sustainable energy production. To date, however, there has been no demonstration of semiconductor photoelectrodes with long-term stable operation in a two-electrode configuration, which is required for any practical application. Herein, we demonstrate the stable operation of a photocathode comprising Si and GaN, the two most produced semiconductors in the world, for 3,000 hrs without any performance degradation in two-electrode configurations. Measurements in both three- and two-electrode configurations suggest that surfaces of the GaN nanowires on Si photocathode transform in situ into Ga-O-N that drastically enhances hydrogen evolution and remains stable for 3,000 hrs. First principles calculations further revealed that the in-situ Ga-O-N species exhibit atomic-scale surface metallization. This study overcomes the conventional dilemma between efficiency and stability imposed by extrinsic cocatalysts, offering a path for practical application of photoelectrochemical devices and systems for clean energy.
Increasing deep-water overflow from the Pacific into the South China Sea revealed by mooring observations
Authors: Zhou Chun , Xiao Xin , Zhao Wei , Yang Jiayan , Huang Xiaodong , Guan Shoude , Zhang Zhiwei , Tian Jiwei
Published: April 2023

Cold and dense water from the North Pacific Ocean that spills through the Luzon Strait, the only deep conduit between the South China Sea (SCS) and the Pacific Ocean, renews deep-water mass, modulates hydrographic and biogeochemical cycles, and drives abyssal and overturning circulations in the SCS. The variability of this key oceanic process, however, has been poorly studied, mainly due to a lack of sustained observations. A comprehensive observational program that started in 2009 has provided 12 years of continuous time series of velocity and volume transport within the Luzon Strait. Here we show the observation-based assessment of decadal trends of deep-water transport through this vital passage. With the estimated 12-year mean volume transport of the deep-water overflow into the SCS of 0.84 ± 0.39 Sv (1 Sv = 106 m3 s−1), a significant linear upward trend of 9% is revealed during this period. This is consistent with long-term changes in satellite-observed ocean bottom pressure. The results of this study may have broad implications for the overturning circulations and biogeochemical processes, including carbon cycles in this region.
Integrative modeling of tumor genomes and epigenomes for enhanced cancer diagnosis by cell-free DNA
Authors: Bae Mingyun , Kim Gyuhee , Lee Tae-Rim , Ahn Jin Mo , Park Hyunwook , Park Sook Ryun , Song Ki Byung , Jun Eunsung , Oh Dongryul , Lee Jeong-Won , Park Young Sik , Song Ki-Won , Byeon Jeong-Sik , Kim Bo Hyun , Sohn Joo Hyuk , Kim Min Hwan , Kim Gun Min , Chie Eui Kyu , Kang Hyun-Cheol , Kong Sun-Young , Woo Sang Myung , Lee Jeong Eon , Ryu Jai Min , Lee Junnam , Kim Dasom , Ki Chang-Seok , Cho Eun-Hae , Choi Jung Kyoon
Published: April 2023

Multi-cancer early detection remains a key challenge in cell-free DNA (cfDNA)-based liquid biopsy. Here, we perform cfDNA whole-genome sequencing to generate two test datasets covering 2125 patient samples of 9 cancer types and 1241 normal control samples, and also a reference dataset for background variant filtering based on 20,529 low-depth healthy samples. An external cfDNA dataset consisting of 208 cancer and 214 normal control samples is used for additional evaluation. Accuracy for cancer detection and tissue-of-origin localization is achieved using our algorithm, which incorporates cancer type-specific profiles of mutation distribution and chromatin organization in tumor tissues as model references. Our integrative model detects early-stage cancers, including those of pancreatic origin, with high sensitivity that is comparable to that of late-stage detection. Model interpretation reveals the contribution of cancer type-specific genomic and epigenomic features. Our methodologies may lay the groundwork for accurate cfDNA-based cancer diagnosis, especially at early stages.
Performance efficient macromolecular mechanics via sub-nanometer shape based coarse graining
Authors: Bryer Alexander J. , Rey Juan S. , Perilla Juan R.
Published: April 2023

Dimensionality reduction via coarse grain modeling is a valuable tool in biomolecular research. For large assemblies, ultra coarse models are often knowledge-based, relying on a priori information to parameterize models thus hindering general predictive capability. Here, we present substantial advances to the shape based coarse graining (SBCG) method, which we refer to as SBCG2. SBCG2 utilizes a revitalized formulation of the topology representing network which makes high-granularity modeling possible, preserving atomistic details that maintain assembly characteristics. Further, we present a method of granularity selection based on charge density Fourier Shell Correlation and have additionally developed a refinement method to optimize, adjust and validate high-granularity models. We demonstrate our approach with the conical HIV-1 capsid and heteromultimeric cofilin-2 bound actin filaments. Our approach is available in the Visual Molecular Dynamics (VMD) software suite, and employs a CHARMM-compatible Hamiltonian that enables high-performance simulation in the GPU-resident NAMD3 molecular dynamics engine.
Coupling acid catalysis and selective oxidation over MoO3-Fe2O3 for chemical looping oxidative dehydrogenation of propane
Authors: Wang Xianhui , Pei Chunlei , Zhao Zhi-Jian , Chen Sai , Li Xinyu , Sun Jiachen , Song Hongbo , Sun Guodong , Wang, Wei , Chang Xin , Zhang Xianhua , Gong Jinlong
Published: April 2023

Redox catalysts play a vital role in chemical looping oxidative dehydrogenation processes, which have recently been considered to be a promising prospect for propylene production. This work describes the coupling of surface acid catalysis and selective oxidation from lattice oxygen over MoO3-Fe2O3 redox catalysts for promoted propylene production. Atomically dispersed Mo species over γ-Fe2O3 introduce effective acid sites for the promotion of propane conversion. In addition, Mo could also regulate the lattice oxygen activity, which makes the oxygen species from the reduction of γ-Fe2O3 to Fe3O4 contribute to selectively oxidative dehydrogenation instead of over-oxidation in pristine γ-Fe2O3. The enhanced surface acidity, coupled with proper lattice oxygen activity, leads to a higher surface reaction rate and moderate oxygen diffusion rate. Consequently, this coupling strategy achieves a robust performance with 49% of propane conversion and 90% of propylene selectivity for at least 300 redox cycles and ultimately demonstrates a potential design strategy for more advanced redox catalysts.
Engineered CRISPR-OsCas12f1 and RhCas12f1 with robust activities and expanded target range for genome editing
Authors: Kong Xiangfeng , Zhang Hainan , Li Guoling , Wang Zikang , Kong Xuqiang , Wang Lecong , Xue Mingxing , Zhang Weihong , Wang Yao , Lin Jiajia , Zhou Jingxing , Shen Xiaowen , Wei Yinghui , Zhong Na , Bai Weiya , Yuan Yuan , Shi Linyu , Zhou Yingsi , Yang Hui
Published: April 2023

The type V-F CRISPR-Cas12f system is a strong candidate for therapeutic applications due to the compact size of the Cas12f proteins. In this work, we identify six uncharacterized Cas12f1 proteins with nuclease activity in mammalian cells from assembled bacterial genomes. Among them, OsCas12f1 (433 aa) from Oscillibacter sp. and RhCas12f1 (415 aa) from Ruminiclostridium herbifermentans, which respectively target 5’ T-rich Protospacer Adjacent Motifs (PAMs) and 5’ C-rich PAMs, show the highest editing activity. Through protein and sgRNA engineering, we generate enhanced OsCas12f1 (enOsCas12f1) and enRhCas12f1 variants, with 5’-TTN and 5’-CCD (D = not C) PAMs respectively, exhibiting much higher editing efficiency and broader PAMs, compared with the engineered variant Un1Cas12f1 (Un1Cas12f1_ge4.1). Furthermore, by fusing the destabilized domain with enOsCas12f1, we generate inducible-enOsCas12f1 and demonstate its activity in vivo by single adeno-associated virus delivery. Finally, dead enOsCas12f1-based epigenetic editing and gene activation can also be achieved in mammalian cells. This study thus provides compact gene editing tools for basic research with remarkable promise for therapeutic applications.
Temporal and spatial variability of dynamic microstate brain network in early Parkinson’s disease
Authors: Chu Chunguang , Zhang Zhen , Wang Jiang , Li Zhen , Shen Xiao , Han Xiaoxuan , Bai Lipeng , Liu Chen , Zhu Xiaodong
Published: April 2023

Changes of brain network dynamics reveal variations in macroscopic neural activity patterns in behavioral and cognitive aspects. Quantification and application of changed dynamics in brain functional connectivity networks may contribute to a better understanding of brain diseases, and ultimately provide better prognostic indicators or auxiliary diagnostic tools. At present, most studies are focused on the properties of brain functional connectivity network constructed by sliding window method. However, few studies have explored evidence-based brain network construction algorithms that reflect disease specificity. In this work, we first proposed a novel approach to characterize the spatiotemporal variability of dynamic functional connectivity networks based on electroencephalography (EEG) microstate, and then developed a classification framework for integrating spatiotemporal variability of brain networks to improve early Parkinson’s disease (PD) diagnostic performance. The experimental results indicated that compared with the brain network construction method based on conventional sliding window, the proposed method significantly improved the performance of early PD recognition, demonstrating that the dynamic spatiotemporal variability of microstate-based brain networks can reflect the pathological changes in the early PD brain. Furthermore, we observed that the spatiotemporal variability of early PD brain network has a specific distribution pattern in brain regions, which can be quantified as the degree of motor and cognitive impairment, respectively. Our work offers innovative methodological support for future research on brain network, and provides deeper insights into the spatiotemporal interaction patterns of brain activity and their variabilities in early PD.
Optimization of Cas9 activity through the addition of cytosine extensions to single-guide RNAs
Authors: Kawamata Masaki , Suzuki Hiroshi I. , Kimura Ryota , Suzuki Atsushi
Published: April 2023

The precise regulation of the activity of Cas9 is crucial for safe and efficient editing. Here we show that the genome-editing activity of Cas9 can be constrained by the addition of cytosine stretches to the 5′-end of conventional single-guide RNAs (sgRNAs). Such a ‘safeguard sgRNA’ strategy, which is compatible with Cas12a and with systems for gene activation and interference via CRISPR (clustered regularly interspaced short palindromic repeats), leads to the length-dependent inhibition of the formation of functional Cas9 complexes. Short cytosine extensions reduced p53 activation and cytotoxicity in human pluripotent stem cells, and enhanced homology-directed repair while maintaining bi-allelic editing. Longer extensions further decreased on-target activity yet improved the specificity and precision of mono-allelic editing. By monitoring indels through a fluorescence-based allele-specific system and computational simulations, we identified optimal windows of Cas9 activity for a number of genome-editing applications, including bi-allelic and mono-allelic editing, and the generation and correction of disease-associated single-nucleotide substitutions via homology-directed repair. The safeguard-sgRNA strategy may improve the safety and applicability of genome editing.
Expanding known viral diversity in the healthy infant gut
Authors: Shah Shiraz A. , Deng Ling , Thorsen Jonathan , Pedersen Anders G. , Dion Moïra B. , Castro-Mejía Josué L. , Silins Ronalds , Romme Fie O. , Sausset Romain , Jessen Leon E. , Ndela Eric Olo , Hjelmsø Mathis , Rasmussen Morten A. , Redgwell Tamsin A. , Leal Rodríguez Cristina , Vestergaard Gisle , Zhang Yichang , Chawes Bo , Bønnelykke Klaus , Sørensen Søren J. , Bisgaard Hans , Enault Francois , Stokholm Jakob , Moineau Sylvain , Petit Marie-Agnès , Nielsen Dennis S.
Published: April 2023

The gut microbiome is shaped through infancy and impacts the maturation of the immune system, thus protecting against chronic disease later in life. Phages, or viruses that infect bacteria, modulate bacterial growth by lysis and lysogeny, with the latter being especially prominent in the infant gut. Viral metagenomes (viromes) are difficult to analyse because they span uncharted viral diversity, lacking marker genes and standardized detection methods. Here we systematically resolved the viral diversity in faecal viromes from 647 1-year-olds belonging to Copenhagen Prospective Studies on Asthma in Childhood 2010, an unselected Danish cohort of healthy mother–child pairs. By assembly and curation we uncovered 10,000 viral species from 248 virus family-level clades (VFCs). Most (232 VFCs) were previously unknown, belonging to theCaudoviricetesviral class. Hosts were determined for 79% of phage using clustered regularly interspaced short palindromic repeat spacers within bacterial metagenomes from the same children. TypicalBacteroides-infecting crAssphages were outnumbered by undescribed phage families infectingClostridialesandBifidobacterium. Phage lifestyles were conserved at the viral family level, with 33 virulent and 118 temperate phage families. Virulent phages were more abundant, while temperate ones were more prevalent and diverse. Together, the viral families found in this study expand existing phage taxonomy and provide a resource aiding future infant gut virome research.
Observation of strong backscattering in valley-Hall photonic topological interface modes
Authors: Rosiek Christian Anker , Arregui Guillermo , Vladimirova Anastasiia , Albrechtsen Marcus , Vosoughi Lahijani Babak , Christiansen Rasmus Ellebæk , Stobbe Søren
Published: April 2023

The unique properties of light underpin the visions of photonic quantum technologies, optical interconnects and a wide range of novel sensors, but a key limiting factor today is losses due to either absorption or backscattering on defects. Recent developments in topological photonics have fostered the vision of backscattering-protected waveguides made from topological interface modes, but, surprisingly, measurements of their propagation losses were so far missing. Here we report on measurements of losses in the slow-light regime of valley-Hall topological waveguides and find no indications of topological protection against backscattering on ubiquitous structural defects. We image the light scattered out from the topological waveguides and find that the propagation losses are due to Anderson localization. The only photonic topological waveguides proposed for materials without intrinsic absorption in the optical domain are quantum spin-Hall and valley-Hall interface states, but the former exhibit strong out-of-plane losses, and our work, therefore, raises fundamental questions about the real-world value of topological protection in reciprocal photonics.
DisP-seq reveals the genome-wide functional organization of DNA-associated disordered proteins
Authors: Xing Yu-Hang , Dong Rui , Lee Lukuo , Rengarajan Shruthi , Riggi Nicolò , Boulay Gaylor , Rivera Miguel N.
Published: April 2023

Intrinsically disordered regions (IDRs) in DNA-associated proteins are known to influence gene regulation, but their distribution and cooperative functions in genome-wide regulatory programs remain poorly understood. Here we describe DisP-seq (disordered protein precipitation followed by DNA sequencing), an antibody-independent chemical precipitation assay that can simultaneously map endogenous DNA-associated disordered proteins genome-wide through a combination of biotinylated isoxazole precipitation and next-generation sequencing. DisP-seq profiles are composed of thousands of peaks that are associated with diverse chromatin states, are enriched for disordered transcription factors (TFs) and are often arranged in large lineage-specific clusters with high local concentrations of disordered proteins and different combinations of histone modifications linked to regulatory potential. We use DisP-seq to analyze cancer cells and reveal how disordered protein-associated islands enable IDR-dependent mechanisms that control the binding and function of disordered TFs, including oncogene-dependent sequestration of TFs through long-range interactions and the reactivation of differentiation pathways upon loss of oncogenic stimuli in Ewing sarcoma.
Comparative analysis of bacterial diversity in two hot springs in Hefei, China
Authors: Zhang Feng-Qin , Liu Jun , Chen Xiao-Ju
Published: April 2023

Hot springs are extreme ecological environments of microbes. The study is the first comparative analysis of bacterial diversity of Tangchi and Bantang hot spring water samples collected in Hefei, China, which is conducive to the further development and utilization of microbial resources in hot springs. Illumina MiSeq system was utilized to sequence and analyze the bacterial 16S rRNA gene from hot spring water samples by bioinformatics, to probe into the bacterial abundance and diversity of two hot springs in Hefei. Results revealed that prevalent bacterial phyla in Tangchi hot spring were Bacillota and Aquificota, and the prevalent bacterial genus was Hydrogenobacter; prevalent phyla in Bantang hot spring were Pseudomonadota followed by Actinobacteriota, and prevalent genera were CL500-29_marine_group and Polynucleobacter. More species and higher evenness in Bantang hot spring than those in Tangchi hot spring. In MetaCyc pathway analysis, the major pathways of metabolism existed in the bacteria from the two hot springs were ‘pyruvate fermentation to isobutanol (engineered)’, ‘acetylene degradation’, ‘carbon fixation pathways in prokaryotes’, ‘nitrate reduction I (denitrification)’, ‘methanogenesis from acetate’, ‘superpathway of glucose and xylose degradation’, etc.
Contact time and disinfectant formulation significantly impact the efficacies of disinfectant towelettes against Candida auris on hard, non-porous surfaces
Authors: Voorn Maxwell G. , Kelley Alyssa M. , Chaggar Gurpreet K. , Li Xiaobao , Teska Peter J. , Oliver Haley F.
Published: April 2023

There has been an increase in Candida auris healthcare-associated infections, which result from cross-contamination from surfaces and equipment. In this study, we tested the efficacies of EPA-registered disinfectant towelettes products that are increasingly used for infection control against C. auris at a range of contact times following modifications to standard EPA protocol MB-33-00. Hydrogen peroxide (HP)-based disinfectant towelettes were more efficacious against C. auris than the quaternary ammonium chloride (QAC)-alcohol-based disinfectant towelettes irrespective of tested contact times. Thirty s contact time was significantly less effective in reducing C. auris compared to 1-, 2-, 3-, and 10-min contact times. However, there were no statistically significant differences in the level of disinfection among 1-min and longer contact times regardless of product chemistry. None of the products achieved a standard six-log10 reduction at any tested contact times. Overall, the HP-based disinfectant towelette was significantly more fungicidal than the QAC-alcohol-based disinfectant towelette. For all product types, 30 s contact time did not achieve the same level of disinfection as 1-min or longer contact times. Overall, disinfectant towelette efficacy is dependent upon product formulation and contact time.
Effects of adipose derived stem cells pretreated with resveratrol on sciatic nerve regeneration in rats
Authors: Zhang Ziqiang , Zhang Mengyu , Sun Yingying , Li Monan , Chang Chenhao , Liu Weiqi , Zhu Xuemin , Wei Lan , Wen Fengyun , Liu Yumei
Published: April 2023

Adipose derived stem cells (ADSCs) are popular in regenerative medicine due to their easy availability, low immunogenicity and lack of controversy regarding their ethical debate use. Although ADSCs can repair nerve damage, the oxidative microenvironment of damaged tissue can induce apoptosis of transplanted stem cells, which weakens the therapeutic efficacy of ADSCs. Resveratrol (Res) is a type of natural polyphenol compound that regulates the proliferation, senescence and differentiation of stem cells. Therefore, we investigated whether incubation of ADSCs with Res improves their to promote peripheral nerve regeneration. ADSCs were cultured in vitro and treated with H2O2 to establish an apoptosis model. The control, H2O2 and Res groups were set up. The cell survival rate was detected by the CCK-8 method. The TUNEL assay was used to detect the apoptosis of the cells. qRT‒PCR was used to analyze the expression of apoptosis-related mRNA, and the effect of Res on the proliferation of ADSCs was investigated. In vivo, 40 SD rats were randomly divided into the control, model, ADSCs and ADSC + Res groups, with 13 rats in each group. The sciatic nerve injury rat model was established by the clamp method. Gait was observed on Days 7, 14, 21, and 28. Sciatic nerve regeneration was detected on Day 28. Res had no effect on the proliferation of ADSCs, and the TUNEL assay confirmed that Res pretreatment could significantly improve H2O2-induced apoptosis in ADSCs. Compared with the control group, caspase-3, Bax and Bcl-2 expression levels were significantly increased in the H2O2 group. Compared with the H2O2 group caspase-3 and Bax expression levels were significantly decreased, and Bcl-2 expression levels were significantly increased in ADSCs + Res group. At 4 weeks after surgery, the functional index of the sciatic nerve in the ADSCs + Res group was significantly higher than that in the model group. On Day 28, the average density of the sciatic nerve myelin sheath in the ADSCs + Res group was significantly increased compared with that in the model group, and Nissl staining showed that the number of motor neurons in the spinal cord was significant compared with that in the model group. Compared with the control group, the wet weight ratio of gastrocnemius muscle and muscle fiber area in ADSCs + Res group were significantly increased. Res enhanced the ability of ADSCs to promote sciatic nerve regeneration in rats.
Investigating the effects of beta-blockers on circadian heart rhythm using heart rate variability in ischemic heart disease with preserved ejection fraction
Authors: Saleem Shiza , Khandoker Ahsan H. , Alkhodari Mohanad , Hadjileontiadis Leontios J. , Jelinek Herbert F.
Published: April 2023

Heart failure is characterized by sympathetic activation and parasympathetic withdrawal leading to an abnormal autonomic modulation. Beta-blockers (BB) inhibit overstimulation of the sympathetic system and are indicated in heart failure patients with reduced ejection fraction. However, the effect of beta-blocker therapy on heart failure with preserved ejection fraction (HFpEF) is unclear. ECGs of 73 patients with HFpEF > 55% were recruited. There were 56 patients in the BB group and 17 patients in the without BB (NBB) group. The HRV analysis was performed for the 24-h period using a window size of 1,4 and 8-h. HRV measures between day and night for both the groups were also compared. Percentage change in the BB group relative to the NBB group was used as a measure of difference. RMSSD (13.27%), pNN50 (2.44%), HF power (44.25%) and LF power (13.53%) showed an increase in the BB group relative to the NBB group during the day and were statistically significant between the two groups for periods associated with high cardiac risk during the morning hours. LF:HF ratio showed a decrease of 3.59% during the day. The relative increase in vagal modulated RMSSD, pNN50 and HF power with a decrease in LF:HF ratio show an improvement in the parasympathetic tone and an overall decreased risk of a cardiac event especially during the morning hours that is characterized by a sympathetic surge.
High-resolution imaging enabled by 100-kW-peak-power parametric source at 5.7 THz
Authors: Kuo Cang-He , Wu Ming-Hsiung , Chen Chieh-Ru , Lin Yan-Jou , Laurell Fredrik , Huang Yen-Chieh
Published: April 2023

Similar to x-ray imaging, THz imaging will require high power and high resolution to advance relevant applications. Previously demonstrated THz imaging usually experiences one or several difficulties in insufficient source power, poor spectral tunability, or limited resolution from a low-wavelength source. A short-wavelength radiation source in the 5–10 THz is relatively scarce. Although a shorter wavelength improves imaging resolution, widely used imaging sensors, such as microbolometers, Schottky diodes, and photoconductive antennas, are usually not sensitive to detect radiation with frequencies above 5 THz. The radiation power of a high-frequency source becomes a key factor to realize low-noise and high-resolution imaging by using an ordinary pyroelectric detector. Here, we report a successful development of a fully coherent, tunable, > 100-kW-peak-power parametric source at 5.7 THz. It is then used together with a low-cost pyroelectric detector for demonstrating high-resolution 5.7-THz imaging in comparison with 2-THz imaging. To take advantage of the wavelength tunability of the source, we also report spectrally resolved imaging between 5.55 and 5.87 THz to reveal the spectroscopic characteristics and spatial distribution of a test drug, Aprovel.
Effects of the Hubbard potential on the NMR shielding and optoelectronic properties of BiMnVO5 compound
Authors: Rahnamaye Aliabad H. A. , Iqbal Muhammad Aamir , Amiri-Shookoh F. , Anwar Nadia , Bakhsh Sunila , Arellano-Ramírez Iván D.
Published: April 2023

This study explores the nuclear magnetic shielding, chemical shifts, and the optoelectronic properties of the BiMnVO5 compound using the full-potential linearized augmented plane wave method within the generalized gradient approximation by employing the Hubbard model (GGA + U). The 209Bi and 51V chemical shifts and bandgap values of the BiMnVO5 compound in a triclinic crystal structure are found to be directly related to Hubbard potential. The relationship between the isotropic nuclear magnetic shielding σiso and chemical shift δiso is obtained with a slope of 1.0231 and − 0.00188 for 209Bi and 51V atoms, respectively. It is also observed that the bandgap, isotropic nuclear magnetic shielding, and chemical shifts increase with the change in Hubbard potentials (U) of 3, 4, 5, 6, and 7.
Reference values for low muscle mass and myosteatosis using tomographic muscle measurements in living kidney donors
Authors: Westenberg Lisa B. , Zorgdrager Marcel , Swaab Tim D. A. , van Londen Marco , Bakker Stephan J. L. , Leuvenink Henri G. D. , Viddeleer Alain R. , Pol Robert A.
Published: April 2023

Low muscle mass and myosteatosis are associated with poor clinical outcomes. Computed tomography (CT) imaging is an objective method for muscle mass and quality assessment; however consensus on cut-off values is lacking. This study assessed age-, sex-, and body mass index (BMI)-specific reference values of skeletal muscle parameters and correlated muscle mass with 24-h urinary creatinine excretion (24-h UCE). In total, 960 healthy subjects were included in this study. Muscle mass and quality were determined using axial CT slices at the vertebral level L3. The muscle area was indexed for height (skeletal muscle index [SMI]). The mean age was 53 ± 11 years, and 50% were male. The SMI reference values for low muscle mass in males were 38.8 cm2/m2 (20–29 years), 39.2 (30–39 years), 39.9 (40–49 years), 39.0 (50–59 years), 37.0 (60–69 years), and 36.8 (70–79 years). For females, these reference values were 37.5 cm2/m2 (20–29 years), 35.5 (30–39 years), 32.8 (40–49 years), 33.2 (50–59 years), 31.2 (60–69 years), and 31.5 (70–79 years). 24-h UCE and SMI were significantly correlated (r = 0.54, p < 0.001) without bias between the two methods of assessing muscle mass. This study provides age-, sex-, and BMI-specific reference values for skeletal muscle parameters that will support clinical decision making.