bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Contrasting Rates of Phosphate Fertiliser Addition in Two Vertisols: Effects of Fresh Application and Residual Fertiliser on Sorption and Plant Uptake
Authors: Raymond Nelly S. , van der Bom Frederik J. T. , Janke Chelsea , Bell Michael J.
Published: June 2024

Cropping systems in many sub-tropical and tropical regions rely on phosphorus (P) fertilisers to maintain crop yields. However, crop responses are often spatially and temporally inconsistent. This study evaluated P availability from dispersed applications of fresh phosphate fertiliser and their residual effect in two contrasting Vertisols - a major soil type for crop production. We collected soils that had received mono-ammonium phosphate (MAP) fertiliser four years prior to sampling (residual), as well as unfertilised soils to which we applied MAP at equivalent rates (‘fresh’). Soil P tests quantified the potential P availability arising from the residual and fresh P applications, and P sorption curves were generated to describe the P sorption/desorption dynamics. A 45-day pot trial evaluated wheat growth and P uptake from fresh and residual P applications in both soils. Soil tests and sorption curves reflected differences in P addition in the two soils, although the sorption characteristics did not differ appreciably in response to residual P. Crop growth and P uptake strongly increased with increasing P availability, with greater responses for the freshly applied P. Low P recovery from aged fertiliser applications demonstrated that the availability of residual P for crop uptake after dispersed applications is limited in Vertisols. P-tests and sorption measurements could collectively capture potential soil P reactions and plant P availability in two contrasting Vertisols. Residual P benefits from dispersed applications remained low. Enrichment in a defined soil volume (i.e., banding) merits further investigation in this soil type.
Generalized Moment Estimators Based on Stein Identities
Authors: Nik Simon , Weiß Christian H.
Published: June 2024

For parameter estimation of continuous and discrete distributions, we propose a generalization of the method of moments (MM), where Stein identities are utilized for improved estimation performance. The construction of these Stein-type MM-estimators makes use of a weight function as implied by an appropriate form of the Stein identity. Our general approach as well as potential benefits thereof are first illustrated by the simple example of the exponential distribution. Afterward, we investigate the more sophisticated two-parameter inverse Gaussian distribution and the two-parameter negative-binomial distribution in great detail, together with illustrative real-world data examples. Given an appropriate choice of the respective weight functions, their Stein-MM estimators, which are defined by simple closed-form formulas and allow for closed-form asymptotic computations, exhibit a better performance regarding bias and mean squared error than competing estimators.
It is not just ‘the opposite of jealousy’: a Buddhist perspective on the emotion of compersion in consensually non-monogamous relationships
Authors: Yuen Hin Sing , Zörlein Luu , Walter Sven
Published: June 2024

Compersion is an affective state commonly discussed in the context of consensually non-monogamous relationships. It is typically described as a positive emotional reaction to one’s partner’s enjoying time and/or intimacy with another person, sort of ‘the opposite of jealousy’. Recent years have seen an increased interest in this seemingly startling emotion. Part of what makes understanding compersion so difficult is the mononormative expectations of our culture. We suggest that a non-Western, in particular Buddhist, perspective might be more helpful to understand that love and/or intimacy need not be an affair between two people only. We approach compersion through a Buddhist lens based on the ‘four immeasurables’, i.e. non-egocentric states that Buddhists take to promote well-being, and their ‘near enemies’, i.e. states which are easily conflated with them, but egocentric and harmful. Our goal is not to formulate a definition of compersion, nor to raise a normative bar for anyone who feels compersion, but to describe important facets of it that stand out more clearly against a Buddhist background than they might otherwise do. Such an approach not only enriches our understanding of compersion but contributes to people’s flourishing in all kinds of relationships and shows that non-monogamous relationships might be compatible with some forms of Buddhist practice.
Navigating the chromium conundrum: a review of heavy metal stress and bioremediation strategies
Authors: Jena Pooja , Hembram Padmalochan
Published: June 2024

Chromium contamination in soil, primarily originating from anthropogenic activities has always been a significant threat to plant and ecosystem health. Key factors influencing Cr-induced stress responses including oxidative stress, altered nutrient uptake and disruption of cellular processes are elucidated. The alterations in the signalling pathways & molecular reactions due to Chromium stress, leads to an abnormal production of certain harmful compounds like ROS and other secondary metabolites in the plant cells. These compounds must either be removed or detoxified for the plant to function normally and survive. This review provides an overview of the different signalling pathways, role of genes and proteins, hormesis effect of Cr, alterations in enzymatic activities and the physiological response of the plants. The role of biochar & microbes in bioremediation, hyper-accumulator plants in phytoremediation emerges as a natural yet effective solution in detoxifying the pollutants. The impacts and potential mitigation strategies to minimize and restore the contamination caused in the ecosystem is emphasized. This review provides valuable insights into the multifaceted interactions between plants and Cr stress. It also focuses on mitigating it by bioremediation mechanisms for sustainable environmental management.
Seasonal and Interannual Variability in the Distribution and Removal of Terrigenous Dissolved Organic Carbon in the Amazon River Plume
Authors: Martineac Rachel P. , Castelao Renato M. , Medeiros Patricia M.
Published: June 2024

The Amazon River is a large source of terrigenous dissolved organic carbon (tDOC) to the Atlantic Ocean. The fate of this tDOC in the ocean remains unclear despite its importance to the global carbon cycle. Here, we used two decades of satellite ocean color to describe variability in tDOC in the Amazon River plume. Our analyses showed that tDOC distribution has a distinct seasonal pattern, reaching northwest toward the Caribbean during high discharge periods, and moving eastward entrained in the North Brazil Current retroflection during low discharge periods. Elevated tDOC content extended beyond the shelfbreak in all months of the year, suggesting that cross‐shelf carbon transport occurs year‐round. Maximum variability was found at the plume core, where seasonality accounted for 40% of the total variance, while interannual variability accounted for 15% of the variance. Our results revealed a seasonal pattern in tDOC removal over the shelf with increased consumption in May when river discharge is high. Anomalies in tDOC removal over the shelf with respect to the seasonal cycle were significantly correlated with anomalies in tDOC concentration offshore of the shelfbreak with a lag of 30–40 days, so that anomalously high inshore tDOC removal was associated with anomalously low tDOC content offshore. This suggests that variability in the offshore transport of tDOC in the Amazon River plume is modulated by interannual changes in tDOC removal over the shelf.
Effect of Iron Content on the Thermal Conductivity and Thermal Diffusivity of Orthopyroxene
Authors: Guo Xinzhuan , Feng Bo , Zhang Baohua , Zhai Shuangmeng , Xue Weihong , Song Yunke , Song Yuping , Yan Xinxin
Published: June 2024

The thermal properties of major minerals play a key role in understanding the internal dynamic mechanism and thermal evolution of the Earth and rocky planets. In this study, we first investigated the effect of Fe on the thermal conductivity (κ) and the thermal diffusivity (D) of orthopyroxene at 1–3 GPa and 293–873 K by the transient plane source method. The κ and D both decrease with increasing temperature and decreasing pressure. With increasing Fe content, the two parameters both quickly decrease from the beginning and then slack off. We further modeled the thermal evolution of S‐type asteroids, which strongly depends on the composition model and the dimension of the planet. Combining the present data with surface heat flow and heat production, the lunar's geotherm until 1,400 km is constructed. The core‐mantle boundary temperature of the Moon is refined from 1,883 to 1,754 K.
A Seasonally Delayed Sea Ice Response and Arctic Amplification During the Last Glacial Inception
Authors: Xu Shan , Krebs‐Kanzow Uta , Lohmann Gerrit
Published: June 2024

The last glacial inception (LGI) marks the transition from the interglacial warm climate to the glacial period with extensive Northern Hemisphere ice sheets and colder climate. This transition is initiated by decreasing boreal summer insolation but requires positive feedbacks to stimulate the appearance of perennial snow. We perform simulations of LGI with climate model AWI‐ESM‐2.1, forced by the astronomical and greenhouse gas forcing of 115,000 years before present. To compare with the preindustrial (PI) simulation, we use a consistent definition of the seasons during the LGI and the PI and evaluate model output on an angular astronomical calendar. Our study reveals a prominent role of the sea‐ice albedo feedback to amplify the delayed climate signal at polar latitudes. Through a radiative budget analysis, we examine that the ice‐albedo feedback exceeds the shortwave radiative forcing, contributing to the cooling and high latitude snow built‐up during LGI.
Integrative single-cell and bulk transcriptomes analyses reveals heterogeneity of serine-glycine-one-carbon metabolism with distinct prognoses and therapeutic vulnerabilities in HNSCC
Authors: Wang Lixuan , Yang Rongchun , Kong Yue , Zhou Jing , Chen Yingyao , Li Rui , Chen Chuwen , Tang Xinran , Chen Xiaobing , Xia Juan , Chen Xijuan , Cheng Bin , Ren Xianyue
Published: June 2024

Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment (TME), which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma (HNSCC) patients. This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology. The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing (scRNA-seq) profiles and validated through bulk transcriptomes. Serine–glycine-one-carbon (SGOC) metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients. A 4-SGOC gene prognostic signature, constructed by LASSO-COX regression analysis, demonstrated good predictive performance for overall survival and therapeutic responses. Patients in the low-risk group exhibited greater infiltration of exhausted CD8+ T cells, and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy. Conversely, high-risk patients exhibited characteristics of cold tumors, with enhanced IMPDH1-mediated purine biosynthesis, resulting in poor responses to current therapies. IMPDH1 emerged as a potential therapeutic metabolic target. Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress. Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.
Mediating effect of adiponectin between free fatty acid and tumor necrosis factor-α in patients with diabetes
Authors: Xia Zhang , Shi Shulong , Ma Xiaoqing , Li Feng , Li Xinya , Gaisano Herbert Y. , Zhao Mingyang , Li Yuhao , He Yan , Jiang Jiajia
Published: June 2024

Background/Objectives

Increased free fatty acid (FFA) promotes adiponectin secretion in healthy subjects and induces inflammation in diabetes. Given the potential pro-inflammatory role of adiponectin in “adiponectin paradox”, we performed this study in patients with type 2 diabetes mellitus (T2DM) to assess the association of FFA with adiponectin and to investigate whether adiponectin mediates FFA-related inflammation.

Methods

This cross-sectional study consisted of adult patients with T2DM. FFA, adiponectin, and tumor necrosis factor-α (TNF-α) were assayed from fasting venous blood after overnight fasting for at least 8 h. Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between FFA and adiponectin. Mediation analysis was performed to determine the mediating effect of adiponectin on the association between FFA and TNF-α.

Results

This study included 495 participants, with 332 males (67.1%) and a mean age of 47.0 ± 11.2 years. FFA was positively associated with adiponectin (b = 0.126, 95%CI: 0.036–0.215, P = 0.006) and was the main contributor to the increase of adiponectin (standardized b = 0.141). The RCS analysis demonstrated that adiponectin increased with FFA when FFA was less than 0.7 mmol/L but did not further increase thereafter (Poverall < 0.001 and Pnon-linear < 0.001). In addition, adiponectin mediated the association between FFA and TNF-α. The mediating effect was 0.08 (95%CI: 0.03–0.13, P = 0.003) and the mediating effect percentage was 26.8% (95%CI: 4.5–49.2, P = 0.02).

Conclusions

In patients with T2DM, FFA was positively associated with adiponectin when FFA was less than 0.7 mmol/L. Elevated adiponectin mediated FFA-related inflammation. This study may provide insights into the pro-inflammatory effect of adiponectin in T2DM.
A novel blood-based epigenetic biosignature in first-episode schizophrenia patients through automated machine learning
Authors: Karaglani Makrina , Agorastos Agorastos , Panagopoulou Maria , Parlapani Eleni , Athanasis Panagiotis , Bitsios Panagiotis , Tzitzikou Konstantina , Theodosiou Theodosis , Iliopoulos Ioannis , Bozikas Vasilios-Panteleimon , Chatzaki Ekaterini
Published: June 2024

Schizophrenia (SCZ) is a chronic, severe, and complex psychiatric disorder that affects all aspects of personal functioning. While SCZ has a very strong biological component, there are still no objective diagnostic tests. Lately, special attention has been given to epigenetic biomarkers in SCZ. In this study, we introduce a three-step, automated machine learning (AutoML)-based, data-driven, biomarker discovery pipeline approach, using genome-wide DNA methylation datasets and laboratory validation, to deliver a highly performing, blood-based epigenetic biosignature of diagnostic clinical value in SCZ. Publicly available blood methylomes from SCZ patients and healthy individuals were analyzed via AutoML, to identify SCZ-specific biomarkers. The methylation of the identified genes was then analyzed by targeted qMSP assays in blood gDNA of 30 first-episode drug-naïve SCZ patients and 30 healthy controls (CTRL). Finally, AutoML was used to produce an optimized disease-specific biosignature based on patient methylation data combined with demographics. AutoML identified a SCZ-specific set of novel gene methylation biomarkers including IGF2BP1, CENPI, and PSME4. Functional analysis investigated correlations with SCZ pathology. Methylation levels of IGF2BP1 and PSME4, but not CENPI were found to differ, IGF2BP1 being higher and PSME4 lower in the SCZ group as compared to the CTRL group. Additional AutoML classification analysis of our experimental patient data led to a five-feature biosignature including all three genes, as well as age and sex, that discriminated SCZ patients from healthy individuals [AUC 0.755 (0.636, 0.862) and average precision 0.758 (0.690, 0.825)]. In conclusion, this three-step pipeline enabled the discovery of three novel genes and an epigenetic biosignature bearing potential value as promising SCZ blood-based diagnostics.
Three-dimensional assessment of obturation volume in lateral canals after three obturation techniques with bioceramic sealer: an in vitro comparative study
Authors: Juha Wahid , Sarkis Elizabeth , Alsayed Tolibah Yasser
Published: June 2024

Objective

This study aimed to evaluate the obturation ability of simulated lateral canal in mandibular premolars at three levels (3, 5, and 7 mm) from the apex using gutta-percha and BC Sealer HiFlow (BCHiF) with different obturation techniques, including continuous wave compaction (CWC), cold lateral condensation (CLC), and single cone (SC) techniques, by a 3D assessment method of the obturation volume with cone beam computed tomography (CBCT) and MIMICS software analysis.

Methods

Thirty intact human mandibular premolars were decoronated, instrumented up to #30 taper 4%, and uniformly irrigated with 5.25% NaOCl and 17% EDTA. Six simulated lateral canals (3 pairs) were prepared at 3, 5, and 7 mm from the apex in each root, using #10 modified C-file. CBCT images were obtained, and lateral canal volumes were calculated using MIMICS software. The samples were divided into three groups: CWC (n = 10), CLC (n = 10), and SC (n = 10). All groups were obturated with BCHiF and gutta-percha. Another CBCT image was taken post-obturation, and 3D lateral canal obturation volume percentages were calculated using MIMICS software. Data were analyzed using SPSS software with One-way ANOVA and Sidak tests (α = 0.05).

Results

Significant differences were observed in the 3D lateral canal obturation volume percentage at all three levels (P < 0.05). Both CWC and CLC techniques demonstrated higher 3D lateral canal obturation volume percentages ($$\bar{x}$$

x

¯

 = 89.64% and $$\bar{x}$$

x

¯

  =  73.28%; respectively) compared to the SC group) $$\bar{x}$$

x

¯

  =  43.10%).

Conclusion

BCHiF combined with the CWC technique has a higher ability to achieve preferable 3D obturation volume in the simulated lateral canal at 3, 5, and 7 mm.

Clinical relevance

In cases requiring endodontic treatment with lateral canals, the CWC obturation technique using BCHiF with gutta-percha may offer better outcomes compared to other obturation techniques.
The Mohawk homeobox gene represents a marker and osteo-inhibitory factor in calvarial suture osteoprogenitor cells
Authors: Wang Yiyun , Qin Qizhi , Wang Ziyi , Negri Stefano , Sono Takashi , Tower Robert J. , Li Zhao , Xing Xin , Archer Mary , Thottappillil Neelima , Zhu Manyu , Suarez Allister , Kim Deok-Ho , Harvey Tyler , Fan Chen-Ming , James Aaron W.
Published: June 2024

The regeneration of the mammalian skeleton’s craniofacial bones necessitates the action of intrinsic and extrinsic inductive factors from multiple cell types, which function hierarchically and temporally to control the differentiation of osteogenic progenitors. Single-cell transcriptomics of developing mouse calvarial suture recently identified a suture mesenchymal progenitor population with previously unappreciated tendon- or ligament-associated gene expression profile. Here, we developed a Mohawk homeobox (MkxCG; R26RtdT) reporter mouse and demonstrated that this reporter identifies an adult calvarial suture resident cell population that gives rise to calvarial osteoblasts and osteocytes during homeostatic conditions. Single-cell RNA sequencing (scRNA-Seq) data reveal that Mkx+ suture cells display a progenitor-like phenotype with expression of teno-ligamentous genes. Bone injury with Mkx+ cell ablation showed delayed bone healing. Remarkably, Mkx gene played a critical role as an osteo-inhibitory factor in calvarial suture cells, as knockdown or knockout resulted in increased osteogenic differentiation. Localized deletion of Mkx in vivo also resulted in robustly increased calvarial defect repair. We further showed that mechanical stretch dynamically regulates Mkx expression, in turn regulating calvarial cell osteogenesis. Together, we define Mkx+ cells within the suture mesenchyme as a progenitor population for adult craniofacial bone repair, and Mkx acts as a mechanoresponsive gene to prevent osteogenic differentiation within the stem cell niche.
Cascading hazards of a major Bengal basin earthquake and abrupt avulsion of the Ganges River
Authors: Chamberlain Elizabeth L. , Goodbred Steven L. , Steckler Michael S. , Wallinga Jakob , Reimann Tony , Akhter Syed Humayun , Bain Rachel , Muktadir Golam , Al Nahian Abdullah , Rahman F. M. Arifur , Rahman Mahfuzur , Seeber Leonardo , von Hagke Christoph
Published: June 2024

Earthquakes present severe hazards for people and economies and can be primary drivers of landscape change yet their impact to river-channel networks remains poorly known. Here we show evidence for an abrupt earthquake-triggered avulsion of the Ganges River at ~2.5 ka leading to relocation of the mainstem channel belt in the Bengal delta. This is recorded in freshly discovered sedimentary archives of an immense relict channel and a paleo-earthquake of sufficient magnitude to cause major liquefaction and generate large, decimeter-scale sand dikes >180 km from the nearest seismogenic source region. Precise luminescence ages of channel sand, channel fill, and breached and partially liquefied floodplain deposits support coeval timing of the avulsion and earthquake. Evidence for reorganization of the river-channel network in the world’s largest delta broadens the risk posed by seismic events in the region and their recognition as geomorphic agents in this and other tectonically active lowlands. The recurrence of comparable earthquake-triggered ground liquefaction and a channel avulsion would be catastrophic for any of the heavily populated, large river basins and deltas along the Himalayan arc (e.g., Indus, Ganges, Brahmaputra, Ayeyarwady). The compounding effects of climate change and human impacts heighten and extend the vulnerability of many lowlands worldwide to such cascading hazards.
HER2-targeting antibody drug conjugate FS-1502 in HER2-expressing metastatic breast cancer: a phase 1a/1b trial
Authors: Li Qiao , Cheng Ying , Tong Zhongsheng , Liu Yunjiang , Wang Xian , Yan Min , Chang Jianhua , Wang Shusen , Du Caiwen , Li Liang , Wu Chunjiao , Wang Mingxia , Wang Zhuo , Wu Zhuli , Wang Xingli , Jin Yongli , Diao Lei , Sun Yi , Zhang Yongjiao , Hui Ai-Min , Xu Binghe
Published: June 2024

Currently approved HER2-targeting antibody-drug conjugates (ADCs) for HER2-positive breast cancer (BC) are associated with safety concerns. In this multicenter, single-arm, dose-escalation (phase 1a) and dose-expansion (phase 1b) phase 1 trial (NCT03944499), patients with HER2-expressing advanced solid tumors received FS-1502 (an anti-HER2 ADC) with a 3 + 3 design in phase 1a; patients with metastatic HER2-positive BC received FS-1502 at the recommended phase 2 dose (RP2D) in phase 1b. The primary end points were dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and RP2D for phase 1a and objective response rate (ORR) for phase 1b. A total of 150 patients with HER2-expressing solid tumors (n = 5) and BC (n = 145) were enrolled (female, n = 146, 97.3%). One DLT each was reported at 3.0 and 3.5 mg/kg; the MTD was not reached. The RP2D was 2.3 mg/kg once every 3 weeks. Five (3.3%) patients experienced pneumonitis; four (2.7%) had grade 3 reversible ocular events. Of 67 HER2-positive BC patients receiving the RP2D, the best ORR was 53.7% (95% CI, 41.1-66.0%), including PRs confirmed (confirmed ORR, 37.5%) and pending for confirmation. FS-1502 was well tolerated with limited ocular and pulmonary findings and demonstrated promising antitumor activity in HER2-positive BC patients.
Rft1 catalyzes lipid-linked oligosaccharide translocation across the ER membrane
Authors: Chen Shuai , Pei Cai-Xia , Xu Si , Li Hanjie , liu Yi-Shi , Wang Yicheng , Jin Cheng , Dean Neta , Gao Xiao-Dong
Published: June 2024

The eukaryotic asparagine (N)-linked glycan is pre-assembled as a fourteen-sugar oligosaccharide on a lipid carrier in the endoplasmic reticulum (ER). Seven sugars are first added to dolichol pyrophosphate (PP-Dol) on the cytoplasmic face of the ER, generating Man5GlcNAc2-PP-Dol (M5GN2-PP-Dol). M5GN2-PP-Dol is then flipped across the bilayer into the lumen by an ER translocator. Genetic studies identified Rft1 as the M5GN2-PP-Dol flippase in vivo but are at odds with biochemical data suggesting Rft1 is dispensable for flipping in vitro. Thus, the question of whether Rft1 plays a direct or an indirect role during M5GN2-PP-Dol translocation has been controversial for over two decades. We describe a completely reconstituted in vitro assay for M5GN2-PP-Dol translocation and demonstrate that purified Rft1 catalyzes the translocation of M5GN2-PP-Dol across the lipid bilayer. These data, combined with in vitro results demonstrating substrate selectivity and rft1∆ phenotypes, confirm the molecular identity of Rft1 as the M5GN2-PP-Dol ER flippase.
Progressive senescence programs induce intrinsic vulnerability to aging-related female breast cancer
Authors: Bai Huiru , Liu Xiaoqin , Lin Meizhen , Meng Yuan , Tang Ruolan , Guo Yajing , Li Nan , Clarke Michael F. , Cai Shang
Published: June 2024

Cancer incidence escalates exponentially with advancing age; however, the underlying mechanism remains unclear. In this study, we build a chronological molecular clock at single-cell transcription level with a mammary stem cell-enriched population to depict physiological aging dynamics in female mice. We find that the mammary aging process is asynchronous and progressive, initiated by an early senescence program, succeeded by an entropic late senescence program with elevated cancer associated pathways, vulnerable to cancer predisposition. The transition towards senescence program is governed by a stem cell factor Bcl11b, loss of which accelerates mammary ageing with enhanced DMBA-induced tumor formation. We have identified a drug TPCA-1 that can rejuvenate mammary cells and significantly reduce aging-related cancer incidence. Our findings establish a molecular portrait of progressive mammary cell aging and elucidate the transcriptional regulatory network bridging mammary aging and cancer predisposition, which has potential implications for the management of cancer prevalence in the aged.
Organic fertilization co-selects genetically linked antibiotic and metal(loid) resistance genes in global soil microbiome
Authors: Liu Zi-Teng , Ma Rui-Ao , Zhu Dong , Konstantinidis Konstantinos T. , Zhu Yong-Guan , Zhang Si-Yu
Published: June 2024

Antibiotic resistance genes (ARGs) and metal(loid) resistance genes (MRGs) coexist in organic fertilized agroecosystems based on their correlations in abundance, yet evidence for the genetic linkage of ARG-MRGs co-selected by organic fertilization remains elusive. Here, an analysis of 511 global agricultural soil metagenomes reveals that organic fertilization correlates with a threefold increase in the number of diverse types of ARG-MRG-carrying contigs (AMCCs) in the microbiome (63 types) compared to non-organic fertilized soils (22 types). Metatranscriptomic data indicates increased expression of AMCCs under higher arsenic stress, with co-regulation of the ARG-MRG pairs. Organic fertilization heightens the coexistence of ARG-MRG in genomic elements through impacting soil properties and ARG and MRG abundances. Accordingly, a comprehensive global map was constructed to delineate the distribution of coexistent ARG-MRGs with virulence factors and mobile genes in metagenome-assembled genomes from agricultural lands. The map unveils a heightened relative abundance and potential pathogenicity risks (range of 4-6) for the spread of coexistent ARG-MRGs in Central North America, Eastern Europe, Western Asia, and Northeast China compared to other regions, which acquire a risk range of 1-3. Our findings highlight that organic fertilization co-selects genetically linked ARGs and MRGs in the global soil microbiome, and underscore the need to mitigate the spread of these co-resistant genes to safeguard public health.
Relatively stable pressure effects and time-increasing thermal contraction control Heber geothermal field deformation
Authors: Jiang Guoyan , Barbour Andrew J. , Skoumal Robert J. , Materna Kathryn , Taron Joshua , Crandall-Bear Aren
Published: June 2024

Due to geological complexities and observational gaps, it is challenging to identify the governing physical processes of geothermal field deformation including ground subsidence and earthquakes. In the west and east regions of the Heber Geothermal Field (HGF), decade-long subsidence was occurring despite injection of heat-depleted brines, along with transient reversals between uplift and subsidence. These observed phenomena contradict current knowledge that injection leads to surface uplift. Here we show that high-yield production wells at the HGF center siphon fluid from surrounding regions, which can cause subsidence at low-rate injection locations. Moreover, the thermal contraction effect by cooling increases with time and eventually overwhelms the pressure effects of pressure fluctuation and poroelastic responses, which keep relatively stable during geothermal operations. The observed subsidence anomalies result from the siphoning effect and thermal contraction. We further demonstrate that thermal contraction dominates long-term trends of surface displacement and seismicity growth, while pressure effects drive near-instantaneous changes.
Engineering ZrO2–Ru interface to boost Fischer-Tropsch synthesis to olefins
Authors: Yu Hailing , Wang Caiqi , Xin Xin , Wei Yao , Li Shenggang , An Yunlei , Sun Fanfei , Lin Tiejun , Zhong Liangshu
Published: June 2024

Understanding the structures and reaction mechanisms of interfacial active sites in the Fisher-Tropsch synthesis reaction is highly desirable but challenging. Herein, we show that the ZrO2-Ru interface could be engineered by loading the ZrO2 promoter onto silica-supported Ru nanoparticles (ZrRu/SiO2), achieving 7.6 times higher intrinsic activity and ~45% reduction in the apparent activation energy compared with the unpromoted Ru/SiO2 catalyst. Various characterizations and theoretical calculations reveal that the highly dispersed ZrO2 promoter strongly binds the Ru nanoparticles to form the Zr-O-Ru interfacial structure, which strengthens the hydrogen spillover effect and serves as a reservoir for active H species by forming Zr-OH* species. In particular, the formation of the Zr-O-Ru interface and presence of the hydroxyl species alter the H-assisted CO dissociation route from the formyl (HCO*) pathway to the hydroxy-methylidyne (COH*) pathway, significantly lowering the energy barrier of rate-limiting CO dissociation step and greatly increasing the reactivity. This investigation deepens our understanding of the metal-promoter interaction, and provides an effective strategy to design efficient industrial Fisher-Tropsch synthesis catalysts.
MOC1 cleaves Holliday junctions through a cooperative nick and counter-nick mechanism mediated by metal ions
Authors: Zhang Danping , Xu Shenjie , Luo Zhipu , Lin Zhonghui
Published: June 2024

Holliday junction resolution is a crucial process in homologous recombination and DNA double-strand break repair. Complete Holliday junction resolution requires two stepwise incisions across the center of the junction, but the precise mechanism of metal ion-catalyzed Holliday junction cleavage remains elusive. Here, we perform a metal ion-triggered catalysis in crystals to investigate the mechanism of Holliday junction cleavage by MOC1. We capture the structures of MOC1 in complex with a nicked Holliday junction at various catalytic states, including the ground state, the one-metal ion binding state, and the two-metal ion binding state. Moreover, we also identify a third metal ion that may aid in the nucleophilic attack on the scissile phosphate. Further structural and biochemical analyses reveal a metal ion-mediated allosteric regulation between the two active sites, contributing to the enhancement of the second strand cleavage following the first strand cleavage, as well as the precise symmetric cleavage across the Holliday junction. Our work provides insights into the mechanism of metal ion-catalyzed Holliday junction resolution by MOC1, with implications for understanding how cells preserve genome integrity during the Holliday junction resolution phase.
Highly efficient dual photoredox/copper catalyzed atom transfer radical polymerization achieved through mechanism-driven photocatalyst design
Authors: Jeon Woojin , Kwon Yonghwan , Kwon Min Sang
Published: June 2024

Atom transfer radical polymerization (ATRP) with dual photoredox/copper catalysis combines the advantages of photo-ATRP and photoredox-mediated ATRP, utilizing visible light and ensuring broad monomer scope and solvent compatibility while minimizing side reactions. Despite its popularity, challenges include high photocatalyst (PC) loadings (10 to 1000 ppm), requiring additional purification and increasing costs. In this study, we discover a PC that functions at the sub-ppm level for ATRP through mechanism-driven PC design. Through studying polymerization mechanisms, we find that the efficient polymerizations are driven by PCs whose ground state oxidation potential—responsible for PC regeneration—play a more important role than their excited state reducing power, responsible for initiation. This is verified by screening PCs with varying redox potentials and triplet excited state generation capabilities. Based on these findings, we identify a highly efficient PC, 4DCDP-IPN, featuring moderate excited state reducing power and a maximized ground state oxidation potential. Employing this PC at 50 ppb, we synthesize poly(methyl methacrylate) with high conversion, narrow molecular weight distribution, and high chain-end fidelity. This system exhibits oxygen tolerance and supports large-scale reactions under ambient conditions. Our findings, driven by the systematic PC design, offer meaningful insights for controlled radical polymerizations and metallaphotoredox-mediated syntheses beyond ATRP.
Combined short-term and long-term emission controls improve air quality sustainably in China
Authors: Wen Zhang , Ma Xin , Xu Wen , Si Ruotong , Liu Lei , Ma Mingrui , Zhao Yuanhong , Tang Aohan , Zhang Yangyang , Wang Kai , Zhang Ying , Shen Jianlin , Zhang Lin , Zhao Yu , Zhang Fusuo , Goulding Keith , Liu Xuejun
Published: June 2024

The effectiveness of national policies for air pollution control has been demonstrated, but the relative effectiveness of short-term emission reduction measures in comparison with national policies has not. Here we show that short-term abatement measures during important international events substantially reduced PM2.5 concentrations, but air quality rebounded to pre-event levels after the measures ceased. Long-term adherence to strict emission reduction policies led to successful decreases of 54% in PM2.5 concentrations in Beijing, and 23% in atmospheric nitrogen deposition in China from 2012 to 2020. Incentivized by “blue skies” type campaigns, economic development and reactive nitrogen pollution are quickly decoupled, showing that a combination of inspiring but aggressive short-term measures and effective but durable long-term policies delivers sustainable air quality improvement. However, increased ammonia concentrations, transboundary pollutant flows, and the complexity to achieving reduction targets under climate change scenarios, underscore the need for the synergistic control of multiple pollutants and inter-regional action.
Topoisomerase I is an evolutionarily conserved key regulator for satellite DNA transcription
Authors: Teng Zhen , Yang Lu , Zhang Qian , Chen Yujue , Wang Xianfeng , Zheng Yiran , Tian Aiguo , Tian Di , Lin Zhen , Deng Wu-Min , Liu Hong
Published: June 2024

RNA Polymerase (RNAP) II transcription on non-coding repetitive satellite DNAs plays an important role in chromosome segregation, but a little is known about the regulation of satellite transcription. We here show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite DNAs on human centromeres. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation. Interestingly, in response to DNA double-stranded breaks (DSBs), α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner, and these DSB-induced α-satellite RNAs form into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.
All-optical steering on the proton emission in laser-induced nanoplasmas
Authors: Sun Fenghao , Qu Qiwen , Li Hui , Jiang Shicheng , Liu Qingcao , Ben Shuai , Pei Yu , Liang Jiaying , Wang Jiawei , Song Shanshan , Gao Jian , Yang Weifeng , Xu Hongxing , Wu Jian
Published: June 2024

Nanoplasmas induced by intense laser fields have attracted enormous attention due to their accompanied spectacular physical phenomena which are vigorously expected by the community of science and industry. For instance, the energetic electrons and ions produced in laser-driven nanoplasmas are significant for the development of compact beam sources. Nevertheless, effective confinement on the propagating charged particles, which was realized through magnetic field modulation and target structure design in big facilities, are largely absent in the microscopic regime. Here we introduce a reliable scheme to provide control on the emission direction of protons generated from surface ionization in gold nanoparticles driven by intense femtosecond laser fields. The ionization level of the nanosystem provides us a knob to manipulate the characteristics of the collective proton emission. The most probable emission direction can be precisely steered by tuning the excitation strength of the laser pulses. This work opens new avenue for controlling the ion emission in nanoplasmas and can vigorously promote the fields such as development of on-chip beam sources at micro-/nano-scales.
Ultrabright and stable top-emitting quantum-dot light-emitting diodes with negligible angular color shift
Authors: Li Mengqi , Li Rui , Wu Longjia , Lin Xiongfeng , Xia Xueqing , Ao Zitong , Sun Xiaojuan , Chen Xingtong , Chen Song
Published: June 2024

Top emission can enhance luminance, color purity, and panel-manufacturing compatibility for emissive displays. Still, top-emitting quantum-dot light-emitting diodes (QLEDs) suffer from poor stability, low light outcoupling, and non-negligible viewing-angle dependence because, for QLEDs with non-red emission, the electrically optimum device structure is incompatible with single-mode optical microcavity. Here, we demonstrate that by improving the way of determining reflection penetration depths and creating refractive-index-lowering processes, the issues faced by green QLEDs can be overcome. This leads to advanced device performance, including a luminance exceeding 1.6 million nits, a current efficiency of 204.2 cd A−1, and a T95 operational lifetime of 15,600 hours at 1000 nits. Meanwhile, our design does not compromise light outcoupling as it offers an external quantum efficiency of 29.2% without implementing light extraction methods. Lastly, an angular color shift of Δu’v’ = 0.0052 from 0° to 60° is achieved by narrowing the emission linewidth of quantum dots.
Environmental and genetic regulation of Streptococcus pneumoniae galactose catabolic pathways
Authors: Kareem Banaz O. , Gazioglu Ozcan , Mueller Brown Karina , Habtom Medhanie , Glanville David G. , Oggioni Marco R. , Andrew Peter W. , Ulijasz Andrew T. , Hiller N. Luisa , Yesilkaya Hasan
Published: June 2024

Efficient utilization of nutrients is crucial for microbial survival and virulence. The same nutrient may be utilized by multiple catabolic pathways, indicating that the physical and chemical environments for induction as well as their functional roles may differ. Here, we study the tagatose and Leloir pathways for galactose catabolism of the human pathogen Streptococcus pneumoniae. We show that galactose utilization potentiates pneumococcal virulence, the induction of galactose catabolic pathways is influenced differentially by the concentration of galactose and temperature, and sialic acid downregulates galactose catabolism. Furthermore, the genetic regulation and in vivo induction of each pathway differ, and both galactose catabolic pathways can be turned off with a galactose analogue in a substrate-specific manner, indicating that galactose catabolic pathways can be potential drug targets.
Breast cancer survivors’ opinion on personalizing endocrine therapy and developing informative tools
Authors: Rassy Elie , Benvenuti Chiara , Akla Sarra , Di Meglio Antonio , Martin Elise , Havas Julie , Rieutord André , Combarel David , Fasse Léonor , Scotté Florian , Guéroult Accolas Laure , Jacob Guillemette , Bergougnoux Anne , Delaloge Suzette , Vaz-Luis Ines , Pistilli Barbara
Published: June 2024

Understanding breast cancer survivors’ perspectives is critical to personalizing endocrine therapy (ET) in the adjuvant setting. A nationwide survey among breast cancer survivors was proposed in France, in collaboration with patient advocacy organizations, to assess their perspectives on personalizing ET and developing dedicated informative tools. This survey explored patients’ preferences regarding ET intake schedule, formulation, presentation (color, taste, shape, size, design, and packaging), combination with agents targeting ET-related adverse events, and a mobile application to support them during ET. Of the 1103 individuals who started the survey, 939 (85.1%) were eligible for enrollment and completed the survey. The majority of the participants considered that a personalized ET should take into consideration the intake schedule (n = 974, 90.7%) and swallowable tablet formulation (n = 606, 64.5%), without a preference for ET presentation (n = 619; 65.9%). The majority of the participants expressed a willingness to participate in a potential clinical trial evaluating the combination of ET with agents targeting ET-related adverse events at the start of ET (n = 752, 80.1%) or in the case of major ET-related adverse events (n = 778, 82.8%). The primary considerations were to have an uncompromised ET efficacy and a guaranteed reduction of adverse events. Last, a dedicated mobile application was considered helpful by 665 participants (70.8%). Informative tools should focus on the recommendations for dealing with adverse events (n = 593, 63.2%), the impact on the patient’s daily life (n = 515, 54.9%), benefits (n = 504, 53.7%), and adverse events (n = 494, 52.6%) of ET. This survey paves the way for multimodal strategies that can include a personalized ET (e.g., ET in combination with agents targeting ET-related adverse events) and dedicated mobile applications to ultimately improve adherence.
Enhancement of erythropoietic output by Cas9-mediated insertion of a natural variant in haematopoietic stem and progenitor cells
Authors: Luna Sofia E. , Camarena Joab , Hampton Jessica P. , Majeti Kiran R. , Charlesworth Carsten T. , Soupene Eric , Selvaraj Sridhar , Jia Kun , Sheehan Vivien A. , Cromer M. Kyle , Porteus Matthew H.
Published: June 2024

Some gene polymorphisms can lead to monogenic diseases, whereas other polymorphisms may confer beneficial traits. A well-characterized example is congenital erythrocytosis—the non-pathogenic hyper-production of red blood cells—that is caused by a truncated erythropoietin receptor. Here we show that Cas9-mediated genome editing in CD34+ human haematopoietic stem and progenitor cells (HSPCs) can recreate the truncated form of the erythropoietin receptor, leading to substantial increases in erythropoietic output. We also show that combining the expression of the cDNA of a truncated erythropoietin receptor with a previously reported genome-editing strategy to fully replace the HBA1 gene with an HBB transgene in HSPCs (to restore normal haemoglobin production in cells with a β-thalassaemia phenotype) gives the edited HSPCs and the healthy red blood cell phenotype a proliferative advantage. Combining knowledge of human genetics with precise genome editing to insert natural human variants into therapeutic cells may facilitate safer and more effective genome-editing therapies for patients with genetic diseases.
Costs of obesity attributable to the consumption of sugar-sweetened beverages in Brazil
Authors: da Silva Bruna Farias , de Arruda Neta Adélia da Costa Pereira , de Alencar Rodrigues Rômulo Eufrosino , de Araújo Jevuks Matheus , Moreira Patrícia Vasconcelos Leitão , Ferreira Flávia Emília Leite Lima , de Toledo Vianna Rodrigo Pinheiro , da Silva Neto José Moreira , de Carli Eduardo , de Lima Rafaela Lira Formiga Cavalcanti
Published: June 2024

Excess sugar is considered one of the primary factors contributing to overweight status. In Brazil, sugar-sweetened beverages (SSBs) contain a significant amount of this nutrient and are consumed excessively. These beverages are associated with adverse health outcomes and impose costs on the healthcare system. The literature currently lacks studies that aim to attribute specific nutrients or foods as causes of diseases and also evaluate their economic impact, especially in middle- and low-income countries. This study aims to estimate the direct and indirect costs of obesity, stratified by sex and age group, resulting from the excessive consumption of sugar-sweetened beverages in Brazil from 2008 to 2020, and to project these costs for the year 2036. The estimation of obesity costs attributable to excessive consumption of SSBs was based on relative risks and the population prevalence of obesity, considering expenditures on hospitalizations and outpatient procedures in the Unified Health System (SUS). Cost information was obtained from the health information systems available at SUS. The highest burden attributable to the consumption of SSBs was observed among younger individuals and progressively decreased with advancing age. The total direct costs in the period between 2008 and 2020 amounted to approximately US$ 6.33 million, 87% of which was related to expenses for females. Additionally, deaths resulting from the consumption of SSBs cost the economy US$ 40 million due to the premature loss of productivity. The total costs of obesity attributable to the consumption of SSBs are substantial, impacting public spending and generating social and productivity losses that burden the economy. It is crucial to develop and implement cost-effective fiscal and regulatory policies aimed at preventing and combating obesity.