bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward climate-resilient and biodiverse agriculture in the Mediterranean region: experiences and perceptions of farmers engaged in sustainable food production
Authors: Heider Katharina , Rodriguez Lopez Juan Miguel , Bischoff Andreas , Balbo Andrea L. , Scheffran Jürgen
Published: November 2023

The abandonment of smallholder agriculture and the expansion of conventional intensive agriculture pose a potential threat to the multifunctionality of agriculture. The adoption of intensive conventional practices generates negative outcomes, such as increased greenhouse gas emissions, biodiversity loss, and degradation of land, water, and ecosystems. An ecological transition in agriculture is urgently needed. This paper collects and systematizes the opinion of farmers in Spain, engaged in different food production systems (e.g., organic agriculture, biodynamic agriculture, regenerative agriculture, and conservation agriculture), as alternatives to intensive conventional agriculture. In collaboration with agricultural associations and networks in Spain, we co-created an exploratory online survey including qualitative and quantitative questions. Based on 60 in-depth questionnaires, we assess (1) the practices used by the consulted farmers, (2) the perceived effects following the introduction of sustainable practices, and (3) the challenges and opportunities for farm profitability. Our preliminary results show that farmers apply nine out of 14 sustainable practices, on average, and 65% of our sample consciously adapt their practices to climate change. Farmers perceived positive changes in soil properties, biodiversity, and pests after using these practices. They mentioned the low income as the most significant challenge. Finally, we conducted an online discussion with representatives of the associations. Farmers’ perceptions of positive changes presented in this paper are not intended to be representative of farmer communities across Spain, but provide a first overview of those engaged in the ecological transition.
Ginsenoside compound-K attenuates OVX-induced osteoporosis via the suppression of RANKL-induced osteoclastogenesis and oxidative stress
Authors: Ding Lingli , Gao Zhao , Wu Siluo , Chen Chen , Liu Yamei , Wang Min , Zhang Yage , Li Ling , Zou Hong , Zhao Guoping , Qin Shengnan , Xu Liangliang
Published: November 2023

Osteoporosis (OP), a systemic and chronic bone disease, is distinguished by low bone mass and destruction of bone microarchitecture. Ginsenoside Compound-K (CK), one of the metabolites of ginsenoside Rb1, has anti-aging, anti-inflammatory, anti-cancer, and hypolipidemic activities. We have demonstrated CK could promote osteogenesis and fracture healing in our previous study. However, the contribution of CK to osteoporosis has not been examined. In the present study, we investigated the effect of CK on osteoclastogenesis and ovariectomy (OVX)-induced osteoporosis. The results showed that CK inhibited receptor activator for nuclear factor-κB ligand (RANKL)-mediated osteoclast differentiation and reactive oxygen species (ROS) activity by inhibiting the phosphorylation of NF-κB p65 and oxidative stress in RAW264.7 cells. In addition, we also demonstrated that CK could inhibit bone resorption using bone marrow-derived macrophages. Furthermore, we demonstrated that CK attenuated bone loss by suppressing the activity of osteoclast and alleviating oxidative stress in vivo. Taken together, these results showed CK could inhibit osteoclastogenesis and prevent OVX-induced bone loss by inhibiting NF-κB signaling pathway.

Graphical Abstract
Contact allergy to medical devices
Authors: Wagner Nicola
Published: November 2023

Background

Medical devices are not subject to any legal obligation to declare ingredients. With an increasing number of available medical devices, increasing reports of contact allergies to these devices result in a more difficult, delayed or lack of diagnosis of the trigger.

Methods

Elaborate chemical methods, such as gas chromatography–mass spectroscopy, were able to detect novel contact allergens in medical devices.

Results

Diabetic patients requiring insulin benefit from sophisticated glucose sensor measurement systems and insulin pump systems, but are limited in their choices by the development of contact allergy. Potential contact allergens in medical adhesives, plasters, and wound dressings require extensive diagnostic testing. Contact allergic reactions to cardiac electronic implants are rare. The potential relevance of a contact allergic reaction to endoluminal stents to restenosis of the treated vascular territory is discussed. Contact dermatitis to medical gloves is usually due to the vulcanization accelerators. Mouth–nose protective or FFP2 mask-associated eczema is often irritant, very rarely allergic in origin.

Conclusion

With continued development of medical devices, new contact allergens are introduced. The declaration of their ingredients is necessary for rapid diagnosis and future prevention.
High-Entropy Layered Oxide Cathode Enabling High-Rate for Solid-State Sodium-Ion Batteries
Authors: Cai Tianxun , Cai Mingzhi , Mu Jinxiao , Zhao Siwei , Bi Hui , Zhao Wei , Dong Wujie , Huang Fuqiang
Published: November 2023

Na-ion O3-type layered oxides are prospective cathodes for Na-ion batteries due to high energy density and low-cost. Nevertheless, such cathodes usually suffer from phase transitions, sluggish kinetics and air instability, making it difficult to achieve high performance solid-state sodium-ion batteries. Herein, the high-entropy design and Li doping strategy alleviate lattice stress and enhance ionic conductivity, achieving high-rate performance, air stability and electrochemically thermal stability for Na0.95Li0.06Ni0.25Cu0.05Fe0.15Mn0.49O2. This cathode delivers a high reversible capacity (141 mAh g−1 at 0.2C), excellent rate capability (111 mAh g−1 at 8C, 85 mAh g−1 even at 20C), and long-term stability (over 85% capacity retention after 1000 cycles), which is attributed to a rapid and reversible O3–P3 phase transition in regions of low voltage and suppresses phase transition. Moreover, the compound remains unchanged over seven days and keeps thermal stability until 279 ℃. Remarkably, the polymer solid-state sodium battery assembled by this cathode provides a capacity of 92 mAh g−1 at 5C and keeps retention of 96% after 400 cycles. This strategy inspires more rational designs and could be applied to a series of O3 cathodes to improve the performance of solid-state Na-ion batteries.
Deformation of pairs and Noether–Lefschetz loci in toric varieties
Authors: Bruzzo Ugo , Montoya William D.
Published: November 2023

We continue our study of the Noether–Lefschetz loci in toric varieties and investigate deformation of pairs (V, X) where V is a complete intersection subvariety and X a quasi-smooth hypersurface in a simplicial projective toric variety $$\mathbb {P}_{\Sigma }^{2k+1}$$

P

Σ

2
k
+
1

, with $$V\subset X$$

V
⊂
X

. The hypersurface X is supposed to be of Macaulay type, which means that its toric Jacobian ideal is Cox–Gorenstein, a property that generalizes the notion of Gorenstein ideal in the standard polynomial ring. Under some assumptions, we prove that the class $$\lambda _V\in H^{k,k}(X)$$

λ
V

∈

H

k
,
k

(
X
)

deforms to an algebraic class if and only if it remains of type (k, k). Actually we prove that locally the Noether–Lefschetz locus is an irreducible component of a suitable Hilbert scheme. This generalizes Theorem 4.2 in our previous work (Bruzzo and Montoya 15(2):682–694, 2021) and the main theorem proved by Dan (in: Analytic and Algebraic Geometry. Hindustan Book Agency, New Delhi, pp 107–115, 2017).
Unappreciated cross-helicity effects in plasma physics: anti-diffusion effects in dynamo and momentum transport
Authors: Yokoi Nobumitsu
Published: November 2023

The cross-helicity (velocity–magnetic-field correlation) effects in the magnetic-field induction and momentum transport in the magnetohydrodynamic (MHD) turbulence are investigated with the aid of the multiple-scale renormalized perturbation expansion analysis, which is a theoretical framework for strongly non-linear and inhomogeneous turbulence. The outline of the theory is presented with reference to the role of the cross-interaction response functions between the velocity and magnetic field. In this formulation, the expressions of the turbulent fluxes: the turbulent electromotive force (EMF) in the mean induction equation and the Reynolds and turbulent Maxwell stresses in the momentum equation are obtained. Related to the expression of EMF, the physical origin of the cross-helicity effect in dynamos, as well as other dynamo effects, is discussed. Properties of dynamo and momentum transport are determined by the spatiotemporal distribution of turbulence. To understand the actual role of the turbulent cross helicity, its transport equations is considered. Several generation mechanisms of cross helicity are discussed with illustrative examples. On the basis of the cross-helicity production mechanisms, its effect in stellar dynamos is discussed. The role of cross helicity in the momentum transport and global flow generation is also argued. One of the situations where the cross-helicity effects both in magnetic-field induction and global flow generation play an important role is the turbulent magnetic reconnection. Characteristic features of turbulence effects in fast reconnection are reviewed with special emphasis on the role of cross helicity in localizing the effective resistivity. Finally, a remark is addressed on an approach that elucidates the structure generation and sustainment in extremely strong turbulence. An appropriate formulation for the anti-diffusion effect, which acts against the usual diffusion effect, is needed. Turbulence modeling approach based on such an analytical formulation is also argued in comparison with the conventional heuristic modeling. The importance of the self-consistent framework treating the non-linear interaction between the mean field and turbulence is stressed as well.
Elusive technologies, elusive responsibilities: on the perceived responsibility of basic AI researchers
Authors: Burema Dafna , Jacobs Mattis , Rozborski Filip
Published: November 2023

This paper studies how researchers who work in the field of basic research of artificial intelligence (AI) perceive their responsibility. A case study is conducted on an inter-university and interdisciplinary research cluster in Germany that specializes in basic artificial intelligence research. The reason for studying responsibility through the lens of such researchers is that working in basic research of AI involves a lot of uncertainty about potential consequences, more so than in other domains of AI development. After conducting focus groups with 21 respondents followed by a thematic analysis, results show that respondents restrict the boundaries of their sociotechnical visions, regard time as an influencing factor in their responsibility, and refer to many other players in the field. These themes indicate that respondents had difficulties explaining what they consider themselves responsible for, and referred to many factors beyond their own control. The only type of responsibility that was explicitly acknowledged by respondents is ex ante responsibility. Respondents define their responsibility in terms of things that are in their immediate control, i.e., responsibilities relating to their role and duties as researchers. According to the respondents, working in the field of basic research makes it difficult to make claims about ex post responsibility. Findings of this case study suggest the need to raise questions about how technological maturity is related to AI ethics.
State and Business in Tanzania's Development
Authors: Wangwe Samuel Mwita
Published: November 2023

It is widely accepted that countries' institutions play a major role in their economic development. Yet, the way they affect, and are affected by, development, and how to reform them are still poorly understood. In this companion volume, State and Business in Tanzania diagnoses the main weaknesses, root causes, and developmental consequences of Tanzania's institutions, and shows that the uncertainty surrounding its development paths and its difficulty in truly 'taking off' are related to institutional challenges. Based on a thorough account of the economic, social, and political development of the country, this diagnostic offers evidence on the quality of its institutions and a detailed analysis of critical institution- and development-sensitive areas among which state-business relations rank high, even though the institutional features of land management, civil service and the power sector are shown to be also of prime importance. This title is also available as Open Access.
Caring for Cultural Heritage
Authors: Woodhead Charlotte
Published: November 2023

This book explores how cultural heritage and its care are translated in UK law and non-law instruments. It analyses how communities of care look after cultural heritage because they care about it. These communities include the international and national community, national and local governments, courts, professional bodies, institutions such as museums as well as community groups. 'Care' refers to the varied ways in which communities engage with cultural heritage to maintain it, sustain relationships about it and with it, use it and provide access to it, with a view to passing it on to future generations. The book also assesses how far these nested practices of care assist communities of care in providing respectful, empathetic and dialogical care to navigate harm to cultural heritage. It will be of interest to scholars of cultural heritage studies across disciplines, including law, sociology and anthropology, as well as policymakers and practitioners in cultural heritage management.
Public Health Emergency Preparedness: Qualitative Analysis of After-Action Reports
Authors: Naik Rupesh , Maxwell Nikki , Jones Terrance , Dopson Stephanie Anne
Published: November 2023

After-Action Reports (AARs) are retrospective summaries that capture key information and lessons learned from emergency response exercises and real incidents. The AAR is a commonly used evaluation tool used by the Centers for Disease Control and Prevention as part of the Public Health Emergency Preparedness (PHEP) program. It is used as a metric of accountability and awardee performance. The objectives of this study were to qualitatively analyze AARs of public health preparedness programs and develop a coding scheme for standardizing future review and analysis of AARs. We evaluated 14 AARs (4 exercises and 10 real incidents) generated between 2012 and 2018. We applied inductive qualitative analyses using ATLAS.Ti software. While, previous exercises focused on medical countermeasure responses, real-world incidents focused on natural disasters and infectious disease outbreaks. Six overarching themes emerged: Communications, Coordination, Resource Distribution, Unified Planning, Surveillance, and Knowledge Sharing. A standardized analysis format is proposed for future use.
Barriers to healthcare-worker adherence to infection prevention and control practices in British Columbia during the coronavirus disease 2019 (COVID-19) pandemic: A cross-sectional study
Authors: Cheng Brooke T. , Ali R. Ayesha , Chen Collet Jun , Donovan Towell Tara , Han Guanghong , Keen Dave , Leung Ka Wai , Mori Julie , Srigley Jocelyn A.
Published: November 2023

Objective:

The coronavirus disease 2019 (COVID-19) pandemic highlighted the importance of robust infection prevention and control (IPAC) practices to maintain patient and staff safety. However, healthcare workers (HCWs) face many barriers that affect their ability to follow these practices. We identified barriers affecting HCW adherence to IPAC practices during the pandemic in British Columbia, Canada.

Design:

Cross-sectional web-based survey.

Setting:

Acute care, long-term care or assisted living, outpatient, mental health, prehospital care, and home care.

Participants:

Eligible respondents included direct-care providers and IPAC professionals working in these settings in all health authorities across British Columbia.

Methods:

We conducted a web-based survey from August to September 2021 to assess respondent knowledge and attitudes toward IPAC within the context of the COVID-19 pandemic. Respondents were asked to rate the extent to which various barriers affected their ability to follow IPAC practices throughout the pandemic and to make suggestions for improvement.

Results:

The final analysis included 2,488 responses; 36% of respondents worked in acute care. Overall, perceptions of IPAC practice among non-IPAC professionals were positive. The main self-perceived barriers to adherence included inadequate staffing to cover absences (58%), limited space in staff rooms (57%), multibed rooms (51%), and confusing messages about IPAC practices (51%). Common suggestions for improvement included receiving more support from IPAC leadership and clearer communication about required IPAC practices.

Conclusions:

Our findings highlight frontline HCW perspectives regarding priority areas of improvement for IPAC practices. They will inform policy and guideline development to prevent transmission of COVID-19 and future emerging infections.
CEO overconfidence and firm performance: A meta-analytic review and future research agenda
Authors: Miao Chao , Coombs Joseph E. , Qian Shanshan , Oh In-Sue
Published: November 2023

We provide a meta-analytic examination of the CEO overconfidence–firm performance relationship. Our results support a positive relationship between these focal variables. Drawing from trait activation theory and national cultural differences literatures, we find that cross-cultural effects moderate the focal relationship. More specifically, we find that the CEO overconfidence–firm performance relationship is stronger in high assertive, low institutional collectivistic, low in-group collectivistic, high future-oriented, high gender egalitarian, high performance-oriented, low power distance, and low uncertainty avoidance cultures. Consistent with the resource orchestration literature, we also find that entrepreneurial orientation mediates the focal relationship between CEO overconfidence and firm performance. Taken together, our results present a more nuanced picture of the CEO trait–firm performance relationship. In the future, researchers may consider examining additional CEO traits as well as additional contextual factors including internal, as well as environmental, factors.
Exclusion from Within: Noncitizens and the Rise of Discriminatory Licensing Laws
Authors: Tirres Allison Brownell
Published: November 2023

In the United States in the early twentieth century, state and local laws discriminating on the basis of alienage proliferated. Progressive reformers, nativist groups, state legislatures, and city councils sought new methods for restricting noncitizen access to the workplace and the marketplace. As this article demonstrates, the primary vehicle they utilized was state and local licensing laws. Licensing proved to be a powerful tool of exclusion; by 1930, citizenship-based licensing restrictions were present in every state and most major cities. Noncitizens challenged some of these laws, pushing for greater protection of their constitutional rights. The resulting court contests over exclusionary licensing laws led to the creation of a new branch of legal doctrine, one that redefined the relationship between noncitizens and state power. This article highlights the significant and underappreciated role played by state and local laws in shaping the immigrant experience in the Progressive Era. It furthers our understanding of the licensing power and illuminates a pivotal moment in the development of immigrant rights. Today, noncitizens are still excluded from a range of economic activities due to licensing restrictions. This article explores the roots and the spread of this little understood – and still consequential – technique of exclusion.
Surgical anatomy of structures adjacent to the thyroid apex and
post-operative voice change (A review-including dissection)
Authors: Yerzingatsian K. L.
Published: November 2023

This paper considers the anatomy of structures contiguous to the upper
pole of the thyroid gland. It also describes the findings of an anatomical
dissection confined to the muscular andcarotid triangles of the neck with
the nerves therein innervating the cricothyroid and infrahyoid muscles. The
segmental nature of the latter is described. The variable course of the
cricothyroid artery with regard to the sternothyroid muscle is noted. A
superficially placed artery is accompanied by branches of the ansa
cervicalis; a deeply placed one is related to the external laryngeal
nerve.

In addition to the external laryngeal nerve there are other nerves,
including branches of the ansa cervicalis, which can be damaged during
operations involving the thyroid apex or adjacent structures. A comment is
made about the significance of these findings with particular reference to
voice change.
Prevention of subglottic stenosis
Authors: Laing I. A. , Cowan D. L. , Hume R.
Published: November 2023

Mechanical ventilation is now widely used in neonatal intensive care.
Methods and materials for endotracheal intubation vary between intensive
care units. Up to eight per cent of ventilated infants may have subglottic
stenosis after discharge from hospital (Jones et
al., 1981).
Seasonal patterns of sickness absence due to diagnosed mental disorders: a nationwide 12-year register linkage study
Authors: Virtanen M. , Törmälehto S. , Partonen T. , Elovainio M. , Ruuhela R. , Hakulinen C. , Komulainen K. , Airaksinen J. , Väänänen A. , Koskinen A. , Sund R.
Published: November 2023

Aims

Although seasonality has been documented for mental disorders, it is unknown whether similar patterns can be observed in employee sickness absence from work due to a wide range of mental disorders with different severity level, and to what extent the rate of change in light exposure plays a role. To address these limitations, we used daily based sickness absence records to examine seasonal patterns in employee sickness absence due to mental disorders.

Methods

We used nationwide diagnosis-specific psychiatric sickness absence claims data from 2006 to 2017 for adult individuals aged 16–67 (n = 636,543 sickness absence episodes) in Finland, a high-latitude country with a profound variation in daylength. The smoothed time-series of the ratio of observed and expected (O/E) daily counts of episodes were estimated, adjusted for variation in all-cause sickness absence rates during the year.

Results

Unipolar depressive disorders peaked in October–November and dipped in July, with similar associations in all forms of depression. Also, anxiety and non-organic sleep disorders peaked in October–November. Anxiety disorders dipped in January–February and in July–August, while non-organic sleep disorders dipped in April–August. Manic episodes reached a peak from March to July and dipped in September–November and in January–February. Seasonality was not dependent on the severity of the depressive disorder.

Conclusions

These results suggest a seasonal variation in sickness absence due to common mental disorders and bipolar disorder, with high peaks in depressive, anxiety and sleep disorders towards the end of the year and a peak in manic episodes starting in spring. Rapid changes in light exposure may contribute to sickness absence due to bipolar disorder. The findings can help clinicians and workplaces prepare for seasonal variations in healthcare needs.
What Controls the Interannual Variation in Rapid Intensification Magnitude of Western North Pacific Tropical Cyclones?
Authors: Song Jinjie , Klotzbach Philip J. , Wei Na , Duan Yihong
Published: November 2023

This study investigates the interannual variability of rapid intensification (RI) magnitude of western North Pacific (WNP) tropical cyclones. There is a significant correlation between basin‐averaged RI magnitude during July–November and the simultaneous Western Pacific (WP) teleconnection index from 1982 to 2021. RI magnitude is, on average, larger (smaller) in positive (negative) WP phases. During a positive WP, RI magnitude changes exhibit a southwest‐northeast dipolar pattern, with significant increases over the southwestern quadrant of the WNP and weak decreases over the northern part of the WNP. The WP teleconnection relates to RI magnitude primarily through modulation of 850–200‐hPa vertical wind shear, with less influence from 850‐hPa relative vorticity. The changes in these two dynamic conditions can be linked to WP‐induced circulation anomalies at lower and upper levels. Our results highlight that different contributors may be responsible for changes in WNP RI occurrence and RI magnitude.
Ionospheric Plasma Density Gradients Associated With Night‐Side Energetic Electron Precipitation
Authors: Zhang Xiao‐Jia , Meng Xing , Artemyev Anton V. , Zou Ying , Mourenas Didier
Published: November 2023

Energetic electron precipitation from the equatorial magnetosphere into the atmosphere plays an important role in magnetosphere‐ionosphere coupling: precipitating electrons alter ionospheric properties, whereas ionospheric outflows modify equatorial plasma conditions affecting electromagnetic wave generation and energetic electron scattering. However, ionospheric measurements cannot be directly related to wave and energetic electron properties measured by high‐altitude, near‐equatorial spacecraft, due to large mapping uncertainties. We aim to resolve this by projecting low‐altitude measurements of energetic electron precipitation by ELFIN CubeSats onto total electron content (TEC) maps serving as a proxy for ionospheric density structures. We examine three types of precipitation on the nightside: precipitation of <200 keV electrons in the plasma sheet, bursty precipitation of <500 keV electrons by whistler‐mode waves, and relativistic (>500 keV) electron precipitation by EMIC waves. All three types of precipitation show distinct features in TEC horizontal gradients, and we discuss possible implications of these features.
BH3 mimetics and azacitidine show synergistic effects on juvenile myelomonocytic leukemia
Authors: Wu Ying , Zehnle Patricia M. A. , Rajak Jovana , Koleci Naile , Andrieux Geoffroy , Gallego-Villar Lorena , Aumann Konrad , Boerries Melanie , Niemeyer Charlotte M. , Flotho Christian , Bohler Sheila , Erlacher Miriam
Published: November 2023

Juvenile myelomonocytic leukemia (JMML) is an aggressive hematopoietic disorder of infancy and early childhood driven by constitutively active RAS signaling and characterized by abnormal proliferation of the granulocytic-monocytic blood cell lineage. Most JMML patients require hematopoietic stem cell transplantation for cure, but the risk of relapse is high for some JMML subtypes. Azacitidine was shown to effectively reduce leukemic burden in a subset of JMML patients. However, variable response rates to azacitidine and the risk of drug resistance highlight the need for novel therapeutic approaches. Since RAS signaling is known to interfere with the intrinsic apoptosis pathway, we combined various BH3 mimetic drugs with azacitidine in our previously established patient-derived xenograft model. We demonstrate that JMML cells require both MCL-1 and BCL-XL for survival, and that these proteins can be effectively targeted by azacitidine and BH3 mimetic combination treatment. In vivo azacitidine acts via downregulation of antiapoptotic MCL-1 and upregulation of proapoptotic BH3-only. The combination of azacitidine with BCL-XL inhibition was superior to BCL-2 inhibition in eliminating JMML cells. Our findings emphasize the need to develop clinically applicable MCL-1 or BCL-XL inhibitors in order to enable novel combination therapies in JMML refractory to standard therapy.
Ceramic thin-film composite membranes with tunable subnanometer pores for molecular sieving
Authors: Zhou Xuechen , Shevate Rahul , Huang Dahong , Cao Tianchi , Shen Xin , Hu Shu , Mane Anil U. , Elam Jeffrey W. , Kim Jae-Hong , Elimelech Menachem
Published: November 2023

Ceramic membranes are a promising alternative to polymeric membranes for selective separations, given their ability to operate under harsh chemical conditions. However, current fabrication technologies fail to construct ceramic membranes suitable for selective molecular separations. Herein, we demonstrate a molecular-level design of ceramic thin-film composite membranes with tunable subnanometer pores for precise molecular sieving. Through burning off the distributed carbonaceous species of varied dimensions within hybrid aluminum oxide films, we created membranes with tunable molecular sieving. Specifically, the membranes created with methanol showed exceptional selectivity toward monovalent and divalent salts. We attribute this observed selectivity to the dehydration of the large divalent ions within the subnanometer pores. As a comparison, smaller monovalent ions can rapidly permeate with an intact hydration shell. Lastly, the flux of neutral solutes through each fabricated aluminum oxide membrane was measured for the demonstration of tunable separation capability. Overall, our work provides the scientific basis for the design of ceramic membranes with subnanometer pores for molecular sieving using atomic layer deposition.
trRosettaRNA: automated prediction of RNA 3D structure with transformer network
Authors: Wang Wenkai , Feng Chenjie , Han Renmin , Wang Ziyi , Ye Lisha , Du Zongyang , Wei Hong , Zhang Fa , Peng Zhenling , Yang Jianyi
Published: November 2023

RNA 3D structure prediction is a long-standing challenge. Inspired by the recent breakthrough in protein structure prediction, we developed trRosettaRNA, an automated deep learning-based approach to RNA 3D structure prediction. The trRosettaRNA pipeline comprises two major steps: 1D and 2D geometries prediction by a transformer network; and 3D structure folding by energy minimization. Benchmark tests suggest that trRosettaRNA outperforms traditional automated methods. In the blind tests of the 15th Critical Assessment of Structure Prediction (CASP15) and the RNA-Puzzles experiments, the automated trRosettaRNA predictions for the natural RNAs are competitive with the top human predictions. trRosettaRNA also outperforms other deep learning-based methods in CASP15 when measured by the Z-score of the Root-Mean-Square Deviation. Nevertheless, it remains challenging to predict accurate structures for synthetic RNAs with an automated approach. We hope this work could be a good start toward solving the hard problem of RNA structure prediction with deep learning.
TDP1 suppresses chromosomal translocations and cell death induced by abortive TOP1 activity during gene transcription
Authors: Rubio-Contreras Diana , Gómez-Herreros Fernando
Published: November 2023

DNA topoisomerase I (TOP1) removes torsional stress by transiently cutting one DNA strand. Such cuts are rejoined by TOP1 but can occasionally become abortive generating permanent protein-linked single strand breaks (SSBs). The repair of these breaks is initiated by tyrosyl-DNA phosphodiesterase 1 (TDP1), a conserved enzyme that unlinks the TOP1 peptide from the DNA break. Additionally, some of these SSBs can result in double strand breaks (DSBs) either during replication or by a poorly understood transcription-associated process. In this study, we identify these DSBs as a source of genome rearrangements, which are suppressed by TDP1. Intriguingly, we also provide a mechanistic explanation for the formation of chromosomal translocations unveiling an error-prone pathway that relies on the MRN complex and canonical non-homologous end-joining. Collectively, these data highlight the threat posed by TOP1-induced DSBs during transcription and demonstrate the importance of TDP1-dependent end-joining in protecting both gene transcription and genome stability.
Observing the universal screening of a Kondo impurity
Authors: Piquard C. , Glidic P. , Han C. , Aassime A. , Cavanna A. , Gennser U. , Meir Y. , Sela E. , Anthore A. , Pierre F.
Published: November 2023

The Kondo effect, deriving from a local magnetic impurity mediating electron-electron interactions, constitutes a flourishing basis for understanding a large variety of intricate many-body problems. Its experimental implementation in tunable circuits has made possible important advances through well-controlled investigations. However, these have mostly concerned transport properties, whereas thermodynamic observations - notably the fundamental measurement of the spin of the Kondo impurity - remain elusive in test-bed circuits. Here, with a novel combination of a ‘charge’ Kondo circuit with a charge sensor, we directly observe the state of the impurity and its progressive screening. We establish the universal renormalization flow from a single free spin to a screened singlet, the associated reduction in the magnetization, and the relationship between scaling Kondo temperature and microscopic parameters. In our device, a Kondo pseudospin is realized by two degenerate charge states of a metallic island, which we measure with a non-invasive, capacitively coupled charge sensor. Such pseudospin probe of an engineered Kondo system opens the way to the thermodynamic investigation of many exotic quantum states, including the clear observation of Majorana zero modes through their fractional entropy.
Aerosols overtake greenhouse gases causing a warmer climate and more weather extremes toward carbon neutrality
Authors: Wang Pinya , Yang Yang , Xue Daokai , Ren Lili , Tang Jianping , Leung L. Ruby , Liao Hong
Published: November 2023

To mitigate climate warming, many countries have committed to achieve carbon neutrality in the mid-21st century. Here, we assess the global impacts of changing greenhouse gases (GHGs), aerosols, and tropospheric ozone (O3) following a carbon neutrality pathway on climate and extreme weather events individually using the Community Earth System Model version 1 (CESM1). The results suggest that the future aerosol reductions significantly contribute to climate warming and increase the frequency and intensity of extreme weathers toward carbon neutrality and aerosol impacts far outweigh those of GHGs and tropospheric O3. It reverses the knowledge that the changing GHGs dominate the future climate changes as predicted in the middle of the road pathway. Therefore, substantial reductions in GHGs and tropospheric O3 are necessary to reach the 1.5 °C warming target and mitigate the harmful effects of concomitant aerosol reductions on climate and extreme weather events under carbon neutrality in the future.
Nde1 promotes Lis1-mediated activation of dynein
Authors: Zhao Yuanchang , Oten Sena , Yildiz Ahmet
Published: November 2023

Cytoplasmic dynein drives the motility and force generation functions towards the microtubule minus end. The assembly of dynein with dynactin and a cargo adaptor in an active transport complex is facilitated by Lis1 and Nde1/Ndel1. Recent studies proposed that Lis1 relieves dynein from its autoinhibited conformation, but the physiological function of Nde1/Ndel1 remains elusive. Here, we investigate how human Nde1 and Lis1 regulate the assembly and subsequent motility of mammalian dynein using in vitro reconstitution and single molecule imaging. We find that Nde1 recruits Lis1 to autoinhibited dynein and promotes Lis1-mediated assembly of dynein-dynactin adaptor complexes. Nde1 can compete with the α2 subunit of platelet activator factor acetylhydrolase 1B (PAF-AH1B) for the binding of Lis1, which suggests that Nde1 may disrupt PAF-AH1B recruitment of Lis1 as a noncatalytic subunit, thus promoting Lis1 binding to dynein. Before the initiation of motility, the association of dynactin with dynein triggers the dissociation of Nde1 from dynein by competing against Nde1 binding to the dynein intermediate chain. Our results provide a mechanistic explanation for how Nde1 and Lis1 synergistically activate the dynein transport machinery.
Large area inkjet-printed OLED fabrication with solution-processed TADF ink
Authors: Kant Chandra , Shukla Atul , McGregor Sarah K. M. , Lo Shih-Chun , Namdas Ebinazar B. , Katiyar Monica
Published: November 2023

This work demonstrates successful large area inkjet printing of a thermally activated delayed fluorescence (TADF) material as the emitting layer of organic light-emitting diodes (OLEDs). TADF materials enable efficient light emission without relying on heavy metals such as platinum or iridium. However, low-cost manufacturing of large-scale TADF OLEDs has been restricted due to their incompatibility with solution processing techniques. In this study, we develop ink formulation for a TADF material and show successful ink jet printing of intricate patterns over a large area (6400 mm2) without the use of any lithography. The stable ink is successfully achieved using a non-chlorinated binary solvent mixture for a solution processable TADF material, 3‐(9,9‐dimethylacridin‐10(9H)‐yl)‐9H‐xanthen‐9‐one dispersed in 4,4’-bis-(N-carbazolyl)-1,1’-biphenyl host. Using this ink, large area ink jet printed OLEDs with performance comparable to the control spin coated OLEDs are successfully achieved. In this work, we also show the impact of ink viscosity, density, and surface tension on the droplet formation and film quality as well as its potential for large-area roll-to-roll printing on a flexible substrate. The results represent a major step towards the use of TADF materials for large-area OLEDs without employing any lithography.
Epigenetic regulation of beta-endorphin synthesis in hypothalamic arcuate nucleus neurons modulates neuropathic pain in a rodent pain model
Authors: Tao Yu , Zhang Yuan , Jin Xiaohong , Hua Nan , Liu Hong , Qi Renfei , Huang Zitong , Sun Yufang , Jiang Dongsheng , Snutch Terrance P. , Jiang Xinghong , Tao Jin
Published: November 2023

Although beta-endorphinergic neurons in the hypothalamic arcuate nucleus (ARC) synthesize beta-endorphin (β-EP) to alleviate nociceptive behaviors, the underlying regulatory mechanisms remain unknown. Here, we elucidated an epigenetic pathway driven by microRNA regulation of β-EP synthesis in ARC neurons to control neuropathic pain. In pain-injured rats miR-203a-3p was the most highly upregulated miRNA in the ARC. A similar increase was identified in the cerebrospinal fluid of trigeminal neuralgia patients. Mechanistically, we found histone deacetylase 9 was downregulated following nerve injury, which decreased deacetylation of histone H3 lysine-18, facilitating the binding of NR4A2 transcription factor to the miR-203a-3p gene promoter, thereby upregulating miR-203a-3p expression. Further, increased miR-203a-3p was found to maintain neuropathic pain by targeting proprotein convertase 1, an endopeptidase necessary for the cleavage of proopiomelanocortin, the precursor of β-EP. The identified mechanism may provide an avenue for the development of new therapeutic targets for neuropathic pain treatment.
Polymer architecture dictates multiple relaxation processes in soft networks with two orthogonal dynamic bonds
Authors: Ge Sirui , Tsao Yu-Hsuan , Evans Christopher M.
Published: November 2023

Materials with tunable modulus, viscosity, and complex viscoelastic spectra are crucial in applications such as self-healing, additive manufacturing, and energy damping. It is still challenging to predictively design polymer networks with hierarchical relaxation processes, as many competing factors affect dynamics. Here, networks with both pendant and telechelic architecture are synthesized with mixed orthogonal dynamic bonds to understand how the network connectivity and bond exchange mechanisms govern the overall relaxation spectrum. A hydrogen-bonding group and a vitrimeric dynamic crosslinker are combined into the same network, and multimodal relaxation is observed in both pendant and telechelic networks. This is in stark contrast to similar networks where two dynamic bonds share the same exchange mechanism. With the incorporation of orthogonal dynamic bonds, the mixed network also demonstrates excellent damping and improved mechanical properties. In addition, two relaxation processes arise when only hydrogen-bond exchange is present, and both modes are retained in the mixed dynamic networks. This work provides molecular insights for the predictive design of hierarchical dynamics in soft materials.
Sphingomyelin-derived nanovesicles for the delivery of the IDO1 inhibitor epacadostat enhance metastatic and post-surgical melanoma immunotherapy
Authors: Wang Zhiren , Li Wenpan , Jiang Yanhao , Tran Tuyen Ba , Cordova Leyla Estrella , Chung Jinha , Kim Minhyeok , Wondrak Georg , Erdrich Jennifer , Lu Jianqin
Published: November 2023

Epacadostat (EPA), the most advanced IDO1 inhibitor, in combination with PD-1 checkpoint inhibitor, has failed in a recent Phase III clinical trial for treating metastatic melanoma. Here we report an EPA nanovesicle therapeutic platform (Epacasome) based on chemically attaching EPA to sphingomyelin via an oxime-ester bond highly responsive to hydrolase cleavage. Via clathrin-mediated endocytosis, Epacasome displays higher cellular uptake and enhances IDO1 inhibition and T cell proliferation compared to free EPA. Epacasome shows improved pharmacokinetics and tumour accumulation with efficient intratumoural drug release and deep tumour penetration. Additionally, it outperforms free EPA for anticancer efficacy, potentiating PD-1 blockade with boosted cytotoxic T lymphocytes (CTLs) and reduced regulatory T cells and myeloid-derived suppressor cells responses in a B16-F10 melanoma model in female mice. By co-encapsulating immunogenic dacarbazine, Epacasome further enhances anti-tumor effects and immune responses through the upregulation of NKG2D-mediated CTLs and natural killer cells responses particularly when combined with the PD-1 inhibitor in the late-stage metastatic B16-F10-Luc2 model in female mice. Furthermore, this combination prevents tumour recurrence and prolongs mouse survival in a clinically relevant, post-surgical melanoma model in female mice. Epacasome demonstrates potential to synergize with PD-1 blockade for improved response to melanoma immunotherapy.
Spatial-linked alignment tool (SLAT) for aligning heterogenous slices
Authors: Xia Chen-Rui , Cao Zhi-Jie , Tu Xin-Ming , Gao Ge
Published: November 2023

Spatially resolved omics technologies reveal the spatial organization of cells in various biological systems. Here we propose SLAT (Spatially-Linked Alignment Tool), a graph-based algorithm for efficient and effective alignment of spatial slices. Adopting a graph adversarial matching strategy, SLAT is the first algorithm capable of aligning heterogenous spatial data across distinct technologies and modalities. Systematic benchmarks demonstrate SLAT’s superior precision, robustness, and speed over existing state-of-the-arts. Applications to multiple real-world datasets further show SLAT’s utility in enhancing cell-typing resolution, integrating multiple modalities for regulatory inference, and mapping fine-scale spatial-temporal changes during development. The full SLAT package is available at https://github.com/gao-lab/SLAT.
Local control of superconductivity in a NbSe2/CrSBr van der Waals heterostructure
Authors: Jo Junhyeon , Peisen Yuan , Yang Haozhe , Mañas-Valero Samuel , Baldoví José J. , Lu Yao , Coronado Eugenio , Casanova Fèlix , Bergeret F. Sebastian , Gobbi Marco , Hueso Luis E.
Published: November 2023

Two-dimensional magnets and superconductors are emerging as tunable building-blocks for quantum computing and superconducting spintronic devices, and have been used to fabricate all two-dimensional versions of traditional devices, such as Josephson junctions. However, novel devices enabled by unique features of two-dimensional materials have not yet been demonstrated. Here, we present NbSe2/CrSBr van der Waals superconducting spin valves that exhibit infinite magnetoresistance and nonreciprocal charge transport. These responses arise from a unique metamagnetic transition in CrSBr, which controls the presence of localized stray fields suitably oriented to suppress the NbSe2 superconductivity in nanoscale regions and to break time reversal symmetry. Moreover, by integrating different CrSBr crystals in a lateral heterostructure, we demonstrate a superconductive spin valve characterized by multiple stable resistance states. Our results show how the unique physical properties of layered materials enable the realization of high-performance quantum devices based on novel working principles.
Release of Histone H3K4-reading transcription factors from chromosomes in mitosis is independent of adjacent H3 phosphorylation
Authors: Harris Rebecca J. , Heer Maninder , Levasseur Mark D. , Cartwright Tyrell N. , Weston Bethany , Mitchell Jennifer L. , Coxhead Jonathan M. , Gaughan Luke , Prendergast Lisa , Rico Daniel , Higgins Jonathan M. G.
Published: November 2023

Histone modifications influence the recruitment of reader proteins to chromosomes to regulate events including transcription and cell division. The idea of a histone code, where combinations of modifications specify unique downstream functions, is widely accepted and can be demonstrated in vitro. For example, on synthetic peptides, phosphorylation of Histone H3 at threonine-3 (H3T3ph) prevents the binding of reader proteins that recognize trimethylation of the adjacent lysine-4 (H3K4me3), including the TAF3 component of TFIID. To study these combinatorial effects in cells, we analyzed the genome-wide distribution of H3T3ph and H3K4me2/3 during mitosis. We find that H3T3ph anti-correlates with adjacent H3K4me2/3 in cells, and that the PHD domain of TAF3 can bind H3K4me2/3 in isolated mitotic chromatin despite the presence of H3T3ph. Unlike in vitro, H3K4 readers are still displaced from chromosomes in mitosis in Haspin-depleted cells lacking H3T3ph. H3T3ph is therefore unlikely to be responsible for transcriptional downregulation during cell division.
Electrocatalytic valorization of lignocellulose-derived aromatics at industrial-scale current densities
Authors: Peng Tao , Zhang Wenbin , Liang Baiyao , Lian Guanwu , Zhang Yun , Zhao Wei
Published: November 2023

Electrocatalytic hydrogenation of lignocellulosic bio-oil to value-added chemicals offers an attractive avenue to use the increasing intermittent renewable electricity and biomass-derived feedstocks. However, to date the partial current densities to target products of these reactions are lower than those needed for industrial-scale productivity, which limits its prospects. Here we report a flow-cell system equipped with a Rh diffusion electrode to hydrogenate lignocellulose-derived aromatic monomers, such as furans and lignin monomers, to value-added chemicals. We achieve high faradaic efficiencies up to 64% at industrial-scale current densities of 300–500 mA cm−2, representing high productivities to target products. A screening of electrocatalysts indicates that only by highly-electrolyte-permeable Rh diffusion electrodes are we able to unite current density with faradaic efficiency. We apply in-situ infrared reflection–absorption spectroscopy to investigate the electrode-potential-dependent reaction pathways and intermediates, confirming a wide potential window for efficient electrocatalytic hydrogenation of lignocellulose-derived aromatics to target products.