bluuebunny/crossref_metadata_2025 huggingface dataset:
The Sino-Malaysian Rubber Trade, 1950-80: A Global History
Authors: Yao Yu , Guo Youxin
Published: September 2023

This article examines the evolution of the Sino-Malaysian rubber trade between 1950 and 1980 from a global perspective. In the 1950s, this trade was one part of a triangular rubber trade extending from Southeast Asia through China to the European socialist countries who were the real buyers of much of the Malayan rubber exported to China. While China stopped its rubber re-exports to the Soviet Union in 1961, the Sino-Malaysian rubber trade continued to evolve under the shadow of global events, especially Malaysia’s economic tensions with industrialized Western countries and China’s military confrontations with its enemies. The engagement of so many global players in this trade brought more pressures, challenges, and opportunities for Malaysia and China as they bargained with each other, consequently contributing to the sharp fluctuation of trade during this period.
Diagnostic Utility of the Perceived Occupational Stress Scale
Authors: Marcatto Francesco , Di Blas Lisa , Ferrante Donatella
Published: September 2023

Abstract: The Perceived Occupational Stress (POS) scale has been recently developed to measure workers’ perception of feeling stressed at work. This cross-sectional study aimed to further study the practical applicability of the POS scale by testing its diagnostic utility for identifying workers with severe somatic symptom strain. A sample of 171 Italian workers filled out a survey containing the POS and the short form of the Giessen Subjective Complaints List (GBB-8). The POS scale was strongly associated with the GBB-8 ( r = .70, p < .001; β = .71, p < .001), and the receiver operating characteristic (ROC) analysis showed its excellent diagnostic accuracy (area under the curve, AUC = .83, p < .001), with a POS value of 3.50 being the optimal cut-off for detecting severe somatic symptoms. Overall, the results show that the POS scale is an economic and non-intrusive tool for identifying workers at high risk of severe psychosomatic strain. Limitations of this study include the use of self-report measures and of a convenience sample, which could lead to common method and selection biases. Future research should re-evaluate the predictive usefulness of the POS scale as a predictor of other outcomes of work-related stress such as anxiety and depression, performance, and turnover intentions.
Economic Impacts of Tropical Cyclone‐Induced Multiple Hazards in China
Authors: Hu L. , Wen T. , Shao Y. , Wang Q. , Fang W. , Yang J. , Liu M. , Wang X. , Zhang H. , Bi J. , Ma Z.
Published: September 2023

Tropical cyclones (TCs) are known to bring heavy rainfall, strong winds and severe storm surges simultaneously, resulting in tremendous damage beyond the effects of a single hazard. However, the compound impacts of TC multi‐hazards remain unexplored in macroeconomic assessments. Here, we provide empirical evidence on the multi‐hazard economic losses of TC for the first time. We used a national panel of provincial economic output in China over 2000–2020. Our results show that the total macroeconomic impact of the severest TC multi‐hazards can represent up to 14 times the value of merely TC winds. Specifically, the vast majority (over 80%) of the combined TC impacts is caused by precipitation, with wider and greater economic impacts than TC winds and storm surges. Furthermore, high‐latitude and interior regions of China are more vulnerable to TCs due to the interactions with temperature variability and TC wind intensity variability. High‐income areas and secondary industries respond markedly to all TC hazards, and the economic impact of TC precipitation is significant over all sectors. Our findings provide new implications for the socio‐economic impact mechanisms of multiple hazards of TCs and valuable insights into the design of climate policy for compound hazard risks.
Systematic Across‐Arc Variations of Molybdenum Isotopes in a Fluid‐Dominated Subduction Zone System
Authors: Willbold M. , Messling N.
Published: September 2023

Mass‐dependent Mo isotope variations are a promising new tracer to study magmatic processes in different geological settings. We report the first Mo isotope data for the Kamchatka arc system in the Northwest Pacific, comprising basaltic lavas of a complete Southeast‐Northwest traverse from the volcanic arc front through to the back arc region. The majority of volcanic centers investigated directly override the Hawaii‐Emperor Seamount Chain, which is currently being subducted underneath the arc system. Our Mo isotope data show systematic trends with Ce/Pb, Ce/Mo, Nb/Zr, La/Sm, and 143Nd/144Nd ratios from the volcanic arc front to the back arc. Arc front lavas have higher δ98/95Mo and lower Ce/Pb, Ce/Mo, Nb/Zr, La/Sm compared to back arc lavas. Because the involvement of subducted sediments can be excluded, we attribute the observed variations to a change in the mantle source composition from the arc front to the back arc regions. The isotopic and chemical budget of arc front lavas is dominated by a slab fluid component (high δ98/95Mo, low Ce/Pb, Ce/Mo), whereas mantle‐like Ce/Pb, Ce/Mo, elevated Nb/Zr and La/Sm in the back arc samples suggest an enriched mantle source. Combined δ98/95Mo, Nd, and Pb isotope data in back arc lavas are very similar to those observed for modern ocean island basalts from Hawaii. We thus explore the possibility that the back arc mantle was contaminated by a Hawaii‐type, enriched asthenospheric mantle component from the subducted Hawaii‐Emperor Seamount Chain.
External and Internal Causes of the Stormtime Intensification of the Dawnside Westward Auroral Electrojet
Authors: Ohtani S. , Sorathia K. , Merkin V. G. , Frey H. U. , Gjerloev J. W.
Published: September 2023

The dawn‐dusk asymmetry of magnetic depression is a characteristic feature of the storm main phase. Recently Ohtani (2021, https://doi.org/10.1029/2021JA029643) reported that its magnitude is correlated with the dawnside westward auroral electrojet (AEJ) intensity, and suggested that the dawnside AEJ intensification is a fundamental process of the stormtime magnetosphere‐ionosphere coupling. In this study we observationally address the cause of the dawnside AEJ intensification in terms of four scenarios. That is, the dawnside AEJ intensifies because (a) the external driving of global convection strengthens, (b) solar wind compression enhances energetic electron precipitation, and therefore, ionospheric conductance, through wave‐particle interaction, (c) the substorm current wedge forms in the dawn sector, and (d) energetic electrons injected by nightside substorms drift dawnward, and the subsequent precipitation enhances ionospheric conductance. We find an event that fits each scenario, and therefore, none of these scenarios can be precluded. However, the result of a superposed epoch analysis shows that some causes are more prevalent than others. More specifically, (a) although the enhancement of external driving may precondition the dawnside AEJ intensification, it is rarely the direct cause; (b) external compression probably explains only a small fraction of the events; (c) prior to the dawnside AEJ intensification, the westward AEJ tends to intensify in the midnight sector along with mid‐latitude positive bays, which suggests that the substorm injection of energetic electrons is the most prevalent cause. This last result may also be explained by the dawnside expansion of the substorm current wedge, which, however, is arguably far less common.
UK cost-effectiveness analysis of endoscopic sleeve gastroplasty versus lifestyle modification alone for adults with class II obesity
Authors: Kelly Jamie , Menon Vinod , O’Neill Frank , Elliot Laura , Combe Emily , Drinkwater Will , Abbott Sally , Hayee BuHussain
Published: September 2023

Background

Endoscopic sleeve gastroplasty (ESG) is a minimally invasive procedure that has been demonstrated in the MERIT randomised, controlled trial to result in substantial and durable additional weight loss in adults with obesity compared with lifestyle modification (LM) alone. We sought to conduct the first cost-effectiveness analysis of ESG versus LM alone in adults with class II obesity (BMI 35.0–39.9 kg/m2) from a national healthcare system perspective in England based on results from this study.

Methods

A 6-state Markov model was developed comprising 5 BMI-based health states and an absorbing death state. Baseline characteristics, utilities, and transition probabilities were informed by patient-level data from the subset of patients with class II obesity in MERIT. Adverse events (AEs) were based on the MERIT safety population. Mortality was estimated by applying BMI-specific hazard ratios from the published literature to UK general population mortality rates. Utilities for the healthy weight and overweight health states were informed from the literature; disutility associated with increasing BMI in the class I-III obesity health states was estimated using MERIT utility data. Disutility due to AEs and the prevalence of obesity-related comorbidities were based on the literature. Costs included intervention costs, AE costs, and comorbidity costs.

Results

ESG resulted in higher overall costs than LM alone but led to an increase in quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) for ESG vs LM alone was £2453/QALY gained. ESG was consistently cost effective across a wide range of sensitivity analyses, with no ICER estimate exceeding £10,000/QALY gained. In probabilistic sensitivity analysis, the mean ICER was £2502/QALY gained and ESG remained cost effective in 98.25% of iterations at a willingness-to-pay threshold of £20,000/QALY.

Conclusion

Our study indicates that ESG is highly cost effective versus LM alone for the treatment of adults with class II obesity in England.
Sounds of danger and post-traumatic stress responses in wild rodents: ecological validity of a translational model of post-traumatic stress disorder
Authors: Cohen Hagit , Matar Michael A. , Todder Doron , Cohen Carmit , Zohar Joseph , Hawlena Hadas , Abramsky Zvika
Published: September 2023

In the wild, animals face a highly variable world full of predators. Most predator attacks are unsuccessful, and the prey survives. According to the conventional perspective, the fear responses elicited by predators are acute and transient in nature. However, the long-term, non-lethal effects of predator exposure on prey behavioral stress sequelae, such as anxiety and post-traumatic symptoms, remain poorly understood. Most experiments on animal models of anxiety-related behavior or post-traumatic stress disorder have been carried out using commercial strains of rats and mice. A fundamental question is whether laboratory rodents appropriately express the behavioral responses of wild species in their natural environment; in other words, whether behavioral responses to stress observed in the laboratory can be generalized to natural behavior. To further elucidate the relative contributions of the natural selection pressures influences, this study investigated the bio-behavioral and morphological effects of auditory predator cues (owl territorial calls) in males and females of three wild rodent species in a laboratory set-up: Acomys cahirinus; Gerbillus henleyi; and Gerbillus gerbillus. Our results indicate that owl territorial calls elicited not only “fight or flight” behavioral responses but caused PTSD-like behavioral responses in wild rodents that have never encountered owls in nature and could cause, in some individuals, enduring physiological and morphological responses that parallel those seen in laboratory rodents or traumatized people. In all rodent species, the PTSD phenotype was characterized by a blunting of fecal cortisol metabolite response early after exposure and by a lower hypothalamic orexin-A level and lower total dendritic length and number in the dentate gyrus granule cells eight days after predator exposure. Phenotypically, this refers to a significant functional impairment that could affect reproduction and survival and thus fitness and population dynamics.
Targeting hyaluronan-mediated motility receptor (HMMR) enhances response to androgen receptor signalling inhibitors in prostate cancer
Authors: Hinneh Josephine A. , Gillis Joanna L. , Mah Chui Yan , Irani Swati , Shrestha Raj K. , Ryan Natalie K. , Atsushi Enomoto , Nassar Zeyad D. , Lynn David J. , Selth Luke A. , Kato Masashi , Centenera Margaret M. , Butler Lisa M.
Published: September 2023

Background

Resistance to androgen receptor signalling inhibitors (ARSIs) represents a major clinical challenge in prostate cancer. We previously demonstrated that the ARSI enzalutamide inhibits only a subset of all AR-regulated genes, and hypothesise that the unaffected gene networks represent potential targets for therapeutic intervention. This study identified the hyaluronan-mediated motility receptor (HMMR) as a survival factor in prostate cancer and investigated its potential as a co-target for overcoming resistance to ARSIs.

Methods

RNA-seq, RT-qPCR and Western Blot were used to evaluate the regulation of HMMR by AR and ARSIs. HMMR inhibition was achieved via siRNA knockdown or pharmacological inhibition using 4-methylumbelliferone (4-MU) in prostate cancer cell lines, a mouse xenograft model and patient-derived explants (PDEs).

Results

HMMR was an AR-regulated factor that was unaffected by ARSIs. Genetic (siRNA) or pharmacological (4-MU) inhibition of HMMR significantly suppressed growth and induced apoptosis in hormone-sensitive and enzalutamide-resistant models of prostate cancer. Mechanistically, 4-MU inhibited AR nuclear translocation, AR protein expression and subsequent downstream AR signalling. 4-MU enhanced the growth-suppressive effects of 3 different ARSIs in vitro and, in combination with enzalutamide, restricted proliferation of prostate cancer cells in vivo and in PDEs.

Conclusion

Co-targeting HMMR and AR represents an effective strategy for improving response to ARSIs.
Immune landscape and redox imbalance during neurological disorders in COVID-19
Authors: Thakur Abhimanyu , Sharma Vartika , Averbek Sera , Liang Lifan , Pandya Nirali , Kumar Gaurav , Cili Alma , Zhang Kui
Published: September 2023

The outbreak of Coronavirus Disease 2019 (COVID-19) has prompted the scientific community to explore potential treatments or vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes the illness. While SARS-CoV-2 is mostly considered a respiratory pathogen, several neurological complications have been reported, raising questions about how it may enter the Central Nervous System (CNS). Receptors such as ACE2, CD147, TMPRSS2, and NRP1 have been identified in brain cells and may be involved in facilitating SARS-CoV-2 entry into the CNS. Moreover, proteins like P2X7 and Panx-1 may contribute to the pathogenesis of COVID-19. Additionally, the role of the immune system in the gravity of COVID-19 has been investigated with respect to both innate and adaptive immune responses caused by SARS-CoV-2 infection, which can lead to a cytokine storm, tissue damage, and neurological manifestations. A redox imbalance has also been linked to the pathogenesis of COVID-19, potentially causing mitochondrial dysfunction, and generating proinflammatory cytokines. This review summarizes different mechanisms of reactive oxygen species and neuro-inflammation that may contribute to the development of severe COVID-19, and recent progress in the study of immunological events and redox imbalance in neurological complications of COVID-19, and the role of bioinformatics in the study of neurological implications of COVID-19.
Levosulpiride for the treatment of diabetic macular oedema: a phase 2 randomized clinical trial
Authors: Núñez-Amaro Carlos D. , López Mariana , Adán-Castro Elva , Robles-Osorio Ma. Ludivina , García-Franco Renata , García-Roa Marlon , Villalpando-Gómez Yolanda , Ramírez-Neria Paulina , Pineiro Nayeli , Rubio-Mijangos Juan Fernando , Sánchez Jorge , Ramírez-Hernández Gabriela , Siqueiros-Márquez Lourdes , Díaz-Lezama Nundehui , López-Star Ellery , Bertsch Thomas , Marínez de la Escalera Gonzalo , Triebel Jakob , Clapp Carmen
Published: September 2023

Background/Objective

The prokinetic levosulpiride elevates vasoinhibin levels in the vitreous of patients with proliferative diabetic retinopathy (PDR) suggesting clinical benefits due to the anti-vasopermeability and anti-angiogenic properties of vasoinhibin. We investigated the biological activity of levosulpiride in centre-involving diabetic macular oedema (DME).

Patients/Methods

Prospective, randomized, double-blinded, dual-centre, phase 2 trial in patients with centre-involving DME orally treated with placebo (n = 17) or levosulpiride (n = 17) for 8 weeks or in patients with PDR undergoing elective pars plana vitrectomy and receiving placebo (n = 18) or levosulpiride (n = 18) orally for the 1 week before vitrectomy.

Results

Levosulpiride improved changes from baseline in best-corrected visual acuity (p ≤ 0.037), central foveal thickness (CFT, p ≤ 0.013), and mean macular volume (MMV, p ≤ 0.002) at weeks 4, 6, and 8 compared to placebo. At 8 weeks, the proportion of eyes gaining ≥5 ETDRS letters at 4 m (41% vs. 28%), losing ≥21 μm in CFT (55% vs. 28%), and dropping ≥0.06 mm3 in MMV (65% vs. 29%) was higher after levosulpiride than placebo. The overall grading of visual and structural parameters improved with levosulpiride (p = 0.029). Levosulpiride reduced VEGF (p = 0.025) and PlGF (p = 0.008) levels in the vitreous of PDR patients. No significant adverse side-effects were detected.

Conclusions

Oral levosulpiride for 8 weeks improved visual and structural outcomes in patients with centre-involving DME by mechanisms that may include intraocular upregulation of vasoinhibin and downregulation of VEGF and PlGF. Larger clinical trials evaluating long-term efficacy and safety are warranted.
Triplet maintenance therapy of olaparib, pembrolizumab and bevacizumab in women with BRCA wild-type, platinum-sensitive recurrent ovarian cancer: the multicenter, single-arm phase II study OPEB-01/APGOT-OV4
Authors: Kim Yoo-Na , Park Boram , Kim Jae Weon , Kim Byoung Gie , Kim Sang Wun , Kim Hee Seung , Choi Chel Hun , Lim Myong Cheol , YL Ngoi Natalie , SP Tan David , Lee Jung-Yun
Published: September 2023

In this multicenter, open-label, single-arm, Phase II study with Simon two-stage optimum design (NCT04361370), we investigate the efficacy and safety of triplet maintenance (olaparib, pembrolizumab, bevacizumab) in patients with platinum-sensitive recurrent ovarian cancer who are wild-type for BRCA 1/2. A total of 44 patients were enrolled, and the median follow-up duration was 22.9 months (interquartile range: 17.4–24.7). The primary outcome was 6-months progression-free survival (PFS), which was 88.6% (95% confidence interval [CI] 75.4–96.2), meeting the pre-specified primary endpoint. The secondary outcomes reported here include median PFS, 12-months PFS, and overall survival and safety. The median PFS was 22.4 months (20.4–∞), with a 12-months PFS rate of 84.0% (95% CI 69.3–92.0). The median overall survival was 28.6 months (27.3–∞). The combination demonstrated tolerable toxicity with manageable side effects. Other secondary outcomes include time-to-progression, time to subsequent treatment, time to second treatment and PFS2; however, this data is not reported, as treatment is still ongoing in a majority of patients. Exploratory analysis shows that patients who were homologous recombination deficiency-positive or had a programmed death-ligand 1 combined positive score ≥1 showed a favorable response (P = 0.043 and P < 0.001, respectively). Thus, triplet maintenance shows durable efficacy with tolerable safety in patients with platinum-sensitive recurrence.
Haldane topological spin-1 chains in a planar metal-organic framework
Authors: Tin Pagnareach , Jenkins Michael J. , Xing Jie , Caci Nils , Gai Zheng , Jin Rongyin , Wessel Stefan , Krzystek J. , Li Cheng , Daemen Luke L. , Cheng Yongqiang , Xue Zi-Ling
Published: September 2023

Haldane topological materials contain unique antiferromagnetic chains with symmetry-protected energy gaps. Such materials have potential applications in spintronics and future quantum computers. Haldane topological solids typically consist of spin-1 chains embedded in extended three-dimensional (3D) crystal structures. Here, we demonstrate that [Ni(μ−4,4′-bipyridine)(μ-oxalate)]n (NiBO) instead adopts a two-dimensional (2D) metal-organic framework (MOF) structure of Ni2+ spin-1 chains weakly linked by 4,4′-bipyridine. NiBO exhibits Haldane topological properties with a gap between the singlet ground state and the triplet excited state. The latter is split by weak axial and rhombic anisotropies. Several experimental probes, including single-crystal X-ray diffraction, variable-temperature powder neutron diffraction (VT-PND), VT inelastic neutron scattering (VT-INS), DC susceptibility and specific heat measurements, high-field electron spin resonance, and unbiased quantum Monte Carlo simulations, provide a detailed, comprehensive characterization of NiBO. Vibrational (also known as phonon) properties of NiBO have been probed by INS and density-functional theory (DFT) calculations, indicating the absence of phonons near magnetic excitations in NiBO, suppressing spin-phonon coupling. The work here demonstrates that NiBO is indeed a rare 2D-MOF Haldane topological material.
Effect of SARS-CoV-2 prior infection and mRNA vaccination on contagiousness and susceptibility to infection
Authors: Mongin Denis , Bürgisser Nils , Laurie Gustavo , Schimmel Guillaume , Vu Diem-Lan , Cullati Stephane ,   Covid-SMC Study Group, Da Silva Mora Lucienne , Després Lena , Dudouit Rachel , Hirsch Béatrice , Müller Barbara , Roux Charlotte , Duc Géraldine , Zahnd Caroline , Caparros Adriana Uribe , Falcone Jean-Luc , Silva Nuno M. , Goeury Thomas , Charpilloz Christophe , Adamou Silas , Brindel Pauline , Petrucci Roberta , Allgöwer Andrea , Kadjangaba Abdel , Loha Christopher Abo , Macher Emilie , Vassant Marc , Donnat Nadia , Pittet Philippe , Joubert Dominique , Carballido Samia , Germain Ariane , Bontemps Sophie , Delaporte Elisabeth , Genecand Camille , Metsini Aliki , Creac’h Valérie , Calatraba Virginie , Flüeli Laura , Piccard Hippolyte , Lebowitz Dan , Tardin Aglaé , Regard Simon , Courvoisier Delphine Sophie
Published: September 2023

The immunity conferred by SARS-CoV-2 vaccines and infections reduces the transmission of the virus. To answer how the effect of immunity is shared between a reduction of infectiousness and an increased protection against infection, we examined >50,000 positive cases and >110,000 contacts from Geneva, Switzerland (June 2020 to March 2022). We assessed the association between secondary attack rate (i.e. proportion of new cases among contacts) and immunity from natural infection and/or vaccination, stratifying per four SARS-CoV-2 variants and adjusting for index cases and contacts’ socio-demographic characteristics and the propensity of the contacts to be tested. Here we show that immunity protected contacts from infection, rather than reducing infectiousness of index cases. Natural infection conferred the strongest immunity. Hybrid immunity did not surpass recent infection. Although of smaller amplitude, the reduction in infectiousness due to vaccination was less affected by time and by the emergence of new SARS-CoV-2 variants than the susceptibility to infection. These findings support the role of vaccine in reducing infectiousness and underscore the complementary role of interventions reducing SARS-CoV-2 propagation, such as mask use or indoor ventilation.
Synchronization of spin-driven limit cycle oscillators optically levitated in vacuum
Authors: Brzobohatý Oto , Duchaň Martin , Jákl Petr , Ježek Jan , Šiler Martin , Zemánek Pavel , Simpson Stephen H.
Published: September 2023

We explore, experimentally and theoretically, the emergence of coherent coupled oscillations and synchronization between a pair of non-Hermitian, stochastic, opto-mechanical oscillators, levitated in vacuum. Each oscillator consists of a polystyrene microsphere trapped in a circularly polarized, counter-propagating Gaussian laser beam. Non-conservative, azimuthal forces, deriving from inhomogeneous optical spin, push the micro-particles out of thermodynamic equilibrium. For modest optical powers each particle shows a tendency towards orbital circulation. Initially, their stochastic motion is weakly correlated. As the power is increased, the tendency towards orbital circulation strengthens and the motion of the particles becomes highly correlated. Eventually, centripetal forces overcome optical gradient forces and the oscillators undergo a collective Hopf bifurcation. For laser powers exceeding this threshold, a pair of limit cycles appear, which synchronize due to weak optical and hydrodynamic interactions. In principle, arrays of such Non-Hermitian elements can be arranged, paving the way for opto-mechanical topological materials or, possibly, classical time crystals. In addition, the preparation of synchronized states in levitated optomechanics could lead to new and robust sensors or alternative routes to the entanglement of macroscopic objects.
Visualizing the membrane disruption action of antimicrobial peptides by cryo-electron tomography
Authors: Chen Eric H.-L. , Wang Chun-Hsiung , Liao Yi-Ting , Chan Feng-Yueh , Kanaoka Yui , Uchihashi Takayuki , Kato Koichi , Lai Longsheng , Chang Yi-Wei , Ho Meng-Chiao , Chen Rita P.-Y.
Published: September 2023

The abuse of antibiotics has led to the emergence of multidrug-resistant microbial pathogens, presenting a pressing challenge in global healthcare. Membrane-disrupting antimicrobial peptides (AMPs) combat so-called superbugs via mechanisms different than conventional antibiotics and have good application prospects in medicine, agriculture, and the food industry. However, the mechanism-of-action of AMPs has not been fully characterized at the cellular level due to a lack of high-resolution imaging technologies that can capture cellular-membrane disruption events in the hydrated state. Previously, we reported PepD2M, a de novo-designed AMP with potent and wide-spectrum bactericidal and fungicidal activity. In this study, we use cryo-electron tomography (cryo-ET) and high-speed atomic force microscopy (HS-AFM) to directly visualize the pepD2M-induced disruption of the outer and inner membranes of the Gram-negative bacterium Escherichia coli, and compared with a well-known pore-forming peptide, melittin. Our high-resolution cryo-ET images reveal how pepD2M disrupts the E. coli membrane using a carpet/detergent-like mechanism. Our studies reveal the direct membrane-disrupting consequence of AMPs on the bacterial membrane by cryo-ET, and this information provides critical insights into the mechanisms of this class of antimicrobial agents.
Field-free spin-orbit switching of perpendicular magnetization enabled by dislocation-induced in-plane symmetry breaking
Authors: Liang Yuhan , Yi Di , Nan Tianxiang , Liu Shengsheng , Zhao Le , Zhang Yujun , Chen Hetian , Xu Teng , Dai Minyi , Hu Jia-Mian , Xu Ben , Shi Ji , Jiang Wanjun , Yu Rong , Lin Yuan-Hua
Published: September 2023

Current induced spin-orbit torque (SOT) holds great promise for next generation magnetic-memory technology. Field-free SOT switching of perpendicular magnetization requires the breaking of in-plane symmetry, which can be artificially introduced by external magnetic field, exchange coupling or device asymmetry. Recently it has been shown that the exploitation of inherent crystal symmetry offers a simple and potentially efficient route towards field-free switching. However, applying this approach to the benchmark SOT materials such as ferromagnets and heavy metals is challenging. Here, we present a strategy to break the in-plane symmetry of Pt/Co heterostructures by designing the orientation of Burgers vectors of dislocations. We show that the lattice of Pt/Co is tilted by about 1.2° when the Burgers vector has an out-of-plane component. Consequently, a tilted magnetic easy axis is induced and can be tuned from nearly in-plane to out-of-plane, enabling the field-free SOT switching of perpendicular magnetization components at room temperature with a relatively low current density (~1011 A/m2) and excellent stability (> 104 cycles). This strategy is expected to be applicable to engineer a wide range of symmetry-related functionalities for future electronic and magnetic devices.
Ancient Clostridium DNA and variants of tetanus neurotoxins associated with human archaeological remains
Authors: Hodgins Harold P. , Chen Pengsheng , Lobb Briallen , Wei Xin , Tremblay Benjamin J. M. , Mansfield Michael J. , Lee Victoria C. Y. , Lee Pyung-Gang , Coffin Jeffrey , Duggan Ana T. , Dolphin Alexis E. , Renaud Gabriel , Dong Min , Doxey Andrew C.
Published: September 2023

The analysis of microbial genomes from human archaeological samples offers a historic snapshot of ancient pathogens and provides insights into the origins of modern infectious diseases. Here, we analyze metagenomic datasets from 38 human archaeological samples and identify bacterial genomic sequences related to modern-day Clostridium tetani, which produces the tetanus neurotoxin (TeNT) and causes the disease tetanus. These genomic assemblies had varying levels of completeness, and a subset of them displayed hallmarks of ancient DNA damage. Phylogenetic analyses revealed known C. tetani clades as well as potentially new Clostridium lineages closely related to C. tetani. The genomic assemblies encode 13 TeNT variants with unique substitution profiles, including a subgroup of TeNT variants found exclusively in ancient samples from South America. We experimentally tested a TeNT variant selected from an ancient Chilean mummy sample and found that it induced tetanus muscle paralysis in mice, with potency comparable to modern TeNT. Thus, our ancient DNA analysis identifies DNA from neurotoxigenic C. tetani in archaeological human samples, and a novel variant of TeNT that can cause disease in mammals.
An electronic origin of charge order in infinite-layer nickelates
Authors: Chen Hanghui , Yang Yi-feng , Zhang Guang-Ming , Liu Hongquan
Published: September 2023

A charge order (CO) with a wavevector $${{{{{{{\bf{q}}}}}}}}\simeq \left(\frac{1}{3},\, 0,\, 0\right)$$
q
≃

1

3

,

0
,

0

is observed in infinite-layer nickelates. Here we use first-principles calculations to demonstrate a charge-transfer-driven CO mechanism in infinite-layer nickelates, which leads to a characteristic Ni1+-Ni2+-Ni1+ stripe state. For every three Ni atoms, due to the presence of near-Fermi-level conduction bands, Hubbard interaction on Ni-d orbitals transfers electrons on one Ni atom to conduction bands and leaves electrons on the other two Ni atoms to become more localized. We further derive a low-energy effective model to elucidate that the CO state arises from a delicate competition between Hubbard interaction on Ni-d orbitals and charge transfer energy between Ni-d orbitals and conduction bands. With physically reasonable parameters, $${{{{{{{\bf{q}}}}}}}}=\left(\frac{1}{3},\, 0,\, 0\right)$$
q
=

1

3

,

0
,

0

CO state is more stable than uniform paramagnetic state and usual checkerboard antiferromagnetic state. Our work highlights the multi-band nature of infinite-layer nickelates, which leads to some distinctive correlated properties that are not found in cuprates.
A cytotoxic T cell inspired oncolytic nanosystem promotes lytic cell death by lipid peroxidation and elicits antitumor immune responses
Authors: Zuo Zhigui , Yin Hao , Zhang Yu , Xie Congying , Wang Qinyang
Published: September 2023

Lytic cell death triggers an antitumour immune response. However, cancer cells evade lytic cell death by several mechanisms. Moreover, a prolonged and uncontrolled immune response conversely leads to T-cell exhaustion. Therefore, an oncolytic system capable of eliciting an immune response by killing cancer cells in a controlled manner is needed. Here, we establish a micro-scale cytotoxic T-cell-inspired oncolytic system (TIOs) to precisely lyse cancer cells by NIR-light-controlled lipid peroxidation. Our TIOs present antigen-based cell recognition, tumour-targeting and catalytic cell-lysis ability; thus, the TIOs induce oncolysis in vivo. We apply TIOs to preclinical cancer models, showing anti-tumor activity with negligible side-effects. Tumour regression is correlated with a T-cell based anti-tumour immune response and TIOs also improve responses to anti-PD-1 therapy or STING activation. Our study provides insights to design oncolytic systems for antitumour immunity. Moreover, activation of STING can reverse T-cell exhaustion in oncolysis.
Accelerated epigenetic aging and decreased natural killer cells based on DNA methylation in patients with untreated major depressive disorder
Authors: Shindo Ryota , Tanifuji Takaki , Okazaki Satoshi , Otsuka Ikuo , Shirai Toshiyuki , Mouri Kentaro , Horai Tadasu , Hishimoto Akitoyo
Published: September 2023

Major depressive disorder (MDD) is known to cause significant disability. Genome-wide DNA methylation (DNAm) profiles can be used to estimate biological aging and as epigenetic clocks. However, information on epigenetic clocks reported in MDD patients is inconsistent. Since antidepressants are likely confounders, we evaluated biological aging using various DNAm-based predictors in patients with MDD who had never received depression medication. A publicly available dataset consisting of whole blood samples from untreated MDD patients (n = 40) and controls (n = 40) was used. We analyzed five epigenetic clocks (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge), DNAm-based telomere length (DNAmTL), and DNAm-based age-related plasma proteins (GrimAge components), as well as DNAm-based white blood cell composition. The results indicate that patients with untreated MDD were significantly associated with epigenetic aging acceleration in HannumAge and GrimAge. Furthermore, a decrease in natural killer cells, based on DNAm, was observed in patients with untreated MDD.
Spatial predictors of immunotherapy response in triple-negative breast cancer
Authors: Wang Xiao Qian , Danenberg Esther , Huang Chiun-Sheng , Egle Daniel , Callari Maurizio , Bermejo Begoña , Dugo Matteo , Zamagni Claudio , Thill Marc , Anton Anton , Zambelli Stefania , Russo Stefania , Ciruelos Eva Maria , Greil Richard , Győrffy Balázs , Semiglazov Vladimir , Colleoni Marco , Kelly Catherine M. , Mariani Gabriella , Del Mastro Lucia , Biasi Olivia , Seitz Robert S. , Valagussa Pinuccia , Viale Giuseppe , Gianni Luca , Bianchini Giampaolo , Ali H. Raza
Published: September 2023

Immune checkpoint blockade (ICB) benefits some patients with triple-negative breast cancer, but what distinguishes responders from non-responders is unclear1. Because ICB targets cell–cell interactions2, we investigated the impact of multicellular spatial organization on response, and explored how ICB remodels the tumour microenvironment. We show that cell phenotype, activation state and spatial location are intimately linked, influence ICB effect and differ in sensitive versus resistant tumours early on-treatment. We used imaging mass cytometry3 to profile the in situ expression of 43 proteins in tumours from patients in a randomized trial of neoadjuvant ICB, sampled at three timepoints (baseline, n = 243; early on-treatment, n = 207; post-treatment, n = 210). Multivariate modelling showed that the fractions of proliferating CD8+TCF1+T cells and MHCII+ cancer cells were dominant predictors of response, followed by cancer–immune interactions with B cells and granzyme B+ T cells. On-treatment, responsive tumours contained abundant granzyme B+ T cells, whereas resistant tumours were characterized by CD15+ cancer cells. Response was best predicted by combining tissue features before and on-treatment, pointing to a role for early biopsies in guiding adaptive therapy. Our findings show that multicellular spatial organization is a major determinant of ICB effect and suggest that its systematic enumeration in situ could help realize precision immuno-oncology.
Pervasive downstream RNA hairpins dynamically dictate start-codon selection
Authors: Xiang Yezi , Huang Wenze , Tan Lianmei , Chen Tianyuan , He Yang , Irving Patrick S. , Weeks Kevin M. , Zhang Qiangfeng Cliff , Dong Xinnian
Published: September 2023

Translational reprogramming allows organisms to adapt to changing conditions. Upstream start codons (uAUGs), which are prevalently present in mRNAs, have crucial roles in regulating translation by providing alternative translation start sites1–4. However, what determines this selective initiation of translation between conditions remains unclear. Here, by integrating transcriptome-wide translational and structural analyses during pattern-triggered immunity in Arabidopsis, we found that transcripts with immune-induced translation are enriched with upstream open reading frames (uORFs). Without infection, these uORFs are selectively translated owing to hairpins immediately downstream of uAUGs, presumably by slowing and engaging the scanning preinitiation complex. Modelling using deep learning provides unbiased support for these recognizable double-stranded RNA structures downstream of uAUGs (which we term uAUG-ds) being responsible for the selective translation of uAUGs, and allows the prediction and rational design of translating uAUG-ds. We found that uAUG-ds-mediated regulation can be generalized to human cells. Moreover, uAUG-ds-mediated start-codon selection is dynamically regulated. After immune challenge in plants, induced RNA helicases that are homologous to Ded1p in yeast and DDX3X in humans resolve these structures, allowing ribosomes to bypass uAUGs to translate downstream defence proteins. This study shows that mRNA structures dynamically regulate start-codon selection. The prevalence of this RNA structural feature and the conservation of RNA helicases across kingdoms suggest that mRNA structural remodelling is a general feature of translational reprogramming.
Surveillance of Vermont wildlife in 2021–2022 reveals no detected SARS-CoV-2 viral RNA
Authors: Despres Hannah W. , Mills Margaret G. , Schmidt Madaline M. , Gov Jolene , Perez Yael , Jindrich Mars , Crawford Allison M. L. , Kohl Warren T. , Rosenblatt Elias , Kubinski Hannah C. , Simmons Benjamin C. , Nippes Miles C. , Goldenberg Anne J. , Murtha Kristina E. , Nicoloro Samantha , Harris Mia J. , Feeley Avery C. , Gelinas Taylor K. , Cronin Maeve K. , Frederick Robert S. , Thomas Matthew , Johnson Meaghan E. , Murphy James , Lenzini Elle B. , Carr Peter A. , Berger Danielle H. , Mehta Soham P. , Floreani Christopher J. , Koval Amelia C. , Young Aleah L. , Fish Jess H. , Wallace Jack , Chaney Ella , Ushay Grace , Ross Rebecca S. , Vostal Erin M. , Thisner Maya C. , Gonet Kyliegh E. , Deane Owen C. , Pelletiere Kari R. , Rockafeller Vegas C. , Waterman Madeline , Barry Tyler W. , Goering Catriona C. , Shipman Sarah D. , Shiers Allie C. , Reilly Claire E. , Duff Alanna M. , Madruga Sarah L. , Shirley David J. , Jerome Keith R. , Pérez-Osorio Ailyn C. , Greninger Alexander L. , Fortin Nick , Mosher Brittany A. , Bruce Emily A.
Published: September 2023

Previous studies have documented natural infections of SARS-CoV-2 in various domestic and wild animals. More recently, studies have been published noting the susceptibility of members of the Cervidae family, and infections in both wild and captive cervid populations. In this study, we investigated the presence of SARS-CoV-2 in mammalian wildlife within the state of Vermont. 739 nasal or throat samples were collected from wildlife throughout the state during the 2021 and 2022 harvest season. Data was collected from red and gray foxes (Vulpes vulples and Urocyon cineroargentus, respectively), fishers (Martes pennati), river otters (Lutra canadensis), coyotes (Canis lantrans), bobcats (Lynx rufus rufus), black bears (Ursus americanus), and white-tailed deer (Odocoileus virginianus). Samples were tested for the presence of SARS-CoV-2 via quantitative RT-qPCR using the CDC N1/N2 primer set and/or the WHO-E gene primer set. Surprisingly, we initially detected a number of N1 and/or N2 positive samples with high cycle threshold values, though after conducting environmental swabbing of the laboratory and verifying with a second independent primer set (WHO-E) and PCR without reverse transcriptase, we showed that these were false positives due to plasmid contamination from a construct expressing the N gene in the general laboratory environment. Our final results indicate that no sampled wildlife were positive for SARS-CoV-2 RNA, and highlight the importance of physically separate locations for the processing of samples for surveillance and experiments that require the use of plasmid DNA containing the target RNA sequence. These negative findings are surprising, given that most published North America studies have found SARS-CoV-2 within their deer populations. The absence of SARS-CoV-2 RNA in populations sampled here may provide insights in to the various environmental and anthropogenic factors that reduce spillover and spread in North American’s wildlife populations.
Adapting blockchain’s proof-of-work mechanism for multiple traveling salesmen problem optimization
Authors: Sabry Nareman , Shabana Bahaa , Handosa Mohamed , Rashad M. Z.
Published: September 2023

The blockchain network uses a Proof-of-Work (PoW) mechanism to validate transactions and keep the blockchain growth safe against tampering, but it is hugely energy-consuming with no benefit to the peer-to-peer network participants. In this paper, we proposed a blockchain network for distributing products to different locations based on the use of the Proof of Useful Work mechanism, in which miners use computing resources to optimize the traveling salesman problem (TSP) as an alternative to solving mathematical problems that represent the basis of the traditional PoW mechanism to get a new block. According to this proposed blockchain, it not only receives and securely stores the distribution locations but also improves the paths for salesmen when traveling between different locations during the transportation process. This strategy aims to take advantage of the miners’ efforts to minimize the traveled distance by applying the clustering technique and computing the shortest path by Guided Local Search (GLS) for each cluster at the same time. According to the tested results on TSP-LIB instances, the used strategy works efficiently with an average of 0.08 compared to the rest of the meta-heuristics, and the proposed architecture reduced total distances with an average of 0.025%. In addition, the block generation time in the blockchain decreased by 11.11% compared to other works.
The effect of N-arachidonoylethanolamide administration on energy and fat metabolism of early lactating dairy cows
Authors: Schwerdtfeger Jessica , Sauerwein Helga , Albrecht Elke , Mazzuoli-Weber Gemma , von Soosten Dirk , Dänicke Sven , Kuhla Björn
Published: September 2023

The aim of the study was to investigate the effect of N-arachidonoylethanolamide (AEA), an endocannabinoid with orexigenic characteristics, on plasma endocannabinoid concentrations, feed intake, energy balance, lipomobilisation, and hepatic lipid metabolism of early-lactating dairy cows. The experiment involved 10 pairs of Holstein half-sibling cows (end of 2nd–3rd pregnancy). Half-sibs of each pair were randomly assigned to either AEA (n = 10) or control (CON) group (n = 10). From day 1 to 30 postpartum, the AEA group received 5 intraperitoneal injections per week of 3 µg/kg body weight AEA and the CON group 0.9% NaCl. In week 1–3 postpartum, AEA administration had no effect on dry matter intake, body weight, or lipomobilisation, but increased plasma triglyceride concentration on d 21 p.p. and mRNA abundances of genes related to hepatic triglyceride synthesis. In week 4 postpartum, the AEA group showed reduced feed intake and whole-body carbohydrate oxidation, but increased whole-body fat oxidation and hepatic lipid accumulation, likely as a result of a counter-regulatory leptin increase. In conclusion, the present study shows a tissue-specific AEA insensitivity and may point to a leptin-controlled regulation of the ECS in early-lactation.
Different environmental response strategies in sympatric corals from Pacific Islands
Authors: Porro Barbara , Zamoum Thamilla , Forcioli Didier , Gilson Eric , Poquet Adrien , Di Franco Eugenio , Barnay-Verdier Stéphanie , Lombard Fabien , Voolstra Christian R. , Hume Benjamin C. C. , Galand Pierre E. , Moulin Clémentine , Boissin Emilie , Bourdin Guillaume , Iwankow Guillaume , Poulain Julie , Romac Sarah , Agostini Sylvain , Banaigs Bernard , Boss Emmanuel , Bowler Chris , de Vargas Colomban , Douville Eric , Flores Michel , Pesant Stéphane , Reynaud Stéphanie , Sullivan Matthew B. , Sunagawa Shinichi , Thomas Olivier P. , Troublé Romain , Thurber Rebecca Vega , Wincker Patrick , Zoccola Didier , Planes Serge , Allemand Denis , Röttinger Eric , Furla Paola
Published: September 2023

Coral reefs are severely threatened by global and local environmental changes. However, susceptibility to perturbations and subsequent mortality varies among coral species. In this study, we tested the contribution of genetic and environmental conditions to coral’s phenotypic response inPocilloporaspp. andPoritesspp. sampled together at a large ecological and temporal scale throughout the Pacific Ocean. We assessed coral phenotype signatures using a multi-biomarker approach (animal and symbiont biomasses, protein carbonylation and ubiquitination and total antioxidant capacities). In both genera, we highlighted a strong anticorrelation between the redox state and the animal and symbiont biomasses. In addition,Pocilloporaexhibited high phenotypic plasticity, responding to various environmental variables such as temperature, nutrients, phosphate, and carbonate chemistry. In contrast,Poritesdisplayed more robust phenotypes influenced by both genetics and past climate events. In conclusion, co-located coral species display different phenotypic response strategies that are influenced by different environmental conditions.
Increased amplitude of atmospheric rivers and associated extreme precipitation in ultra-high-resolution greenhouse warming simulations
Authors: Nellikkattil Arjun Babu , Lee June-Yi , Guan Bin , Timmermann Axel , Lee Sun-Seon , Chu Jung-Eun , Lemmon Danielle
Published: September 2023

Atmospheric rivers play an integral role in the global water cycle, but predicting their future changes remains uncertain due to inter-model and inter-detection-method differences. Using ultra-high-resolution Community Earth System Model simulations and a novel detection algorithm based on geometric shape extraction, we quantify global changes in atmospheric rivers and the associated precipitation events in response to doubling and quadrupling of atmospheric CO2 concentrations. We find that, atmospheric rivers are projected to become more frequent and more likely to be associated with extreme precipitation events, increasing their contribution to global mean precipitation. While the water vapor transport within these structures follow Clausius-Clapeyron scaling, the changes in maximum precipitation intensity resemble other saturated atmospheric environments like tropical cyclone cores. The increased amplitude of atmospheric rivers and the associated increase in mean and extreme precipitation have important implications for future water management and adaptation policies.