bluuebunny/crossref_metadata_2025 huggingface dataset:
Path instability of deformable bubbles rising in Newtonian liquids: a linear study
Authors: Bonnefis Paul , Sierra-Ausin Javier , Fabre David , Magnaudet Jacques
Published: January 2024

The first stages of the path instability phenomenon affecting the buoyancy-driven motion of gas bubbles rising in weakly or moderately viscous liquids are examined using a recently developed numerical approach designed to assess the global linear stability of incompressible flows involving freely evolving interfaces. Predictions for the critical bubble size and frequency of the most unstable mode are found to agree well with reference data obtained in ultrapure water and in several silicone oils. By varying the bubble size, stability diagrams are built for several specific fluids, revealing three distinct regimes with different bifurcation sequences. The spatial structure of the unstable modes is analysed, together with the variations of the bubble shape, position and orientation. For this purpose, displacements of the bubble surface are split into rigid-body components and volume-preserving deformations, allowing us to determine how the relative magnitude of the latter varies with the fluid properties and bubble size. Predictions obtained with freely deformable bubbles are compared with those found by maintaining the bubble shape determined in the base state frozen during the stability analysis. This comparison reveals that deformations leave the phenomenology of the first bifurcations unchanged in low-viscosity fluids, especially water. Hence, in such fluids, bubbles behave essentially as freely moving rigid bodies submitted to constant-force and zero-torque constraints, at the surface of which the fluid obeys a shear-free condition. In contrast, deformations change the nature of the primary bifurcation in oils slightly more viscous than water, whereas, somewhat surprisingly, they leave the near-threshold phenomenology unchanged in more viscous oils.
Effects of horizontal magnetic fields on turbulent Rayleigh–Bénard convection in a cuboid vessel with aspect ratio Γ = 5
Authors: Chen Long , Wang Zhao-Bo , Ni Ming-Jiu
Published: January 2024

Direct numerical simulations have been conducted to investigate turbulent Rayleigh– Bénard convection (RBC) of liquid metal in a cuboid vessel with aspect ratio

$\varGamma =5$

under an imposed horizontal magnetic field. Flows with Prandtl number

$Pr=0.033$

, Rayleigh numbers ranging up to

$Ra\leq 10^{7}$

, and Chandrasekhar numbers up to

$Q\leq 9 \times 10^6$

are considered. For weak magnetic fields, our findings reveal that a previously undiscovered decreasing region precedes the enhancement of heat transfer and kinetic energy. For moderate magnetic fields, we have reproduced the reversals of the large-scale flow, which are considered a reorganization process of the roll-like structures that were reported experimentally by Yanagisawa et al. (Phys. Rev. E, vol. 83, 2011, 036307). Nevertheless, the proposed approach of skewed-varicose instability has been substantiated as insufficient to elucidate fundamentally the phenomenon of flow reversal, an occurrence bearing a striking resemblance to the large-scale intermittency observed in magnetic channel flows. As we increase the magnetic field strength further, we observe that the energy dissipation of the system comes primarily from the viscous dissipation within the boundary layer. Consequently, the dependence of Reynolds number

$Re$

on

$Q$

approaches a scaling as

$Re\,Pr/Ra^{2/3} \sim Q^{-1/3}$

. At the same time, we find the law for the cutoff frequency that separates large quasi-two-dimensional scales from small three-dimensional ones in RBC flow, which scales with the interaction parameter as

${\sim }N^{1/3}$

.
Salvage treatments for barnyardgrass (Echinochloa crus-galli) control in rice following simulated failed herbicide application
Authors: Bowman Hunter D. , Bond Jason A. , Allen Thomas W. , Reynolds Daniel B. , Bararpour Taghi , Dodds Darrin M. , Eubank Thomas W.
Published: January 2024

Florpyrauxifen-benzyl was commercialized in 2018 to target barnyardgrass and aquatic or broadleaf weeds. Field studies were conducted from 2019 to 2021 in Stoneville, MS, to evaluate barnyardgrass control following a simulated failure of florpyrauxifen-benzyl or other common postemergence rice herbicides. In the first field study, florpyrauxifen-benzyl was applied at 0 and 15 g ai ha–1 to rice at the two- to three-leaf stage to simulate a failed application targeting barnyardgrass. Sequential herbicide treatments included no herbicide and full rates of imazethapyr, quinclorac, bispyribac-Na, and cyhalofop applied 7 or 14 d after florpyrauxifen-benzyl treatment. The second field study was designed to evaluate barnyardgrass control with florpyrauxifen-benzyl following simulated failure of postemergence rice herbicides. Initial herbicide treatments included no herbicide and half rates of imazethapyr, quinclorac, bispyribac-Na, and propanil. Sequential applications at 7 or 14 d after the initial herbicide treatments included florpyrauxifen-benzyl at 0 and 30 g ai ha–1. Results from the first study indicated barnyardgrass control 21 d after final treatment (DAFT) was greater with sequential treatments at 7 compared with 14 d after initial treatment (DA-I) with no initial application of florpyrauxifen-benzyl. Therefore, delaying sequential treatments until 14 d after initial florpyrauxifen-benzyl at 15 g ha–1 allowed barnyardgrass to become too large to control with other rice herbicides. Rough rice yield was reduced in plots where quinclorac application was delayed from 7 to 14 DA-I with no initial application of florpyrauxifen-benzyl. The second study suggested that florpyrauxifen-benzyl application should be delayed 14 d after a herbicide failure. Although no differences in barnyardgrass control 21 DAFT were detected whether florpyrauxifen-benzyl was applied 7 or 14 DA-I of any herbicide utilized, >85% control was only achieved when florpyrauxifen-benzyl application was delayed 14 DA-I. These results demonstrate barnyardgrass control options following simulated failed applications of common rice herbicides.
Geochemical and Sr‐Nd‐Pb‐Fe Isotopic Constraints on the Formation of Fe‐Si Oxyhydroxide Deposits at the Ultraslow‐Spreading Southwest Indian Ridge
Authors: Li Jiangtao , Sun Mingxue , Qi Wenlong , Zhou Zhe , Hohl Simon V. , He Zhiwei
Published: January 2024

Modern Fe‐Si oxyhydroxide deposits occur in global marine hydrothermal vent sites. Despite their role as biogenic substrates and potential ore resources, much remains unknown about their formation processes. Here, we apply analyses of major and trace elements as well as Sr‐Nd‐Pb‐Fe isotopes combined with 238U‐230Th dating to Fe‐Si oxyhydroxides obtained from several hydrothermal fields along the Southwest Indian Ridge. These mineralized oxyhydroxides primarily consist of poorly crystalline two‐line ferrihydrite and amorphous opal‐A, with lesser amounts of nontronite and birnessite. The ubiquitous and characteristic Fe‐rich ultrastructures in the oxyhydroxides directly indicate microbial activity. The 238U‐230Th dating constrains their crystallization ages from ca. 11,873 to 384 years old. The seawater‐like 87Sr/86Sr and varying 143Nd/144Nd ratios underline a high proportion of seawater mixed with hydrothermal fluids. The radiogenic Pb isotopic patterns suggest a primary derivation of Pb leached from substrate basalts and to a lesser extent Pb from seawater. Stable iron isotopic compositions for different oxyhydroxides display a remarkable range between −1.47 and 0.82‰, which were interpreted as reflecting the fractionation processes during the formation of the deposits under evolving depositional redox conditions. The partial oxidation of Fe(II) and the subsurface removal of isotopically heavy Fe oxyhydroxides are suggested to play a vital role in shifting the Fe isotopic signature toward more negative values. Given that these Fe‐Si oxyhydroxide deposits exhibit features similar to certain ancient iron formations (IFs), Fe isotope systematics of these deposits may hold significant potential for fingerprinting the biological Fe oxidation processes that drove IF deposition on early Earth.
A New Method for Eliminating Dust Effects When Quantifying the Light Absorption Properties of Brown Carbon
Authors: Tang Chenguang , Tian Pengfei , Zhang Xinghua , Lin Yingjing , Cao Xianjie , Liang Jiening , Ren Yan , Li Jiayun , Xu Jianzhong , Zhang Lei , Deng Tao , Deng Xuejiao
Published: January 2024

Accurate quantification of the absorption properties of brown carbon (BrC) aerosols is crucial to assess the Earth‐atmosphere radiative impacts of BrC. However, the BrC absorption properties were often misestimated in field observations, due to neglecting the contribution of dust absorption. This study solved this problem by coupling a method for calculating the dust concentration into the traditional model for quantifying BrC absorption. The results show that dust absorption was up to 16.8% of the sum of BrC and dust absorption in northwestern China. The potential contribution of dust to the sum of BrC and dust absorption was significantly higher in the Asia‐located studies (0.4%–16.8%) than in the Americas‐located (<1.2%) and Europe‐located (<2.3%) studies. This work underscores the necessity of eliminating the negative effect of dust in BrC quantitative model. It prompts us to revisit the BrC absorption properties resolved by previous studies, especially in dust‐influenced areas such as Asia.
Cost-effectiveness of weight-management pharmacotherapies in Canada: a societal perspective
Authors: Olivieri Anamaria-Vera , Muratov Sergey , Larsen Sara , Luckevich Maria , Chan Katalina , Lamotte Mark , Lau David C. W.
Published: January 2024

Objectives

This study aimed to assess the cost-effectiveness of weight-management pharmacotherapies approved by Canada Health, i.e., orlistat, naltrexone 32 mg/bupropion 360 mg (NB-32), liraglutide 3.0 mg and semaglutide 2.4 mg as compared to the current standard of care (SoC).

Methods

Analyses were conducted using a cohort with a mean starting age 50 years, body mass index (BMI) 37.5 kg/m2, and 27.6% having type 2 diabetes. Using treatment-specific changes in surrogate endpoints from the STEP trials (BMI, glycemic, blood pressure, lipids), besides a network meta-analysis, the occurrence of weight-related complications, costs, and quality-adjusted life-years (QALYs) were projected over lifetime.

Results

From a societal perspective, at a willingness-to-pay (WTP) threshold of CAD 50 000 per QALY, semaglutide 2.4 mg was the most cost-effective treatment, at an incremental cost-utility ratio (ICUR) of CAD 31 243 and CAD 29 014 per QALY gained versus the next best alternative, i.e., orlistat, and SoC, respectively. Semaglutide 2.4 mg extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg and remained cost-effective both under a public and private payer perspective. Results were robust to sensitivity analyses varying post-treatment catch-up rates, longer treatment durations and using real-world cohort characteristics. Semaglutide 2.4 mg was the preferred intervention, with a likelihood of 70% at a WTP threshold of CAD 50 000 per QALY gained. However, when the modeled benefits of weight-loss on cancer, mortality, cardiovascular disease (CVD) or osteoarthritis surgeries were removed simultaneously, orlistat emerged as the best value for money compared with SoC, with an ICUR of CAD 35 723 per QALY gained.

Conclusion

Semaglutide 2.4 mg was the most cost-effective treatment alternative compared with D&E or orlistat alone, and extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg. Results were sensitive to the inclusion of the combined benefits of mortality, cancer, CVD, and knee osteoarthritis.
Oligogenic inheritance in severe adult obesity
Authors: Almansoori Sumaya , Alsters Suzanne I. , Yiorkas Andrianos M. , Nor Hashim Nikman Adli , Walters Robin G. , Chahal Harvinder S. , Purkayastha Sanjay , Lessan Nader , Blakemore Alexandra I. F.
Published: January 2024

Background/objective

The genetic architecture of extreme non-syndromic obesity in adults remains to be elucidated. A range of genes are known to cause monogenic obesity, but even when pathogenic mutations are present, there may be variable penetrance.

Methods

Whole-exome sequencing (WES) was carried out on a 15-year-old male proband of Pakistani ancestry who had severe obesity. This was followed by family segregation analysis, using Sanger sequencing. We also undertook re-analysis of WES data from 91 unrelated adults with severe obesity (86% white European ancestry) from the Personalised Medicine for Morbid Obesity (PMMO) cohort, recruited from the UK National Health Service.

Results

We identified an oligogenic mode of inheritance of obesity in the proband’s family—this provided the impetus to reanalyze existing sequence data in a separate dataset. Analysis of PMMO participant data revealed two further patients who carried more than one rare, predicted-deleterious mutation in a known monogenic obesity gene. In all three cases, the genes involved had known autosomal dominant inheritance, with incomplete penetrance.

Conclusion

Oligogenic inheritance may explain some of the variable penetrance in Mendelian forms of obesity. We caution clinicians and researchers to avoid confining sequence analysis to individual genes and, in particular, not to stop looking when the first potentially-causative mutation is found.
Magnesium promotes vascularization and osseointegration in diabetic states
Authors: Liu Linfeng , Wang Feiyu , Song Wei , Zhang Danting , Lin Weimin , Yin Qi , Wang Qian , Li Hanwen , Yuan Quan , Zhang Shiwen
Published: January 2024

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants successfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.
In the era of Bortezomib-based Induction, intensification of Melphalan-based conditioning with Bortezomib does not improve Survival Outcomes in newly diagnosed Multiple Myeloma: a study from the Chronic Malignancies Working Party of the EBMT
Authors: Beksac Meral , Eikema Diderik-Jan , Koster Linda , Hulin Cyrille , Poiré Xavier , Hamladji Rose-Marie , Gromek Tomasz , Bazarbachi Ali , Ozkurt Zubeyde Nur , Pabst Thomas , Ben Othman Tarek , Finke Jürgen , Pirogova Olga , Wu Depei , Hayat Amjad , Hilgendorf Inken , Tholouli Eleni , de Wreede Liesbeth C. , Schönland Stefan , Garderet Laurent , Drozd-Sokolowska Joanna , Raj Kavita , Hayden Patrick J. , Yakoub-Agha Ibrahim , McLornan Donal P.
Published: January 2024

Bortezomib (Vel)- Melphalan 200 mg/m2 (Mel200) (Vel-Mel) has been utilised to intensify conditioning in autologous hematopoietic stem cell transplantation (AHCT) for multiple myeloma (MM). This EBMT registry-based study compared Vel-Mel with Mel200 during upfront AHCT. Between 2010 and 2017, MM patients who received Vel-Mel (n = 292) conditioning were compared with 4,096 Mel200 patients in the same 58 centres. Pre-AHCT, compared to Mel200 patients, Vel-Mel patients had similar International Staging System (ISS) scores and cytogenetic risk profiles; a similar proportion had received bortezomib-based induction (85% and 87.3%, respectively) though they were younger with a better performance status. Vel-Mel patients were more likely to achieve CR post-induction (40.6% vs 20.3%, p < 0.001) and by day 100 of AHCT (CR/VGPR: 70.2 % vs. 57.2%, p < 0.001). There was no difference in 3-year PFS (49% vs 46%, p = 0.06) or early post-AHCT mortality. In multivariable analysis, Vel-Mel associated with inferior PFS (HR: 1.69 (1.27–2.25, p < 0.001) and OS (HR:1.46 (1.14–1.86,p = 0.002), similar to negative effects on PFS of advanced ISS (HR:1.56 (1.33–1.83, p < 0.001), high-risk cytogenetics (HR:1.43(1.18–1.74, p < 0.001) and poor post-induction response(<=PR)(HR: 1.43(1.25–1.62, p < 0.001) Overall, despite superior pre- and post-AHCT responses, there was no improvement in PFS or OS following Vel-Mel. This data supports the findings of the smaller prospective IFM study.
Cytoskeleton remodeling induced by SMYD2 methyltransferase drives breast cancer metastasis
Authors: Casanova Alexandre G. , Roth Gael S. , Hausmann Simone , Lu Xiaoyin , Bischoff Ludivine J. M. , Froeliger Emilie M. , Belmudes Lucid , Bourova-Flin Ekaterina , Flores Natasha M. , Benitez Ana Morales , Chasan Tourkian , Caporicci Marcello , Vayr Jessica , Blanchet Sandrine , Ielasi Francesco , Rousseaux Sophie , Hainaut Pierre , Gozani Or , Le Romancer Muriel , Couté Yohann , Palencia Andres , Mazur Pawel K. , Reynoird Nicolas
Published: January 2024

Malignant forms of breast cancer refractory to existing therapies remain a major unmet health issue, primarily due to metastatic spread. A better understanding of the mechanisms at play will provide better insights for alternative treatments to prevent breast cancer cell dispersion. Here, we identify the lysine methyltransferase SMYD2 as a clinically actionable master regulator of breast cancer metastasis. While SMYD2 is overexpressed in aggressive breast cancers, we notice that it is not required for primary tumor growth. However, mammary-epithelium specific SMYD2 ablation increases mouse overall survival by blocking the primary tumor cell ability to metastasize. Mechanistically, we identify BCAR3 as a genuine physiological substrate of SMYD2 in breast cancer cells. BCAR3 monomethylated at lysine K334 (K334me1) is recognized by a novel methyl-binding domain present in FMNLs proteins. These actin cytoskeleton regulators are recruited at the cell edges by the SMYD2 methylation signaling and modulate lamellipodia properties. Breast cancer cells with impaired BCAR3 methylation lose migration and invasiveness capacity in vitro and are ineffective in promoting metastases in vivo. Remarkably, SMYD2 pharmacologic inhibition efficiently impairs the metastatic spread of breast cancer cells, PDX and aggressive mammary tumors from genetically engineered mice. This study provides a rationale for innovative therapeutic prevention of malignant breast cancer metastatic progression by targeting the SMYD2-BCAR3-FMNL axis.
Wide-field imaging with smartphone based fundus camera: grading of severity of diabetic retinopathy and locating peripheral lesions in diabetic retinopathy
Authors: Rajalakshmi Ramachandran , Mohammed Rajah , Vengatesan Kalaivani , PramodKumar Thyparambil Aravindakshan , Venkatesan Ulagamathesan , Usha Manoharan , Arulmalar Subramanian , Prathiba Vijayaraghavan , Mohan Viswanathan
Published: January 2024

Aim

To assess the performance of smartphone based wide-field retinal imaging (WFI) versus ultra-wide-field imaging (UWFI) for assessment of sight-threatening diabetic retinopathy (STDR) as well as locating predominantly peripheral lesions (PPL) of DR.

Methods

Individuals with type 2 diabetes with varying grades of DR underwent nonmydriatic UWFI with Daytona Plus camera followed by mydriatic WFI with smartphone-based Vistaro camera at a tertiary care diabetes centre in South India in 2021–22. Grading of DR as well as identification of PPL (DR lesions beyond the posterior pole) in the retinal images of both cameras was performed by senior retina specialists. STDR was defined by the presence of severe non-proliferative DR, proliferative DR or diabetic macular oedema (DME). The sensitivity and specificity of smartphone based WFI for detection of PPL and STDR was assessed. Agreement between the graders for both cameras was compared.

Results

Retinal imaging was carried out in 318 eyes of 160 individuals (mean age 54.7 ± 9 years; mean duration of diabetes 16.6 ± 7.9 years). The sensitivity and specificity for detection of STDR by Vistaro camera was 92.7% (95% CI 80.1–98.5) and 96.6% (95% CI 91.5–99.1) respectively and 95.1% (95% CI 83.5–99.4) and 95.7% (95% CI 90.3–98.6) by Daytona Plus respectively. PPL were detected in 89 (27.9%) eyes by WFI by Vistaro camera and in 160 (50.3%) eyes by UWFI. However, this did not translate to any significant difference in the grading of STDR between the two imaging systems. In both devices, PPL were most common in supero-temporal quadrant (34%). The prevalence of PPL increased with increasing severity of DR with both cameras (p < 0.001). The kappa comparison between the 2 graders for varying grades of severity of DR was 0.802 (p < 0.001) for Vistaro and 0.753 (p < 0.001) for Daytona Plus camera.

Conclusion

Mydriatic smartphone-based widefield imaging has high sensitivity and specificity for detecting STDR and can be used to screen for peripheral retinal lesions beyond the posterior pole in individuals with diabetes.
GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region
Authors: Ishikawa Yuki , Tanaka Nao , Asano Yoshihide , Kodera Masanari , Shirai Yuichiro , Akahoshi Mitsuteru , Hasegawa Minoru , Matsushita Takashi , Saito Kazuyoshi , Motegi Sei-ichiro , Yoshifuji Hajime , Yoshizaki Ayumi , Kohmoto Tomohiro , Takagi Kae , Oka Akira , Kanda Miho , Tanaka Yoshihito , Ito Yumi , Nakano Kazuhisa , Kasamatsu Hiroshi , Utsunomiya Akira , Sekiguchi Akiko , Niiro Hiroaki , Jinnin Masatoshi , Makino Katsunari , Makino Takamitsu , Ihn Hironobu , Yamamoto Motohisa , Suzuki Chisako , Takahashi Hiroki , Nishida Emi , Morita Akimichi , Yamamoto Toshiyuki , Fujimoto Manabu , Kondo Yuya , Goto Daisuke , Sumida Takayuki , Ayuzawa Naho , Yanagida Hidetoshi , Horita Tetsuya , Atsumi Tatsuya , Endo Hirahito , Shima Yoshihito , Kumanogoh Atsushi , Hirata Jun , Otomo Nao , Suetsugu Hiroyuki , Koike Yoshinao , Tomizuka Kohei , Yoshino Soichiro , Liu Xiaoxi , Ito Shuji , Hikino Keiko , Suzuki Akari , Momozawa Yukihide , Ikegawa Shiro , Tanaka Yoshiya , Ishikawa Osamu , Takehara Kazuhiko , Torii Takeshi , Sato Shinichi , Okada Yukinori , Mimori Tsuneyo , Matsuda Fumihiko , Matsuda Koichi , Amariuta Tiffany , Imoto Issei , Matsuo Keitaro , Kuwana Masataka , Kawaguchi Yasushi , Ohmura Koichiro , Terao Chikashi
Published: January 2024

Here we report the largest Asian genome-wide association study (GWAS) for systemic sclerosis performed to date, based on data from Japanese subjects and comprising of 1428 cases and 112,599 controls. The lead SNP is in the FCGR/FCRL region, which shows a penetrating association in the Asian population, while a complete linkage disequilibrium SNP, rs10917688, is found in a cis-regulatory element for IRF8. IRF8 is also a significant locus in European GWAS for systemic sclerosis, but rs10917688 only shows an association in the presence of the risk allele of IRF8 in the Japanese population. Further analysis shows that rs10917688 is marked with H3K4me1 in primary B cells. A meta-analysis with a European GWAS detects 30 additional significant loci. Polygenic risk scores constructed with the effect sizes of the meta-analysis suggest the potential portability of genetic associations beyond populations. Prioritizing the top 5% of SNPs of IRF8 binding sites in B cells improves the fitting of the polygenic risk scores, underscoring the roles of B cells and IRF8 in the development of systemic sclerosis. The results also suggest that systemic sclerosis shares a common genetic architecture across populations.
Bacterial protoplast-derived nanovesicles carrying CRISPR-Cas9 tools re-educate tumor-associated macrophages for enhanced cancer immunotherapy
Authors: Zhao Mingming , Cheng Xiaohui , Shao Pingwen , Dong Yao , Wu Yongjie , Xiao Lin , Cui Zhiying , Sun Xuedi , Gao Chuancheng , Chen Jiangning , Huang Zhen , Zhang Junfeng
Published: January 2024

The CRISPR-Cas9 system offers substantial potential for cancer therapy by enabling precise manipulation of key genes involved in tumorigenesis and immune response. Despite its promise, the system faces critical challenges, including the preservation of cell viability post-editing and ensuring safe in vivo delivery. To address these issues, this study develops an in vivo CRISPR-Cas9 system targeting tumor-associated macrophages (TAMs). We employ bacterial protoplast-derived nanovesicles (NVs) modified with pH-responsive PEG-conjugated phospholipid derivatives and galactosamine-conjugated phospholipid derivatives tailored for TAM targeting. Utilizing plasmid-transformed E. coli protoplasts as production platforms, we successfully load NVs with two key components: a Cas9-sgRNA ribonucleoprotein targeting Pik3cg, a pivotal molecular switch of macrophage polarization, and bacterial CpG-rich DNA fragments, acting as potent TLR9 ligands. This NV-based, self-assembly approach shows promise for scalable clinical production. Our strategy remodels the tumor microenvironment by stabilizing an M1-like phenotype in TAMs, thus inhibiting tumor growth in female mice. This in vivo CRISPR-Cas9 technology opens avenues for cancer immunotherapy, overcoming challenges related to cell viability and safe, precise in vivo delivery.
Flexible power generators by Ag2Se thin films with record-high thermoelectric performance
Authors: Yang Dong , Shi Xiao-Lei , Li Meng , Nisar Mohammad , Mansoor Adil , Chen Shuo , Chen Yuexing , Li Fu , Ma Hongli , Liang Guang Xing , Zhang Xianghua , Liu Weidi , Fan Ping , Zheng Zhuanghao , Chen Zhi-Gang
Published: January 2024

Exploring new near-room-temperature thermoelectric materials is significant for replacing current high-cost Bi2Te3. This study highlights the potential of Ag2Se for wearable thermoelectric electronics, addressing the trade-off between performance and flexibility. A record-high ZT of 1.27 at 363 K is achieved in Ag2Se-based thin films with 3.2 at.% Te doping on Se sites, realized by a new concept of doping-induced orientation engineering. We reveal that Te-doping enhances film uniformity and (00l)-orientation and in turn carrier mobility by reducing the (00l) formation energy, confirmed by solid computational and experimental evidence. The doping simultaneously widens the bandgap, resulting in improved Seebeck coefficients and high power factors, and introduces TeSe point defects to effectively reduce the lattice thermal conductivity. A protective organic-polymer-based composite layer enhances film flexibility, and a rationally designed flexible thermoelectric device achieves an output power density of 1.5 mW cm−2 for wearable power generation under a 20 K temperature difference.
Slow light topological photonics with counter-propagating waves and its active control on a chip
Authors: Kumar Abhishek , Tan Yi Ji , Navaratna Nikhil , Gupta Manoj , Pitchappa Prakash , Singh Ranjan
Published: January 2024

Topological slow light exhibits potential to achieve stopped light by virtue of its widely known robust and non-reciprocal behaviours. Conventional approach for achieving topological slow light often involves flat-band engineering without disentangling the underlying physical mechanism. Here, we unveil the presence of counter-propagating waves within valley kink states as the distinctive hallmark of the slow light topological photonic waveguides. These counter-propagating waves, supported by topological vortices along glide-symmetric interface, provide significant flexibility for controlling the slowness of light. We tune the group velocity of light by changing the spatial separation between vortices adjacent to the glide-symmetric interface. We also dynamically control the group delay by introducing a non-Hermitian defect using photoexcitation to adjust the relative strength of the counter-propagating waves. This study introduces active slow light topological photonic device on a silicon chip, opening new horizons for topological photon transport through defects, topological light-matter interactions, nonlinear topological photonics, and topological quantum photonics.
Homo sapiens reached the higher latitudes of Europe by 45,000 years ago
Authors: Mylopotamitaki Dorothea , Weiss Marcel , Fewlass Helen , Zavala Elena Irene , Rougier Hélène , Sümer Arev Pelin , Hajdinjak Mateja , Smith Geoff M. , Ruebens Karen , Sinet-Mathiot Virginie , Pederzani Sarah , Essel Elena , Harking Florian S. , Xia Huan , Hansen Jakob , Kirchner André , Lauer Tobias , Stahlschmidt Mareike , Hein Michael , Talamo Sahra , Wacker Lukas , Meller Harald , Dietl Holger , Orschiedt Jörg , Olsen Jesper V. , Zeberg Hugo , Prüfer Kay , Krause Johannes , Meyer Matthias , Welker Frido , McPherron Shannon P. , Schüler Tim , Hublin Jean-Jacques
Published: January 2024

The Middle to Upper Palaeolithic transition in Europe is associated with the regional disappearance of Neanderthals and the spread of Homo sapiens. Late Neanderthals persisted in western Europe several millennia after the occurrence of H. sapiens in eastern Europe1. Local hybridization between the two groups occurred2, but not on all occasions3. Archaeological evidence also indicates the presence of several technocomplexes during this transition, complicating our understanding and the association of behavioural adaptations with specific hominin groups4. One such technocomplex for which the makers are unknown is the Lincombian–Ranisian–Jerzmanowician (LRJ), which has been described in northwestern and central Europe5–8. Here we present the morphological and proteomic taxonomic identification, mitochondrial DNA analysis and direct radiocarbon dating of human remains directly associated with an LRJ assemblage at the site Ilsenhöhle in Ranis (Germany). These human remains are among the earliest directly dated Upper Palaeolithic H. sapiens remains in Eurasia. We show that early H. sapiens associated with the LRJ were present in central and northwestern Europe long before the extinction of late Neanderthals in southwestern Europe. Our results strengthen the notion of a patchwork of distinct human populations and technocomplexes present in Europe during this transitional period.
Single-neuronal elements of speech production in humans
Authors: Khanna Arjun R. , Muñoz William , Kim Young Joon , Kfir Yoav , Paulk Angelique C. , Jamali Mohsen , Cai Jing , Mustroph Martina L. , Caprara Irene , Hardstone Richard , Mejdell Mackenna , Meszéna Domokos , Zuckerman Abigail , Schweitzer Jeffrey , Cash Sydney , Williams Ziv M.
Published: January 2024

Humans are capable of generating extraordinarily diverse articulatory movement combinations to produce meaningful speech. This ability to orchestrate specific phonetic sequences, and their syllabification and inflection over subsecond timescales allows us to produce thousands of word sounds and is a core component of language1,2. The fundamental cellular units and constructs by which we plan and produce words during speech, however, remain largely unknown. Here, using acute ultrahigh-density Neuropixels recordings capable of sampling across the cortical column in humans, we discover neurons in the language-dominant prefrontal cortex that encoded detailed information about the phonetic arrangement and composition of planned words during the production of natural speech. These neurons represented the specific order and structure of articulatory events before utterance and reflected the segmentation of phonetic sequences into distinct syllables. They also accurately predicted the phonetic, syllabic and morphological components of upcoming words and showed a temporally ordered dynamic. Collectively, we show how these mixtures of cells are broadly organized along the cortical column and how their activity patterns transition from articulation planning to production. We also demonstrate how these cells reliably track the detailed composition of consonant and vowel sounds during perception and how they distinguish processes specifically related to speaking from those related to listening. Together, these findings reveal a remarkably structured organization and encoding cascade of phonetic representations by prefrontal neurons in humans and demonstrate a cellular process that can support the production of speech.
Ultracold field-linked tetratomic molecules
Authors: Chen Xing-Yan , Biswas Shrestha , Eppelt Sebastian , Schindewolf Andreas , Deng Fulin , Shi Tao , Yi Su , Hilker Timon A. , Bloch Immanuel , Luo Xin-Yu
Published: January 2024

Ultracold polyatomic molecules offer opportunities1 in cold chemistry2,3, precision measurements4 and quantum information processing5,6, because of their rich internal structure. However, their increased complexity compared with diatomic molecules presents a challenge in using conventional cooling techniques. Here we demonstrate an approach to create weakly bound ultracold polyatomic molecules by electroassociation7 (F.D. et al., manuscript in preparation) in a degenerate Fermi gas of microwave-dressed polar molecules through a field-linked resonance8–11. Starting from ground-state NaK molecules, we create around 1.1 × 103 weakly bound tetratomic (NaK)2 molecules, with a phase space density of 0.040(3) at a temperature of 134(3) nK, more than 3,000 times colder than previously realized tetratomic molecules12. We observe a maximum tetramer lifetime of 8(2) ms in free space without a notable change in the presence of an optical dipole trap, indicating that these tetramers are collisionally stable. Moreover, we directly image the dissociated tetramers through microwave-field modulation to probe the anisotropy of their wavefunction in momentum space. Our result demonstrates a universal tool for assembling weakly bound ultracold polyatomic molecules from smaller polar molecules, which is a crucial step towards Bose–Einstein condensation of polyatomic molecules and towards a new crossover from a dipolar Bardeen–Cooper–Schrieffer superfluid13–15 to a Bose–Einstein condensation of tetramers. Moreover, the long-lived field-linked state provides an ideal starting point for deterministic optical transfer to deeply bound tetramer states16–18.
First experimental demonstration of real-time neutron capture discrimination in helium and carbon ion therapy
Authors: Kielly Marissa , Caracciolo Anita , Chacon Andrew , Vohradsky James , Di Vita Davide , Hamato Akram , Tashima Hideaki , Franklin Daniel R. , Yamaya Taiga , Rosenfeld Anatoly , Carminati Marco , Fiorini Carlo , Guatelli Susanna , Safavi-Naeini Mitra
Published: January 2024

This work provides the first experimental proof of an increased neutron capture photon signal following the introduction of boron to a PMMA phantom during helium and carbon ion therapies in Neutron Capture Enhanced Particle Therapy (NCEPT). NCEPT leverages $$^{10}$$

10

B neutron capture, leading to the emission of detectable 478 keV photons. Experiments were performed at the Heavy Ion Medical Accelerator in Chiba, Japan, with two Poly(methyl methacrylate) (PMMA) targets, one bearing a boron insert. The BeNEdiCTE gamma-ray detector measured an increase in the 478 keV signal of 45 ± 7% and 26 ± 2% for carbon and helium ion irradiation, respectively. Our Geant4 Monte Carlo simulation model, developed to investigate photon origins, found less than 30% of detected photons originated from the insert, while boron in the detector’s circuit boards contributed over 65%. Further, the model investigated detector sensitivity, establishing its capability to record a 10% increase in 478 keV photon detection at a target $$^{10}$$

10

B concentration of 500 ppm using spectral windowing alone, and 25% when combined with temporal windowing. The linear response extended to concentrations up to 20,000 ppm. The increase in the signal in all evaluated cases confirm the potential of the proposed detector design for neutron capture quantification in NCEPT.
A language-independent hearing screening self-test at school-entry
Authors: Van den Borre Elien , Tufatulin Gaziz , Zupan Lea , Božanić Urbančič Nina , Lavie Limor , Holube Inga , Swarnalatha Nagaraj Vinay , Gurses Emre , Denys Sam , van Wieringen Astrid , Wouters Jan
Published: January 2024

The usage of a tablet-based language-independent self-test involving the recognition of ecological sounds in background noise, the Sound Ear Check, was investigated. The results of 692 children, aged between 5 and 9 years and 4 months, recruited in seven different countries, were used to analyze the validity and the cultural independence of test. Three different test procedures, namely a monaural adaptive procedure, a procedure presenting the sounds dichotically in diotic noise, and a procedure presenting all the sounds with a fixed signal-to-noise ratio and a stopping rule were studied. Results showed high sensitivity and specificity of all three procedures to detect conductive, sensorineural and mixed hearing loss > 30 dB HL. Additionally, the data collected from different countries were consistent, and there were no clinically relevant differences observed between countries. Therefore, the Sound Ear Check can offer an international hearing screening test for young children at school entry, solving the current lack of hearing screening services on a global scale.
DEEPOMICS FFPE, a deep neural network model, identifies DNA sequencing artifacts from formalin fixed paraffin embedded tissue with high accuracy
Authors: Heo Dong-hyuk , Kim Inyoung , Seo Heejae , Kim Seong-Gwang , Kim Minji , Park Jiin , Park Hongsil , Kang Seungmo , Kim Juhee , Paik Soonmyung , Hong Seong-Eui
Published: January 2024

Formalin-fixed, paraffin-embedded (FFPE) tissue specimens are routinely used in pathological diagnosis, but their large number of artifactual mutations complicate the evaluation of companion diagnostics and analysis of next-generation sequencing data. Identification of variants with low allele frequencies is challenging because existing FFPE filtering tools label all low-frequency variants as artifacts. To address this problem, we aimed to develop DEEPOMICS FFPE, an AI model that can classify a true variant from an artifact. Paired whole exome sequencing data from fresh frozen and FFPE samples from 24 tumors were obtained from public sources and used as training and validation sets at a ratio of 7:3. A deep neural network model with three hidden layers was trained with input features using outputs of the MuTect2 caller. Contributing features were identified using the SHapley Additive exPlanations algorithm and optimized based on training results. The performance of the final model (DEEPOMICS FFPE) was compared with those of existing models (MuTect filter, FFPolish, and SOBDetector) by using well-defined test datasets. We found 41 discriminating properties for FFPE artifacts. Optimization of property quantification improved the model performance. DEEPOMICS FFPE removed 99.6% of artifacts while maintaining 87.1% of true variants, with an F1-score of 88.3 in the entire dataset not used for training, which is significantly higher than those of existing tools. Its performance was maintained even for low-allele-fraction variants with a specificity of 0.995, suggesting that it can be used to identify subclonal variants. Different from existing methods, DEEPOMICS FFPE identified most of the sequencing artifacts in the FFPE samples while retaining more of true variants, including those of low allele frequencies. The newly developed tool DEEPOMICS FFPE may be useful in designing capture panels for personalized circulating tumor DNA assay and identifying candidate neoepitopes for personalized vaccine design. DEEPOMICS FFPE is freely available on the web (http://deepomics.co.kr/ffpe) for research.
Increasing risks of extreme salt intrusion events across European estuaries in a warming climate
Authors: Lee Jiyong , Biemond Bouke , de Swart Huib , Dijkstra Henk A.
Published: January 2024

Over the last decade, many estuaries worldwide have faced increased salt intrusion as a result of human activities and a changing climate. Despite its socio-economic importance, our current projections on the statistics of future salt intrusion are limited to case studies in certain regions. Here, we show that, compared to present-day conditions, river discharge in the summer months is projected to be reduced by 10–60% in 17 out of 22 investigated major European river basins at the end of the 21st century under the high CO2 emission scenario (Shared Socioeconomic Pathways, SSP 3-7.0). We find that the reduced future river discharge in the summer months, in turn, increases salt intrusion lengths by 10–30% in 9 representative European estuaries at low and mid latitudes. Our analysis further indicates that the European estuaries are projected to experience more than five times more frequent extreme salt intrusion events.
Interaction network of human early embryonic transcription factors
Authors: Gawriyski Lisa , Tan Zenglai , Liu Xiaonan , Chowdhury Iftekhar , Malaymar Pinar Dicle , Zhang Qin , Weltner Jere , Jouhilahti Eeva-Mari , Wei Gong-Hong , Kere Juha , Varjosalo Markku
Published: January 2024

Embryonic genome activation (EGA) occurs during preimplantation development and is characterized by the initiation of de novo transcription from the embryonic genome. Despite its importance, the regulation of EGA and the transcription factors involved in this process are poorly understood. Paired-like homeobox (PRDL) family proteins are implicated as potential transcriptional regulators of EGA, yet the PRDL-mediated gene regulatory networks remain uncharacterized. To investigate the function of PRDL proteins, we are identifying the molecular interactions and the functions of a subset family of the Eutherian Totipotent Cell Homeobox (ETCHbox) proteins, seven PRDL family proteins and six other transcription factors (TFs), all suggested to participate in transcriptional regulation during preimplantation. Using mass spectrometry-based interactomics methods, AP-MS and proximity-dependent biotin labeling, and chromatin immunoprecipitation sequencing we derive the comprehensive regulatory networks of these preimplantation TFs. By these interactomics tools we identify more than a thousand high-confidence interactions for the 21 studied bait proteins with more than 300 interacting proteins. We also establish that TPRX2, currently assigned as pseudogene, is a transcriptional activator.
A bowl-shaped phosphangulene-protected cubic Cu58 nanocluster
Authors: Zhang Qian , Zheng Hao , Zhou Jie , Yang Jia-Ji , Xu Kai-Yue , Shen Lian-Yun , Guan Zong-Jie , Yang Yang
Published: January 2024

The structure, cluster-to-cluster transformation and interaction with fullerenes to improve the properties of a bowl-shaped phosphangulene-protected cubic Cu58 nanocluster are reported.
A “solo-solvent de novo liquid-phase” method for synthesizing sulfide solid electrolyte Li6PS5Cl
Authors: Wang Xinyu , Xu Shijie , Han Aiguo , Sun Yujiang , Zhang Yuzhe , Yang Shunjin , Sun Xiao , Yan Yifan , Qian Haoran , Wang Yanru , Wang Jiakai , Yang Yongan
Published: January 2024

We report a “solo-solvent de novo liquid-phase” method of synthesizing a highly-favored sulfide electrolyte (Li6PS5Cl) for developing all-solid-state lithium batteries.
Scaffold-directed growth of metal halide perovskite hopper crystals
Authors: Zhou Qintian , Kim Min-Woo , Zhang Yuze , Alaei Aida , Shtukenberg Alexander G. , Kalyon Dilhan M. , Lee Stephanie S.
Published: January 2024

Metal halide perovskite crystals grown on close-packed titanium dioxide colloidal monolayers exhibit hopper-like 3D morphologies, with growth initially directed vertically from the substrate before transitioning to the parallel direction.
Composition modulation of a hematite photoanode for highly efficient photoelectrochemical water oxidation
Authors: Wang Jingnan , Lin Kaijie , Cao Yu , Ran Jianhua , Liu Xueqin , Chen Yihuang , Li Yingzhe , Hu Xiaoqin
Published: January 2024

In this work, oxygen vacancy (VO) and hydrogen (H) impurity defects were introduced to control the chemical composition of α-Fe2O3. Our work verifies the relationship between the semiconductor electrode performance and its composition and provides effective guidance for further optimization.
Quantum hardware calculations of the activation and dissociation of nitrogen on iron clusters and surfaces
Authors: Christopoulou Georgia , Di Paola Cono , Elzinga Floris Eelke , Jallat Aurelie , Muñoz Ramo David , Krompiec Michal
Published: January 2024

Quantum-enhanced catalytic reaction modeling on iron clusters and surfaces using a prototype hybrid quantum-classical workflow.
MOF-derived NiAl2O4/NiCo2O4 porous materials as supercapacitors with high electrochemical performance
Authors: Hu Changyu , Xie Huidong , Wang Yibo , Liu Hu , Zhao Yajuan , Yang Chang
Published: January 2024

We prepared NiAl2O4/NiCo2O4 electrode materials with a high specific capacitance of 2870.83 F g−1 at 1 A g−1 using metal–organic frameworks (MOFs) as precursors. The NiAl2O4/NiCo2O4//AC device showed a retention of 72.9% after 2000 cycles.
Quantum rotational dynamics of l-C4(3Σ−g) by H2 at low temperatures employing a machine learning augmented potential energy surface
Authors: Chahal Pooja , Kushwaha Apoorv , Dhilip Kumar T. J.
Published: January 2024

Rotational transitions due to collision of linear carbon cluster with hydrogen: PES aided with neural networks.
An alternative catalytic cycle for selective methane oxidation to methanol with Cu clusters in zeolites
Authors: Gallego Mario , Corma Avelino , Boronat Mercedes
Published: January 2024

The limited activation of O2 on Cu5 clusters supported on CHA zeolite favors the selective oxidation of methane to methanol.
Enhanced supercapacitor performance of porous carbon through tuning maceral composition proportion of coal
Authors: Zhao Ruirui , Hao Jian , Yang Xiao , Zhang Ruyi , Chi Caixia , Zhang Hui , Guo Qingjie
Published: January 2024

Interconnected porous carbon materials with graphite microcrystalline structures were obtained by adjusting the ratio of vitrinite to inertinite. PC-900-40 used as a supercapacitor electrode showed improved cycling and rate performance.
Effect of electric fields on tungsten distribution in Na2WO4–WO3 molten salt
Authors: Guo Yuliang , Sun Xiaobo , Jiao Handong , Zhang Liwen , Qin Wenxuan , Xi Xiaoli , Nie Zuoren
Published: January 2024

The effect of electric field on the microstructure of molten salts was explored by Raman measurements and molecular dynamics with deep potential.
Restructuring of aqueous electrolytes using a soft-acidic/hard-basic zwitterion for low-temperature anode-free Zn batteries
Authors: Kim Hong-I , Lee Kyung Min , Kim Won-Yeong , Kweon Seong Hyeon , Wang Xiao , Zheng Shuanghao , Kim Seung-Hyeok , Ha Jee Ho , Kang Seok Ju , Wu Zhong-Shuai , Kwak Sang Kyu , Lee Sang-Young
Published: January 2024

Restructuring of aqueous electrolytes using a soft-acidic/hard-basic zwitterion enabled low-temperature anode-free Zn batteries, with a focus on enhancing anti-freezing phenomena and Zn2+ desolvation kinetics at electrolyte–electrode interfaces.
Therapeutic effects of a walnut-derived peptide on NLRP3 inflammasome activation, synaptic plasticity, and cognitive dysfunction in T2DM mice
Authors: Li Yanru , Dang Qiao , Shen Yue , Guo Linxin , Liu Chunlei , Wu Dan , Fang Li , Leng Yue , Min Weihong
Published: January 2024

NLRP3 inflammasome activation plays a key role in the development of diabetes-induced cognitive impairment.
Joint associations among non-essential heavy metal mixtures and nutritional factors on glucose metabolism indexes in US adults: evidence from the NHANES 2011–2016
Authors: Chen Xiaolang , Li Peipei , Huang Yuanhao , Lv Yingnan , Xu Xia , Nong Huiyun , Zhang Lulu , Wu Huabei , Yu Chao , Chen Lina , Liu Di , Wei Lancheng , Zhang Haiying
Published: January 2024

By using the CVEK model, we identified that a lower E-DII, a lower intake of carbohydrates and phosphorus, and a higher consumption of magnesium seem to attenuate the positive association between metals and glucose metabolism indexes.