bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategic leadership in spatial planning formulation: the practice in Hainan Province
Authors: Wu Zhiqiang Siegfried , Liu Xiaochang , Zhang Cheng , Zhang Xiuning , Shao Hua
Published: February 2023

Strategic planning of space is an important part of the spatial planning system. With its flexibility and comprehensive features, it can work with statutory planning to build a basic framework for future spatial development to meet various challenges in the future. It is forward-looking, strategic and leading. This paper analyzes the basic characteristics and development trends of global strategic planning of space. Taking the “Special Research in the Strategic Leadership of Territorial Spatial Planning in Hainan Province” as an example, based on the principle of setting goals, improving quality, keeping the bottom line, seeking motive powers, configuring systems and creating new points, it has a forward-looking insight into Hainan’s development trend, accurately formulates Hainan’s development strategy and scientifically constructs Hainan’s development pattern, and constantly promotes the closed loop of the planning subject of “Goal and Vision—Path Selection—Development Motivation—Communication and Decision—Evaluation and Optimization” in practice, and globally leads the formulation of “Territorial Spatial Planning of Hainan Province (2020–2035)”.
Optimisation of perioperative procedural factors to reduce the risk of surgical site infection in patients undergoing surgery: a systematic review
Authors: Calò P. , Catena F. , Corsaro D. , Costantini L. , Falez F. , Moretti B. , Parrinello V. , Romanini E. , Spinarelli A. , Vaccaro G. , Venneri F.
Published: February 2023

Surgical site infections (SSI) are the leading cause of hospital readmission after surgical procedures with significant impact on post-operative morbidity and mortality. Modifiable risk factors for SSI include procedural aspects, which include the possibility of instrument contamination, the duration of the operation, the number of people present and the traffic in the room and the ventilation system of the operating theatre.The aim of this systematic review was to provide literature evidence on the relationship between features of surgical procedure sets and the frequency of SSI in patients undergoing surgical treatment, and to analyse how time frames of perioperative processes and operating theatre traffic vary in relation to the features of the procedure sets use, in order tooptimise infection control in OT. The results of the systematic review brought to light observational studies that can be divided into two categories: evidence of purely clinical significance and evidence of mainly organisational, managerial and financial significance. These two systems are largely interconnected, and reciprocally influence each other. The decision to use disposable devices and instruments has been accompanied by a lower incidence in surgical site infections and surgical revisions for remediation. A concomitant reduction in post-operative functional recovery time has also been observed. Also, the rationalisation of traditional surgical sets has also been observed in conjunction with outcomes of clinical significance.
CULTURAL DIMENSIONS OF WARFARE IN THE MAYA WORLD
Authors: Kim Nam C. , Hernandez Christopher , Bracken Justin , Seligson Kenneth
Published: February 2023

Archaeological studies worldwide have revealed a wide range of cultural contexts within which practices of violence and warfare have occurred. In Mesoamerica, ongoing studies have enriched our understanding of social contexts of violence and warfare in Maya societies. This expanding body of field data allows deeper exploration of the ways violence was intricately linked to different aspects of cultural life for many Maya communities. In this article, we contemplate the culturally embedded nature of violence and warfare with a specific focus on the Classic period and questions related to political strategy, ritual practices, and total warfare. We provide empirical frameworks for the study of war to address issues of ritual warfare and societal impact, and we emphasize a regional scale of analysis.
Percutaneous closure of an atrial septal defect in adult patients with congenitally corrected transposition of the great arteries
Authors: Khajali Zahra , Sayyadi Amin , Firouzi Atta , Aliramezany Maryam
Published: February 2023

Congenitally corrected transposition of great arteries is a rare anomaly which are responsible for 0.5% of all CHDs and can be associated with other congenital cardiac abnormalities. Association of congenitally corrected transposition of great arteries and isolated atrial septal defect is a very rare condition, and management of this association is challenging. In this paper, we describe three patients with congenitally corrected transposition of great arteries and isolated atrial septal defect who were admitted to our clinic and all of them underwent percutaneous closure of defect. From 2017 to 2020, we visited three patients with congenitally corrected transposition of great arteries and isolated atrial septal defect. Our patients’ ages ranged from 28 to 38 years. All of them underwent percutaneous atrial septal defect device closure without any complications. Patients were discharged from hospital in good condition with a daily dose of Aspirin 80 mg and Plavix 75 mg. For all of them, follow-up echocardiography was performed the day after the procedure at 1, 3, and 6 months later and showed the function of the right-sided left ventricle improvement and the severity of the mitral regurgitation was reduced. Furthermore, clinical evaluation also indicated functional class improvement. Although the cases of percutaneous transcatheter closure are few and cannot be regarded as strong evidence to recommend this procedure, the outcomes are promising and can demonstrate that this approach is practical.
Whatever it takes to save the planet? Central banks and unconventional green policy
Authors: Ferrari Alessandro , Nispi Landi Valerio
Published: February 2023

We study the transmission mechanism of a Green QE, defined as a policy that tilts the central bank’s balance sheet toward green bonds, that is bonds issued by non-polluting firms. We merge a DSGE framework with an environmental model, in which CO2 emissions increase the stock of atmospheric carbon, which in turn decreases total factor productivity. Imperfect substitutability between green and brown bonds is a necessary condition for the effectiveness of Green QE. However, even under this assumption, the effect of Green QE in reducing emissions is negligible and in some cases close to nil.
Supportive Care Needs Survey: A reliability generalization meta-analysis
Authors: Lee Hyungran , Jang Yubeen , Jeong Younhee
Published: February 2023

Objectives

The purpose of this study is to investigate the reliability generalization of 2 forms of the Supportive Care Needs Survey (SCNS), the questionnaires commonly used to assess the unmet needs of cancer patients.

Methods

Reviewed articles were retrieved through databases including PubMed, Ovid, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Web of Science, Scopus, and ProQuest. The inclusion criteria were quantitative studies that assessed the unmet needs of cancer patients using the SCNS and presented reliability coefficients with sample size. Two independent reviewers examined the studies according to inclusion criteria and quality. The final studies included in the meta-analysis were determined by consensus. A random effects model was adopted for the analysis. To estimate reliability coefficients, the alpha coefficients for each study were transformed into the Z statistic for normalization and back to alpha. The values were weighted by the inverse of the studies’ variance. The Higgins I2 statistic was used to test for heterogeneity, and the Egger’s test and funnel plot were performed to evaluate publication bias.

Results

Out of 12,522 studies, 26 studies were included in the meta-analysis. The overall mean weighted effect size of the SCNS long-form (LF) was 0.90 and the subdomains ranged from 0.90 to 0.97. The overall alpha for the SCNS short-form (SF) was 0.92, and the alphas for the subdomains were between 0.81 and 0.92. The estimated reliability coefficients in both LF and SF were highest in psychological and health information needs and lowest in sexuality. No publication bias was indicated in this study.

Significance of results

In this study, the overall reliability of SCNS was presented and the factors affecting the reliability of SCNS were identified. The results of this study may help clinicians or researchers make decisions about selecting tools to measure unmet needs of cancer patients.
Potential Vorticity Dynamics Explain How Extratropical Oceans and the Arctic Modulate Wintertime Land‐Temperature Variations
Authors: Xie Yongkun , Huang Jianping , Wu Guoxiong , Liu Yimin
Published: February 2023

Temperature variations across the continental northern hemisphere at the interdecadal scale are thought to be remotely modulated by oceanic internal climate variability and the Arctic. Nevertheless, further elucidating the dynamics is essential for clarifying ongoing debates. We show that potential vorticity (PV) dynamics provide a concise explanation for these teleconnections. Our findings demonstrate that extratropical oceans and the Arctic can remotely modulate the wintertime continental temperature variations by stimulating PV anomalies, which are constrained by climatological PV gradients and jet streams. A causal explanation includes anomalous temperature and precipitation over oceans and the Arctic inducing local PV anomalies via diabatic heating. Subsequently, meridional and downstream advection distributes the anomalous PV to remote land regions where the climatological PV gradients are strong, that is, involving PV fronts, as well as jet streams; therefore, PV fronts and jet streams jointly indicate land regions that are largely and frequently impacted. However, land can also modulate other regions through the same mechanism when variations over land occur in advance. Clear causality depends on which factor is independent, while interactions among those regions may convolute the causality, thereby causing further debates.
Ambient Noise Tomography of the Lipari Volcanic Island (Southern Italy) From a Dense Nodal Array
Authors: Calò Marco , Di Luccio Francesca , Persaud Patricia , Ventura Guido
Published: February 2023

We applied ambient noise tomography to continuous data recorded by a dense seismic array deployed on the volcanic island of Lipari in the southern Tyrrhenian Sea. Since most of Lipari's seismicity occurs offshore and is not evenly distributed, this technique allowed us to obtain the first high‐resolution images beneath the island down to ∼2.5 km depth. Results show a complex seismic structure related to the various ages and compositions of the volcanic products characteristic of the different regions of the island. High shear wave velocities are found in western Lipari, where active hydrothermal vents and N‐S faults are mapped. Low wave speeds are revealed beneath southern and northeastern Lipari, where more recent volcanic activity developed along N‐S dike‐like structures that are aligned with rhyolitic vents. We suggest these dikes likely represent the probable pathways of future volcanic eruptions.
Imaging Radar Observations of the Daytime F‐Region Irregularities in Low‐Latitudes of China
Authors: He Zhiqiu , Chen Gang , Yan Chunxiao , Zhang Shaodong , Yang Guotao , Li Yaxian , Gong Wanlin , Wang Jie , Zhang Min
Published: February 2023

Hainan COherent scatter Phased Array Radar has recorded four patches of daytime F‐region field‐aligned irregularities on 31 May 2021, and it is the first time to investigate the daytime irregularities by the radar imaging technique. In‐beam radar images are plotted on the curved plane transverse to the geomagnetic field lines. The displayed daytime irregularities present the obliquely elongated band‐like structures and the corresponding scatter regions extend to hundreds of kilometers in range and narrow to a few kilometers in the zonal direction. The diffuse and isolated structures were also observed in the radar images. The radar image sequences indicate that the irregularities were continuous in height as they drifted westward. The daytime irregularities maintained the oblique elongated structures that resemble the morphological features of the nighttime equatorial plasma bubbles. Combined with the in situ satellite measurements, these daytime F‐region irregularities are interpreted to be the remnants of the previous night's bubbles and come from the higher altitudes near the magnetic equator.
Three‐Dimensional Simulation of Equatorial Spread F: Effects of Field‐Aligned Plasma Flow and Ionospheric Conductivity
Authors: Li Zezhong , Lei Jiuhou , Zhang Binzheng
Published: February 2023

Recently a Three‐dimensional EquatoriaL spread F (TELF) model using high‐resolving power advection schemes have been developed at the University of Science and Technology of China. With the inclusion of the field‐aligned plasma flow and realistic ionospheric conductivity configuration, the TELF model reproduced typical features of the observed equatorial spread F (ESF) phenomena, including plasma depletions along flux tubes, geomagnetic conjugate irregularities, and ESF morphology as seen in ground optical and satellite observations. Through control simulations, the effects of field‐aligned plasma flow and ionospheric conductivity on ESF are investigated. It is found that field‐aligned plasma flow could inhibit the growth of bubbles by modulating the ionospheric conductivity distribution along field lines, and the plasma bubbles from the TELF model behave more physically in the topside F‐region than those from the 2D model due to the realistic ionospheric conductivity specification. Additionally, the simulations demonstrate that the amplitude and altitude of the initial perturbations can also affect the growth rate of ESF by modulating the polarization electric fields.
ANGPTL4 stabilizes atherosclerotic plaques and modulates the phenotypic transition of vascular smooth muscle cells through KLF4 downregulation
Authors: Cho Dong Im , Ahn Min Joo , Cho Hyang Hee , Cho Meeyoung , Jun Ju Hee , Kang Bo Gyeong , Lim Soo Yeon , Yoo Soo Ji , Kim Mi Ra , Kim Hyung-Seok , Lee Su-Jin , Dat Le Thanh , Lee Changho , Kim Yong Sook , Ahn Youngkeun
Published: February 2023

Atherosclerosis, the leading cause of death, is a vascular disease of chronic inflammation. We recently showed that angiopoietin-like 4 (ANGPTL4) promotes cardiac repair by suppressing pathological inflammation. Given the fundamental contribution of inflammation to atherosclerosis, we assessed the role of ANGPTL4 in the development of atherosclerosis and determined whether ANGPTL4 regulates atherosclerotic plaque stability. We injected ANGPTL4 protein twice a week into atherosclerotic Apoe−/− mice and analyzed the atherosclerotic lesion size, inflammation, and plaque stability. In atherosclerotic mice, ANGPTL4 reduced atherosclerotic plaque size and vascular inflammation. In the atherosclerotic lesions and fibrous caps, the number of α-SMA(+), SM22α(+), and SM-MHC(+) cells was higher, while the number of CD68(+) and Mac2(+) cells was lower in the ANGPTL4 group. Most importantly, the fibrous cap was significantly thicker in the ANGPTL4 group than in the control group. Smooth muscle cells (SMCs) isolated from atherosclerotic aortas showed significantly increased expression of CD68 and Krüppel-like factor 4 (KLF4), a modulator of the vascular SMC phenotype, along with downregulation of α-SMA, and these changes were attenuated by ANGPTL4 treatment. Furthermore, ANGPTL4 reduced TNFα-induced NADPH oxidase 1 (NOX1), a major source of reactive oxygen species, resulting in the attenuation of KLF4-mediated SMC phenotypic changes. We showed that acute myocardial infarction (AMI) patients with higher levels of ANGPTL4 had fewer vascular events than AMI patients with lower levels of ANGPTL4 (p < 0.05). Our results reveal that ANGPTL4 treatment inhibits atherogenesis and suggest that targeting vascular stability and inflammation may serve as a novel therapeutic strategy to prevent and treat atherosclerosis. Even more importantly, ANGPTL4 treatment inhibited the phenotypic changes of SMCs into macrophage-like cells by downregulating NOX1 activation of KLF4, leading to the formation of more stable plaques.
A role of STING signaling in obesity-induced lung inflammation
Authors: Qi Yong , Wu Zhuhua , Chen Dan , Zhu Li , Yang Yunlei
Published: February 2023

Background

It is established that pulmonary disorders are comorbid with metabolic disorders such as obesity. Previous studies show that the stimulator of interferon genes (STING) signaling plays crucial roles in obesity-induced chronic inflammation via TANK-binding kinase 1 (TBK1) pathways. However, it remains unknown whether and how the STING signaling is implicated in the inflammatory processes in the lung in obesity.

Methods

Human lung tissues were obtained from obese patients (n = 3) and controls (n = 3). Mice were fed with the high-fat diet or regular control diet to establish the diet-induced obese (DIO) and lean mice, and were treated with C-176 (a specific STING inhibitor) or vehicle respectively. The lung macrophages were exposed to palmitic acid (PA) in vitro. The levels of STING singaling and metabolic inflammation factors were detected and anlyzed.

Results

We find that STING+/CD68+ macrophages are increased in lung tissues in patients with obesity. Our data also show that the expressions of STING and the levels of proinflammatory cytokines are increased both in lung tissues and bronchoalveolar lavage fluid (BALF) in obesity compared to controls, and inhibition of the STING blunted the obesity-induced lung inflammation. Mechanistically, our data demonstrate that the STING signaling pathway is involved in the PA-induced inflammation through the STING-TBK1-IRF3 (interferon regulatory factor 3)/NF-κB (nuclear factor kappa B) pathways in the lung macrophages.

Conclusions

Our results collectively suggest that the STING signaling contributes to obesity-associated inflammation by stimulating proinflammatory processes in lung macrophages, one that may serve as a therapeutic target in ameliorating obesity-related lung dysfunctions.
Rab31 promotes metastasis and cisplatin resistance in stomach adenocarcinoma through Twist1-mediated EMT
Authors: Chen Ke , Xu Ji , Tong Yu-ling , Yan Jia-Fei , Pan Yu , Wang Wei-jia , Zheng Li , Zheng Xiao-xiao , Hu Can , Hu Xiu , Shen Xian , Chen Wei
Published: February 2023

Stomach adenocarcinoma (STAD) is one of the leading causes of cancer-related death globally. Metastasis and drug resistance are two major causes of failures in current chemotherapy. Here, we found that the expression of Ras-related protein 31 (Rab31) is upregulated in human STAD tissues and high expression of Rab31 is closely associated with poor survival time. Furthermore, we revealed that Rab31 promotes cisplatin resistance and metastasis in human STAD cells. Reduced Rab31 expression induces tumor cell apoptosis and increases cisplatin sensitivity in STAD cells; Rab31 overexpression yielded the opposite result. Rab31 silencing prevented STAD cell migration, whereas the overexpression of Rab31 increased the metastatic potential. Further work showed that Rab31 mediates cisplatin resistance and metastasis via epithelial-mesenchymal transition (EMT) pathway. In addition, we found that both Rab31 overexpression and cisplatin treatment results in increased Twist1 expression. Depletion of Twist1 enhances sensitivity to cisplatin in STAD cells, which cannot be fully reversed by Rab31 overexpression. Rab31 could activate Twist1 by activating Stat3 and inhibiting Mucin 1 (MUC-1). The present study also demonstrates that Rab31 knockdown inhibited tumor growth in mice STAD models. These findings indicate that Rab31 is a novel and promising biomarker and potential therapeutic target for diagnosis, treatment and prognosis prediction in STAD patients. Our data not only identifies a novel Rab31/Stat3/MUC-1/Twist1/EMT pathway in STAD metastasis and drug resistance, but it also provides direction for the exploration of novel strategies to predict and treat STAD in the future.
Dynamic differentiation of F4/80+ tumor-associated macrophage and its role in tumor vascularization in a syngeneic mouse model of colorectal liver metastasis
Authors: Qiao Ting , Yang Wanli , He Xiangchuan , Song Ping , Chen Xiao , Liu Ruijie , Xiao Jian , Yang Xiaoli , Li Mingqi , Gao Yudan , Chen Guoan , Lu Yi , Zhang Jian , Leng Jing , Ren Huan
Published: February 2023

Tumor-associated macrophages (TAMs) are highly heterogeneous and play vital roles in tumor progression. Here we adopted a C57BL/6 mouse model imitating the late-stage colorectal liver metastasis (CRLM) by Mc38 colorectal cancer cell injection via the portal vein. With serial sections of CRLM biopsies, we defined 7–9 days post-injection as the critical period for tumor neovascularization, which was initiated from the innate liver vessels via vessel cooption and extended by vascular mimicry and thereof growth of CD34+cells. In samples with increasing-sized liver metastases, the infiltrated Ly6C+ CD11b+ F4/80− monocytes steadily gained the expression of F4/80, a Kupffer cell marker, before transformed into Ly6C− CD11bint F4/80+ cells, which, the same phenotype was also adapted by Ly6C− CD11b− F4/80+ Kupffer cells. F4/80+ TAMs showed proximity to neovascularization and tumor vessels, functionally angiogenic in vivo; and greatly promoted the activation of a few key angiogenic markers such as VEGFA, Ki67, etc. in endothelial cells in vitro. Depletion of macrophages or diversion of macrophage polarization during neovascularization impeded tumor growth and vascularization and resulted in greatly reduced F4/80+ TAMs, yet increased CD11b+ cells due to inhibition of TAM differentiation. In summary, our results showed dynamic and spatial–temporal F4/80+ TAM transformation within the tumor microenvironment and strengthened its role as perivascular and angiogenic TAMs in CRLM.
FKBP51 plays an essential role in Akt ubiquitination that requires Hsp90 and PHLPP
Authors: Tufano Martina , Marrone Laura , D’Ambrosio Chiara , Di Giacomo Valeria , Urzini Simona , Xiao Yichuan , Matuozzo Monica , Scaloni Andrea , Romano Maria Fiammetta , Romano Simona
Published: February 2023

FKBP51 plays a relevant role in sustaining cancer cells, particularly melanoma. This cochaperone participates in several signaling pathways. FKBP51 forms a complex with Akt and PHLPP, which is reported to dephosphorylate Akt. Given the recent discovery of a spliced FKBP51 isoform, in this paper, we interrogate the canonical and spliced isoforms in regulation of Akt activation. We show that the TPR domain of FKBP51 mediates Akt ubiquitination at K63, which is an essential step for Akt activation. The spliced FKBP51, lacking such domain, cannot link K63-Ub residues to Akt. Unexpectedly, PHLPP silencing does not foster phosphorylation of Akt, and its overexpression even induces phosphorylation of Akt. PHLPP stabilizes levels of E3-ubiquitin ligase TRAF6 and supports K63-ubiquitination of Akt. The interactome profile of FKBP51 from melanoma cells highlights a relevant role for PHLPP in improving oncogenic hallmarks, particularly, cell proliferation.
Extending density functional theory with near chemical accuracy beyond pure water
Authors: Song Suhwan , Vuckovic Stefan , Kim Youngsam , Yu Hayoung , Sim Eunji , Burke Kieron
Published: February 2023

Density functional simulations of condensed phase water are typically inaccurate, due to the inaccuracies of approximate functionals. A recent breakthrough showed that the SCAN approximation can yield chemical accuracy for pure water in all its phases, but only when its density is corrected. This is a crucial step toward first-principles biosimulations. However, weak dispersion forces are ubiquitous and play a key role in noncovalent interactions among biomolecules, but are not included in the new approach. Moreover, naïve inclusion of dispersion in HF-SCAN ruins its high accuracy for pure water. Here we show that systematic application of the principles of density-corrected DFT yields a functional (HF-r2SCAN-DC4) which recovers and not only improves over HF-SCAN for pure water, but also captures vital noncovalent interactions in biomolecules, making it suitable for simulations of solutions.
Tailored compliant mechanisms for reconfigurable electromagnetic devices
Authors: Mackertich-Sengerdy Galestan , Campbell Sawyer D. , Werner Douglas H.
Published: February 2023

Reconfigurable electromagnetic devices, specifically reconfigurable antennas, have shown to be integral to the future of communication systems. However, mechanically robust designs that can survive real-world, harsh environment applications and high-power conditions remain rare to this day. In this paper, the general framework for a field of both discrete and continuously mechanically reconfigurable devices is established by combining compliant mechanisms with electromagnetics. To exemplify this new concept, a reconfigurable compliant mechanism antenna is demonstrated which exhibits continuously tunable performance across a broad band of frequencies. Moreover, three additional examples are also introduced that further showcase the versatility and advanced capabilities of compliant mechanism enabled electromagnetic devices. Unlike previous approaches, this is achieved with minimal part counts, additive manufacturing techniques, and high reliability, which mechanical compliant mechanism devices are known for. The results presented exemplify how compliant mechanisms have the capacity to transform the broader field of reconfigurable electromagnetic devices.
Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation
Authors: Crotta Stefania , Villa Matteo , Major Jack , Finsterbusch Katja , Llorian Miriam , Carmeliet Peter , Buescher Joerg , Wack Andreas
Published: February 2023

Epithelial tissues provide front-line barriers shielding the organism from invading pathogens and harmful substances. In the airway epithelium, the combined action of multiciliated and secretory cells sustains the mucociliary escalator required for clearance of microbes and particles from the airways. Defects in components of mucociliary clearance or barrier integrity are associated with recurring infections and chronic inflammation. The timely and balanced differentiation of basal cells into mature epithelial cell subsets is therefore tightly controlled. While different growth factors regulating progenitor cell proliferation have been described, little is known about the role of metabolism in these regenerative processes. Here we show that basal cell differentiation correlates with a shift in cellular metabolism from glycolysis to fatty acid oxidation (FAO). We demonstrate both in vitro and in vivo that pharmacological and genetic impairment of FAO blocks the development of fully differentiated airway epithelial cells, compromising the repair of airway epithelia. Mechanistically, FAO links to the hexosamine biosynthesis pathway to support protein glycosylation in airway epithelial cells. Our findings unveil the metabolic network underpinning the differentiation of airway epithelia and identify novel targets for intervention to promote lung repair.
Amniotes co-opt intrinsic genetic instability to protect germ-line genome integrity
Authors: Sun Yu H. , Cui Hongxiao , Song Chi , Shen Jiafei Teng , Zhuo Xiaoyu , Wang Ruoqiao Huiyi , Yu Xiaohui , Ndamba Rudo , Mu Qian , Gu Hanwen , Wang Duolin , Murthy Gayathri Guru , Li Pidong , Liang Fan , Liu Lei , Tao Qing , Wang Ying , Orlowski Sara , Xu Qi , Zhou Huaijun , Jagne Jarra , Gokcumen Omer , Anthony Nick , Zhao Xin , Li Xin Zhiguo
Published: February 2023

Unlike PIWI-interacting RNA (piRNA) in other species that mostly target transposable elements (TEs), >80% of piRNAs in adult mammalian testes lack obvious targets. However, mammalian piRNA sequences and piRNA-producing loci evolve more rapidly than the rest of the genome for unknown reasons. Here, through comparative studies of chickens, ducks, mice, and humans, as well as long-read nanopore sequencing on diverse chicken breeds, we find that piRNA loci across amniotes experience: (1) a high local mutation rate of structural variations (SVs, mutations ≥ 50 bp in size); (2) positive selection to suppress young and actively mobilizing TEs commencing at the pachytene stage of meiosis during germ cell development; and (3) negative selection to purge deleterious SV hotspots. Our results indicate that genetic instability at pachytene piRNA loci, while producing certain pathogenic SVs, also protects genome integrity against TE mobilization by driving the formation of rapid-evolving piRNA sequences.
Proteasome inhibition targets the KMT2A transcriptional complex in acute lymphoblastic leukemia
Authors: Kamens Jennifer L. , Nance Stephanie , Koss Cary , Xu Beisi , Cotton Anitria , Lam Jeannie W. , Garfinkle Elizabeth A. R. , Nallagatla Pratima , Smith Amelia M. R. , Mitchell Sharnise , Ma Jing , Currier Duane , Wright William C. , Kavdia Kanisha , Pagala Vishwajeeth R. , Kim Wonil , Wallace LaShanale M. , Cho Ji-Hoon , Fan Yiping , Seth Aman , Twarog Nathaniel , Choi John K. , Obeng Esther A. , Hatley Mark E. , Metzger Monika L. , Inaba Hiroto , Jeha Sima , Rubnitz Jeffrey E. , Peng Junmin , Chen Taosheng , Shelat Anang A. , Guy R. Kiplin , Gruber Tanja A.
Published: February 2023

Rearrangments in Histone-lysine-N-methyltransferase 2A (KMT2Ar) are associated with pediatric, adult and therapy-induced acute leukemias. Infants with KMT2Ar acute lymphoblastic leukemia (ALL) have a poor prognosis with an event-free-survival of 38%. Herein we evaluate 1116 FDA approved compounds in primary KMT2Ar infant ALL specimens and identify a sensitivity to proteasome inhibition. Upon exposure to this class of agents, cells demonstrate a depletion of histone H2B monoubiquitination (H2Bub1) and histone H3 lysine 79 dimethylation (H3K79me2) at KMT2A target genes in addition to a downregulation of the KMT2A gene expression signature, providing evidence that it targets the KMT2A transcriptional complex and alters the epigenome. A cohort of relapsed/refractory KMT2Ar patients treated with this approach on a compassionate basis had an overall response rate of 90%. In conclusion, we report on a high throughput drug screen in primary pediatric leukemia specimens whose results translate into clinically meaningful responses. This innovative treatment approach is now being evaluated in a multi-institutional upfront trial for infants with newly diagnosed ALL.
Engineering nanoscale H supply chain to accelerate methanol synthesis on ZnZrOx
Authors: Lee Kyungho , Mendes Paulo C. D. , Jeon Hyungmin , Song Yizhen , Dickieson Maxim Park , Anjum Uzma , Chen Luwei , Yang Tsung-Cheng , Yang Chia-Min , Choi Minkee , Kozlov Sergey M. , Yan Ning
Published: February 2023

Metal promotion is the most widely adopted strategy for enhancing the hydrogenation functionality of an oxide catalyst. Typically, metal nanoparticles or dopants are located directly on the catalyst surface to create interfacial synergy with active sites on the oxide, but the enhancement effect may be compromised by insufficient hydrogen delivery to these sites. Here, we introduce a strategy to promote a ZnZrOxmethanol synthesis catalyst by incorporating hydrogen activation and delivery functions through optimized integration of ZnZrOxand Pd supported on carbon nanotube (Pd/CNT). The CNT in the Pd/CNT + ZnZrOxsystem delivers hydrogen activated on Pd to a broad area on the ZnZrOxsurface, with an enhancement factor of 10 compared to the conventional Pd-promoted ZnZrOxcatalyst, which only transfers hydrogen to Pd-adjacent sites. In CO2hydrogenation to methanol, Pd/CNT + ZnZrOxexhibits drastically boosted activity—the highest among reported ZnZrOx-based catalysts—and excellent stability over 600 h on stream test, showing potential for practical implementation.
Electroacupuncture improves swallowing function in a post-stroke dysphagia mouse model by activating the motor cortex inputs to the nucleus tractus solitarii through the parabrachial nuclei
Authors: Yao Lulu , Ye Qiuping , Liu Yun , Yao Shuqi , Yuan Si , Xu Qin , Deng Bing , Tang Xiaorong , Shi Jiahui , Luo Jianyu , Wu Junshang , Wu Zhennan , Liu Jianhua , Tang Chunzhi , Wang Lin , Xu Nenggui
Published: February 2023

As a traditional medical therapy, stimulation at the Lianquan (CV23) acupoint, located at the depression superior to the hyoid bone, has been shown to be beneficial in dysphagia. However, little is known about the neurological mechanism by which this peripheral stimulation approach treats for dysphagia. Here, we first identified a cluster of excitatory neurons in layer 5 (L5) of the primary motor cortex (M1) that can regulate swallowing function in male mice by modulating mylohyoid activity. Moreover, we found that focal ischemia in the M1 mimicked the post-stroke dysphagia (PSD) pathology, as indicated by impaired water consumption and electromyographic responses in the mylohyoid. This dysfunction could be rescued by electroacupuncture (EA) stimulation at the CV23 acupoint (EA-CV23) in a manner dependent on the excitatory neurons in the contralateral M1 L5. Furthermore, neuronal activation in both the parabrachial nuclei (PBN) and nucleus tractus solitarii (NTS), which was modulated by the M1, was required for the ability of EA-CV23 treatment to improve swallowing function in male PSD model mice. Together, these results uncover the importance of the M1-PBN-NTS neural circuit in driving the protective effect of EA-CV23 against swallowing dysfunction and thus reveal a potential strategy for dysphagia intervention.
Cross-protective antibodies against common endemic respiratory viruses
Authors: Cabán Madelyn , Rodarte Justas V. , Bibby Madeleine , Gray Matthew D. , Taylor Justin J. , Pancera Marie , Boonyaratanakornkit Jim
Published: February 2023

Respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and human parainfluenza virus types one (HPIV1) and three (HPIV3) can cause severe disease and death in immunocompromised patients, the elderly, and those with underlying lung disease. A protective monoclonal antibody exists for RSV, but clinical use is limited to high-risk infant populations. Hence, therapeutic options for these viruses in vulnerable patient populations are currently limited. Here, we present the discovery, in vitro characterization, and in vivo efficacy testing of two cross-neutralizing monoclonal antibodies, one targeting both HPIV3 and HPIV1 and the other targeting both RSV and HMPV. The 3 × 1 antibody is capable of targeting multiple parainfluenza viruses; the MxR antibody shares features with other previously reported monoclonal antibodies that are capable of neutralizing both RSV and HMPV. We obtained structures using cryo-electron microscopy of these antibodies in complex with their antigens at 3.62 Å resolution for 3 × 1 bound to HPIV3 and at 2.24 Å for MxR bound to RSV, providing a structural basis for in vitro binding and neutralization. Together, a cocktail of 3 × 1 and MxR could have clinical utility in providing broad protection against four of the respiratory viruses that cause significant morbidity and mortality in at-risk individuals.
Ultrarobust subzero healable materials enabled by polyphenol nano-assemblies
Authors: Wang Nan , Yang Xin , Zhang Xinxing
Published: February 2023

Bio-inspired self-healing materials hold great promise for applications in wearable electronics, artificial muscles and soft robots, etc. However, self-healing at subzero temperatures remains a great challenge because the reconstruction of interactions will experience resistance of the frozen segments. Here, we present an ultrarobust subzero healable glassy polymer by incorporating polyphenol nano-assemblies with a large number of end groups into polymerizable deep eutectic solvent elastomers. The combination of multiple dynamic bonds and rapid secondary relaxations with low activation energy barrier provides a promising method to overcome the limited self-healing ability of glassy polymers, which can rarely be achieved by conventional dynamic cross-linking. The resulted material exhibits remarkably improved adhesion force at low temperature (promotes 30 times), excellent mechanical properties (30.6 MPa) and desired subzero healing efficiencies (85.7% at −20 °C). We further demonstrated that the material also possesses reliable cryogenic strain-sensing and functional-healing ability. This work provides a viable approach to fabricate ultrarobust subzero healable glassy polymers that are applicable for winter sports wearable devices, subzero temperature-suitable robots and artificial muscles.
Illumination of a progressive allosteric mechanism mediating the glycine receptor activation
Authors: Shi Sophie , Lefebvre Solène N. , Peverini Laurie , Cerdan Adrien H. , Milán Rodríguez Paula , Gielen Marc , Changeux Jean-Pierre , Cecchini Marco , Corringer Pierre-Jean
Published: February 2023

Pentameric ligand-gated ion channel mediate signal transduction at chemical synapses by transiting between resting and open states upon neurotransmitter binding. Here, we investigate the gating mechanism of the glycine receptor fluorescently labeled at the extracellular-transmembrane interface by voltage-clamp fluorometry (VCF). Fluorescence reports a glycine-elicited conformational change that precedes pore opening. Low concentrations of glycine, partial agonists or specific mixtures of glycine and strychnine trigger the full fluorescence signal while weakly activating the channel. Molecular dynamic simulations of a partial agonist bound-closed Cryo-EM structure show a highly dynamic nature: a marked structural flexibility at both the extracellular-transmembrane interface and the orthosteric site, generating docking properties that recapitulate VCF data. This work illuminates a progressive propagating transition towards channel opening, highlighting structural plasticity within the mechanism of action of allosteric effectors.
Global ocean redox changes before and during the Toarcian Oceanic Anoxic Event
Authors: Kunert Alexandra , Kendall Brian
Published: February 2023

Mesozoic oceanic anoxic events are recognized as widespread deposits of marine organic-rich mudrocks temporally associated with mass extinctions and large igneous province emplacement. The Toarcian Oceanic Anoxic Event is one example during which expanded ocean anoxia is hypothesized in response to environmental perturbations associated with emplacement of the Karoo–Ferrar igneous province. However, the global extent of total seafloor anoxia and the relative extent of euxinic (anoxic and sulfide-rich) and non-euxinic anoxic conditions during the Toarcian Oceanic Anoxic Event are poorly constrained. Here we present estimates of the global total anoxic and euxinic seafloor areas before and during the Toarcian Oceanic Anoxic Event based on rhenium and molybdenum enrichments, respectively, in organic-rich mudrocks of the Fernie Formation (British Columbia, Canada). We find that mass balance models depict an expansion of up to ~7% total seafloor anoxia, which was dominated by euxinia, at the onset of the Toarcian Oceanic Anoxic Event, followed by a contraction before the end of the event. The global ocean redox trends revealed by the rhenium data mirrors the collapse and recovery patterns of global ammonite and foraminiferal biodiversity.
Reversible transformations between the non-porous phases of a flexible coordination network enabled by transient porosity
Authors: Nikolayenko Varvara I. , Castell Dominic C. , Sensharma Debobroto , Shivanna Mohana , Loots Leigh , Forrest Katherine A. , Solanilla-Salinas Carlos J. , Otake Ken-ichi , Kitagawa Susumu , Barbour Leonard J. , Space Brian , Zaworotko Michael J.
Published: February 2023

Flexible metal–organic materials that exhibit stimulus-responsive switching between closed (non-porous) and open (porous) structures induced by gas molecules are of potential utility in gas storage and separation. Such behaviour is currently limited to a few dozen physisorbents that typically switch through a breathing mechanism requiring structural contortions. Here we show a clathrate (non-porous) coordination network that undergoes gas-induced switching between multiple non-porous phases through transient porosity, which involves the diffusion of guests between discrete voids through intra-network distortions. This material is synthesized as a clathrate phase with solvent-filled cavities; evacuation affords a single-crystal to single-crystal transformation to a phase with smaller cavities. At 298 K, carbon dioxide, acetylene, ethylene and ethane induce reversible switching between guest-free and gas-loaded clathrate phases. For carbon dioxide and acetylene at cryogenic temperatures, phases showing progressively higher loadings were observed and characterized using in situ X-ray diffraction, and the mechanism of diffusion was computationally elucidated.
A rapid realist review of universal interventions to promote inclusivity and acceptance of diverse sexual and gender identities in schools
Authors: Schlief Merle , Stefanidou Theodora , Wright Talen , Levy Grace , Pitman Alexandra , Lewis Gemma
Published: February 2023

Universal interventions to promote inclusivity and acceptance of diverse sexual and gender identities in schools could help to prevent mental health problems in this population. We reviewed evidence and developed programme theories to explain which universal interventions work, for whom, in which contexts and why. We conducted a rapid realist review and extracted data in context–mechanism–outcome configurations, to develop and refine programme theories. We included 53 sources and identified five intervention themes: student pride clubs, inclusive antibullying and harassment policies, inclusive curricula, workshops and staff training. Here, we show that these interventions could work by reducing discrimination, bullying and marginalization. Interventions appear to work best when school staff are trained and the school climate is supportive and may be less effective for boys, gender minority students and bisexual students. Our findings provide guiding principles for schools to develop interventions and should encourage primary research to confirm, refute or refine our programme theories.
Diagnostic, clustering, and immune cell infiltration analysis of m6A regulators in patients with sepsis
Authors: Li Fenghui , Zhang Yuan , Peng Zhiyun , Wang Yingjing , Zeng Zhaoshang , Tang Zhongxiang
Published: February 2023

RNA N6-methladenosine (m6A) regulators are required for a variety of biological processes, including immune responses, and increasing evidence indicates that their dysregulation is closely associated with many diseases. However, the potential roles of m6A regulators in sepsis remain unknown. We comprehensively analyzed the transcriptional variations in and interactions of 26 m6A regulators in sepsis based on the Gene Expression Omnibus (GEO) database. A random forest (RF) model and nomogram were established to predict the occurrence and risk of sepsis in patients. Then, two different m6A subtypes were defined by consensus clustering analysis, and we explored the correlation between the subtypes and immune cells. We found that 17 of the 26 m6A regulators were significantly differentially expressed between patients with and without sepsis, and strong correlations among these 17 m6A regulators were revealed. Compared with the support vector machine (SVM) model, the RF model had better predictive ability, and therefore was used to construct a reliable nomogram containing 10 candidate m6A regulators to predict the risk of sepsis in patients. In addition, a consensus clustering algorithm was used to identify two different subtypes of m6A, which helped us distinguish different levels of immune cell infiltration and inflammation in patients with sepsis. Comprehensive analysis of m6A regulators in sepsis revealed their potential roles in sepsis occurrence, immune cell infiltration and inflammation in patients with sepsis. This study may contribute to the development of follow-up treatment strategies for sepsis.
A machine learning pipeline to classify foetal heart rate deceleration with optimal feature set
Authors: Das Sahana , Obaidullah Sk Md , Mahmud Mufti , Kaiser M. Shamim , Roy Kaushik , Saha Chanchal Kumar , Goswami Kaushik
Published: February 2023

Deceleration is considered a commonly practised means to assess Foetal Heart Rate (FHR) through visual inspection and interpretation of patterns in Cardiotocography (CTG). The precision of deceleration classification relies on the accurate estimation of corresponding event points (EP) from the FHR and the Uterine Contraction Pressure (UCP). This work proposes a deceleration classification pipeline by comparing four machine learning (ML) models, namely, Multilayer Perceptron (MLP), Random Forest (RF), Naïve Bayes (NB), and Simple Logistics Regression. Towards an automated classification of deceleration from EP using the pipeline, it systematically compares three approaches to create feature sets from the detected EP: (1) a novel fuzzy logic (FL)-based approach, (2) expert annotation by clinicians, and (3) calculated using National Institute of Child Health and Human Development guidelines. The classification results were validated using different popular statistical metrics, including receiver operating characteristic curve, intra-class correlation coefficient, Deming regression, and Bland-Altman Plot. The highest classification accuracy (97.94%) was obtained with MLP when the EP was annotated with the proposed FL approach compared to RF, which obtained 63.92% with the clinician-annotated EP. The results indicate that the FL annotated feature set is the optimal one for classifying deceleration from FHR.
Automatic measurement and prediction of Chinese Grown Pigs weight using multilayer perceptron neural networks
Authors: Ositanwosu Obiajulu Emenike , Huang Qiong , Liang Yun , Nwokoye Chukwunonso H.
Published: February 2023

The knowledge of body size/weight is necessary for the general growth enhancement of swine as well as for making informed decisions that concern their health, productivity, and yield. Therefore, this work aims to automate the collection of pigs’ body parameters using images from Kinect V2 cameras, and the development of Multilayer Perceptron Neural Network (MLP NN) models to predict their weight. The dataset obtained using 3D light depth cameras contains 9980 pigs across the S21 and S23 breeds, and then grouped into 70:15:15 training, testing, and validation sets, respectively. Initially, two MLP models were built and evaluations revealed that model 1 outperformed model 2 in predicting pig weights, with root mean squared error (RMSE) values of 5.5 and 6.0 respectively. Moreover, employing a normalized dataset, two new models (3 and 4) were developed and trained. Subsequently, models 2, 3, and 4 performed significantly better with a RMSE value of 5.29 compared to model 1, which has a RMSE value of 6.95. Model 3 produced an intriguing discovery i.e. accurate forecasting of pig weights using just two characteristics, age and abdominal circumference, and other error values show corresponding results