bluuebunny/crossref_metadata_2025 huggingface dataset:
The Spelling Problem
Authors: Bainbridge Anthony F.
Published: March 2024

It is generally accepted by scholars that the songs of Homer were first written in ~ 700 BCE; the text seems to spring fully formed into a still illiterate world, demonstrating in a sophisticated vocabulary the first example of the use of a new alphabet. The language used is a never-spoken construct; its construction represents the first use of an alphabet enabling words to be written. This paper aims to open a discussion on the means by which spelling emerged, either democratically or as the work of one man.
Registering Race: Inclusionand Omissionin Bolivian Military-Service Records 1900–1960
Authors: Shesko Elizabeth
Published: March 2024

Through presence or absence, indigeneity has long been at the center of Bolivian politics, culture, and nationalism.1 It carries immense social import. Yet what Indigenous means and who gets counted as part of this umbrella category has never been clear or static. Although Bolivia's racial and ethnic categories seem as etched in stone as the Andes themselves, individual classification is fluid and situational based on sociocultural markers that change over time. These markers include occupation, literacy, dress, language, surname, and residence. Individuals may move through these categories (and not only in one direction) over the course of their lives. This fluidity, combined with changing meaning and the valorization of indigeneity at the national and international levels, has led to wild fluctuations in official statistics on race since independence. The social construction of these categories came to the fore in 2012 when the census reported that Bolivians who identified as Indigenous had dropped to 40 percent of the population, down from 62 percent only eleven years earlier. International observers were left wondering, where did all the Indigenous people go?2
Differences in risk profile associated with varicose veins and	chronic venous insufficiency – results from the Bonn Vein Study	1
Authors: Kraus Anna-Lena , Rabe Eberhard , Kowall Bernd , Schuldt Katrin , Bock Eva , Stang Andreas , Jöckel Karl-Heinz , Pannier Felizitas
Published: March 2024

Summary: Background: The aim of this publication is to demonstrate similarities and differences in the association of risk factors with the prevalence of different manifestations of chronic venous disease (CVD), like varicose veins (VV), venous oedema (C3) and severe chronic venous insufficiency (CVI) in the population-based cross-sectional Bonn Vein Study 1 (BVS). Patients and methods: In the BVS 1 between 13.11.2000 and 15.3.2002, 3.072 participants, 1350 men and 1722 women, from a simple random sample of the general population of the city of Bonn and two rural townships aged 18–79 years were included. The overall response proportion was 59%. All participants answered a standardized questionnaire including information about socio-economic data, lifestyle, physical activity, medical history, and quality of life. Venous investigations were performed clinically and by a standardized duplex examination by trained investigators. The CEAP classification in the version of 1996 was used to classify the findings. Logistic regression models were performed for the association of possible risk factors with VV, venous edema (C3) and severe CVI (C4–C6). The predictive risk (PR) describes the association of the diseases and the possible influencing factors. Results: VV, venous oedema (C3) and severe CVI (C4–C6) have common risk factors like higher age, number of pregnancies, family history of VV and overweight or obesity. Female gender is significantly associated with VV and C3 but not with severe CVI (C4–C6). High blood pressure and urban living are only associated with C3 and C4–C6 disease whereas prolonged sitting is associated with C3 and lower social class with C4–C6 exclusively. Discussion: In many epidemiological studies risk factors were associated with chronic venous disorders in general. Our data show that VV, venous edema and severe CVI may have different risk profiles. Venous edema is more often associated with arterial hypertension and sedentary lifestyle whereas lower social class seems to be a risk factor for severe CVI including venous ulcers. Conclusions: The differences in the association of risk factors to VV, venous edema and severe CVI should be considered if prevention and treatment of chronic venous diseases are planned. As examples, compression stockings could be proposed in sitting profession to prevent oedema, VV patients with risk factors like obesity might benefit from early treatment for VV and obesity. More longitudinal evaluation of risk factors is necessary to evaluate the true risk profile of CVD.
Fluid‐Driven Mass Transfer During Retrograde Metamorphism and Exhumation of the UHP Western Gneiss Region Terrane, Norway
Authors: Shulaker D. Z. , Gordon S. M. , Hammerli J. , DesOrmeau J. W.
Published: March 2024

Dehydration reactions within subducted oceanic crust are important for fluid‐mediated element transfer within the subducting plate and potentially to the mantle wedge. The effects of metamorphic reactions and fluid flow on element recycling that occur during retrogression and exhumation of subducted continental crust from mantle depths are poorly understood. We study two metabasite pods with fresh eclogite cores and retrogressed amphibolite‐facies rims and surrounding host gneiss within the Western Gneiss Region (WGR), Norway, to better understand element mobility and mass transfer during exhumation of subducted continental crust. Bulk‐rock data were collected from samples taken across the pod and into the host gneiss. Phengite breakdown in eclogite and epidote recrystallization in veins and/or gneiss within pod cores contributed large ion lithophile elements and REE to retrogressed eclogite closest to the pod cores. In gneiss hosting the pods, phengite and epidote breakdown provided fluid that mediated elemental transfer and redistribution to the pod rim or tail. Compared to the studied pod in the southern WGR, the pod in the northern WGR underwent higher P‐T conditions, partial melting and higher strain rates. This resulted in the infiltration of external fluid farther into the pod interior from the rim and facilitated larger mass gain in trace elements in the amphibolite tail of the pod relative to fresh eclogite in the core. The results show clear evidence for retrogression dehydration reactions driving significant fluid‐mediated element redistribution as observed on the outcrop scale during exhumation following ultrahigh‐pressure metamorphism, which directly impacts element signatures within the exhuming crust.
Seismological Constraints on the Causes of Intraplate Earthquakes in Yangjiang Region, South China
Authors: Li Lun , Zhang Jinming , Shen Xuzhang , Wang Xiaona , He Jialong , Zhao Lingfeng , Deng Zhihui , Gao Rui
Published: March 2024

Large earthquakes that occur away from plate boundaries (i.e., large intraplate earthquakes), though rare, could cause heavy damage. Understanding their causes could help with seismic hazard assessment. In this study, we image the seismogenic structure under the 1969 Ms6.4 Yangjiang intraplate earthquake within the stable South China Block with a high‐resolution three‐dimensional shear‐wave velocity model constructed from ambient noise tomography based on a dense nodal seismic array. The model images relatively low velocities at a fault intersection region from the surface to at least 13 km depth in the Yangjiang seismogenic zone. Given spatial links among the intersection zone of faults, surface seawater, and low velocities, we interpret the low velocities to reflect the presence of seawater‐filled, highly fractured rocks created by the intersection of faults. We infer that the seawater infiltration through densely‐fractures could have elevated pore pressure in the long term, as evidenced by low earthquake b values at 8–13 km depths. We hypothesize that this long‐term seawater infiltration could have lowered the stress threshold of earthquake occurrence and contributed to the generation of the 1969 Ms6.4 Yangjiang earthquake. We propose that the large intraplate earthquakes within stable plates tend to occur in regional weakening regions (e.g., fault intersections) favorable to stress buildup. Given sufficient tectonic stress accumulation, the long‐term hydrologically driven crustal stress variations could play an essential role in triggering large intraplate earthquakes. This study could potentially contribute to improving seismic hazard assessment in the Guangdong‐Hong Kong‐Macao‐Greater‐Bay‐Area, China.
The Manantiales Basin, Southern Central Andes (∼32°S), Preserves a Record of Late Eocene–Miocene Episodic Growth of an East‐Vergent Orogenic Wedge
Authors: Ronemus Chance B. , Howlett Caden J. , DeCelles Peter G. , Carrapa Barbara , George Sarah W. M.
Published: March 2024

The Manantiales basin contains >4 km of nonmarine sedimentary strata that accumulated at 31.75–32.5°S during construction of the High Andes. We report field and analytical data from the underexplored northern portion of this basin. The basin contains upper Eocene–middle Miocene strata that accumulated in back‐bulge or distal foredeep through inner‐wedge‐top depozones of the Andean foreland basin as it migrated through this region. A revised accumulation history for the basin‐filling Río de los Patos and Chinches Formations supports a regional pattern of flexure in front of an east‐vergent orogenic wedge. The former formation consists of eolian and localized fluviolacustrine deposits which accumulated between ca. 38 Ma and ≤34 Ma during thrust belt development in Chile. A subsequent ≤12 Myr hiatus may reflect passage of the flexural forebulge or cessation of subsidence during orogenic quiescence. The overlying Chinches Formation records a transition from the foredeep to wedge‐top depozones. Foredeep deposits of east‐flowing, meandering streams were incised prior to ca. 18 Ma, after which deposits of axial rivers, playas, and perennial lakes ponded in a depression behind orogenic topography to the east. After ca. 15 Ma, alluvial‐fan deposits were syndepositionally deformed adjacent to growing thrust‐belt structures along the western basin margin. Although the basin record supports a westward step in the locus of deformation during Early–Middle Miocene time, it conflicts with models involving west‐vergence of the orogenic wedge. Rather, this pattern can be explained as out‐of‐sequence deformation alternating with wedge forward propagation, consistent with Coulomb wedge models incorporating syntectonic sedimentation.
Synergistic toxicity with copper contributes to NAT2-associated isoniazid toxicity
Authors: Yoon Jihoon G. , Jang Dong Geon , Cho Sung-Gyu , Lee Chaeyoung , Noh Shin Hye , Seo Soo Kyung , Yu Jung Woo , Chung Hyeon Woo , Han KyeoRe , Kwon Soon Sung , Han Dai Hoon , Oh Jaeseong , Jang In-Jin , Kim Sang-Hoon , Jee Young-Koo , Lee Hyun , Park Dong Won , Sohn Jang Won , Yoon Ho Joo , Kim Chul Hoon , Lee Jae Myun , Kim Sang-Heon , Lee Min Goo
Published: March 2024

Anti-tuberculosis (AT) medications, including isoniazid (INH), can cause drug-induced liver injury (DILI), but the underlying mechanism remains unclear. In this study, we aimed to identify genetic factors that may increase the susceptibility of individuals to AT-DILI and to examine genetic interactions that may lead to isoniazid (INH)-induced hepatotoxicity. We performed a targeted sequencing analysis of 380 pharmacogenes in a discovery cohort of 112 patients (35 AT-DILI patients and 77 controls) receiving AT treatment for active tuberculosis. Pharmacogenome-wide association analysis was also conducted using 1048 population controls (Korea1K). NAT2 and ATP7B genotypes were analyzed in a replication cohort of 165 patients (37 AT-DILI patients and 128 controls) to validate the effects of both risk genotypes. NAT2 ultraslow acetylators (UAs) were found to have a greater risk of AT-DILI than other genotypes (odds ratio [OR] 5.6 [95% confidence interval; 2.5–13.2], P = 7.2 × 10−6). The presence of ATP7B gene 832R/R homozygosity (rs1061472) was found to co-occur with NAT2 UA in AT-DILI patients (P = 0.017) and to amplify the risk in NAT2 UA (OR 32.5 [4.5–1423], P = 7.5 × 10−6). In vitro experiments using human liver-derived cell lines (HepG2 and SNU387 cells) revealed toxic synergism between INH and Cu, which were strongly augmented in cells with defective NAT2 and ATP7B activity, leading to increased mitochondrial reactive oxygen species generation, mitochondrial dysfunction, DNA damage, and apoptosis. These findings link the co-occurrence of ATP7B and NAT2 genotypes to the risk of INH-induced hepatotoxicity, providing novel mechanistic insight into individual AT-DILI susceptibility.
Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer
Authors: Bae Taegeun , Hallis Steffanus Pranoto , Kwak Mi-Kyoung
Published: March 2024

Oxygen is crucial for life and acts as the final electron acceptor in mitochondrial energy production. Cells adapt to varying oxygen levels through intricate response systems. Hypoxia-inducible factors (HIFs), including HIF-1α and HIF-2α, orchestrate the cellular hypoxic response, activating genes to increase the oxygen supply and reduce expenditure. Under conditions of excess oxygen and resulting oxidative stress, nuclear factor erythroid 2-related factor 2 (NRF2) activates hundreds of genes for oxidant removal and adaptive cell survival. Hypoxia and oxidative stress are core hallmarks of solid tumors and activated HIFs and NRF2 play pivotal roles in tumor growth and progression. The complex interplay between hypoxia and oxidative stress within the tumor microenvironment adds another layer of intricacy to the HIF and NRF2 signaling systems. This review aimed to elucidate the dynamic changes and functions of the HIF and NRF2 signaling pathways in response to conditions of hypoxia and oxidative stress, emphasizing their implications within the tumor milieu. Additionally, this review explored the elaborate interplay between HIFs and NRF2, providing insights into the significance of these interactions for the development of novel cancer treatment strategies.
IL-27-induced PD-L1highSca-1+ innate lymphoid cells suppress contact hypersensitivity in an IL-10-dependent manner
Authors: Min Keun Young , Kim Do-Kyun , Jo Min Geun , Choi min Yeong , Lee Dajeong , Park Jeong Won , Park Young-Jun , Chung Yeonseok , Kim Young Mi , Park Yeong-Min , Kim Hyuk Soon , Choi Wahn Soo
Published: March 2024

Innate lymphoid cells (ILCs) play an important role in maintaining tissue homeostasis and various inflammatory responses. ILCs are typically classified into three subsets, as is the case for T-cells. Recent studies have reported that IL-10-producing type 2 ILCs (ILC210s) have an immunoregulatory function dependent on IL-10. However, the surface markers of ILC210s and the role of ILC210s in contact hypersensitivity (CHS) are largely unknown. Our study revealed that splenic ILC210s are extensively included in PD-L1highSca-1+ ILCs and that IL-27 amplifies the development of PD-L1highSca-1+ ILCs and ILC210s. Adoptive transfer of PD-L1highSca-1+ ILCs suppressed oxazolone-induced CHS in an IL-10-dependent manner Taken together, our results demonstrate that ILC210s are critical for the control of CHS and suggest that ILC210s can be used as target cells for the treatment of CHS.
Expert consensus on irrigation and intracanal medication in root canal therapy
Authors: Zou Xiaoying , Zheng Xin , Liang Yuhong , Zhang Chengfei , Fan Bing , Liang Jingping , Ling Junqi , Bian Zhuan , Yu Qing , Hou Benxiang , Chen Zhi , Wei Xi , Qiu Lihong , Chen Wenxia , He Wenxi , Xu Xin , Meng Liuyan , Zhang Chen , Chen Liming , Deng Shuli , Lei Yayan , Xie Xiaoli , Wang Xiaoyan , Yu Jinhua , Zhao Jin , Shen Song , Zhou Xuedong , Yue Lin
Published: March 2024

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes. Additionally, ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified. Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes. Indeed, clinicians have been aware of these concerns for years. Based on the current evidence of studies, this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions. The evolution of different kinetic irrigation methods, their effects, limitations, the paradigm shift, current indications, and effective operational procedures regarding intracanal medication are also discussed. This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication, thus facilitating a better understanding of infection control, standardizing clinical practice, and ultimately improving the success of endodontic therapy.
Expert consensus on difficulty assessment of endodontic therapy
Authors: Huang Dingming , Wang Xiaoyan , Liang Jingping , Ling Junqi , Bian Zhuan , Yu Qing , Hou Benxiang , Chen Xinmei , Li Jiyao , Ye Ling , Cheng Lei , Xu Xin , Hu Tao , Wu Hongkun , Guo Bin , Su Qin , Chen Zhi , Qiu Lihong , Chen Wenxia , Wei Xi , Huang Zhengwei , Yu Jinhua , Lin Zhengmei , Zhang Qi , Yang Deqin , Zhao Jin , Pan Shuang , Yang Jian , Wu Jiayuan , Pan Yihuai , Xie Xiaoli , Deng Shuli , Huang Xiaojing , Zhang Lan , Yue Lin , Zhou Xuedong
Published: March 2024

Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy (RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system’s anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.
Photo-responsive functional materials based on light-driven molecular motors
Authors: Deng Yanping , Long Guiying , Zhang Yang , Zhao Wei , Zhou Guofu , Feringa Ben L. , Chen Jiawen
Published: March 2024

In the past two decades, the research and development of light-triggered molecular machines have mainly focused on developing molecular devices at the nanoscale. A key scientific issue in the field is how to amplify the controlled motion of molecules at the nanoscale along multiple length scales, such as the mesoscopic or the macroscopic scale, or in a more practical perspective, how to convert molecular motion into changes of properties of a macroscopic material. Light-driven molecular motors are able to perform repetitive unidirectional rotation upon irradiation, which offers unique opportunities for responsive macroscopic systems. With several reviews that focus on the design, synthesis and operation of the motors at the nanoscale, photo-responsive macroscopic materials based on light-driven molecular motors have not been comprehensively summarized. In the present review, we first discuss the strategy of confining absolute molecular rotation into relative rotation by grafting motors on surfaces. Secondly, examples of self-assemble motors in supramolecular polymers with high internal order are illustrated. Moreover, we will focus on building of motors in a covalently linked system such as polymeric gels and polymeric liquid crystals to generate complex responsive functions. Finally, a perspective toward future developments and opportunities is given. This review helps us getting a more and more clear picture and understanding on how complex movement can be programmed in light-responsive systems and how man-made adaptive materials can be invented, which can serve as an important guideline for further design of complex and advanced responsive materials.
Contactin-associated protein-like 2 (CNTNAP2) mutations impair the essential α-secretase cleavages, leading to autism-like phenotypes
Authors: Zhang Qing , Xing Mengen , Bao Zhengkai , Xu Lu , Bai Yang , Chen Wanqi , Pan Wenhao , Cai Fang , Wang Qunxian , Guo Shipeng , Zhang Jing , Wang Zhe , Wu Yili , Zhang Yun , Li Jia-Da , Song Weihong
Published: March 2024

Mutations in the Contactin-associated protein-like 2 (CNTNAP2) gene are associated with autism spectrum disorder (ASD), and ectodomain shedding of the CNTNAP2 protein plays a role in its function. However, key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown, and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain elusive. In this report we showed that CNTNAP2 undergoes sequential cleavages by furin, ADAM10/17-dependent α-secretase and presenilin-dependent γ-secretase. We identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96, and the main α-cleavage product C79 by ADAM10 is required for the subsequent γ-secretase cleavage to generate CNTNAP2 intracellular domain (CICD). ASD-associated CNTNAP2 mutations impair the α-cleavage to generate C79, and the inhibition leads to ASD-like repetitive and social behavior abnormalities in the Cntnap2-I1254T knock-in mice. Finally, exogenous expression of C79 improves autism-like phenotypes in the Cntnap2-I1254T knock-in and Cntnap2−/− knockout mice. This data demonstrates that the α-secretase is essential for CNTNAP2 processing and its function. Our study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis, and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.
TRIB3 promotes malignancy of head and neck squamous cell carcinoma via inhibiting ferroptosis
Authors: Chen Li , Lin Wanzun , Zhang Haojiong , Geng Shikai , Le Ziyu , Wan Fangzhu , Huang Qingting , Chen Huaiyuan , Liu Xingyu , Lu Jiade J. , Kong Lin
Published: March 2024

Tribbles pseudokinase 3 (TRIB3) has been identified recently as a novel oncogene in several cancers. Still, further extensive research is imperative to elucidate its function and the molecular mechanisms underlying its involvement in the progression of head and neck squamous cell carcinoma (HNSCC). In our study, we found that TRIB3 silencing significantly promoted cell death by inducing ferroptosis. The interaction of TRIB3 with Transcription Factor 4 (TCF4) and β-catenin created a heterotrimeric complex, which directly interacts with the ALOXE3 promoter, detrimentally impacting its activation. The consequential partial neutralization of ferroptosis induced by TRIB3 deficiency is observed through the implementation of ALOXE3 knockdown. Furthermore, the study demonstrated that the molecular inhibitor hesperidin, targeting TRIB3, not only reduced cell malignancy but also induced ferroptosis, thereby suppressing tumor growth. Overall, our findings unequivocally validate the proposition that TRIB3 deficiency precipitates the iron death mechanism, thereby indicating that the strategic targeting of TRIB3 could emerge as an innovative therapeutic strategy for HNSCC.
Depletion of the N6-Methyladenosine (m6A) reader protein IGF2BP3 induces ferroptosis in glioma by modulating the expression of GPX4
Authors: Deng Limei , Di Yunbo , Chen Caiyun , Xia Juan , Lei Bingxi , Li Ning , Zhang Qingyu
Published: March 2024

Emerging evidence highlights the multifaceted contributions of m6A modifications to glioma. IGF2BP3, a m6A modification reader protein, plays a crucial role in post-transcriptional gene regulation. Though several studies have identified IGF2BP3 as a poor prognostic marker in glioma, the underlying mechanism remains unclear. In this study, we demonstrated that IGF2BP3 knockdown is detrimental to cell growth and survival in glioma cells. Notably, we discovered that IGF2BP3 regulated ferroptosis by modulating the protein expression level of GPX4 through direct binding to a specific motif on GPX4 mRNA. Strikingly, the m6A modification at this motif was found to be critical for GPX4 mRNA stability and translation. Furthermore, IGF2BP3 knockdown glioma cells were incapable of forming tumors in a mouse xenograft model and were more susceptible to phagocytosis by microglia. Our findings shed light on an unrecognized regulatory function of IGF2BP3 in ferroptosis. The identification of a critical m6A site within the GPX4 transcript elucidates the significance of post-transcriptional control in ferroptosis.
Mechanisms and significance of entosis for tumour growth and progression
Authors: Gaptulbarova Ksenia Аndreevna , Tsydenova Irina Alexandrovna , Dolgasheva Daria Sergeevna , Kravtsova Ekaterina Andreevna , Ibragimova Marina Konstantinovna , Vtorushin Sergey Vladimirovich , Litviakov Nikolai Vasilievich
Published: March 2024

To date, numerous mechanisms have been identified in which one cell engulfs another, resulting in the creation of ‘cell-in-cell’ (CIC) structures, which subsequently cause cell death. One of the mechanisms of formation of these structures is entosis, which is presumably associated with possible carcinogenesis and tumour progression. The peculiarity of the process is that entotic cells themselves actively invade the host cell, and afterwards have several possible variants of fate. Entotic formations are structures where one cell is engulfed by another cell, creating a cell-in-cell structure. The nucleus of the outer cell has a crescent shape, while the inner cell is surrounded by a large entotic vacuole. These characteristics differentiate entosis from cell cannibalism. It’s worth noting that entotic formations are not necessarily harmful and may even be beneficial in some cases. In this article we will consider the mechanism of entosis and variants of entotic cell death, and also put forward hypothesis about possible variants of participation of this process on the formation and progression of cancer. This article also presents our proposed classification of functional forms of entosis.
Biodegradable triboelectric nanogenerator as a implantable power source for embedded medicine devices
Authors: Jian Gang , Zhu Shangtao , Yuan Xiao , Fu Shengqiao , Yang Ning , Yan Chao , Wang Xu , Wong Ching-Ping
Published: March 2024

Implantable medical devices have played an important role in human medicine in recent decades. However, traditional implanted devices require battery replacement and a second surgery for device removal, which can cause pain to the patient. This work presents a biodegradable triboelectric nanogenerator (BI-TENG) made from both natural and synthetic biodegradable materials that is utilized to collect mechanical energy in vivo and transduce it into electricity. Reed film and polylactic acid were chosen among different biodegradable materials as the triboelectric layers due to having the best generator output performance by providing voltages that reached 368 V. The biocompatibility of the friction layer and the device was verified via a blood test. After implantation in mice, the BI-TENG exhibited an open-circuit voltage of 0.176 V and a short-circuit current of 192 nA as generated from body movement. The BI-TENG was connected to an interdigital electrode to generate an electric field, which stimulated the accelerated release of doxorubicin (DOX) from red blood cells in targeted drug delivery systems. After stopping the electric field, the release of DOX normalized, facilitating the precise killing of cancer cells. Our work demonstrates the broad potential of BI-TENGs in the field of cancer treatment.
Gestational vitamin D and offspring fracture risk: do associations persist into mid adolescence?
Authors: Percival Mia A. , Anderson Kara B. , Pasco Julie A. , Hosking Sarah M. , Williams Lana J. , Holloway-Kew Kara L. , Wark John D. , Hyde Natalie K.
Published: March 2024

Background

Previous studies report that maternal vitamin D exposure during pregnancy is associated with offspring later-life bone health. A study in the Vitamin D in Pregnancy (VIP) cohort reported sexually dimorphic effects of maternal 25-hydroxyvitamin-D (25(OH)D) and offspring fracture profiles at 10 years of age. We, therefore, aimed to determine associations between maternal 25(OH)D status and offspring fracture risk at 16 years of age in this cohort.

Methods

In total, 475 mother-child pairs were recruited to the VIP study in southeastern Australia. Maternal serum samples were obtained at recruitment (<16 weeks’ gestation) and/or 28–32 weeks’ gestation and analysed for 25(OH)D. Radiologically-confirmed incident fractures in children were ascertained from date of birth (2002–2004) until July 16, 2019. Cox proportional hazard models were used to determine associations between maternal 25(OH)D and childhood fracture risk, and final models included maternal age at recruitment, offspring sex, birth weight, gestation length and season of 25(OH)D sample.

Results

Data were available for 400 children (mean age 16.1 years). There were 122 (30.5%) children who sustained at least one fracture. Higher maternal 25(OH)D (per 10 nmol/L) in early gestation was associated with a decreased fracture risk in boys (HR 0.87; 95% CI: 0.77, 0.99); the pattern was reversed in girls (HR 1.10; 95% CI 1.00, 1.22). At late gestation, higher maternal 25(OH)D was associated with an increased fracture risk in girls (HR 1.14; 95% CI: 1.04, 1.24).

Conclusions

While our findings must be interpreted within the constraints of our limitations, we report that the contradictory risk profiles observed at early childhood in this cohort remain in adolescence.
Competing itinerant and local spin interactions in kagome metal FeGe
Authors: Chen Lebing , Teng Xiaokun , Tan Hengxin , Winn Barry L. , Granroth Garrett E. , Ye Feng , Yu D. H. , Mole R. A. , Gao Bin , Yan Binghai , Yi Ming , Dai Pengcheng
Published: March 2024

The combination of a geometrically frustrated lattice, and similar energy scales between degrees of freedom endows two-dimensional Kagome metals with a rich array of quantum phases and renders them ideal for studying strong electron correlations and band topology. The Kagome metal, FeGe is a noted example of this, exhibiting A-type collinear antiferromagnetic (AFM) order at TN ≈ 400 K, then establishes a charge density wave (CDW) phase coupled with AFM ordered moment below TCDW ≈ 110 K, and finally forms a c-axis double cone AFM structure around TCanting ≈ 60 K. Here we use neutron scattering to demonstrate the presence of gapless incommensurate spin excitations associated with the double cone AFM structure of FeGe at temperatures well above TCanting and TCDW that merge into gapped commensurate spin waves from the A-type AFM order. Commensurate spin waves follow the Bose factor and fit the Heisenberg Hamiltonian, while the incommensurate spin excitations, emerging below TN where AFM order is commensurate, start to deviate from the Bose factor around TCDW, and peaks at TCanting. This is consistent with a critical scattering of a second order magnetic phase transition with decreasing temperature. By comparing these results with density functional theory calculations, we conclude that the incommensurate magnetic structure arises from the nested Fermi surfaces of itinerant electrons and the formation of a spin density wave order.
CD8+ T cell priming that is required for curative intratumorally anchored anti-4-1BB immunotherapy is constrained by Tregs
Authors: Palmeri Joseph R. , Lax Brianna M. , Peters Joshua M. , Duhamel Lauren , Stinson Jordan A. , Santollani Luciano , Lutz Emi A. , Pinney William , Bryson Bryan D. , Dane Wittrup K.
Published: March 2024

Although co-stimulation of T cells with agonist antibodies targeting 4-1BB (CD137) improves antitumor immune responses in preclinical studies, clinical success has been limited by on-target, off-tumor activity. Here, we report the development of a tumor-anchored ɑ4-1BB agonist (ɑ4-1BB-LAIR), which consists of a ɑ4-1BB antibody fused to the collagen-binding protein LAIR. While combination treatment with an antitumor antibody (TA99) shows only modest efficacy, simultaneous depletion of CD4+ T cells boosts cure rates to over 90% of mice. Mechanistically, this synergy depends on ɑCD4 eliminating tumor draining lymph node regulatory T cells, resulting in priming and activation of CD8+ T cells which then infiltrate the tumor microenvironment. The cytotoxic program of these newly primed CD8+ T cells is then supported by the combined effect of TA99 and ɑ4-1BB-LAIR. The combination of TA99 and ɑ4-1BB-LAIR with a clinically approved ɑCTLA-4 antibody known for enhancing T cell priming results in equivalent cure rates, which validates the mechanistic principle, while the addition of ɑCTLA-4 also generates robust immunological memory against secondary tumor rechallenge. Thus, our study establishes the proof of principle for a clinically translatable cancer immunotherapy.
Voltage-based magnetization switching and reading in magnetoelectric spin-orbit nanodevices
Authors: Vaz Diogo C. , Lin Chia-Ching , Plombon John J. , Choi Won Young , Groen Inge , Arango Isabel C. , Chuvilin Andrey , Hueso Luis E. , Nikonov Dmitri E. , Li Hai , Debashis Punyashloka , Clendenning Scott B. , Gosavi Tanay A. , Huang Yen-Lin , Prasad Bhagwati , Ramesh Ramamoorthy , Vecchiola Aymeric , Bibes Manuel , Bouzehouane Karim , Fusil Stephane , Garcia Vincent , Young Ian A. , Casanova Fèlix
Published: March 2024

As CMOS technologies face challenges in dimensional and voltage scaling, the demand for novel logic devices has never been greater, with spin-based devices offering scaling potential, at the cost of significantly high switching energies. Alternatively, magnetoelectric materials are predicted to enable low-power magnetization control, a solution with limited device-level results. Here, we demonstrate voltage-based magnetization switching and reading in nanodevices at room temperature, enabled by exchange coupling between multiferroic BiFeO3 and ferromagnetic CoFe, for writing, and spin-to-charge current conversion between CoFe and Pt, for reading. We show that, upon the electrical switching of the BiFeO3, the magnetization of the CoFe can be reversed, giving rise to different voltage outputs. Through additional microscopy techniques, magnetization reversal is linked with the polarization state and antiferromagnetic cycloid propagation direction in the BiFeO3. This study constitutes the building block for magnetoelectric spin-orbit logic, opening a new avenue for low-power beyond-CMOS technologies.
Superconductivity in a van der Waals layered quasicrystal
Authors: Tokumoto Yuki , Hamano Kotaro , Nakagawa Sunao , Kamimura Yasushi , Suzuki Shintaro , Tamura Ryuji , Edagawa Keiichi
Published: March 2024

Van der Waals layered transition-metal chalcogenides are drawing significant attention owing to their intriguing physical properties. This group of materials consists of abundant members with various elements, having a variety of different structures. However, they are all crystalline materials, and the physical properties of van der Waals layered quasicrystals have never been studied to date. Here, we report on the discovery of superconductivity in a van der Waals layered quasicrystal of Ta1.6Te. The electrical resistivity, magnetic susceptibility, and specific heat of the quasicrystal unambiguously validate the occurrence of bulk superconductivity at a transition temperature of ~1 K. This discovery can promote new research on assessing the physical properties of novel van der Waals layered quasicrystals as well as two-dimensional quasicrystals; moreover, it paves the way toward new frontiers of superconductivity in thermodynamically stable quasicrystals.
Protein NirP1 regulates nitrite reductase and nitrite excretion in cyanobacteria
Authors: Kraus Alexander , Spät Philipp , Timm Stefan , Wilson Amy , Schumann Rhena , Hagemann Martin , Maček Boris , Hess Wolfgang R.
Published: March 2024

When the supply of inorganic carbon is limiting, photosynthetic cyanobacteria excrete nitrite, a toxic intermediate in the ammonia assimilation pathway from nitrate. It has been hypothesized that the excreted nitrite represents excess nitrogen that cannot be further assimilated due to the missing carbon, but the underlying molecular mechanisms are unclear. Here, we identified a protein that interacts with nitrite reductase, regulates nitrogen metabolism and promotes nitrite excretion. The protein, which we named NirP1, is encoded by an unannotated gene that is upregulated under low carbon conditions and controlled by transcription factor NtcA, a central regulator of nitrogen homeostasis. Ectopic overexpression of nirP1 in Synechocystis sp. PCC 6803 resulted in a chlorotic phenotype, delayed growth, severe changes in amino acid pools, and nitrite excretion. Coimmunoprecipitation experiments indicated that NirP1 interacts with nitrite reductase, a central enzyme in the assimilation of ammonia from nitrate/nitrite. Our results reveal that NirP1 is widely conserved in cyanobacteria and plays a crucial role in the coordination of C/N primary metabolism by targeting nitrite reductase.
Dynamic control of DNA condensation
Authors: Agarwal Siddharth , Osmanovic Dino , Dizani Mahdi , Klocke Melissa A. , Franco Elisa
Published: March 2024

Artificial biomolecular condensates are emerging as a versatile approach to organize molecular targets and reactions without the need for lipid membranes. Here we ask whether the temporal response of artificial condensates can be controlled via designed chemical reactions. We address this general question by considering a model problem in which a phase separating component participates in reactions that dynamically activate or deactivate its ability to self-attract. Through a theoretical model we illustrate the transient and equilibrium effects of reactions, linking condensate response and reaction parameters. We experimentally realize our model problem using star-shaped DNA motifs known as nanostars to generate condensates, and we take advantage of strand invasion and displacement reactions to kinetically control the capacity of nanostars to interact. We demonstrate reversible dissolution and growth of DNA condensates in the presence of specific DNA inputs, and we characterize the role of toehold domains, nanostar size, and nanostar valency. Our results will support the development of artificial biomolecular condensates that can adapt to environmental changes with prescribed temporal dynamics.
The proteasome modulates endocytosis specifically in glomerular cells to promote kidney filtration
Authors: Sachs Wiebke , Blume Lukas , Loreth Desiree , Schebsdat Lisa , Hatje Favian , Koehler Sybille , Wedekind Uta , Sachs Marlies , Zieliniski Stephanie , Brand Johannes , Conze Christian , Florea Bogdan I. , Heppner Frank , Krüger Elke , Rinschen Markus M. , Kretz Oliver , Thünauer Roland , Meyer-Schwesinger Catherine
Published: March 2024

Kidney filtration is ensured by the interaction of podocytes, endothelial and mesangial cells. Immunoglobulin accumulation at the filtration barrier is pathognomonic for glomerular injury. The mechanisms that regulate filter permeability are unknown. Here, we identify a pivotal role for the proteasome in a specific cell type. Combining genetic and inhibitor-based human, pig, mouse, and Drosophila models we demonstrate that the proteasome maintains filtration barrier integrity, with podocytes requiring the constitutive and glomerular endothelial cells the immunoproteasomal activity. Endothelial immunoproteasome deficiency as well as proteasome inhibition disrupt the filtration barrier in mice, resulting in pathologic immunoglobulin deposition. Mechanistically, we observe reduced endocytic activity, which leads to altered membrane recycling and endocytic receptor turnover. This work expands the concept of the (immuno)proteasome as a control protease orchestrating protein degradation and antigen presentation and endocytosis, providing new therapeutic targets to treat disease-associated glomerular protein accumulations.
A comprehensive transformer-based approach for high-accuracy gas adsorption predictions in metal-organic frameworks
Authors: Wang Jingqi , Liu Jiapeng , Wang Hongshuai , Zhou Musen , Ke Guolin , Zhang Linfeng , Wu Jianzhong , Gao Zhifeng , Lu Diannan
Published: March 2024

Gas separation is crucial for industrial production and environmental protection, with metal-organic frameworks (MOFs) offering a promising solution due to their tunable structural properties and chemical compositions. Traditional simulation approaches, such as molecular dynamics, are complex and computationally demanding. Although feature engineering-based machine learning methods perform better, they are susceptible to overfitting because of limited labeled data. Furthermore, these methods are typically designed for single tasks, such as predicting gas adsorption capacity under specific conditions, which restricts the utilization of comprehensive datasets including all adsorption capacities. To address these challenges, we propose Uni-MOF, an innovative framework for large-scale, three-dimensional MOF representation learning, designed for multi-purpose gas prediction. Specifically, Uni-MOF serves as a versatile gas adsorption estimator for MOF materials, employing pure three-dimensional representations learned from over 631,000 collected MOF and COF structures. Our experimental results show that Uni-MOF can automatically extract structural representations and predict adsorption capacities under various operating conditions using a single model. For simulated data, Uni-MOF exhibits remarkably high predictive accuracy across all datasets. Additionally, the values predicted by Uni-MOF correspond with the outcomes of adsorption experiments. Furthermore, Uni-MOF demonstrates considerable potential for broad applicability in predicting a wide array of other properties.
Warming underpins community turnover in temperate freshwater and terrestrial communities
Authors: Khaliq Imran , Rixen Christian , Zellweger Florian , Graham Catherine H. , Gossner Martin M. , McFadden Ian R. , Antão Laura , Brodersen Jakob , Ghosh Shyamolina , Pomati Francesco , Seehausen Ole , Roth Tobias , Sattler Thomas , Supp Sarah R. , Riaz Maria , Zimmermann Niklaus E. , Matthews Blake , Narwani Anita
Published: March 2024

Rising temperatures are leading to increased prevalence of warm-affinity species in ecosystems, known as thermophilisation. However, factors influencing variation in thermophilisation rates among taxa and ecosystems, particularly freshwater communities with high diversity and high population decline, remain unclear. We analysed compositional change over time in 7123 freshwater and 6201 terrestrial, mostly temperate communities from multiple taxonomic groups. Overall, temperature change was positively linked to thermophilisation in both realms. Extirpated species had lower thermal affinities in terrestrial communities but higher affinities in freshwater communities compared to those persisting over time. Temperature change’s impact on thermophilisation varied with community body size, thermal niche breadth, species richness and baseline temperature; these interactive effects were idiosyncratic in the direction and magnitude of their impacts on thermophilisation, both across realms and taxonomic groups. While our findings emphasise the challenges in predicting the consequences of temperature change across communities, conservation strategies should consider these variable responses when attempting to mitigate climate-induced biodiversity loss.
Predictive role of ctDNA in esophageal squamous cell carcinoma receiving definitive chemoradiotherapy combined with toripalimab
Authors: Chen Baoqing , Liu Shiliang , Zhu Yujia , Wang Ruixi , Cheng Xingyuan , Chen Biqi , Dragomir Mihnea P. , Zhang Yaru , Hu Yonghong , Liu Mengzhong , Li Qiaoqiao , Yang Hong , Xi Mian
Published: March 2024

The combination of toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) demonstrated encouraging efficacy against locally advanced esophageal squamous cell carcinoma (ESCC) in the EC-CRT-001 phase II trial (NCT04005170). The primary endpoint of this trial was the clinical complete response rate (cCR), and the secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response, and quality of life. The exploratory analyses of EC-CRT-001 include exploring the role of circulating tumor DNA (ctDNA) and blood-based tumor mutational burden (bTMB) in predicting the response and survival. In total, 118 blood and 35 tissue samples from 42 enrolled patients were included in the analyses. We found that ctDNA-negative patients achieved a higher cCR compared to those with detectable ctDNA during CRT (83%, 19/23 vs. 39%, 7/18; p = 0.008) or post-CRT (78%, 21/27 vs. 30%, 3/10; p = 0.017). Patients with detectable ctDNA during CRT had shorter PFS (p = 0.014). Similarly, patients with post-CRT detectable ctDNA had a significantly shorter PFS (p = 0.012) and worse OS (p = 0.004). Moreover, patients with high bTMB levels during CRT had prolonged OS (p = 0.027). In conclusion, ctDNA and bTMB have the potential to predict treatment efficacy and survival in ESCC treated with CRT and immunotherapy.
Modulation-free laser stabilization technique using integrated cavity-coupled Mach-Zehnder interferometer
Authors: Idjadi Mohamad Hossein , Kim Kwangwoong , Fontaine Nicolas K.
Published: March 2024

Stable lasers play a significant role in precision optical systems where an electro-optic laser frequency stabilization system, such as the Pound-Drever-Hall technique, measures laser frequency and actively stabilizes it by comparing it to a frequency reference. Despite their excellent performance, there has been a trade-off between complexity, scalability, and noise measurement sensitivity. Here, we propose and experimentally demonstrate a modulation-free laser stabilization method using an integrated cavity-coupled Mach-Zehnder interferometer as a frequency noise discriminator. The proposed architecture maintains the sensitivity of the Pound-Drever-Hall architecture without the need for any modulation. This significantly simplifies the architecture and makes miniaturization into an integrated photonic platform easier. The implemented chip suppresses the frequency noise of a semiconductor laser by 4 orders-of-magnitude using an on-chip silicon microresonator with a quality factor of 2.5 × 106. The implemented passive photonic chip occupies an area of 0.456 mm2 and is integrated on AIM Photonics 100 nm silicon-on-insulator process.