bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intermittent fasting promotes adipocyte mitochondrial fusion through Sirt3-mediated deacetylation of Mdh2
Authors: Li Yizhou , Liang Juntong , Tian Xin , Chen Qi , Zhu Longbo , Wang Han , Liu Zunhai , Dai Xulei , Bian Chenqi , Sun Chao 
Published: February 2023

AbstractFat deposition and lipid metabolism are closely related to the morphology, structure and function of mitochondria. The morphology of mitochondria between fusion and fission processes is mainly regulated by protein posttranslational modification. Intermittent fasting (IF) promotes high expression of Sirtuin 3 (Sirt3) and induces mitochondrial fusion in high-fat diet (HFD)-fed mice. However, the mechanism by which Sirt3 participates in mitochondrial protein acetylation during IF to regulate mitochondrial fusion and fission dynamics remains unclear. This article demonstrates that IF promotes mitochondrial fusion and improves mitochondrial function in HFD mouse inguinal white adipose tissue. Proteomic sequencing revealed that IF increased protein deacetylation levels in HFD mice and significantly increased Sirt3 mRNA and protein expression. After transfecting with Sirt3 overexpression or interference vectors into adipocytes, we found that Sirt3 promoted adipocyte mitochondrial fusion and improved mitochondrial function. Furthermore, Sirt3 regulates the JNK-FIS1 pathway by deacetylating malate dehydrogenase 2 (MDH2) to promote mitochondrial fusion. In summary, our study indicates that IF promotes mitochondrial fusion and improves mitochondrial function by upregulating the high expression of Sirt3 in HFD mice, promoting deacetylation of MDH2 and inhibiting the JNK-FIS1 pathway. This research provides theoretical support for studies related to energy limitation and animal lipid metabolism.
Health technology assessment 2025 and beyond: lifecycle approaches to promote engagement and efficiency in health technology assessment
Authors: Trowman Rebecca , Migliore Antonio , Ollendorf Daniel A. 
Published: February 2023

AbstractLifecycle considerations have always been part of health technology assessment (HTA). However, the concept of taking a fuller, more holistic “lifecycle approach” is gaining interest in the HTA community. The 2022 HTAi Global Policy Forum (GPF) discussed how adopting a lifecycle approach could promote stakeholder engagement and robust evidence generation, and whether it could enhance information sharing and transparency across stakeholder groups. This article summarizes the discussions held at the 2022 HTAi GPF and subsequent HTAi Annual Meeting panel session that debated some of the key challenges and opportunities, with particular focus on the pre- and postmarket and disinvestment phase activities. Core themes and recommendations identified that collaboration and patient involvement are happening but still needs to be strengthened, and moving to disease-based approaches may help, although individual contexts still need to be considered. Appropriately developed and mandated core outcome sets may help with information sharing and efficiency in all lifecycle activities. Further, methods for the appropriate use of big data and digital data collection should be developed and driven by the HTA community. The value of lifecycle activities should be reviewed; in particular, scientific advice appears valuable, but the magnitude of effect is somewhat unknown due to the challenges around the confidential nature of these activities. Not all lifecycle activities can be conducted for every technology, and while there is a move away from disinvestment phase activities, more structured prioritization criteria are required. This article ends with suggested next steps to bring forward some of the priority recommendations.
Which rural settlements have lost the most population? An analysis of a case study of north-east Spain (Aragón) (1900–2001)
Authors: Ayuda María Isabel , Gómez Pablo , Pinilla Vicente 
Published: February 2023

AbstractThe aim of this article is to investigate how the characteristics of the different types of human settlements explain their demographic dynamics and, therefore, which of these have been affected to a greater extent by depopulation processes. For this purpose, we analyse the evolution of the population of Aragón (north-east Spain) in the period 1900–2001, according to the different types of population settlements that exist. Our results show that access to public services has played an essential role, especially when the construction of the welfare state made the rural population feel that there was a penalty for residing in settlements with problems to access them. The main settlements, headquarters of the municipal administration, have had advantages over the secondary settlements. Finally, the scattered population was the most affected and, therefore, emigrated to a greater extent, until this form of residence practically disappeared.
How did COVID-19 affect the labor force participation of older workers in the first year of the pandemic?
Authors: Davis Owen F. , Quinby Laura D. , Rutledge Matthew S. , Wettstein Gal 
Published: February 2023

AbstractThis paper uses the Current Population Survey to study older workers' transitions out of employment and into retirement during the first year of the pandemic. We find that, among workers ages 55 to 79, the likelihood of leaving employment over the course of a year rose by 6.7 percentage points, a 43-percent increase over baseline. Workers without a college degree, Asian–Americans, those whose jobs were not amenable to social distancing, and part-time workers saw disproportionate impacts. In contrast, the likelihood of retiring increased by 1 percentage point, and there was no immediate retirement boom for full-time workers under 70.
Northward Extent of Atmospheric Mercury Transboundary Transport to the Himalayas and Tibetan Plateau Region
Authors: Huang Jie , Kang Shichang , Feng Xinbin , Tang Wenjun , Ram Kirpa , Guo Junming , Zhang Qianggong , Sharma Chhatra Mani , Li Chaoliu , Tripathee Lekhendra , Wang Feiyue 
Published: February 2023

AbstractIndian monsoon circulation is the primary driver of the long‐range transboundary mercury (Hg) pollution from South Asia to the Himalayas and Tibet Plateau region, yet the northward extent of this transport remains unknown. In this study, a strong δ202Hg signature overlapping was found between Lake Gokyo and Indian anthropogenic sources, which is an indicative of the Hg source regions from South Asia. Most of the sediment samples were characterized with relatively large positive Δ199Hg values (mean = 0.07‰–0.44‰) and small positive Δ200Hg values (mean = 0.03‰–0.08‰). Notably, the Δ199Hg values in the lake sediments progressively increased from southwest to northeast. Moreover, the Δ199Hg values peaked at Lake Tanglha (mean = 0.44‰ ± 0.04‰) before decreased at Lake Qinghai that is under the influence of the westerlies. Our results suggest that transboundary atmospheric transport could transport Hg from South Asia northwards to at least the Tanglha Mountains in the northern Himalaya‐Tibet.
Apparent Low‐Velocity Belt in the Shallow Anninghe Fault Zone in SW China and Its Implications for Seismotectonics and Earthquake Hazard Assessment
Authors: Luo Song , Yao Huajian , Wen Jian , Yang Hongfeng , Tian Baofeng , Yan Mengxuan 
Published: February 2023

AbstractThe Anninghe fault forms the eastern boundary of the Sichuan‐Yunnan block in Southwest China and has been identified as an earthquake gap zone. This study intends to construct the upper crustal shear wave velocity (Vs) structure beneath the Anninghe fault to understand its seismotectonics and potential large earthquake hazards. We deployed a dense seismic array along the southern central Anninghe fault valley. From the 3‐month continuous records, we calculated vertical‐component cross‐correlation functions (CCFs). However, the surface wave signals in the CCFs are intensely interfered by near zero‐time‐lag noise. We proposed a mode separation method based on the high‐resolution linear Radon transform, which suppressed the interfered noise and greatly enhanced the surface wave signals for ambient noise tomography of the Vs structure. The fine upper crustal structure reveals a distinct narrow low‐velocity belt within a depth of 3 km beneath the Anninghe fault zone. At deeper depths (4.5–8 km), the narrow low‐velocity belt shifts to the east and correlates with the distribution of local earthquakes. Combining previous results with our new findings, we presented a seismotectonic model of the southern central Anninghe fault, which interprets the narrow low‐velocity belt as a water‐contained fracture zone that forms a seismogenic zone at deeper depths under transpression. In addition, we demonstrated through scenario earthquake simulations that fine structures play a significant role in the assessment of earthquake hazards along the Anninghe fault. As such, this study provides a typical window into seismotectonics and large earthquake hazards in the active southeastern Tibetan Plateau.
A Large Winter Chlorophyll‐a Bloom in the Southeastern Bay of Bengal Associated With the Extreme Indian Ocean Dipole Event in 2019
Authors: Li Zhiyuan , Long Yu , Huang Saihua , Xie Huawei , Zhou Yu , Yang Bin , Bai Yu , Zhu Xiao‐Hua 
Published: February 2023

AbstractA large Chlorophyll‐a (Chla) bloom developed in the southeastern Bay of Bengal (BoB) (4°N–10°N, 88°E−95°E) during winter 2019 and was observed from Moderate Resolution Imaging Spectroradiometer‐Aqua Chla data. By analyzing various observational and reanalysis datasets, we found that remote Equatorial Indian Ocean (EIO) upwelling waves and local Ekman pumping associated with the extreme Indian Ocean Dipole (IOD) event in 2019 were responsible for the Chla bloom. The extreme IOD 2019 favored strong upwelling Kelvin waves propagating from the eastern EIO into the BoB along the eastern boundary. These Kelvin waves were reflected into the central BoB as upwelling Rossby waves manifested by eddylike sea surface height propagating westward approximately along 5°N. In addition, local wind stress curl generated strong Ekman pumping in the southeastern BoB. As a result, upwelling processes associated with westward‐propagating Rossby waves and local Ekman pumping together uplifted the thermocline, breaking the stratification so that subsurface nutrient‐rich water was transported to the surface to cause a large Chla bloom in the southeastern BoB during winter 2019. The Chla bloom had a ring structure and its spatial shape was modulated by westward upwelling Rossby waves and cyclonic eddies. This study highlights the important role of IOD events in the formation of Chla bloom in the southeastern BoB during winter.
Reducing the Uncertainty in the Satellite Altimetry Estimates of Global Mean Sea Level Trends Using Highly Stable Water Vapor Climate Data Records
Authors: Barnoud Anne , Picard Bruno , Meyssignac Benoît , Marti Florence , Ablain Michaël , Roca Rémy 
Published: February 2023

AbstractThe global mean sea level (GMSL) has risen by 3.3 ± 0.2 mm.yr−1 (68% confidence level) over 1993–2021. The wet troposphere correction (WTC) used to compute the altimetry‐based mean sea level data is known to be a large source of error in the GMSL long‐term stability. The WTC is derived from the microwave radiometers (MWR) on board the altimetry missions. In order to improve the long‐term estimates of the GMSL, we propose an alternative WTC computation based on highly stable climate data records (CDRs) of water vapor derived from independent MWR measurements on board meteorological satellites. A polynomial model is applied to convert water vapor to WTC. The CDR‐derived WTC enables reducing the low frequency uncertainty of the WTC applied to the altimetry data, hence reducing the uncertainty of the GMSL trend estimate. Furthermore, over 2016–2021, the comparison of MWR‐based with CDR‐based WTC shows a likely drift of the Jason‐3 MWR WTC on the order of −0.5 mm.yr−1 that would lead to an overestimation of the GMSL trend from 2016.
Longitudinal metabolomics of increasing body-mass index and waist-hip ratio reveals two dynamic patterns of obesity pandemic
Authors: Mäkinen Ville-Petteri , Kettunen Johannes , Lehtimäki Terho , Kähönen Mika , Viikari Jorma , Perola Markus , Salomaa Veikko , Järvelin Marjo-Riitta , Raitakari Olli T. , Ala-Korpela Mika 
Published: February 2023

Abstract
Background/Objective
This observational study dissects the complex temporal associations between body-mass index (BMI), waist-hip ratio (WHR) and circulating metabolomics using a combination of longitudinal and cross-sectional population-based datasets and new systems epidemiology tools.

Subjects/Methods
Firstly, a data-driven subgrouping algorithm was employed to simplify high-dimensional metabolic profiling data into a single categorical variable: a self-organizing map (SOM) was created from 174 metabolic measures from cross-sectional surveys (FINRISK, n = 9708, ages 25–74) and a birth cohort (NFBC1966, n = 3117, age 31 at baseline, age 46 at follow-up) and an expert committee defined four subgroups of individuals based on visual inspection of the SOM. Secondly, the subgroups were compared regarding BMI and WHR trajectories in an independent longitudinal dataset: participants of the Young Finns Study (YFS, n = 1286, ages 24–39 at baseline, 10 years follow-up, three visits) were categorized into the four subgroups and subgroup-specific age-dependent trajectories of BMI, WHR and metabolic measures were modelled by linear regression.

Results
The four subgroups were characterised at age 39 by high BMI, WHR and dyslipidemia (designated TG-rich); low BMI, WHR and favourable lipids (TG-poor); low lipids in general (Low lipid) and high low-density-lipoprotein cholesterol (High LDL-C). Trajectory modelling of the YFS dataset revealed a dynamic BMI divergence pattern: despite overlapping starting points at age 24, the subgroups diverged in BMI, fasting insulin (three-fold difference at age 49 between TG-rich and TG-poor) and insulin-associated measures such as triglyceride-cholesterol ratio. Trajectories also revealed a WHR progression pattern: despite different starting points at the age of 24 in WHR, LDL-C and cholesterol-associated measures, all subgroups exhibited similar rates of change in these measures, i.e. WHR progression was uniform regardless of the cross-sectional metabolic profile.

Conclusions
Age-associated weight variation in adults between 24 and 49 manifests as temporal divergence in BMI and uniform progression of WHR across metabolic health strata.
The hTERT-p50 homodimer inhibits PLEKHA7 expression to promote gastric cancer invasion and metastasis
Authors: Wu Yu-Yun , Xiao Yu-Feng , Tian Li-Xing , He Bing , Liu Jiao , Li Zhi-Bin , Yang Huan , Chen Yang , Luo Qiang , Li Bo-Sheng , Yang Shi-Ming 
Published: February 2023

AbstractAlthough accumulating evidence has highlighted the molecular mechanisms by which hTERT promotes tumour cell invasion and metastasis, the molecular mechanisms of the properties enabling hTERT to contribute to invasion and metastasis have not been clearly illustrated. Here, we report that hTERT promotes gastric cancer invasion and metastasis by recruiting p50 to synergistically inhibit PLEKHA7 expression. We observed that the expression of PLEKHA7 in gastric cancer was significantly negatively associated with the TNM stage and lymphatic metastasis and that decreased PLEKHA7 expression dramatically increased invasion and metastasis in gastric cancer cells. Further mechanistic research showed that hTERT directly regulates PLEKHA7 expression by binding p50 and recruiting the hTERT/p50 complex to the PLEKHA7 promoter. Increased hTERT dramatically decreased PLEKHA7 expression and promoted invasion and metastasis in gastric cancer cells. The hTERT-mediated invasion/metastasis properties at least partially depended on PLEKHA7. Our work uncovers a novel molecular mechanism underlying invasion/metastasis in gastric cancer orchestrated by hTERT and p50.
Genetic propensity, socioeconomic status, and trajectories of depression over a course of 14 years in older adults
Authors: Kosciuszko Martyna , Steptoe Andrew , Ajnakina Olesya 
Published: February 2023

AbstractDepression is one of the leading causes of disability worldwide and is a major contributor to the global burden of disease among older adults. The study aimed to investigate the interplay between socio-economic markers (education and financial resources) and polygenic predisposition influencing individual differences in depressive symptoms and their change over time in older adults, which is of central relevance for preventative strategies. The sample encompassing n = 6202 adults aged ≥50 years old with a follow-up period of 14 years was utilised from the English Longitudinal Study of Ageing. Polygenic scores for depressive symptoms were calculated using summary statistics for (1) single-trait depressive symptoms (PGS-DSsingle), and (2) multi-trait including depressive symptoms, subjective well-being, neuroticism, loneliness, and self-rated health (PGS-DSmulti-trait). The depressive symptoms over the past week were measured using the eight-item Centre for Epidemiologic Studies Depression Scale. One standard deviation increase in each PGS was associated with a higher baseline score in depressive symptoms. Each additional year of completed schooling was associated with lower baseline depression symptoms (β = −0.06, 95%CI = −0.07 to −0.05, p < 0.001); intermediate and lower wealth were associated with a higher baseline score in depressive symptoms. Although there was a weak interaction effect between PGS-DSs and socio-economic status in association with the baseline depressive symptoms, there were no significant relationships of PGS-DSs, socio-economic factors, and rate of change in the depressive symptoms during the 14-year follow-up period. Common genetic variants for depressive symptoms are associated with a greater number of depressive symptoms onset but not with their rate of change in the following 14 years. Lower socio-economic status is an important factor influencing individual levels of depressive symptoms, independently from polygenic predisposition to depressive symptoms.
PIN1 and CDK1 cooperatively govern pVHL stability and suppressive functions
Authors: Chen Jiayi , Li Mei , Liu Yeqing , Guan Tangming , Yang Xiao , Wen Yalei , Zhu Yingjie , Xiao Zeyu , Shen Xiangchun , Zhang Haoxing , Tang Hui , Liu Tongzheng 
Published: February 2023

AbstractThe VHL protein (pVHL) functions as a tumor suppressor by regulating the degradation or activation of protein substrates such as HIF1α and Akt. In human cancers harboring wild-type VHL, the aberrant downregulation of pVHL is frequently detected and critically contributes to tumor progression. However, the underlying mechanism by which the stability of pVHL is deregulated in these cancers remains elusive. Here, we identify cyclin-dependent kinase 1 (CDK1) and peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) as two previously uncharacterized regulators of pVHL in multiple types of human cancers harboring wild-type VHL including triple-negative breast cancer (TNBC). PIN1 and CDK1 cooperatively modulate the protein turnover of pVHL, thereby conferring tumor growth, chemotherapeutic resistance and metastasis both in vitro and in vivo. Mechanistically, CDK1 directly phosphorylates pVHL at Ser80, which primes the recognition of pVHL by PIN1. PIN1 then binds to phosphorylated pVHL and facilitates the recruitment of the E3 ligase WSB1, therefore targeting pVHL for ubiquitination and degradation. Furthermore, the genetic ablation or pharmacological inhibition of CDK1 by RO-3306 and PIN1 by all-trans retinoic acid (ATRA), the standard care for Acute Promyelocytic Leukemia could markedly suppress tumor growth, metastasis and sensitize cancer cells to chemotherapeutic drugs in a pVHL dependent manner. The histological analyses show that PIN1 and CDK1 are highly expressed in TNBC samples, which negatively correlate with the expression of pVHL. Taken together, our findings reveal the previous unrecognized tumor-promoting function of CDK1/PIN1 axis through destabilizing pVHL and provide the preclinical evidence that targeting CDK1/PIN1 is an appealing strategy in the treatment of multiple cancers with wild-type VHL.
Interplay of diruthenium catalyst in controlling enantioselective propargylic substitution reactions with visible light-generated alkyl radicals
Authors: Zhang Yulin , Tanabe Yoshiaki , Kuriyama Shogo , Sakata Ken , Nishibayashi Yoshiaki 
Published: February 2023

AbstractTransition metal-catalyzed enantioselective free radical substitution reactions have recently attracted attention as convenient and important building tools in synthetic chemistry, although construction of stereogenic carbon centers at the propargylic position of propargylic alcohols by reactions with free radicals remains unchallenged. Here we present a strategy to control enantioselective propargylic substitution reactions with alkyl radicals under photoredox conditions by applying dual photoredox and diruthenium catalytic system, where the photoredox catalyst generates alkyl radicals from 4-alkyl-1,4-dihydropyridines, and the diruthenium core with a chiral ligand traps propargylic alcohols and alkyl radicals to guide enantioselective alkylation at the propargylic position, leading to high yields of propargylic alkylated products containing a quaternary stereogenic carbon center at the propargylic position with a high enantioselectivity. The result described in this paper provides the successful example of transition metal-catalyzed enantioselective propargylic substitution reactions with free alkyl radicals.
11β-HSD1 inhibition in men mitigates prednisolone-induced adverse effects in a proof-of-concept randomised double-blind placebo-controlled trial
Authors: Othonos Nantia , Pofi Riccardo , Arvaniti Anastasia , White Sarah , Bonaventura Ilaria , Nikolaou Nikolaos , Moolla Ahmad , Marjot Thomas , Stimson Roland H. , van Beek André P. , van Faassen Martijn , Isidori Andrea M. , Bateman Elizabeth , Sadler Ross , Karpe Fredrik , Stewart Paul M. , Webster Craig , Duffy Joanne , Eastell Richard , Gossiel Fatma , Cornfield Thomas , Hodson Leanne , Jane Escott K. , Whittaker Andrew , Kirik Ufuk , Coleman Ruth L. , Scott Charles A. B. , Milton Joanne E. , Agbaje Olorunsola , Holman Rury R. , Tomlinson Jeremy W. 
Published: February 2023

AbstractGlucocorticoids prescribed to limit inflammation, have significant adverse effects. As 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoid, we investigated whether 11β-HSD1 inhibition with AZD4017 could mitigate adverse glucocorticoid effects without compromising their anti-inflammatory actions. We conducted a proof-of-concept, randomized, double-blind, placebo-controlled study at Research Unit, Churchill Hospital, Oxford, UK (NCT03111810). 32 healthy male volunteers were randomized to AZD4017 or placebo, alongside prednisolone treatment. Although the primary endpoint of the study (change in glucose disposal during a two-step hyperinsulinemic, normoglycemic clamp) wasn’t met, hepatic insulin sensitivity worsened in the placebo-treated but not in the AZD4017-treated group. Protective effects of AZD4017 on markers of lipid metabolism and bone turnover were observed. Night-time blood pressure was higher in the placebo-treated but not in the AZD4017-treated group. Urinary (5aTHF+THF)/THE ratio was lower in the AZD4017-treated but remained the same in the placebo-treated group. Most anti-inflammatory actions of prednisolone persisted with AZD4017 co-treatment. Four adverse events were reported with AZD4017 and no serious adverse events. Here we show that co-administration of AZD4017 with prednisolone in men is a potential strategy to limit adverse glucocorticoid effects.