bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthetic polyploidization induces enhanced phytochemical profile and biological activities in Thymus vulgaris L. essential oil
Authors: Gupta Neha , Bhattacharya Soham , Dutta Adrish , Tauchen Jan , Landa Přemysl , Urbanová Klára , Houdková Markéta , Fernández-Cusimamani Eloy , Leuner Olga 
Published: March 2024

AbstractEssential oil from Thymus vulgaris L. has valuable therapeutic potential that is highly desired in pharmaceutical, food, and cosmetic industries. Considering these advantages and the rising market demand, induced polyploids were obtained using oryzalin to enhance essential oil yield. However, their therapeutic values were unexplored. So, this study aims to assess the phytochemical content, and antimicrobial, antioxidant, and anti-inflammatory activities of tetraploid and diploid thyme essential oils. Induced tetraploids had 41.11% higher essential oil yield with enhanced thymol and γ-terpinene content than diploid. Tetraploids exhibited higher antibacterial activity against all tested microorganisms. Similarly, in DPPH radical scavenging assay tetraploid essential oil was more potent with half-maximal inhibitory doses (IC50) of 180.03 µg/mL (40.05 µg TE/mg) than diploid with IC50 > 512 µg/mL (12.68 µg TE/mg). Tetraploids exhibited more effective inhibition of in vitro catalytic activity of pro-inflammatory enzyme cyclooxygenase-2 (COX-2) than diploids at 50 µg/mL concentration. Furthermore, molecular docking revealed higher binding affinity of thymol and γ-terpinene towards tested protein receptors, which explained enhanced bioactivity of tetraploid essential oil. In conclusion, these results suggest that synthetic polyploidization using oryzalin could effectively enhance the quality and quantity of secondary metabolites and can develop more efficient essential oil-based commercial products using this induced genotype.
Male–female disparity in clinical features and significance of mild vertebral fractures in community-dwelling residents aged 50 and over
Authors: Ikegami Shota , Uehara Masashi , Tokida Ryosuke , Nishimura Hikaru , Sakai Noriko , Horiuchi Hiroshi , Kato Hiroyuki , Takahashi Jun 
Published: March 2024

AbstractThis investigation examined the clinical implications of mild vertebral fractures in older community-dwelling residents. Focusing on the locomotion health of older individuals, the earlier reported Obuse study enrolled 415 randomly sampled Japanese residents aged between 50 and 89 years, 411 of whom underwent X-ray evaluations for pre-existing vertebral fractures. A blinded assessment of vertebral fractures based on Genant’s criteria was conducted on the T5-L5 spine for rating on a severity scale. Grade 1 mild fractures were not linked to age in males, but increased with aging in females. Female participants had fewer Grade 1 and 2 fractures (P = 0.003 and 0.035, respectively) but more Grade 3 fractures (P = 0.013) than did males independently of age (Grade 1, 2, and 3: 25%, 16%, and 9% in females and 40%, 22%, and 6% in males, respectively). Weak negative correlations were observed between the number of fractures and bone mineral density in females for all fracture grades (Spearman’s rho: 0.23 to 0.36, P < 0.05). Our study showed that Grade 1 mild vertebral fractures in males lacked pathological significance, while in females they potentially indicated fragility fractures and were related to poor lumbopelvic alignment.
Connectivity mapping-based identification of pharmacological inhibitor targeting HDAC6 in aggressive pancreatic ductal adenocarcinoma
Authors: Atri Pranita , Shah Ashu , Natarajan Gopalakrishnan , Rachagani Satyanarayana , Rauth Sanchita , Ganguly Koelina , Carmicheal Joseph , Ghersi Dario , Cox Jesse L. , Smith Lynette M. , Jain Maneesh , Kumar Sushil , Ponnusamy Moorthy P. , Seshacharyulu Parthasarathy , Batra Surinder K. 
Published: March 2024

AbstractPancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to limited therapeutic options and expensive/burdensome drug discovery processes. Utilizing genomic-data-driven Connectivity Mapping (CMAP) to identify a drug closer to real-world PC targeting may improve pancreatic cancer (PC) patient outcomes. Initially, we mapped CMAP data to gene expression from 106 PC patients, identifying nine negatively connected drugs. These drugs were further narrowed down using a similar analysis for PC cell lines, human tumoroids, and patient-derived xenografts datasets, where ISOX emerged as the most potent agent to target PC. We used human and mouse syngeneic PC cells, human and mouse tumoroids, and in vivo mice to assess the ability of ISOX alone and in combination with 5FU to inhibit tumor growth. Global transcriptomic and pathway analysis of the ISOX-LINCS signature identified HDAC 6/cMyc as the target axis for ISOX. Specifically, we discovered that genetic and pharmacological targeting of HDAC 6 affected non-histone protein cMyc acetylation, leading to cMyc instability, thereby disrupting PC growth and metastasis by affecting cancer stemness. Finally, KrasG12D harboring tumoroids and mice responded effectively against ISOX and 5FU treatment by enhancing survival and controlling metastasis incidence. Overall, our data validate ISOX as a new drug to treat advanced PC patients without toxicity to normal cells. Our study supports the clinical utility of ISOX along with 5FU in future PC clinical trials.
Exploring the limitations of mitochondrial dye as a genuine horizontal mitochondrial transfer surrogate
Authors: Chen Chuanfang , Li Haige , Zhang Jia , Cheng Shih-Chin 
Published: March 2024

AbstractRosamine-based mitochondrial dyes, such as Mitotracker Red, have commonly been employed to visualize mitochondrial localization within cells due to their preferential accumulation in organelles with membrane potential. Consequently, Mitotracker Red has often served as a surrogate indicator for tracking mitochondrial movement between neighboring cells. However, it is important to note that the presence of membrane potential in the cell membrane and other organelles may lead to the non-specific partial enrichment of Mitotracker Red in locations other than mitochondria. This study comprehensively investigates the reliability of mitochondrial dye as a marker for studying horizontal mitochondrial transfer (HMT). By meticulous replicating of previous experiments and comparing the efficiency of mitochondrial dye transfer with that of mito-targeted GFP, our findings confirm that HMT occurs at significantly lower efficiency than previously indicated by Mitotracker dye. Subsequent experiments involving mitochondria-deficient cells robustly demonstrates the non-specificity of mitochondrial dye as indicator for mitochondria. We advocate for a thorough reevaluation of existing literature in this field and propose exploration of alternative techniques to enhance the investigation of HMT. By addressing these pivotal aspects, we can advance our understanding of cellular dynamics and pave the way for future explorations in this captivating field.
SAM68 directs STING signaling to apoptosis in macrophages
Authors: van der Horst Demi , Kurmasheva Naziia , Marqvorsen Mikkel H. S. , Assil Sonia , Rahimic Anna H. F. , Kollmann Christoph F. , Silva da Costa Leandro , Wu Qi , Zhao Jian , Cesari Eleonora , Iversen Marie B. , Ren Fanghui , Jensen Trine I. , Narita Ryo , Schack Vivien R. , Zhang Bao-cun , Bak Rasmus O. , Sette Claudio , Fenton Robert A. , Mikkelsen Jacob G. , Paludan Søren R. , Olagnier David 
Published: March 2024

AbstractDNA is a danger signal sensed by cGAS to engage signaling through STING to activate innate immune functions. The best-studied downstream responses to STING activation include expression of type I interferon and inflammatory genes, but STING also activates other pathways, including apoptosis. Here, we report that STING-dependent induction of apoptosis in macrophages occurs through the intrinsic mitochondrial pathway and is mediated via IRF3 but acts independently of gene transcription. By intersecting four mass spectrometry datasets, we identify SAM68 as crucial for the induction of apoptosis downstream of STING activation. SAM68 is essential for the full activation of apoptosis. Still, it is not required for STING-mediated activation of IFN expression or activation of NF-κB. Mechanistic studies reveal that protein trafficking is required and involves SAM68 recruitment to STING upon activation, with the two proteins associating at the Golgi or a post-Golgi compartment. Collectively, our work identifies SAM68 as a STING-interacting protein enabling induction of apoptosis through this DNA-activated innate immune pathway.
Efficient retrosynthetic planning with MCTS exploration enhanced A* search
Authors: Zhao Dengwei , Tu Shikui , Xu Lei 
Published: March 2024

AbstractRetrosynthetic planning, which aims to identify synthetic pathways for target molecules from starting materials, is a fundamental problem in synthetic chemistry. Computer-aided retrosynthesis has made significant progress, in which heuristic search algorithms, including Monte Carlo Tree Search (MCTS) and A*search, have played a crucial role. However, unreliable guiding heuristics often cause search failure due to insufficient exploration. Conversely, excessive exploration also prevents the search from reaching the optimal solution. In this paper, MCTS exploration enhanced A*(MEEA*) search is proposed to incorporate the exploratory behavior of MCTS into A*by providing a look-ahead search. Path consistency is adopted as a regularization to improve the generalization performance of heuristics. Extensive experimental results on 10 molecule datasets demonstrate the effectiveness of MEEA*. Especially, on the widely used United States Patent and Trademark Office (USPTO) benchmark, MEEA*achieves a 100.0% success rate. Moreover, for natural products, MEEA*successfully identifies bio-retrosynthetic pathways for 97.68% test compounds.
Hydrological drought forecasts using precipitation data depend on catchment properties and human activities
Authors: Sutanto Samuel Jonson , Syaehuddin Wahdan Achmad , de Graaf Inge 
Published: March 2024

AbstractHydrological Drought Early Warning Systems play a crucial role in effective drought planning and management, as the impacts of drought are more closely associated with hydrological droughts than meteorological ones. However, current systems primarily focus on meteorological drought forecasts due to the limited access to hydrological data. Here we assess the feasibility of forecasting drought in streamflow and groundwater by solely using precipitation data. The results demonstrate that meteorological drought forecasts derived from the Standardized Precipitation Index with 6-month accumulation periods and various lag times hold the potential to predict streamflow and groundwater droughts. This study also highlights the importance of catchment properties in hydrological drought predictions. Our findings present an opportunity for developing hydrological drought early warning system globally to reach the goal of the Sendai framework for disaster risk reduction by 2030 and support the initiative of early warnings for all.
Actuation of microstructures with spin-current volume effect
Authors: Huang Yi-Te , Suzuki Kenta , Arisawa Hiroki , Kikkawa Takashi , Saitoh Eiji , Ono Takahito 
Published: March 2024

AbstractMicroactuators are essential for advances in micro-optics, ultrasonic transducers and microsensors, and there is a growing demand for miniaturization and improved power. Here we demonstrate the actuation of micromechanical structures based on spin-current volume effect using an amorphous magnetic film of TbFeCo with volume magnetostriction. A 2 mm-diameter circular polyimide diaphragm coated with thin TbFeCo/non-magnetic metal films is prepared as the micromechanical structure. When an alternating charge current flows through the TbFeCo/non-magnetic metal films on the diaphragm under an external magnetic field orthogonal to the charge current, an alternating spin-current flows in the non-magnetic metal film due to the spin-Hall effect. In the spin-current volume effect, the spin-current transports angular momentum from the non-magnetic metal to TbFeCo film, and the spin-transfer torque modulates the magnetization fluctuation of the TbFeCo film, causing the diaphragm to vibrate due to spin-lattice coupling. The power density of the TbFeCo/Pt films actuator is larger than 1.17 × 106 W m−3at 20 mA charge current under 7.2 kOe magnetic field. This value is much higher than that of various existing film-type microactuators. This spin-current volume effect is effective as a new actuation mechanism for microactuators used in micro-optical systems, acoustic diagnostic equipment, and micro-fluidic systems etc.
Applying continuous-time models to ecological momentary assessments: A practical introduction to the method and demonstration with clinical data
Authors: Abplanalp Samuel J. , Reavis Eric A. , Le Thanh P. , Green Michael F. 
Published: March 2024

AbstractEcological momentary assessment (EMA) is a frequently used approach among clinical researchers to collect naturalistic data in real time. EMA data can provide insights into the temporal dynamics of psychological processes. Traditional methods used to analyze EMA data, such as hierarchical linear modeling and multilevel vector auto-regression, paint an incomplete picture of the dynamics of psychological processes because they cannot capture how variables evolve outside predefined measurement occasions. Continuous-time models, an analytical approach that treats variables as dynamical systems that evolve continuously, overcome this limitation. Time advances smoothly in continuous-time models, contrasting with standard discrete-time models in which time progresses in finite jumps. This paper presents a practical introduction to continuous-time models for analyzing EMA data. To illustrate the method and its interpretation, we provide an empirical demonstration of a continuous-time model utilizing EMA data of real-time loneliness and mood states (happiness, sadness, and anxiety) from a clinical sample comprising Veterans with a history of mental illness. Psychological variables, such as feelings of loneliness or sadness, can often change many times throughout the day. However, standard ways of analyzing these variables do not accurately capture these changes and fluctuations. Here, we highlight the benefits of continuous-time models, a method that can capture subtle changes in such psychological variables over time.
BAG5 regulates HSPA8-mediated protein folding required for sperm head-tail coupling apparatus assembly
Authors: Gan Shiming , Zhou Shumin , Ma Jinzhe , Xiong Mengneng , Xiong Wenjing , Fan Xu , Liu Kuan , Gui Yiqian , Chen Bei , Zhang Beibei , Wang Xiaoli , Wang Fengli , Li Zhean , Yan Wei , Ma Meisheng , Yuan Shuiqiao 
Published: March 2024

AbstractTeratozoospermia is a significant cause of male infertility, but the pathogenic mechanism of acephalic spermatozoa syndrome (ASS), one of the most severe teratozoospermia, remains elusive. We previously reported Spermatogenesis Associated 6 (SPATA6) as the component of the sperm head-tail coupling apparatus (HTCA) required for normal assembly of the sperm head-tail conjunction, but the underlying molecular mechanism has not been explored. Here, we find that the co-chaperone protein BAG5, expressed in step 9-16 spermatids, is essential for sperm HTCA assembly. BAG5-deficient male mice show abnormal assembly of HTCA, leading to ASS and male infertility, phenocopying SPATA6-deficient mice. In vivo and in vitro experiments demonstrate that SPATA6, cargo transport-related myosin proteins (MYO5A and MYL6) and dynein proteins (DYNLT1, DCTN1, and DNAL1) are misfolded upon BAG5 depletion. Mechanistically, we find that BAG5 forms a complex with HSPA8 and promotes the folding of SPATA6 by enhancing HSPA8’s affinity for substrate proteins. Collectively, our findings reveal a novel protein-regulated network in sperm formation in which BAG5 governs the assembly of the HTCA by activating the protein-folding function of HSPA8.
Cormorant-inspired macro-porous hydrogel thin film evaporators for boosting cost-effective solar water purification
Authors: Ma Guang-Lei , Qi Xi-Yan , Wei Qing-Cong , Shi Xiao-Fang , Chang Yi , Guo Yu-Ming , Hu Zhi-Guo , Ma Xiao-Ming 
Published: March 2024

We develop a macro-porous hydrogel film strategy for solar water purification inspired by the structure of cormorant wings. The evaporation rate can reach 4.14 kg m−2 h−1 and the energy efficiency can reach 98% under one sun.
Is There a Cumulative Effect for Congenital Heart Defects in Monochorionic Twins after Assisted Reproduction? – A Retrospective Analysis at a Tertiary Referral Center
Authors: Zdanowicz Jarmila A. , Yildrim Gülay , Fonseca Andreia , Hecher Kurt , Tavares de Sousa Manuela 
Published: March 2024

AbstractThe aim of our study was to compare maternal, chorionicity and neonatal complications in monochorionic (MC) twins between spontaneously conceived (SC) and assisted reproductive technologies (ART) pregnancies.This was a retrospective cohort study between January 2010 to December 2019 at a tertiary referral University center. All consecutive pregnancies with MC twins that delivered at our University hospital were included. Maternal, chorionicity and neonatal complications were recorded and compared between SC and ART pregnancies.393 MC pregnancies were included for final analysis, including 353 (89.8%) SC and 40 (10.2%) pregnancies conceived after ART. Hypothyroidism was the only maternal condition seen significantly more often in ART pregnancies (35.0% vs 12.5%, p = 0.001). There were no significant differences in chorionicity complications, such as twin-twin transfusion syndrome, selective fetal growth restriction and twin anemia-polycythemia sequence (40.0% in ART pregnancies vs 31.6% in SC pregnancies, p = 0.291). At least one congenital anomaly in one twin was seen significantly more often in ART pregnancies (18.8% vs 8.1%, p = 0.004), especially congenital heart defects (16.3% vs 6.2%, p = 0.005). There were no other significant differences in neonatal outcomes between both groups, however, there were non-significant trends in gestational age at delivery (34 weeks in ART pregnancies vs 35 weeks, p = 0.078) and birthweight (1951 g ± 747 in ART pregnancies vs 2143 g ± 579, p = 0.066).This is the largest cohort study to date comparing maternal, chorionicity and neonatal complications between MC twin pregnancies after ART and after SC. Hypothyroidism was the only maternal condition occurring more frequently in pregnancies conceived after ART. There were no significant differences in chorionicity complications, in contrast to previously reported studies. While MC twins and ART pregnancies per se are known to be at risk for congenital heart defects, there seems to be a cumulative effect in MC pregnancies conceived after ART.
Relationship Between Urinary Iodine Concentration and the Prevalence
of Thyroid Nodules and Subclinical Hypothyroidism
Authors: Zhu Huachao , Chen Pu , Ding Xi , Zhao Yanru 
Published: March 2024

AbstractThe aim of the study was to investigate the iodine intake in the resident
population in Xi’an and analyze the relationship between iodine nutritional
status and the prevalence of subclinical hypothyroidism and thyroid nodules
(TNs). A total of 2507 people were enrolled in Xi’an. Venous serum thyroid
stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) and thyroglobulin
antibody (TgAb), urinary iodine concentration (UIC), and thyroid ultrasonography
were collected. Patients with abnormal TSH were checked for free thyroxine (FT4)
and triiodothyronine (FT3). Adults in Xi’an had median UICs of 220.80 μg/L and
178.56 μg/l, respectively. A sum of 16.78% of people had subclinical
hypothyroidism. Both iodine excess and iodine deficit increased the frequency of
subclinical hypothyroidism. The lowest was around 15.09% in females with urine
iodine levels between 200 and 299 μg/l. With a rate of 10.69%, the lowest
prevalence range for males was 100–199 μg/l. In Xi’an, 11.37% of people have
TNs. In comparison to other UIC categories, TN occurrences were higher in
females (18.5%) and males (12%) when UIC were below 100 μg/l. In conclusion,
iodine intake was sufficient in the Xi’an area, while the adults’ UIC remains
slightly higher than the criteria. Iodine excess or deficiency can lead to an
increase in the prevalence of subclinical hypothyroidism. Patients with iodine
deficiency are more likely to develop TNs.
Dysregulation of miR-335-5p in People with Obesity and its Predictive
Value for Metabolic Syndrome
Authors: Lu Liting , He Yufeng 
Published: March 2024

AbstractThe epidemic of obesity and metabolic syndrome has become the most serious global
public health problem. The part played by microRNA (miRNA) in the onset and
progression of obesity and metabolic syndrome has been increasingly focused
upon. The goal of this study was to explore miR-335-5p as a potential predictive
biomarker or therapeutic target for obesity and metabolic syndrome. The
expression level of miR-335-5p was detected by qRT-PCR. The diagnostic value of
miR-335-5p was evaluated by ROC curve. The association between serum miR-335-5p
levels and various clinical parameters was assessed using the chi-square test.
Logistic regression analysis was used to evaluate the risk factors of metabolic
syndrome in obese population. The biological processes and molecular mechanisms
are studied through GO and KEGG enrichment analysis. The ROC curve analysis
revealed that miR-335-5p could serve as a predictive indicator for the
development of obesity accompanied by metabolic syndrome. Logistic regression
analysis revealed that BMI, TG, FBG, HOMA-IR, and miR-335-5p expression
represent independent risk factors of metabolic syndrome occurrence. Chi-square
test analysis revealed that patients with higher values of BMI, SBP, DBP, TG,
FBG, and HOMA-IR exhibited a more significantly increased expression of
miR-335-5p in their serum. In conclusion, miR-335-5p holds predictive and
diagnostic value for obesity and metabolic syndrome and has potential to serve
as a biomarker for these conditions.