bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Media Sentiment and Classification Shifting
Authors: Wu Peng , Gu Yiyang , Hou Liya
Published: February 2025

This study investigates the role of social media sentiment in classification shifting. Prior literature finds that social media can either reduce accruals management by reducing information asymmetry or increase it by raising market expectations. Using a sample of 21,635 firm‐year observations based on data from Chinese A‐share listed firms from 2009 to 2020, we examine how social media sentiment from the stock forum EastMoney affects classification shifting in China. We find that managers increase classification shifting in response to negative social media sentiment, and our channel tests support the market pressure hypothesis. We confirm that negative social media sentiment increases classification shifting by exerting greater market pressure on managers. We also find that, if accruals or real earnings management is constrained, firms resort to classification shifting to address negative social media sentiment. Finally, we show that negative social media sentiment triggers more stock volatility and price drops. Our study contributes to the earnings management literature by providing novel evidence that sheds light on the market pressure exerted by social media in shaping earnings management strategies.
MdZFP7 integrates JA and GA signals via interaction with MdJAZ2 and MdRGL3a in regulating anthocyanin biosynthesis and undergoes degradation by the E3 ubiquitin ligase MdBRG3
Authors: Ji Xing‐Long , Zhao Ling‐Ling , Liu Baoyou , Yuan Yong‐Bing , Han Yuepeng , You Chun‐Xiang , An Jian‐Ping
Published: February 2025

Jasmonic acid (JA) and gibberellin (GA) coordinate many aspects of plant growth and development, including anthocyanin biosynthesis. However, the crossover points of JA and GA signals and the pathways through which they interact to regulate anthocyanin biosynthesis are poorly understood. Here, we investigated the molecular mechanism by which the zinc finger protein (ZFP) transcription factor Malus domestica ZFP7 (MdZFP7) regulates anthocyanin biosynthesis by integrating JA and GA signals at the transcriptional and post‐translational levels. MdZFP7 is a positive regulator of anthocyanin biosynthesis, which fulfills its role by directly activating the expression of MdMYB1 and enhancing the transcriptional activation of MdWRKY6 on the target genes MdDFR and MdUF3GT. MdZFP7 integrates JA and GA signals by interacting with the JA repressor apple JASMONATE ZIM‐DOMAIN2 (MdJAZ2) and the GA repressor apple REPRESSOR‐of‐ga1‐3‐like 3a (MdRGL3a). MdJAZ2 weakens the transcriptional activation of MdMYB1 by MdZFP7 and disrupts the MdZFP7–MdWRKY6 interaction, thereby reducing the anthocyanin biosynthesis promoted by MdZFP7. MdRGL3a contributes to the stimulation of anthocyanin biosynthesis by MdZFP7 by sequestering MdJAZ2 from the MdJAZ2–MdZFP7 complex. The E3 ubiquitin ligase apple BOI‐related E3 ubiquitin‐protein ligase 3 (MdBRG3), which is antagonistically regulated by JA and GA, targets the ubiquitination degradation of MdZFP7. The MdBRG3‐MdZFP7 module moves the crosstalk of JA and GA signals from the realm of transcriptional regulation and into the protein post‐translational modification. In conclusion, this study not only elucidates the node‐role of MdZFP7 in the integration of JA and GA signals, but also describes the transcriptional and post‐translational regulatory network of anthocyanin biosynthesis with MdZFP7 as the hub.
Comparative accuracy of digital impressions using universal dual‐purpose scan jigs for maxillary implant full arch impressions: An in vitro study
Authors: Almalki Abdulrahman , Akl Mohammed A. , Robaian Ali , Althubaitiy Ramzi , Alnasser Abdullah , Anadioti Evanthia
Published: February 2025

Purpose

To assess the accuracy of intraoral scanners (IOSs) for final impressions using dual‐purpose scan jigs (DPSJs) and standard scan bodies (SBs).

Materials and Methods

An edentulous typodont model with multiunit abutment analogs in the lateral incisor (L), premolar (P), and molar (M) regions was used for intraoral scanning following the manufacturer's recommended protocol. This process involved digitally scanning standard SBs and DPSJs, with the obtained data superimposed and compared against the reference model. Three‐dimensional (3D) evaluation software (Geomagic Control X) was then employed to identify any deviations in the data, followed by statistical analysis using ANOVA one‐way tests and Bonferroni post hoc tests to determine differences at each location.

Results

The overall accuracy ranged from 21.8 to 16.8 µm for DPSJs and from 25.3 to 16.1 µm for SBs. Statistical analysis showed no significant differences between DPSJs and SBs across lateral incisor (L), premolar (P), and molar (M) locations. Specifically, SBs exhibited higher accuracy in lateral incisors (16.8 µm) compared to DPSJs (21.8 µm), but this difference lacked statistical significance. Similarly, in premolar locations, SBs were slightly more accurate (16.1 µm) than DPSJs (17.3 µm), with no statistical significance. Conversely, DPSJs showed slightly better accuracy in molar locations (17.3 µm) than SBs (19.1 µm), which was not statistically significant.

Conclusion

The in vitro study concluded that intraoral digital scanning with DPSJs showed comparable accuracy to standard scan bodies for fully edentulous arches. Furthermore, the 3D deviation of implant positions using both DPSJs and SBs fell within clinically acceptable ranges.
Cultural Difference in the Effect of Bowing on Perceptions of Attractiveness
Authors: Osugi Takayuki , Kawahara Jun I.
Published: February 2025

In Japan, it is customary to show respect to or greet someone by bowing, which involves lowering the head and bending the upper body. Previous studies have shown that a three‐dimensional computer‐generated model performing a bowing motion is perceived as more attractive than a model who is standing still. Furthermore, attractiveness is greater with a longer‐duration bowing motion, including the bending motion, the bent posture, and the stretching motion. These results suggest that bowing is associated with politeness and submissiveness, and it has a synergistic effect with physical attractiveness to enhance overall attractiveness in cultures where bowing is common. However, previous studies mainly focused on Japanese university students, and it remains unclear whether the increase in attractiveness due to bowing is evident in other cultural contexts. The present study examined the cultural dependency of the bowing effect on personal impressions in multiple cultural groups. The effect of bowing on personal impressions was compared among cultural groups. Experiment 1 involved participants from Japan, the United States, Brazil, and India, while Experiment 2 included participants from Japan, the United States, China, and Taiwan. The results indicated that the bowing effect was smaller or not observed in the non‐Japanese cultural groups, particularly for formal bowing. These findings suggest that the increase in attractiveness due to bowing is closely related to the Japanese cultural context.
Relationship Between the Words of Prayer, Psychological Well‐being, and Sense of Coherence
Authors: Fukuromoto Kumiko , Abe Shingo
Published: February 2025

Scientific studies on prayer provide little empirical evidence on the relationship between prayer and well‐being. Furthermore, although prayer was shown to be related to a sense of coherence, an ability concept for stress coping and health maintenance, studies have not examined the type of prayer linked to this association. Our study focused on words of prayer and clarified their association with psychological well‐being and sense of coherence. A questionnaire survey was conducted with 294 participants. No significant correlation was observed between words used in prayers and sense of coherence. However, specific words of prayer had different effects on psychological well‐being. Prayers of thanksgiving and vows consistently yielded positive outcomes regarding psychological well‐being and frequency and internal aspects of the prayer. Therefore, this study suggests that certain prayers may be more effective at improving well‐being than others. Nevertheless, in order to reach a definitive conclusion, it is necessary to focus on other aspects of prayer and to examine causal relationships in the future.
Targeting the Infrapatellar Branch of the Saphenous Nerve for Pain Relief in Patients With Acute or Chronic Knee Pain: A Systematic Review of Randomized Controlled Trials and Cohort Studies
Authors: Li Qiangqiang , Aierken Aikeremu , Qin Jianghui , Chen Dongyang , Jiang Qing
Published: February 2025

Blocking the infrapatellar branch of the saphenous nerve (IPBSN) can provide analgesic benefits for patients with postoperative acute pain or chronic pain, with minimal adverse effects. To evaluate the analgesic efficacy and potential adverse events associated with IPBSN block in patients suffering from acute or chronic knee pain. We conducted a systematic review across PubMed, Cochrane, Web of Science, and Embase to identify all relevant randomized controlled trials (RCTs) and cohort studies according to predefined selection criteria. The study quality of the RCTs was evaluated using the Cochrane risk of bias assessment tool, while cohort studies were assessed using the ROBINS‐I risk of bias tool. The primary outcomes measured were pain intensity and opioid consumption following the nerve block. A total of eight studies were included in this systematic review, encompassing 613 subjects with 276 participants in the control group and 337 participants in the IPBSN block group. The level of evidence was rated high for the RCTs and moderate for the cohort studies. The nerve block was administrated either through the injection of local anesthetic or percutaneous cryoneurolysis targeting the IPBSN. The results indicated that the IPBSN block significantly improved pain relief and reduced opioid consumption in patients with acute postoperative or chronic pain, with no significant difference in the rate of adverse events relating to the procedures or device. The IPBSN block holds promise for improving pain relief and reducing opioid consumption. However, further well‐designed randomized controlled trials are needed to confirm these results.
Upgrading of the genetic engineering toolkit accelerated the discovery process of the virulence effect of PsGH7d on Phytophthora sojae invasion
Authors: Liu Changqing , Tan Xinwei , Wang Jiayu , Sun Yujing , Xu Qian , Han Chao , Wang Qunqing
Published: February 2025

The genus of Phytophthora includes numerous phytopathogens that have devastating impacts on agricultural production. However, the limited availability of selection markers for numerous pathogenicity pathogens of the genus Phytophthora genetic transformation hinders further research on their pathogenic functional genes. Here we report a gene of NAT I, which serves as a novel selection marker for the Phytophthora sojae transformation. Additionally, we developed a new genetic manipulation toolkit based on vectors containing NAT I, which facilitates gene editing in P. sojae. With the toolkit, the gene PsGH7d of P. sojae, which encodes a glycosyl hydrolase, was edited consecutively via the CRISPR/Cas9 system to obtain gene knockout and enzymatic active site mutation strains. The pathogenicity analysis of these transformants revealed that PsGH7d is a virulence factor dependent on its bifunctional glucanase‐xylanase activities. This study develops an updated toolkit for the genus Phytophthora genetic transformation and provides initial insights into the virulence of the bifunctional enzyme PsGH7d.
Identification of Four Novel HLA Alleles: HLA‐C*03:09:02:01, ‐C*07:04:32, ‐C*07:1152 and ‐C*08:300
Authors: Fabreti‐Oliveira Raquel Aparecida , de Oliveira Cintia Keilla Fabreti , da Silva Assis Aline , Nascimento Evaldo
Published: February 2025

Identification of four novel HLA alleles, HLA‐C*03:09:02:01, ‐C*07:04:32, ‐C*07:1152, and ‐C*08:300, in Brazilian individuals.
A Cautionary Tale: ABO Genotyping in Kidney Transplantation of ABO A2 Kidneys Into B or O Recipients
Authors: Murphey Cathi L. , Bailey Amanda , Kapturczak Matthias , Gebel Howard M. , Bray Robert A.
Published: February 2025

The US 2014 kidney allocation system (KAS) allows ABO A2 donor kidneys to be transplanted into ABO B candidates, thereby broadening the donor pool for a traditionally disadvantaged population. Safely transplanting these patients relies heavily on two components: (1) recipient ABO antibody titres and (2) ABO A subtyping of the donor. While lectin‐based serological methods remain the gold standard for ABO typing, recent data show ABO molecular genotyping is a more reliable approach to accurately assign the A2 subtype. ABO titres were performed using Ortho Diagnostics gel cards using haemagglutination by both antiglobulin‐enhanced and dithiothreitol methods. ABO genotyping was performed using innotrain diagnostiks Real‐Time PCR. Here, we present two cases where ABO lectin testing incorrectly identified the donors as ABO A2 and A2B instead of A1 and A1B. Consequently, the transplants proceeded but had deleterious outcomes. These two cases support the concept that ABO genotyping by molecular methodology should be mandatory to confirm the A2 donor subtype when transplanting kidneys from deceased donors into ABO B candidates on the waitlist and for virtual crossmatching (VXM) donors being considered for transplantation into ABO B and O recipients.
Anthocyanin biosynthesis and transport synergistically modulated by RcMYB75 and RcGSTFL11 play a pivotal role in the feedforward loop in response to drought stress
Authors: Ma Mengni , Li Runhui , Li Yajun , Dai Wenhao , Shang Junzhong , He Yanhong , Xiang Fayun , Yang Yuanyuan , Wang Jihua , Huang Zifeng , Luo Hong , Zhang Jie , Ning Guogui
Published: February 2025

Anthocyanins, the important antioxidants and signaling molecules, are natural polyphenolic compounds widely present in plants and essential for plant defense. However, little is known about the mechanisms underlying plant anthocyanin accumulation in relation to drought stress. This study reveals that drought stress induces significant anthocyanin accumulation in Rosa chinensis, alongside an increase in the expression of the MYB transcription factor (TF) gene RcMYB75 and the glutathione S‐transferase (GST) gene RcGSTFL11. When overexpressed, RcMYB75 markedly increases anthocyanin contents in both roses and tobaccos; conversely, reducing its expression significantly lowers anthocyanin contents in rose petals. RcGSTFL11 was confirmed as an anthocyanin transporter and overexpression of RcGSTFL11 can restore the anthocyanin‐deficient phenotype in the Arabidopsis tt19 mutant. Transgenic roses overexpressing RcGSTFL11 exhibit enhanced anthocyanin accumulation, while those with downregulated RcGSTFL11 have reduced contents. Transcriptomic analysis indicates that RcMYB75 upregulates the expression of key genes in the anthocyanin biosynthetic pathway and the anthocyanin transport gene RcGSTFL11. Ultimately, we also found that anthocyanin accumulation in these transgenics further enhances plant resistance to drought stress. Taken together, RcMYB75 and RcGSTFL11 promote the synthesis and transport of anthocyanins and play a key role in the feedforward loop responding to drought stress in roses. This study provides insights into the molecular mechanisms by which MYB TFs contribute to anthocyanin biosynthesis and transport, as well as the adaptive strategies of roses in response to drought stress.
Genetic dissection of internode length confers improvement for ideal plant architecture in maize
Authors: Duan Haiyang , Li Jianxin , Xue Zhengjie , Yang Lu , Sun Yan , Ju Xiaolong , Zhang Jihong , Xu Guoqiang , Xiong Xuehang , Sun Li , Xu Shuhao , Xie Huiling , Ding Dong , Zhang Xuebin , Zhang Xuehai , Tang Jihua
Published: February 2025

The optimal plant architecture, characterized by short stature, helps mitigate lodging, enables high‐density planting, and facilitates mechanized harvesting. Internode length (IL), a crucial component of plant height in maize, plays a significant role in these processes. However, the genetic mechanisms underlying internode elongation remain poorly understood. In this study, we conducted a genome‐wide association study to dissect the genetic architecture of IL in maize. The lengths of five internodes above and below the ear (referred as IL‐related traits) were collected across multiple environments, revealing substantial variation. A total of 108 quantitative trait loci (QTL) were associated with 11 IL‐related traits, with 17 QTL co‐detected by different traits. Notably, three QTL have been selected in maize breeding progress. Three hundred and three genes associated with IL were found to operate through plant hormone signal transduction, receptor activity, and carbon metabolism pathways, influencing internode elongation. ZmIL1, which encodes alcohol dehydrogenase, exhibited a high expression level in internodes during the vegetative stage and has been selected in Chinese modern maize breeding. Additionally, ZmIL2 and ZmIL3 emerged as other crucial regulators of IL. Importantly, ZmIL1 has potential applications in maize varieties in the Huang‐Huai‐Hai region. This study represents the first comprehensive report on the genetic architecture of nearly all ILs in maize, providing profound insights into internode elongation mechanisms and genetic resources. These findings hold significant implications for dwarf breeding programs aimed at optimizing plant architecture for enhancing agronomic performance.
The link between sarcopenic obesity and Alzheimer's disease: a brain‐derived neurotrophic factor point of view
Authors: Copeland Emily N. , LeBlanc Paul J. , Duarte‐Guterman Paula , Fajardo Val A. , MacPherson Rebecca E. K.
Published: February 2025

Age‐related diseases are becoming more prominent as the lifespan of the global population rises. Many of these diseases coincide with each other and can even influence the onset of additional comorbidities. Sarcopenic obesity is described as age‐related loss of muscle mass that concurs with excessive weight gain and tends to increase the risk of comorbidity development, including Alzheimer's disease (AD). Though the exact link between sarcopenic obesity and AD is not known, this review explores the possibility that reduced levels of brain‐derived neurotrophic factor (BDNF) throughout the body may serve as the underlying commonality. In AD, reductions in BDNF signalling through its receptor promote the activation of glycogen synthase kinase 3 beta (GSK3β), which subsequently increases the production of amyloid beta (Aβ) peptides and neurofibrillary tangles (NFTs). In the skeletal muscle, lower BDNF concentrations are linked to impaired muscle fibre repair and regeneration, increasing the likelihood of sarcopenia. Furthermore, the absence of BDNF impairs mitochondrial function, leading to insulin resistance and increased adiposity. BDNF concentration has a negative relationship with obesogenic markers in adipose tissue, and as such, lower concentrations of BDNF lead to weight gain. Collectively, current literature suggests that BDNF attenuates AD pathology while improving skeletal muscle mitochondrial function, whole‐body insulin resistance and facilitating adipocyte browning. Therefore, BDNF may be a viable target for multiple age‐related diseases, but more research is required to substantiate this claim, with a particular focus on examining any potential influence of biological sex, as women are at a higher risk for both AD and sarcopenic obesity.

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Pattern Optimization to Minimize Dynamic Impacts of Wrapping Cables in Plate-like Space Structures: Experimental Validation
Authors: Oluyemi Momoiyioluwa , Agrawal Pranav , Salehian Armaghan
Published: February 2025

In lightweight space structures, incorporating power and control signal transmission cables significantly impacts the dynamics of the host structures. This study presents an experimental effort to provide proof of concept for the mathematical modeling techniques developed for the ideal cable placement to preserve the dynamic properties of host plate structures. By assuming a periodic cable wrapping pattern, the cable-harnessed structure is modeled using repeating fundamental elements. This periodicity enables the application of an energy-equivalence homogenization method, leading to partial differential equations that describe the out-of-plane vibrations of the cable-harnessed plate system. The presented test results further validate several optimal wrapping designs for host plate structures. The frequency response functions for the optimal cable pattern from the analytical model are compared against the test results, demonstrating excellent agreement.
Plasma atomic layer etching of tantalum nitride with surface fluorination and Ar ion sputtering
Authors: Kang Hojin , Lee Sangbae , Jeon Minsung , Chae Heeyeop
Published: February 2025

A comparative study on the atomic layer etching (ALE) process window was conducted for tantalum nitride (TaN) using nitrogen trifluoride (NF3) and carbon tetrafluoride (CF4) plasmas. The TaN surface was fluorinated with NF3 or CF4 plasmas, followed by the removal of the fluorinated layer through Ar ion sputtering. The fluorine radical density in the plasma was analyzed via optical emission spectroscopy, and the chemical composition and bonding of the fluorinated layers were characterized using x-ray photoelectron spectroscopy. Ta–Fx bonds were identified in the NF3 plasma fluorinated layer, while both Ta–Fx and Ta–Cx bonds were observed in the CF4 plasma fluorinated layer. Secondary ion mass spectrometry revealed that the fluorinated layer formed by NF3 plasma was slightly deeper than that formed by CF4 plasma. During the removal step, a wider ALE process window (50–90 V) was observed with the NF3 plasma compared to the CF4 plasma (70–90 V). The etch per cycle of TaN was saturated at 180 s of Ar ion sputtering for both plasmas. The ALE process provided lower fluorine etch residues and surface roughness compared to reactive ion etching.
Exploring the Development of Fundamental Movement Skills in Children With Physical Disabilities: A Scoping Review
Authors: Hebinck Margaux , Labbé Mariève , Lavoie Marie-Denise , Best Krista L. , Robert Maxime T.
Published: February 2025

Introduction: Fundamental movement skills (FMS) are categorized into three groups (stability, locomotion, and object control) and are crucial for enabling the practice of physical activity in children with physical disabilities. Their development is influenced by the specific nature of each child’s disability. FMS can be evaluated by process- (movement execution) or product-oriented (movement outcome) assessments. This scoping review explored FMS development in children with physical disabilities and its relationship with physical activity. Method: Following Preferred Reporting Items for Systematic review and Meta-Analysis extension for scoping reviews guidelines, the search was conducted across six databases (MEDLINE, CINAHL, Web of Science, SPORTDiscus, EMBASE and PsycINFO) and used keywords related to FMS, physical literacy, and physical disabilities. Articles were included if participants had physical disabilities, were aged between 3 and 18 years, and if they explored the relationship between FMS and physical activity and/or physical literacy. Results: Twenty-two studies were included. Both process- and product-oriented assessments reported lower FMS proficiency in children with physical disabilities. Older children demonstrated better proficiency. Most studies highlighted a significant relationship between FMS and physical activity. Conclusion: Enhanced knowledge of effective strategies and evidence-based practices will enable practitioners to create supportive environments, encourage active participation, and track progress, ultimately leading to improved motor skills and overall well-being in children.
Diabetes potentiates the emergence and expansion of antibiotic resistance
Authors: Shook John C. , Genito Christopher J. , Darwitz Benjamin P. , Tyson Kaleb J. , Velez Amanda Z. , Bridwell Sophia K. , Parsons Joshua B. , Rowe Sarah E. , Marshall Christopher W. , Conlon Brian P. , Thurlow Lance R.
Published: February 2025

Individuals with diabetes mellitus frequently develop severe skin and soft tissue infections (SSTIs) that are recalcitrant to antibiotic treatment. We examined how diabetes affects the emergence of antibiotic resistance in a
Staphylococcus aureus
SSTI. We determined that
S. aureus
evolves antibiotic resistance rapidly in diabetic mice, while resistance did not occur in nondiabetic mice over the course of infection. Diabetes-associated immune cell dysfunction plays a minor role in the emergence of resistance, while hyperglycemia plays a dominant role facilitating the expansion and takeover of resistant mutants in diabetic infections. Furthermore, vancomycin intermediate resistant isolates display a pronounced fitness defect in nondiabetic mice but not in diabetic mice. Together, these data suggest that the diabetic infection environment represents an ideal reservoir for the emergence and proliferation of antibiotic resistance. Controlling the blood sugar of diabetic mice with insulin resulted in significantly decreased incidence of antibiotic-resistant
S. aureus
.
Inverse conjugate additions of acrylic amides and esters with F/Cl/O/N-nucleophiles and CF
3
+
reagents
Authors: Liu Xiaoxiao , Kou Yuan , Wu Hao , Liu Tong-Xin , Liu Qingfeng , Zhang Zhiguo , Zhang Xingjie , Zhang Guisheng
Published: February 2025

The conjugate additions of nucleophiles to conjugate acceptors are among the most powerful hetero-carbon bond formation reactions. The conjugate addition normally occurs via a β-nucleophilic addition, resulting in the formation of a stabilized α-carbanion intermediate that can be subsequently quenched by electrophiles or protons. Nevertheless, the inverse conjugate addition involving an α-specific nucleophilic addition remains less explored because of the electronic mismatch. In this research, we disclosed an α-specific nucleophilic addition of the nucleophiles including Py·HF, TBACl, HOR, H
2
O, H
2
18
O, RCO
2
H, and pyrazole to conjugate acceptors concurrent with a trifluoromethylation. This umpolung and inversely regioselective conjugate addition, enabled by a visible light–induced redox photocatalysis, occurred via an unusual α-nucleophilic addition other than the normal β-nucleophilic addition to efficiently generate diverse α-functionalized CF
3
-containing amides/esters. The broad substrate scope, excellent functional-group tolerance, and versatile late-stage derivatizations as well as the biologically and functionally important CF
3
-containing products demonstrated the potential applications of this protocol in materials, agrochemicals, and pharmaceutical chemistry.
Flexible pyroelectric energy harvesters from nanocomposites of liquid crystal elastomers/lead zirconate titanate nanoparticles
Authors: Li Shangsong , Wang Yuchen , Liu Zixiao , Chen Baohong , Liu Mingzhu , He Ximin , Yang Shu
Published: February 2025

Pyroelectric materials that can generate electric charges when subjected to temperature changes are of interest for renewable energy. However, current flexible pyroelectric energy harvesters suffer from low output. Here, we present a nanocomposite of liquid crystalline elastomer (LCE) and pyroelectric lead zirconate titanate (PZT) nanoparticles and demonstrate a flexible heat harvesting device with high output. The overall pyroelectricity is enhanced by the secondary pyroelectricity generated from the thermal stress imposed on the LCE. Calculations and simulations corroborate with experiments, suggesting that the monodomain LCE/PZT with fixed boundaries offers the most enhancement. At a maximum heating rate of 0.20 kelvin per second, the fixed monodomain film (42.7 weight % PZT) shows an output current of 2.81 nanoamperes and a voltage of 6.23 volts, corresponding to a pyroelectric coefficient
p
of −4.01 nanocoulombs per square centimeter per kelvin, 49% higher than that of the widely used polyvinylidene fluoride. Our energy harvester can charge capacitors and power electronic devices such as light-emitting diodes.
Biohybrid hand actuated by multiple human muscle tissues
Authors: Ren Xinzhu , Morimoto Yuya , Takeuchi Shoji
Published: February 2025

Cultured muscle tissue serves as a power source in biohybrid robots that demonstrate diverse motions. However, current designs typically only drive simple substrates on a small scale, limiting flexibility and controllability. To address this, we proposed a biohybrid hand with multijointed fingers powered by multiple muscle tissue actuators (MuMuTAs), bundles of thin muscle tissues. The MuMuTA can provide linear actuation with high contractile force (~8 millinewtons) and high contractile length (~4 millimeters), which can be converted into the flexion of multijointed fingers by a cable-driven mechanism. We successfully powered the biohybrid hand achieving individual control of fingers and a variety of motions using different signaling controls. This study showcases the potential of MuMuTAs as a driving source for advanced biohybrid robotics.
Bioinspired design of a tissue-engineered ray with machine learning
Authors: Zimmerman John F. , Drennan Daniel J. , Ikeda James , Jin Qianru , Ardoña Herdeline Ann M. , Kim Sean L. , Ishii Ryoma , Parker Kevin Kit
Published: February 2025

In biomimetic design, researchers recreate existing biological structures to form functional devices. For biohybrid robotic swimmers assembled with tissue engineering, this is problematic because most devices operate at different length scales than their naturally occurring counterparts, resulting in reduced performance. To overcome these challenges, here, we demonstrate how machine learning–directed optimization (ML-DO) can be used to inform the design of a biohybrid robot, outperforming other nonlinear optimization techniques, such as Bayesian optimization, in the selection of high-performance geometries. We show how this approach can be used to maximize the thrust generated by a tissue-engineered mobuliform miniray. This results in devices that can swim at the millimeter scale while more closely preserving natural locomotive scaling laws. Overall, this work provides a quantitatively rigorous approach for the engineering design of muscular structure-function relationships in an automated fashion.
Intestinal epithelium–derived IL-34 reprograms macrophages to mitigate gastrointestinal tract graft-versus-host disease
Authors: Rayasam Aditya , Moe Alison , Kudek Matthew , Shah Ravi K. , Yuan Cheng-Yin , Miller James M. , Rau Mary , Patton Mollie , Wanat Karolyn , Colonna Marco , Zamora Anthony E. , Drobyski William R.
Published: February 2025

Gastrointestinal (GI) tract graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation and is attributable to dysregulation that occurs between the effector and regulatory arms of the immune system. Whereas regulatory T cells have a primary role in counterbalancing GVHD-induced inflammation, identifying and harnessing other pathways that promote immune tolerance remain major goals in this disease. Herein, we identified interleukin-34 (IL-34) as an intestinal epithelium–derived cytokine that was able to mitigate the severity of GVHD within the GI tract. Specifically, we observed that the absence of recipient IL-34 production exacerbated GVHD lethality, promoted intestinal epithelial cell death, and compromised barrier integrity. Mechanistically, the absence of host IL-34 skewed donor macrophages toward a proinflammatory phenotype and augmented the accumulation of pathogenic CD4
+
granulocyte-macrophage colony-stimulating factor (GM-CSF)
+
T cells within the colon. Conversely, the administration of recombinant IL-34 substantially reduced GVHD mortality and inflammation, which was dependent on the expression of apolipoprotein E in donor macrophages. Complementary genetic and imaging approaches in mice demonstrated that intestinal epithelial cells were the relevant source of IL-34. These results were supported by colonic biopsies from patients with GVHD, which displayed IL-34 expression in intestinal epithelial cells and apolipoprotein E in lamina propria macrophages, validating similar cellular localization in humans. These studies indicate that IL-34 acts as a tissue-intrinsic cytokine that regulates GVHD severity in the GI tract and could serve as a potential therapeutic target for amelioration of this disease.
Early detection of pancreatic cancer by a high-throughput protease-activated nanosensor assay
Authors: Montoya Mira Jose L. , Quentel Arnaud , Patel Ranish K. , Keith Dove , Sousa Megan , Minnier Jessica , Kingston Benjamin R. , David Larry , Esener Sadik C. , Sears Rosalie C. , Lopez Charles D. , Sheppard Brett C. , Demirci Utkan , Wong Melissa H. , Fischer Jared M.
Published: February 2025

Pancreatic ductal adenocarcinoma (PDAC) is among the top causes of cancer-related death. Patients are frequently diagnosed in the more advanced stages when effective treatment options are limited; however, earlier detection of PDAC by liquid biopsy may expand treatment options and improve survival outcomes. Here, we developed a noninvasive detection assay for PDAC based on serum protease activity to leverage the increase in cancer-associated protease activity in the peripheral blood of patients with PDAC. We screened a series of protease-cleavable peptide probes for the discrimination of PDAC samples versus healthy controls and noncancerous pancreatic disease. We identified a single MMP-sensitive probe, which could distinguish PDAC from controls with 79 ± 6% accuracy. We further developed this probe into a rapid magnetic nanosensor assay, termed PAC-MANN, that measures serum protease cleavage of a target-probe nanosensor with a simple fluorescent readout. In a longitudinal cohort of patients undergoing surgical removal of the primary tumor, the probe cleavage signal was reduced by 16 ± 24% after surgery. In a separate blinded retrospective study, the PAC-MANN assay identified PDAC samples with 98% specificity and 73% sensitivity across all stages and distinguished 100% of patients with noncancer pancreatic disease relative to patients with PDAC. The PAC-MANN assay combined with the clinical biomarker CA 19-9 was 85% sensitive for detection of stage I PDAC with 96% specificity. Therefore, the PAC-MANN assay is a rapid, high-throughput method that uses small blood volumes with the potential to enhance early PDAC detection, specifically among individuals at high risk of developing PDAC.
Microfluidic droplets with amended culture media cultivate a greater diversity of soil microorganisms
Authors: Dai Jing , Ouyang Yang , Gupte Rohit , Liu Xiao Jun A. , Li Yuwen , Yang Fang , Chen Shaorong , Provin Tony , Van Schaik Erin , Samuel James E. , Jayaraman Arul , Zhou Aifen , de Figueiredo Paul , Zhou Jizhong , Han Arum
Published: February 2025

Uncultivated but abundant soil microorganisms have untapped potential for producing broad ranges of natural products, as well as for bioremediation. However, cultivating soil microorganisms while maintaining a broad microorganism diversity to enable phenotyping and functional analysis of as diverse individual isolates as possible remains challenging. In this study, we developed and tested the ability of several culture media formulations that contain defined soil metabolites or soil extracts to maintain microorganism diversity during culture. We also assessed their performance in microfluidic droplet cultivation where single-soil microorganism isolates were encapsulated and cultivated in picoliter-volume water-in-oil emulsion droplets to enable clonal growth needed for downstream functional analyses. Our results show that droplet cultivation with media supplemented by soil extract or soil metabolites enables the recovery of soil microorganisms with higher diversity (up to 1.5-fold higher richness) compared to bulk cultivation methods. Importantly, 1.7-fold more of less abundant (<1%) phyla and 11-fold more of unique genera were recovered, demonstrating the utility of this method for interrogating highly diverse soil microorganisms for broad ranges of applications.

IMPORTANCE

Although soil microorganisms hold a significant value in bioproduction and bioremediation, only a small fraction—less than 1%—can be cultured under specific media and cultivation conditions. This indicates that there are ample opportunities in harvesting the diverse environmental microorganisms if isolating and recovering these uncultured microorganisms are possible. This paper presents a new cultivation technique composed of isolating single-soil microorganism cell from an
in situ
soil microorganism community in microfluidic droplets and conducting in-droplet cultivation in media supplemented by soil extract or soil metabolites. This method enables the recovery of a broader diversity of the original microorganism community, laying the groundwork for a high-throughput phenotyping of these diverse microorganisms from their natural habitats.
Plus-strand RNA viruses hijack Musashi homolog 1 to shield viral RNA from cytoplasmic ribonuclease degradation
Authors: Zhou Defang , Xu Menglu , Liu Qingjie , Xin Ruixue , Cui Gege , Ding Longying , Liu Xiaoyang , Zhang Xinyue , Yan Tianxing , Zhou Jing , He Shuhai , Yang Liangyu , Xiang Bin , Cheng Ziqiang
Published: February 2025

A successful strategy employed by RNA viruses to achieve replication is to evade host cell RNase degradation. However, the mechanisms through which plus-strand RNA viruses effectively shield viral RNA from cellular ribonuclease degradation remain unclear. In this study, we identified the phenomenon whereby plus-strand RNA viruses, including avian leukosis virus subgroup J (ALV-J), reticuloendotheliosis virus (REV), chicken astrovirus (CAstV), and porcine epidemic diarrhea virus (PEDV), hijacked host cellular Musashi homolog 1 (MSI1). These viruses upregulated MSI1 expression and facilitated its translocation from the cytoplasmic periphery to a position proximal to and within the nucleus, thereby protecting viral RNA from degradation. Mechanistic analyses revealed that these viruses use distinct regions, the unique (U3) region or three prime untranslated region (3′UTR), to engage with MSI1, consequently shielding their viral RNA from cytoplasmic ribonuclease degradation. These results offer significant implications for understanding the replication tactics used by plus-strand RNA viruses, thereby advancing our understanding of their biological behaviors.

IMPORTANCE

The intricate interplay between RNA viruses and host cell RNA regulation encompasses viral mechanisms designed to circumvent RNase-mediated degradation. However, the specific strategies employed by plus-strand RNA viruses to shield their RNA from host ribonucleases remain inadequately characterized. In this study, Musashi homolog 1 (MSI1) is predominantly localized in the cytoplasm of normal cells, distinct from the nucleus. Following infection by plus-strand RNA viruses such as avian leukosis virus subgroup J (ALV-J), reticuloendotheliosis virus (REV), chicken astrovirus (CAstV), and porcine epidemic diarrhea virus (PEDV), these viruses hijack MSI1 to relocate near and within the nucleus. This hijacking is facilitated by specific regions, including unique or three prime untranslated regions, thereby preventing viral RNA from degradation by cytoplasmic ribonucleases. These findings have significant implications for elucidating the replication strategies of plus-strand RNA viruses, thereby advancing our understanding of their biological mechanisms.
FBXO45 restricts HIV-1 replication by inducing SQSTM1/p62-mediated autophagic degradation of Tat
Authors: Xu Mingxiu , Hu Haobo , Yang Weijing , Zhang Jiaxiang , Wang Hong , Zhang Wenyan , Huan Chen
Published: February 2025

As a key regulator of human immunodeficiency virus type 1 (HIV-1) transcription, Tat plays an essential role in viral replication and latency, making it a promising target for designing viral control strategies. Identifying host factors that modulate Tat and exploring the underlying mechanisms will benefit our understanding of HIV-1 transcriptional regulation and provide valuable insights into Tat-based therapeutic strategies. Here, by employing the TurboID approach, we discovered high-affinity binding between FBXO45 and Tat. Our findings demonstrate that FBXO45 negatively regulates Tat by promoting Tat ubiquitination and directing it to autophagic degradation. Autophagic degradation of Tat has been reported, but the specific underlying mechanisms remain unidentified. We elucidated this issue by providing evidence that FBXO45-mediated Tat polyubiquitination is an essential prerequisite for this process. Silencing of FBXO45 leads to a deficiency of autophagy receptor SQSTM1/p62 to bind and facilitate the autophagic degradation of Tat. Our results further underscore the crosstalk between post-translational modifications of Tat by demonstrating that the phosphorylation site of the Tat S62 residue is required for ubiquitination induced by FBXO45. Furthermore, in the context of the regulation of HIV-1, FBXO45 inhibits viral replication and maintains the latency of HIV-1 by suppressing viral transcription. Importantly, FBXO45 overexpression significantly attenuated viral rebound after antiretroviral therapy withdrawal. In summary, our findings suggest a novel role for FBXO45 in regulating HIV-1 replication by inducing the ubiquitination and SQSTM1/p62-dependent autophagic degradation of Tat. Considering the indispensable role of Tat in the regulation of HIV-1 replication and reactivation, FBXO45 may be a potential target for therapeutic intervention against HIV-1.

IMPORTANCE

HIV-1 Tat plays an indispensable role in regulating viral transcription and is a promising target for achieving a functional cure for AIDS. Identifying the host factors that modulate Tat expression could benefit the development of anti-HIV-1 strategies targeting Tat. Using TurboID assay, we identified a significant interaction between FBXO45 and Tat. Functionally, FBXO45 ubiquitinates and directs Tat for SQSTM1/p62-mediated autophagic degradation, thereby effectively restricting HIV-1 replication and maintaining HIV-1 latency by suppressing Tat-dependent viral transcription. These findings uncover a novel role for FBXO45 in regulating Tat and broaden our understanding of the host mechanisms involved in Tat processing.
Draft genomes of three
Sneathia vaginalis
isolates from a patient with bacterial vaginosis
Authors: Panzer Jonathan J. , McGinnis Natalie , Blom Jochen , Winters Andrew D. , Sobel Jack D. , Theis Kevin R.
Published: February 2025

Sneathia vaginalis,
a fastidious pathogen of the female reproductive tract, is implicated in obstetric and gynecologic pathologies, including spontaneous preterm birth and bacterial vaginosis. Here, we report the successful cultivation and genomic sequencing of three
Sneathia vaginalis
isolates collected via a vaginal swab from a patient with bacterial vaginosis.
Motility-dependent processes in
Toxoplasma gondii
tachyzoites and bradyzoites: same same but different
Authors: Kent Robyn S. , Ward Gary E.
Published: February 2025

During infection,
Toxoplasma gondii
tachyzoites must be able to move in order to migrate through tissues, cross biological barriers, and penetrate into and egress from cells they infect. Bradyzoite-stage parasites, which establish infection in naïve hosts, also require motility to escape from cysts after they are ingested and to subsequently migrate to the gut wall, where they either invade cells of the intestinal epithelium or squeeze between these cells to infect the underlying tissue. Little is known about the motility of bradyzoites, which we analyze in detail here and compare to the well-characterized motility and motility-dependent processes of tachyzoites. Unexpectedly, bradyzoites were found to be as motile as tachyzoites in a three-dimensional model extracellular matrix, and they showed increased invasion into and transmigration across monolayers of certain cell types, consistent with their need to establish infection in the gut. The motility of the two stages was inhibited to the same extent by cytochalasin D and KNX-002, compounds known to target the parasite’s actomyosin-based motor. Other compounds that impact tachyzoite motility (tachyplegin and enhancer 5) have a reduced effect on bradyzoites. Furthermore, rapid bradyzoite egress from infected cells is not triggered by treatment with calcium ionophores, as it is with tachyzoites. The similarities and differences between these two life cycle stages highlight the need to characterize both tachyzoites and bradyzoites for a more complete understanding of the role of motility in the parasite life cycle and the effect that motility-targeting therapeutics will have on disease establishment and progression.

IMPORTANCE

Toxoplasma gondii
is a parasite that chronically infects around one-third of the world's population.
Toxoplasma
uses motility for multiple purposes during infection, including extracellular migration, invasion into host cells, and host cell egress. These motility-dependent processes have been extensively studied in the life cycle stage responsible for acute infection, the tachyzoite. In contrast, motility and motility-dependent processes are poorly understood in bradyzoite-stage parasites, which are responsible for both establishing infection after consumption of infected meat and initiating potentially life-threatening reactivated infections in the brains of immunocompromised individuals. We show here that the motility and motility-dependent processes of bradyzoites are similar in many respects to those of tachyzoites but markedly different in others. The results of this study highlight the need to consider both life cycle stages in attempts to develop drugs targeting parasite motility and the signaling processes that regulate motility-dependent processes during infection by these important human pathogens.