bluuebunny/crossref_metadata_2025 huggingface dataset:
A population-based study of transformed marginal zone lymphoma: identifying outcome-related characteristics
Authors: Bult Johanna A. A. , Huisman Francien , Zhong Yujie , Veltmaat Nick , Kluiver Joost , Tonino Sanne H. , Vermaat Joost S. P. , Chamuleau Martine E. D. , Diepstra Arjan , van den Berg Anke , Plattel Wouter J. , Brink Mirian , Nijland Marcel
Published: September 2023

Histological transformation of marginal zone lymphoma (tMZL) into diffuse large B-cell lymphoma is associated with poor outcomes. Clinical characteristics associated with transformation risk and outcome after transformation are largely unknown due to scarcity of data. In this population-based study, competing risk analyses were performed to elucidate clinical characteristics associated with developing transformation among 1793 MZL patients using the Netherlands Cancer Registry. Cox regression analyses were performed to elucidate clinical characteristics associated with risk of relapse and mortality after transformation. Transformation occurred in 75 (4%) out of 1793 MZL patients. Elevated LDH and nodal MZL subtype at MZL diagnosis were associated with an increased risk, and radiotherapy with a reduced risk of developing tMZL. Most tMZL patients received R-(mini)CHOP (n = 53, 71%). Age >60 years and (immuno)chemotherapy before transformation were associated with an increased risk of relapse and mortality after transformation. Two-year progression-free survival (PFS) and overall survival (OS) were 66% (95% CI 52–77%) and 75% (95% CI 62–85%) for R-(mini)CHOP-treated tMZL patients, as compared to a PFS and OS both of 41% (95% CI 19–63%) for patients treated otherwise. Our study offers comprehensive insights into characteristics associated with transformation and survival after transformation, thereby optimizing guidelines and patient counseling.
'You just don't have the time to keep bringing them back, bringing them back': the experience of primary care dental professionals in England when treating young children with carious teeth
Authors: Timms Laura , Rodd Helen , Deery Chris , Brocklehurst Paul , Marshman Zoe
Published: September 2023

Introduction Caries in the primary dentition affects around one-quarter of children in England. There is uncertainty and varying practice regarding the management of these children within NHS primary dental care. Silver diamine fluoride (SDF) is an approach that is not well-adopted nationally. This study aims to explore the factors affecting treatment choices for caries management in young children within primary dental care, including the use of SDF.

Methods Semi-structured interviews were carried out via video conferencing with general dental practitioners and therapists working in NHS primary care. The topic guide covered factors which influence the management of caries in primary teeth, with SDF-specific questions. These were transcribed verbatim and analysed using thematic analysis.

Results A total of 13 interviews were conducted with dental professionals working across Yorkshire and the East Midlands. Decision-making for caries management was dependent on inter-related factors, which also influenced SDF use. Treatment decisions were taken on a case-by-case basis, but were influenced by the child, their parents, the dental professional and service factors, along with the clinical technique.

Conclusion Many individual- and system-level factors influence treatment decisions for early childhood caries. However, issues relating to remuneration and governance appear to be specific barriers to adoption of SDF in primary dental care.
Improving the cytotoxic response of tumor-infiltrating lymphocytes towards advanced stage ovarian cancer with an oncolytic adenovirus expressing a human vIL-2 cytokine
Authors: Quixabeira D. C. A. , Jirovec E. , Pakola S. , Havunen R. , Basnet S. , Santos J. M. , Kudling T. V. , Clubb J. H. A. , Haybout L. , Arias V. , Grönberg-Vähä-Koskela S. , Cervera-Carrascon V. , Pasanen A. , Anttila M. , Tapper J. , Kanerva A. , Hemminki A.
Published: September 2023

While the presence of tumor-infiltrating lymphocytes (TILs) associates with improved survival prognosis in ovarian cancer (OvCa) patients, TIL therapy benefit is limited. Here, we evaluated an oncolytic adenovirus coding for a human variant IL-2 (vIL-2) cytokine, Ad5/3-E2F-d24-vIL2 (vIL-2 virus), also known as TILT-452, as an immunotherapeutic strategy to enhance TIL responsiveness towards advanced stage OvCa tumors. Fragments of resected human OvCa tumors were processed into single-cell suspensions, and autologous TILs were expanded from said samples. OvCa tumor specimens were co-cultured with TILs plus vIL-2 virus, and cell killing was assessed in real time through cell impedance measurement. Combination therapy was further evaluated in vivo through a patient-derived xenograft (PDX) ovarian cancer murine model. The combination of vIL-2 virus plus TILs had best cancer cell killing ex vivo compared to TILs monotherapy. These results were supported by an in vivo experiment, where the best OvCa tumor control was obtained when vIL-2 virus was added to TIL therapy. Furthermore, the proposed therapy induced a highly cytotoxic phenotype demonstrated by increased granzyme B intensity in NK cells, CD4+ T, and CD8+ T cells in treated tumors. Our results demonstrate that Ad5/3-E2F-d24-vIL2 therapy consistently improved TILs therapy cytotoxicity in treated human OvCa tumors.
TGR5 supresses cGAS/STING pathway by inhibiting GRP75-mediated endoplasmic reticulum-mitochondrial coupling in diabetic retinopathy
Authors: Li Yan , Zhu Lingpeng , Cai Meng-Xia , Wang Zi-Li , Zhuang Miao , Tan Cheng-Ye , Xie Tian-Hua , Yao Yong , Wei Ting-Ting
Published: September 2023

Diabetic retinopathy (DR) is a serious and relatively under-recognized complication of diabetes. Müller glial cells extend throughout the retina and play vital roles in maintaining retinal homeostasis. Previous studies have demonstrated that TGR5, a member of the bile acid-activated GPCR family, could ameliorate DR. However, the role of TGR5 in regulating Müller cell function and the underlying mechanism remains to be ascertained. To address this, high glucose (HG)-treated human Müller cells and streptozotocin-treated Sprague-Dawley rats were used in the study. The IP3R1-GRP75-VDAC1 axis and mitochondrial function were assessed after TGR5 ablation or agonism. Cytosolic mitochondrial DNA (mtDNA)-mediated cGAS-STING activation was performed. The key markers of retinal vascular leakage, apoptosis, and inflammation were examined. We found that mitochondrial Ca2+ overload and mitochondrial dysfunction were alleviated by TGR5 agonist. Mechanically, TGR5 blocked the IP3R1-GRP75-VDAC1 axis mediated Ca2+ efflux from the endoplasmic reticulum into mitochondria under diabetic condition. Mitochondrial Ca2+ overload led to the opening of the mitochondrial permeability transition pore and the release of mitochondrial DNA (mtDNA) into the cytosol. Cytoplasmic mtDNA bound to cGAS and upregulated 2’3’ cyclic GMP-AMP. Consequently, STING-mediated inflammatory responses were activated. TGR5 agonist prevented retinal injury, whereas knockdown of TGR5 exacerbated retinal damage in DR rats, which was rescued by the STING inhibitor. Based on the above results, we propose that TGR5 might be a novel therapeutic target for the treatment of DR.
Knockdown of ANXA10 induces ferroptosis by inhibiting autophagy-mediated TFRC degradation in colorectal cancer
Authors: Wang Xinyuan , Zhou Yujie , Ning Lijun , Chen Jinnan , Chen Huimin , Li Xiaobo
Published: September 2023

Annexin A10 (ANXA10) belongs to a family of membrane-bound calcium-dependent phospholipid-binding proteins, but its precise function remains unclear. Further research is required to understand its role in sessile serrated lesions (SSL) and colorectal cancer (CRC). We conducted transcriptome sequencing on pairs of SSL and corresponding normal control (NC) samples. Bioinformatic methods were utilized to assess ANXA10 expression in CRC. We knocked down and overexpressed ANXA10 in CRC cells to examine its effects on cell malignant ability. The effect of ANXA10 on lung metastasis of xenograft tumor cells in nude mice was also assessed. Furthermore, we used quantitative polymerase chain reaction, western blotting, and flow cytometry for reactive oxygen species (ROS), lipid ROS, and intracellular Fe2+ to measure ferroptosis. Immunoblotting and Immunofluorescence staining were used to detect autophagy. We found that ANXA10 was significantly overexpressed in SSL compared to NC. ANXA10 was also highly expressed in BRAF mutant CRCs and was associated with poor prognosis. ANXA10 knockdown reduced the survival, proliferation, and migration ability of CRC cells. Knockdown of ANXA10 inhibited lung metastasis of CRC cells in mice. ANXA10 knockdown increased transferrin receptor (TFRC) protein levels and led to downregulation of GSH/GSSG, increased Fe2+, MDA concentration, and ROS and lipid ROS in cells. Knockdown of ANXA10 inhibited TFRC degradation and was accompanied by an accumulation of autophagic flux and an increase in SQSTM1. Finally, Fer-1 rescued the migration and viability of ANXA10 knockdown cell lines. In brief, the knockdown of ANXA10 induces cellular ferroptosis by inhibiting autophagy-mediated TFRC degradation, thereby inhibiting CRC progression. This study reveals the mechanism of ANXA10 in ferroptosis, suggesting that it may serve as a potential therapeutic target for CRC of the serrated pathway.
Acid-sensing ion channel 1a modulation of apoptosis in acidosis-related diseases: implications for therapeutic intervention
Authors: Zhang Zhenyu , Chen Minnan , Zhan Wenjing , Chen Yuechun , Wang Tongtong , Chen Zhonghua , Fu Yifei , Zhao Gang , Mao Dong , Ruan Jingjing , Yuan Feng-Lai
Published: September 2023

Acid-sensing ion channel 1a (ASIC1a), a prominent member of the acid-sensing ion channel (ASIC) superfamily activated by extracellular protons, is ubiquitously expressed throughout the human body, including the nervous system and peripheral tissues. Excessive accumulation of Ca2+ ions via ASIC1a activation may occur in the acidified microenvironment of blood or local tissues. ASIC1a-mediated Ca2+‑induced apoptosis has been implicated in numerous pathologies, including neurological disorders, cancer, and rheumatoid arthritis. This review summarizes the role of ASIC1a in the modulation of apoptosis via various signaling pathways across different disease states to provide insights for future studies on the underlying mechanisms and development of therapeutic strategies.
The role and implication of autophagy in cholangiocarcinoma
Authors: Khizar Hayat , Hu Yufei , Wu Yanhua , Yang Jianfeng
Published: September 2023

Cholangiocarcinoma (CCA) is a malignant tumor that originates from the biliary epithelial cells. It is characterized by a difficult diagnosis and limited treatment options. Autophagy is a cellular survival mechanism that maintains nutrient and energy homeostasis and eliminates intracellular pathogens. It is involved in various physiological and pathological processes, including the development of cancer. However, the role, mechanism, and potential therapeutic targets of autophagy in CCA have not been thoroughly studied. In this review, we introduce the classification, characteristics, process, and related regulatory genes of autophagy. We summarize the regulation of autophagy on the progression of CCA and collect the latest research progress on some autophagy modulators with clinical potential in CCA. In conclusion, combining autophagy modulators with immunotherapy, chemotherapy, and targeted therapy has great potential in the treatment of CCA. This combination may be a potential therapeutic target for CCA in the future.
Dissociable roles of human frontal eye fields and early visual cortex in presaccadic attention
Authors: Hanning Nina M. , Fernández Antonio , Carrasco Marisa
Published: September 2023

Shortly before saccadic eye movements, visual sensitivity at the saccade target is enhanced, at the expense of sensitivity elsewhere. Some behavioral and neural correlates of this presaccadic shift of attention resemble those of covert attention, deployed during fixation. Microstimulation in non-human primates has shown that presaccadic attention modulates perception via feedback from oculomotor to visual areas. This mechanism also seems plausible in humans, as both oculomotor and visual areas are active during saccade planning. We investigated this hypothesis by applying TMS to frontal or visual areas during saccade preparation. By simultaneously measuring perceptual performance, we show their causal and differential roles in contralateral presaccadic attention effects: Whereas rFEF+ stimulation enhanced sensitivity opposite the saccade target throughout saccade preparation, V1/V2 stimulation reduced sensitivity at the saccade target only shortly before saccade onset. These findings are consistent with presaccadic attention modulating perception through cortico-cortical feedback and further dissociate presaccadic and covert attention.
Designing nanohesives for rapid, universal, and robust hydrogel adhesion
Authors: Pan Zhao , Fu Qi-Qi , Wang Mo-Han , Gao Huai-Ling , Dong Liang , Zhou Pu , Cheng Dong-Dong , Chen Ying , Zou Duo-Hong , He Jia-Cai , Feng Xue , Yu Shu-Hong
Published: September 2023

Nanoparticles-based glues have recently been shown with substantial potential for hydrogel adhesion. Nevertheless, the transformative advance in hydrogel-based application places great challenges on the rapidity, robustness, and universality of achieving hydrogel adhesion, which are rarely accommodated by existing nanoparticles-based glues. Herein, we design a type of nanohesives based on the modulation of hydrogel mechanics and the surface chemical activation of nanoparticles. The nanohesives can form robust hydrogel adhesion in seconds, to the surface of arbitrary engineering solids and biological tissues without any surface pre-treatments. A representative application of hydrogel machine demonstrates the tough and compliant adhesion between dynamic tissues and sensors via nanohesives, guaranteeing accurate and stable blood flow monitoring in vivo. Combined with their biocompatibility and inherent antimicrobial properties, the nanohesives provide a promising strategy in the field of hydrogel based engineering.
DNA nanopores as artificial membrane channels for bioprotonics
Authors: Luo Le , Manda Swathi , Park Yunjeong , Demir Busra , Sanchez Jesse , Anantram M. P. , Oren Ersin Emre , Gopinath Ashwin , Rolandi Marco
Published: September 2023

Biological membrane channels mediate information exchange between cells and facilitate molecular recognition. While tuning the shape and function of membrane channels for precision molecular sensing via de-novo routes is complex, an even more significant challenge is interfacing membrane channels with electronic devices for signal readout, which results in low efficiency of information transfer - one of the major barriers to the continued development of high-performance bioelectronic devices. To this end, we integrate membrane spanning DNA nanopores with bioprotonic contacts to create programmable, modular, and efficient artificial ion-channel interfaces. Here we show that cholesterol modified DNA nanopores spontaneously and with remarkable affinity span the lipid bilayer formed over the planar bio-protonic electrode surface and mediate proton transport across the bilayer. Using the ability to easily modify DNA nanostructures, we illustrate that this bioprotonic device can be programmed for electronic recognition of biomolecular signals such as presence of Streptavidin and the cardiac biomarker B-type natriuretic peptide, without modifying the biomolecules. We anticipate this robust interface will allow facile electronic measurement and quantification of biomolecules in a multiplexed manner.
Turing structuring with multiple nanotwins to engineer efficient and stable catalysts for hydrogen evolution reaction
Authors: Gu Jialun , Li Lanxi , Xie Youneng , Chen Bo , Tian Fubo , Wang Yanju , Zhong Jing , Shen Junda , Lu Jian
Published: September 2023

Low-dimensional nanocrystals with controllable defects or strain modifications are newly emerging active electrocatalysts for hydrogen-energy conversion and utilization; however, a crucial challenge remains in insufficient stability due to spontaneous structural degradation and strain relaxation. Here we report a Turing structuring strategy to activate and stabilize superthin metal nanosheets by incorporating high-density nanotwins. Turing configuration, realized by constrained orientation attachment of nanograins, yields intrinsically stable nanotwin network and straining effects, which synergistically reduce the energy barrier of water dissociation and optimize the hydrogen adsorption free energy for hydrogen evolution reaction. Turing PtNiNb nanocatalyst achieves 23.5 and 3.1 times increase in mass activity and stability index, respectively, compared against commercial 20% Pt/C. The Turing PtNiNb-based anion-exchange-membrane water electrolyser with a low Pt mass loading of 0.05 mg cm−2 demonstrates at least 500 h stability at 1000 mA cm−2, disclosing the stable catalysis. Besides, this new paradigm can be extended to Ir/Pd/Ag-based nanocatalysts, illustrating the universality of Turing-type catalysts.
Addressing mechanism bias in model-based impact forecasts of new tuberculosis vaccines
Authors: Tovar M. , Moreno Y. , Sanz J.
Published: September 2023

In tuberculosis (TB) vaccine development, multiple factors hinder the design and interpretation of the clinical trials used to estimate vaccine efficacy. The complex transmission chain of TB includes multiple routes to disease, making it hard to link the vaccine efficacy observed in a trial to specific protective mechanisms. Here, we present a Bayesian framework to evaluate the compatibility of different vaccine descriptions with clinical trial outcomes, unlocking impact forecasting from vaccines whose specific mechanisms of action are unknown. Applying our method to the analysis of the M72/AS01E vaccine trial -conducted on IGRA+ individuals- as a case study, we found that most plausible models for this vaccine needed to include protection against, at least, two over the three possible routes to active TB classically considered in the literature: namely, primary TB, latent TB reactivation and TB upon re-infection. Gathering new data regarding the impact of TB vaccines in various epidemiological settings would be instrumental to improve our model estimates of the underlying mechanisms.
Sustainable reference points for multispecies coral reef fisheries
Authors: Zamborain-Mason Jessica , Cinner Joshua E. , MacNeil M. Aaron , Graham Nicholas A. J. , Hoey Andrew S. , Beger Maria , Brooks Andrew J. , Booth David J. , Edgar Graham J. , Feary David A. , Ferse Sebastian C. A. , Friedlander Alan M. , Gough Charlotte L. A. , Green Alison L. , Mouillot David , Polunin Nicholas V. C. , Stuart-Smith Rick D. , Wantiez Laurent , Williams Ivor D. , Wilson Shaun K. , Connolly Sean R.
Published: September 2023

Sustainably managing fisheries requires regular and reliable evaluation of stock status. However, most multispecies reef fisheries around the globe tend to lack research and monitoring capacity, preventing the estimation of sustainable reference points against which stocks can be assessed. Here, combining fish biomass data for >2000 coral reefs, we estimate site-specific sustainable reference points for coral reef fisheries and use these and available catch estimates to assess the status of global coral reef fish stocks. We reveal that >50% of sites and jurisdictions with available information have stocks of conservation concern, having failed at least one fisheries sustainability benchmark. We quantify the trade-offs between biodiversity, fish length, and ecosystem functions relative to key benchmarks and highlight the ecological benefits of increasing sustainability. Our approach yields multispecies sustainable reference points for coral reef fisheries using environmental conditions, a promising means for enhancing the sustainability of the world’s coral reef fisheries.
Impact of dietary interventions on pre-diabetic oral and gut microbiome, metabolites and cytokines
Authors: Shoer Saar , Shilo Smadar , Godneva Anastasia , Ben-Yacov Orly , Rein Michal , Wolf Bat Chen , Lotan-Pompan Maya , Bar Noam , Weiss Ervin I. , Houri-Haddad Yael , Pilpel Yitzhak , Weinberger Adina , Segal Eran
Published: September 2023

Diabetes and associated comorbidities are a global health threat on the rise. We conducted a six-month dietary intervention in pre-diabetic individuals (NCT03222791), to mitigate the hyperglycemia and enhance metabolic health. The current work explores early diabetes markers in the 200 individuals who completed the trial. We find 166 of 2,803 measured features, including oral and gut microbial species and pathways, serum metabolites and cytokines, show significant change in response to a personalized postprandial glucose-targeting diet or the standard of care Mediterranean diet. These changes include established markers of hyperglycemia as well as novel features that can now be investigated as potential therapeutic targets. Our results indicate the microbiome mediates the effect of diet on glycemic, metabolic and immune measurements, with gut microbiome compositional change explaining 12.25% of serum metabolites variance. Although the gut microbiome displays greater compositional changes compared to the oral microbiome, the oral microbiome demonstrates more changes at the genetic level, with trends dependent on environmental richness and species prevalence in the population. In conclusion, our study shows dietary interventions can affect the microbiome, cardiometabolic profile and immune response of the host, and that these factors are well associated with each other, and can be harnessed for new therapeutic modalities.
Nonporous amorphous superadsorbents for highly effective and selective adsorption of iodine in water
Authors: Zhou Wei , Li Aimin , Zhou Min , Xu Yiyao , Zhang Yi , He Qing
Published: September 2023

Adsorbents widely utilized for environmental remediation, water purification, and gas storage have been usually reported to be either porous or crystalline materials. In this contribution, we report the synthesis of two covalent organic superphane cages, that are utilized as the nonporous amorphous superadsorbents for aqueous iodine adsorption with the record–breaking iodine adsorption capability and selectivity. In the static adsorption system, the cages exhibit iodine uptake capacity of up to 8.41 g g−1 in I2 aqueous solution and 9.01 g g−1 in I3− (KI/I2) aqueous solution, respectively, even in the presence of a large excess of competing anions. In the dynamic flow-through experiment, the aqueous iodine adsorption capability for I2 and I3− can reach up to 3.59 and 5.79 g g−1, respectively. Moreover, these two superphane cages are able to remove trace iodine in aqueous media from ppm level (5.0 ppm) down to ppb level concentration (as low as 11 ppb). Based on a binding–induced adsorption mechanism, such nonporous amorphous molecular materials prove superior to all existing porous adsorbents. This study can open up a new avenue for development of state–of–the–art adsorption materials for practical uses with conceptionally new nonporous amorphous superadsorbents (NAS).
Layer-dependent exciton polarizability and the brightening of dark excitons in few-layer black phosphorus
Authors: Lei Yuchen , Ma Junwei , Luo Jiaming , Huang Shenyang , Yu Boyang , Song Chaoyu , Xing Qiaoxia , Wang Fanjie , Xie Yuangang , Zhang Jiasheng , Mu Lei , Ma Yixuan , Wang Chong , Yan Hugen
Published: September 2023

The evolution of excitons from 2D to 3D is of great importance in photo-physics, yet the layer-dependent exciton polarizability hasn’t been investigated in 2D semiconductors. Here, we determine the exciton polarizabilities for 3- to 11-layer black phosphorus—a direct bandgap semiconductor regardless of the thickness—through frequency-resolved photocurrent measurements on dual-gate devices and unveil the carrier screening effect in relatively thicker samples. By taking advantage of the broadband photocurrent spectra, we are also able to reveal the exciton response for higher-index subbands under the gate electrical field. Surprisingly, dark excitons are brightened with intensity even stronger than the allowed transitions above certain electrical field. Our study not only sheds light on the exciton evolution with sample thickness, but also paves a way for optoelectronic applications of few-layer BP in modulators, tunable photodetectors, emitters and lasers.
Decorated bacteria-cellulose ultrasonic metasurface
Authors: Li Zong-Lin , Chen Kun , Li Fei , Shi Zhi-Jun , Sun Qi-Li , Li Peng-Qi , Peng Yu-Gui , Huang Lai-Xin , Yang Guang , Zheng Hairong , Zhu Xue-Feng
Published: September 2023

Cellulose, as a component of green plants, becomes attractive for fabricating biocompatible flexible functional devices but is plagued by hydrophilic properties, which make it easily break down in water by poor mechanical stability. Here we report a class of SiO2-nanoparticle-decorated bacteria-cellulose meta-skin with superior stability in water, excellent machining property, ultrathin thickness, and active bacteria-repairing capacity. We further develop functional ultrasonic metasurfaces based on meta-skin paper-cutting that can generate intricate patterns of ~10 μm precision. Benefited from the perfect ultrasound insulation of surface Cassie-Baxter states, we utilize meta-skin paper-cutting to design and fabricate ultrathin (~20 μm) and super-light (<20 mg) chip-scale devices, such as nonlocal holographic meta-lens and the 3D imaging meta-lens, realizing complicated acoustic holograms and high-resolution 3D ultrasound imaging in far fields. The decorated bacteria-cellulose ultrasonic metasurface opens the way for exploiting flexible and biologically degradable metamaterial devices with functionality customization and key applications in advanced biomedical engineering technologies.
Antigravitropic PIN polarization maintains non-vertical growth in lateral roots
Authors: Roychoudhry Suruchi , Sageman-Furnas Katelyn , Wolverton Chris , Grones Peter , Tan Shutang , Molnár Gergely , De Angelis Martina , Goodman Heather L. , Capstaff Nicola , Lloyd James P. B. , Mullen Jack , Hangarter Roger , Friml Jiří , Kepinski Stefan
Published: September 2023

Lateral roots are typically maintained at non-vertical angles with respect to gravity. These gravitropic setpoint angles are intriguing because their maintenance requires that roots are able to effect growth response both with and against the gravity vector, a phenomenon previously attributed to gravitropism acting against an antigravitropic offset mechanism. Here we show how the components mediating gravitropism in the vertical primary root—PINs and phosphatases acting upon them—are reconfigured in their regulation such that lateral root growth at a range of angles can be maintained. We show that the ability of Arabidopsis lateral roots to bend both downward and upward requires the generation of auxin asymmetries and is driven by angle-dependent variation in downward gravitropic auxin flux acting against angle-independent upward, antigravitropic flux. Further, we demonstrate a symmetry in auxin distribution in lateral roots at gravitropic setpoint angle that can be traced back to a net, balanced polarization of PIN3 and PIN7 auxin transporters in the columella. These auxin fluxes are shifted by altering PIN protein phosphoregulation in the columella, either by introducing PIN3 phosphovariant versions or via manipulation of levels of the phosphatase subunit PP2A/RCN1. Finally, we show that auxin, in addition to driving lateral root directional growth, acts within the lateral root columella to induce more vertical growth by increasing RCN1 levels, causing a downward shift in PIN3 localization, thereby diminishing the magnitude of the upward, antigravitropic auxin flux.
Structural basis for abscisic acid efflux mediated by ABCG25 in Arabidopsis thaliana
Authors: Ying Wei , Liao Lianghuan , Wei Hong , Gao Yongxiang , Liu Xin , Sun Linfeng
Published: September 2023

Abscisic acid (ABA) is a phytohormone essential to the regulation of numerous aspects of plant growth and development. The cellular level of ABA is critical to its signalling and is determined by its rate of biosynthesis, catabolism and the rates of ABA transport. ABCG25 in Arabidopsis thaliana has been identified to be an ABA exporter and play roles in regulating stomatal closure and seed germination. However, its ABA transport mechanism remains unknown. Here we report the structures of ABCG25 under different states using cryo-electron microscopy single particle analysis: the apo state and ABA-bound state of the wild-type ABCG25 and the ATP-bound state of the ATPase catalytic mutant. ABCG25 forms a homodimer. ABA binds to a cone-shaped, cytosolic-facing cavity formed in the middle of the transmembrane domains. Key residues in ABA binding are identified and verified by a cell-based ABA transport assay. ATP binding leads to closing of the nucleotide-binding domains of opposing monomers and conformational transitions of the transmembrane domains. Together, these results provide insights into the substrate recognition and transport mechanisms of ABCG25 in Arabidopsis, and facilitate our understanding of the ABA transport and signalling pathway in plants.
Colonic phosphocholine is correlated with Candida tropicalis and promotes diarrhea and pathogen clearance
Authors: Zhou Xihong , He Yiwen , Chen Jingqing , Xiong Xia , Yin Jie , Liang Jing , Peng Can , Huang Chunxia , Guan Guiping , Yin Yulong
Published: September 2023

Diarrhea is characterized by alterations in the gut microbiota, metabolites, and host response to these changes. Studies have focused on the role of commensal bacteria in diarrhea; however, the effect of fungi on its pathogenesis remains unexplored. Here, using post-weaned piglets with or without diarrhea, we found an unexpected decrease in the abundance of Candida tropicalis in diarrheal piglets. We also observed increased accumulation of reactive oxygen species (ROS) and the formation of neutrophil extracellular traps (NETs) in the colonic tissues of diarrheal piglets. Using dectin-1-knockout mice, we found that the over-accumulation of ROS killed C. tropicalis by promoting NET formation, which was dependent on dectin-1. The decreased abundance of C. tropicalis resulted in reduced phosphocholine consumption. Then, colonic phosphocholine accumulation drives water efflux by increasing cAMP levels by activating adenylyl cyclase, which promotes the clearance of pathogenic bacteria. Collectively, we demonstrated that phosphocholine is correlated with colonic C. tropicalis and promotes diarrhea and pathogen clearance. Our results suggest that mycobiota colonizing the colon might be involved in maintaining intestinal metabolic homeostasis through the consumption of certain metabolites.
Transverse energy injection scales at the base of the solar corona
Authors: Sharma Rahul , Morton Richard J.
Published: September 2023

Alfvén wave turbulence models lie at the heart of many investigations into the winds and extreme-ultraviolet and X-ray emission from cool, solar-like stars. The models provide insights into mass loss, magnetic spin down and exoplanet habitability. Yet they currently rely on ad hoc estimates of critical parameters. One critical but unknown parameter is the perpendicular correlation length, which controls the turbulent heating rate and, hence, has a role in determining the properties of coronal plasma. Here, using the Coronal Multi-channel Polarimeter, we measure the correlation length of Alfvénic waves at the base of the corona. The measurements are an order of magnitude closer to the Sun than previous estimates for the perpendicular correlation length. Our analysis shows the values are broadly homogeneous through the corona and have a distribution sharply peaked around 7.6–9.3 Mm. The measured correlation length is comparable to the expected scales associated with supergranulation. The results provide a stringent constraint for Alfvén wave turbulence modelling.
Unveiling global species abundance distributions
Authors: Callaghan Corey T. , Borda-de-Água Luís , van Klink Roel , Rozzi Roberto , Pereira Henrique M.
Published: September 2023

Whether most species are rare or have some intermediate abundance is a long-standing question in ecology. Here, we use more than one billion observations from the Global Biodiversity Information Facility to assess global species abundance distributions (gSADs) of 39 taxonomic classes of eukaryotic organisms from 1900 to 2019. We show that, as sampling effort increases through time, the shape of the gSAD is unveiled; that is, the shape of the sampled gSAD changes, revealing the underlying gSAD. The fraction of species unveiled for each class decreases with the total number of species in that class and increases with the number of individuals sampled, with some groups, such as birds, being fully unveiled. The best statistical fit for almost all classes was the Poisson log-normal distribution. This strong evidence for a universal pattern of gSADs across classes suggests that there may be general ecological or evolutionary mechanisms governing the commonness and rarity of life on Earth.
Single-cell RNA sequencing of murine hearts for studying the development of the cardiac conduction system
Authors: Ren Huiying , Zhou Xiaolin , Yang Jun , Kou Kun , Chen Tangting , Pu Zhaoli , Ye Kejun , Fan Xuehui , Zhang Dan , Kang Xinjiang , Fan Zhongcai , Lei Ming , Sun Tianyi , Tan Xiaoqiu , Ou Xianhong
Published: September 2023

The development of the cardiac conduction system (CCS) is essential for correct heart function. However, critical details on the cell types populating the CCS in the mammalian heart during the development remain to be resolved. Using single-cell RNA sequencing, we generated a large dataset of transcriptomes of ~0.5 million individual cells isolated from murine hearts at six successive developmental corresponding to the early, middle and late stages of heart development. The dataset provides a powerful library for studying the development of the heart’s CCS and other cardiac components. Our initial analysis identified distinct cell types between 20 to 26 cell types across different stages, of which ten are involved in forming the CCS. Our dataset allows researchers to reuse the datasets for data mining and a wide range of analyses. Collectively, our data add valuable transcriptomic resources for further study of cardiac development, such as gene expression, transcriptional regulation and functional gene activity in developing hearts, particularly the CCS.
Simulating individual movement in fish
Authors: Pike Thomas W. , Burman Oliver H. P.
Published: September 2023

Accurately quantifying an animal’s movement is crucial for developing a greater empirical and theoretical understanding of its behaviour, and for simulating biologically plausible movement patterns. However, we have a relatively poor understanding of how animals move at fine temporal scales and in three-dimensional environments. Here, we collected high temporal resolution data on the three-dimensional spatial positions of individual three-spined sticklebacks (Gasterosteus aculeatus), allowing us to derive statistics describing key geometric characteristics of their movement and to quantify the extent to which this varies between individuals. We then used these statistics to develop a simple model of fish movement and evaluated the biological plausibility of simulated movement paths using a Turing-type test, which quantified the association preferences of live fish towards animated conspecifics following either ‘real’ (i.e., based on empirical measurements) or simulated movements. Live fish showed no difference in their response to ‘real’ movement compared to movement simulated by the model, although significantly preferred modelled movement over putatively unnatural movement patterns. The model therefore has the potential to facilitate a greater understanding of the causes and consequences of individual variation in movement, as well as enabling the construction of agent-based models or real-time computer animations in which individual fish move in biologically feasible ways.
A hybrid in silico/in-cell controller for microbial bioprocesses with process-model mismatch
Authors: Ohkubo Tomoki , Soma Yuki , Sakumura Yuichi , Hanai Taizo , Kunida Katsuyuki
Published: September 2023

Bioprocess optimization using mathematical models is prevalent, yet the discrepancy between model predictions and actual processes, known as process-model mismatch (PMM), remains a significant challenge. This study proposes a novel hybrid control system called the hybrid in silico/in-cell controller (HISICC) to address PMM by combining model-based optimization (in silico feedforward controller) with feedback controllers utilizing synthetic genetic circuits integrated into cells (in-cell feedback controller). We demonstrated the efficacy of HISICC using two engineered Escherichia coli strains, TA1415 and TA2445, previously developed for isopropanol (IPA) production. TA1415 contains a metabolic toggle switch (MTS) to manage the competition between cell growth and IPA production for intracellular acetyl-CoA by responding to external input of isopropyl β-d-1-thiogalactopyranoside (IPTG). TA2445, in addition to the MTS, has a genetic circuit that detects cell density to autonomously activate MTS. The combination of TA2445 with an in silico controller exemplifies HISICC implementation. We constructed mathematical models to optimize IPTG input values for both strains based on the two-compartment model and validated these models using experimental data of the IPA production process. Using these models, we evaluated the robustness of HISICC against PMM by comparing IPA yields with two strains in simulations assuming various magnitudes of PMM in cell growth rates. The results indicate that the in-cell feedback controller in TA2445 effectively compensates for PMM by modifying MTS activation timing. In conclusion, the HISICC system presents a promising solution to the PMM problem in bioprocess engineering, paving the way for more efficient and reliable optimization of microbial bioprocesses.
110-million-years-old fossil suggests early parasitism in shrimps
Authors: Lima Daniel , Alencar Damares R. , Santana William , Oliveira Naiara C. , Saraiva Antônio Á. F. , Oliveira Gustavo R. , Boyko Christopher B. , Pinheiro Allysson P.
Published: September 2023

Direct evidence of paleo-parasitism in crustaceans is very scarce. Epicaridean isopods are obligatory parasites of crustaceans, including decapods such as crabs, shrimps, and lobsters. Their interaction with hosts is known from fossils as far back as the Jurassic through deformations of the branchial cuticle on the hosts. Their small size and low fossilization potential, outside of those larvae that have been found in amber, makes understanding the group’s evolution challenging. Here, we report the oldest evidence of paleo-parasitism in marine shrimps and an imprint of a putative adult parasite that appears to be an epicaridean isopod. Our results suggest that the parasite–host interaction between epicaridean isopods and marine shrimps started at least 110 million years ago, and the Tethys Sea was a possible dispersal pathway for this lineage of parasites during the Jurassic and Cretaceous, as known for other marine organisms through most of the Mesozoic and Cenozoic. The oldest fossil records of bopyrid swellings associated with a large number of decapods from the Jurassic in Europe suggest that the Tethys region was a center of epicaridean distribution as a whole. Recent parasitic isopods found on dendrobranchiate shrimps are restricted to the Indo-Pacific and may represent a relict group of a lineage of parasites more widely distributed in the Mesozoic.
Brainwave activities reflecting depressed mood: a pilot study
Authors: Morita Masahiko , Otsu Ryusei , Kawasaki Masahiro
Published: September 2023

Early diagnosis and treatment of depression are desirable but currently difficult due to a lack of established biomarkers. Although biomarkers for depression based on electroencephalogram (EEG) data have long been explored, most existing methods are thought to capture cognitive decline caused by depression and are unsuccessful in detecting signs of depression. Here we report that some brainwave activities involving phase resetting reflect the depressed mood at the time, which can be easily monitored by measuring the resting EEG with eyes closed for 1 min with a few electrodes. We instructed 10 participants (nine healthy and one diagnosed with depression, aged 18–34) to record their EEG for 14–26 days. We found that indicators of depressed mood were correlated with the occurrence frequency of EEG phase resetting. For most participants, the correlation coefficients swung systematically between large positive and large negative values with respect to EEG frequency; however, the frequencies at which they were maximum or minimum differed among participants. Although this study is in the pilot phase and needs further experimentation, the results are expected to lead to innovative biomarkers for early detection of depression and may contribute to a better understanding and treatment of depression.
The fuzzy Kullback–Leibler divergence for estimating parameters of the probability distribution in fuzzy data: an application to classifying Vietnamese Herb Leaves
Authors: Le Hoa , Sang Vu Ngoc Thanh , Lam Thuy Le Nhi , Bao Pham The
Published: September 2023

In this paper, we address the challenge of estimating probability distributions which are typically represented by parameter-based values. However, this estimation is prone to errors and does not comprehensively capture the nature of real-world data. Additionally, real-world data often follows a mixed form of probability distributions, where sub-datasets may contain incomplete information. To enhance flexibility, especially in classification problems, we propose a new method for describing parameters estimated through Bayesian statistics. Our method introduces fuzzy parameters and assesses the similarity between probability distributions using the fuzzy extended Kullback–Leibler divergence. We demonstrate the practical application of our approach in Vietnamese Herb Leaves classification. By incorporating fuzzy parameters and leveraging Bayesian statistics, our method provides more robust estimations of probability distributions and enables improved flexibility in classification tasks.
Ecology and resistance to UV light and antibiotics of microbial communities on UV cabins in the dermatology service of a Spanish hospital
Authors: Molina-Menor Esther , Carlotto Nicolás , Vidal-Verdú Àngela , Pérez-Ferriols Amparo , Pérez-Pastor Gemma , Porcar Manuel
Published: September 2023

Microorganisms colonize all possible ecological habitats, including those subjected to harsh stressors such as UV radiation. Hospitals, in particular the UV cabins used in phototherapy units, constitute an environment in which microbes are intermittently subjected to UV irradiation. This selective pressure, in addition to the frequent use of antibiotics by patients, may represent a threat in the context of the increasing problem of antimicrobial resistance. In this work, a collection of microorganisms has been established in order to study the microbiota associated to the inner and outer surfaces of UV cabins and to assess their resistance to UV light and the antibiotics frequently used in the Dermatology Service of a Spanish hospital. Our results show that UV cabins harbor a relatively diverse biocenosis dominated by typically UV-resistant microorganisms commonly found in sun-irradiated environments, such as Kocuria, Micrococcus or Deinococcus spp., but also clinically relevant taxa, such as Staphylococcus or Pseudomonas spp. The UV-radiation assays revealed that, although some isolates displayed some resistance, UV is not a major factor shaping the biocenosis living on the cabins, since a similar pool of resistant microorganisms was identified on the external surface of the cabins. Interestingly, some Staphylococcus spp. displayed resistance to one or more antibiotics, although the hospital reported no cases of antibiotic-resistance infections of the patients using the cabins. Finally, no association between UV and antibiotic resistances was found.
Thermal tolerance and vulnerability to warming differ between populations of wild Oncorhynchus mykiss near the species’ southern range limit
Authors: Dressler T. L. , Han Lee V. , Klose K. , Eliason E. J.
Published: September 2023

Fish habitat temperatures are increasing due to human impacts including climate change. For broadly distributed species, thermal tolerance can vary at the population level, making it challenging to predict which populations are most vulnerable to warming. Populations inhabiting warm range boundaries may be more resilient to these changes due to adaptation or acclimatization to warmer temperatures, or they may be more vulnerable as temperatures may already approach their physiological limits. We tested functional and critical thermal tolerance of two populations of wild Oncorhynchus mykiss near the species’ southern range limit and, as predicted, found population-specific responses to temperature. Specifically, the population inhabiting the warmer stream, Piru Creek, had higher critical thermal maxima and higher functional thermal tolerance compared to the population from the cooler stream, Arroyo Seco. Arroyo Seco O. mykiss are more likely to experience a limitation of aerobic scope with warming. Piru Creek O. mykiss, however, had higher resting metabolic rates and prolonged exercise recovery, meaning that they could be more vulnerable to warming if prey or dissolved oxygen become limited. Temperature varies widely between streams near the O. mykiss southern range limit and populations will likely have unique responses to warming based on their thermal tolerances and metabolic requirements.
Pedogenesis of typical zonal soil drives belowground bacterial communities of arable land in the Northeast China Plain
Authors: Hou Meng , Zhao Xiaorui , Wang Yao , Lv Xuemei , Chen Yimin , Jiao Xiaoguang , Sui Yueyu
Published: September 2023

Belowground bacterial communities play essential roles in maintaining ecosystem multifunction, while our understanding of how and why their distribution patterns and community compositions may change with the distinct pedogenetic conditions of different soil types is still limited. Here, we evaluated the roles of soil physiochemical properties and biotic interactions in driving belowground bacterial community composition across three typical zonal soil types, including black calcium soil (QS), typical black soil (HL) and dark brown soil (BQL), with distinct pedogenesis on the Northeast China Plain. Changes in soil bacterial diversity and community composition in these three zonal soil types were strongly correlated with soil pedogenetic features. SOC concentrations in HL were higher than in QS and BQL, but bacterial diversity was low, and the network structure revealed greater stability and connectivity. The composition of the bacterial community correlated significantly with soil pH in QS but with soil texture in BQL. The bacterial co-occurrence network of HL had higher density and clustering coefficients but lower edges, and different keystone species of networks were also detected. This work provides a basic understanding of the driving mechanisms responsible for belowground bacterial biodiversity and distribution patterns over different pedogenetic conditions in agroecosystems.