bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial production of the plant flavanone hesperetin from caffeic acid
Authors: Hanko Erik K. R. , Correia João , Souza Caio S. , Green Alison , Chromy Jakub , Stoney Ruth , Yan Cunyu , Takano Eriko , Lousa Diana , Soares Cláudio M. , Breitling Rainer
Published: September 2023

Objective
Hesperetin is an important O-methylated flavonoid produced by citrus fruits and of potential pharmaceutical relevance. The microbial biosynthesis of hesperetin could be a viable alternative to plant extraction, as plant extracts often yield complex mixtures of different flavonoids making it challenging to isolate pure compounds. In this study, hesperetin was produced from caffeic acid in the microbial host Escherichia coli. We combined a previously optimised pathway for the biosynthesis of the intermediate flavanone eriodictyol with a combinatorial library of plasmids expressing three candidate flavonoid O-methyltransferases. Moreover, we endeavoured to improve the position specificity of CCoAOMT7, a flavonoid O-methyltransferase from Arabidopsis thaliana that has been demonstrated to O-methylate eriodictyol in both the para- and meta-position, thus leading to a mixture of hesperetin and homoeriodictyol.
Results
The best performing flavonoid O-methyltransferase in our screen was found to be CCoAOMT7, which could produce up to 48.4 µM hesperetin and 12.7 µM homoeriodictyol from 3 mM caffeic acid in E. coli 5-alpha. Using a platform for enzyme engineering that scans the mutational space of selected key positions, predicting their structures using homology modelling and inferring their potential catalytic improvement using docking simulations, we were able to identify a CCoAOMT7 mutant with a two-fold higher position specificity for hesperetin. The mutant’s catalytic activity, however, was considerably diminished. Our findings suggest that hesperetin can be created from central carbon metabolism in E. coli following the introduction of a caffeic acid biosynthesis pathway.
Association Between Traditional Chinese Medicine and Medication Adherence in Hypertensive Patients in Mainland China: A Real-World Population-Based Cohort Study
Authors: Zhou Jifang , Shang Lili , Bao Yuqing , Cheng Yan , Huang Ruijian , Kong Desong , Gu Ning , Ma Aixia
Published: September 2023

Background: Hypertension and associated CVD are the major public health challenges in China. Medication adherence is the cornerstone for achieving hypertension control and reduce the risk of CVD and mortality. Considering that more and more people have turned on complementary and alternative medicine(CAM) , combined with pharmacotherapy for treating hypertension, including Traditional Chinese Medicine(TCM).However, the relationship between medication adherence and TCM usage remains unknown. This study aimed to assess the association between non-pharmacological therapies of TCM and adherence to anti-hypertensive medication in mainland China.
Methods: Data was extracted from the electronic health records of a Chinese medical hospital. A retrospective cohort study was conducted on hypertension patients enrolled between January 2016 and April 2021. Propensity score matching (PSM) was employed, resulting in 1179 patients in the TCM user group and 257 patients in the no TCM user group. Medication possession ratios (MPR) were used to measure medication adherence in the presence or absence of TCM. Generalized estimating equations (GEE) were applied to identify factors associated with adherence, including TCM exposure, age and sex.
Results: Medication compliance in the real world was generally low, at approximately 10%. The percentage of TCM exposure among differed significantly between the two groups throughout the follow-up period. The proportions of optimal adherence (MPR≥ 80) and continuous treatment rate showed no significant difference. GEE regression results indicated that TCM visits could improve medication adherence to anti-hypertensive drugs. Subgroup analysis revealed that TCM use had a positive impact on optimal adherence for male patients and patients aged 60 years and above (p<0.05). Conversely, there was no association between TCM use and MPR in female patients.
Conclusions: Notably, medication compliance was higher among TCM users compared to no TCM users. TCM exposure appeared to have a positive effect on medication adherence in hypertensive patients, suggesting its potential as a complementary approach to conventional Western drug therapy. This study provides important insights for integrating Chinese and Western medicine to enhance adherence to anti-hypertensive medications.
BiœmuS: A new tool for neurological disorders studies through real-time emulation and hybridization using biomimetic Spiking Neural Network
Authors: Levi Timothee , Beaubois Romain , Cheslet Jérémy , Duenki Tomoya , Khoyratee Farad , Branchereau Pascal , Ikeuchi Yoshiho
Published: September 2023

Characterization and modeling of biological neural networks is a field opening to major advances in our understanding of the mechanisms governing the functioning of the brain and the different pathologies that can affect it. Recent researches in bioelectronics and neuromorphic engineering lead to the design of the new generation of neuroprosthesis. Here we show a novel real-time, biomimetic and energy-efficient neural network for bio-hybrid experiments and parallel emulation. This novel system is used to investigate and reproduce neural network dynamics. The setup is running on a digital platform using a System on Chip (SoC) featuring both Programmable Logic (PL) and processors in a Processing System (PS) part. The FPGA part is computing the biomimetic and real-time electrical activities of Hodgkin-Huxley neural network while the processors handle monitoring and communication. New methods of resource and power optimization has been applied to the FPGA to allow detailed neuron modeling with synapses showing short term plasticity. The system is validated by comparison with biological data and model. We also demonstrate the feasibility of bio-hybrid experiments with different bio-physical interface and different biological cells. The complete setup achieves communication with a fully flexible real-time device thus constituting a step towards neuromorphic-based neuroprosthesis for bioelectrical therapeutics.
Geometric design of Cu2Se-based thermoelectric device for enhancing power generation
Authors: Son Jae Sung , Choo Seungjun , Lee Jungsoo , Sisik Bengisu , Jung Sung-Jin , Kim Keonkuk , Yang Seong Eun , Jo Seungki , Nam Changhyeon , Ahn Sangjoon , Lee Ho Seong , Chae Han Gi , Kim Seong Keun , LeBlanc Saniya
Published: September 2023

Waste heat, an abundant energy source generated by both industries and nature, has the potential to be harnessed into electricity via thermoelectric power generation. The performance of thermoelectric modules, typically composed of cuboid-shaped materials, depends on both the materials’ intrinsic properties and the temperature difference created. Despite significant advancements in the development of efficient materials, macroscopic thermal designs capable of accommodating larger temperature differences have been largely underexplored because of the challenges associated with processing bulk thermoelectric materials. Herein, we present the design strategy for Cu2Se thermoelectric materials for high-temperature power generation using a combination of finite element modelling and 3D printing. The macroscopic geometries and microscopic defects in Cu2Se materials are precisely engineered by optimising the 3D printing and post-treatment processes, leading to significant enhancements in the material efficiency and temperature difference within devices, where the hourglass geometry exhibits maximised output powers. The proposed approach paves the way for designing efficient thermoelectric power generators.
Molecular basis for proofreading by the unique exonuclease domain of Family-D DNA polymerases
Authors: Sauguet Ludovic , Betancurt-Anzola Leonardo , Martinez-Carranza Markel , Delarue Marc , Zatopek Kelly , Gardner Andrew
Published: September 2023

Replicative DNA polymerases duplicate entire genomes at high fidelity. This feature is shared among the three domains of life and is facilitated by their dual polymerase and exonuclease activities. Family D replicative DNA polymerases (PolD), found exclusively in Archaea, contain an unusual RNA polymerase-like catalytic core, and a unique Mre11-like proofreading active site. Here, we present cryo-EM structures of PolD trapped in a proofreading mode, revealing an unanticipated correction mechanism that extends the repertoire of protein domains known to be involved in DNA proofreading. Based on our experimental structures, mutants of PolD were designed and their contribution to mismatch bypass and exonuclease kinetics was determined. This study sheds light on the convergent evolution of structurally distinct families of DNA polymerases, and the domain acquisition and exchange mechanism that occurred during the evolution of the replisome in the three domains of life.
Do the elderly and those with comorbid chronic physical conditions have improved access to outpatient psychotherapy post structural reforms in Germany? Results of the ES-RiP study
Authors: Jedamzik Johanna , Kampling Hanna , Christoffer Andrea , Szardenings Carsten , Heuft Gereon , Friederich Hans-Christoph , Kruse Johannes
Published: September 2023

Background:
In 2017, a reform of the German outpatient psychotherapy guideline was carried out, aiming to reduce waiting times and facilitate low-threshold access. This study analyzes the extent to which the implementation of the two new service elements ‘psychotherapeutic consultation times’ and ‘acute short-term psychotherapeutic interventions’ improved psychotherapeutic care for patients with mental disorders and chronic physical conditions (cMPs), for patients with mental disorders without chronic physical conditions (MnoP), and elderly patients.
Methods:
In a quantitative secondary analysis we analyzed health insurance data of patients with psychotherapy billing codes obtained from the National Association of Statutory Health Insurance Physicians (KBV) for the years 2015-2019, evaluating descriptive statistical parameters for specific patient groups and care services.
Results:
Between 2015 and 2019, the number of mentally ill receiving psychotherapy at least once in the corresponding year increased by 30.7%. Among these, the proportion of cMPs-patients increased from 26.8% to 28.2% (+1.4%), while that of MnoP-patients decreased from 68.3% to 66.4% (-1.9%). The number of elderly people receiving treatment also increased.
Conclusion:
Since increases and decreases in the percentage shares occur evenly over the years investigated, it is questionable whether the reform in 2017 has had a direct influence on these changes.
Registration:
Approval was obtained from the Ethics Committee of the Justus Liebig University Giessen and Marburg – Faculty of Medicine (approval number: AZ 107/20; 6th October 2020). The Study is registered by Register-ID DRKS00020344.
Splenic-preserving laparoscopic distal pancreatectomy Kimura technique versus Warshaw technique: study protocol for a single-center, patient-blinded, randomized controlled clinical trial
Authors: Cai Yu , Chen Qiangxin , Fu Yangzhi , Chen Zixin , Cheng Ke , Gao Pan , Cai He , Meng Lingwei , Wu Shangdi , Li Jun , Zhang Jing , Xia Qi , Ouyang Guo , Li Yongbin , You Jiaying , Wang Xin , Wu Zhong , Cai Yunqiang , Peng Bing
Published: September 2023

Background
Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) has widely been used to manage benign and low-grade malignant tumors of the body and tail of the pancreas. Two commonly employed procedures are the Kimura and Warshaw techniques. However, the comparative benefits of these techniques for patient outcomes remain unclear. Consequently, we have undertaken a randomized controlled clinical trial to comprehensively compare the advantages and disadvantages of the laparoscopic Kimura and Warshaw techniques, and here we present the protocol of this clinical trial.
Methods
This trial is a single-center, parallel-group, patient-blinded, randomized controlled clinical trial. Patients diagnosed with benign or low-grade malignant tumors of the body and tail of the pancreas are recruited. Patients in the test group underwent the laparoscopic Kimura technique, while patients in the control group underwent the laparoscopic Warshaw technique. The primary outcome for short- and long-term follow-up are intraoperative blood loss, and perigastric varices, respectively. Secondary outcomes include spleen preservation, conversion, postoperative mortality, pancreatic fistula, delayed gastric emptying, abdominal infection, reoperation, and splenic infarction.
Conclusion
A prospective interventional clinical randomized controlled trial (RCT) is expected to elucidate the benefits and drawbacks of the laparoscopic Kimura technique compared to the Warshaw technique for managing benign and low-grade malignant tumors of the body and tail of the pancreas.
Trial registration: ChiCTR2200057763
Harnessing Synthetic Active Particles for Physical Reservoir Computing
Authors: Cichos Frank , Wang Xiangzun
Published: September 2023

The processing of information is an indispensable property of living systems realized by networks of active processes with enormous complexity. They have inspired many variants of modern machine learning one of them being reservoir computing, in which stimulating a network of nodes with fading memory enables computations and complex predictions. Reservoirs are implemented on computer hardware, but also on unconventional physical substrates such as mechanical oscillators, spins, or bacteria often summarized as physical reservoir computing.
Here we demonstrate physical reservoir computing with a synthetic active microparticle system that self-organizes from an active and passive component into inherently noisy nonlinear dynamical units. The self-organization and dynamical response of the unit is the result of a delayed propulsion of the microswimmer to a passive target. A reservoir of such units with a self-coupling via the delayed response can perform predictive tasks despite the strong noise resulting from the Brownian motion of the microswimmers. To achieve efficient noise suppression, we introduce a special architecture that uses historical reservoir states for output. Our results pave the way for the study of information processing in synthetic self-organized active particle systems.
The deep water oxygen deficit in stratified shallow seas is mediated by diapycnal mixing
Authors: Rippeth Tom , Shen Sijing , Lincoln Ben , Scannell Brian , Meng Xin , Hopkins Joanne , Sharples Jonathan
Published: September 2023

Seasonally stratified shelf seas are amongst the most biologically productive on the planet. A consequence is that the deeper waters can become oxygen deficient in late summer, with predictions that global warming will accelerate this deficiency. Here we integrate novel turbulence timeseries with vertical profiles of water column properties from a seasonal stratified shelf sea to estimate oxygen and biogeochemical fluxes. The profiles reveal a significant subsurface chlorophyll maximum (SCM). We show for the first time that the associated mid-water oxygen maximum supports both upward and downwards O2 fluxes. The upward flux will out-gas to the atmosphere whilst the downward flux will partially off-set the deep water O2 deficit. These new results show that the fluxes are sensitive to both the water column structure and mixing rates indicating that the development of the seasonal O2 deficit is mediated by diapcynal mixing. Analysis of current shear indicate that whilst tidal mixing supports the downward flux, the upwards flux is dominated by wind driven near-inertial shear. Summer storminess therefore plays an important role in determining the development of the deep water O2 deficit.
Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI.
Authors: Flores-Mireles Ana , Molina Jonathan , Kohler Kurt , Gager Christopher , Andersen Marissa , Wongso Ellsa , Lucas Elizabeth , Paik Andrew , Xu Wei , Donahue Deborah , Bergeron Karla , Klim Aleksandra , Caparon Michael , Hultgren Scott , Desai Alana , Ploplis Victoria , Flick Matthew , Castellino Francis J
Published: September 2023

Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat due to multi-drug resistance development among the CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition in the catheterized bladder, are predisposed to severe CAUTI and septicemia by diverse uropathogens in mono- and poly-microbial infections. Furthermore, we found that E. faecalis, a prevalent CAUTI pathogen, uses the secreted protease, SprE, to induce fibrin accumulation and create a niche ideal for growth, biofilm formation, and persistence during CAUTI.
Scalable Quantum State Tomography with Locally Purified Density Operators and Local Measurements
Authors: Yang Shuo , Guo Yuchen
Published: September 2023

Understanding quantum systems holds significant importance for assessing the performance of quantum hardware and software, as well as exploring quantum control and quantum sensing. An efficient representation of quantum states enables realizing quantum state tomography with minimal measurements. In this study, we propose a new approach to state tomography that uses tensor network representations of mixed states through locally purified density operators and employs a classical optimization algorithm requiring only local measurements. Through numerical simulations of one-dimensional pure and mixed states and two-dimensional random tensor network states up to size $8\times 8$, we demonstrate the efficiency, accuracy, and robustness of our proposed methods. Experiments on the IBM Quantum platform complement these numerical simulations. Our study opens new avenues in quantum state tomography for two-dimensional systems using tensor network formalism.
Exposure to low levels of antidiabetic glibenclamide had no evident adverse effects on intestinal microbial composition and metabolic profiles in amphibian larvae
Authors: Liu Jia-Hui , Meng Qin-Yuan , Chen Yu , Yang Jia-Meng , Gao Jian-Fang , Lu Hongliang
Published: September 2023

Unmetabolized human pharmaceuticals may enter aquatic environments, and potentially exert adverse effects on the survival of non-target organisms. Here, Pelophylax nigromaculatus tadpoles were exposed to different concentrations of antidiabetic glibenclamide (GLB) for 30 days to evaluate its potential ecotoxicological effects in amphibians. The mortality rate of GLB-exposed groups appeared to be lower than that of the control group. Despite not being statistically significant, there was a tendency for a decrease in intestinal microbial diversity after exposure. The abundance of Firmicutes was shown to decrease, but those of other phyla did not in GLB-exposed tadpoles. Some potentially pathogenic bacteria (e.g., Clostridium, Bilophila, Hafnia) decrease unexpectedly, while some beneficial bacteria (e.g., Akkermansia, Faecalibacterium) increased in GLB-exposed tadpoles. Accordingly, GLB-induced changes in intestinal microbial compositions did not seem harmful to animal health. Moreover, minor changes in a few intestinal metabolites were observed after GLB exposure. Overall, our results suggested that exposure to low levels of GLB did not necessarily exert an adverse impact on aquatic organisms.
REPAIR_GETUG P16 - Relapse in previously irradiated Prostate bed: a phase I/II study of stereotactic Ablative reirradiation potentiated by Metformine study protocol
Authors: Joly Alexandre , Blanc-Lapierre Audrey , Rio Emmanuel , Vaugier Loig , Supiot Stéphane , Guimas Valentine
Published: September 2023

Introduction: Salvage prostatic bed radiotherapy (PBRT) is a standard in case of biochemical recurrence following radical prostatectomy (RP) for prostate cancer. The management of isolated prostatic bed recurrence following RP and PBRT is debated. Reirradiation within stereotactic body radiotherapy (SBRT) guided by metabolic imaging could be a relevant option in this case. In parallel, metformin, an economically viable and well-tolerated oral antidiabetic agent, has demonstrated its radiosensitizing properties. This phase I/II clinical trial aims to i) determine the optimal dose for SBRT reirradiation, ii) conduct safety assessments, and iii) evaluate the efficacy of the metformin and SBRT combination.
Methods and Analysis: We conduct a prospective, non-randomized, open-label, multicenter, dose escalation, phase I/II study involving a minimum of 44 patients. Eligible patients must have biochemical recurrence (PSA > 0.2 ng/ml and confirmed ascending trend in at least 2 successive assays), occurring at least 2 years after PBRT and prior RP for prostate cancer (including low, intermediate, and high risk with a single risk factor) and no CTCAE grade >=3 toxicity following PBRT. The recurrence should be visible on MRI and/or PET Choline and/or PET PSMA, without evidence of pelvic lymph node recurrence or metastatic disease. The primary objective of the phase I is to determine the optimal SBRT dose (5×6, 6×6, or 5×5 Gy) based on dose-limiting toxicity (DLT). The dose will be chosen using a time-to-event continual reassessment method based on DLT, defined as CTCAE grade ≥3 gastrointestinal or genitourinary toxicity, or any other grade 4 adverse event. The primary outcome of the phase II is to estimate the efficacy of SBRT in combination with metformin in terms of biological relapse-free survival (bRFS) rate at 3 years. Secondary outcomes include 5-year bRFS rate, early/late genitourinary and gastrointestinal toxicities, quality of life, biochemical response rate, clinical progression-free survival, and overall survival.
Ethics and Dissemination: Ethical approval has been obtained from the Ethics committee "SUD EST III Bron" and the National Agency for the Safety of Medicines (ANSM). The study's findings will be disseminated through publications and conference presentations.
Identification and Validation of Autophagy-Related Genes in Hirschsprung’s Disease
Authors: Yao Ting , Hao Zenghui , Fan Wei , Han Jinbao , Wang Shuyu , Jiang Zaiqun , Wang Yunting , Xu Zhilin
Published: September 2023

Background
Hirschsprung's disease (HSCR) is a congenital disorder characterized by aganglionosis in the intermuscular and submucosal nerve plexus of the intestines, resulting in impaired gastrointestinal function. The exact etiology and pathogenesis of HSCR are yet not fully understood. Accumulating evidence suggests that autophagy plays an important role in the pathogenesis of HSCR, but its specific mechanism needs to be further studied.
Methods
This study used the online Gene Expression Omnibus (GEO) microarray expression profiling datasets GSE96854 and GSE98502. R software was used to identify autophagy-related genes that displayed potential differential expression in HSCR. The differentially expressed autophagy-related genes were analyzed using correlation analysis, tissue-specific gene expression profiling, gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis. Finally, HSCR specimens were utilized for in vitro verification of mRNA levels of key genes using quantitative real-time polymerase chain reaction (qRT-PCR).
Results
A total of 20 autophagy-related genes exhibiting differential expression were identified, comprising 15 up-regulated and five down-regulated genes. Enrichment analysis with the GO and KEGG pathways revealed significant enrichment in pathways associated with the regulation of autophagy, specifically macroautophagy. By conducting PPI network analysis and constructing key modules, we identified nine hub genes. Subsequently, the consistency between SIRT1 expression in the HSCR model and bioinformatics analysis of mRNA chip results was confirmed through qRT-PCR validation.
Conclusion
Through bioinformatics analysis, we identified 20 potential autophagy-related genes associated with HSCR. Among them, the upregulation of SIRT1 expression may impact the occurrence and progression of HSCR by regulating autophagy pathways. This provides a fresh outlook on the etiology of Hirschsprung's disease.
Assessment of artificial intelligence model and manual morphokinetic annotation system as embryo grading methods for successful live birth prediction: a retrospective monocentric study
Authors: Papamentzelopoulou Myrto , Prifti Ilectra-Niki , Mavrogianni Despoina , Tseva Thomais , Soyhan Ntilay , Athanasiou Aikaterini , Athanasiou Antonia , Athanasiou Adamantios , Vogiatzi Paraskevi , Konomos George , Loutradis Dimitrios , Sakellariou Maria
Published: September 2023

Purpose
The introduction of the time-lapse monitoring system (TMS) and the development of predictive algorithms could contribute to the optimal embryos selection for transfer. Therefore, the present study aims at investigating the efficiency of KIDScore and iDAScore systems for blastocyst stage embryos in predicting live birth events.
Methods
The present retrospective study was conducted in a private IVF Unit setting throughout a 10-month period from October 2021 to July 2022, and included the analysis of 429 embryos deriving from 91 IVF/ICSI cycles conducted due to infertility of various etiologies. Embryos incubated at the Embryoscope+ timelapse incubator were analyzed through the established scoring systems: KIDScore and iDAScore®. The main outcome measure was the comparison of the two scoring systems in terms of live birth prediction. Embryos with the higher scores at day 5 (KID5 score/iDA5 score) were transferred or cryopreserved for later use.
Results
Embryos with high KID5 and iDA5 scores positively correlated with the probability of successful live birth, with KID5 score yielding a higher efficiency in predicting a successful reproductive outcome compared to a proportionally high iDA5 score. KID5 demonstrated conservative performance in successfully predicting live birth compared to iDA5 score, indicating that an efficient prediction can be either provided by a relatively lower KID5 score or a relatively higher iDA5 score.
Conclusion
The developed artificial intelligence tools should be implemented in clinical practice in conjunction with the conventional morphological assessment for the conduction of optimized embryo transfer in terms of a successful live birth.
Burkholderia pseudomallei BipD hijacks host KLHL9/KLHL13/CUL3 E3 ligase to ubiquitinate IMMT that initiates mitophagy to evade killing
Authors: Li Qian , Nan Dongqi , Rao Chenglong , Tang Zhiheng , Yang Wenbo , Wu Pan , Chen Jiangao , Xia Yupei , Yan Jingmin , Liu Wenzheng , Hu Zhiqiang , Chen Hai , Liao Yaling , Liu Xiaoyun , Mao Xuhu
Published: September 2023

Mitophagy is critical for mitochondrial quality control and function to clear damaged mitochondria. Here, we found that Burkholderia pseudomallei maneuvered host mitophagy for its intracellular survival through the type Ⅲ secretion system needle tip protein BipD. We identified BipD, interacting with BTB-containing proteins KLHL9 and KLHL13 by binding to the Back and Kelch domains, recruited NEDD8 family RING E3 ligase CUL3 in response to B. pseudomallei infection. Although evidently not involved in regulation of infectious diseases, KLHL9/KLHL13/CUL3 E3 ligase complex was essential for BipD-dependent ubiquitination of mitochondria in mouse macrophages. Mechanistically, we discovered the inner mitochondrial membrane IMMT via host ubiquitome profiling as a new substrate of KLHL9/KLHL13/CUL3 complex. Notably, K63-linked ubiquitination of IMMT K211 was required for initiating host mitophagy, thereby reducing mitochondrial ROS production. Together, our findings reveal a unique mechanism used by bacterial pathogens that hijacks host mitophagy for their survival.
Single-Soma Deep RNA Sequencing of Human Dorsal Root Ganglion Neurons Reveals Novel Molecular and Cellular Mechanisms Underlying Somatosensation
Authors: Luo Wenqin
Published: September 2023

The versatility of somatosensation arises from heterogeneous dorsal root ganglion (DRG) neurons. However, soma transcriptomes of individual human DRG (hDRG) neurons – critical information to decipher their functions – are lacking due to technical difficulties. Here, we developed a novel approach to isolate individual hDRG neuron somas for deep RNA sequencing (RNA-seq). On average, >9,000 unique genes per neuron were detected, and 16 neuronal types were identified. Cross-species analyses revealed remarkable divergence among pain-sensing neurons and the exist-ence of human-specific nociceptor types. Our deep RNA-seq dataset was especially powerful for providing insight into the molecular mechanisms underlying human somatosensation and identify-ing high potential novel drug targets. Our dataset also guided the selection of molecular markers to visualize different types of human afferents and the discovery of novel functional properties using single-cell in vivo electrophysiological recordings. In summary, by employing a novel soma se-quencing method, we generated an unprecedented hDRG neuron atlas, providing new insights into human somatosensation, establishing a critical foundation for translational work, and clarifying human species-specific properties.
Breaking the Echo Chamber Effect in Social Media 🤔: An Impossibility Result
Authors: Avin Chen , Daltrophe Hadassa , Lotker Zvi
Published: September 2023

As scientists, we are proud of our role in developing the current digital age that enables billions of people to communicate rapidly with others via social media. However, when things go wrong, we are also responsible for taking an ethical stand and trying to solve problems, and this work aims to take a step in this direction. Our goal is to set the foundation for a mathematically formal study of how we might regulate social media and, in particular, address the problem of the echo chamber effect.An echo chamber is a closed system where other voices are excluded by omission, causing your beliefs to become amplified or reinforced. In turn, these bubbles can boost social polarization and extreme political views, and, unfortunately, there is strong evidence that echo chambers exist in social media. The fundamental question we try to answer is: how and can a regulation “break” or reduce the echo chamber effect in social media?Sadly, the paper’s main result is an impossibility result: a general regulation function that achieves this goal while obeying the core values of democratic societies (freedom of expression and user privacy) does not exist, which leaves us with hard future choices to make.
QSOX2 Deficiency-induced short stature, gastrointestinal dysmotility and immune dysfunction
Authors: Storr Helen , Maharaj Avinaash , Andrews Afiya , Rybak Anna , Elfeky Reem , Ishida Miho , Joensuu Anni , Kantojärvi Katri , Jia Raina , Perry John , O'Toole Edel , Hwa Vivian
Published: September 2023

Postnatal growth failure is often attributed to dysregulated somatotropin action, however marked genetic and phenotypic heterogeneity exist. We report four patients from two families who present with short stature, immune dysfunction, atopic eczema and gut-associated pathology associated with recessive variants in QSOX2. QSOX2 encodes a nuclear membrane protein linked to disulphide isomerase and oxidoreductase activity. Loss of QSOX2 disrupts GH-mediated STAT5B nuclear translocation despite enhanced GH-induced STAT5B phosphorylation. Moreover, patient-derived dermal fibroblasts demonstrate novel GH-induced mitochondriopathy and reduced mitochondrial membrane potential. We describe a definitive role of QSOX2 in modulating human growth likely due to impairment of STAT5B downstream activity and mitochondrial dynamics leading to growth failure, immune dysregulation and gut dysfunction. Located at the nuclear membrane, QSOX2 acts as a gatekeeper for regulating stabilisation and import of p-STAT5B. Furthermore, our work suggests that therapeutic recombinant IGF-1 may circumvent the GH-mediated STAT5B molecular defect and potentially alleviate organ specific disease.
AI-driven remote sensing enhances Mediterranean seagrass monitoring and conservation to combat climate change and anthropogenic impacts
Authors: Chowdhury Masuma , Martínez-Sansigre Alejo , Mole Maruška , Peleato Eduardo Alonso , Basos Nadiia , Blanco Jose Manuel , Ramirez Maria , Caballero Isabel , Calle Ignacio de la
Published: September 2023

Seagrasses are undergoing widespread loss due to anthropogenic pressure and climate change. Since 1960, the Mediterranean seascape lost 13–50% of the areal extent of its dominant and endemic seagrass- Posidonia oceanica, which regulates its ecosystem. Many conservation and restoration projects failed due to poor site selection and lack of long-term monitoring. Here, we present a fast and efficient operational approach based on a deep-learning artificial intelligence model using Sentinel-2 data to map the spatial extent of the meadows, enabling short and long-term monitoring, and identifying the impacts of natural and human-induced stressors and changes at different timescales. We apply ACOLITE atmospheric correction to the satellite data and use the output to train the model along with the ancillary data and map the extent of the meadows. We apply noise-removing filters to enhance the map quality. We obtain 74–92% of overall accuracy, 72–91% of user’s accuracy, and 81–92% of producer’s accuracy, where high accuracies are observed at 0-25m depth. Our model is easily adaptable to other regions and can produce maps in in-situ data-scarce regions, providing a first-hand overview. Our approach can help restoration practitioners, conservationists and ecosystem managers to make rational decisions to protect this species and promote sustainability.
All-natural 2D nanofluidics as high-efficient osmotic energy generator
Authors: Zhang Qianqian , Tang Jiadong , Wang Yun , Yang Hongyang , Wang Ce , Li Leyuan , Zheng Zilong , Jin Yuhong , Wang Hao , Gu Yifan , Zuo Tieyong
Published: September 2023

Two-dimension nanofluidics constructed based on naturally abundant clay are good candidates for harvesting blue osmotic energy between the sea and river from the perspective of commercialization and environmental sustainability. However, clay-based nanofluidic membranes outputting long-term considerable osmotic power remain extremely challenging to achieve due to the lacks of surface charge and mechanical strength. Here, a two-dimension all-natural nanofluidic (2D-NNF) is developed as robust and high-efficient osmotic energy generator based on an interlocking configuration of the stacked montmorillonite nanosheets (from natural clay) and their intercalated cellulose nanofibers (from natural wood). The formed nano-confined interlamellar channels with abundant surface and space negative charges facilitate the selective and fast hopping transport of cations in the 2D-NNF. This contributes to a remarkable osmotic power output of ~ 8.61 W m−2 by mixing artificial seawater and river water, much higher than all reported state-of-the-art 2D nanofluidics. When the 2D nanofluidic membrane is scaled up to 700 cm2, it could also delivery a uniform high-power output of over 8.0 W m−2 at any test sites as well as a long-term stability for 30 days. Such excellent structure uniformity and stability of the large-area membrane are the basic to achieve real-world applications in natural osmotic energy harvesting. Moreover, the 2D-NNF demonstrates superior economic, environment and energy benefits according to a detailed life cycle assessment (LCA), promising a good sustainability for large-scale and highly-efficient osmotic power generation.
Electrical on-chip detection of propagating surface plasmon with near-field coupling
Authors: Guan Zhiqiang , Li Xiangqian , Liu Weikang , Wang Huijie , Chen Li , Xu Hongxing
Published: September 2023

Plasmonic devices show great potential for integration with the microelectronic chips due to small size and fast speed, in order to create high-performance hybrid optoelectronic circuits. However, the on-chip plasmon detector remains to be explored, for the conventional far field photodetectors are not compatible with plasmon devices because of the complex collecting light path and vertical structure. Here we propose an electrical on-chip plasmon detector by placing an externally biased silicon stripe in the near-field range of plasmon waveguide. Through improving the near-field coupling efficiency and optimizing the plasmon waveguide on SOI, we succeed to achieve a subwavelength plasmon detector where an responsivity of photocurrent is "0.14 mA/W". These results demonstrate the potential of our device as an interface between plasmonic circuits and electronic chips, particularly in applications where the plasmon signals need to be converted into electrical signals for detection or communication.
Lipid metabolism gene ECI2 affects neutrophil extracellular traps by inhibiting ether lipid production to suppress colorectal cancer invasion and metastasis
Authors: LI XUENONG , CHEN LIXIA , DAI PEILING , LIU LEI , CHEN YUJIA , LU YANXIA , Zheng Lin , WANG HAOWEI , YUAN QINZI
Published: September 2023

Abnormalities in ether lipid metabolism as well as neutrophil extracellular trap formation are recently identified as adverse factors affecting tumorigenesis and progression. However, the role of abnormal ether lipid metabolism in colorectal cancer (CRC) evolution has not been reported. Here, we show that the lipid metabolism-related gene, enoyl-CoA delta isomerase 2 (ECI2), plays a tumor-suppressive role in CRC and is negatively associated with poor prognosis in CRC patients. Mechanistically, we demonstrate that ECI2 inhibits ether lipogenesis by restraining the peroxisomal localization of AGPS, the rate-limiting enzyme in ether lipid synthesis. This subsequently suppresses IL-8-mediated neutrophil recruitment and extracellular trap formation, ultimately leading to inhibition of CRC proliferation and metastasis. These findings not only enhance our comprehension of the role of metabolic reprogramming and neutrophil interactions in CRC development, but also offer novel insights for identifying potential diagnostic markers and therapeutic targets for CRC.
Ultraviolet Light Blocking Optically Clear Adhesives for Foldable Displays via Highly Efficient Visible-Light Curing
Authors: Kwon Min Sang , Kim Youngdo , Lee Jaesang
Published: September 2023

The design of a new foldable smartphone's organic light-emitting diode (OLED) panel, developed to reduce power consumption, necessitates the utilization of an advanced optically clear adhesive (OCA) capable of blocking UV light, in addition to its conventional functions of adhesion and strain relief. However, a challenge arises due to the presence of a UV blocking agent within the OCA. This presents a technical limitation, preventing the application of UV curing technology widely utilized in the OCA manufacturing process. Recently, a method for producing UV-blocking OCA through visible-light curing has been proposed, utilizing a new photo-initiating system (PIS). Nevertheless, the curing speed remains significantly slow, which hinders its commercialization. In this study, we have developed a highly efficient photo-initiating system (PIS) that enables the rapid production of UV-blocking OCAs suitable for commercialization under visible-light irradiation. Through a mechanistic analysis of existing PIS, we suggested that the photocatalysts (PCs) in the excited state dissipates upon the occurrence of the triplet-triplet energy transfer (EnT) or energy transfer (ET) with UV blocking agents, thereby impeding the curing rate. To address this, we employed a newly designed PC to reduce both EnT and ET rates when combined with UV absorbers, in comparison to a previously reported PC. Combining the PC with carefully chosen co-initiators, we created a new PIS that generates radicals rapidly through electron transfer. Under 452 nm visible light, we achieved UV-blocking OCAs at a rate approximately 10 times faster than before, while maintaining excellent UV-blocking ability, optical transparency, and viscoelastic properties. In UV-blocking tests, covered OLED device covered with the UV-blocking OCA demonstrated superior UV-blocking performance, indicating broad applications in protecting diverse smart devices with various form factors from UV irradiation.
Cross-species epigenetic regulation of nucleus accumbens KCNN3 transcripts by excessive ethanol drinking.
Authors: Juanes Rita Cervera , Mulholland Patrick , Padula Audrey , Wilhelm Larry , Park Byung , Grant Kathleen , Ferguson Betsy
Published: September 2023

The underlying genetic and epigenetic mechanisms driving functional adaptations in neuronal excitability and excessive alcohol intake are poorly understood. Small-conductance Ca2+-activated K+ (KCa2 or SK) channels encoded by the KCNN family of genes have emerged from preclinical studies as a key contributor to alcohol-induced functional neuroadaptations in alcohol-drinking monkeys and alcohol dependent mice. Here, this cross-species analysis focused on KCNN3 DNA methylation, gene expression, and single nucleotide polymorphisms including alternative promoters in KCNN3 that could influence surface trafficking and function of KCa2 channels. Bisulfite sequencing analysis of the nucleus accumbens tissue from alcohol-drinking monkeys and alcohol dependent mice revealed a differentially methylated region in exon 1A of KCNN3 that overlaps with a predicted promoter sequence. The hypermethylation of KCNN3 in the accumbens paralleled an increase in expression of alternative transcripts that encode apamin-insensitive and dominant-negative KCa2 channel isoforms. A polymorphic repeat in macaque KCNN3 encoded by exon 1 did not correlate with alcohol drinking. At the protein level, KCa2.3 channel expression in the accumbens was significantly reduced in very heavy drinking monkeys. Together, our cross-species findings on epigenetic dysregulation of KCNN3 represent a complex mechanism that utilizes alternative promoters to impact firing of accumbens neurons. Thus, these results provide support for hypermethylation of KCNN3 as a possible key molecular mechanism underlying harmful alcohol intake and alcohol use disorder.
Simultaneous Treatment of Oil and Dye-Contaminated Water by A Novel Composite
Authors: Joshi Deepika P. , Negi Vivek , Bora Neetu
Published: September 2023

Expanded Graphite (EG) has been widely used for treating oil-polluted water. Removal of dye pigments from oily wastewater is the biggest challenge for paint industries. So, the present work focuses on treating simultaneously oil and dye-contaminated water by introducing TiO2/ EG composite. EG samples with the highest exfoliation volume have been prepared by microwave irradiation by optimizing time and tested through an oil adsorption study with different oils. TiO2 NPs have been synthesized by the sol-gel method. A novel EG/TiO2 composite has been synthesized by mixing TiO2 NPs in GIC (precursor) and exfoliating the mixture for the optimized irradiation time. A comparative study of the effect of EG, TiO2 NPs, and EG/TiO2 composite on oil and dye-polluted water has been performed in direct sunlight. Results of UV-visible spectroscopy showed that the addition of TiO2 NPs with EG accomplished the dye degradation along with the adsorption of oil from polluted water.
A novel iterative detection method based on a lattice reduction-aided algorithm for MIMO OFDM systems
Authors: Liu Haitao , Cheng Xuchao , Li Wenqing , Feng Fan , Wang Liguo , Xiao Ying , Fu Shiqi
Published: September 2023

The lattice reduction-aided algorithm has received broad attention from researchers since it operates as a maximum likelihood receiver with better system performance for multiple-input multiple-output orthogonal frequency division multiplexing systems and contains a full diversity. A novel iterative detection algorithm canceling parallel iterations that employ the lattice reduction-aided approach is proposed. Soft information is exchanged through the detector itself. Its iteration occurs inside the detector, which reduces much of the exchange cost between the multiple-input multiple-output orthogonal frequency division multiplexing detector and the turbo decoder. Since the parallel interference cancellation algorithm is constrained by the accuracy of the initial value of the detection, it is easy to form error propagation after several iterations. Due to the lattice reduction-aided algorithm, its performance is approximated with the maximum likelihood algorithm. Therefore, the lattice reduction-aided algorithm is introduced into the parallel interference cancellation algorithm to make its detection algorithm more accurate and overcome the effect of error propagation in the manuscript. Simulation results indicate that the proposed algorithm leads to an improvement of 0.8 dB to 2 dB when the bit error rate is set to 10− 4 when compared to other algorithms.
CICADA: a circRNA effort to Ghost proteome
Authors: Sun Liang , Fan Liyuan , Zhou Xinyuan , Li Mian , Gao Anwei , Yu Haojie , Tian Hui , Liao Liandi , Xu Liyan
Published: September 2023

Coding genes constitute only a small portion of the human genome. Recently, circular RNAs (circRNAs), commonly thought to be noncoding, have been demonstrated to be translated into novel proteins, which might mediate diverse biological processes. However, it remains challenging to identify translatable circRNAs and circRNA-coded proteins. Here, we introduce CICADA, an algorithm capable of evaluating the coding ability of circRNAs and inferring circRNA-coded products. We find that CICADA's performance is highly efficient and cost-effective compared to existing algorithms. Moreover, we used CICADA to successfully identify functional translatable circRNAs in esophageal squamous cell carcinoma and construct circRNA translation profiles across various cancers. CICADA provides an efficient tool to explore the hidden proteome encoded by translatable circRNAs.