bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultra-high spatio-temporal resolution imaging with parallel acquisition-readout structured illumination microscopy (PAR-SIM)
Authors: Xu Xinzhu , Wang Wenyi , Qiao Liang , Fu Yunzhe , Ge Xichuan , Zhao Kun , Zhanghao Karl , Guan Meiling , Chen Xin , Li Meiqi , Jin Dayong , Xi Peng
Published: May 2024

Structured illumination microscopy (SIM) has emerged as a promising super-resolution fluorescence imaging technique, offering diverse configurations and computational strategies to mitigate phototoxicity during real-time imaging of biological specimens. Traditional efforts to enhance system frame rates have concentrated on processing algorithms, like rolling reconstruction or reduced frame reconstruction, or on investments in costly sCMOS cameras with accelerated row readout rates. In this article, we introduce an approach to elevate SIM frame rates and region of interest (ROI) coverage at the hardware level, without necessitating an upsurge in camera expenses or intricate algorithms. Here, parallel acquisition-readout SIM (PAR-SIM) achieves the highest imaging speed for fluorescence imaging at currently available detector sensitivity. By using the full frame-width of the detector through synchronizing the pattern generation and image exposure-readout process, we have achieved a fundamentally stupendous information spatial-temporal flux of 132.9 MPixels · s−1, 9.6-fold that of the latest techniques, with the lowest SNR of −2.11 dB and 100 nm resolution. PAR-SIM demonstrates its proficiency in successfully reconstructing diverse cellular organelles in dual excitations, even under conditions of low signal due to ultra-short exposure times. Notably, mitochondrial dynamic tubulation and ongoing membrane fusion processes have been captured in live COS-7 cell, recorded with PAR-SIM at an impressive 408 Hz. We posit that this novel parallel exposure-readout mode not only augments SIM pattern modulation for superior frame rates but also holds the potential to benefit other complex imaging systems with a strategic controlling approach.
Differences in autophagy marker levels at birth in preterm vs. term infants
Authors: Künstle Noëmi , Gorlanova Olga , Marten Andrea , Müller Loretta , Sharma Pawan , Röösli Martin , Sinues Pablo , Schär Primo , Schürmann David , Rüttimann Céline , Da Silva Sena Carla Rebeca , Nahum Uri , Usemann Jakob , Steinberg Ruth , Yammine Sophie , Schulzke Sven , Latzin Philipp , Frey Urs ,   on behalf of the BILD study group, Beck Fiona , Bovermann Xenia , Casaulta Carmen , Curdy Marion , Da Silva Sena Carla Rebeca , de Hoogh Kees , Frauchiger Bettina , Ho Dac Léa Kim-Mi , Kieninger Elisabeth , Korten Insa , Oestreich Marc-Alexander , Stöcklin Benjamin , Streibel Carmen , Wyler Florian
Published: May 2024

Background

Preterm infants are susceptible to oxidative stress and prone to respiratory diseases. Autophagy is an important defense mechanism against oxidative-stress-induced cell damage and involved in lung development and respiratory morbidity. We hypothesized that autophagy marker levels differ between preterm and term infants.

Methods

In the prospective Basel-Bern Infant Lung Development (BILD) birth cohort we compared cord blood levels of macroautophagy (Beclin-1, LC3B), selective autophagy (p62) and regulation of autophagy (SIRT1) in 64 preterm and 453 term infants.

Results

Beclin-1 and LC3B did not differ between preterm and term infants. However, p62 was higher (0.37, 95% confidence interval (CI) 0.05;0.69 in log2-transformed level, p = 0.025, padj = 0.050) and SIRT1 lower in preterm infants (−0.55, 95% CI −0.78;−0.31 in log2-transformed level, padj < 0.001). Furthermore, p62 decreased (padj-value for smoothing function was 0.018) and SIRT1 increased (0.10, 95% CI 0.07;0.13 in log2-transformed level, padj < 0.001) with increasing gestational age.

Conclusion

Our findings suggest differential levels of key autophagy markers between preterm and term infants. This adds to the knowledge of the sparsely studied field of autophagy mechanisms in preterm infants and might be linked to impaired oxidative stress response, preterm birth, impaired lung development and higher susceptibility to respiratory morbidity in preterm infants.

Impact

To the best of our knowledge, this is the first study to investigate autophagy marker levels between human preterm and term infants in a large population-based sample in cord blood plasma

This study demonstrates differential levels of key autophagy markers in preterm compared to term infants and an association with gestational age

This may be linked to impaired oxidative stress response or developmental aspects and provide bases for future studies investigating the association with respiratory morbidity
Final analysis of a phase II trial of daratumumab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma without transplant
Authors: Derman Benjamin A. , Cooperrider Jennifer , Rosenblatt Jacalyn , Avigan David E. , Rampurwala Murtuza , Barnidge David , Major Ajay , Karrison Theodore , Jiang Ken , Ramsland Aubrianna , Kubicki Tadeusz , Jakubowiak Andrzej J.
Published: May 2024

We evaluated the efficacy and safety of 24 cycles of Dara in combination with carfilzomib (K), lenalidomide (R), and dexamethasone (d) without autologous stem cell transplant (ASCT) in newly diagnosed multiple myeloma (NDMM) irrespective of ASCT eligibility in a single-arm, phase II study. The primary endpoint was the rate of stringent complete response (sCR) and/or measurable residual disease (MRD) < 10−5 by next-generation sequencing (NGS) at the end of cycle 8 (C8). MRD was also assessed on peripheral blood samples using both the EXENT® system and liquid chromatography–mass spectrometry (LC–MS). Forty-two patients entered the treatment phase; forty were evaluable for the primary endpoint. The rate of sCR and/or MRD < 10−5 following C8 was 30/40 (75%), meeting the statistical threshold for efficacy. The 10−6 MRD negative rate improved with treatment beyond C8. Agreement between EXENT® and NGS was high and increased over time; agreement between LC-MS and NGS was lower. The estimated 3-year progression-free survival progression-free survival was 85%, and 3-year overall survival was 95%. Upper respiratory infections occurred in 67% (7% grade 3–4). There were no treatment-related deaths. Extended frontline Dara-KRd induced a high rate of sCR and/or MRD negativity; the rate and depth of MRD negativity improved beyond C8.
Recent advances in structurally elaborate triptycenes, triptycene-containing polymers and assemblies: structures, functions and applications
Authors: Ishiwari Fumitaka , Shoji Yoshiaki , Martin Colin J. , Fukushima Takanori
Published: May 2024

Triptycene, a rigid propeller-shaped molecule, was first synthesized in the early 1940s. More recently, many triptycene-containing polymers and molecular assemblies have been developed for a wide range of applications, including guest recognition, material transport, separation, catalysis, and as device components. The advantages of triptycenes lie in their ability to introduce a variety of functional groups on their three-dimensional backbone, with changes in substitution patterns as well as the type of substituents present having a significant impact on the material properties. In this review, we describe the synthesis of triptycene derivatives and polymers, detailing selected examples of triptycene-containing functional polymers. We also focus on the construction of triptycene-based two-dimensional assemblies and polymers, where space-filling designs based on rigid propeller-shaped skeletons are essential. Through a thorough literature survey, future directions and possibilities for the development of triptycene-containing functional materials are discussed.
Liver and pancreatic-targeted interleukin-22 as a therapeutic for metabolic dysfunction-associated steatohepatitis
Authors: Sajiir Haressh , Keshvari Sahar , Wong Kuan Yau , Borg Danielle J. , Steyn Frederik J. , Fercher Christian , Taylor Karin , Taylor Breten , Barnard Ross T. , Müller Alexandra , Moniruzzaman Md , Miller Gregory , Wang Ran , Fotheringham Amelia , Schreiber Veronika , Sheng Yong Hua , Hancock Janelle Louise , Loo Dorothy , Burr Lucy , Huynh Tony , Lockett Jack , Ramm Grant A. , Macdonald Graeme A. , Prins Johannes B. , McGuckin Michael A. , Hasnain Sumaira Z.
Published: May 2024

Metabolic dysfunction-associated steatohepatitis (MASH) is the most prevalent cause of liver disease worldwide, with a single approved therapeutic. Previous research has shown that interleukin-22 (IL-22) can suppress β-cell stress, reduce local islet inflammation, restore appropriate insulin production, reverse hyperglycemia, and ameliorate insulin resistance in preclinical models of diabetes. In clinical trials long-acting forms of IL-22 have led to increased proliferation in the skin and intestine, where the IL-22RA1 receptor is highly expressed. To maximise beneficial effects whilst reducing the risk of epithelial proliferation and cancer, we designed short-acting IL-22-bispecific biologic drugs that successfully targeted the liver and pancreas. Here we show 10-fold lower doses of these bispecific biologics exceed the beneficial effects of native IL-22 in multiple preclinical models of MASH, without off-target effects. Treatment restores glycemic control, markedly reduces hepatic steatosis, inflammation, and fibrogenesis. These short-acting IL-22-bispecific targeted biologics are a promising new therapeutic approach for MASH.
The evolution of antibiotic resistance islands occurs within the framework of plasmid lineages
Authors: Wang Yiqing , Dagan Tal
Published: May 2024

Bacterial pathogens carrying multidrug resistance (MDR) plasmids are a major threat to human health. The acquisition of antibiotic resistance genes (ARGs) in plasmids is often facilitated by mobile genetic elements that copy or translocate ARGs between DNA molecules. The agglomeration of mobile elements in plasmids generates resistance islands comprising multiple ARGs. However, whether the emergence of resistance islands is restricted to specific MDR plasmid lineages remains understudied. Here we show that the agglomeration of ARGs in resistance islands is biased towards specific large plasmid lineages. Analyzing 6784 plasmids in 2441 Escherichia, Salmonella, and Klebsiella isolates, we quantify that 84% of the ARGs in MDR plasmids are found in resistance islands. We furthermore observe rapid evolution of ARG combinations in resistance islands. Most regions identified as resistance islands are shared among closely related plasmids but rarely among distantly related plasmids. Our results suggest the presence of barriers for the dissemination of ARGs between plasmid lineages, which are related to plasmid genetic properties, host range and the plasmid evolutionary history. The agglomeration of ARGs in plasmids is attributed to the workings of mobile genetic elements that operate within the framework of existing plasmid lineages.
Breast cancer cell-secreted miR-199b-5p hijacks neurometabolic coupling to promote brain metastasis
Authors: Ruan Xianhui , Yan Wei , Cao Minghui , Daza Ray Anthony M. , Fong Miranda Y. , Yang Kaifu , Wu Jun , Liu Xuxiang , Palomares Melanie , Wu Xiwei , Li Arthur , Chen Yuan , Jandial Rahul , Spitzer Nicholas C. , Hevner Robert F. , Wang Shizhen Emily
Published: May 2024

Breast cancer metastasis to the brain is a clinical challenge rising in prevalence. However, the underlying mechanisms, especially how cancer cells adapt a distant brain niche to facilitate colonization, remain poorly understood. A unique metabolic feature of the brain is the coupling between neurons and astrocytes through glutamate, glutamine, and lactate. Here we show that extracellular vesicles from breast cancer cells with a high potential to develop brain metastases carry high levels of miR-199b-5p, which shows higher levels in the blood of breast cancer patients with brain metastases comparing to those with metastatic cancer in other organs. miR-199b-5p targets solute carrier transporters (SLC1A2/EAAT2 in astrocytes and SLC38A2/SNAT2 and SLC16A7/MCT2 in neurons) to hijack the neuron–astrocyte metabolic coupling, leading to extracellular retention of these metabolites and promoting cancer cell growth. Our findings reveal a mechanism through which cancer cells of a non-brain origin reprogram neural metabolism to fuel brain metastases.
Haplotype-resolved gapless genome and chromosome segment substitution lines facilitate gene identification in wild rice
Authors: Huang Jingfen , Zhang Yilin , Li Yapeng , Xing Meng , Lei Cailin , Wang Shizhuang , Nie Yamin , Wang Yanyan , Zhao Mingchao , Han Zhenyun , Sun Xianjun , Zhou Han , Wang Yan , Zheng Xiaoming , Xiao Xiaorong , Fan Weiya , Liu Ziran , Guo Wenlong , Zhang Lifang , Cheng Yunlian , Qian Qian , He Hang , Yang Qingwen , Qiao Weihua
Published: May 2024

The abundant genetic variation harbored by wild rice (Oryza rufipogon) has provided a reservoir of useful genes for rice breeding. However, the genome of wild rice has not yet been comprehensively assessed. Here, we report the haplotype-resolved gapless genome assembly and annotation of wild rice Y476. In addition, we develop two sets of chromosome segment substitution lines (CSSLs) using Y476 as the donor parent and cultivated rice as the recurrent parents. By analyzing the gapless reference genome and CSSL population, we identify 254 QTLs associated with agronomic traits, biotic and abiotic stresses. We clone a receptor-like kinase gene associated with rice blast resistance and confirm its wild rice allele improves rice blast resistance. Collectively, our study provides a haplotype-resolved gapless reference genome and demonstrates a highly efficient platform for gene identification from wild rice.
Low-temperature strain-free encapsulation for perovskite solar cells and modules passing multifaceted accelerated ageing tests
Authors: Mariani Paolo , Molina-García Miguel Ángel , Barichello Jessica , Zappia Marilena Isabella , Magliano Erica , Castriotta Luigi Angelo , Gabatel Luca , Thorat Sanjay Balkrishna , Del Rio Castillo Antonio Esaú , Drago Filippo , Leonardi Enrico , Pescetelli Sara , Vesce Luigi , Di Giacomo Francesco , Matteocci Fabio , Agresti Antonio , De Giorgi Nicole , Bellani Sebastiano , Di Carlo Aldo , Bonaccorso Francesco
Published: May 2024

Perovskite solar cells promise to be part of the future portfolio of photovoltaic technologies, but their instability is slow down their commercialization. Major stability assessments have been recently achieved but reliable accelerated ageing tests on beyond small-area cells are still poor. Here, we report an industrial encapsulation process based on the lamination of highly viscoelastic semi-solid/highly viscous liquid adhesive atop the perovskite solar cells and modules. Our encapsulant reduces the thermomechanical stresses at the encapsulant/rear electrode interface. The addition of thermally conductive two-dimensional hexagonal boron nitride into the polymeric matrix improves the barrier and thermal management properties of the encapsulant. Without any edge sealant, encapsulated devices withstood multifaceted accelerated ageing tests, retaining >80% of their initial efficiency. Our encapsulation is applicable to the most established cell configurations (direct/inverted, mesoscopic/planar), even with temperature-sensitive materials, and extended to semi-transparent cells for building-integrated photovoltaics and Internet of Things systems.
Mucus production, host-microbiome interactions, hormone sensitivity, and innate immune responses modeled in human cervix chips
Authors: Izadifar Zohreh , Cotton Justin , Chen Siyu , Horvath Viktor , Stejskalova Anna , Gulati Aakanksha , LoGrande Nina T. , Budnik Bogdan , Shahriar Sanjid , Doherty Erin R. , Xie Yixuan , To Tania , Gilpin Sarah E. , Sesay Adama M. , Goyal Girija , Lebrilla Carlito B. , Ingber Donald E.
Published: May 2024

Modulation of the cervix by steroid hormones and commensal microbiome play a central role in the health of the female reproductive tract. Here we describe organ-on-a-chip (Organ Chip) models that recreate the human cervical epithelial-stromal interface with a functional epithelial barrier and production of mucus with biochemical and hormone-responsive properties similar to living cervix. When Cervix Chips are populated with optimal healthy versus dysbiotic microbial communities (dominated by Lactobacillus crispatus and Gardnerella vaginalis, respectively), significant differences in tissue innate immune responses, barrier function, cell viability, proteome, and mucus composition are observed that are similar to those seen in vivo. Thus, human Cervix Organ Chips represent physiologically relevant in vitro models to study cervix physiology and host-microbiome interactions, and hence may be used as a preclinical testbed for development of therapeutic interventions to enhance women’s health.
Catalytic asymmetric synthesis of planar-chiral dianthranilides via (Dynamic) kinetic resolution
Authors: Guan Chun-Yan , Zou Shuai , Luo Can , Li Zhen-Yu , Huang Mingjie , Huang Lihua , Xiao Xiao , Wei Donghui , Wang Min-Can , Mei Guang-Jian
Published: May 2024

Chirality constitutes an inherent attribute of nature. The catalytic asymmetric synthesis of molecules with central, axial, and helical chirality is a topic of intense interest and is becoming a mature field of research. However, due to the difficulty in synthesis and the lack of a prototype, less attention has been given to planar chirality arising from the destruction of symmetry on a single planar ring. Herein, we report the catalytic asymmetric synthesis of planar-chiral dianthranilides, a unique class of tub-shaped eight-membered cyclic dilactams. This protocol is enabled by cinchona alkaloid-catalyzed (dynamic) kinetic resolution. Under mild conditions, various C2- or C1-symmetric planar-chiral dianthranilides have been readily prepared in high yields with excellent enantioselectivity. These dianthranilides can serve as an addition to the family of planar-chiral molecules. Its synthetic value has been demonstrated by kinetic resolution of racemic amines via acyl transfer, enantiodivergent synthesis of the natural product eupolyphagin, and preliminary antitumor activity studies.
Development of a novel non-invasive biomarker panel for hepatic fibrosis in MASLD
Authors: Verschuren Lars , Mak Anne Linde , van Koppen Arianne , Özsezen Serdar , Difrancesco Sonia , Caspers Martien P. M. , Snabel Jessica , van der Meer David , van Dijk Anne-Marieke , Rashu Elias Badal , Nabilou Puria , Werge Mikkel Parsberg , van Son Koen , Kleemann Robert , Kiliaan Amanda J. , Hazebroek Eric J. , Boonstra André , Brouwer Willem P. , Doukas Michail , Gupta Saurabh , Kluft Cornelis , Nieuwdorp Max , Verheij Joanne , Gluud Lise Lotte , Holleboom Adriaan G. , Tushuizen Maarten E. , Hanemaaijer Roeland
Published: May 2024

Accurate non-invasive biomarkers to diagnose metabolic dysfunction-associated steatotic liver disease (MASLD)-related fibrosis are urgently needed. This study applies a translational approach to develop a blood-based biomarker panel for fibrosis detection in MASLD. A molecular gene expression signature identified from a diet-induced MASLD mouse model (LDLr−/−.Leiden) is translated into human blood-based biomarkers based on liver biopsy transcriptomic profiles and protein levels in MASLD patient serum samples. The resulting biomarker panel consists of IGFBP7, SSc5D and Sema4D. LightGBM modeling using this panel demonstrates high accuracy in predicting MASLD fibrosis stage (F0/F1: AUC = 0.82; F2: AUC = 0.89; F3/F4: AUC = 0.87), which is replicated in an independent validation cohort. The overall accuracy of the model outperforms predictions by the existing markers Fib-4, APRI and FibroScan. In conclusion, here we show a disease mechanism-related blood-based biomarker panel with three biomarkers which is able to identify MASLD patients with mild or advanced hepatic fibrosis with high accuracy.
Rapid response of fly populations to gene dosage across development and generations
Authors: Li Xueying C. , Gandara Lautaro , Ekelöf Måns , Richter Kerstin , Alexandrov Theodore , Crocker Justin
Published: May 2024

Although the effects of genetic and environmental perturbations on multicellular organisms are rarely restricted to single phenotypic layers, our current understanding of how developmental programs react to these challenges remains limited. Here, we have examined the phenotypic consequences of disturbing the bicoid regulatory network in early Drosophila embryos. We generated flies with two extra copies of bicoid, which causes a posterior shift of the network’s regulatory outputs and a decrease in fitness. We subjected these flies to EMS mutagenesis, followed by experimental evolution. After only 8–15 generations, experimental populations have normalized patterns of gene expression and increased survival. Using a phenomics approach, we find that populations were normalized through rapid increases in embryo size driven by maternal changes in metabolism and ovariole development. We extend our results to additional populations of flies, demonstrating predictability. Together, our results necessitate a broader view of regulatory network evolution at the systems level.
Temporal interference stimulation disrupts spike timing in the primate brain
Authors: Vieira Pedro G. , Krause Matthew R. , Pack Christopher C.
Published: May 2024

Electrical stimulation can regulate brain activity, producing clear clinical benefits, but focal and effective neuromodulation often requires surgically implanted electrodes. Recent studies argue that temporal interference (TI) stimulation may provide similar outcomes non-invasively. During TI, scalp electrodes generate multiple electrical fields in the brain, modulating neural activity only at their intersection. Despite considerable enthusiasm for this approach, little empirical evidence demonstrates its effectiveness, especially under conditions suitable for human use. Here, using single-neuron recordings in non-human primates, we establish that TI reliably alters the timing, but not the rate, of spiking activity. However, we show that TI requires strategies—high carrier frequencies, multiple electrodes, and amplitude-modulated waveforms—that also limit its effectiveness. Combined, these factors make TI 80 % weaker than other forms of non-invasive brain stimulation. Although unlikely to cause widespread neuronal entrainment, TI may be ideal for disrupting pathological oscillatory activity, a hallmark of many neurological disorders.
Observation of phonon Stark effect
Authors: Huang Zhiheng , Bai Yunfei , Zhao Yanchong , Liu Le , Zhao Xuan , Wu Jiangbin , Watanabe Kenji , Taniguchi Takashi , Yang Wei , Shi Dongxia , Xu Yang , Zhang Tiantian , Zhang Qingming , Tan Ping-Heng , Sun Zhipei , Meng Sheng , Wang Yaxian , Du Luojun , Zhang Guangyu
Published: May 2024

Stark effect, the electric-field analogue of magnetic Zeeman effect, is one of the celebrated phenomena in modern physics and appealing for emergent applications in electronics, optoelectronics, as well as quantum technologies. While in condensed matter it has prospered only for excitons, whether other collective excitations can display Stark effect remains elusive. Here, we report the observation of phonon Stark effect in a two-dimensional quantum system of bilayer 2H-MoS2. The longitudinal acoustic phonon red-shifts linearly with applied electric fields and can be tuned over ~1 THz, evidencing giant Stark effect of phonons. Together with many-body ab initio calculations, we uncover that the observed phonon Stark effect originates fundamentally from the strong coupling between phonons and interlayer excitons (IXs). In addition, IX-mediated electro-phonon intensity modulation up to ~1200% is discovered for infrared-active phonon A2u. Our results unveil the exotic phonon Stark effect and effective phonon engineering by IX-mediated mechanism, promising for a plethora of exciting many-body physics and potential technological innovations.
Low-frequency conductivity of low wear high-entropy alloys
Authors: Yeh Cheng-Hsien , Hsu Wen-Dung , Liu Bernard Haochih , Yang Chan-Shan , Kuan Chen-Yun , Chang Yuan-Chun , Huang Kai-Sheng , Jhang Song-Syun , Lu Chia-Yen , Liaw Peter K. , Shih Chuan-Feng
Published: May 2024

High-entropy alloys (HEAs) provide new research avenues for alloy combinations in the periodic table, opening numerous possibilities in novel-alloy applications. However, their electrical characteristics have been relatively underexplored. The challenge in establishing an HEA electrical conductivity model lies in the changes in electronic characteristics caused by lattice distortion and complexity of nanostructures. Here we show a low-frequency electrical conductivity model for the Nb-Mo-Ta-W HEA system. The cocktail effect is found to explain trends in electrical-conductivity changes in HEAs, while the magnitude of the reduction is understood by the calculated plasma frequency, free electron density, and measured relaxation time by terahertz spectroscopy. As a result, the refractory HEA Nb15Mo35Ta15W35 thin film exhibits both high hardness and excellent conductivity. This combination of Nb15Mo35Ta15W35 makes it suitable for applications in atomic force microscopy probe coating, significantly improving their wear resistance and atomic-scale image resolution.
Non-invasive stimulation of the human striatum disrupts reinforcement learning of motor skills
Authors: Vassiliadis Pierre , Beanato Elena , Popa Traian , Windel Fabienne , Morishita Takuya , Neufeld Esra , Duque Julie , Derosiere Gerard , Wessel Maximilian J. , Hummel Friedhelm C.
Published: May 2024

Reinforcement feedback can improve motor learning, but the underlying brain mechanisms remain underexplored. In particular, the causal contribution of specific patterns of oscillatory activity within the human striatum is unknown. To address this question, we exploited a recently developed non-invasive deep brain stimulation technique called transcranial temporal interference stimulation (tTIS) during reinforcement motor learning with concurrent neuroimaging, in a randomized, sham-controlled, double-blind study. Striatal tTIS applied at 80 Hz, but not at 20 Hz, abolished the benefits of reinforcement on motor learning. This effect was related to a selective modulation of neural activity within the striatum. Moreover, 80 Hz, but not 20 Hz, tTIS increased the neuromodulatory influence of the striatum on frontal areas involved in reinforcement motor learning. These results show that tTIS can non-invasively and selectively modulate a striatal mechanism involved in reinforcement learning, expanding our tools for the study of causal relationships between deep brain structures and human behaviour.
Van der Waals polarity-engineered 3D integration of 2D complementary logic
Authors: Guo Yimeng , Li Jiangxu , Zhan Xuepeng , Wang Chunwen , Li Min , Zhang Biao , Wang Zirui , Liu Yueyang , Yang Kaining , Wang Hai , Li Wanying , Gu Pingfan , Luo Zhaoping , Liu Yingjia , Liu Peitao , Chen Bo , Watanabe Kenji , Taniguchi Takashi , Chen Xing-Qiu , Qin Chengbing , Chen Jiezhi , Sun Dongming , Zhang Jing , Wang Runsheng , Liu Jianpeng , Ye Yu , Li Xiuyan , Hou Yanglong , Zhou Wu , Wang Hanwen , Han Zheng
Published: May 2024

Vertical three-dimensional integration of two-dimensional (2D) semiconductors holds great promise, as it offers the possibility to scale up logic layers in the z axis1–3. Indeed, vertical complementary field-effect transistors (CFETs) built with such mixed-dimensional heterostructures4,5, as well as hetero-2D layers with different carrier types6–8, have been demonstrated recently. However, so far, the lack of a controllable doping scheme (especially p-doped WSe2 (refs. 9–17) and MoS2 (refs. 11,18–28)) in 2D semiconductors, preferably in a stable and non-destructive manner, has greatly impeded the bottom-up scaling of complementary logic circuitries. Here we show that, by bringing transition metal dichalcogenides, such as MoS2, atop a van der Waals (vdW) antiferromagnetic insulator chromium oxychloride (CrOCl), the carrier polarity in MoS2 can be readily reconfigured from n- to p-type via strong vdW interfacial coupling. The consequential band alignment yields transistors with room-temperature hole mobilities up to approximately 425 cm2 V−1 s−1, on/off ratios reaching 106 and air-stable performance for over one year. Based on this approach, vertically constructed complementary logic, including inverters with 6 vdW layers, NANDs with 14 vdW layers and SRAMs with 14 vdW layers, are further demonstrated. Our findings of polarity-engineered p- and n-type 2D semiconductor channels with and without vdW intercalation are robust and universal to various materials and thus may throw light on future three-dimensional vertically integrated circuits based on 2D logic gates.
Structural basis for pegRNA-guided reverse transcription by a prime editor
Authors: Shuto Yutaro , Nakagawa Ryoya , Zhu Shiyou , Hoki Mizuki , Omura Satoshi N. , Hirano Hisato , Itoh Yuzuru , Zhang Feng , Nureki Osamu
Published: May 2024

The prime editor system composed of Streptococcus pyogenes Cas9 nickase (nSpCas9) and engineered Moloney murine leukaemia virus reverse transcriptase (M-MLV RT) collaborates with a prime editing guide RNA (pegRNA) to facilitate a wide variety of precise genome edits in living cells1. However, owing to a lack of structural information, the molecular mechanism of pegRNA-guided reverse transcription by the prime editor remains poorly understood. Here we present cryo-electron microscopy structures of the SpCas9–M-MLV RTΔRNaseH–pegRNA–target DNA complex in multiple states. The termination structure, along with our functional analysis, reveals that M-MLV RT extends reverse transcription beyond the expected site, resulting in scaffold-derived incorporations that cause undesired edits at the target loci. Furthermore, structural comparisons among the pre-initiation, initiation and elongation states show that M-MLV RT remains in a consistent position relative to SpCas9 during reverse transcription, whereas the pegRNA–synthesized DNA heteroduplex builds up along the surface of SpCas9. On the basis of our structural insights, we rationally engineered pegRNA variants and prime-editor variants in which M-MLV RT is fused within SpCas9. Collectively, our findings provide structural insights into the stepwise mechanism of prime editing, and will pave the way for the development of a versatile prime editing toolbox.
A bistable inhibitory optoGPCR for multiplexed optogenetic control of neural circuits
Authors: Wietek Jonas , Nozownik Adrianna , Pulin Mauro , Saraf-Sinik Inbar , Matosevich Noa , Gowrishankar Raajaram , Gat Asaf , Malan Daniela , Brown Bobbie J. , Dine Julien , Imambocus Bibi Nusreen , Levy Rivka , Sauter Kathrin , Litvin Anna , Regev Noa , Subramaniam Suraj , Abrera Khalid , Summarli Dustin , Goren Eva Madeline , Mizrachi Gili , Bitton Eyal , Benjamin Asaf , Copits Bryan A. , Sasse Philipp , Rost Benjamin R. , Schmitz Dietmar , Bruchas Michael R. , Soba Peter , Oren-Suissa Meital , Nir Yuval , Wiegert J. Simon , Yizhar Ofer
Published: May 2024

Information is transmitted between brain regions through the release of neurotransmitters from long-range projecting axons. Understanding how the activity of such long-range connections contributes to behavior requires efficient methods for reversibly manipulating their function. Chemogenetic and optogenetic tools, acting through endogenous G-protein-coupled receptor pathways, can be used to modulate synaptic transmission, but existing tools are limited in sensitivity, spatiotemporal precision or spectral multiplexing capabilities. Here we systematically evaluated multiple bistable opsins for optogenetic applications and found that the Platynereis dumerilii ciliary opsin (PdCO) is an efficient, versatile, light-activated bistable G-protein-coupled receptor that can suppress synaptic transmission in mammalian neurons with high temporal precision in vivo. PdCO has useful biophysical properties that enable spectral multiplexing with other optogenetic actuators and reporters. We demonstrate that PdCO can be used to conduct reversible loss-of-function experiments in long-range projections of behaving animals, thereby enabling detailed synapse-specific functional circuit mapping.
Respiratory muscle strength can improve the prognostic assessment in COPD
Authors: Silva Rebeca Nunes , Goulart Cássia da Luz , de Oliveira Claudio R. , Mendes Renata Gonçalves , Arena Ross , Myers Jonathan , Borghi-Silva Audrey
Published: May 2024

Impaired lung function, respiratory muscle weakness and exercise intolerance are present in COPD and contribute to poor prognosis. However, the contribution of the combination of these manifestations to define prognosis in COPD is still unknown. This study aimed to define cut-off points for both inspiratory and expiratory muscle strength (MIP and MEP, respectively) for mortality prediction over 42-months in patients with COPD, and to investigate its combination with other noninvasive established prognostic measures (FEV1, V̇O2peak and 6MWD) to improve risk identification. Patients with COPD performed pulmonary function, respiratory muscle strength, six-minute walk and cardiopulmonary exercise tests, and were followed over 42 months to analyze all-cause mortality. A total of 79 patients were included. The sample was mostly (91.1%) comprised of severe (n = 37) and very severe (n = 34) COPD, and 43 (54%) patients died during the follow-up period. Cut-points of ≤ 55 and ≤ 80 cmH2O for MIP and MEP, respectively, were associated with increased risk of death (log-rank p = 0.0001 for both MIP and MEP) in 42 months. Furthermore, MIP and MEP substantially improved the mortality risk assessment when combined with FEV1 (log-ranks p = 0.006 for MIP and p < 0.001 for MEP), V̇O2peak (log-rank: p < 0.001 for both MIP and MEP) and 6MWD (log-ranks: p = 0.005 for MIP; p = 0.015 for MEP). Thus, patients severely affected by COPD presenting MIP ≤ 55 and/or MEP ≤ 80 cmH2O are at increased risk of mortality. Furthermore, MIP and MEP substantially improve the mortality risk assessment when combined with FEV1, V̇O2peak and 6MWD in patients with COPD.
Decoding bee cleptoparasitism through comparative transcriptomics of Coelioxoides waltheriae and its host Tetrapedia diversipes
Authors: Ricardo Paulo Cseri , Arias Maria Cristina , de Souza Araujo Natalia
Published: May 2024

Cleptoparasitism, also known as brood parasitism, is a widespread strategy among bee species in which the parasite lays eggs into the nests of the host species. Even though this behavior has significant ecological implications for the dynamics of several species, little is known about the molecular pathways associated with cleptoparasitism. To shed some light on this issue, we used gene expression data to perform a comparative analysis between two solitary neotropical bees: Coelioxoides waltheriae, an obligate parasite, and their specific host Tetrapedia diversipes. We found that ortholog genes involved in signal transduction, sensory perception, learning, and memory formation were differentially expressed between the cleptoparasite and the host. We hypothesize that these genes and their associated molecular pathways are engaged in cleptoparasitism-related processes and, hence, are appealing subjects for further investigation into functional and evolutionary aspects of cleptoparasitism in bees.
Resident marine sportfishing effort in the United States varied non-monotonically with COVID policy stringency
Authors: Gordan Alexander , Carter David , Liese Christopher
Published: May 2024

Governments responded to the Covid-19 pandemic with different policies to curtail the spread of the virus. We show how sportfishing levels are related to the stringency of Covid-19 policies. Specifically, we relate the total number of resident sportfishing trips taken each month in each of 16 U.S. states to a state-level index of COVID policy stringency. We model the number of recreational fishing trips taken in each state-month using a fixed effect Poisson regression model with state-specific seasonality and time trends. We estimate separate models for different fishing modes, and find that for fishing trips taken on private boats the number of trips may have increased by approximately 20% at moderate levels of stringency, while at high levels of stringency like those experienced in many states in March and April of 2020, trips may have stayed constant or declined by 10–20%. Similar inverse-U shaped relationships between trips and stringency are found for fishing trips from the shore and from charter boats.
Ensemble machine learning for predicting in-hospital mortality in Asian women with ST-elevation myocardial infarction (STEMI)
Authors: Kasim Sazzli , Amir Rudin Putri Nur Fatin , Malek Sorayya , Ibrahim Khairul Shafiq , Wan Ahmad Wan Azman , Fong Alan Yean Yip , Lin Wan Yin , Aziz Firdaus , Ibrahim Nurulain
Published: May 2024

The accurate prediction of in-hospital mortality in Asian women after ST-Elevation Myocardial Infarction (STEMI) remains a crucial issue in medical research. Existing models frequently neglect this demographic's particular attributes, resulting in poor treatment outcomes. This study aims to improve the prediction of in-hospital mortality in multi-ethnic Asian women with STEMI by employing both base and ensemble machine learning (ML) models. We centred on the development of demographic-specific models using data from the Malaysian National Cardiovascular Disease Database spanning 2006 to 2016. Through a careful iterative feature selection approach that included feature importance and sequential backward elimination, significant variables such as systolic blood pressure, Killip class, fasting blood glucose, beta-blockers, angiotensin-converting enzyme inhibitors (ACE), and oral hypoglycemic medications were identified. The findings of our study revealed that ML models with selected features outperformed the conventional Thrombolysis in Myocardial Infarction (TIMI) Risk score, with area under the curve (AUC) ranging from 0.60 to 0.93 versus TIMI's AUC of 0.81. Remarkably, our best-performing ensemble ML model was surpassed by the base ML model, support vector machine (SVM) Linear with SVM selected features (AUC: 0.93, CI: 0.89–0.98 versus AUC: 0.91, CI: 0.87–0.96). Furthermore, the women-specific model outperformed a non-gender-specific STEMI model (AUC: 0.92, CI: 0.87–0.97). Our findings demonstrate the value of women-specific ML models over standard approaches, emphasizing the importance of continued testing and validation to improve clinical care for women with STEMI.
Nascent chains derived from a foldable protein sequence interact with specific ribosomal surface sites near the exit tunnel
Authors: Masse Meranda M. , Guzman-Luna Valeria , Varela Angela E. , Mahfuza Shapla Ummay , Hutchinson Rachel B. , Srivastava Aniruddha , Wei Wanting , Fuchs Andrew M. , Cavagnero Silvia
Published: May 2024

In order to become bioactive, proteins must be translated and protected from aggregation during biosynthesis. The ribosome and molecular chaperones play a key role in this process. Ribosome-bound nascent chains (RNCs) of intrinsically disordered proteins and RNCs bearing a signal/arrest sequence are known to interact with ribosomal proteins. However, in the case of RNCs bearing foldable protein sequences, not much information is available on these interactions. Here, via a combination of chemical crosslinking and time-resolved fluorescence-anisotropy, we find that nascent chains of the foldable globin apoHmp1–140 interact with ribosomal protein L23 and have a freely-tumbling non-interacting N-terminal compact region comprising 63–94 residues. Longer RNCs (apoHmp1–189) also interact with an additional yet unidentified ribosomal protein, as well as with chaperones. Surprisingly, the apparent strength of RNC/r-protein interactions does not depend on nascent-chain sequence. Overall, foldable nascent chains establish and expand interactions with selected ribosomal proteins and chaperones, as they get longer. These data are significant because they reveal the interplay between independent conformational sampling and nascent-protein interactions with the ribosomal surface.
Changes in sleep patterns in primary care workers during the first wave of the COVID-19 pandemic in 2022 in Shanghai: a cross-sectional study
Authors: Cao Wenshu , Li Xiaoting , Yan Yini , Zhou Jianfeng , Ye Jizhong , Lv Qiwei
Published: May 2024

The coronavirus disease (COVID-19) pandemic has significantly affected the sleep health of healthcare workers (HCWs); however, no studies have assessed this effect in primary HCWs. This cross-sectional, web-based study explored the prevalence and factors associated with sleep disorders among primary HCWs during the first COVID-19 outbreak in Shanghai from 12 July to 15 August 2022. Sociodemographic and work-related characteristics, various sleep dimensions, and exposure to patients with COVID-19 were assessed. They were screened for common mental disorders (depression, burnout, and stress). Overall, 313 primary HCWs were recruited. At least one sleep dimension in 84% of respondents deteriorated compared with that observed pre-pandemic; sleep quality (decline of 66%) and daytime sleepiness (increase of 56%) were the most affected domains. After excluding 145 primary HCWs with pre-pandemic ‘poor sleep’, depression (odds ratio [OR] 3.08; 95% confidence interval [CI] 1.59–5.98), weekly burnout symptoms (OR 2.57; 95% CI 1.32–5.03), and high psychological stress (OR 4.51; 95% CI 2.09–9.72) were associated with poor sleep patterns during the pandemic. After adjusting for significant differences between groups, for every 1-point increase in the Perceived Stress Scale score, an associated 12% increased risk of poor sleep (adjusted OR 1.12; 95% CI 1.05–1.21; p = 0.002) was observed. Most primary HCWs showed significant worsening of sleep quality, with increases in daytime sleepiness during the first wave of the COVID-19 pandemic in Shanghai. HCWs with high stress levels were at greater risks of sleep disorders.
Identification of modules and key genes associated with breast cancer subtypes through network analysis
Authors: Mares-Quiñones María Daniela , Galán-Vásquez Edgardo , Pérez-Rueda Ernesto , Pérez-Ishiwara D. Guillermo , Medel-Flores María Olivia , Gómez-García María del Consuelo
Published: May 2024

Breast cancer is the most common malignancy in women around the world. Intratumor and intertumoral heterogeneity persist in mammary tumors. Therefore, the identification of biomarkers is essential for the treatment of this malignancy. This study analyzed 28,143 genes expressed in 49 breast cancer cell lines using a Weighted Gene Co-expression Network Analysis to determine specific target proteins for Basal A, Basal B, Luminal A, Luminal B, and HER2 ampl breast cancer subtypes. Sixty-five modules were identified, of which five were characterized as having a high correlation with breast cancer subtypes. Genes overexpressed in the tumor were found to participate in the following mechanisms: regulation of the apoptotic process, transcriptional regulation, angiogenesis, signaling, and cellular survival. In particular, we identified the following genes, considered as hubs: IFIT3, an inhibitor of viral and cellular processes; ETS1, a transcription factor involved in cell death and tumorigenesis; ENSG00000259723 lncRNA, expressed in cancers; AL033519.3, a hypothetical gene; and TMEM86A, important for regulating keratinocyte membrane properties, considered as a key in Basal A, Basal B, Luminal A, Luminal B, and HER2 ampl breast cancer subtypes, respectively. The modules and genes identified in this work can be used to identify possible biomarkers or therapeutic targets in different breast cancer subtypes.
Activation of peroxymonosulfate with ZIF-67-derived Co/N-doped porous carbon nanocubes for the degradation of Congo red dye
Authors: Khamis Aya , Mahmoud Aya S. , El Naga Ahmed O. Abo , Shaban Seham A. , Youssef Nadia A.
Published: May 2024

In this study, porous carbon nanocubes encapsulated magnetic metallic Co nanoparticles (denoted as Co@N-PCNC) was prepared via pyrolyzing ZIF-67 nanocubes precursor at 600 °C and characterized by various technologies. It was used to activate peroxymonosulfate (PMS) to degrade Congo red (CR) dye efficiently. Over 98.45% of 50 mg L−1 CR was degraded using 0.033 mM PMS activated by 75 mg L−1 Co@N-PCNC within 12 min. The free radical quenching experiments were performed to reveal the nature of the reactive oxygen species radicals generated throughout the catalytic oxidation of CR. The effects of common inorganic anions and the water matrix on CR removal were studied. Moreover, the results of the kinetic study revealed the suitability of the pseudo-first-order and Langmuir–Hinshelwood kinetic models for illustrating CR degradation using the Co@N-PCNC/PMS system. Ultimately, the Co@N-PCNC displayed good operational stability, and after five cycles, the CR removal rate can still maintain over 90% after 12 min.
Intravenous high-dose anakinra drops venous thrombosis and acute coronary syndrome in severe and critical COVID-19 patients: a propensity score matched study
Authors: Çakmak Ramazan , Yüce Servet , Ay Mustafa , Uyar Muhammed Hamdi , Kılıç Muhammed İkbal , Bektaş Murat
Published: May 2024

In our study, we aimed to evaluate the effect of high-dose intravenous anakinra treatment on the development of thrombotic events in severe and critical COVID-19 patients. This retrospective observational study was conducted at a tertiary referral center in Aksaray, Turkey. The study population consisted of two groups as follows; the patients receiving high-dose intravenous anakinra (anakinra group) added to background therapy and the patients treated with standard of care (SoC) as a historical control group. Age, gender, mcHIS scores, and comorbidities such as diabetes mellitus, hypertension, and coronary heart disease of the patients were determined as the variables to be matched. We included 114 patients in SoC and 139 patients in the Anakinra group in the study. Development of any thromboembolic event (5% vs 12.3%, p = 0.038; OR 4.3) and PTE (2.9% vs 9.6%, p = 0.023; OR 5.1) were lower in the Anakinra group than SoC. No patient experienced cerebrovascular accident and/or clinically evident deep venous thrombosis both in two arms. After 1:1 PS matching, 88 patients in SoC and 88 patients in the Anakinra group were matched and included in the analysis. In survival analysis, the development of any thromboembolic event, pulmonary thromboembolism, and acute coronary syndrome (ACS) were higher in SoC compared to Anakinra. Survival rate was also lower in patients with SoC arm than Anakinra in patients who had any thromboembolic event as well as ACS. In our study, the development of thrombosis was associated with hyperinflammation in patients with severe and critical COVID-19. Intravenous high-dose anakinra treatment decreases both venous and arterial events in patients with severe and critical COVID-19.