bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and genetic analysis of Niemann-Pick disease type C with a novel NPC1 variant
Authors: Neissi Mostafa , Al-Badran Adnan Issa , Mohammadi-Asl Misagh , Al-Badran Raed Abdulelah , Sheikh-Hosseini Motahareh , Roghani Mojdeh , Mohammadi-Asl Javad
Published: July 2024

Background

Niemann-Pick disease type C poses a significant challenge within the landscape of rare genetic disorders, marked by its connection to variants in the NPC1 or NPC2 genes. This autosomal recessive lipid storage disorder unfolds with a relentless progression of neurological deterioration and a distinctive hallmark of hepatosplenomegaly.

Case presentation

This case report delves into the intricate presentation of a 9-year-old Iraqi boy exhibiting heightened walking instability and speech slurring. His medical history unfolds a series of challenges, including neonatal hyperbilirubinemia, hepatosplenomegaly, and recurrent nasal bleeding. A comprehensive physical examination reveals motor and neurological abnormalities such as an inability to squat and rise, vertical gaze palsy, and dysdiadochokinesia. Further investigations, encompassing laboratory tests and imaging studies, coupled with the identification of foamy cells in bone marrow smears, raise significant concerns about Niemann-Pick disease type C. By utilizing whole exome sequencing, we pinpointed a previously unreported homozygous variant—c.2925_2928delCTGC; p.Cys976PhefsTer6—found within exon 20 (NM_000271.5) of the proband’s NPC1 gene.

Conclusions

This study significantly advances our understanding of the c.2925_2928del (C976Ffs*6) variant in the NPC1 gene, shedding light on the complexities of Niemann-Pick disease type C. Beyond its scientific significance, the findings provide crucial insights for familial genetic counseling and prenatal diagnoses. This research expands our knowledge of the variant’s genetic landscape, making it a valuable resource in both academic and clinical settings, particularly for families dealing with Niemann-Pick disease type C.
Evaluation of the Water Mass Composition in the Sea of Okhotsk and Its Long‐Term Change Using an Advanced Mapping Technique
Authors: Mensah Vigan , Ohshima Kay I. , Drucker Robert , Riser Stephen
Published: July 2024

The Sea of Okhotsk is a marginal sea that plays a major role in the ventilation of the North Pacific, being the key location where Dense Shelf Water (DSW) forms at the surface and sinks to the intermediate layer. The Okhotsk Sea Intermediate Water (OSIW) is a key water mass because it includes large amounts of DSW, outflows to the North Pacific, and supplies the ocean with the micronutrient iron. OSIW has been warming over the past few decades, which is attributed to a decreasing trend in DSW production. The acquisition of numerous hydrographic data after 2000 in the Kuril Basin, especially dissolved oxygen from profiling floats, offers an opportunity to better quantify the water mass composition of OSIW, and the changes in OSIW properties and DSW volume. Here, we used all available hydrographic records and a mapping technique specially adapted to polar and sub‐polar regions to revisit the Sea of Okhotsk water properties and document their long‐term changes. Our analysis revealed that the volume of heavier DSW (potential density above 26.9 kg.m−3) has decreased over the past three decades by 3,600 km3, or 15% of the volume present before 1990. This decline is nearly entirely compensated for by an increase in lighter DSW. This shift toward lighter DSW is possibly a sign of the weakening of the intermediate overturning circulation starting in the Okhotsk Sea. Additionally, we found that dense Soya Current Water only accounts for about 1% of OSIW, against the 5% previously estimated.
Origins of Low‐Oxygen Bottom Water Influenced by Tide and ENSO on the Outer‐Edge Shelf of East China Sea: Multi‐Chemical Tracer Approaches
Authors: Deng Wenjie , Zhang Jing , Zhu Siteng Justin , Horikawa Keiji , Endoh Takahiro , Matsuno Takeshi , Kondo Yoshiko , Inoue Mutsuo , Nagao Seiya
Published: July 2024

The East China Sea (ECS) is one of the largest marginal seas in the world with high primary productivity and a large area of low dissolved oxygen. This study observed the low‐oxygen bottom water on the outer‐edge shelf of ECS in summer seasons of 2018–2020. The contributions of various water masses to low‐oxygen waters were quantified, and the interaction between low‐oxygen water and Kuroshio water was validated by a mixing model using heavy rare earth elements (HREEs) together with potential temperature, and salinity. For further reliability verification, tracers such as δ34S and 226Ra were additionally utilized to avoid the non‐conservative processes on the shelf area. The low‐oxygen water on the shelf was clarified to be linked to the inner/middle shelf water, and dominated by Kuroshio Subsurface Water (KSSW, 81% ± 3%) and influenced by a non‐negligible extent of pore water (3.0% ± 0.5%). Our findings revealed the transport of low‐oxygen water from the outer‐shelf edge to the Kuroshio area, whose dissolved inorganic nitrogen and dissolved inorganic phosphorus contributions to Kuroshio were 34%–82% and 35%–83%, respectively. The nutrients of low‐oxygen water were regulated primarily by the origins of water and secondarily by organic matter remineralization (DIN: ∼17% and DIP: ∼24%). As control factors, the tide, especially spring tide largely enhanced the water contribution of pore water to low‐oxygen water by 67%, and the El Niño‐Southern Oscillation potentially affected the contributions of KSSW and mid‐shelf water to low‐oxygen water.
The risks for major psychiatric disorders in the siblings of probands with major depressive disorder
Authors: Rhee Sang Jin , Abrahamsson Linda , Sundquist Jan , Sundquist Kristina , Kendler Kenneth S.
Published: July 2024

Using a case-controlled study including siblings of major depression (MD) and control probands, born 1970–1990 and followed through 2018, we sought to clarify the degree to which the familial liability to MD is reflected in its clinical features, and the pattern of psychiatric disorders at elevated risk in the siblings of MD probands. The study population included full-siblings of 197,309 MD and matched 197,309 control probands. The proband-sibling tetrachoric correlation of for MD was +0.20. Both linear and quadratic effects of younger AAO and number of episodes significantly increased the risk of MD in siblings. Male sex, anxiety disorder, alcohol use disorder (AUD), inpatient treatment, psychotic symptoms, severity, and antidepressant prescription in MD probands increased the risk of MD in siblings. Cox proportional hazard models (hazard ratios, 95% CI) revealed a significantly increased risk of attention deficit hyperactivity disorder (1.82, 1.76–1.88), generalized anxiety disorder (1.79, 1.74–1.85), bipolar disorder (1.78, 1.70–1.85), MD (1.74, 1.72–1.76), obsessive-compulsive disorder (1.72, 1.65–1.80), phobic anxiety disorder (1.71, 1.65–1.76), and panic disorder (1.68, 1.64–1.72) in MD co-siblings. The HRs for AUD (1.64, 1.60–1.68), post-traumatic stress disorder (1.62, 1.59–1.66) were modestly lower, and the lowest was seen for schizophrenia (1.42, 1.30–1.54). The overall pattern of increased risk of these disorders was similar in reared-apart half-siblings and cousins of MD probands. Our findings suggest that MD is familial, and a range of important clinical factors predict its familial liability. The familial liability to MD, mostly due to genetic factors, is shared with a broad range of psychiatric disorders.
Assessment of oral health status and quality of life in hearing-impaired children from Syria
Authors: Ghannam Alemar Nazeeh , Dashash Mayssoon , Darjazini Nahhas Louei
Published: July 2024

Aim

This study aimed to evaluate the oral health status of children with hearing impairments and assess the relationship between various oral health factors and the Pediatric Oral Health-Related Quality of Life.

Materials and methods

This observational cohort study involved 90 hearing-impaired children aged 6–12 years. Diagnostic tools such as pure-tone audiometry were used to evaluate their hearing abilities. Dental health was assessed by calculating DMFT, dmft, Plaque and Gingival indices. The oral health-related quality of life was measured using the POHRQoL.

Results

The severity of hearing impairment varied with 3% having severe hearing loss, 13% having profound hearing loss, and 83% having complete hearing loss. A high prevalence of dental cavities with 93% of children affected was found. DMFT score was similar between males and females (2.5 ± 0.3 vs. 2.3 ± 0.3 respectively). Males exhibited a higher mean dmft score (4.1 ± 0.5 vs. 3.3 ± 0.5), and a higher mean Plaque Index (1.9 ± 0.1 vs. 1.5 ± 0.1). On the other hand, females showed a higher mean Gingival Index (0.9 ± 0.1 vs. 1.1 ± 0.2). Results indicated a decreased OHRQoL with a mean POQL score of 6.4 ± 2.89. Spearman’s test revealed a significant positive correlation between POQL total score and DMFT scores (P = 0.000), dmft scores (P = 0.000), Plaque Index scores (P = 0.000), and Gingival Index scores (P = 0.038). There was a weak positive correlation between hearing impairment severity and POQL total score, it was not statistically significant.

Conclusions

Children who have hearing impairments exhibit poor oral health, and levels of dental caries, which can negatively impact their overall POHRQoL. Therefore, it is highly recommended to start specialized oral health education and comprehensive dental care programs to improve their OHRQoL.
Inhibition of PKC-δ retards kidney fibrosis via inhibiting cGAS-STING signaling pathway in mice
Authors: Wang Dongyun , Li Yue , Li Guiying , Liu Mengyu , Zhou Zihui , Wu Ming , Song Shan , Bian Yawei , Dong Jiajia , Li Xinran , Du Yunxia , Zhang Tao , Shi Yonghong
Published: July 2024

Kidney fibrosis is considered to be the ultimate aggregation pathway of chronic kidney disease (CKD), but its underlying mechanism remains elusive. Protein kinase C-delta (PKC-δ) plays critical roles in the control of growth, differentiation, and apoptosis. In this study, we found that PKC-δ was highly upregulated in human biopsy samples and mouse kidneys with fibrosis. Rottlerin, a PKC-δ inhibitor, alleviated unilateral ureteral ligation (UUO)-induced kidney fibrosis, inflammation, VDAC1 expression, and cGAS-STING signaling pathway activation. Adeno-associated virus 9 (AAV9)-mediated VDAC1 silencing or VBIT-12, a VDAC1 inhibitor, attenuated renal injury, inflammation, and activation of cGAS-STING signaling pathway in UUO mouse model. Genetic and pharmacologic inhibition of STING relieved renal fibrosis and inflammation in UUO mice. In vitro, hypoxia resulted in PKC-δ phosphorylation, VDAC1 oligomerization, and activation of cGAS-STING signaling pathway in HK-2 cells. Inhibition of PKC-δ, VDAC1 or STING alleviated hypoxia-induced fibrotic and inflammatory responses in HK-2 cells, respectively. Mechanistically, PKC-δ activation induced mitochondrial membrane VDAC1 oligomerization via direct binding VDAC1, followed by the mitochondrial DNA (mtDNA) release into the cytoplasm, and subsequent activated cGAS-STING signaling pathway, which contributed to the inflammation leading to fibrosis. In conclusion, this study has indicated for the first time that PKC-δ is an important regulator in kidney fibrosis by promoting cGAS-STING signaling pathway which mediated by VDAC1. PKC-δ may be useful for treating renal fibrosis and subsequent CKD.
Genetic therapies for cardiomyopathy: survey of attitudes of the patient community for the CureHeart project
Authors: Ormondroyd Elizabeth , Grace Christopher , Borsari Wendy , Goel Anuj , McDonough Barbara , Rose Joel , Seidman Christine , Watkins Hugh
Published: July 2024

Cardiomyopathies are a group of inherited heart muscle disorders. Expressivity is variable and while sometimes mild, complications can result in sudden cardiac death (SCD) at any age, heart failure and stroke. In around a third of patients a monogenic cause is identifiable, and development of genetic therapies that aim to correct the underlying genetic defect is underway. Here we describe results of a survey designed to understand preliminary views of the patient community about genetic therapies in the context of disease burden. The internet survey was publicized with a bespoke information video via patient support groups in the UK and USA; 634 people responded of whom 96% had a personal and/or family history of cardiomyopathy. Findings show that concern about cardiomyopathy-related issues with a future dimension, such as disease progression, is significantly greater than concern about current issues. A total of 93.6% thought that genetic therapies should be developed for cardiomyopathy. A majority would consider participation in a genetic therapy trial in six scenarios varying by age and clinical situation significantly more in the scenario of an adult with symptomatic disease and evident progression than an asymptomatic adult with SCD risk, or a child. In all scenarios, a majority said that the chance genetic therapy would stop or slow progression, and risk of serious adverse and unintended effects, were important considerations. Qualitative analysis of free-text responses found that concern was often informed by family experience. Patient consideration of genetic therapy is likely to require individualized assessment of the benefits and risks.
The human VGLUT3-pT8I mutation elicits uneven striatal DA signaling, food or drug maladaptive consumption in male mice
Authors: Favier Mathieu , Martin Garcia Elena , Icick Romain , de Almeida Camille , Jehl Joachim , Desplanque Mazarine , Zimmermann Johannes , Henrion Annabelle , Mansouri-Guilani Nina , Mounier Coline , Ribeiro Svethna , Henderson Fiona , Geoffroy Andrea , Mella Sebastien , Poirel Odile , Bernard Véronique , Fabre Véronique , Li Yulong , Rosenmund Christian , Jamain Stéphane , Vorspan Florence , Mourot Alexandre , Duriez Philibert , Pinhas Leora , Maldonado Rafael , Pietrancosta Nicolas , Daumas Stéphanie , El Mestikawy Salah
Published: July 2024

Cholinergic striatal interneurons (ChIs) express the vesicular glutamate transporter 3 (VGLUT3) which allows them to regulate the striatal network with glutamate and acetylcholine (ACh). In addition, VGLUT3-dependent glutamate increases ACh vesicular stores through vesicular synergy. A missense polymorphism, VGLUT3-p.T8I, was identified in patients with substance use disorders (SUDs) and eating disorders (EDs). A mouse line was generated to understand the neurochemical and behavioral impact of the p.T8I variant. In VGLUT3T8I/T8I male mice, glutamate signaling was unchanged but vesicular synergy and ACh release were blunted. Mutant male mice exhibited a reduced DA release in the dorsomedial striatum but not in the dorsolateral striatum, facilitating habit formation and exacerbating maladaptive use of drug or food. Increasing ACh tone with donepezil reversed the self-starvation phenotype observed in VGLUT3T8I/T8I male mice. Our study suggests that unbalanced dopaminergic transmission in the dorsal striatum could be a common mechanism between SUDs and EDs.
Diversity of visual inputs to Kenyon cells of the Drosophila mushroom body
Authors: Ganguly Ishani , Heckman Emily L. , Litwin-Kumar Ashok , Clowney E. Josephine , Behnia Rudy
Published: July 2024

The arthropod mushroom body is well-studied as an expansion layer representing olfactory stimuli and linking them to contingent events. However, 8% of mushroom body Kenyon cells in Drosophila melanogaster receive predominantly visual input, and their function remains unclear. Here, we identify inputs to visual Kenyon cells using the FlyWire adult whole-brain connectome. Input repertoires are similar across hemispheres and connectomes with certain inputs highly overrepresented. Many visual neurons presynaptic to Kenyon cells have large receptive fields, while interneuron inputs receive spatially restricted signals that may be tuned to specific visual features. Individual visual Kenyon cells randomly sample sparse inputs from combinations of visual channels, including multiple optic lobe neuropils. These connectivity patterns suggest that visual coding in the mushroom body, like olfactory coding, is sparse, distributed, and combinatorial. However, the specific input repertoire to the smaller population of visual Kenyon cells suggests a constrained encoding of visual stimuli.
Distinct pulmonary and systemic effects of dexamethasone in severe COVID-19
Authors: Neyton Lucile P. A. , Patel Ravi K. , Sarma Aartik ,   UCSF COMET Consortium, Ansel K. Mark , Christenson Stephanie , Adkisson Michael , Eckalbar Walter , Maliskova Lenka , Schroeder Andrew , Bueno Raymund , Gordon Gracie , Hartoularos George , Kushnoor Divya , Lee David , McCarthy Elizabeth , Ogorodnikov Anton , Spitzer Matthew , Hiam Kamir , Song Yun S. , Sun Yang , Tumurbaatar Erden , van der Wijst Monique , Whatley Alexander , Jones Chayse , Caldera Saharai , DeVoe Catherine , Serpa Paula Hayakawa , Love Christina , Mick Eran , Phelps Maira , Tsitsiklis Alexandra , Leroux Carolyn , Rashid Sadeed , Rodriguez Nicklaus , Tang Kevin , Altamirano Luz Torres , Leligdowicz Aleksandra , Matthay Michael , Wilson Michael , Ye Jimmie , Chak Suzanna , Ghale Rajani , Jauregui Alejandra , Lee Deanna , Nguyen Viet , Sigman Austin , Kangelaris Kirsten N. , Asthana Saurabh , Collins Zachary , Patel Ravi , Rao Arjun , Samad Bushra , Shaw Cole , Lea Tasha , Ward Alyssa , Jones Norman , Milush Jeff , Chan Vincent , Chew Nayvin , Combes Alexis , Courau Tristan , Hu Kenneth , Huang Billy , Kumar Nitasha , Mahboob Salman , Muñoz-Sandoval Priscila , Parada Randy , Reeder Gabriella , Shen Alan , Tsui Jessica , Zha Shoshana , Zhu Wandi S. , Willmore Andrew , Haller Sidney C. , Kangelaris Kirsten N. , Eckalbar Walter L. , Erle David J. , Krummel Matthew F. , Hendrickson Carolyn M. , Woodruff Prescott G. , Langelier Charles R. , Calfee Carolyn S. , Fragiadakis Gabriela K.
Published: July 2024

Dexamethasone is the standard of care for critically ill patients with COVID-19, but the mechanisms by which it decreases mortality and its immunological effects in this setting are not understood. Here we perform bulk and single-cell RNA sequencing of samples from the lower respiratory tract and blood, and assess plasma cytokine profiling to study the effects of dexamethasone on both systemic and pulmonary immune cell compartments. In blood samples, dexamethasone is associated with decreased expression of genes associated with T cell activation, including TNFSFR4 and IL21R. We also identify decreased expression of several immune pathways, including major histocompatibility complex-II signaling, selectin P ligand signaling, and T cell recruitment by intercellular adhesion molecule and integrin activation, suggesting these are potential mechanisms of the therapeutic benefit of steroids in COVID-19. We identify additional compartment- and cell- specific differences in the effect of dexamethasone that are reproducible in publicly available datasets, including steroid-resistant interferon pathway expression in the respiratory tract, which may be additional therapeutic targets. In summary, we demonstrate compartment-specific effects of dexamethasone in critically ill COVID-19 patients, providing mechanistic insights with potential therapeutic relevance. Our results highlight the importance of studying compartmentalized inflammation in critically ill patients.
Nickel-catalyzed asymmetric hydrogenation for the preparation of α-substituted propionic acids
Authors: Li Bowen , Wang Zhiling , Luo Yicong , Wei Hanlin , Chen Jianzhong , Liu Delong , Zhang Wanbin
Published: July 2024

Transition metal-catalyzed asymmetric hydrogenation is one of the most efficient methods for the preparation of chiral α-substituted propionic acids. However, research on this method, employing cleaner earth-abundant metal catalysts, is still insufficient in both academic and industrial contexts. Herein, we report an efficient nickel-catalyzed asymmetric hydrogenation of α-substituted acrylic acids affording the corresponding chiral α-substituted propionic acids with up to 99.4% ee (enantiomeric excess) and 10,000 S/C (substrate/catalyst). In particular, this method can be used to obtain (R)-dihydroartemisinic acid with 99.8:0.2 dr (diastereomeric ratio) and 5000 S/C, which is an essential intermediate for the preparation of the antimalarial drug Artemisinin. The reaction mechanism has been investigated via experiments and DFT (Density Functional Theory) calculations, which indicate that the protonolysis of the C-Ni bond of the key intermediate via an intramolecular proton transfer from the carboxylic acid group of the substrate, is the rate-determining step.
Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia
Authors: Mulet-Lazaro Roger , van Herk Stanley , Nuetzel Margit , Sijs-Szabo Aniko , Díaz Noelia , Kelly Katherine , Erpelinck-Verschueren Claudia , Schwarzfischer-Pfeilschifter Lucia , Stanewsky Hanna , Ackermann Ute , Glatz Dagmar , Raithel Johanna , Fischer Alexander , Pohl Sandra , Rijneveld Anita , Vaquerizas Juan M. , Thiede Christian , Plass Christoph , Wouters Bas J. , Delwel Ruud , Rehli Michael , Gebhard Claudia
Published: July 2024

Leukemias with ambiguous lineage comprise several loosely defined entities, often without a clear mechanistic basis. Here, we extensively profile the epigenome and transcriptome of a subgroup of such leukemias with CpG Island Methylator Phenotype. These leukemias exhibit comparable hybrid myeloid/lymphoid epigenetic landscapes, yet heterogeneous genetic alterations, suggesting they are defined by their shared epigenetic profile rather than common genetic lesions. Gene expression enrichment reveals similarity with early T-cell precursor acute lymphoblastic leukemia and a lymphoid progenitor cell of origin. In line with this, integration of differential DNA methylation and gene expression shows widespread silencing of myeloid transcription factors. Moreover, binding sites for hematopoietic transcription factors, including CEBPA, SPI1 and LEF1, are uniquely inaccessible in these leukemias. Hypermethylation also results in loss of CTCF binding, accompanied by changes in chromatin interactions involving key transcription factors. In conclusion, epigenetic dysregulation, and not genetic lesions, explains the mixed phenotype of this group of leukemias with ambiguous lineage. The data collected here constitute a useful and comprehensive epigenomic reference for subsequent studies of acute myeloid leukemias, T-cell acute lymphoblastic leukemias and mixed-phenotype leukemias.
Designing highly efficient interlocking interactions in anisotropic active particles
Authors: Riedel Solenn , Hoffmann Ludwig A. , Giomi Luca , Kraft Daniela J.
Published: July 2024

Cluster formation of microscopic swimmers is key to the formation of biofilms and colonies, efficient motion and nutrient uptake, but, in the absence of other interactions, requires high swimmer concentrations to occur. Here we experimentally and numerically show that cluster formation can be dramatically enhanced by an anisotropic swimmer shape. We analyze a class of model microswimmers with a shape that can be continuously tuned from spherical to bent and straight rods. In all cases, clustering can be described by Michaelis-Menten kinetics governed by a single scaling parameter that depends on particle density and shape only. We rationalize these shape-dependent dynamics from the interplay between interlocking probability and cluster stability. The bent rod shape promotes assembly in an interlocking fashion even at vanishingly low particle densities and we identify the most efficient shape to be a semicircle. Our work provides key insights into how shape can be used to rationally design out-of-equilibrium self-organization, key to creating active functional materials and processes that require two-component assembly with high fidelity.
Humid heat environment causes anxiety-like disorder via impairing gut microbiota and bile acid metabolism in mice
Authors: Weng Huandi , Deng Li , Wang Tianyuan , Xu Huachong , Wu Jialin , Zhou Qinji , Yu Lingtai , Chen Boli , Huang Li’an , Qu Yibo , Zhou Libing , Chen Xiaoyin
Published: July 2024

Climate and environmental changes threaten human mental health, but the impacts of specific environmental conditions on neuropsychiatric disorders remain largely unclear. Here, we show the impact of a humid heat environment on the brain and the gut microbiota using a conditioned housing male mouse model. We demonstrate that a humid heat environment can cause anxiety-like behaviour in male mice. Microbial 16 S rRNA sequencing analysis reveals that a humid heat environment caused gut microbiota dysbiosis (e.g., decreased abundance of Lactobacillus murinus), and metabolomics reveals an increase in serum levels of secondary bile acids (e.g., lithocholic acid). Moreover, increased neuroinflammation is indicated by the elevated expression of proinflammatory cytokines in the serum and cortex, activated PI3K/AKT/NF-κB signalling and a microglial response in the cortex. Strikingly, transplantation of the microbiota from mice reared in a humid heat environment readily recapitulates these abnormalities in germ-free mice, and these abnormalities are markedly reversed by Lactobacillus murinus administration. Human samples collected during the humid heat season also show a decrease in Lactobacillus murinus abundance and an increase in the serum lithocholic acid concentration. In conclusion, gut microbiota dysbiosis induced by a humid heat environment drives the progression of anxiety disorders by impairing bile acid metabolism and enhancing neuroinflammation, and probiotic administration is a potential therapeutic strategy for these disorders.
Directional integration and pathway enrichment analysis for multi-omics data
Authors: Slobodyanyuk Mykhaylo , Bahcheli Alexander T. , Klein Zoe P. , Bayati Masroor , Strug Lisa J. , Reimand Jüri
Published: July 2024

Omics techniques generate comprehensive profiles of biomolecules in cells and tissues. However, a holistic understanding of underlying systems requires joint analyses of multiple data modalities. We present DPM, a data fusion method for integrating omics datasets using directionality and significance estimates of genes, transcripts, or proteins. DPM allows users to define how the input datasets are expected to interact directionally given the experimental design or biological relationships between the datasets. DPM prioritises genes and pathways that change consistently across the datasets and penalises those with inconsistent directionality. To demonstrate our approach, we characterise gene and pathway regulation inIDH-mutant gliomas by jointly analysing transcriptomic, proteomic, and DNA methylation datasets. Directional integration of survival information in ovarian cancer reveals candidate biomarkers with consistent prognostic signals in transcript and protein expression. DPM is a general and adaptable framework for gene prioritisation and pathway analysis in multi-omics datasets.
Engineered cytosine base editor enabling broad-scope and high-fidelity gene editing in Streptomyces
Authors: Wang Jian , Wang Ke , Deng Zhe , Zhong Zhiyu , Sun Guo , Mei Qing , Zhou Fuling , Deng Zixin , Sun Yuhui
Published: July 2024

Base editing (BE) faces protospacer adjacent motif (PAM) constraints and off-target effects in both eukaryotes and prokaryotes. For Streptomyces, renowned as one of the most prolific bacterial producers of antibiotics, the challenges are more pronounced due to its diverse genomic content and high GC content. Here, we develop a base editor named eSCBE3-NG-Hypa, tailored with both high efficiency and -fidelity for Streptomyces. Of note, eSCBE3-NG-Hypa recognizes NG PAM and exhibits high activity at challenging sites with high GC content or GC motifs, while displaying minimal off-target effects. To illustrate its practicability, we employ eSCBE3-NG-Hypa to achieve precise key amino acid conversion of the dehydratase (DH) domains within the modular polyketide synthase (PKS) responsible for the insecticide avermectins biosynthesis, achieving domains inactivation. The resulting DH-inactivated mutants, while ceasing avermectins production, produce a high yield of oligomycin, indicating competitive relationships among multiple biosynthetic gene clusters (BGCs) in Streptomyces avermitilis. Leveraging this insight, we use eSCBE3-NG-Hypa to introduce premature stop codons into competitor gene cluster of ave in an industrial S. avermitilis, with the mutant Δolm exhibiting the highest 4.45-fold increase in avermectin B1a compared to the control. This work provides a potent tool for modifying biosynthetic pathways and advancing metabolic engineering in Streptomyces.
Hematopoietic stem and progenitor cell membrane-coated vesicles for bone marrow-targeted leukaemia drug delivery
Authors: Li Jinxin , Wu Honghui , Yu Zebin , Wang Qiwei , Zeng Xin , Qian Wenchang , Lu Siqi , Jiang Lingli , Li Jingyi , Zhu Meng , Han Yingli , Gao Jianqing , Qian Pengxu
Published: July 2024

Leukemia is a kind of hematological malignancy originating from bone marrow, which provides essential signals for initiation, progression, and recurrence of leukemia. However, how to specifically deliver drugs to the bone marrow remains elusive. Here, we develop biomimetic vesicles by infusing hematopoietic stem and progenitor cell (HSPC) membrane with liposomes (HSPC liposomes), which migrate to the bone marrow of leukemic mice via hyaluronic acid-CD44 axis. Moreover, the biomimetic vesicles exhibit superior binding affinity to leukemia cells through intercellular cell adhesion molecule-1 (ICAM-1)/integrin β2 (ITGB2) interaction. Further experiments validate that the vesicles carrying chemotherapy drug cytarabine (Ara-C@HSPC-Lipo) markedly inhibit proliferation, induce apoptosis and differentiation of leukemia cells, and decrease number of leukemia stem cells. Mechanically, RNA-seq reveals that Ara-C@HSPC-Lipo treatment induces apoptosis and differentiation and inhibits the oncogenic pathways. Finally, we verify that HSPC liposomes are safe in mice. This study provides a method for targeting bone marrow and treating leukemia.
Stable and efficient CsPbI3 quantum-dot light-emitting diodes with strong quantum confinement
Authors: Li Yanming , Deng Ming , Zhang Xuanyu , Xu Ting , Wang Ximeng , Yao Zhiwei , Wang Qiangqiang , Qian Lei , Xiang Chaoyu
Published: July 2024

Even though lead halide perovskite has been demonstrated as a promising optoelectronic material for next-generation display applications, achieving high-efficiency and stable pure-red (620~635 nm) emission to cover the full visible wavelength is still challenging. Here, we report perovskite light-emitting diodes emitting pure-red light at 628 nm achieving high external quantum efficiencies of 26.04%. The performance is attributed to successful synthesizing strongly confined CsPbI3 quantum dots with good stability. The strong binding 2-naphthalene sulfonic acid ligands are introduced after nucleation to suppress Ostwald ripening, meanwhile, ammonium hexafluorophosphate exchanges long chain ligands and avoids regrowth by strong binding during the purification process. Both ligands enhance the charge transport ability of CsPbI3 quantum dots. The state-of-the-art synthesis of pure red CsPbI3 quantum dots achieves 94% high quantum efficiency, which can maintain over 80% after 50 days, providing a method for synthesizing stable strong confined perovskite quantum dots.
Molecular and supramolecular adaptation by coupled stimuli
Authors: Dünnebacke Torsten , Niemeyer Niklas , Baumert Sebastian , Hochstädt Sebastian , Borsdorf Lorenz , Hansen Michael Ryan , Neugebauer Johannes , Fernández Gustavo
Published: July 2024

Adaptation transcends scale in both natural and artificial systems, but delineating the causative factors of this phenomenon requires urgent clarification. Herein, we unravel the molecular requirements for adaptation and establish a link to rationalize adaptive behavior on a self-assembled level. These concepts are established by analyzing a model compound exhibiting both light- and pH-responsive units, which enable the combined or independent application of different stimuli. On a molecular level, adaptation arises from coupled stimuli, as the final outcome of the system depends on their sequence of application. However, in a self-assembled state, a single stimulus suffices to induce adaptation as a result of collective molecular behavior and the reversibility of non-covalent interactions. Our findings go beyond state-of-the-art (multi)stimuli-responsive systems and allow us to draw up design guidelines for adaptive behavior both at the molecular and supramolecular levels, which are fundamental criteria for the realization of intelligent matter.
Pedestrians' safety using projected time-to-collision to electric scooters
Authors: Jafari Alireza , Liu Yen-Chen
Published: July 2024

Safety concern among electric scooter riders drives them onto sidewalks, endangering pedestrians and making them uncomfortable. Regulators’ solutions are inconsistent and conflicting worldwide. Widely accepted pedestrian safety metrics may lead to converging solutions. Adapting the time-to-collision from car traffic safety, we define projected time-to-collision and experimentally study pedestrians’ objective and subjective safety. We design isolated and crowd experiments using e-scooter-to-pedestrian interactions to assess the impact of various factors on objective safety. In addition, we conducted a pedestrian survey to relate the subjective safety and the metric. We report a strong correlation between subjective safety and the projected time-to-collision when agents face each other and no relation when the e-scooter overtakes a pedestrian. As a near-miss metric correlated with pedestrian comfort, projected time-to-collision is implementable in policy-making, urban architecture, and e-scooter design to enhance pedestrian safety.
Genetic diversity, determinants, and dissemination of Burkholderia pseudomallei lineages implicated in melioidosis in Northeast Thailand
Authors: Seng Rathanin , Chomkatekaew Chalita , Tandhavanant Sarunporn , Saiprom Natnaree , Phunpang Rungnapa , Thaipadungpanit Janjira , Batty Elizabeth M. , Day Nicholas P. J. , Chantratita Wasun , West T. Eoin , Thomson Nicholas R. , Parkhill Julian , Chewapreecha Claire , Chantratita Narisara
Published: July 2024

Melioidosis is an often-fatal neglected tropical disease caused by an environmental bacterium Burkholderia pseudomallei. However, our understanding of the disease-causing bacterial lineages, their dissemination, and adaptive mechanisms remains limited. To address this, we conduct a comprehensive genomic analysis of 1,391 B. pseudomallei isolates collected from nine hospitals in northeast Thailand between 2015 and 2018, and contemporaneous isolates from neighbouring countries, representing the most densely sampled collection to date. Our study identifies three dominant lineages, each with unique gene sets potentially enhancing bacterial fitness in the environment. We find that recombination drives lineage-specific gene flow. Transcriptome analyses of representative clinical isolates from each dominant lineage reveal increased expression of lineage-specific genes under environmental conditions in two out of three lineages. This underscores the potential importance of environmental persistence for these dominant lineages. The study also highlights the influence of environmental factors such as terrain slope, altitude, and river direction on the geographical dispersal of B. pseudomallei. Collectively, our findings suggest that environmental persistence may play a role in facilitating the spread of B. pseudomallei, and as a prerequisite for exposure and infection, thereby providing useful insights for informing melioidosis prevention and control strategies.
Dataset for quantum-mechanical exploration of conformers and solvent effects in large drug-like molecules
Authors: Medrano Sandonas Leonardo , Van Rompaey Dries , Fallani Alessio , Hilfiker Mathias , Hahn David , Perez-Benito Laura , Verhoeven Jonas , Tresadern Gary , Kurt Wegner Joerg , Ceulemans Hugo , Tkatchenko Alexandre
Published: July 2024

We here introduce the Aquamarine (AQM) dataset, an extensive quantum-mechanical (QM) dataset that contains the structural and electronic information of 59,783 low-and high-energy conformers of 1,653 molecules with a total number of atoms ranging from 2 to 92 (mean: 50.9), and containing up to 54 (mean: 28.2) non-hydrogen atoms. To gain insights into the solvent effects as well as collective dispersion interactions for drug-like molecules, we have performed QM calculations supplemented with a treatment of many-body dispersion (MBD) interactions of structures and properties in the gas phase and implicit water. Thus, AQM contains over 40 global and local physicochemical properties (including ground-state and response properties) per conformer computed at the tightly converged PBE0+MBD level of theory for gas-phase molecules, whereas PBE0+MBD with the modified Poisson-Boltzmann (MPB) model of water was used for solvated molecules. By addressing both molecule-solvent and dispersion interactions, AQM dataset can serve as a challenging benchmark for state-of-the-art machine learning methods for property modeling and de novo generation of large (solvated) molecules with pharmaceutical and biological relevance.
A comprehensive city-level final energy consumption dataset including renewable energy for China, 2005–2021
Authors: Yang Guanglei , Zhang Guoxing , Cao Dongqin , Gao Xiulin , Wang Xiaojuan , Yang Shaowen , Jiang Pansong , Zha Donglan , Shan Yuli
Published: July 2024

The role of China is increasingly pivotal in climate change mitigation, and the formulation of energy conservation and emission reduction policies requires city-level information. The effectiveness of national policy implementation is contingent upon the support and involvement of local governments. Accurate data on final energy consumption is vital to formulate and implement city-level energy transitions and energy conservation and emission reduction policies. However, there is a dearth of data sources pertaining to China’s city-level final energy consumption. To address these gaps, we developed computational modeling techniques along with top-down and downscaling methods to estimate China’s city-level final energy consumption. In this way, we compiled a final energy consumption inventory for 331 Chinese cities from 2005 to 2021, covering seven economic sectors, 30 fossil fuels, and four clean power sources. Moreover, we discussed the validity of the estimation results from multiple perspectives to enhance estimation accuracy. This dataset can be utilized for analysis in various cutting-edge research fields such as energy transition dynamics, transition risk management strategies, and policy formulation processes.
Multi-omics and single cell characterization of cancer immunosenescence landscape
Authors: Wei Qiuxia , Chen Ruizhi , He Xue , Qu Yanan , Yan Changjian , Liu Xiaoni , Liu Jing , Luo Jiahao , Yu Zining , Hu Wenping , Wang Liqun , Lin Xiaoya , Wu Chaoling , Xiao Jinyuan , Zhou Haibo , Wang Jing , Zhu Mingxia , Yang Ping , Chen Yingtong , Tan Qilong , Yuan Xiaoliang , Jing Hongmei , Zhang Weilong
Published: July 2024

Cellular senescence (CS) is closely related to tumor progression. However, the studies about CS genes across human cancers have not explored the relationship between cancer senescence signature and telomere length. Additionally, single-cell analyses have not revealed the evolutionary trends of malignant cells and immune cells at the CS level. We defined a CS-associated signature, called “senescence signature”, and found that patients with higher senescence signature had worse prognosis. Higher senescence signature was related to older age, higher genomic instability, longer telomeres, increased lymphocytic infiltration, higher pro-tumor immune infiltrates (Treg cells and MDSCs), and could predict responses to immune checkpoint inhibitor therapy. Single-cell analysis further reveals malignant cells and immune cells share a consistent evolutionary trend at the CS level. MAPK signaling pathway and apoptotic processes may play a key role in CS, and senescence signature may effectively predict sensitivity of MEK1/2 inhibitors, ERK1/2 inhibitors and BCL-2 family inhibitors. We also developed a new CS prediction model of cancer survival and established a portal website to apply this model (https://bio-pub.shinyapps.io/cs_nomo/).
Telomere-to-telomere genome assembly of the goose Anser cygnoides
Authors: Zhao Hongchang , Zhou Hao , Sun Guobo , Dong Biao , Zhu Wenqi , Mu Xiaohui , Li Xiaoming , Wang Jun , Zhao Mengli , Yang Wenhao , Zhang Gansheng , Ji Rongchao , Geng Tuoyu , Gong Daoqing , Meng He , Wang Jian
Published: July 2024

Our study presents the assembly of a high-quality Taihu goose genome at the Telomere-to-Telomere (T2T) level. By employing advanced sequencing technologies, including Pacific Biosciences HiFi reads, Oxford Nanopore long reads, Illumina short reads, and chromatin conformation capture (Hi-C), we achieved an exceptional assembly. The T2T assembly encompasses a total length of 1,197,991,206 bp, with contigs N50 reaching 33,928,929 bp and scaffold N50 attaining 81,007,908 bp. It consists of 73 scaffolds, including 38 autosomes and one pair of Z/W sex chromosomes. Importantly, 33 autosomes were assembled without any gap, resulting in a contiguous representation. Furthermore, gene annotation efforts identified 34,898 genes, including 436,162 RNA transcripts, encompassing 806,158 exons, 743,910 introns, 651,148 coding sequences (CDS), and 135,622 untranslated regions (UTR). The T2T-level chromosome-scale goose genome assembly provides a vital foundation for future genetic improvement and understanding the genetic mechanisms underlying important traits in geese.
Dataset of soil hydraulic parameters in the Yellow River Basin based on in situ deep sampling
Authors: Tong Yongping , Wang Yunqiang , Zhou Jingxiong , Guo Xiangyu , Wang Ting , Xu Yuting , Sun Hui , Zhang Pingping , Li Zimin , Lauerwald Ronny
Published: July 2024

Soil hydraulic parameters are vital for precisely characterizing soil hydrological processes, which are critical indicators for regulating climate change effects on terrestrial ecosystems and governing feedbacks between water, energy, and carbon–nitrogen cycles. Although many studies have integrated comprehensive soil datasets, data quality and cost challenges result in data completeness deficiencies, especially for deep soil information. These gaps not only impede methodological endeavours but also constrain soil parameter-based ecosystem process studies spanning from local profiles to global earth system models. We established a soil dataset across the entire Yellow River Basin (YRB) (795,000 km2) using high-density in situ field sampling. This observation-based dataset contains records of soil texture (2924), bulk density (2798), saturated hydraulic conductivity (2782), and water retention curve parameters (1035) down to a maximum depth of 5 m. This dataset, which extends the recorded data range for deep soil hydraulic parameters, is valuable as a direct data resource for environmental, agronomical and hydrological studies in the YRB and regions with similar pedological and geological backgrounds around the world.
Hybrid ant colony-based inter-cluster routing protocol for FANET
Authors: Yang Siwei , Wang Shu , Li Tingli , Hu Tao , Xu Ziliang , He Renze , Zhang Bing
Published: July 2024

This study addresses the challenges in large-scale unmanned aerial vehicle (UAV) clusters, specifically the scalability issues and limitations of using reactive routing protocols for inter-cluster routing. These traditional methods place an excessive burden on cluster heads and struggle to adapt to frequently changing topologies, leading to decreased network performance. To solve these problems, we propose an innovative inter-cluster routing protocol (ICRP), which is based on a hybrid ant colony algorithm. During the route establishment phase, ICRP uses this algorithm to identify the optimal relay node. This approach is inspired by the foraging behavior of Physarum polycephalum, combining factors such as the number of hops from the source node, the load condition of the node, and its weight in the pheromone calculation. In the route maintenance phase, ICRP uses a predictive repair and contraction mechanism to dynamically maintain routes, accommodating the high mobility of UAVs. Comparative simulations in OMNeT +  + showed that this protocol surpasses ad-hoc on-demand distance vector (AODV), fuzzy-logic-assisted-AODV, and Enhanced-Ant-AODV routing protocols in packet delivery rate and end-to-end transmission delay. Furthermore, it showed superior adaptation to network environments with high-speed node mobility.
Improving prediction of blood cancer using leukemia microarray gene data and Chi2 features with weighted convolutional neural network
Authors: Alabdulqader Ebtisam Abdullah , Alarfaj Aisha Ahmed , Umer Muhammad , Eshmawi Ala’ Abdulmajid , Alsubai Shtwai , Kim Tai-hoon , Ashraf Imran
Published: July 2024

Blood cancer has emerged as a growing concern over the past decade, necessitating early diagnosis for timely and effective treatment. The present diagnostic method, which involves a battery of tests and medical experts, is costly and time-consuming. For this reason, it is crucial to establish an automated diagnostic system for accurate predictions. A particular field of focus in medical research is the use of machine learning and leukemia microarray gene data for blood cancer diagnosis. Even with a great deal of research, more improvements are needed to reach the appropriate levels of accuracy and efficacy. This work presents a supervised machine-learning algorithm for blood cancer prediction. This work makes use of the 22,283-gene leukemia microarray gene data. Chi-squared (Chi2) feature selection methods and the synthetic minority oversampling technique (SMOTE)-Tomek resampling is used to overcome issues with imbalanced and high-dimensional datasets. To balance the dataset for each target class, SMOTE-Tomek creates synthetic data, and Chi2 chooses the most important features to train the learning models from 22,283 genes. A novel weighted convolutional neural network (CNN) model is proposed for classification, utilizing the support of three separate CNN models. To determine the importance of the proposed approach, extensive experiments are carried out on the datasets, including a performance comparison with the most advanced techniques. Weighted CNN demonstrates superior performance over other models when coupled with SMOTE-Tomek and Chi2 techniques, achieving a remarkable 99.9% accuracy. Results from k-fold cross-validation further affirm the supremacy of the proposed model.