bluuebunny/crossref_metadata_2025 huggingface dataset:
Ubiquitin ligase and signalling hub MYCBP2 is required for efficient EPHB2 tyrosine kinase receptor function
Authors: Chang Chao , Banerjee Sara L. , Park Sung Soon , Zhang Xiaolei , Cotnoir-White David , Desbois Muriel , Grill Brock , Kania Artur
Published: July 2023

Eph receptor tyrosine kinases participate in a variety of normal and pathogenic processes during development and throughout adulthood. This versatility is likely facilitated by the ability of Eph receptors to signal through diverse cellular signalling pathways: primarily by controlling cytoskeletal dynamics, but also by regulating cellular growth, proliferation, and survival. Despite many proteins linked to these signalling pathways interacting with Eph receptors, the specific mechanisms behind such links and their coordination remain to be elucidated. In a proteomics screen for novel EPHB2 multi-effector proteins, we identified human MYC binding protein 2 (MYCBP2 or PAM or Phr1). MYCBP2 is a large signalling hub involved in diverse processes such as neuronal connectivity, synaptic growth, cell division, neuronal survival, and protein ubiquitination. Our biochemical experiments demonstrate that the formation of a complex containing EPHB2 and MYCBP2 is facilitated by FBXO45, a protein known to select substrates for MYCBP2 ubiquitin ligase activity. Formation of the MYCBP2-EPHB2 complex does not require EPHB2 tyrosine kinase activity and is destabilised by binding of ephrin-B ligands, suggesting that the MYCBP2-EPHB2 association is a prelude to EPHB2 signalling. Paradoxically, the loss of MYCBP2 results in increased ubiquitination of EPHB2 and a decrease of its protein levels suggesting that MYCBP2 stabilises EPHB2. Commensurate with this effect, our cellular experiments reveal that MYCBP2 is essential for efficient EPHB2 signalling responses in cell lines and primary neurons. Finally, our genetic studies in C. elegans provide in vivo evidence that the ephrin receptor VAB-1 functions within the MYCBP2 signalling network. Together, our results align with the similarity of neurodevelopmental phenotypes caused by MYCBP2 and EPHB2 loss of function, and our findings couple EPHB2 to a signaling effector controlling diverse cellular functions.
Análise da geração de resíduos de serviços de saúde nos laboratórios de uma universidade pública do estado de Mato Grosso do Sul
Authors: De Arruda Junior Luiz Mario , De Almeida Vera Luci , Oesterreich Silvia Aparecida
Published: July 2023

Os Resíduos de Serviços de Saúde (RSS) representam uma pequena parcela do total de resíduos gerados no Brasil. Atividades desenvolvidas por instituições de ensino e pesquisa, na área da saúde, geram quantidade significativa de resíduos que, por suas características podem causar enormes danos ambientais e à saúde humana. Neste contexto, a Faculdade de Ciências da Saúde (FCS), da Fundação Universidade Federal da Grande Dourados (UFGD) gera, no desenvolvimento das suas atividades de ensino e pesquisa, RSS que, devido suas características, necessitam atenção especial por parte dos gestores. Assim, o presente estudo teve como objetivo realizar a análise dos RSS gerados nos laboratórios de ciências da saúde da FCS, da UFGD, com a finalidade de desenvolver um Plano de Gerenciamento de Resíduos de Serviços de Saúde (PGRSS). A metodologia utilizada foi: revisão bibliográfica para análise de legislações, normas, artigos, dentre outras fontes; abordagem qualitativa, quantitativa e exploratória através de estudo de caso.  O estudo foi realizado com as informações obtidas junto à Prefeitura Universitária, coletadas de 2019 à 2022. A análise foi realizada a partir de dados da geração total dos resíduos por grupo de classificação, que totalizaram cerca de 1.400 Kg por ano. Foi possível identificar que a FCS da UFGD necessita da implantação de um PGRSS visto que maneja uma grande quantidade de RSS, que são resíduos perigosos à saúde e ao meio ambiente.
Effect of 3D‐Printable Anisotropic Fibrous Hydrogels on Fabricating Artificial Skeletal Muscle Constructs
Authors: Kim Kyoungryong , Jin Subin , Shin Mikyung
Published: July 2023

The use of fibrous hydrogel constructs is a promising strategy in tissue engineering because of their ability to closely mimic the anisotropic structure of biological tissues. In skeletal muscle tissue engineering, fiber alignment is considered a crucial factor for achieving muscle functions originating from the uniaxially aligned structure of myofibers; however, the fabrication process of hydrogel constructs with aligned fibers requires complex and laborious techniques. In this study, the effect of 3D‐printed constructs with randomly oriented fibers on myoblast differentiation is evaluated. To this end, 3D‐printable gelatin methacryloyl (GelMA) hydrogel microfibers through the mechanical fragmentation of electrospun GelMA sheets is prepared. The bulk rheological and tensile properties of the hydrogels with microfibers are stronger than those of the hydrogels without microfibers. Interestingly, when myoblast‐embedded constructs are 3D‐printed with and without randomly oriented GelMA hydrogel microfibers and incubated for cell differentiation, the microfibers in the constructs effectively promote myotubule‐like cell formation. In addition, the uniaxial 3D printed design enables anisotropic myotubule formation. This shows that hydrogels with only fibers distributed randomly can be applied to achieve more effective artificial muscle constructs than those achieved using normal bulk hydrogels and are easier to use than aligned fibers.
RNautophagic regulation of DNMT3a‐dependent DNA methylation by Linc00942 enhances chemoresistance in gastric cancer
Authors: Zhu Liyuan , Zhu Yiran , Li Fang , Meng Yuan , Wang Hanying , Xu Wenxia , Luo Jingfeng , Wang Xian , Feng Lifeng , Jin Hongchuan
Published: July 2023

Background

Energy balance has long been known to extend lifespans and inhibit carcinogenesis in multiple species by slowing age‐related epigenetic changes while the underlying mechanisms remain largely unknown. Herein, we found that starvation activated autophagy to remodel the DNA methylation profile by inhibiting DNMT3a expression.

Methods

Illumina Infinium MethylationEPIC BeadChip and dot blot assay were performed to quantify the global DNA methylation level. Protein−RNA interactions were validated through RNA immunoprecipitation and RNA pull‐down assay. In vitro and in vivo experiments were carried out to testify the effect of DNMT3a on chemoresistance.

Results

Autophagy is impaired in chemoresistance which was associated with differential DNA methylation and could be reversed by DNMT3a inhibition. Autophagy activation decreases the expression of DNMT3a mRNA, accompanied with the downregulation of chemoresistance‐related Linc00942. Knockdown of Linc00942 reduces DNMT3a expression and genome‐wide DNA methylation while Linc00942 overexpression increased DNMT3a expression and correlated hypermethylation in cancer cells and primary tumour tissues. Mechanistically, Linc00942 recruits RNA methyltransferase METTL3 to stimulate N6‐methyladenosine (m6A) deposit on DNMT3a transcripts, triggering IGF2BP3/HuR to recognize modified mRNA for reinforced stability. SQSTM1/p62 recruits Linc00942 for autophagic degradation which can be abrogated after autophagy inhibition by p62 knockdown or chloroquine treatment.

Conclusions

Inhibition of autophagy increases Linc00942 expression to promote chemoresistance and autophagy activation or hypomethylating agent decitabine restores chemosensitivity by reducing global DNA methylation. Overall, this study identifies a novel methylation cascade linking impaired RNautophagy to global hypermethylation in chemoresistance, and provides a rationale for repurposing decitabine to overcome chemoresistance in cancer treatment.
Ureteral Stent‐Related Symptoms and Pharmacotherapy: A Brief Narrative Review
Authors: Bellos Themistoklis Ch. , Katsimperis Stamatios N. , Kapsalos‐Dedes Sotirios G. , Tzelves Lazaros I. , Kostakopoulos Nikolaos A. , Mitsogiannis Iraklis C. , Varkarakis Ioannis M. , Papatsoris Athanasios G. , Deliveliotis Charalampos N.
Published: July 2023

The purpose of this article is to review the effects of different types of pharmacotherapy on symptoms that affect the quality of a patient's life after stent insertion. A thorough Medline/PubMed nonsystematic review was conducted from 1987 to January 2023, using the terms: “pigtail” OR “ureteral stents” AND “lower urinary tracts symptoms” OR “LUTS” AND “pharmacotherapy” OR “drugs”. Relevant studies conducted in humans and reported in English language were included. The available reviews and articles associating the use of drugs with stent‐related symptoms (SRS) provide conflicting results. Most of them show a clear benefit of alpha blockers, particularly alfuzosin, on treating urinary SRS, and hence there is a strong recommendation for the use of alpha blockers for the treatment of SRS in the guidelines of the European Association of Urology. Anticholinergics and mirabegron have shown a significant benefit in dealing with irritative bladder symptoms. In contrast, the findings for combination therapies are contradictory, with some studies showing that combination therapy is no superior to monotherapy with regards to most of the subsets of the Ureteral Stent Symptom Questionnaire (USSQ), whereas others present a clear benefit of combination therapies, specifically silodosin and solifenacin, in treating stent‐associated lower urinary tract symptoms (LUTS), in comparison with any other type of monotherapy or combination therapy. Many studies suggest that some categories of pharmacotherapy, such as alpha blockers, can alleviate SRS. However, there is conflicting evidence concerning most other types of medical treatment. Randomized trials with the largest number of patients are needed to investigate the effectiveness of novel approaches on SRS.
Epidemiology of Modic changes in dogs: Prevalence, possible risk factors, and association with spinal phenotypes
Authors: Beukers Martijn , Grinwis Guy C. M. , Vernooij Johannes C. M. , van der Hoek Lisanne , Tellegen Anna R. , Meij Björn P. , Veraa Stefanie , Samartzis Dino , Tryfonidou Marianna A. , Bach Frances C.
Published: July 2023

Background

Chronic low back pain, a leading contributor to disease burden worldwide, is often caused by intervertebral disc (IVD) degeneration. Modic changes (MCs) are MRI signal intensity changes due to lesions in vertebral bone marrow adjacent to degenerated IVDs. Only a few studies described the histopathological changes associated with MC to date. MC type 1 is suggested to be associated with bone marrow infiltration of fibrovascular tissue, type 2 with fatty infiltration, and type 3 with bone sclerosis in humans.

Methods

This study investigated whether the dog can be a valuable animal model to research MCs, by examining the prevalence, imaging, and histological characteristics of lumbar MCs in dogs (340 dogs, 2496 spinal segments).

Results

Logistic regression analysis indicated that the presence of lumbosacral MCs was associated with age and disc herniation (annulus fibrosis protrusion and/or nucleus pulposus extrusion). According to MRI analysis, MCs were mostly detected at the lumbosacral junction in dogs. Most signal intensity changes represented MC type 3, while previous spinal surgery seemed to predispose for the development of MC type 1 and 2. Histological analysis (16 dogs, 39 spinal segments) indicated that IVDs with MCs showed more histopathological abnormalities in the endplate and vertebral bone marrow than IVDs without MCs. Mostly chondroid proliferation in the bone marrow was encountered, while the histologic anomalies described in humans associated with MCs, such as fibrovascular or fatty infiltration, were scarcely detected.

Conclusions

Dogs spontaneously develop MCs, but may exhibit other pathological processes or more chronic bone marrow pathologies than humans with MCs. Therefore, more research is needed to determine the translatability of the MCs encountered in dog low‐back‐pain patients.
Children's Oncology Group's 2023 blueprint for research: Renal tumors
Authors: Geller James I. , Hong Andrew L. , Vallance Kelly L. , Evageliou Nick , Aldrink Jennifer H. , Cost Nicholas G. , Treece Amy L. , Renfro Lindsay A. , Mullen Elizabeth A. ,   the COG Renal Tumor Committee
Published: July 2023

Every year, approximately 600 infants, children, and adolescents are diagnosed with renal cancer in the United States. In addition to Wilms tumor (WT), which accounts for about 80% of all pediatric renal cancers, clear cell sarcoma of the kidney, renal cell carcinoma, malignant rhabdoid tumor, as well as more rare cancers (other sarcomas, rare carcinomas, lymphoma) and benign tumors can originate within the kidney. WT itself can be divided into favorable histology (FHWT), with a 5‐year overall survival (OS) exceeding 90%, and anaplastic histology, with 4‐year OS of 73.7%. Outcomes of the other pediatric renal cancers include clear cell sarcoma (5‐year OS: 90%), malignant rhabdoid tumor (5‐year OS: 10% for stages 3 and 4), and renal cell carcinoma (4‐year OS: 84.8%). Recent clinical trials have identified novel biological prognostic markers for FHWT, and a series of Children's Oncology Group (COG) trials have demonstrated improving outcomes with therapy modification, and opportunities for further care refinement.
Spatial and Sexual Divergence of Gut Bacterial Communities in Field Cricket Teleogryllus occipitalis (Orthoptera: Gryllidae)
Authors: Hirata Kazuya , Asahi Toru , Kataoka Kosuke
Published: July 2023

The insect gut is colonized by microbes that confer a myriad of beneficial services to the host, including nutritional support, immune enhancement, and even influence behavior. Insect gut microbes show dynamic changes due to the gut compartments, sex, and seasonal and geographic influences. Crickets are omnivorous hemimetabolous insects that have sex-specific roles, such as males producing chirping sounds for communication and exhibiting fighting behavior. However, limited information is available on their gut bacterial communities, hampering studies on functional compartmentalization of the gut and sex-specific roles of the gut microbiota in omnivorous insects. Here, we report a metagenomic analysis of the gut bacteriome of the field cricket Teleogryllus occipitalis using 16S rRNA V3-V4 amplicon sequencing to identify sex- and compartment-dependent influences on its diversity and function. The structure of the gut microbiota is strongly influenced by their gut compartments rather than sex. The species richness and diversity analyses revealed large difference in the bacterial communities between the gut compartments while minor differences were observed between the sexes. Analysis of relative abundance and predicted functions revealed that nitrogen- and oxygen-dependent metabolism and amino acid turnover were subjected to functional compartmentalization in the gut. Comparisons between the sexes revealed differences in the gut microbiota, reflecting efficiency in energy use, including glycolytic and carbohydrate metabolism, suggesting a possible involvement in egg production in females. This study provides insights into the gut compartment dependent and sex-specific roles of host-gut symbiont interactions in crickets and the industrial production of crickets.
Exposure Risks and Potential Control Measures for a Fire Behavior Lab Training Structure: Part B—Chemical Gas Concentrations
Authors: Horn Gavin P. , Stakes Keith , Neumann Danielle L. , Madrzykowski Daniel , Fent Kenneth W.
Published: July 2023

Firefighters’ or instructors’ exposure to airborne chemicals during live-fire training may depend on fuels being burned, fuel orientation and participants’ location within the structure. This study was designed to evaluate the impact of different control measures on exposure risk to combustion byproducts during fire dynamics training where fuel packages are mounted at or near the ceiling. These measures included substitution of training fuels (low density wood fiberboard, oriented strand board (OSB), pallets, particle board, plywood) and adoption of engineering controls such as changing the location of the instructor and students using the structure. Experiments were conducted for two different training durations: the typical six ventilation cycle (six-cycle) and a shorter three ventilation cycle (three-cycle) with a subset of training fuels. In Part A of this series, we characterized the fire dynamics within the structure, including the ability of each fuel to provide an environment that achieves the training objectives. Here, in Part B, airborne chemical concentrations are reported at the location where fire instructors would typically be operating. We hypothesized that utilizing a training fuel package with solid wood pallets would result in lower concentrations of airborne contaminants at the rear instructor location than wood-based sheet products containing additional resins and/or waxes. In the six-cycle experiments (at the rear instructor location), OSB-fueled fires produced the highest median concentrations of benzene and 1,3 butadiene, plywood-fueled fires produced the highest total polycyclic aromatic hydrocarbon (PAH) concentrations, particle board-fueled fires produced the highest methyl isocyanate concentrations, and pallet-fueled fires produced the highest hydrogen chloride concentrations. All fuels other than particle board produced similarly high levels of formaldehyde at the rear instructor location. The OSB fuel package created the most consistent fire dynamics over six-cycles, while fiberboard resulted in consistent fire dynamics only for the first three cycles. In the follow-on three-cycle experiment, PAH, benzene, and aldehyde concentrations were similar for the OSB and fiberboard-fueled fires. Air sampling did not identify any clear differences between training fires from burning solid wood pallets and those that incorporate wood-based sheet products for this commonly employed fuel arrangement with fuels mounted high in the compartment. However, it was found that exposure can be reduced by moving firefighters and instructors lower in the compartment and/or by moving the instructor in charge of ventilation from the rear of the structure (where highest concentrations were consistently measured) to an outside position.
Distinct Requirements for Adaptor Proteins NCK1 and NCK2 in Mammary Gland Development
Authors: Golding Adam P. , Ferrier Benjamin , New Laura A. , Lu Peihua , Martin Claire E. , Shata Erka , Jones Robert A. , Moorehead Roger A. , Jones Nina
Published: July 2023

The adaptor proteins NCK1 and NCK2 are well-established signalling nodes that regulate diverse biological processes including cell proliferation and actin dynamics in many tissue types. Here we have investigated the distribution and function of Nck1 and Nck2 in the developing mouse mammary gland. Using publicly available single-cell RNA sequencing data, we uncovered distinct expression profiles between the two paralogs. Nck1 showed widespread expression in luminal, basal, stromal and endothelial cells, while Nck2 was restricted to luminal and basal cells, with prominent enrichment in hormone-sensing luminal subtypes. Next, using mice with global knockout of Nck1 or Nck2, we assessed mammary gland development during and after puberty (5, 8 and 12 weeks of age). Mice lacking Nck1 or Nck2 displayed significant defects in ductal outgrowth and branching at 5 weeks compared to controls, and the defects persisted in Nck2 knockout mice at 8 weeks before normalizing at 12 weeks. These defects were accompanied by an increase in epithelial cell proliferation at 5 weeks and a decrease at 8 weeks in both Nck1 and Nck2 knockout mice. We also profiled expression of several key genes associated with mammary gland development at these timepoints and detected temporal changes in transcript levels of hormone receptors as well as effectors of cell proliferation and migration in Nck1 and Nck2 knockout mice, in line with the distinct phenotypes observed at 5 and 8 weeks. Together these studies reveal a requirement for NCK proteins in mammary gland morphogenesis, and suggest that deregulation of Nck expression could drive breast cancer progression and metastasis.
Radon indoor concentration time-variation model
Authors: Orabi M.
Published: July 2023

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Inhibition of CARM1 suppresses proliferation of multiple myeloma cells through activation of p53 signaling pathway
Authors: Yang Lan , Ma Le , Gong Qiang , Chen JiePing , Huang Qilin
Published: July 2023

Background

Multiple myeloma (MM) is a malignant proliferative disease of plasma cells, the incidence of which is increasing every year and remains incurable. The enzyme co-activator-associated arginine methyltransferase 1 (CARM1) is highly expressed in a variety of cancers, such as Hodgkin's lymphoma and acute myeloid leukemia, and CARM1 is closely associated with tumor cell proliferation. However, the role of CARM1 in MM has not been elucidated.

Methods and results

In this study, we found that CARM1 is overexpressed in MM and closely associated with poor prognosis in MM. CCK-8 and colony formation assays showed that the proliferation of MM cell lines was downregulated when CARM1 expression was knockdown by specific shRNA. Knockdown of CARM1 reduced the proportion of MM cell lines in the S phase and increased the proportion in G0/G1 phase. RNA-seq analysis of the CARM1-KD cell line revealed that it was closely associated with apoptosis and activated the p53 pathway. CCK-8 and apoptosis results showed that CARM1 knockdown made MM cells more sensitive to standard-of-care drugs.

Conclusion

This study provides an experimental basis for elucidating the pathogenesis of multiple myeloma and searching for potential therapeutic targets.
The Associations Between Neuropsychiatric Symptoms and Cognition in People with Dementia: A Systematic Review and Meta-Analysis
Authors: Sabates Julieta , Chiu Wei-Hsuan , Loi Samantha , Lampit Amit , Gavelin Hanna M. , Chong Terence , Launder Nathalie , Goh Anita M. Y. , Brodtmann Amy , Lautenschlager Nicola , Bahar-Fuchs Alex
Published: July 2023

Most people with dementia experience neuropsychiatric symptoms (NPS), including anxiety, depression or disinhibition. There is growing interest in the relationship between NPS and cognitive impairment, but data is still limited. This study aimed to investigate the specific associations between NPS and cognition in people with dementia. MEDLINE, EMBASE and PsycINFO were searched for published, peer-reviewed studies of associations between at least one NPS and one cognitive ability in people with dementia. The quality of the studies was assessed with the NIH National Heart, Lung and Blood Institute’s quality assessment tools. A meta-analysis was conducted using Robumeta package for R. Ninety studies were included. We found significant associations between NPS, global cognition and cognitive domains, e.g. apathy was associated with global cognitive and memory impairment; dysphoria was associated with worse attention; delusions with executive dysfunction. Increased NPS in people with dementia are associated with worse cognitive performance. There were few studies looking at associations between some neuropsychiatric clusters and cognitive abilities, and there was little research on causal relationships. Our review was limited by the inclusion of studies that reported associations in specific formats, and most included people with a diagnosis of Alzheimer’s disease (AD). However, given the large number of studies, this is unlikely to have biased results. More research is needed that includes diverse people with different dementia syndromes. Registration: PROSPERO 2020 CRD42020165565.
Persistence in UK Historical Data on Life Expectancy
Authors: Caporale Guglielmo Maria , Infante Juan , del Rio Marta , Gil-Alana Luis A.
Published: July 2023

This paper provides estimates of persistence in historical UK data on life expectancy applying fractional integration methods to both an annual series from 1842 to 2019 and a 5-year average from 1543 to 2019. This method is the most appropriate for our purposes since it is more general and flexible than the classical methods based on integer differentiation. The results indicate that the former exhibits an upward trend and is persistent but mean reverting; the same holds for the latter, though its degree of persistence is higher. Similar results are obtained for the logged values. On the whole, this evidence suggests that the effects of shocks to the series are transitory though persistent, which is useful information for policy makers whose task is to take appropriate measures to increase life expectancy.
Efficient Super‐Resolution of Near‐Surface Climate Modeling Using the Fourier Neural Operator
Authors: Jiang Peishi , Yang Zhao , Wang Jiali , Huang Chenfu , Xue Pengfei , Chakraborty T. C. , Chen Xingyuan , Qian Yun
Published: July 2023

Downscaling methods are critical in efficiently generating high‐resolution atmospheric data. However, state‐of‐the‐art statistical or dynamical downscaling techniques either suffer from the high computational cost of running a physical model or require high‐resolution data to develop a downscaling tool. Here, we demonstrate a recently proposed zero‐shot super‐resolution method, the Fourier neural operator (FNO), to efficiently perform downscaling without the need for high‐resolution data. Because the FNO learns dynamics in Fourier space, FNO is a resolution‐invariant emulator; it can be trained at a coarse resolution and produces emulation at any high resolution. We applied FNO to downscale a 4‐km resolution Weather Research and Forecasting (WRF) Model simulation of near‐surface heat‐related variables over the Great Lakes region. The FNO is driven by the atmospheric forcings and topographic features used in the WRF model at the same resolution. We incorporated a physics‐constrained loss in FNO by using the Clausius–Clapeyron relation to better constrain the relations among the emulated states. Trained on merely 600 WRF snapshots at 4‐km resolution, the FNO shows comparable performance with a widely‐used convolutional network, U‐Net, achieving averaged modified Kling–Gupta Efficiency of 0.88 and 0.94 on the test data set for temperature and pressure, respectively. We then employed the FNO to produce 1‐km emulations to reproduce the fine climate features. Further, by taking the WRF simulation as ground truth, we show consistent performances at the two resolutions, suggesting the reliability of FNO in producing high‐resolution dynamics. Our study demonstrates the potential of using FNO for zero‐shot super‐resolution in generating first‐order estimation on atmospheric modeling.
White matter alterations in Attention-Deficit/Hyperactivity Disorder (ADHD): a systematic review of 129 diffusion imaging studies with meta-analysis
Authors: Parlatini Valeria , Itahashi Takashi , Lee Yeji , Liu Siwei , Nguyen Thuan T. , Aoki Yuta Y. , Forkel Stephanie J. , Catani Marco , Rubia Katya , Zhou Juan H. , Murphy Declan G. , Cortese Samuele
Published: July 2023

Aberrant anatomical brain connections in attention-deficit/hyperactivity disorder (ADHD) are reported inconsistently across diffusion weighted imaging (DWI) studies. Based on a pre-registered protocol (Prospero: CRD42021259192), we searched PubMed, Ovid, and Web of Knowledge until 26/03/2022 to conduct a systematic review of DWI studies. We performed a quality assessment based on imaging acquisition, preprocessing, and analysis. Using signed differential mapping, we meta-analyzed a subset of the retrieved studies amenable to quantitative evidence synthesis, i.e., tract-based spatial statistics (TBSS) studies, in individuals of any age and, separately, in children, adults, and high-quality datasets. Finally, we conducted meta-regressions to test the effect of age, sex, and medication-naïvety. We included 129 studies (6739 ADHD participants and 6476 controls), of which 25 TBSS studies provided peak coordinates for case-control differences in fractional anisotropy (FA)(32 datasets) and 18 in mean diffusivity (MD)(23 datasets). The systematic review highlighted white matter alterations (especially reduced FA) in projection, commissural and association pathways of individuals with ADHD, which were associated with symptom severity and cognitive deficits. The meta-analysis showed a consistent reduced FA in the splenium and body of the corpus callosum, extending to the cingulum. Lower FA was related to older age, and case-control differences did not survive in the pediatric meta-analysis. About 68% of studies were of low quality, mainly due to acquisitions with non-isotropic voxels or lack of motion correction; and the sensitivity analysis in high-quality datasets yielded no significant results. Findings suggest prominent alterations in posterior interhemispheric connections subserving cognitive and motor functions affected in ADHD, although these might be influenced by non-optimal acquisition parameters/preprocessing. Absence of findings in children may be related to the late development of callosal fibers, which may enhance case-control differences in adulthood. Clinicodemographic and methodological differences were major barriers to consistency and comparability among studies, and should be addressed in future investigations.
Targeting N-glycosylation of 4F2hc mediated by glycosyltransferase B3GNT3 sensitizes ferroptosis of pancreatic ductal adenocarcinoma
Authors: Ma Heng , Chen Xianlong , Mo Shengwei , Zhang Yue , Mao Xinxin , Chen Jingci , Liu Yilin , Tong Wei-Min , Lu Zhaohui , Yu Shuangni , Chen Jie
Published: July 2023

Pancreatic ductal adenocarcinoma (PDAC) remains a highly fatal malignancy partially due to the acquired alterations related to aberrant protein glycosylation that pathologically remodel molecular biological processes and protect PDAC cells from death. Ferroptosis driven by lethal lipid peroxidation provides a targetable vulnerability for PDAC. However, the crosstalk between glycosylation and ferroptosis remains unclear. Here, we identified 4F2hc, a subunit of the glutamate-cystine antiporter system Xc–, and its asparagine (N)-glycosylation is involved in PDAC ferroptosis by N- and O-linked glycoproteomics. Knockdown of SLC3A2 (gene name of 4F2hc) or blocking the N-glycosylation of 4F2hc potentiates ferroptosis sensitization of PDAC cells by impairing the activity of system Xc– manifested by a marked decrease in intracellular glutathione. Mechanistically, we found that the glycosyltransferase B3GNT3 catalyzes the glycosylation of 4F2hc, stabilizes the 4F2hc protein, and enhances the interaction between 4F2hc and xCT. Knockout of B3GNT3 or deletion of enzymatically active B3GNT3 sensitizes PDAC cells to ferroptosis. Reconstitution of 4F2hc-deficient cells with wildtype 4F2hc restores ferroptosis resistance while glycosylation-mutated 4F2hc does not. Additionally, upon combination with a ferroptosis inducer, treatment with the classical N-glycosylation inhibitor tunicamycin (TM) markedly triggers the overactivation of lipid peroxidation and enhances the sensitivity of PDAC cells to ferroptosis. Notably, we confirmed that genetic perturbation of SLC3A2 or combination treatment with TM significantly augments ferroptosis-induced inhibition of orthotopic PDAC. Clinically, high expression of 4F2hc and B3GNT3 contributes to the progression and poor survival of PDAC patients. Collectively, our findings reveal a previously unappreciated function of N-glycosylation of 4F2hc in ferroptosis and suggest that dual targeting the vulnerabilities of N-glycosylation and ferroptosis may be an innovative therapeutic strategy for PDAC.
Exploring the role of retinal fluid as a biomarker for the management of diabetic macular oedema
Authors: Khoramnia Ramin , Nguyen Quan Dong , Kertes Peter J. , Sararols Ramsay Laura , Vujosevic Stela , Anderesi Majid , Igwe Franklin , Eter Nicole
Published: July 2023

Anti-VEGF therapies are associated with significant gains in visual acuity and fluid resolution in the treatment of diabetic macular oedema (DMO) and have become the standard of care. However, despite their efficacy, outcomes can be unpredictable, vary widely between individual eyes, and a large proportion of patients have persistent fluid following initial treatment, with a negative impact on visual outcomes. Anatomical parameters measured by optical coherence tomography (OCT), in addition to visual acuity, are key to monitoring treatment effectiveness and guiding retreatment decisions; however, existing guidelines on the management of DMO lack clear recommendations for interpretation of OCT parameters, or proposed thresholds of various markers to guide retreatment decisions. Although central subfield thickness (CSFT) has been widely used as a marker for retreatment decisions in clinical trials in DMO, and a reduction in CSFT has generally been shown to accompany improvements in best-corrected visual acuity with treatment, analyses of the relationship between these parameters show that the correlation is small to moderate. A more direct relationship can be seen between an increased magnitude of CSFT fluctuations over time and poorer visual acuity, suggesting that control of CSFT could be important in maximising visual outcomes. The relationship between visual outcomes and qualitatively assessed intraretinal fluid and subretinal fluid is also unclear, although quantitative assessments of fluid parameters suggest that untreated intraretinal fluid and subretinal fluid negatively impact visual outcomes. These findings highlight a need for clearer guidelines on the management of retinal fluid to improve visual outcomes for patients with DMO.
Catalytic activity of a new dioxidomolybdenum(vi) complex with a bipodal N2O-donor ligand in sulfur compound oxidation
Authors: Machado Paula M. A. , Barreto Juliana M. , Motta Ramon da S. , Rodrigues José Guilherme A. , de Souza Wladmir F. , Maldonado Igor A. V. , Allão Cassaro Rafael A. , dos Santos Gustavo R. C. , Carneiro Gabriel R. A. , Pereira Henrique M. G. , D’Elia Eliane , Horn Adolfo , Lachter Elizabeth Roditi
Published: July 2023

A new dinuclear dioxidomolybdenum(vi) complex [(MoO2)2(BPA)2(μ-O)] was synthesized and evaluated as a catalyst in the reaction involving the oxidation of sulfur compounds.
pH-tunable phosphorescence and light harvesting in cucurbit[8]uril host–guest assemblies
Authors: Bhaumik Shubhra Kanti , Panda Sourav Kumar , Banerjee Supratim
Published: July 2023

Host–guest assemblies based on cucurbit[8]uril and halo-phenyl pyridines exhibit pH-responsive phosphorescence under ambient conditions, and they were further exploited to fabricate light-harvesting systems in aqueous media.
To touch or not to touch? Fingerprint-assisted grinding of carbamazepine form III
Authors: Zheltikova Daria , Losev Evgeniy , Boldyreva Elena
Published: July 2023

Mechanically induced polymorphic transformation of polymorph III of carbamazepine into polymorph IV was accelerated and brought to completion by contaminating deliberately a milling jar and ball by touching them with fingers.
Cu2O/Cu2S microstructure regulation towards high efficiency photocatalytic hydrogen production and its theoretical mechanism analysis
Authors: Qiao Fen , Qian Sen , Liu Wenjie , Zhou Taihang , Yang Jing , Zhao Jikang , Yuan Jiaren
Published: July 2023

Compared with cubic Cu2O, the Cu2O/Cu2S composite exhibits better photocatalytic hydrogen production. The catalytic hydrogen production of the Cu2O/Cu2S heterostructure reached 1076.95 μmol g−1 after 5 h of illumination.
Conversion of La2Ti2O7 to LaTiO2N via ammonolysis: a first-principles investigation
Authors: Ricca Chiara , Blandenier Tristan , Werner Valérie , Wang Xing , Pokrant Simone , Aschauer Ulrich
Published: July 2023

Density functional theory shows oxynitride synthesis by thermal ammonolysis to be strongly affected by defects in the oxide precursor.
Aqueous hydroboration of alkynes via nonclassical generation of N-heterocyclic carbenes
Authors: Tao Sheng , Wang Yang , Pan Qianxiu , Zhao Jixing , Bu Qingqing , Chen Fei , Liu Jichang , Dai Bin , Wei Donghui , Liu Ning
Published: July 2023

We report a nonclassical strategy of generation of N-heterocyclic carbenes for aqueous hydroboration of alkynes.
Noble gas mass-spectrometry for extraterrestrial micro-samples: analyses of asteroid matter returned by Hayabusa2 JAXA mission
Authors: Meshik Alexander , Pravdivtseva Olga , Okazaki Ryuji , Yogata Kasumi , Yada Toru , Kitajima Fumio , Yurimoto Hisayoshi , Nakamura Tomoki , Noguchi Takaaki , Yabuta Hikaru , Naraoka Hiroshi , Sakamoto Kanako , Tachibana Shogo , Nishimura Masahiro , Nakato Aiko , Miyazaki Akiko , Abe Masanao , Okada Tatsuaki , Usui Tomohiro , Yoshikawa Makoto , Sakai Takanao , Tanaka Satoshi , Terui Fuyuto , Nakazawa Satoru , Watanabe Seiichiro , Tsuda Yuichi , Hayabusa2 Initial Analysis Volatile Team
Published: July 2023

Mass spectrometry of noble gas isotopes from the asteroid materials delivered by robotic space missions requires high sensitivity, high ion transmission, low detection limit, and other characteristics not readily available in commercial instruments.
High-precision broadband linear polarimetry of early-type binaries
Authors: Abdul Qadir Yasir , Berdyugin Andrei V. , Piirola Vilppu , Sakanoi Takeshi , Kagitani Masato
Published: July 2023

Aims. DH Cephei is a well-known massive O+O-type binary system on the northern sky, situated at the center of young open cluster NGC 7380. Our high-precision multi-band polarimetry clearly reveals that variations of linear polarization in this system are synchronous with the phase of the orbital period. We used the observed variations of Stokes parameters q and u to derive the orbital inclination i, orientation Ω, and the direction of rotation. Moreover, in order to obtain a rough estimation of the interstellar polarization in the vicinity of DH Cep, we observed polarization arising from the neighboring stars in the cluster.

Methods. We used the Dipo1–2 polarimeter in combination with the remotely controlled 60 cm Tohoku T60 telescope to obtain linear polarization measurements of DH Cep in the B, V, and R passbands at the accuracy level of ~0.003%. To obtain an estimation of interstellar polarization of DH Cep, we observed more than a dozen field stars identified as members of NGC 7380 and in the close proximity to DH Cep. A Lomb-Scargle period search was applied to the acquired polarization data to reveal the dominating frequency in polarization variations. We used a standard analytical method based on a two-harmonics Fourier fit to derive the inclination, orientation, and the direction of rotation of the binary orbit.

Results. The variations of Stokes parameters in all three B, V, and R passbands clearly suggest an unambiguous periodic signal at 1.055 d with an amplitude of variations of ~0.2%, which corresponds to half of the known orbital period of 2.11 d. This type of polarization variability is expected for a binary system with light-scattering material distributed symmetrically with respect to the orbital plane. In addition to the regular polarization variability, there is a nonperiodic component, which is strongest in the B passband. In the V passband, we obtained our most reliable values for the orbital inclination i = 46° + 11°/ − 46° and an orientation of the orbit on the sky of Ω = 105° ± 55°, with 1σ confidence intervals. Using our best estimate of i and the polametric amplitude in the V passband, we estimated that the mass loss from the system is ~3.4 × 10−7 M⊙ yr−1. The direction of the binary system rotation on the plane of the sky is clockwise. Our polarimetric observations of neighboring stars of DH Cep in NGC 7380 reveal that the polarization of the cluster stars is most likley due to aligned interstellar dust in the foreground.
Pericentrin interacts with Kinesin-1 to drive centriole motility
Authors: Hannaford Matthew R. , Liu Rong , Billington Neil , Swider Zachary T. , Galletta Brian J. , Fagerstrom Carey J. , Combs Christian , Sellers James R. , Rusan Nasser M.
Published: July 2023

Centrosome positioning is essential for their function. Typically, centrosomes are transported to various cellular locations through the interaction of centrosomal microtubules (MTs) with motor proteins anchored at the cortex or the nuclear surface. However, it remains unknown how centrioles migrate in cellular contexts in which they do not nucleate MTs. Here, we demonstrate that during interphase, inactive centrioles move directly along the interphase MT network as Kinesin-1 cargo. We identify Pericentrin-Like-Protein (PLP) as a novel Kinesin-1 interacting molecule essential for centriole motility. In vitro assays show that PLP directly interacts with the cargo binding domain of Kinesin-1, allowing PLP to migrate on MTs. Binding assays using purified proteins revealed that relief of Kinesin-1 autoinhibition is critical for its interaction with PLP. Finally, our studies of neural stem cell asymmetric divisions in the Drosophila brain show that the PLP–Kinesin-1 interaction is essential for the timely separation of centrioles, the asymmetry of centrosome activity, and the age-dependent centrosome inheritance.
Lysosomal cholesterol overload in macrophages promotes liver fibrosis in a mouse model of NASH
Authors: Itoh Michiko , Tamura Atsushi , Kanai Sayaka , Tanaka Miyako , Kanamori Yohei , Shirakawa Ibuki , Ito Ayaka , Oka Yasuyoshi , Hidaka Isao , Takami Taro , Honda Yasushi , Maeda Mitsuyo , Saito Yasuyuki , Murata Yoji , Matozaki Takashi , Nakajima Atsushi , Kataoka Yosky , Ogi Tomoo , Ogawa Yoshihiro , Suganami Takayoshi
Published: July 2023

Accumulation of lipotoxic lipids, such as free cholesterol, induces hepatocyte death and subsequent inflammation and fibrosis in the pathogenesis of nonalcoholic steatohepatitis (NASH). However, the underlying mechanisms remain unclear. We have previously reported that hepatocyte death locally induces phenotypic changes in the macrophages surrounding the corpse and remnant lipids, thereby promoting liver fibrosis in a murine model of NASH. Here, we demonstrated that lysosomal cholesterol overload triggers lysosomal dysfunction and profibrotic activation of macrophages during the development of NASH. β-cyclodextrin polyrotaxane (βCD-PRX), a unique supramolecule, is designed to elicit free cholesterol from lysosomes. Treatment with βCD-PRX ameliorated cholesterol accumulation and profibrotic activation of macrophages surrounding dead hepatocytes with cholesterol crystals, thereby suppressing liver fibrosis in a NASH model, without affecting the hepatic cholesterol levels. In vitro experiments revealed that cholesterol-induced lysosomal stress triggered profibrotic activation in macrophages predisposed to the steatotic microenvironment. This study provides evidence that dysregulated cholesterol metabolism in macrophages would be a novel mechanism of NASH.
Insights into Stevens–Johnson syndrome/toxic epidermal necrolysis lifetime burden: assessing life expectancy, healthcare costs and quality of life
Authors: Liu Yi , Li Qing , Chu Chenyu , Zhou Yin
Published: July 2023

This study highlights the need for further exploration of factors that influence the declining incidence rate of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), interventions to mitigate loss-of-life expectancy and healthcare costs, and impact on quality of life. The findings emphasize the importance of ongoing efforts to minimize the burden of SJS/TEN and optimize patient care.
The burden of cardiovascular disease attributable to high body mass index—an observational study
Authors: Dong Xin-Jiang , Zhang Xiao-Qi , Wang Bei-Bei , Hou Fei-Fei , Jiao Yang , Wang Jian-Gang
Published: July 2023

Aim

This study aims to provide a timely and comprehensive estimate of the current burden and temporal trend of cardiovascular disease (CVD) attributable to high body mass index (HBMI).

Methods

We systematically assessed the current burden and temporal trend of CVD attributable to HBMI by calendar year, age, sex, region, nation, socioeconomic status, and specific CVD based on the most recent Global Burden of Disease Study (GBD) 2019.

Results

Globally, the numbers of CVD-related disability-adjusted life years (DALYs) and deaths attributable to HBMI has more than doubled from 1990 to 2019. Conversely, the age-standardized rates (ASRs) of CVD-related DALYs and deaths attributable to HBMI showed a slight downward trend, with estimated annual percentage change (EAPC) of −0.18 and −0.43, respectively. The ASRs of CVD-related DALYs and deaths attributable to HBMI were lower in low and high Socio-demographic Index (SDI) regions in 2019, but higher in middle and high-middle SDI regions. The ASRs of CVD-related DALYs and deaths attributable to HBMI showed a downward trend in the high SDI regions from 1990 to 2019, but showed an upward trend in the low and low-middle SDI regions. The leading causes of CVD burden attributable to HBMI were ischemic heart disease, stroke, hypertensive heart disease, and atrial fibrillation/flutter in 2019.

Conclusion

The CVD burden attributable to HBMI remains a challenging global health concern. Policymakers in high and increasing burden regions can learn from some valuable experiences of low and decreasing burden regions and develop more targeted and specific strategies to prevent and reduce CVD burden attributable to HBMI.