bluuebunny/crossref_metadata_2025_split huggingface dataset:
SNX8 enables lysosome reformation and reverses lysosomal storage disorder
Authors: Li Xinran , Xiang Cong , Zhu Shilei , Guo Jiansheng , Liu Chang , Wang Ailian , Cao Jin , Lu Yan , Neculai Dante , Xu Pinglong , Feng Xin-Hua 
Published: March 2024

AbstractLysosomal Storage Disorders (LSDs), which share common phenotypes, including enlarged lysosomes and defective lysosomal storage, are caused by mutations in lysosome-related genes. Although gene therapies and enzyme replacement therapies have been explored, there are currently no effective routine therapies against LSDs. During lysosome reformation, which occurs when the functional lysosome pool is reduced, lysosomal lipids and proteins are recycled to restore lysosome functions. Here we report that the sorting nexin protein SNX8 promotes lysosome tubulation, a process that is required for lysosome reformation, and that loss of SNX8 leads to phenotypes characteristic of LSDs in human cells. SNX8 overexpression rescued features of LSDs in cells, and AAV-based delivery of SNX8 to the brain rescued LSD phenotypes in mice. Importantly, by screening a natural compound library, we identified three small molecules that enhanced SNX8–lysosome binding and reversed LSD phenotypes in human cells and in mice. Altogether, our results provide a potential solution for the treatment of LSDs.
Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma
Authors: Ramirez Christel F. A. , Taranto Daniel , Ando-Kuri Masami , de Groot Marnix H. P. , Tsouri Efi , Huang Zhijie , de Groot Daniel , Kluin Roelof J. C. , Kloosterman Daan J. , Verheij Joanne , Xu Jing , Vegna Serena , Akkari Leila 
Published: March 2024

AbstractMyeloid cells are abundant and plastic immune cell subsets in the liver, to which pro-tumorigenic, inflammatory and immunosuppressive roles have been assigned in the course of tumorigenesis. Yet several aspects underlying their dynamic alterations in hepatocellular carcinoma (HCC) progression remain elusive, including the impact of distinct genetic mutations in shaping a cancer-permissive tumor microenvironment (TME). Here, in newly generated, clinically-relevant somatic female HCC mouse models, we identify cancer genetics’ specific and stage-dependent alterations of the liver TME associated with distinct histopathological and malignant HCC features. Mitogen-activated protein kinase (MAPK)-activated,NrasG12D-driven tumors exhibit a mixed phenotype of prominent inflammation and immunosuppression in a T cell-excluded TME. Mechanistically, we report aNrasG12Dcancer cell-driven, MEK-ERK1/2-SP1-dependent GM-CSF secretion enabling the accumulation of immunosuppressive and proinflammatory monocyte-derived Ly6Clowcells. GM-CSF blockade curbs the accumulation of these cells, reduces inflammation, induces cancer cell death and prolongs animal survival. Furthermore, GM-CSF neutralization synergizes with a vascular endothelial growth factor (VEGF) inhibitor to restrain HCC outgrowth. These findings underscore the profound alterations of the myeloid TME consequential to MAPK pathway activation intensity and the potential of GM-CSF inhibition as a myeloid-centric therapy tailored to subsets of HCC patients.
Structural basis for peroxidase encapsulation inside the encapsulin from the Gram-negative pathogen Klebsiella pneumoniae
Authors: Jones Jesse A. , Andreas Michael P. , Giessen Tobias W. 
Published: March 2024

AbstractEncapsulins are self-assembling protein nanocompartments capable of selectively encapsulating dedicated cargo proteins, including enzymes involved in iron storage, sulfur metabolism, and stress resistance. They represent a unique compartmentalization strategy used by many pathogens to facilitate specialized metabolic capabilities. Encapsulation is mediated by specific cargo protein motifs known as targeting peptides (TPs), though the structural basis for encapsulation of the largest encapsulin cargo class, dye-decolorizing peroxidases (DyPs), is currently unknown. Here, we characterize a DyP-containing encapsulin from the enterobacterial pathogen Klebsiella pneumoniae. By combining cryo-electron microscopy with TP and TP-binding site mutagenesis, we elucidate the molecular basis for cargo encapsulation. TP binding is mediated by cooperative hydrophobic and ionic interactions as well as shape complementarity. Our results expand the molecular understanding of enzyme encapsulation inside protein nanocompartments and lay the foundation for rationally modulating encapsulin cargo loading for biomedical and biotechnological applications.
Mutations in the efflux pump regulator MexZ shift tissue colonization by Pseudomonas aeruginosa to a state of antibiotic tolerance
Authors: Laborda Pablo , Lolle Signe , Hernando-Amado Sara , Alcalde-Rico Manuel , Aanæs Kasper , Martínez José Luis , Molin Søren , Johansen Helle Krogh 
Published: March 2024

AbstractMutations in mexZ, encoding a negative regulator of the expression of the mexXY efflux pump genes, are frequently acquired by Pseudomonas aeruginosa at early stages of lung infection. Although traditionally related to resistance to the first-line drug tobramycin, mexZ mutations are associated with low-level aminoglycoside resistance when determined in the laboratory, suggesting that their selection during infection may not be necessarily, or only, related to tobramycin therapy. Here, we show that mexZ-mutated bacteria tend to accumulate inside the epithelial barrier of a human airway infection model, thus colonising the epithelium while being protected against diverse antibiotics. This phenotype is mediated by overexpression of lecA, a quorum sensing-controlled gene, encoding a lectin involved in P. aeruginosa tissue invasiveness. We find that lecA overexpression is caused by a disrupted equilibrium between the overproduced MexXY and another efflux pump, MexAB, which extrudes quorum sensing signals. Our results indicate that mexZ mutations affect the expression of quorum sensing-regulated pathways, thus promoting tissue invasiveness and protecting bacteria from the action of antibiotics within patients, something unnoticeable using standard laboratory tests.
An ARF gene mutation creates flint kernel architecture in dent maize
Authors: Wang Haihai , Huang Yongcai , Li Yujie , Cui Yahui , Xiang Xiaoli , Zhu Yidong , Wang Qiong , Wang Xiaoqing , Ma Guangjin , Xiao Qiao , Huang Xing , Gao Xiaoyan , Wang Jiechen , Lu Xiaoduo , Larkins Brian A. , Wang Wenqin , Wu Yongrui 
Published: March 2024

AbstractDent and flint kernel architectures are important characteristics that affect the physical properties of maize kernels and their grain end uses. The genes controlling these traits are unknown, so it is difficult to combine the advantageous kernel traits of both. We found mutation of ARFTF17 in a dent genetic background reduces IAA content in the seed pericarp, creating a flint-like kernel phenotype. ARFTF17 is highly expressed in the pericarp and encodes a protein that interacts with and inhibits MYB40, a transcription factor with the dual functions of repressing PIN1 expression and transactivating genes for flavonoid biosynthesis. Enhanced flavonoid biosynthesis could reduce the metabolic flux responsible for auxin biosynthesis. The decreased IAA content of the dent pericarp appears to reduce cell division and expansion, creating a shorter, denser kernel. Introgression of the ARFTF17 mutation into dent inbreds and hybrids improved their kernel texture, integrity, and desiccation, without affecting yield.
Strain regulates the photovoltaic performance of thick-film perovskites
Authors: Shi Pengju , Xu Jiazhe , Yavuz Ilhan , Huang Tianyi , Tan Shaun , Zhao Ke , Zhang Xu , Tian Yuan , Wang Sisi , Fan Wei , Li Yahui , Jin Donger , Yu Xuemeng , Wang Chenyue , Gao Xingyu , Chen Zhong , Shi Enzheng , Chen Xihan , Yang Deren , Xue Jingjing , Yang Yang , Wang Rui 
Published: March 2024

AbstractPerovskite photovoltaics, typically based on a solution-processed perovskite layer with a film thickness of a few hundred nanometres, have emerged as a leading thin-film photovoltaic technology. Nevertheless, many critical issues pose challenges to its commercialization progress, including industrial compatibility, stability, scalability and reliability. A thicker perovskite film on a scale of micrometres could mitigate these issues. However, the efficiencies of thick-film perovskite cells lag behind those with nanometre film thickness. With the mechanism remaining elusive, the community has long been under the impression that the limiting factor lies in the short carrier lifetime as a result of defects. Here, by constructing a perovskite system with extraordinarily long carrier lifetime, we rule out the restrictions of carrier lifetime on the device performance. Through this, we unveil the critical role of the ignored lattice strain in thick films. Our results provide insights into the factors limiting the performance of thick-film perovskite devices.
Importance of modifiable non-radiographic functional parameters for adult spinal deformity
Authors: Mizutani Kozaburo , Kobayashi Tetsuya , Senoo Issei , Shimizu Mutsuya , Okayasu Hiroki 
Published: March 2024

AbstractWe clarified non-radiographic physical parameters associated with the severity of adult spinal deformity (ASD) using community-dwelling adult volunteers. They were subjected to upright entire spine radiographs for standard radiographic parameters and the number of sagittal modifiers of SRS-Schwab ASD classification (Schwab-SM). Clinical evaluations included isometric muscle strength of trunk extensor (TEX), trunk flexor (TFL), quadriceps femoris (QF), gluteus maximus, and iliopsoas; range of motion (ROM) of hip, knee, ankle, and active back extension (BET); SF36 physical component score (PCS), VAS for back and knee pain, and the degree of ambulatory kyphosis (dTIA). Each muscle strength was calibrated by body weight (BW) and expressed as BW ratio. According to our previous study, dTIA ≥ 7.6° was defined as pathological and dTIA ≤ 3.5° as normal. A final total of 409 female volunteers were included, and their demographics were; age 67.0 ± 5.5 years, Schwab-SM 2.1 ± 1.8, TEX 0.90 ± 0.33BW, TFL 0.48 ± 0.15BW, QF 0.45 ± 0.19BW, PCS 33.5 ± 6.5. Subjects were classified as clinical ASD group (cASD, n = 10) with PCS ≤ 27(mean-1SD) and pathological dTIA, robust group (n = 19) with PCS ≥ 40 (mean + 1SD) and normal dTIA, and the rest (non-cASD, n = 338). Statistical analyses showed significant differences in TEX, TFL, QF, knee extension (KEX), and BET between robust and cASD, and the mean values of robust group (TEX ≥ 1.1BW, TFL ≥ 0.5BW, QF ≥ 0.5BW, KEX ≥ 0° and BET ≥ 14 cm) were used as ‘ASD-MJ’ index. Subjects with fully achieving ASD-MJ goals showed significantly better radiographic and clinical outcomes than those with unmet goals. In conclusion, upon prescribing conservative or physical therapies for ASD patients, modifiable clinical goals should be clarified, and ASD-MJ could be a benchmark.
Elevated postoperative carcinoembryonic antigen guides adjuvant chemotherapy for stage II colon cancer: a multicentre cohort retrospective study
Authors: Pu Hongjiang , Yang Wei , Liu Mengmei , Pang Xiaolin , Chen Yaxue , Xiong Qiuxia 
Published: March 2024

AbstractMost clinical doctors rely on high-risk factors recommended by guidelines to decide whether to undergo adjuvant chemotherapy for stage II colon cancer. However, these high-risk factors do not include postoperative carcinoembryonic antigen (CEA). This study aims to explore the elevation of postoperative CEA as a risk factor, in addition to other high-risk factors, to guide adjuvant chemotherapy for patients with stage II colon cancer. A retrospective analysis was conducted on stage II colon cancer patients who underwent curative surgery at Yunnan Cancer Hospital and The Sixth Affiliated Hospital of Sun Yat-Sen University from April 2008 to January 2019. Patients were classified into three groups based on high-risk factors recommended by guidelines and postoperative CEA levels: low-risk with normal postoperative CEA, low-risk with elevated postoperative CEA and high-risk. COX regression analysis was used to identify independent prognostic factors affecting patients’ recurrence free survival (RFS). The Kaplan–Meier method was used to create the patients’ RFS curve. The restricted cubic spline (RCS) curve was used to assess the correlation between postoperative CEA and RFS on a continuous scale. Among 761 patients, there were 444 males (62.01%), with a median [IQR] age of 58.0 (18.0–88.0) years. A group of 425 high-risk patients had a 3-year RFS of 82.2% (95% CI 78.5–86.1%), while a group of 291 low-risk patients had a 3-year RFS of 89.7% (95% CI 86.1–93.5%). There was a statistically significant difference between the two groups (HR 1.83; 95% CI 1.22–2.74; P = 0.0067). Among them, the 3-year RFS of 261 low-risk patients with normal postoperative CEA was 93.6% (95% CI 90.5–96.8%), while the 3-year RFS of 30 low-risk patients with elevated postoperative CEA was 57.3% (95% CI 41.8–71.4%). There was a significant difference compared to the 3-year RFS of 425 high-risk patients (overall log-rank P < 0.0001). The multivariate analysis adjusted by the COX proportional hazards model showed that low-risk patients with elevated postoperative CEA patients (HR 14.95, 95% CI 4.51–49.63, P < 0.0001) was independently associated with a 3-year RFS. The restricted cubic spline model showed that in stage II colon cancer patients with tumor diameter > 1.955 ng/mL, the risk of postoperative recurrence increased with increasing postoperative CEA levels. Patients with elevated postoperative CEA levels have a significantly increased risk of recurrence. They should be included as high-risk factors to guide adjuvant chemotherapy for stage II colon cancer.
Screening and verification of hub genes in esophageal squamous cell carcinoma by integrated analysis
Authors: Wu Hongqiang , Zhu Peiyao , Shu Peng , Zhang Shuguang 
Published: March 2024

AbstractEsophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors. However, the mechanisms underlying ESCC tumorigenesis have not been fully elucidated. Thus, we aimed to determine the key genes involved in ESCC tumorigenesis. The following bioinformatics analyses were performed: identification of differentially expressed genes (DEGs); gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis; integrated analysis of the protein–protein interaction network and Gene Expression Profiling Interactive Analysis database for validation of hub genes. Finally, western blotting and qPCR were used to explore the expression of cell division cycle 6 (CDC6) in ESCC cell lines. Immunohistochemistry analysis of ESCC samples from patients and matched clinical characteristics was used to determine the effects of CDC6. A total of 494 DEGs were identified, and functional enrichment was mainly focused on cell cycle and DNA replication. Biological pathway analysis of the hub genes was closely related to the cell cycle. We found that CDC6 was upregulated in ESCC cell lines and patient tissues and was related to the clinicopathological characteristics of ESCC. In conclusion, this study identified hub genes and crucial biological pathways related to ESCC tumorigenesis and integrated analyses indicated that CDC6 may be a novel diagnostic and therapeutic target for ESCC.
Development and validation of the information-motivation-behavioural skills model-based human immunodeficiency virus education kit for adolescents in Malaysia
Authors: Wan Mohamad Darani Wan Nur Syamimi , Mat Ruzlin Aimi Nadira , Azhar Zahir Izuan , Chen Xin Wee 
Published: March 2024

AbstractThe growing Human Immunodeficiency Virus (HIV) incidences and insufficient HIV knowledge among Malaysian late adolescents necessitate immediate attention to HIV prevention via education. This study aims to develop and validate an Information-Motivation-Behavioural skills (IMB) model-based education kit for adolescents, PREM-Kit, to educate on HIV prevention among Malaysian late adolescents. Utilizing the Analysis, Design, Development, Implementation, and Evaluation model, we conducted the study in three phases: needs assessment, development of PREM-Kit, and validation of PREM-Kit by applying the IMB model to map the PREM-Kit’s contents. PREM-Kit, developed in Malay language, consisted of an infographic flip chart and videos. Five multi-disciplinary experts validated the PREM-Kit using the content validity index (CVI), and 13 end-users validated the PREM-Kit using the Malay version of the Patient Education Materials Assessment Tool for Printable and Audiovisual Materials. The infographic flip chart comprised three modules covering 15 topics, and an animated video accompanied each module. PREM-Kit achieved CVI scores of 1.0 and median scores of over 80% for understandability and actionability. Overall, the newly developed IMB model-based HIV education kit has good content validity, is simple to comprehend and apply, and is ready for testing its effectiveness in improving adolescents’ knowledge, attitudes, and practices for HIV prevention.
Real-time polarization compensation method in quantum communication based on channel Muller parameters detection
Authors: Tan Yongjian , Wang Jianyu , Wu Jincai , He Zhiping 
Published: March 2024

AbstractPolarization drift in fiber and free-space optical links is a major factor in the dynamic increase of bit error rate in polarization-coded quantum key distribution (QKD) systems. A dynamic polarization compensation method applicable to both links is a challenge. Here we propose a universally applicable real-time polarization compensation method, that the Muller parameters of the optical links are first detected using a polarization detector, and then the optimal parameters of the controller are obtained by gradient descent algorithm. Simulation results indicate advantages over current methods, with fewer waveplates, faster speed, and wider applicability for various optical links. In equivalent experiments of both satellite and fiber optical links, the average polarization extinction ratio of 27.9 dB and 32.2 dB are respectively achieved. The successful implementation of our method will contribute to the real-time polarization design of fiber and free-space QKD systems, while also contributing to the design of laser-based polarization systems.
La paléoneurologie
Authors: Estrems Velazquez Emma , Ferton Evaëlle , Colombo Antony 
Published: March 2024

Dans le cadre du Master 2 Sciences du Vivant de l’université EPHE-PSL (cursus IMaGHE, parcours Physiopathologie Intégrative, PPI), des étudiants se sont confrontés à la rédaction d’une Nouvelle scientifique. Selon la spécialisation choisie par les étudiants (Neurosciences ou Cancérologie), l’équipe pédagogique leur a proposé de faire une synthèse d’articles sur deux thématiques : (i) la paléoneurologie, qui permet d’analyser la transformation du cerveau de l’Homme au cours de l’évolution et (ii) la recherche bio-inspirée, qui permet de reproduire ce qui existe dans la nature pour développer des surfaces bactéricides évitant l’usage d’antibiotiques. Organisés en binôme, les étudiants ont rédigé deux Nouvelles qui soulignent l’intérêt des travaux analysés, ainsi que leur originalité. Ils se sont pleinement investis dans cette tâche et ont su faire preuve d’un bel esprit de synthèse. Ils ont apprécié cet exercice nouveau pour eux, mais qui leur a permis d’avoir un aperçu de l’exercice de la publication scientifique, inhérent au métier de chercheur auquel ils se destinent.
Anaplastic Thyroid Carcinoma versus Metastatic SCC: A Diagnostic Dilemma in a Rare Presentation of Post-Radiation Thyroid Swelling
Authors: Rao Vrushab , Zade Bhooshan 
Published: March 2024

AbstractA 71-year-old male with type 2 diabetes and hypertension was diagnosed with carcinoma of the pyriform fossa in 2019. The biopsy was reported as a moderately differentiated squamous cell carcinoma, and positron emission tomography-computed tomography (PET-CT) scan showed an fluorodeoxyglucose (FDG)-avid lesion in the pyriform fossa and the aryepiglottic fold with few nodes in level II and level III. The paitent was treated with radical chemoradiotherapy. A follow-up PET-CT scan done in 2022 revealed an FDG-avid soft tissue thickening in the left palatine tonsillar region and an uptake in the thyroid that was reported as not significant. A punch biopsy from the tonsillar fossa lesion revealed squamous cell carcinoma. The lesion was treated as a second primary and treated with radiotherapy with curative intent. The patient was complaining of dysphagia, difficulty in breathing, and weight loss around 6 months after treatment that were addressed medically. There was a significant reduction in size and FDG activity of the ill-defined thickening in the left tonsillar region which was seen in the response-assessment PET done 6 months after RT. A heterogeneously enhancing nodules were seen in both lobes of the thyroid in which the largest one measured 3.5 × 3.1 cm seen in the right lobe. The patient underwent a biopsy from the thyroid that revealed a benign thyroid gland infiltrated by clusters and nests of poorly differentiated malignant cells. The histomorphology was suggestive of a poorly differentiated carcinoma, likely anaplastic carcinoma thyroid, or metastasis of the squamous cell carcinoma. Curative treatment was ruled out in this case due to his comorbidities, pulmonary symptoms, and radiation delivered to the neck.
SFM Fetal Therapy Practice Guidelines: Intrauterine Blood Transfusion
Authors: Vikraman Seneesh Kumar , Krishnan Manikandan 
Published: March 2024

AbstractDespite routine antenatal anti-D prophylaxis with immunoglobulin, Rh alloimmunization and hemolytic disease of the fetus and newborn continue to occur due to a myriad of reasons. Intrauterine intravascular transfusion (IUT) or fetal blood transfusion is a therapeutic prenatal procedure in which specifically prepared and treated unit of donor red blood cells is injected intravascularly into the umbilical vein under ultrasound guidance. Originally introduced in the year 1963, it continues to be the standard treatment for severe fetal anemia. The objective of this guideline is to provide an evidence-based update of IUT for the perinatal healthcare providers.
2.11 Covalent Attachment on a Solid Support
Authors: Franzini R. M. 
Published: March 2024

AbstractDNA oligonucleotides are polyfunctional molecules, and their various functional groups can interfere with DNA-encoded library synthesis. DNA that is attached to the support used for solid-phase synthesis has functional groups (e.g., exocyclic amines) protected. It is therefore possible to use harsher reaction conditions than would be possible with unprotected DNA, and the use of water-free solvents is also facilitated. For example, amide-bond formation on a solid support tends to be higher yielding than reactions in solution phase.
3.2.2.2 Peptide Nucleic Acid (PNA) Encoded Libraries
Authors: Farrera-Soler L. , Vummidi B. R. , Barluenga S. , Winssinger N. 
Published: March 2024

AbstractDNA-encoded libraries (DELs) have enabled the screening of dual-pharmacophore libraries but have thus far not allowed the recombination of those fragments after each round of selection. Herein we report the screening of suprabodies, a macromolecular PNA–DNA structure, which allow the shuffling of the library fragments after each round of selection. This technology has been applied to the discovery of new PD-L1 ligands.