bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucose-6-Phosphatase-Dehydrogenase activity as modulative association between Parkinson’s disease and periodontitis
Authors: Laugisch Oliver , Ruppert-Jungck Marina C. , Auschill Thorsten M. , Eick Sigrun , Sculean Anton , Heumann Christian , Timmermann Lars , Pedrosa David J. , Eggers Carsten , Arweiler Nicole B.
Published: February 2024

The association between periodontitis (PD) and Parkinson’s disease (PK) is discussed due to the inflammatory component of neurodegenerative processes. PK severity and affected areas were determined using the following neuropsychological tests: Unified Parkinson’s Disease Rating Score (UPDRS) and Hoehn and Yahr; non-motoric symptoms by Non-Motor Symptoms Scale (NMSS), and cognitive involvement by Mini-Mental State Examination (MMSE). Neuroinflammation and the resulting Glucose-6-Phosphatase-Dehydrogenase (G6PD) dysfunction are part of the pathophysiology of PK. This study aimed to evaluate these associations in periodontal inflammation. Clinical data and saliva-, serum-, and RNA-biobank samples of 50 well-characterized diametric patients with PK and five age- and sex-matched neurologically healthy participants were analyzed for G6PD function, periodontal pathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Campylobacter rectus, Fusobacterium nucleatum, and Filifactor alocis), monocyte chemoattractant protein (MCP) 1, and interleukin (IL) 1-beta. Regression analysis was used to identify associations between clinical and behavioral data, and t-tests were used to compare health and disease. Compared with PK, no pathogens and lower inflammatory markers (p < 0.001) were detectible in healthy saliva and serum, PK-severity/UPDRS interrelated with the occurrence of Prevotella intermedia in serum as well as IL1-beta levels in serum and saliva (p = 0.006, 0.019, 0.034), Hoehn and Yahr correlated with Porphyromonas gingivalis, Prevotella intermedia, RNA IL1-beta regulation, serum, and saliva IL1-beta levels, with p-values of 0.038, 0.011, 0.008, <0.001, and 0.010, while MMSE was associated with Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, serum MCP 1 levels, RNA IL1-beta regulation and G6PD serum activity (p = 0.036, 0.003, 0.045, <0.001, and 0.021). Cognitive and motor skills seem to be important as representative tests are associated with periodontal pathogens and oral/general inflammation, wherein G6PD-saliva dysfunction might be involved.

Clinical trial registration

https://www.bfarm.de/DE/Das-BfArM/Aufgaben/Deutsches-Register-Klinischer-Studien/_node.html, identifier DRKS00005388.
Choice of adjuvant and antigen composition alters the immunogenic profile of a SARS-CoV-2 subunit vaccine
Authors: Lykins William R. , Pollet Jeroen , White Jessica A. , Keegan Brian , Versteeg Leroy , Strych Ulrich , Chen Wen-Hsiang , Mohamath Raodoh , Ramer-Denisoff Gabi , Reed Sierra , Beaver Samuel , Gerhardt Alana , Voigt Emily A. , Tomai Mark A. , Sitrin Robert , Choy Robert K. M. , Cassels Frederick J. , Hotez Peter J. , Bottazzi Maria Elena , Fox Christopher B.
Published: February 2024

Introduction: Since their introduction, adjuvanted recombinant subunit vaccines against COVID-19 have played a pivotal role in protecting global populations. Optimizing the immune response’s quality, amplitude, and durability to these vaccines depends on the appropriate adjuvant choice and dose in combination with the selected antigen.

Methods: Here, we employed a preclinical mouse model to study the adaptive humoral and cellular immune responses to a SARS-CoV-2 receptor binding domain (RBD) antigen formulated with one of four different immune agonists [GLA, 3M-052, CpG-1826 (CpG), and dmLT], in combination with one of two different immune-stimulating formulations, a stabilized squalene emulsion (SE) or aluminum hydroxide (Alum). Using a weighted desirability index, we established an immunogenicity ranking for each adjuvant in combination with the RBD antigen.

Results: We found that formulations of the RBD with Alum in combination with either 3M-052 or CpG led to at least a 2-log increase in serum IgG production and a 1.3- to 2.2-log increase in the number of bone marrow-derived antibody-secreting cells compared to the RBD formulated with Alum without an additional agonist. In contrast, the RBD formulated with SE in combination with 3M-052 or CpG did not elicit an IgG response greater than the unadjuvanted control. Additionally, RBD formulated with 3M-052 or CpG on Alum generated a 0.8- or 1.6-log lower splenocyte IL-5 response (a pro-Th2 marker), respectively, than Alum without an additional agonist. When formulated with 3M-052-Alum, a bivalent vaccine containing the original lineage (Wuhan-Hu-1) and the Delta variant (B.1.617.2) RBD antigens led to a more than 2-log increase in neutralizing antibodies against an Omicron variant (B.1.1.529) pseudovirus in vaccinated animals compared to animals that received the monovalent RBD antigen.

Discussion: Our results suggest that optimal immune responses to subunit antigens may be achieved through an orthogonal approach that applies adjuvant formulation, antigen combination, and advances in rational vaccine development techniques.
Diatom-based inferences of environmental changes from an alpine lake on the southeast edge of the Tibetan plateau over the last 4000 years
Authors: Zhang Yunxia , Peng Wei , Li Yanling , Xiao Xiayun , Hillman Aubrey
Published: February 2024

To better understand how global and regional-scale climate has changed, high-resolution records for environmental changes are still needed in southwestern (SW) China during the Late Holocene epoch. This study presents a well-dated high-resolution diatom analysis from a 1.66-m-long sediment core taken from Lake Cuogeda (CGD) on the southeast (SE) edge of the Tibetan Plateau to document environmental changes over the past ∼4000 years. Diatom and other geochemical proxies show that, from 3850 to 3430 cal yr BP (before present, 0 BP=1950 AD, 1900 to 1480 BC), the environment of Lake CGD is acidic, oligotrophic, and enriched with humic acids. And the lake ice cover duration is short during this period. During 3430–1550 cal yr BP (1480 BC-400 AD), Lake CGD has less humic acid and a relatively high pH environment. The ice cover duration is longer, and the temperature drops during this period. Our multi-indicator recorded two environment fluctuations at ∼2800 cal yr BP (850 BC) and 2210–1950 cal yr BP (260 BC-0 AD). From 1550 to 3.6 cal yr BP (400–1946 AD), the lake ecosystem changed to a higher pH condition and had a prolonged freezing time. From 3.6 cal yr BP (1946 AD) to the present, Lake CGD’s water was acidic, with an environment of shorter duration of ice cover and stronger lake water turbulence. Comparisons between the CGD records and other climate reconstructions underscore the relevance of the CGD record for regional and global environments. Comparisons indicate that the environment evolution pattern of SW China during the Late Holocene was greatly affected by solar radiation and North Atlantic sea surface temperature.
Together or separate? Tracing classroom pedagogies of (un)belonging for newcomer migrant pupils in two Austrian schools
Authors: Wagner Josefine , Szelei Nikolett , Eloff Irma , Acquah Emmanuel
Published: February 2024

Even though receiving newcomer pupils in schools is not a new phenomenon, many education systems grapple with finding adequate schooling arrangements that foster belonging and inclusion. Over the years, policy-makers and school practitioners seem to echo recurring dilemmas in terms of what language support models may promote optimal inclusion, and whether and how to support the language of schooling while also building on students’ cultural and linguistic repertoires. In this article, we present classroom observations from two Austrian primary schools that implemented German language support in two distinct ways. School 1 implemented pull-out classes, whereas School 2 used a model of individualized learning for all students in the mainstream classroom. Utilizing the cultural-linguistic aspects of ‘belonging’ in pedagogical enactments, we analyze how teachers’ instructional strategies to organize curricular learning for newly arrived migrant pupils set conditions for pedagogies of (un)belonging in the classroom. Findings show that pedagogies of (un)belonging seemed to be formed via chains of patterned interactions, activities and utterances based on three key logics: marking students’ ‘fitness’ to the mainstream classroom, creating cultural (in)visibility, and as creating language hierarchies. While the two classroom practices remarkably differed in how they enabled German language learning and fitting to mainstream pedagogical norms, both seemed to uphold monolingualism and monoculturalism. Recommendations are given in order to expand narrow notions of belonging in educational policy and practice.
The association of an elevated Th/Ts ratio and lupus anticoagulant with symptomatic osteonecrosis in systemic lupus erythematosus patients
Authors: Hou Ruihong , Lei Jiamin , Xue Dengfeng , Jing Yukai , Mi Liangyu , Guo Qianyu , Xu Ke , Zhang Liyun
Published: February 2024

Objective

This study aimed to assess the risk factors for symptomatic osteonecrosis (ON) in systemic lupus erythematosus (SLE) and identify clinical characteristics and laboratory markers for predicting symptomatic ON occurrence in SLE patients.

Methods

Seventy (6.0%) of 1175 SLE patients diagnosed with symptomatic ON were included in this study. An equal number of SLE patients without symptomatic ON, matched in terms of age and gender, were enrolled in the control group. Clinical symptoms, routine laboratory examinations, lymphocyte subsets, and treatments of these patients were retrospectively reviewed and compared between the two groups. Logistic regression analysis was employed to identify risk factors associated with symptomatic ON in SLE.

Results

Among the 70 cases in the symptomatic ON group, 62 (88.6%) patients experienced femoral head necrosis, with bilateral involvement observed in 58 patients. Bone pain was reported in 32 cases (51.6%), and 19 cases (30.6%) presented with multiple symptoms. Univariate analysis revealed significant differences between the two groups in various factors, including disease duration (months), cumulative steroid exposure time, history of thrombosis, neurological involvement, the number of affected organs, myalgia/myasthenia, and the use of medications such as glucocorticoids, immunosuppressants, aspirin, and statins (P<0.05). Moreover, lupus anticoagulant (LA) levels were significantly higher in the symptomatic ON group than in the control group (P<0.05). Furthermore, notable distinctions were observed in peripheral blood immune cells, including an elevated white blood cell count (WBC), a decreased percentage of Ts cells (CD3+CD8+), and an elevated Th/Ts ratio. Logistic regression analysis revealed that a history of thrombosis, LA positivity, and an elevated Th/Ts ratio remained positive factors associated with symptomatic ON (P<0.05).

Conclusion

Decreased Ts cells and changes in the T lymphocyte subset play an important regulatory role in the development of symptomatic ON. A history of thrombosis and LA are associated with an increased probability of symptomatic ON in SLE and may serve as potential predictors.
Tumor-specific activation of folate receptor beta enables reprogramming of immune cells in the tumor microenvironment
Authors: Zhang Fenghua , Huang Bo , Utturkar Sagar M. , Luo Weichuan , Cresswell Gregory , Herr Seth A. , Zheng Suilan , Napoleon John V. , Jiang Rina , Zhang Boning , Liu Muyi , Lanman Nadia , Srinivasarao Madduri , Ratliff Timothy L. , Low Philip S.
Published: February 2024

Folate receptors can perform folate transport, cell adhesion, and/or transcription factor functions. The beta isoform of the folate receptor (FRβ) has attracted considerable attention as a biomarker for immunosuppressive macrophages and myeloid-derived suppressor cells, however, its role in immunosuppression remains uncharacterized. We demonstrate here that FRβ cannot bind folate on healthy tissue macrophages, but does bind folate after macrophage incubation in anti-inflammatory cytokines or cancer cell-conditioned media. We further show that FRβ becomes functionally active following macrophage infiltration into solid tumors, and we exploit this tumor-induced activation to target a toll-like receptor 7 agonist specifically to immunosuppressive myeloid cells in solid tumors without altering myeloid cells in healthy tissues. We then use single-cell RNA-seq to characterize the changes in gene expression induced by the targeted repolarization of tumor-associated macrophages and finally show that their repolarization not only changes their own phenotype, but also induces a proinflammatory shift in all other immune cells of the same tumor mass, leading to potent suppression of tumor growth. Because this selective reprogramming of tumor myeloid cells is accompanied by no systemic toxicity, we propose that it should constitute a safe method to reprogram the tumor microenvironment.
Human-induced rapid siltation within a macro-tidal bay during past decades
Authors: Liu Yifei , Xia Xiaoming , Wang Xinkai , Cai Tinglu , Zheng Jun
Published: February 2024

Tidal bay evolution is the result of the comprehensive influence of multiple factors. It is crucial to analyze the primary factors to disassemble the comprehensive effects. In this study, remote sensing and bathymetric data were used to investigate anthropogenic activities and geomorphological changes in Puba Bay, China. From 1964 to 2020, the intertidal zone area decreased by 64.5% due to mariculture ponds and coastal reclamation, with the former accounting for 60.4% of the total area. Over five decades, the bay experienced significant silting, with a 61.5% decrease in underwater area, an 88.4% decrease in volume, and considerable reductions in maximum water depth, cross-sectional terrain depth, and width. Anthropogenic activities led to a reduction in tidal prism and tidal velocity, resulting in increased flood dominance and decreased ebb dominance in the main channel, leading to more siltation. Negative and positive feedback mechanisms were observed between anthropogenic activities, seaward expansion of intertidal flats, and bay siltation. The influence of mariculture ponds, as the major factor, on geomorphological changes was found to be similar to that of coastal reclamation. To maintain water depth and capacity for material exchange in the bay, preliminary suggestions for mariculture pond management are proposed.
Organic carbon burial and their implication on sea surface primary productivity in the middle Okinawa Trough over the past 200 ka
Authors: Jing Yunge , Zhang Taoliang , Zhu Ben , Zhao Jingtao , Zhao Xiaoxiao , Dou Yanguang , Li Qing , Cai Feng , Hu Bangqi , Dong Liang
Published: February 2024

The long-term burial of organic carbon in marginal seas plays a critical role in Earth’s carbon cycle and climate change. However, the mechanism of organic carbon (OC) burial in the Okinawa Trough (OT) during glacial-interglacial timescales remains unclear. In this study, we analyzed the foraminiferal carbon isotopes, total organic carbon (TOC), and δ13C-TOC over the past 200 ka in core Z1 collected in the central OT. We aimed to reveal the history of OC burial in the middle Okinawa Trough during the past 200 ka, and we combined our findings with relevant paleoenvironmental indices to reveal underlying mechanisms. We found reduced surface primary productivity during MIS 6, which may indicate changes in the pathways of the Kuroshio Current (KC). Furthermore, we observed decoupling between high TOC flux and low OC burial during glacial periods. We proposed that the dilution effect caused by the high sedimentation rate and poor OC preservation during the glacial period resulted in the low TOC content. Ventilation of the North Pacific Intermediate Water (NPIW) regulated the redox conditions of the intermediate water in the Okinawa Trough. Additionally, the intensified Kuroshio Current during interglacial phases led to water column stratification, creating reducing conditions in the bottom water and facilitating improved OC preservation. Subsequently, the enhanced water column oxygenation resulting from the oxygen carried by the intensified glacial NPIW weakened the burial of OC. This study sheds new light on our understanding of the carbon cycle in marginal seas on a glacial-interglacial timescale.
Preimplantation genetic testing for aneuploidy optimizes reproductive outcomes in recurrent reproductive failure: a systematic review
Authors: Mei Youwen , Lin Yonghong , Chen Ying , Zheng Jiafeng , Ke Xue , Liang Xuefei , Wang Fang
Published: February 2024

Introduction

Recurrent reproductive failure (RRF) is a common pregnancy complication, imposing great physical, emotional and financial burden for the suffered couples. The leading cause of RRF is believed to be aneuploid embryo, which could be solved by preimplantation genetic testing for aneuploidy (PGT-A) in theory. With molecular genetic development, PGT-A based on comprehensive chromosomal screening (CCS) procedures and blastocyst biopsy is widely applied in clinical practice. However, its effects in RRF were not defined yet.

Methods

A systematic bibliographical search was conducted without temporal limits up to June, 2023. Studies about the effects of PGT-A based on CCS procedures and blastocyst biopsy in RRF were included.

Results

Twenty studies about the effects of PGT-A based on CCS procedures and blastocyst biopsy in RRF were included. It revealed that PGT-A could optimise the reproductive outcomes of RRF sufferers, especially in those with advanced age. However, in patients with multiple occurrences of pregnancy losses, the benefits of PGT-A were limited.

Discussion

More randomized controlled trials with large sample size are required to evaluate the benefits of PGT-A in RRF sufferers and identify which population would benefit the most.
Epidemiological and clinical characteristics of open globe injuries in Southwest China
Authors: Chen Qin , Liang Licong , Shi Yuzhuo , Lu Fang
Published: February 2024

Background

Open globe injuries (OGIs) are one of the leading causes of monocular vision loss, and the clinical characteristics of OGIs are region specific. The features and patterns of OGIs in Southwest China are poorly known and not well studied. Our study aimed to review the epidemiological and clinical characteristics of patients hospitalized for OGIs in Southwest China.

Methods

A retrospective study of OGI patients admitted to the West China Hospital from January 1st, 2015, to December 31st, 2019, was performed. Demographic characteristics and injury details were recorded. The Birmingham Eye Trauma Terminology system and the ocular trauma score (OTS) were used.

Results

A total of 3,014 patients were included. The male-to-female ratio was 5.2:1, and the mean age was 35.6 ± 19.1 years. 15.2% of patients were from the ethnic groups. The highest-risk occupation was the farmer (30.3%), followed by the worker (28.5%). OGIs occurred more frequently in people with middle (37.0%) and primary school (33.1%) education levels. Types of injuries included 46.8% penetration, 21.2% rupture, 2.9% perforation, and 29.1% intraocular foreign body (IOFB). The injuries types differed between age and occupation groups (p < 0.001). IOFBs had a higher risk of causing endophthalmitis, retinal detachment, and traumatic cataracts (p < 0.001). The most common injuries resulted from sharp objects (72.7%). The causes of the injuries were significantly associated with age, ethnicity, and occupation (p < 0.001). Explosion injuries and attacks by animals were more common among people of Tibetan and Yi ethnicities. Blunt trauma, vehicle crashes, falls and age older than 60 years were risk factors for a lack of light perception and lower OTS scores prognosis.

Conclusion

OGIs in Southwest China mainly affected working-aged males, especially workers or farmers. Severe vision loss and IOFBs are more common findings. OGIs in older patients and ethnic minorities requires additional attention.
Changes in gait performances during walking with head movements in older adults with chronic neck pain
Authors: Madsalae Thanya , Thongprong Tanapat , Chaikeeree Nithinun , Boonsinsukh Rumpa
Published: February 2024

Background

Chronic neck pain (CNP) can lead to altered gait which is worse when combined with head movement. Gait parameters for indicating speed and symmetry have not been thoroughly investigated in older adults with CNP. This study aimed to compare gait performance in term of speed and symmetry in older adults with and without CNP during walking with head movement.

Methods

Fifty young older adults, consisting of 36 healthy controls without neck pain (OLDs) and 14 older adults with CNP, participated in the study. Participants completed the Neck Disability Index and Activities-specific Balance Confidence Scale. The 10-Meter Walk Test (10MWT) was used to assess gait performance. Participants were instructed to walk at preferred speed under three different head movement patterns: no head movement (NM), horizontal head movement (HM), and vertical head movement (VM). The Inertial Measurement Unit was used to capture gait performance, and its software was used to analyze gait variables; gait speed, Locomotor Rehabilitation Index (LRI), gait asymmetry index, Phase Coordination Index (PCI).

Results

The CNP group reported moderate neck pain with mild disability in activities of daily living, and less balance confidence than the OLD group (p < 0.05). The CNP group showed significantly slower gait speed and lower LRI during walking with both the HM and VM (p < 0.05), which corresponded to lower stride length and cadence. The gait asymmetry index in the CNP group was significantly higher than the OLD group during walking with VM (p < 0.05), whereas the PCI was significantly higher than the OLD group during walking with both HM and VM (p < 0.05).

Conclusion

Chronic neck pain affects both speed and symmetry when walking with head movement. Gait parameters in this study could be implemented to identify changes in speed and symmetry of gait in older adults with CNP who have mild disability and high physical functioning.
High diversity, close genetic relatedness, and favorable living conditions benefit species co-occurrence of gut microbiota in Brandt’s vole
Authors: Cheng Chaoyuan , Li Guoliang , Yang Xifu , Zhao Jidong , Liu Jing , Zheng Aihua , Zhang Zhibin
Published: February 2024

Introduction

Revealing factors and mechanisms in determining species co-existence are crucial to community ecology, but studies using gut microbiota data are still lacking.

Methods

Using gut microbiota data of 556 Brandt’s voles from 37 treatments in eight experiments, we examined the relationship of species co-occurrence of gut microbiota in Brandt’s voles (Lasiopodomys brandtii) with genetic distance (or genetic relatedness), community diversity, and several environmental variables.

Results

We found that the species co-occurrence index (a larger index indicates a higher co-occurrence probability) of gut microbiota in Brandt’s voles was negatively associated with the genetic distance between paired ASVs and the number of cohabitating voles in the experimental space (a larger number represents more crowding social stress), but positively with Shannon diversity index, grass diets (representing natural foods), and non-physical contact within an experimental space (representing less stress).

Discussion

Our study demonstrated that high diversity, close genetic relatedness, and favorable living conditions would benefit species co-occurrence of gut microbiota in hosts. Our results provide novel insights into factors and mechanisms that shape the community structure and function of gut microbiota and highlight the significance of preserving the biodiversity of gut microbiota.
Chaperonin TRiC/CCT subunit CCT7 is involved in the replication of canine parvovirus in F81 cells
Authors: Su Xia , Zhou Hongzhuan , Xu Fuzhou , Zhang Jin , Xiao Bing , Qi Qi , Lin Lulu , Yang Bing
Published: February 2024

Canine parvovirus (CPV) is one of the most common lethal viruses in canines. The virus disease is prevalent throughout the year, with high morbidity and mortality rate, causing serious harm to dogs and the dog industry. Previously, yeast two hybrid method was used to screen the protein chaperonin containing TCP-1 (CCT7) that interacts with VP2. However, the mechanism of interactions between CCT7 and VP2 on CPV replication remains unclear. In this study, we first verified the interaction between CCT7 and viral VP2 proteins using yeast one-to-one experiment and co-immunoprecipitation (CoIP) experiment. Laser confocal microscopy observation showed that CCT7 and VP2 were able to co-localize and were mostly localized in the cytoplasm. In addition, the study of VP2 truncated mutant found that the interaction region of VP2 with CCT7 was located between amino acids 231 and 320. Cycloheximide (CHX) chase experiments showed that CCT7 can improve the stability of VP2 protein. After further regulation of CCT7 expression in F81 cells, it was found that the expression level of VP2 protein was significantly reduced after knocking down CCT7 expression by RNA interference (RNAi) or HSF1A inhibitor, and increased after overexpressing host CCT7. The study reveals the role of VP2 interacting protein CCT7 in the replication process of CPV, which could provide a potential target for the prevention and control of CPV.
Purine metabolism in plant pathogenic fungi
Authors: Sun Manli , Dai Pengbo , Cao Zhiyan , Dong Jingao
Published: February 2024

In eukaryotic cells, purine metabolism is the way to the production of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) and plays key roles in various biological processes. Purine metabolism mainly consists of de novo, salvage, and catabolic pathways, and some components of these pathways have been characterized in some plant pathogenic fungi, such as the rice blast fungus Magnaporthe oryzae and wheat head blight fungus Fusarium graminearum. The enzymatic steps of the de novo pathway are well-conserved in plant pathogenic fungi and play crucial roles in fungal growth and development. Blocking this pathway inhibits the formation of penetration structures and invasive growth, making it essential for plant infection by pathogenic fungi. The salvage pathway is likely indispensable but requires exogenous purines, implying that purine transporters are functional in these fungi. The catabolic pathway balances purine nucleotides and may have a conserved stage-specific role in pathogenic fungi. The significant difference of the catabolic pathway in planta and in vitro lead us to further explore and identify the key genes specifically regulating pathogenicity in purine metabolic pathway. In this review, we summarized recent advances in the studies of purine metabolism, focusing on the regulation of pathogenesis and growth in plant pathogenic fungi.
Chemogenetic inhibition of the ventral hippocampus but not its direct projection to the prelimbic cortex attenuates context-specific operant responding
Authors: Thomas Callum M. P. , Bouton Mark E. , Green John T.
Published: February 2024

Previous work has demonstrated the importance of the prelimbic cortex (PL) in contextual control of operant behavior. However, the associated neural circuitry responsible for providing contextual information to the PL is not well understood. In Pavlovian fear conditioning the ventral hippocampus (vH) and its projection to the PL have been shown to be important in supporting the effects of context on learning. The present experiments used chemogenetic inhibition of the direct vH-PL projection or the vH to determine involvement in expression of context-specific operant behavior. Rats were injected with an inhibitory DREADD (hM4Di) or mCherry-only into the vH, and subsequently trained to perform a lever press response for a food pellet in a distinct context. The DREADD ligand clozapine-n-oxide (CNO) was then delivered directly into the PL (experiment 1) and then systemically (experiment 2) prior to tests of the response in the training context as well as an equally familiar but untrained context. vH (systemic CNO) but not vH-PL (intra-PL CNO) inhibition was found to attenuate operant responding in its acquisition context. A third experiment, using the same rats, showed that chemogenetic inhibition of vH also reduced Pavlovian contextual fear. The present results suggest that multisynapatic connections between the vH and PL may be responsible for integration of contextual information with operant behavior.
Functional blindsight and its diagnosis
Authors: Lane Timothy Joseph , Liou Tsan-Hon , Kung Yi-Chia , Tseng Philip , Wu Changwei W.
Published: February 2024

Even when brain scans fail to detect a striate lesion, functional evidence for blindsight can be adduced. In the aftermath of an automobile accident, JK became blind. Results of ophthalmic exams indicated that the blindness must be cortical. Nevertheless, multiple MRI scans failed to detect structural damage to the striate cortex. Prior to the accident JK had been an athlete; after the accident he retained some athletic abilities, arousing suspicions that he might be engaged in fraud. His residual athletic abilities—e.g., hitting a handball or baseball, or catching a Frisbee—coupled with his experienced blindness, suggested blindsight. But due to the apparent absence of striate lesions, we designed a series of tasks for temporal and spatial dimensions in an attempt to detect functional evidence of his disability. Indeed, test results revealed compelling neural evidence that comport with his subjective reports. This spatiotemporal task-related method that includes contrasts with healthy controls, and detailed understanding of the patient's conscious experience, can be generalized for clinical, scientific and forensic investigations of blindsight.
Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA
Authors: Warner-Schmidt Jennifer , Stogniew Martin , Mandell Blake , Rowland R. Scott , Schmidt Eric F. , Kelmendi Benjamin
Published: February 2024

Background

Post-traumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder that can become chronic and debilitating when left untreated. Available pharmacotherapies are limited, take weeks to show modest benefit and remain ineffective for up to 40% of patients. Methylone is currently in clinical development for the treatment of PTSD. Preclinical studies show rapid, robust and long-lasting antidepressant-like and anxiolytic effects. The mechanism of action underlying these effects is not yet fully understood. This study investigated the downstream gene expression changes and signaling pathways affected by methylone in key brain areas linked to PTSD and MDD. It also sought to determine whether neuroplasticity-related genes were involved. We compared effects of methylone with MDMA to explore similarities and differences in their brain effects because MDMA-assisted psychotherapy has recently shown benefit in clinical trials for PTSD and methylone is a structural analog of MDMA.

Methods

Monoamine binding, uptake and release studies were performed and a high-throughput-screen evaluated agonist/antagonist activities at 168 GPCRs in vitro. We used RNA sequencing (RNA-seq) to probe drug-induced gene expression changes in the amygdala and frontal cortex, two brain areas responsible for emotional learning that are affected by PTSD and MDD. Rats were treated with methylone or MDMA (both 10 mg/kg, IP), and their responses were compared with controls. We performed functional enrichment analysis to identify which pathways were regulated by methylone and/or MDMA. We confirmed changes in gene expression using immunohistochemistry.

Results

Methylone, a monoamine uptake inhibitor and releaser, demonstrated no off-target effects at 168 GPCRs, unlike MDMA, which showed activity at 5HT2A and 5HT2C receptors. RNA-seq results revealed significant regulation of myelin-related genes in the amygdala, confirmed by immunohistochemistry. In the frontal cortex, methylone significantly upregulated genes implicated in neuroplasticity.

Conclusion

Results suggest that (1) methylone is a rapid-acting neuroplastogen that affects key brain substrates for PTSD and MDD and that (2) methylone appears to exhibit higher specificity and fewer off-target effects than MDMA. Together, these results are consistent with the reported clinical experiences of methylone and MDMA and bolster the potential use of methylone in the treatment of PTSD and, potentially, other neuropsychiatric disorders.
Effects of deep frying and baking on the quality attributes, water distribution, and flavor characteristics of duck jerky
Authors: Pei Yamin , Guo Xingyue , Shu Xionghui , Han Yahong , Ai Youwei , Wang Hongxun , Hou Wenfu
Published: February 2024

Introduction

The nutritional value of duck meat is well acknowledged due to its low cholesterol and high protein content. Nevertheless, the impacts of deep-frying and baking on its quality characteristics are not extensively documented in literature.

Methods

The objective of this study is to examine the effects of deep-frying, pre-boilingdeep-frying, baking, and pre-boiling-baking on the quality attributes, water distribution, microstructure, and flavor characteristics of duck jerky.

Results and discussion

The findings revealed that the deep-frying group had better quality attributes than the baking, pre-boiling-deep-frying, and pre-boiling-baking groups. The deepfried duck jerky had a higher a* value (4.25) and a lower b* value (5.87), with a more appropriate texture profile, and had the highest comprehensive impression score (5.84). Moreover, the drying rate was faster, and the intensity of the free water and oil signal was significantly elevated in the deep-frying group. The microstructure results indicated that the muscle fibers in the deep-frying group were closely packed, whereas those in the baking group were relatively loose. Furthermore, the GC-IMS test revealed that the deep-fried duck jerky had a wider range of volatile flavor compounds, including 11 unique compounds that were only found in this particular product.
Psychological approaches to obesity in young adults: state of the art
Authors: Alves Rafaela , Petitjean Hugues , Druzhinenko-Silhan Daria
Published: February 2024

Background

Obesity has become a significant health concern among young adults aged 18–35 years. Addressing this issue is crucial, and exploring psychological treatments and perspectives specifically for this population is essential.

Methods

This literature review examines psychological treatments for obesity in young adults over the past decade. It focuses on interventions and discussions particularly relevant to this age group.

Discussion

Research on obesity often overlooks young adults, with most interventions primarily focusing on weight loss and neglecting emotional aspects. Cognitive-behavioral approaches are commonly used for self-regulation and motivation, but psychodynamic perspectives remain underutilized. While group-based methods lack a detailed analysis of benefits, hybrid approaches demonstrate higher engagement compared to technology-only interventions. There is a notable gap in tailoring obesity interventions to meet the unique needs of young adults during this transitional life phase. It’s imperative to shift the focus from merely weight loss to a broader consideration of psychological, emotional, and unconscious factors. Integrating group modalities with psychodynamic approaches might offer additional benefits.

Conclusion

This review highlights the need for further research into the psychological well-being of young adults with obesity. A more comprehensive approach is required to address their distinct needs and psychological factors.
Influence of cultivation substrate on antioxidant activities and triterpenoid profiles of the fruiting body of Ganoderma lucidum
Authors: Luo Gelian , Pan Zhibin , Liu Zhibin , Cheng Weiqing , Yu Tingting
Published: February 2024

Introduction

The fruiting body of Ganoderma lucidum has been believed to possess a wide range of therapeutic effects. There are two main methods for artificial cultivation of G. lucidum to produce the fruiting body, namely wood log cultivation and substitute cultivation. The impact of cultivation substrates on the composition of bioactive compounds remains largely unexplored. This study aims to compare the antioxidant activities and triterpenoid profiles of the fruiting bodies of G. lucidum that cultivated through wood log cultivation (WGL) and substitute cultivation (SGL) methods.

Methods

The antioxidant activities, including the DPPH radical scavenging, hydroxyl radical scavenging, superoxide radical scavenging, and total antioxidant activities, were assessed in both WGL and SGL samples. Furthermore, the UHPLC-Q-Orbitrap-MS technique was employed to compare their phytochemical profiles, with a specific emphasis on triterpenoid constituents.

Results and discussion

It was found that WGL samples exhibited significantly higher total triterpenoid content, DPPH radical scavenging activity, and total antioxidant activity. Furthermore, an untargeted metabolomics approach employing UHPLC-Q-Orbitrap-MS tentatively identified a total of 96 triterpenoids. Distinguishingly different triterpenoid profiles between the two types of G. lucidum samples were revealed via the utilization of principal component analysis (PCA) and hierarchical cluster analysis (HCA). Specifically, 17 triterpenoids showed significant differences. Of these triterpenoids, 6 compounds, such as ganosporelactone B, ganoderol A, ganoderic acid A, ganoderic acid alpha, were significantly higher in SGL samples; 11 compounds, such as lucidenic acid A, lucidenic acid D1, lucidenic acid F, lucidenic acid G, lucidenic acid J, ganoderic acid E, and ganoderic acid O, were significantly higher in WGL samples. These findings expand our knowledge regarding the impact of cultivation substrate on the antioxidant activities and triterpenoid profiles of G. lucidum, and offer practical implications for its cultivation.
Tolerability and efficacy of the cancer vaccine UV1 in patients with recurrent or metastatic PD-L1 positive head and neck squamous cell carcinoma planned for first-line treatment with pembrolizumab – the randomized phase 2 FOCUS trial
Authors: Brandt Anna , Schultheiss Christoph , Klinghammer Konrad , Schafhausen Philippe , Busch Chia-Jung , Blaurock Markus , Hinke Axel , Tometten Mareike , Dietz Andreas , Müller-Richter Urs , Hahn Dennis , Alt Jürgen , Stein Alexander , Binder Mascha
Published: February 2024

Background

Globally, head and neck squamous cell carcinoma (HNSCC) is the seventh most common malignancy. Despite aggressive multimodal treatment approaches, recurrent and/or metastatic (R/M) disease develops in >50% of patients. In this setting, pembrolizumab was approved for patients with PD-L1 expression. However, response rates with checkpoint inhibitor monotherapy remain limited and strategies to strengthen tumor-directed immune responses are needed.

Objective

The FOCUS trial is designed to estimate the effectiveness of UV1 vaccination in combination with pembrolizumab versus pembrolizumab as a single agent in patients with R/M HNSCC.

Methods and analysis

The FOCUS trial is a two-armed, randomized, multicenter phase II study which was designed to evaluate the efficacy and feasibility of the hTERT-targeted cancer vaccine UV1 as add-on to pembrolizumab in the 1st line treatment of patients with R/M PD-L1 positive (combined positive score ≥1) HNSCC. Secondary objectives are the exploration of patient subgroups most likely deriving benefit from this novel combination and the establishment of liquid biopsy tumor monitoring in HNSCC.

Ethics and dissemination

This clinical study was designed and will be conducted in compliance with Good Clinical Practice and in accordance with the Declaration of Helsinki. It is intended to publish the results of this study in peer-reviewed scientific journals and to present its content at academic conferences.

Conclusions

A significant number of patients with R/M HNSCC are frail and may not tolerate chemotherapy, these patients may only be suitable for pembrolizumab monotherapy. However, long term disease stabilizations remain the exception and there is a need for the development of efficacious combination regimens for this patient population. The FOCUS study aims to optimize treatment of R/M HNSCC patients with this promising new treatment approach.

Clinical Trial Registration

https://clinicaltrials.gov/study/NCT05075122, identifier NCT05075122.
Development and validation of a nomogram for predicting cardiovascular mortality risk for diffuse large B-cell lymphoma in children, adolescents, and adults
Authors: Mu Kai , Zhang Jing , Gu Yan , Huang Guoying
Published: February 2024

Objective

This study aimed to construct and validate a nomogram for predicting cardiovascular mortality (CVM) for child, adolescent, and adult patients with diffuse large B-cell lymphoma (DLBCL).

Materials and methods

Patients with only one primary tumor of DLBCL first diagnosed between 2000 and 2019 in the SEER database were extracted. We used the cumulative incidence function (CIF) to evaluate the cumulative rate of CVM. The outcome of interest was CVM, which was analyzed using a competing risk model, accounting for death due to other causes. The total database was randomly divided into a training cohort and an internal validation cohort at a ratio of 7:3. Adjustments were for demographics, tumor characteristics, and treatment modalities. Nomograms were constructed according to these risk factors to predict CVM risk at 5, 10, and 15 years. Validation included receiver operating characteristic (ROC) curves, time-dependent ROC, C-index, calibration curves, and decision curve analysis.

Results

One hundred four thousand six hundred six patients following initial diagnosis of DLBCL were included (58.3% male, median age 64 years, range 0–80, White 83.98%). Among them, 5.02% died of CVM, with a median follow-up time of 61 (31–98) months. Nomograms based on the seven risk factors (age at diagnosis, gender, race, tumor grade, Ann Arbor stage, radiation, chemotherapy) with hazard ratios ranging from 0.19–1.17 showed excellent discrimination, and calibration plots demonstrated satisfactory prediction. The 5-, 10-, and 15-year AUC and C-index of CVM in the training set were 0.716 (0.714–0.718), 0.713 (0.711–0.715), 0.706 (0.704–0.708), 0.731, 0.727, and 0.719; the corresponding figures for the validation set were 0.705 (0.688–0.722), 0.704 (0.689–0.718), 0.707 (0.693–0.722), 0.698, 0.698, and 0.699. Decision curve analysis revealed a clinically beneficial net benefit.

Conclusions

We first built the nomogram model for DLBCL patients with satisfactory prediction and excellent discrimination, which might play an essential role in helping physicians enact better treatment strategies at the time of initial diagnosis.
Elucidation of the mechanism of action of ailanthone in the treatment of colorectal cancer: integration of network pharmacology, bioinformatics analysis and experimental validation
Authors: Ma Shanbo , Guo Xiaodi , Han Ruisi , Meng Qian , Zhang Yan , Quan Wei , Miao Shan , Yang Zhao , Shi Xiaopeng , Wang Siwang
Published: February 2024

Background: Ailanthone, a small compound derived from the bark of Ailanthus altissima (Mill.) Swingle, has several anti-tumour properties. However, the activity and mechanism of ailanthone in colorectal cancer (CRC) remain to be investigated. This study aims to comprehensively investigate the mechanism of ailanthone in the treatment of CRC by employing a combination of network pharmacology, bioinformatics analysis, and molecular biological technique.

Methods: The druggability of ailanthone was examined, and its targets were identified using relevant databases. The RNA sequencing data of individuals with CRC obtained from the Cancer Genome Atlas (TCGA) database were analyzed. Utilizing the R programming language, an in-depth investigation of differentially expressed genes was carried out, and the potential target of ailanthone for anti-CRC was found. Through the integration of protein-protein interaction (PPI) network analysis, GO and KEGG enrichment studies to search for the key pathway of the action of Ailanthone. Then, by employing molecular docking verification, flow cytometry, Transwell assays, and Immunofluorescence to corroborate these discoveries.

Results: Data regarding pharmacokinetic parameters and 137 target genes for ailanthone were obtained. Leveraging The Cancer Genome Atlas database, information regarding 2,551 differentially expressed genes was extracted. Subsequent analyses, encompassing protein–protein interaction network analysis, survival analysis, functional enrichment analysis, and molecular docking verification, revealed the PI3K/AKT signaling pathway as pivotal mediators of ailanthone against CRC. Additionally, the in vitro experiments indicated that ailanthone substantially affects the cell cycle, induces apoptosis in CRC cells (HCT116 and SW620 cells), and impedes the migration and invasion capabilities of these cells. Immunofluorescence staining showed that ailanthone significantly inhibited the phosphorylation of AKT protein and suppressed the activation of the PI3K/AKT signaling pathway, thereby inhibiting the proliferation and metastasis of CRC cells.

Conclusion: Therefore, our findings indicate that Ailanthone exerts anti-CRC effects primarily by inhibiting the activation of the PI3K/AKT pathway. Additionally, we propose that Ailanthone holds potential as a therapeutic agent for the treatment of human CRC.
Soluble guanylate cyclase stimulators and activators: new horizons in the treatment of priapism associated with sickle cell disease
Authors: Pereira Dalila Andrade , Silveira Tammyris Helena Rebecchi , Calmasini Fabiano Beraldi , Silva Fábio Henrique
Published: February 2024

Priapism, defined as a prolonged and often painful penile erection occurring without sexual stimulation or desire, is a common complication in sickle cell disease (SCD), affecting up to 48% of male patients. This condition presents significant clinical challenges and can lead to erectile dysfunction if not properly managed. Current pharmacological treatments for SCD-related priapism are primarily reactive rather than preventative, highlighting a gap in effective medical intervention strategies. A critical factor in developing priapism is the reduced basal bioavailability of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) in erectile tissues. New prevention strategies should ideally target the underlying pathophysiology of the disease. Compounds that stimulate and activate soluble guanylate cyclase (sGC) emerge as potential therapeutic candidates since these compounds have the property of inducing cGMP production by sGC. This review explores the potential of sGC stimulators and activators in treating priapism associated with SCD. We discuss the advantages of these agents in the face of the challenging pathophysiology of SCD. Additionally, the review underscores the impact of intravascular hemolysis and oxidative stress on priapism pathophysiology in SCD, areas in which sGC stimulators and activators may also have beneficial therapeutic effects.