bluuebunny/crossref_metadata_2025 huggingface dataset:
PIH1D3-knockout rats exhibit full ciliopathy features and dysfunctional pre-assembly and loading of dynein arms in motile cilia
Authors: Zhang Tingting , Cui Shiquan , Xiong Xinrui , Liu Ying , Cao Qilin , Xia Xu-Gang , Zhou Hongxia
Published: October 2023

Background: Recessive mutation of the X-linked gene, PIH1 domain-containing protein 3 (PIH1D3), causes familial ciliopathy. PIH1D3 deficiency is associated with the defects of dynein arms in cilia, but how PIH1D3 specifically affects the structure and function of dynein arms is not understood yet. To gain insights into the underlying mechanisms of the disease, it is crucial to create a reliable animal model. In humans, rats, and mice, one copy of the PIH1D3 gene is located on the X chromosome. Interestingly, mice have an additional, intronless copy of the Pih1d3 gene on chromosome 1. To develop an accurate disease model, it is best to manipulate the X-linked PIH1D3 gene, which contains essential regulatory sequences within the introns for precise gene expression. This study aimed to develop a tailored rat model for PIH1D3-associated ciliopathy with the ultimate goal of uncovering the intricate molecular mechanisms responsible for ciliary defects in the disease.

Methods: Novel Pih1d3-knockout (KO) rats were created by using TALEN-mediated non-homologous DNA recombination within fertilized rat eggs and, subsequently, underwent a comprehensive characterization through a battery of behavioral and pathological assays. A series of biochemical and histological analyses were conducted to elucidate the identity of protein partners that interact with PIH1D3, thus shedding light on the intricate molecular mechanisms involved in this context.

Results: PIH1D3-KO rats reproduced the cardinal features of ciliopathy including situs inversus, defects in spermatocyte survival and mucociliary clearance, and perinatal hydrocephalus. We revealed the novel function of PIH1D3 in cerebrospinal fluid circulation and elucidated the mechanism by which PIH1D3 deficiency caused communicating hydrocephalus. PIH1D3 interacted with the proteins required for the pre-assembly and uploading of outer (ODA) and inner dynein arms (IDA), regulating the integrity of dynein arm structure and function in cilia.

Conclusion: PIH1D3-KO rats faithfully reproduced the cardinal features of ciliopathy associated with PIH1D3 deficiency. PIH1D3 interacted with the proteins responsible for the pre-assembly and uploading of dynein arms in cilia, and its deficiency led to dysfunctional cilia and, thus, to ciliopathy by affecting the pre-assembly and uploading of dynein arms. The resultant rat model is a valuable tool for the mechanistic study of PIH1D3-caused diseases.
Radiochemical and biological assessments of a PSMA-I&S cold kit for fast and inexpensive 99mTc-labeling for SPECT imaging and radioguided surgery in prostate cancer
Authors: Fuscaldi Leonardo Lima , Sobral Danielle Vieira , Durante Ana Claudia Ranucci , Mendonça Fernanda Ferreira , Miranda Ana Cláudia Camargo , Salgueiro Carla , de Castiglia Silvia Gomez , Yamaga Lilian Yuri Itaya , da Cunha Marcelo Livorsi , Malavolta Luciana , de Barboza Marycel Figols , Mejia Jorge
Published: October 2023

The expression of prostate-specific membrane antigen (PSMA) is upregulated in prostate cancer (PCa) cells and PSMA-ligands have been radiolabeled and used as radiopharmaceuticals for targeted radionuclide therapy (TRT), single photon emission computed tomography (SPECT) or positron emission tomography (PET) molecular imaging, and radioguided surgery in PCa patients. Herein, we aimed at radiolabeling the PSMA-I&S cold kit with 99mTc, resulting in a radiopharmaceutical with high radiochemical yield (RCY) and stability for SPECT imaging and radioguided surgery in PCa malignancies. Various pre-clinical assays were conducted to evaluate the [99mTc]Tc-PSMA-I&S obtained by the cold kit. These assays included assessments of RCY, radiochemical stability in saline, lipophilicity, serum protein binding (SPB), affinity for LNCaP-PCa cells (binding and internalization studies), and ex vivo biodistribution profile in naive and LNCaP-PCa-bearing mice. The radiopharmaceutical was obtained with good RCY (92.05% ± 2.20%) and remained stable for 6 h. The lipophilicity was determined to be −2.41 ± 0.06, while the SPB was ∼97%. The binding percentages to LNCaP cells were 9.41% ± 0.57% (1 h) and 10.45% ± 0.45% (4 h), with 63.12 ± 0.93 (1 h) and 65.72% ± 1.28% (4 h) of the bound material being internalized. Blocking assays, employing an excess of unlabeled PSMA-I&S, resulted in a reduction in the binding percentage by 2.6 times. The ex vivo biodistribution profile confirmed high accumulation of [99mTc]Tc-PSMA-I&S in the tumor and the tumor-to-contralateral muscle ratio was ∼6.5. In conclusion, [99mTc]Tc-PSMA-I&S was successfully obtained by radiolabeling the cold kit using freshly eluted [99mTc]NaTcO4, exhibiting good RCY and radiochemical stability. The preclinical assays demonstrated that the radiopharmaceutical shows favorable characteristics for SPECT imaging and radioguided surgery in PCa patients.
Carbon dots with light-responsive oxidase-like activity for colorimetric detection of dopamine and the catalytic mechanism
Authors: Jia Zhenzhen , Liu Yuna , Cheng Liangliang , Deng Zhichao , Zhang Mingzhen , Tuo Hang
Published: October 2023

Introduction: Dopamine is one of the most significant neurotransmitters and plays an important role in the management of cognitive functions such as learning, memory, and behavior. The disorder of dopamine is associated with many major mental diseases. It is necessary to develop selective methods for the detection of dopamine.

Methods: In this work, carbon dots (CDs) were synthesized by a solvothermal route using glutathione, L-histidine, and formamide as sources.

Results: Under light irradiation, The CDs convert dissolved oxygen to singlet oxygen (1O2), which could oxidize TMB. When reduced dopamine was present, it suppressed the catalysis of CDs, then the absorption of the CDs-coupled TMB complex at 652 nm was diminished. Furthermore, it was revealed that the surface groups including hydroxyl, amino, carbonyl, and carboxyl groups of CDs were related to their light-responsive catalytic activity by surface modification. In the range of 0.5-15 μM, the CDs could afford a LOD of 0.25 μM for dopamine detection with fine linearity, also showing good selectivity.

Discussion: The results from fetal bovine serum indicated the good applicability of the CDs in the determination of dopamine.
The anal pore route is efficient to infect Amblyomma spp. ticks with Rickettsia rickettsii and allows the assessment of the role played by infection control targets
Authors: Nassar Marcelly Bastos , Pavanelo Daniel B. , Labruna Marcelo B. , Daffre Sirlei , Esteves Eliane , Fogaça Andréa C.
Published: October 2023

Adult Amblyomma sculptum and Amblyomma aureolatum ticks are partially refractory to Rickettsia rickettsii when fed on infected hosts, hindering the functional characterization of potentially protective targets in the bacterial acquisition. In the current study, we used the anal pore route to infect adult A. sculptum and A. aureolatum ticks with R. rickettsii and to assess the effects of the knockdown of microplusin in infection control. The anal pore route was efficient to infect both species, resulting in a prevalence of around 100% of infected ticks. Higher loads of R. rickettsii were detected in microplusin-silenced A. aureolatum in relation to the control, as previously obtained when microplusin-silenced ticks were fed on R. rickettsii-infected rabbits. This is the first report showing R. rickettsii infection through the anal pore in Amblyomma ticks, highlighting this route as a powerful tool to assess the role played by additional targets in the control of pathogens.
A combination of restudy and retrieval practice maximizes retention of briefly encountered facts
Authors: Ashby Stefania R. , Zeithamova Dagmar
Published: October 2023

Introduction

Is retrieval practice always superior to restudy? In a classic study by Roediger and Karpicke, long-term retention of information contained in prose passages was found to be best when opportunities to restudy were replaced with opportunities to self-test. We were interested whether this striking benefit for repeated testing at the expense of any restudy replicates when study opportunities are brief, akin to a single mention of a fact in an academic lecture. We were also interested in whether restudying after a test would provide any additional benefits compared to restudying before test.

Method

In the current study, participants encountered academically relevant facts a total of three times; each time either studied (S) or self-tested (T). During study, participants predicted how likely they were to remember each fact in the future. During self-test, participants performed covert cued recall and self-reported their recall success. Final test followed immediately or after a delay (Experiment 1: 2 days, Experiment 2: 7 days).

Results

Contrary to prior work, long-term memory was superior for facts the were restudied in addition to self-tested (SST > STT = SSS). We further investigated whether restudy after a test (STS) provides additional benefits compared to restudy before test (SST). Restudying after a retrieval attempt provided an additional benefit compared to restudying before a retrieval attempt on an immediate test, but this benefit did not carry over a delay. Finally, exploratory analyses indicated that restudy after test improved the accuracy of participants' subjective predictions of encoding success.

Discussion

Together, our results qualify prior work on the benefits of repeated testing, indicating that balancing testing with repetition may allow for more information to be learned and retained. These findings offer new insights into the conditions that promote encoding and long-term retention, provide new constraints for existing cognitive theories of testing effects, and have practical implications for education.
Significance of fatty liver index to detect prevalent ischemic heart disease: evidence from national health and nutrition examination survey 1999–2016
Authors: Niu Yuyu , Wang Guifang , Feng Xianjun , Niu Hongyi , Shi Wenrui
Published: October 2023

Background

Non-alcoholic fatty liver disease (NAFLD) contributes to the development of ischemic heart disease via multiple mechanisms. Fatty liver index (FLI) has been proposed as an accurate, convenient, and economic surrogate of the severity of NAFLD. Our present study aims to assess the association between FLI and the prevalent IHD and to evaluate the potential value of FLI to refine the detection of prevalent IHD in the general population.

Methods

Our work recruited 32,938 subjects from the National Health and Nutrition Examination Survey 1999–2016. IHD was diagnosed according to the subjects’ self-report. FLI was determined based on triglycerides, BMI, γ-glutamyltransferase, and waist circumference.

Results

2,370 (7.20%) subjects were diagnosed with IHD. After adjustment of age, sex, race, current smoking, current drinking, PIR, BMI, WC, TC, TG, GGT, Scr, FPG, SBP, anti-hypertensive therapy, anti-diabetic therapy, and lipid-lowering therapy, one standard deviation increase of FLI resulted in a 27.0% increment of the risk of prevalent IHD. In the quartile analysis, we observed a 1.684 times risk of prevalent IHD when comparing the fourth quartile with the first quartile, and there was a trend towards higher risk across the quartiles. The smooth curve fitting displayed a linear relationship between FLI and the presence of IHD without any threshold or saturation effect. Subgroup analysis revealed a robust association in conventional cardiovascular subpopulations, and the association could be more prominent in female subjects and diabetes patients. ROC analysis demonstrated an incremental value of FLI for detecting prevalent IHD after introducing it to conventional cardiovascular risk factors (AUC: 0.823 vs. 0.859, P for comparison <0.001). Also, results from reclassification analysis implicated that more IHD patients could be correctly identified by introducing FLI into conventional cardiovascular risk factors (continuous net reclassification index: 0.633, P < 0.001; integrated discrimination index: 0.034, P < 0.001).

Conclusion

The current analysis revealed a positive and linear relationship between FLI and the prevalent IHD. Furthermore, our findings suggest the incremental value of FLI to refine the detection of prevalent IHD in the general population.
No evidence of a causal relationship between ankylosing spondylitis and cardiovascular disease: a two-sample Mendelian randomization study
Authors: Zhong Yan , Chen YingWen , Zhang XinYue , Cai WenJun , Zhao ChangWei , Zhao WenHai
Published: October 2023

Objective

Observational studies have suggested an increased risk of cardiovascular disease in individuals with ankylosing spondylitis. However, these studies are prone to confounding factors and reverse causality. To address these limitations, we conducted a Mendelian randomization study to assess the causal relationship between AS and CVD.

Methods

The study population comprises 9,069 individuals with ankylosing spondylitis and 509,093 individuals with either of six common cardiovascular diseases and a related indicator. Causal analysis using summary effect estimates and inverse variance weighting were employed as the main methods.

Results

The CAUSE analysis showed no evidence of a causal relationship between AS and CVD. The odds ratios for total CVD, heart failure, myocardial infarction, valvular heart disease, ischemic heart disease, and venous thromboembolism, Arterial stiffness index, were as follows: OR, 1.01; 95% confidence interval, 0.96–1.05; P = 0.91; OR, 1.03; 95% CI, 0.99–1.08; P = 0.50; OR, 0.94; 95% CI, 0.86–1.03; P = 0.53; OR, 0.99; 95% CI, 0.94–1.04; P = 0.99; OR, 0.98; 95% CI, 0.91–1.04; P = 0.94; OR, 0.98; 95% CI, 0.91–1.04; P = 0.99; β, −0.0019; 95% CI, 0.97–1.01; P = 0.99. The IVW and weighted median methods also yielded consistent results, and no heterogeneity or pleiotropy was found. Likewise, a reverse Mendelian randomization analysis did not uncover a heritable causal relationship between AS and CVD.

Conclusion

This Mendelian randomization study does not support a causal relationship between AS and CVD. Further research is needed to confirm this association.
Efficacy and safety of sodium-glucose cotransporter-2 inhibitors for heart failure with mildly reduced or preserved ejection fraction: a systematic review and meta-analysis of randomized controlled trials
Authors: Cheema Huzaifa Ahmad , Shafiee Arman , Athar Mohammad Mobin Teymouri , Rafiei Mohammad Ali , Mehmannavaz Atefe , Jafarabady Kyana , Shahid Abia , Ahmad Adeel , Ijaz Sardar Hassan , Dani Sourbha S. , Minhas Abdul Mannan Khan , Nashwan Abdulqadir J. , Fudim Marat , Fonarow Gregg C.
Published: October 2023

Aims

We sought to conduct a meta-analysis to evaluate the efficacy and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and HF with mildly reduced ejection fraction (HFmrEF).

Methods

We searched the Cochrane Library, MEDLINE (via PubMed), Embase, and ClinicalTrials.gov till March 2023 to retrieve all randomized controlled trials of SGLT2i in patients with HFpEF or HFmrEF. Risk ratios (RRs) and standardized mean differences (SMDs) with their 95% conﬁdence intervals (95% CIs) were pooled using a random-effects model.

Results

We included data from 14 RCTs. SGLT2i reduced the risk of the primary composite endpoint of first HF hospitalization or cardiovascular death (RR 0.81, 95% CI: 0.76, 0.87; I2 = 0%); these results were consistent across the cohorts of HFmrEF and HFpEF patients. There was no significant decrease in the risk of cardiovascular death (RR 0.96, 95% CI: 0.82, 1.13; I2 = 36%) and all-cause mortality (RR 0.97, 95% CI: 0.89, 1.05; I2 = 0%). There was a significant improvement in the quality of life in the SGLT2i group (SMD 0.13, 95% CI: 0.06, 0.20; I2 = 51%).

Conclusion

The use of SGLT2i is associated with a lower risk of the primary composite outcome and a higher quality of life among HFpEF/HFmrEF patients. However, further research involving more extended follow-up periods is required to draw a comprehensive conclusion.

Systematic Review Registration

PROSPERO (CRD42022364223).
Catchment-scale patterns of geomorphic activity and vegetation distribution in an alpine glacier foreland (Kaunertal Valley, Austria)
Authors: Haselberger Stefan , Scheper Simon , Otto Jan-Christoph , Zangerl Ulrich , Ohler Lisa-Maria , Junker Robert R. , Kraushaar Sabine
Published: October 2023

The interaction between geomorphological and ecological processes plays a significant role in determining landscape patterns in glacier forelands. However, the spatial organization of this biogeomorphic mosaic remains unclear due to limited catchment-scale data. To address this gap, we used a multi-proxy analysis to map potential geomorphic activity related to surface changes induced by sediment transport on drift-mantled slopes and a glaciofluvial plain. High-resolution vegetation data were used to generate a catchment-scale map delineating vegetation cover and stability thresholds. The two maps were integrated, and an exploratory regression analysis was conducted to investigate the influence of geomorphic activity on vegetation colonization. The multi-proxy analysis resulted in an accurate mapping of catchment-wide geomorphic activity, with a validation accuracy ranging from 75.3% through field mapping to 85.9% through plot sampling. Through vegetation cover mapping, we identified biogeomorphic stability thresholds, revealing a mosaic of vegetation distribution. Distinct colonization patterns emerged across different geomorphic process groups, influenced by process magnitude and the time since the last disturbance event. The exploratory regression analysis showed that vegetation distribution is significantly affected by geomorphic processes. Based on the overlay of results regarding geomorphic activity and vegetation distribution, we suggest an age-independent framework that indicates four potential situations of biogeomorphic succession.
Effects of family and neighborhood vulnerability on dual language learner and monolingual children’s preschool outcomes
Authors: Frechette Liz , Castle Sherri , Jeon Shinyoung , Horm Diane , Martinez Irving , Vega Ruvalcaba Denise , Schaefer Shawn
Published: October 2023

Introduction

Research has documented that home and neighborhood contexts of children from low-income families are associated with lower cognitive and social–emotional skills than their higher-income peers. Even though over a third of young children growing up in poverty are dual language learners (DLLs), little research has examined how contextual effects differ between DLL and monolingual children. The current study examines how these two contexts, neighborhood vulnerability and family socioeconomic risk, impact executive function (EF) and social–emotional skills in DLL and monolingual preschoolers.

Methods

A secondary analysis was completed on data from two Head Start programs. A series of cross-classified models with interactions were conducted to examine the moderating role of DLL status on associations between neighborhood vulnerability and family risk and preschoolers’ EF and social-emotional skills.

Results

Proficient bilingual children’s EF skills were not impacted by neighborhood risks, suggesting that proficient bilingual children may have more opportunities to grow their EF skills when switching between English and Spanish regardless of neighborhood context. An unexpected result occurred for emergent bilingual children who were reported to demonstrate fewer behavior problems regardless of family risk, highlighting the importance of ensuring all DLL families have access to resources to promote their children’s social–emotional skills; and teachers have the proper training to support the behaviors of children in their classroom with varying levels of English proficiency.

Discussion

Although speaking two languages may be a protective factor for young DLLs growing up in poverty, little research has examined how contextual effects differ between DLL and monolingual children. The current study contributes by examining how DLL status, especially two different DLL statuses (i.e., Proficient Bilinguals and Emergent Bilinguals), may vary as a buffer in moderating the negative associations between collective neighborhood vulnerability, individual family risk, and children’s EF and social–emotional skills.
Hs1Cas12a and Ev1Cas12a confer efficient genome editing in plants
Authors: Li Gen , Zhang Yingxiao , Dailey Micah , Qi Yiping
Published: October 2023

Cas12a, also known as Cpf1, is a highly versatile CRISPR-Cas enzyme that has been widely used in genome editing. Unlike its well-known counterpart, Cas9, Cas12a has unique features that make it a highly efficient genome editing tool at AT-rich genomic regions. To enrich the CRISPR-Cas12a plant genome editing toolbox, we explored 17 novel Cas12a orthologs for their genome editing capabilities in plants. Out of them, Ev1Cas12a and Hs1Cas12a showed efficient multiplexed genome editing in rice and tomato protoplasts. Notably, Hs1Cas12a exhibited greater tolerance to lower temperatures. Moreover, Hs1Cas12a generated up to 87.5% biallelic editing in rice T0 plants. Both Ev1Cas12a and Hs1Cas12a achieved effective editing in poplar T0 plants, with up to 100% of plants edited, albeit with high chimerism. Taken together, the efficient genome editing demonstrated by Ev1Cas12a and Hs1Cas12a in both monocot and dicot plants highlights their potential as promising genome editing tools in plant species and beyond.
Disitamab Vedotin plus anti-PD-1 antibody show good efficacy in refractory primary urethral cancer with low HER2 expression: a case report
Authors: Zheng Yue , Xue Yin-Yin , Zhao Ya-Qin , Chen Ye , Li Zhi-Ping
Published: October 2023

Primary urethral carcinoma (PUC) has a low incidence, but with high aggressiveness. Most of the patients are found in late stage, with poor prognosis. At present, chemotherapy is still the main treatment for metastatic PUC, but it has limited effect. Here, we report a case of metastatic PUC with low HER2 expression that developed disease progression after multiline therapy including chemotherapy, programmed death-1 (PD-1) inhibitors and multi-targeted receptor tyrosine kinase (RTK) inhibitor. After receiving Disitamab Vedotin(a novel antibody drug conjugate, ADC) and toripalimab (a PD-1 inhibitor), the patient achieved persistent PR, and the PFS exceeded 12 months up to now. Our report indicates that, despite the patient of metastatic PUC has low expression of HER2, it is still possible to benefit from Disitamab Vedotin combined with PD-1 inhibitor, which may reverse the drug resistance of PD-1 inhibitor and chemotherapy to a certain extent. But larger sample studies are needed to determine the efficacy of this treatment strategy and its impact on survival.
Targeting myeloid-derived suppressor cells with gemcitabine to enhance efficacy of adoptive cell therapy in bladder cancer
Authors: Bazargan Sarah , Bunch Brittany , Ojwang‘ Awino Maureiq E. , Blauvelt Jamie , Landin Annick , Ali Johannes , Abrahams Dominique , Cox Cheryl , Hall Amy M. , Beatty Matthew S. , Poch Michael , Rejniak Katarzyna A. , Pilon-Thomas Shari
Published: October 2023

Background

New therapeutics in development for bladder cancer need to address the recalcitrant nature of the disease. Intravesical adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) can potentially induce durable responses in bladder cancer while maximizing T cells at the tumor site. T cells infused into the bladder directly encounter immunosuppressive populations, such as myeloid derived suppressor cells (MDSCs), that can attenuate T cell responses. Intravesical instillation of gemcitabine can be used as a lymphodepleting agent to precondition the bladder microenvironment for infused T cell products.

Methods

Urine samples from bladder cancer patients and healthy donors were analyzed by flow cytometry and cytometric bead array for immune profiling and cytokine quantification. MDSCs were isolated from the urine and cocultured with stimulated T cells to assess effects on proliferation. An orthotopic murine model of bladder cancer was established using the MB49-OVA cell line and immune profiling was performed. MDSCs from tumor-bearing mice were cocultured with OT-I splenocytes to assess T cell proliferation. Mice received intravesical instillation of gemcitabine and depletion of immune cells was measured via flow cytometry. Bladder tumor growth of mice treated with intravesical gemcitabine, OT-I transgenic T cells, or combination was monitored via ultrasound measurement.

Results

In comparison to healthy donors, urine specimen from bladder cancer patients show high levels of MDSCs and cytokines associated with myeloid chemotaxis, T cell chemotaxis, and inflammation. T cells isolated from healthy donors were less proliferative when cocultured with MDSCs from the urine. Orthotopic murine bladder tumors also presented with high levels of MDSCs along with enrichment of cytokines found in the patient urine samples. MDSCs isolated from spleens of tumor-bearing mice exerted suppressive effects on the proliferation of OT-I T cells. Intravesical instillation of gemcitabine reduced overall immune cells, MDSCs, and T cells in orthotopic bladder tumors. Combination treatment with gemcitabine and OT-I T cells resulted in sustained anti-tumor responses in comparison to monotherapy treatments.

Conclusion

MDSCs are enriched within the microenvironment of bladder tumors and are suppressive to T cells. Gemcitabine can be used to lymphodeplete bladder tumors and precondition the microenvironment for intravesical ACT.
The role of TEMRA cell-mediated immune senescence in the development and treatment of HIV disease
Authors: Guo Lihui , Liu Xudong , Su Xin
Published: October 2023

Human Immunodeficiency Virus (HIV) has plagued human society for a long time since its discovery, causing a large number of patients to suffer and costing hundreds of millions of medical services every year. Scientists have found that HIV and antiretroviral therapy accelerate immune aging by inducing mitochondrial dysfunction, and that terminal effector memory T cells (TEMRA cells) are crucial in immune aging. This specific subset of effector memory T cells has terminally differentiated properties and exhibits high cytotoxicity and proinflammatory capacity. We therefore explored and described the interplay between exhaustion features, essential markers, functions, and signaling pathways from previous studies on HIV, antiretroviral therapy, immune senescence, and TEMRA cells. Their remarkable antiviral capacity is then highlighted by elucidating phenotypic changes in TEMRA cells during HIV infection, describing changes in TEMRA cells before, during, and after antiretroviral therapy and other drug treatments. Their critical role in complications and cytomegalovirus (CMV)-HIV superinfection is highlighted. These studies demonstrate that TEMRA cells play a key role in the antiviral response and immune senescence during HIV infection. Finally, we review current therapeutic strategies targeting TEMRA cells that may be clinically beneficial, highlight their potential role in HIV-1 vaccine development, and provide perspectives and predictions for related future applications.
DNA metabarcoding reveals evidence of inter- and intra-guild predation by Scylla paramamosain in a marine ecosystem
Authors: Saqib Hafiz Sohaib Ahmed , Yuan Ye , Kazmi Syed Shabi Ul Hassan , Tayyab Muhammad , Xiang Zifei , Ikhwanuddin Mhd , Ma Hongyu
Published: October 2023

Introduction

Crustacean predators exhibit diverse trophic interactions across various habitats in aquatic ecosystems. To assess their ecological roles, it is essential to understand their complete dietary spectrum. Recently, DNA-based techniques such as DNA metabarcoding and high-throughput sequencing have provided insights into trophic networks and their response to environmental drivers.

Methods

In this study, we used these methods to investigate the impact of salinity gradients on the trophic networks of mud crabs (Scylla paramamosain) in marine ecosystems.

Results

Our results revealed that mud crabs prey on a wide range of taxa, including crabs (other than the host species), fish, shrimps, and other prey factions. Salinity gradients had a significant influence on the specific prey items, such as high predation on Metapenaeus, and Trigonopterus species in high salinity sites. Notably, crabs exhibited a greater infestation of Portunion parasites in environments with high salinity levels, in contrast to environments with lower salinity levels. Ordination analysis showed that mud crabs adapt their diet according to environmental constraints.

Discussion

Furthermore, the results indicate that mud crabs showed opportunistic predation behavior as they were observed preying on other Portunidae species sharing the same trophic guild. Overall, these findings demonstrate the dietary plasticity and associated parasite infestation of an important crustacean predator, and provide evidence that environmental changes may affect incidences of the associated parasites as well as the specific predator-prey interactions indirectly through fluctuations in marine ecosystems.
Assessing larval fish diversity and conservation needs in the Luzon strait using DNA barcoding
Authors: Li Haitao , Chen Yiyong , Li Xi , Zhou Peng , Xiong Xiaofei
Published: October 2023

Introduction

Accurate species identification and biodiversity assessment of larval fish are essential for effective management and conservation of fisheries resources, as it allows for the estimation of parent stocks, assessment of future recruitment, and prediction of spawning and nursing grounds. However, traditional morphology-based identification methods have inherent limitations, highlighting the need for accurate and efficient techniques to address these challenges effectively. The Luzon Strait, a crucial channel connecting the South China Sea to Western Pacific Ocean, is renowned for its fish biodiversity. However, our knowledge of the biodiversity status of larval fish species in this region remains insufficient.

Methods

Here we employed DNA barcoding to assess larval fish species diversity in the Luzon Strait and adjacent waters. We investigated the species composition, diversity, and geographical distribution of larval fish communities in the region. Moreover, we assessed habitat types, human uses, and IUCN conservation status of each larval fish species.

Results

A total of 385 larval fish individuals were collected from 15 stations, and 354 individuals were successfully barcoded and identified, representing 147 species from 93 genera, 44 families, and 22 orders. The interspecific Kimura 2-parameter (K2P) divergence exhibited a significant increase of approximately 55-fold higher than intraspecific divergence. The phylogenetic neighbor-joining tree confirmed the distinct lineages for each taxonomic level, demonstrating the feasibility of DNA barcoding. We observed notable variations in fish species diversity and community composition among sampling stations. Non-metric multidimensional scaling analysis revealed greater diversity and dissimilarity of larval fish community compositions in the western regions compared to the eastern regions. This pattern corresponded to the grouping based on the path of the Kuroshio current, suggesting its influence on the fish community structure. Additionally, economically valuable species were identified at these stations, highlighting their ecological significance as potential spawning or nursery grounds for larval fish. We also examined the habitat type, human use, and conservation status of each larval fish species, providing comprehensive insights into their ecological significance and conservation needs.

Discussion

The establishment of a local DNA sequences database through DNA barcoding will greatly enhance the accuracy of species identification in environmental DNA (eDNA) metabarcoding applications. Altogether, this study offers valuable information for identifying important spawning and nursing grounds of fish populations, thereby supporting sustainable management and conservation of fisheries resources in this region.
Floating microplastic inventories in the southern Beaufort Sea, Arctic Ocean
Authors: Ikenoue Takahito , Nakajima Ryota , Mishra Pravakar , Ramasamy Eswara Venkatesaperumal , Fujiwara Amane , Nishino Shigeto , Murata Akihiko , Watanabe Eiji , Itoh Motoyo
Published: October 2023

The microplastics inflow into the Arctic Ocean may increase environmental stress on the Arctic marine ecosystem on the Pacific side, where sea ice has been significantly reduced because of global warming. However, quantitative data on microplastics are very limited in the Beaufort Sea, which is covered by sea ice for most of the year, even in summer. We therefore observed microplastic concentrations over a wide area of the southern Beaufort Sea using a neuston net from 30 August to 10 September 2022 to estimate the total number (particle inventory) and mass (mass inventory) of microplastics in the entire water column. The particle inventory during the sampling period ranged from 937 to 28,081 pieces km−2 (mean ± standard deviation, 7570 ± 7600 pieces km−2). The mass inventory of microplastics ranged from 22 to 664 g km−2 (179 ± 180 g km−2). Relatively high microplastic inventories (>6500 pieces km−2) were observed off Utqiaġvik and the mouth of the Mackenzie River, suggesting that some microplastics originate not only in the Pacific but also in the Arctic. These values indicate that waters in the southern Beaufort Sea is contaminated with microplastics to the same order of magnitude as the Chukchi Sea.
Chinese Clinical Trial Registry 13-year data collection and analysis: geographic distribution, financial support, research phase, duration, and disease categories
Authors: Fan Ruitai , Zheng Yufei , Zhou Runze , Beeraka Narasimha M. , Sukocheva Olga A. , Zhao Ruiwen , Li Shijie , Zhao Xiang , Liu Chunying , He Song , Mahesh P. A. , Gurupadayya B. M. , Nikolenko Vladimir N. , Zhao Di , Liu Junqi
Published: October 2023

Objective

To evaluate the current status of trial registration on the Chinese Clinical Trial Registry (ChiCTR).

Design

In this descriptive study, a multi-dimensional grouping analysis was conducted to estimate trends in the annual trial registration, geographical distribution, sources of funding, targeted diseases, and trial subtypes.

Setting

We have analyzed all clinical trial records (over 30,000) registered on the Chinese Clinical Trial Registry (ChiCTR) from 2007 to 2020 executed in China.

Main outcome(s) and measure(s)

The main outcome was the baseline characteristics of registered trials. These trials were categorized and analyzed based on geographical distribution, year of implementation, disease type, resource and funding type, trial duration, trial phase, and the type of experimental approach.

Results

From 2008 to 2017, a consistent upward trend in clinical trial registrations was observed, showing an average annual growth rate of 29.2%. The most significant year-on-year (yoy%) growth in registrations occurred in 2014 (62%) and 2018 (68.5%). Public funding represented the predominant source of funding in the Chinese healthcare system. The top five ChiCTR registration sites for all disease types were highly populated urban regions of China, including Shanghai (5,658 trials, 18%), Beijing (5,127 trials, 16%), Guangdong (3,612 trials, 11%), Sichuan (2,448 trials, 8%), and Jiangsu (2,196 trials, 7%). Trials targeting neoplastic diseases accounted for the largest portion of registrations, followed by cardio/cerebrovascular disease (CCVD) and orthopedic diseases-related trials. The largest proportions of registration trial duration were 1–2 years, less than 1 year, and 2–3 years (at 27.36, 26.71, and 22.46%). In the case of the research phase, the top three types of all the registered trials are exploratory research, post-marketing drugs, and clinical trials of new therapeutic technology.

Conclusion and relevance

Oncological and cardiovascular diseases receive the highest share of national public funding for medical clinical trial-based research in China. Publicly funded trials represent a major segment of the ChiCTR registry, indicating the dominating role of public governance in this health research sector. Furthermore, the growing number of analyzed records reflect the escalation of clinical research activities in China. The tendency to distribute funding resources toward exceedingly populated areas with the highest incidence of oncological and cardiovascular diseases reveals an aim to reduce the dominating disease burden in the urban conglomerates in China.
Pathogenicity and functional analysis of CFAP410 mutations causing cone-rod dystrophy with macular staphyloma
Authors: Yang Shaoqing , Li Ya , Yang Lin , Guo Qingge , You Ya , Lei Bo
Published: October 2023

Background

Cone-rod dystrophy (CORD) caused by pathogenic variants in CFAP410 is a very rare disease. The mechanisms by which the variants caused the disease remained largely unknown. CFAP410 pathogenic variants were identified in a cone-rod dystrophy with macular staphyloma patient. We explored the pathogenicity and performed functional analysis of two compound heterozygous mutations.

Methods

A 6-year-old boy complained decreased vision for 1 year, underwent ocular examinations together with systemic X-ray check. Blood sample was taken for targeted next generation sequencing (Tg-NGS). Pathogenicity of identified variants was determined by ACMG guideline. Mutated plasmids were constructed and transferred to HEK293T cells. Cell cycle, protein stability, and protein ubiquitination level was measured.

Results

The best-corrected visual acuity of proband was 0.20 bilaterally. Fundus showed macular staphyloma and uneven granular pigment disorder in the periphery of the retina. SS-OCT showed thinning and atrophy of the outer retina, residual ellipsoid zone (EZ) in the fovea. Scotopic and photopic ERG responses severe reduced. Two heterozygous missense pathogenic variants, c.319 T > C (p.Tyr107His) and c.347 C > T (p.Pro116Leu) in exon 4 of the CFAP410, were found and were pathogenic by the ACMG guideline. In vitro, pathogenic variants affect cell cycle. Immunofluorescence and western blotting showed that the mutant proteins decreased expression levels protein stability. Meanwhile, co-IP data suggested that ubiquitination level was altered in cells transferred with the mutated plasmids.

Conclusion

Compound heterozygous pathogenic variants c.319 T > C and c.347 C > T in CFAP410 caused CORD with macular staphyloma. The pathogenic mechanisms may be associated with alternations of protein stability and degradation through the ubiquitin-proteasome pathway.
Identification of the chemical profile and evaluation of the antimicrobial effect of Eryngium billardieri Delar essential oil component against bacterial species of agricultural and food interest
Authors: Hajian-Maleki Habibeh , Shams-bakhsh Masoud
Published: October 2023

Studies on the antibacterial activity of the essential oil of E. billardieri are limited. In this study, we identified this herb as a natural complex effective against several bacteria by employing disk diffusion and broth microdilution susceptibility methods. Primary estimation of the antimicrobial effect of this herbal compound by disk diffusion method showed that the oil could inhibit the growth of the tested bacteria by the appearance of haloes between 8.25 and 21.25 mm. In the next step, the oil was found to be active against all 24 tested Gram-negative and Gram-positive bacteria in the broth media, at minimum inhibitory concentrations ranging from 0.67 to 34.17 g L−1. Furthermore, Enterococcus faecalis and Curtobacterium flaccumfaciens pv. flaccumfaciens were the most sensitive food and plant pathogenic bacteria, respectively. Gas chromatography–mass spectrometry analysis was conducted to assign the ingredients present in the oil; 34 different components representing 95.71% of the total oil were identified, with n-hexadecanoic acid being the dominant component, followed by 2-Pentadecanone, 6,10,14-trimethyl, 1H-Indene, 1-ethylideneoctahydro-, and Cinnamyl tiglate. These findings demonstrate, for the first time, a broad spectrum of the antibacterial capacity of E. billardieri. Based on these observations, the oil could be applied as a natural preservative with the potential for designing novel products. Its bioactive agents can also be isolated for further use in the food and agricultural industries.
Transcriptomic and metabolomic analyses to study the key role by which Ralstonia insidiosa induces Listeria monocytogenes to form suspended aggregates
Authors: Zuo Xifeng , Chen Meilin , Zhang Xinshuai , Guo Ailing , Cheng Si , Zhang Rong
Published: October 2023

Ralstonia insidiosa can survive in a wide range of aqueous environments, including food processing areas, and is harmful to humans. It can induce Listeria monocytogenes to form suspended aggregates, resulting from the co-aggregation of two bacteria, which allows for more persistent survival and increases the risk of L. monocytogenes contamination. In our study, different groups of aggregates were analyzed and compared using Illumina RNA sequencing technology. These included R. insidiosa under normal and barren nutrient conditions and in the presence or absence of L. monocytogenes as a way to screen for differentially expressed genes (DEGs) in the process of aggregate formation. In addition, sterile supernatants of R. insidiosa were analyzed under different nutrient conditions using metabolomics to investigate the effect of nutrient-poor conditions on metabolite production by R. insidiosa. We also undertook a combined analysis of transcriptome and metabolome data to further investigate the induction effect of R. insidiosa on L. monocytogenes in a barren environment. The results of the functional annotation analysis on the surface of DEGs and qPCR showed that under nutrient-poor conditions, the acdx, puuE, and acs genes of R. insidiosa were significantly upregulated in biosynthetic processes such as carbon metabolism, metabolic pathways, and biosynthesis of secondary metabolites, with Log2FC reaching 4.39, 3.96, and 3.95 respectively. In contrast, the Log2FC of cydA, cyoB, and rpsJ in oxidative phosphorylation and ribosomal pathways reached 3.74, 3.87, and 4.25, respectively. Thirty-one key components were identified while screening for differential metabolites, which mainly included amino acids and their metabolites, enriched to the pathways of biosynthesis of amino acids, phenylalanine metabolism, and methionine metabolism. Of these, aminomalonic acid and Proximicin B were the special components of R. insidiosa that were metabolized under nutrient-poor conditions.
A first draft genome of holm oak (Quercus ilex subsp. ballota), the most representative species of the Mediterranean forest and the Spanish agrosylvopastoral ecosystem “dehesa”
Authors: Rey María-Dolores , Labella-Ortega Mónica , Guerrero-Sánchez Víctor M. , Carleial Rômulo , Castillejo María Ángeles , Ruggieri Valentino , Jorrín-Novo Jesús V.
Published: October 2023

The holm oak (Quercus ilex subsp. ballota) is the most representative species of the Mediterranean Basin and the agrosylvopastoral Spanish “dehesa” ecosystem. Being part of our life, culture, and subsistence since ancient times, it has significant environmental and economic importance. More recently, there has been a renewed interest in using the Q. ilex acorn as a functional food due to its nutritional and nutraceutical properties. However, the holm oak and its related ecosystems are threatened by different factors, with oak decline syndrome and climate change being the most worrying in the short and medium term. Breeding programs informed by the selection of elite genotypes seem to be the most plausible biotechnological solution to rescue populations under threat. To achieve this and other downstream analyses, we need a high-quality and well-annotated Q. ilex reference genome. Here, we introduce the first draft genome assembly of Q. ilex using long-read sequencing (PacBio). The assembled nuclear haploid genome had 530 contigs totaling 842.2 Mbp (N50 = 3.3 Mbp), of which 448.7 Mb (53%) were repetitive sequences. We annotated 39,443 protein-coding genes of which 94.80% were complete and single-copy genes. Phylogenetic analyses showed no evidence of a recent whole-genome duplication, and high synteny of the 12 chromosomes between Q. ilex and Quercus lobata and between Q. ilex and Quercus robur. The chloroplast genome size was 142.3 Kbp with 149 protein-coding genes successfully annotated. This first draft should allow for the validation of omics data as well as the identification and functional annotation of genes related to phenotypes of interest such as those associated with resilience against oak decline syndrome and climate change and higher acorn productivity and nutraceutical value.
4-Ethylphenol—fluxes, metabolism and excretion of a gut microbiome derived neuromodulator implicated in autism
Authors: Day Francesca , O’Sullivan Justin , Pook Chris
Published: October 2023

Gut-microbiome-derived metabolites, such as 4-Ethylphenol [4EP], have been shown to modulate neurological health and function. Although the source of such metabolites is becoming better understood, knowledge gaps remain as to the mechanisms by which they enter host circulation, how they are transported in the body, how they are metabolised and excreted, and the way they exert their effects. High blood concentrations of host-modified 4EP, 4-ethylphenol sulfate [4EPS], are associated with an anxiety phenotype in autistic individuals. We have reviewed the existing literature and discuss mechanisms that are proposed to contribute influx from the gut microbiome, metabolism, and excretion of 4EP. We note that increased intestinal permeability is common in autistic individuals, potentially explaining increased flux of 4EP and/or 4EPS across the gut epithelium and the Blood Brain Barrier [BBB]. Similarly, kidney dysfunction, another complication observed in autistic individuals, impacts clearance of 4EP and its derivatives from circulation. Evidence indicates that accumulation of 4EPS in the brain of mice affects connectivity between subregions, particularly those linked to anxiety. However, we found no data on the presence or quantity of 4EP and/or 4EPS in human brains, irrespective of neurological status, likely due to challenges sampling this organ. We argue that the penetrative ability of 4EP is dependent on its form at the BBB and its physicochemical similarity to endogenous metabolites with dedicated active transport mechanisms across the BBB. We conclude that future research should focus on physical (e.g., ingestion of sorbents) or metabolic mechanisms (e.g., conversion to 4EP-glucuronide) that are capable of being used as interventions to reduce the flux of 4EP from the gut into the body, increase the efflux of 4EP and/or 4EPS from the brain, or increase excretion from the kidneys as a means of addressing the neurological impacts of 4EP.