bluuebunny/crossref_metadata_2025 huggingface dataset:
A conserved element in the first intron of Cd4 has a lineage specific, TCR signal-responsive, canonical enhancer function that matches the timing of cell surface CD4 upregulation required to prevent lineage choice error
Authors: Swan Gregory A. , Fujii Chika , Guzynski Mia E. , Page Sheridan M. , Meyers Isabelle V. , Penev Yordan P. , Littleton Sejiro , Azzahra Adinda , Richardson Christine , Sarafova Sophia D.
Published: January 2025

Introduction

The regulation of Cd4 expression during T-cell development and immune responses is essential for proper lineage commitment and function in the periphery. However, the mechanisms of genetic and epigenetic regulation are complex, and their interplay not entirely understood. Previously, we demonstrated the need for CD4 upregulation during positive selection to ensure faithful commitment of MHC-II-restricted T cells to the CD4 lineage. In this study, we investigate whether a conserved region, here called NCE, that is proximal to the Cd4 silencer and contains E4m has the required developmental-stage-specific canonical enhancer function and TCR responsiveness to mediate the CD4 upregulation required to prevent lineage errors.

Methods

To investigate the role of NCE, transient transfection of reporter plasmids was performed in thymoma cell lines arrested at the double-positive (DP, CD4+CD8+) and intermediate (INT, CD4+CD8lo) stages of development. CRISPR/Cas9-mediated deletion of the coreNCE/E4m region was carried out in these cell lines to assess its impact on CD4 surface expression, re-expression rates, and TCR signaling responsiveness. To avoid developmental alterations from direct manipulation of the endogenous Cd4 locus in vivo, BAC-transgenic reporter mice were generated with the locus modified to express EGFP in the presence or absence of NCE. EGFP mRNA levels were measured via RT-qPCR, and EGFP fluorescence was analyzed in post-selection thymocytes.

Results

Our in vitro experiments demonstrate that NCE by itself can function as an enhancer at the INT, but not the DP stage of development. Furthermore, CRISPR/Cas9-mediated deletion of coreNCE/E4m resulted in reduced CD4 surface levels, slower re-expression rates, and reduced TCR signaling responsiveness in INT cells, but not in DP cells. In vivo, NCE-sufficient transgenic mice exhibited upregulation of Cd4 reporter EGFP mRNA levels at the INT stage and a corresponding upregulation of EGFP fluorescence, whereas NCE-deficient mice showed a significant loss of Cd4 reporter EGFP mRNA and no detectable EGFP production in any post-selection thymocytes.

Discussion

This study demonstrates that the canonical enhancer function of coreNCE/E4m is essential for CD4 upregulation following positive selection. The NCE region, with its developmental-stage-specific activity and its known epigenetic regulatory capabilities, ensures faithful lineage commitment to the CD4 lineage.
Spinal cord injury enhances lung inflammation and exacerbates immune response following exposure to LPS
Authors: Berk Bradford C. , Pereira Amanda , Vizcarra Velia Sofia , Pröschel Christoph , Hsu Chia George
Published: January 2025

Introduction

The severity of spinal cord injury (SCI) is closely tied to pulmonary function, especially in cases of higher SCI levels. Despite this connection, the underlying pathological mechanisms in the lungs post-SCI are not well understood. Previous research has established a connection between disrupted sympathetic regulation and splenocyte apoptosis in high thoracic SCI, leading to pulmonary dysfunction. The aim of this study was to investigate whether mice with low-level SCI exhibit increased susceptibility to acute lung injury by eliciting systemic inflammatory responses that operate independently of the sympathetic nervous system.

Methods

Here, we employed T9 contusion SCI and exposed mice to aerosolized lipopolysaccharide (LPS) to simulate lung inflammation associated with acute respiratory distress syndrome (ARDS). Twenty-four hours post-LPS exposure, lung tissues and bronchoalveolar lavage (BAL) fluid were analyzed.

Results

LPS markedly induced proinflammatory gene expression (SAA3, IRG1, NLRP3, IL-1beta, MCP-1) and cytokine release (IL-1beta, IL-6, MCP-1) in SCI mice compared to controls, indicating an exaggerated inflammatory response. Infiltration of Ly6G/C positive neutrophils and macrophages was significantly higher in SCI mice lungs post-LPS exposure. Interestingly, spleen size and weight did not differ between control and SCI mice, suggesting that T9 SCI alone does not cause spleen atrophy. Notably, bone-marrow-derived macrophages (BMDMs) from SCI mice exhibited hyper-responsiveness to LPS.

Discussions

This study demonstrated an increase in lung inflammation and immune responses subsequent to low-level T9 SCI, underscoring the widespread influence of systemic inflammation post-SCI, especially pronounced in specific organs like the lungs.
Differences in the intrahepatic expression of immune checkpoint molecules on T cells and natural killer cells in chronic HBV patients
Authors: Dumolard Lucile , Hilleret Marie-Noelle , Costentin Charlotte , Mercey-Ressejac Marion , Sturm Nathalie , Gerster Theophile , Decaens Thomas , Jouvin-Marche Evelyne , Marche Patrice N. , Macek Jilkova Zuzana
Published: January 2025

Background

Patients with chronic hepatitis B virus (HBV) infection are characterized by impaired immune response that fails to eliminate HBV. Immune checkpoint molecules (ICMs) control the amplitude of the activation and function of immune cells, which makes them the key regulators of immune response.

Methods

We performed a multiparametric flow cytometry analysis of ICMs and determined their expression on intrahepatic lymphocyte subsets in untreated and treated patients with HBV in comparison with non-pathological liver tissue.

Results

The liver of untreated HBV patients exhibited a high accumulation of PD-1+CD8+ T cells, while the frequencies of 4-1BB+ T cells, 4-1BB+ natural killer (NK) cells, and TIM-3+CD8+ T cells were the highest in the chronic hepatitis phase. Our findings showed that the HBeAg status is linked to a distinct immune phenotype of intrahepatic CD8+ T cells and NK cells characterized by high expression of ICMs, particularly 4-1BB. Importantly, antiviral treatment partially restored the normal expression of ICMs. Finally, we described important differences in ICM expression between intrahepatic and circulating NK cells in HBV patients.

Conclusions

Our study shows clear differences in the intrahepatic expression of ICMs on NK cells and T cells in chronic HBV patients depending on their clinical stage.
The impact of signaling pathways on the desmosome ultrastructure in pemphigus
Authors: Schmitt Thomas , Huber Julia , Pircher Julia , Schmidt Enno , Waschke Jens
Published: January 2025

Introduction

The autoantibody-driven disease pemphigus vulgaris (PV) impairs desmosome adhesion in the epidermis. In desmosomes, the pemphigus autoantigens desmoglein 1 (Dsg1) and Dsg3 link adjacent cells. Dsgs are clustered by plaque proteins and linked to the keratin cytoskeleton by desmoplakin (Dp). The aim of this study was to identify the impact of several PV-related signaling pathways on desmosome ultrastructure.

Methods

STED microscopy, Dispase-based dissociation assay.

Results

As observed using STED microscopy, pemphigus autoantibodies (PV-IgG) reduced desmosome number, decreased desmosome size, increased plaque distance and thickness and caused loss of adhesion. Decreased desmosome number, increased plaque distance and thickness and loss of adhesion correlate with features found for newly assembled immature desmosomes, observed after Ca2+ depletion and repletion. This was paralleled by plaque asymmetry, keratin filament retraction and fragmentation of Dsg1 and Dsg3 immunostaining. Inhibition of each individual signaling pathway investigated here prevented the loss of adhesion and ameliorated keratin retraction. In addition, inhibition of p38MAPK or PLC completely rescued all parameters of desmosomes ultrastructure and increased desmosome number under basal conditions. In contrast, inhibition of MEK1/2 was only partially protective for desmosome size and plaque thickness, whereas inhibition of Src or increase of cAMP decreased desmosome size but increased the desmosome number even in the presence of PV-IgG.

Discussion

Alterations of the desmosomal plaque ultrastructure are closely related to loss of adhesion and regulated differently by signaling pathways involved in pemphigus pathogenesis. This insight may allow identification of novel treatment options targeting specific steps of desmosome turn-over in the future.
Elusive modes of Foxp3 activity in versatile regulatory T cells
Authors: He Minghong , Feng Yongqiang
Published: January 2025

Foxp3-expressing CD4 regulatory T (Treg) cells play a crucial role in suppressing autoimmunity, tolerating food antigens and commensal microbiota, and maintaining tissue integrity. These multifaceted functions are guided by environmental cues through interconnected signaling pathways. Traditionally, Treg fate and function were believed to be statically determined by the forkhead box protein Foxp3 that directly binds to DNA. However, this model has not been rigorously tested in physiological and pathological conditions where Treg cells adapt their function in response to environmental cues, raising questions about the contribution of Foxp3-dependent gene regulation to their versatility. Recent research indicates that Foxp3 primarily functions as a transcriptional cofactor, whose chromatin interaction is influenced by other DNA-binding proteins that respond to cell activation, stimulation, or differentiation. This new perspective offers an opportunity to reevaluate Foxp3’s activity modes in diverse biological contexts. By exploring this paradigm, we aim to unravel the fundamental principles of Treg cell biology.
Spatiotemporal dynamics and influencing factors of native and invasive saltmarshes in a rapidly silting bay during 1985–2023
Authors: Xu Mingshan , Gu Jiali , Yun Peng , Gan Jianjun , Fan Wenzhou , Chen Zhentao , Shao Jie , Zhang Guangzhi , Zeng Jian
Published: January 2025

Globally, native saltmarshes are declining, while invasive saltmarshes are expanding rapidly. However, the underlying processes and driving mechanisms behind these trends remain poorly understood, particularly in rapidly silting coastal bays. Here, we investigated the spatiotemporal dynamics and influencing factors of native saltmarshes (Scirpus mariqueter and Phragmites australis) and invasive Spartina alterniflora in Yueqing Bay, eastern China, by interpreting Landsat series images during 1985-2023. Results showed that native saltmarshes significantly decreased from 632.24 ha to complete disappearance, while S. alterniflora expanded from zero to 2872.90 ha in Yueqing Bay during 1985-2023. Specifically, S. mariqueter experienced a notable decline from 1985 to 1995, subsequent growth between 2000 and 2005, and another reduction from 2005 to 2010. P. australis expanded from 2005 to 2010 but shrank from 2010 to 2015 as S. alterniflora encroached upon its habitats. By contrast, S. alterniflora consistently expanded annually, except when it was eradicated by human interference. Both natural factors and human activities influenced native and invasive saltmarshes; for instance, mudflat reclamation facilitated saltmarsh expansion by creating suitable habitats during a certain period, particularly for S. alterniflora. From 1984 to 2018, the coastline extended seaward, causing sedimentation and landward transformation, which contributed to the expansion of S. alterniflora. However, the 118.05 ha mangrove forests negatively impacted S. alterniflora, as planting mangroves often involves the removal of existing S. alterniflora. Additionally, maximum tidal range and mean annual temperature positively affected saltmarshes. Our study highlighted the influence of natural factors and human activities on the spatiotemporal dynamics of both native and invasive saltmarshes in rapidly silting bays, underscoring the urgent need for conservation, restoration, and management of native saltmarshes.
Distribution and environmental drivers of macrofaunal nematode communities across gradients of methane seepage at cold seeps on Hikurangi Margin (New Zealand) and potential implications of disturbance from gas hydrate extraction
Authors: Leduc Daniel , Rowden Ashley A. , Seabrook Sarah , Bowden David A. , Thurber Andrew R. , Halliday Jane , Law Cliff S. , Pereira Olivia S. , Whitten Bethany G. , Marriner Andrew
Published: January 2025

Cold seeps are areas characterised by specialized biological communities that rely on chemosynthesis for their nutrition. To date, research conducted on New Zealand’s Hikurangi Margin seep communities has focused on communities at 650-1200 m water depth. Here, we characterize the macrofaunal nematode communities of New Zealand cold seeps for the first time, and at deeper (> 1200 m) seep locations (Maungaroa, Glendhu and Urutī South). There were no significant difference in nematode abundance, species richness, diversity and evenness among the seep areas, which may reflect the lack of difference in most sediment variables. However, a consistent spatial pattern in nematode abundance was observed within all the seep areas on the Hikurangi Margin: abundance was highest at or near the seep centre, decreased steeply away from the centre and was low in the periphery. These spatially consistent patterns reflect the influence of methane seepage, which appears limited to the inner 150-200 m radius of each area, on nematode abundance via input of chemosynthetic food sources. We found significant differences in nematode community structure among all three areas, with most of the heterogeneity in community structure between the shallow Urutī South area and deeper Maungaroa and Glendhu areas, and differences among nematode communities of high, medium and low abundance associated with site-specific gradients in methane seepage. Within area variability in nematode community structure was mainly correlated with food availability and sediment grain size. Consistent with previous investigations of seep nematodes, we did not find evidence of seep endemics. Although deposit feeders were generally the most abundant feeding group, there were differences in the relative abundances of different feeding groups such as microvores and epigrowth feeders among the seep areas, and as a function of distance from the centre of the seep areas. Impact on seep communities from gas hydrate extraction processes may occur via reduction or potentially cessation of free-gas methane supply to the seafloor, ‘sand’ production at the seafloor due to the physical degradation of the substrate structure, or alteration of the structural integrity of the seafloor substrate. Any spatial management options considered for managing these impacts should reflect the differences in benthic community structure between depths and locations on the Hikurangi Margin.
Particle composition-based water classification method for estimating chlorophyll-a in coastal waters from OLCI images
Authors: Gao Siwen , Zhou Chao , Jiang Lingling , Xu Jingping
Published: January 2025

The complex composition of seawater presents significant challenges for accurately estimating biogeochemical data through optical measurements, both in situ and via satellite data. To address the regional applicability of single bio-optical or remote sensing algorithms caused by these challenges, we explored a water optical classification method based on inherent optical properties and particle composition. The ratio of organic particulate matter to total suspended particulate matter concentration (POM/SPM) serves as an optical discriminator of water bodies based on the proportions of organic and mineral particles. The boundary value is determined by the relationship between the particulate backscattering coefficient bbp(λ) and POM/SPM. By analyzing in situ data collected from the coastal waters of Qinhuangdao in the Bohai Sea, China, we developed empirical algorithms to estimate both the POM/SPM ratio and chlorophyll-a (Chl-a) concentration, the latter being a key parameter derived from current ocean remote sensing that indicates phytoplankton abundance. The evaluation of our algorithms demonstrates that accounting for POM/SPM variations significantly improves Chl-a estimate accuracy across the optically-complex coastal waters near Qinhuangdao compared to algorithms that do not consider changes in particle composition, such as the well-known OC4Me algorithm. Furthermore, we determined the distribution of monthly averaged Chl-a concentration and POM/SPM ratio on the coast of Qinhuangdao, Bohai Sea, in 2023. Our results show, for the first time, that the monthly average variations of the POM/SPM ratio in the Bohai Sea and Chl-a concentrations exhibit pronounced seasonal fluctuations.
Experimental investigation of the second-mode internal solitary wave in continuous pycnocline and the applicability of weakly nonlinear theoretical models
Authors: Wang Shaodong , Du Hui , Wei Gang , Chen Zhentao , Shi Jianqiao , Lan Zhenyang
Published: January 2025

The research on the propagation and evolution of the second-mode internal solitary waves(ISWs) is receiving more and more attention. In this study, second-mode internal solitary waves in continuous stratification are physically simulated in a laboratory-stratified fluid flume. Meanwhile, the second-mode ISWs and their induced flow field in the same stratification environment are solved based on the eigenvalue problem of the TG equation (Taylor-Goldstein), combined with the weakly non-linear ISW theoretical models. The experimental and theoretical results show that the symmetry of the second-mode ISW wave-flow field can be improved as the thickness ratio of the upper fluid layer and lower one approaches 1. The ISW speed and horizontal and vertical velocity range values in the continuous pycnocline are positively correlated with the changing ISW amplitude, while only the wavelength is negatively correlated with the iSW amplitude. The waveflow fields of the second-mode ISWs calculated by Korteweg-de Vries (KdV) and extended KdV (eKdV) models in the large amplitude cases are more consistent with the experimental results than those in the small amplitude cases. The two theoretical models used to describe second-mode ISWs can be significantly improved when the thickness ratio of the upper and lower fluid layers approaches 1. In this case, the eKdV model is more applicable than the KdV model.
SOM neural network-based port function analysis: a case study in 21st-century Maritime Silk Road
Authors: Xie Fahao , Zhang Le , Zheng Shanshui , Xu Aijun , Li Zhitao , Dai Jiaxin , Xu Lang
Published: January 2025

The 21st-century Maritime Silk Road initiative by the Chinese government has garnered growing global attention. As pivotal facilitators of international trade, the maritime routes and ports along this route are attracting the interest of various stakeholders. There is a pressing need for extensive research to augment the existing theoretical frameworks. This paper introduces a Self-Organizing Map (SOM) neural network-based methodology for port function clustering, applied to 24 major ports spanning from the South China Sea to the ASEAN region in 2023. The clustering outcomes are cross-validated against port rankings derived from Principal Component Analysis. The study reveals several key insights: (1) Singapore Port, Hong Kong Port, Shenzhen Port, and Guangzhou Port emerge as the principal shipping hubs within the region; (2) The relationship between China and Singapore is identified as a linchpin for the sustainable development of the 21st-century Maritime Silk Road; (3) Guangdong Province is highlighted as a central economic and logistical node. Finally, the recommendations for the accelerated development of the Hainan Free Trade Port and Fujian Coastal Port is concluded.
Re-evaluating large for gestational age: differential effects on perinatal outcomes in term and premature births
Authors: Kuo Chun-Heng , Wu Yi-Ling , Chen Chi-Nien , Lo Yu-Ru , Yen I-Weng , Fan Kang-Chih , Tai Yi-Yun , Lin Ming-Wei , Hsu Chih-Cheng , Li Hung-Yuan
Published: January 2025

Objective

Pregnancies with large-for-gestational-age (LGA) fetuses are associated with increased risks of various adverse perinatal outcomes. While existing research primarily focuses on term neonates, less is known about preterm neonates. This study aims to explore the risks of adverse maternal and neonatal perinatal outcomes associated with LGA in term neonates and neonates with different degrees of prematurity, compared to appropriate-for-gestational-age (AGA) neonates.

Methods

Using the Birth Reporting Databases (2007–2018) linked to Taiwan's National Health Insurance Research Database, we conducted a retrospective nationwide cohort study of singleton neonates delivered between 24 and 42 weeks of gestation. Based on gestational age at delivery, the enrolled neonates were classified into term (37–42 weeks of gestation), late preterm (34–36 weeks of gestation), moderate preterm (32–33 weeks of gestation), very preterm (28–31 weeks of gestation), and extremely preterm (24–27 weeks of gestation). LGA was defined by the 2013 World Health Organization (WHO) growth standard and the Taiwan growth standard. Perinatal outcomes were compared between LGA and AGA neonates across different gestational age groups.

Results

Among the 1,602,638 neonates, 44,359 were classified as LGA by the 2013 WHO growth standard. Compared to AGA neonates, LGA neonates in term and late preterm groups exhibited higher risks of primary cesarean section, prolonged labor, neonatal hypoglycemia, birth trauma, hypoxic ischemic encephalopathy, jaundice needing phototherapy, respiratory distress, neonatal intensive care unit (NICU) admission, newborn sepsis, and fetal death. However, most of these risks were not increased in moderate, very, and extremely preterm groups. Conversely, being LGA was associated with lower risks of primary cesarean section (very preterm group), jaundice needing phototherapy (moderate and very preterm groups), respiratory distress (moderate and very preterm groups), NICU admission (moderate and very preterm groups), newborn sepsis (very preterm group), retinopathy of prematurity (late, moderate, and very preterm groups), and bronchopulmonary dysplasia (very preterm group). These findings remained consistent when the Taiwan growth standard was applied.

Conclusion

Being LGA is associated with increased risks of perinatal complications in term and late preterm neonates, but not in earlier preterm groups. These findings underscore the importance of tailoring management strategies for LGA neonates to consider different degrees of prematurity.
Trends in the prevalence of Chronic Kidney Disease in the United States, 1999–2018
Authors: Zhuang Mansi , Lv Xiaogang , Zhu Yanan , Zheng Nan , Zhan Yiqiang
Published: January 2025

Background

Chronic Kidney Disease (CKD) is an escalating public health concern in the United States, linked with significant morbidity, mortality, and healthcare costs. Despite known risk factors like age, hypertension, and diabetes, comprehensive studies examining temporal trends in CKD prevalence are scarce. This study aims to analyze these trends using data from the National Health and Nutrition Examination Survey (NHANES).

Methods

This cross-sectional study analyzed NHANES data spanning 20 years (1999–2018), including 55,081 adults aged 20 years and above. Key renal function indicators like estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) were assessed, and CKD stages were categorized accordingly.

Results

A fluctuating trend in CKD prevalence was observed, with early CKD stages (G1–G3) increasing from 9.28% in 1999–2000 to 12.93% in 2017–2018. Advanced CKD stages (G4–G5) showed a slight increase in prevalence from 0.3% in 1999–2000 to 0.51% in 2017–2018. Notable disparities were observed across age groups, diabetes status, and racial categories. Relatively, the elderly, women, and non-Hispanic whites have a higher prevalence of CKD, while individuals with diabetes have a consistently higher prevalence of early CKD from 1999 to 2018. The increasing prevalence of diabetes during the study period highlights its significant role as a CKD risk factor.

Conclusion

The prevalence of CKD in the U.S. has been rising over the period 1999–2018, and varying across demographic groups, underscoring significant disparities and risk factors. These insights are crucial for healthcare planning, policy formulation, and targeted interventions for CKD management.
Influence of kinesiophobia on activity, function, and anxiety levels in patients with rheumatoid arthritis
Authors: Xueying Shang , Yanli You , Wei Xu , Lingling Zhang , Lili Li
Published: January 2025

Background

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that causes joint inflammation and affects quality of life. Appropriate physical activity can enhance joint function and lower cardiovascular disease risk. However, individuals with RA often have reduced physical activity levels, likely due to kinesiophobia, or fear of movement.

Aim

This study aimed to assess the prevalence of kinesiophobia among RA patients and its influence on functional impairment, physical activity, and pain-related anxiety.

Methods

Using a convenience sampling method, we surveyed 350 RA patients attending outpatient clinics in the rheumatology and immunology departments of three tertiary hospitals in Henan Province, China, from August 18 to September 1, 2023. Participants completed the Tampa Scale of Kinesiophobia (TSK), the Signals of Functional Impairment Scale (SOFI), the International Physical Activity Scale—Short Form (IPAQ-SF), and the Pain Anxiety Symptoms Scale-20 (PASS-20). The Disease Activity Score 28 (DAS28) was retrieved for each participant to assess disease activity in RA patients. Descriptive analysis, Chi-square tests, Spearman correlation, and multiple linear regression assessed factors influencing kinesiophobia, with significance set at p < 0.05.

Results

Results indicated that 70.86% of participants experienced kinesiophobia, which was positively correlated with functional impairment and pain-related anxiety, while inversely related to physical activity levels (p < 0.001). Regression analysis revealed that kinesiophobia was explained by 65.5% of the variance, with gender, education level, functional impairment, pain-related anxiety, and pain severity identified as significant predictors (p < 0.05).

Conclusion

The findings suggest that RA patients exhibit a high prevalence of kinesiophobia, predominantly influenced by factors such as gender, lower educational attainment, increased pain levels, greater functional impairment, and pain-related anxiety. Notably, physical activity levels did not serve as a predictor of kinesiophobia in this cohort.
Cell therapy for scleroderma: progress in mesenchymal stem cells and CAR-T treatment
Authors: Chen Liting , Huang Rongshan , Huang Chaoshuo , Nong Guiming , Mo Yuanyuan , Ye Lvyin , Lin Kunhong , Chen Anping
Published: January 2025

Cell therapy is an emerging strategy for precision treatment of scleroderma. This review systematically summarizes the research progress of mesenchymal stem cell (MSC) and chimeric antigen receptor T cell (CAR-T) therapies in scleroderma and discusses the challenges and future directions for development. MSCs possess multiple functions, including immunomodulation, anti-fibrosis, and promotion of vascular regeneration, all of which can improve multiple pathological processes associated with scleroderma. Studies have demonstrated that MSCs can alleviate skin fibrosis by inhibiting CCL2 production and reducing the recruitment of pathological macrophages; their paracrine effects can exert extensive regulatory functions. CAR-T cell therapy ca specifically target and eliminate autoreactive immune cells, exhibiting enhanced specificity and personalized potential. Different cell therapies may have complementary and synergistic effects in treating scleroderma, such as MSCs exerting their effects through paracrine mechanisms while CAR-T cells specifically eliminate pathological cells. Furthermore, cell-free therapies derived from MSCs, such as extracellular vesicles or exosomes, may help circumvent the limitations of MSC therapy. Although cell therapy has opened new avenues for the precision treatment of scleroderma, it still faces numerous challenges. In the future, it is essential to strengthen integration of basic and clinical research, establish standardized protocols for cell preparation and quality control, develop personalized treatment plans, and rationally combine cell therapy with existing treatment methods to maximize its advantages and improve patient prognosis and quality of life.
Therapeutic benefits of glycerol in dry eye disease
Authors: Ronderos Victoria , Bollag Wendy B.
Published: January 2025

Dry eye disease (DED) is one of the most commonly diagnosed eye disorders, with a prevalence ranging from 5 to 50%, depending on the geographic location. DED is a multifactorial disorder of the tears and ocular surface, which results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is also accompanied by increased osmolarity of the tear film and inflammation of the surface of the eye. Multiple therapeutic agents have been used to treat DED, with glycerol emerging as a promising component of ophthalmic preparations, due to its humectant, lubricant, demulcent, and osmoprotective properties. This review aims to evaluate the current evidence concerning the therapeutic benefits of glycerol in managing DED, focusing on its possible mechanisms of action, clinical efficacy, and potential advantages over other treatments.
Transcriptional activity of ammonia oxidisers in response to soil temperature, moisture and nitrogen amendment
Authors: Chisholm Chris , Di Hong , Cameron Keith , Podolyan Andriy , Shen Jupei , Zhang Limei , Sirisena Kosala , Che Xueying
Published: January 2025

The contrasting response of AOA, AOB, and comammox Nitrospira amoA transcript abundance to temperature, moisture, and nitrogen was investigated using soil microcosms. The moisture, temperature, and nitrogen treatments were selected to represent conditions typically found in a New Zealand (NZ) dairy farm. AOB dominated all synthetic urine treated soils. Peak AOB amoA transcript abundance was positively correlated with estimated soil ammonia availability. While AOB gDNA abundance and nitrification rate trends were similar. AOA were strongly influenced by soil temperature. At 20°C, AOA amoA peak transcript abundance averaged over 1 order of magnitude higher than at 8°C. Within the AOA community a member of the Nitrosocosmicus clade was positively correlated with ammonium and estimated ammonia concentrations. The presence and relative increase of an AOA community member in a high nitrogen environment poses an interesting contrast to current scientific opinion in NZ. Comammox Nitrospira abundance showed no correlation with soil moisture. This suggests that previously found associations are more complex than originally thought. Further research is required to determine the drivers of comammox Nitrospira abundance in a high moisture environment. Overall, these results indicate that AOB are the main drivers of nitrification in New Zealand dairy farm soils.
The IclR-family transcriptional regulator XyrR controls flotation, motility, antibiotic production and virulence in Serratia sp. ATCC 39006
Authors: Sandoval Carlo Miguel Castro , Salmond George P. C.
Published: January 2025

The opportunistic pathogen Serratia sp. ATCC 39006 (S39006) is a rod-shaped, motile, Gram-negative bacterium that produces a 𝛽-lactam antibiotic (a carbapenem) and a bioactive red-pigmented tripyrrole antibiotic, prodigiosin. It is also the only known enterobacterium that naturally produces intracellular gas vesicles (GVs), enabling cells to float in static water columns. Regulation of GVs and secondary metabolites in S39006 can be coordinated but such pleiotropy is still poorly understood. To uncover novel inputs to this complex regulatory network, we used transposon mutagenesis to identify a mutant with an insertion in an IclR-type transcriptional regulator gene. The iclR mutant showed diminished production of carbapenem, prodigiosin, GVs and cellulase. Furthermore, the mutant also showed increased swimming and swarming motilities but exhibited attenuated virulence in planta and ability to kill the nematode C. elegans. Using differential expression analysis of the intracellular proteomes of the wild type and iclR mutant, we confirmed that the mutation negatively impacted expression of the corresponding GV, carbapenem and prodigiosin gene clusters. In contrast, flagellar and chemotaxis proteins were overexpressed, consistent with the increased motility of the mutant. We also found that the proteins encoded by a putative yagEF-yjhF operon, involved in xylonate catabolism and transport, showed a 5- to 7-fold increase in expression. Finally, we show that IclR is a repressor of xylonate catabolism in S39006 and suggest that xylonate is potentially involved in controlling carbapenem and prodigiosin biosynthesis. Our results indicate that IclR is a global regulator that controls antibiotic biosynthesis, flotation through modulating GV assembly, and has pleiotropic impacts on the physiology and virulence of S39006. Based on these findings, we propose the designation of this IclR-family transcriptional regulator as XyrR (Xylonate response Regulator).
Effect of acupuncture on the gait disturbance and hemodynamic changes in the prefrontal cortex: a study protocol for a randomized controlled trial
Authors: Hong Zhenmei , Zhang Shuijing , Zhang Shuqing , Zhao Yuqi , Ye Xiancong , Shu Xinxin , Chen Yufan , Yan Shuding , Ma Ruijie
Published: January 2025

Background

Alzheimer’s disease (AD) is characterized by cognitive impairment and behavioral impairment. The gait of AD patients is attracting the increasing attention. The aim of this randomized controlled trial (RCT) is to explore the effect of acupuncture on the cognitive function, gait performance, and hemodynamic changes in the prefrontal cortices.

Methods

In this RCT, a total of 108 AD patients will be randomly assigned into acupuncture group or control group for 8 weeks. The primary outcome will be three-dimensional gait analysis and cerebral hemodynamics using functional near-infrared spectroscopy (fNIRS). Secondary outcomes will include Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Barthel Index (BI).

Discussion

This trial is expected to explore the effect of acupuncture on cognitive function, gait performance, and hemodynamic changes in the prefrontal cortices for AD patients.
Hydrophilic polymer coating delamination during neurointerventional treatment after microcatheter withdrawal: particulate identification through attenuated total reflection Fourier-transform infrared spectroscopy
Authors: Müller Sebastian J. , Albiña-Palmarola Pablo , Konieczny Stefan , Manke Gregor , Fischer Sebastian , Henkes Hans
Published: January 2025

Hydrophilic coating embolism (HCE) is a rare and underreported complication in neurointerventional practice that can lead to serious medical consequences. Two endovascular procedures were interrupted at our institution after a cloudy liquid content was observed inside the rotating hemostatic valves (RHV) during microcatheter withdrawal. In both cases, the same type of microcatheter (Prowler Select Plus) and RHV (Merit) were being used, and coating dislodgement was suspected. Attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) was used to identify the nature of such debris and compared it to samples obtained from different parts of an unused microcatheter and RHV. In an independent second analysis, an in vitro simulation of the withdrawal maneuver was conducted, followed by ATR-FTIR analysis. During both in vivo and in vitro observations, the presence of polyvinylpyrrolidone, a hydrophilic polymer commonly used for intravascular devices manufacture, was confirmed inside the RHV, and its origin was traced back to the surface coating of the distal and middle portions of the Prowler Select Plus microcatheter. This constitutes the first clinical report where hydrophilic coating dislodgement is linked to the microcatheter withdrawal maneuver using a specific microcatheter type, further replicated in an in vitro setting.
A free association semantic task for fNIRS-based perinatal depression assessment
Authors: Chen Danni , Yang Xuanjin , Liang Yuanyuan , Huang Chen , Zhang Suhan , Li Yini , Li Ye , Li Xiaofei , Mu Wenting , Zhang Dan , Ma Liangkun
Published: January 2025

Perinatal depression (PD) is a highly prevalent psychological disorder that has a detrimental effect on infant and maternal physical and mental health, but effective and objective assessment of PD is still insufficient. In recent years, the functional near-infrared spectroscopy (fNIRS) has been acknowledged as an effective non-invasive tool for clinical assessment of depression. This study proposed a free association semantic task (FAST) paradigm for fNIRS-based assessment of PD. To better address the emotion characteristics of PD, the participants are required to generate a dynamic concept chain based on positive, negative or neutral seed words, while 48-channel fNIRS recordings over frontal and bilateral temporal regions. Results from twenty-two late-pregnant women revealed that, the oxyhemoglobin (oxy-Hb) changes during the FAST with the positive and negative seed words over the frontal region were correlated with PD severity, which was different from the correlation patterns in the FAST with neutral seed word and the classical verbal fluency test (VFT). Furthermore, distinct correlation patterns were also observed in the FAST with the positive and negative seed words, manifested in fNIRS channels corresponding to the right dorsolateral prefrontal cortex (DLPFC) and right inferior frontal gyrus (IFG), respectively. Moreover, regression analyses showed that the FAST with positive and negative seed words can well explain the severity of PD. Our findings suggest the proposed FAST paradigm as a promising approach for PD assessment.
Exploring the clinical significance of anti-acetylcholine receptor antibody titers, changes, and change rates in Myasthenia Gravis
Authors: Luo Lijun , Zhu Xinyi , Wen Chunbei , Guo Yifan , Yang Jie , Wei Dongsheng , Yu Ping , Wan Mei
Published: January 2025

Introduction/Aims

Myasthenia Gravis (MG) is a common neuromuscular junction disorder that is primarily mediated by anti-acetylcholine receptor antibodies (AChR-Ab). However, using AChR-Ab titers to predict MG severity and improvement remains controversial. This study aims to explore the relationship between AChR-Ab titers and AChR-Ab rate of change (RR-AChR-Ab, %) and MG scores.

Methods

We used a prospective study approach, and included 62 patients with generalized MG (GMG) who were positive for AChR-Ab. We measured AChR-Ab titers, MGFA-QMGS, and MG-ADL scores at baseline (before treatment) and at 3 and 6 months into treatment. Pearson and Spearman correlation analyses were used to study the relationships between changes in AChR-Ab titers, rates of change, and MG scores.

Results

(1) At baseline, there was no correlation between AChR-Ab titers and age, duration of illness, gender, MGFA classification, or presence of thymic abnormalities. (2) The trend of decreasing AChR-Ab titers matched the trend of reduced QMGS and ADL scores. (3) Six months into treatment,there was a correlation between AChR-Ab titer changes and changes in ADL scores. (4) Three months into treatment, RR-AChRAb showed a correlation with the rate of change in ADL at the same time point.

Conclusion

We found the trend of decreased AChR-Ab titers after standardized treatment that was consistent with reductions in QMGS and ADL scores. Additionally, the rate of change in AChR-Ab titers at 3 months and the change in AChR-Ab titers at 6 months into treatment did reflect improvements in activities of daily living for MG patients.
Long COVID-19–related and non-COVID-19 postviral olfactory dysfunction a comparative MRI study focusing on the olfactory cleft and bulbs
Authors: Li Yifan , Liu Mengfan , Zhang Ruoqi , Wang Yibei , Liu Jianfeng
Published: January 2025

Objective

To compare the magnetic resonance imaging (MRI) features of the olfactory cleft (OC) and olfactory bulbs (OBs) in patients with long COVID-19-related (LCOD) and non-COVID-19 postviral olfactory dysfunction (NCPVOD) to explore mechanisms underlying persistent olfactory dysfunction.

Methods

This retrospective analysis included patients diagnosed with LCOD or NCPVOD at the China–Japan Friendship Hospital between February 2023 and July 2024. All patients underwent olfactory psychophysical testing (Sniffin’ Sticks), a visual analogue scale (VAS) for olfactory function, and high-resolution MRI scans of the olfactory pathway. MRI features, including OC opacity, OB morphology, OB volume, and olfactory sulcus depth, were compared between groups. Correlations between MRI findings and olfactory test scores were assessed.

Results

Seventy patients were included (35 LCOD, 35 NCPVOD). LCOD patients had significantly higher OC opacity scores than NCPVOD patients (p < 0.001). No significant differences were found in OB morphology, abnormal OB signals, OB volume reduction, or distances between OBs and surrounding structures (p > 0.05). LCOD patients had significantly greater right olfactory sulcus depth than NCPVOD patients (p = 0.026), with negative correlation to age (r = −0.25, p = 0.04). OB volumes positively correlated with TDI and VAS scores.

Conclusion

LCOD patients exhibited greater OC opacity than NCPVOD patients, suggesting OC inflammation may contribute to persistent olfactory dysfunction. Treating inflammation in the OC could improve long-term olfactory outcomes. OB volume reduction was common in both groups.
Executive function, limbic circuit dynamics and repetitive and restricted behaviors in children with autism spectrum disorder
Authors: Zheng Xiangyu , Wang Xinyue , Song Ruochen , Tian Junbin , Yang Li
Published: January 2025

Objective

Repetitive and restricted behaviors (RRBs) are a core symptom of autism spectrum disorder (ASD), but effective treatment approaches are still lacking. Executive function (EF) has been identified as a promising target, as research increasingly shows a link between EF deficits and the occurrence of RRBs. However, the neural mechanisms that connect the two remain unclear. Since the orbitofrontal cortex (OFC) plays a role in both EF and RRBs, its functional connectivity dynamics could offer valuable insights into this relationship.

Methods

This study analyzed data from the Autism Brain Imaging Data Exchange (ABIDE) II database to explore brain function in 93 boys with ASD and 110 typically developing (TD) boys. Time-varying functional connectivity was analyzed between eight OFC subregions and other brain areas. By employing linear regression, the study assessed how atypical connectivity dynamics and EF influence RRBs. Additionally, mediation analysis with bootstrapping was used to determine how EF mediates the relationship between atypical connectivity and RRBs.

Results

We found significant differences in the variance of FC between ASD and TD groups, specifically in the OFC subregion in L-prefrontal and the left amygdala (t = 5.00, FDR q < 0.01). Regression analyses revealed that increased variance of this FC and EF significantly impacted RRBs, with inhibition, emotional control, and monitor showing strong associations (standardized β = 0.60 to 0.62, p < 0.01), which also had significant indirect effects on the relationship between the above dynamic FC and RRBs, which accounted for 59% of the total effect.

Conclusion

This study highlights the critical role of EFs as a key mechanism in addressing RRBs in ASD. Specifically, it points out that EFs mediate the influence of atypical time-varying interactions within the OFC-amygdala circuit on RRBs.
Human platelet lysate: a potential therapeutic for intracerebral hemorrhage
Authors: Qiu Dachang , Wang Lin , Wang Lanlan , Dong Yongfei
Published: January 2025

Intracerebral hemorrhage (ICH) is a major public health challenge worldwide, and is associated with elevated rates of mortality, disability, and morbidity, especially in low- and middle-income nations. However, our knowledge of the detailed molecular processes involved in ICH remains insufficient, particularly those involved in the secondary injury stage, resulting in a lack of effective treatments for ICH. Human platelet lysates (HPL) are abundant in bioactive factors, and numerous studies have demonstrated their beneficial effects on neurological diseases, including their anti-neuroinflammatory ability, anti-oxidant effects, maintenance of blood–brain barrier integrity, and promotion of neurogenesis. In this review, we thoroughly explore the potential of HPL for treating ICH from three critical perspectives: the rationale for selecting HPL as a treatment for ICH, the mechanisms through which HPL contributes to ICH management, and the additional measures necessary for HPL as a treatment for ICH. We elucidate the role of platelets in ICH pathophysiology and highlight the limitations of the current treatment options and advancements in preclinical research on the application of HPL in neurological disorders. Furthermore, historical developments and preparation methods of HPL in the field of biomedicine are discussed. Additionally, we summarize the bioactive molecules present in HPL and their potential therapeutic effects in ICH. Finally, we outline the issues that must be addressed regarding utilizing HPL as a treatment modality for ICH.
Evaluation of Bacillus coagulans LMG S-31876 for immunomodulation and stress: a double-blind, placebo-controlled clinical trial
Authors: Kallur Ranjith Kumar , Madapati Sreenadh , Banerjee Mayuri , Mathur Ankita , Bhattacharya Sourish
Published: January 2025

Objective

The study aimed to analyze the safety and effectiveness of the ProBC Plus (Bacillus coagulans LMG S-31876) supplement across various health parameters, including stress levels, immunoglobulin levels, biochemical parameters, and vital signs.

Methods

A randomized, double-blind, placebo-controlled clinical trial study was conducted involving 50 subjects diagnosed with ailments related to immune system dysfunction and stress related disorders. Patients were treated with ProBC Plus (2 billion colony-forming units [CFU]) along with a placebo capsule administered once daily for a period of 8 weeks.

Results

The effects of ProBC Plus exhibited a positive response on stress relief, lipid parameters, immune status, and vital signs, which is further statistically significant (p value <0.05, 5% marginal error at 95% CI).

Conclusion

The study on ProBC Plus showed positive results. Over the course of 8 weeks, an improvement in the immune status was observed, as indicated by the immune status questionnaire. Enzymatic markers exhibited a significant decline in predicting a positive response toward treatment. In terms of lipid profile, ProBC Plus helps to maintain the value within the normal range, thereby predicting its potential as cardiovascular support. The vital signs remained within the normal range throughout the study. Therefore, ProBC Plus is considered safe for consumption and contributes to the overall well-being of individuals.

Clinical trial registration

https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=77914&EncHid=24313.96864&userName=CTRI/2023/01/048720, CTRI/2023/01/048720.