bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex-specific NLRP3 activation in neutrophils promotes neutrophil recruitment and NETosis in the murine model of diffuse alveolar hemorrhage
Authors: Jarrot Pierre-André , Kim Jiyoun , Chan William , Heger Lukas , Schommer Nicolas , Cunin Pierre , Silva Camila M. S. , Robert Stéphane , Nigrovic Peter A. , Ewenstein Bruce , Wagner Denisa D.
Published: November 2024

Objectives

Diffuse alveolar hemorrhage (DAH) is a life-threatening complication of systemic lupus erythematosus and small vessel vasculitis. We previously showed that neutrophil extracellular traps (NETs) were associated with the pathogenesis of pristane-induced DAH and demonstrated that neutrophil NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome assembly participated in NET generation under sterile stimulation. We investigated whether NLRP3 inflammasome assembly in neutrophils may drive pulmonary NETosis in a mouse model of pristane-induced DAH.

Methods

C57BL/6J mice received a single intraperitoneal injection of 0.5mL of pristane. Neutrophil NLRP3 inflammasome assembly and NETs were characterized by immunofluorescence staining of apoptosis-associated speck-like protein a CARD (ASC), co-staining of DNA, and citrullinated histones, respectively. Clinical status of mice was assessed 11 days after pristane injection by measurement of arterial oxygen saturation and of weight loss; severity of lung injury was determined using a quantification score from hematoxylin-eosin-stained slides.

Results

Pristane induced ASC speck formation in neutrophils and we confirmed that NLRP3 inflammasome was involved in NET generation after pristane stimulation in vitro. NLRP3 deficiency reduced the severity of pristane-induced DAH in female, but not male mice. Interestingly, NLRP3 deficiency reduced the number of neutrophils and NETs in the lungs of females compared to males.

Conclusions

Our results suggest a link between female sex-specific NLRP3 inflammasome activation and subsequent pulmonary NETosis in the development of pristane-induced DAH. Therefore, we identified NLRP3 inflammasome as a potential new therapeutic target in this severe complication of pro-female autoimmune disease for which specific inhibitors of NLRP3 are currently developed.
Thymic hyperplasia after autologous hematopoietic stem cell transplantation in multiple sclerosis: a case series
Authors: Mariottini Alice , Boncompagni Riccardo , Cozzi Diletta , Simonetti Edoardo , Repice Anna Maria , Damato Valentina , Giordano Mirella , Miele Vittorio , Nozzoli Chiara , Massacesi Luca
Published: November 2024

Introduction

Reactivation of thymopoiesis in adult patients with autoimmune disorders treated with autologous haematopoietic stem cell transplantation (AHSCT) is supported by studies exploring immunoreconstitution. Radiological evidence of thymic hyperplasia after AHSCT was previously reported in patients with systemic sclerosis, but, to our knowledge, it has not been described in multiple sclerosis (MS), where premature thymic involution has been observed and immunosenescence might be accelerated by disease-modifying treatments (DMTs).

Participants and methods

monocentric case series including MS patients who performed a chest CT scan for clinical purposes after having received AHSCT (BEAM/ATG regimen) for aggressive MS failing DMTs. Chest CT exams were reviewed by a thoracic radiologist: thymic hyperplasia was defined as a rounded mass in the thymic loggia with a density around 40 Hounsfield Units (HU) and thickness >1.3 cm.

Results

Fifteen MS patients were included; the median time interval between AHSCT and chest CT scan was 2 (range 1-18) months. All the patients were free from new inflammatory events and DMTs over a median follow-up of 36 months (range 12-84) after AHSCT. Thymic hyperplasia was detected in 3/15 (20%) cases in an exam taken 1 to 3 months after AHSCT; all these patients were females, and aged 30 to 40 years. Lung infections and secondary autoimmunity were diagnosed in 5 and 1 cases, respectively, none of which showed thymic hyperplasia. No associations between thymic hyperplasia and clinical-demographic characteristics or post-AHSCT outcomes were observed.

Conclusions

Thymic hyperplasia was detected in 20% of MS patients recently treated with AHSCT. These results are consistent with previous immunological studies showing that AHSCT promotes thymus reactivation in MS patients, further supporting de-novo thymopoiesis as a cornerstone of immune reconstitution after AHSCT in this population.
B7-H3 in glioblastoma and beyond: significance and therapeutic strategies
Authors: Babič Davor , Jovčevska Ivana , Zottel Alja
Published: November 2024

Cancer has emerged as the second most prevalent disease and the leading cause of death, claiming the lives of 10 million individuals each year. The predominant varieties of cancer encompass breast, lung, colon, rectal, and prostate cancers. Among the more aggressive malignancies is glioblastoma, categorized as WHO stage 4 brain cancer. Following diagnosis, the typical life expectancy ranges from 12 to 15 months, as current established treatments like surgical intervention, radiotherapy, and chemotherapy using temozolomide exhibit limited effectiveness. Beyond conventional approaches, the exploration of immunotherapy for glioblastoma treatment is underway. A methodology involves CAR-T cells, monoclonal antibodies, ADCC and nanobodies sourced from camelids. Immunotherapy’s recent focal point is the cellular ligand B7-H3, notably abundant in tumor cells while either scarce or absent in normal ones. Its expression elevates with cancer progression and serves as a promising prognostic marker. In this article, we delve into the essence of B7-H3, elucidating its function and involvement in signaling pathways. We delineate the receptors it binds to and its significance in glioblastoma and other cancer types. Lastly, we examine its role in immunotherapy and the utilization of nanobodies in this domain.
Coexistent pleural effusion is found to be associated with aggravated subclinical myocardial injury in systemic lupus erythematous using cardiovascular magnetic resonance imaging
Authors: Zhi Yang , Zhang Tian-yue , Zhu Yong , Zou Hao , You Yi , Wen Miao , Wang Zhong , Gao Liang-chao , Bing Fu , Pan Shu-yue
Published: November 2024

Objective

Pleural effusion (PE) is a common pulmonary manifestation in patients with systemic lupus erythematosus (SLE), and is associated with disease activity. However, little is known regarding the additive effects of PE on cardiac function. Therefore, this study aimed to investigate multi-parameter cardiovascular magnetic resonance imaging (CMR) findings in SLE patients with PE and to explore whether cardiac involvement is associated with PE.

Methods

Patients with SLE and age-matched/sex-matched healthy controls were included in this study. Patients with SLE were diagnosed according to the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria. Moreover, the PE diagnosis was based on computed tomography, and the height of the effusion was > 5 mm. All enrolled individuals underwent CMR imaging, including cine and late gadolinium enhancement (LGE), T1, and T2 mapping imaging. The left and right ventricular function, LGE, T1, extracellular volume (ECV), and T2 values were evaluated.

Results

A total of 111 patients with SLE were enrolled, of whom 26 (23.42%) had PE. White cell count, hemoglobin, CRP, ESR, and lactate dehydrogenase levels were higher in SLE patients with PE than in SLE patients without PE (P<0.05). LGE was more prevalent in SLE patients with PE compared with those without PE (P<0.001). In addition, Native T1 (1348 ± 65 ms vs. 1284 ± 67 ms vs. 1261 ± 41 ms; P<0.001), ECV (31.92 ± 4.16% vs. 28.61 ± 3.60% vs. 26.54 ± 2.94%; P<0.001), and T2 (44.76 ± 3.68 ms vs. 41.96 ± 3.62 ms vs. 39.21 ± 2.85 ms; P<0.001) values were high in SLE patients with PE, intermediate in SLE patients without PE, and the lowest in the control group. Linear regression analysis demonstrated that PE was independently associated with LGE (β=0.329; P<0.05), T1 (β=0.346; P<0.05), ECV (β=0.353; P<0.05), and T2 (β=0.201; P<0.05).

Conclusions

SLE patients with PE have a higher prevalence of LGE and more diffuse myocardial fibrosis and edema than SLE patients without PE. Moreover, PE is associated with increased diffuse interstitial fibrosis and edema.
The effects of acupuncture on patients with premature ovarian insufficiency and polycystic ovary syndrome: an umbrella review of systematic reviews and meta-analyses
Authors: Bai Tianyu , Deng Xinyun , Bi Jieyu , Ni Linlin , Li Zhaohui , Zhuo Xiumei
Published: November 2024

Background

Previous studies have suggested that acupuncture could improve the clinical outcomes of women with premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS). However recent meta-analyses have provided inconclusive findings. This umbrella meta-analysis aimed to explore the effect of acupuncture therapies on PCOS and POI outcomes.

Methods

A systematic literature search was carried out in in PubMed, Scopus, Web of Science, and Chinese databases, including Wan Fang Data Knowledge Service Platform, CBM, CNKI, and VIP up until April 2024 to gather relevant studies. Inclusion criteria were meta-analyses on the effect of acupuncture or combined therapies with standard medications or traditional Chinese medicine (TCM) on PCOS and POI. The outcomes were pregnancy rates, ovulation rates, hormone levels, glycemic indices, resumption of menstruation, endometrial thickness, live birth rates, abortion rates, and body mass index (BMI). Studies with irrelevant interventions, animal studies, reviews without quantitative analysis, and studies with insufficient data were excluded. Standardized mean difference (SMD) with a 95% confidence interval (CI) and relative risk (RR) with a 95% CI were used as effect sizes to pool the data using a random effects model.

Results

A total of 38 meta-analyses, 20 studies (sample size: 27,106 patients) for PCOS and 18 studies (sample size: 19,098 patients) for POI, were included. Overall, in women with PCOS, acupuncture therapies were significantly associated with a higher pregnancy rate, ovulation rate, and reduced serum levels of luteinizing hormone (LH), testosterone, LH/follicle-stimulating hormone (FSH), insulin resistance, and BMI. Moreover, FSH, fasting glucose, and fasting insulin levels were improved in subgroup analyses. For POI, acupuncture significantly improved serum levels of LH, FSH, LH/FSH ratio, and estradiol.

Conclusion

Acupuncture-related therapies improve pregnancy rate, and metabolic and hormonal imbalances in patients with POI and PCOS.

Systematic review registration

The protocol of the study was registered in PROSPERO (CRD42024572893). Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024572893.
Reflexive eye saccadic parameters in Parkinson’s disease
Authors: Pah Nemuel D. , Ngo Quoc C. , McConnell Nicole , Polus Barbara , Kempster Peter , Bhattacharya Arup , Raghav Sanjay , Kumar Dinesh K.
Published: November 2024

Introduction

Abnormal reactive saccade, with reduced saccadic gain, impaired smooth pursuit, and unwarranted reactions are clinically used to assess people with Parkinson’s disease (PwPD). However, there are inconsistent findings related to other saccade parameters such as latency and transition times. This study aimed to identify differences in the reflexive saccade parameters of early stage PwPD and aged-matched control (AMC).

Methods

In this observational study, the reactive eye-gaze was recorded for 70 participants (42 PwPD) and parameters of reflexive saccades and eye-gaze fluctuations were extracted. These parameters were then statistically analyzed using the Mann–Whitney U-test.

Results

Results showed that PwPD had significantly shorter latency than AMC for reflexive saccadic movement away from the center of the screen. The overshoot as a fraction of the screen width, a measure of the inaccuracy in reaching the target, was also significantly higher for PwPD. PwPD had greater horizontal and vertical eye gaze fluctuation with a steady target. The numbers of invalid saccades, i.e., when the gaze goes in the opposite direction from the target movement or is considered anticipatory, were similar for both groups; PwPD with 33.43% and AMC with 25.71%.

Discussion

This study shows that there are significant differences in the reflexive saccade of PwPD and AMC measured using an inexpensive eye-tracking device. The presence of invalid saccade trials, and differences between towards and away from screen center, both of which were not considered in earlier studies, may explain the discrepancies between earlier studies. The outcome of this study has the potential to be made a device that would assist neurologists in the assessment of PwPD.
5′-untranslated region sequences enhance plasmid-based protein production in Sulfolobus acidocaldarius
Authors: Kuschmierz Laura , Wagner Alexander , Schmerling Christian , Busche Tobias , Kalinowski Jörn , Bräsen Christopher , Siebers Bettina
Published: November 2024

Sulfolobus acidocaldarius, a thermoacidophilic archaeon of the phylum Thermoproteota (former Crenarchaeota), is a widely used model organism for gene deletion studies and recombinant protein production. Previous research has demonstrated the efficacy of the saci_2122 promoter (Para), providing low basal activity and high pentose-dependent induction. However, the available expression vector does not include a 5′-terminal untranslated region (5’-UTR), a typical element found in bacterial expression vectors that usually enhances protein production in bacteria. To establish S. acidocaldarius as a production strain in biotechnology in the long term, it is intrinsically relevant to optimize its tools and capacities to increase production efficiencies. Here we show that protein production is increased by the integration of S. acidocaldarius 5’-UTRs into Para expression plasmids. Using the esterase Saci_1116 as a reporter protein, we observed a four-fold increase in soluble and active protein yield upon insertion of the saci_1322 (alba) 5’-UTR. Screening of four additional 5’-UTRs from other highly abundant proteins (thα, slaA, slaB, saci_0330) revealed a consistent enhancement in target protein production. Additionally, site-directed mutagenesis of the Shine-Dalgarno (SD) motif within the alba 5’-UTR revealed its significance for protein synthesis. Ultimately, the alba 5’-UTR optimized expression vector improved the expression of various proteins, including six glycosyltransferases and one hydroxyacyl-CoA dehydratase from S. acidocaldarius, and a malto-oligosyltrehalose trehalohydrolase from Saccharolobus solfataricus, demonstrating its applicability. Our results show that the integration of SD-motif containing 5’-UTRs significantly enhanced plasmid-based protein production in S. acidocaldarius. This advancement in recombinant expression not only broadens the utility of S. acidocaldarius as an archaeal expression platform but also marks an important step toward potential biotechnological applications.
Regulation of cochlear hair cell function by intracellular calcium stores
Authors: Sinha Ghanshyam P. , Frolenkov Gregory I.
Published: November 2024

Introduction

Mammalian hearing depends on the dual mechanosensory and motor functions of cochlear hair cells. Both these functions may be regulated by Ca2+ release from intracellular stores. However, it is still unclear how exactly intracellular Ca2+ release may affect either hair cell mechano-electrical transduction (MET) or prestin-dependent electromotility in outer hair cells (OHCs).

Methods

Here, we used photo-activatable (caged) compounds to generate fast increases of either Ca2+ or inositol-3-phosphate (IP3) in the cytosol of young postnatal rodent auditory hair cells, thereby stimulating either Ca2+- or IP3- induced releases of Ca2+ from intracellular stores. Fast Ca2+ imaging was used to monitor propagation of Ca2+ signals along the length of a hair cell. To access potential physiological role(s) of intracellular Ca2+ releases, we used whole cell patch clamp to record: i) OHC voltage-dependent capacitance, a known electrical correlate of prestin-based electromotility, and ii) MET currents evoked by stereocilia bundle deflections with fluid-jet. In the latter experiments, changes of mechanical stiffness of the hair bundles were also quantified from video recordings of stereocilia movements.

Results

Ca2+ uncaging at the OHC apex initiated Ca2+ wave propagating to the base of the cell with subsequent Ca2+ build-up there. Ca2+ uncaging at the OHC base generated long-lasting and apparently self-sustained Ca2+ responses, further confirming Ca2+-induced Ca2+ release in the OHC basal region. Photoactivated IP3 initiated a slow increase of cytosolic Ca2+ ([Ca2+]i) throughout the whole OHC, confirming the presence of slow-activated IP3-gated Ca2+ stores in OHCs. Interestingly, Ca2+ uncaging produced no effects on OHC voltage-dependent capacitance. In an OHC, the rise of [Ca2+]i is known to decrease axial stiffness of the cell and may modulate the stiffness of mechanosensory stereocilia bundles. To separate these two phenomena, we explored the potential effects of intracellular Ca2+ release on mechanical properties of stereocilia bundles in cochlear inner hair cells (IHCs). Ca2+ uncaging at the apex of an IHC caused a long-lasting increase in mechanical stiffness of stereocilia bundle without any changes in the amplitude or deflection sensitivity of the MET current.

Discussion

We concluded that the most likely physiological role of IP3-gated Ca2+ release at the apex of the cell is the regulation of hair bundle stiffness. In contrast, Ca2+-induced Ca2+ release at the base of OHCs seems to regulate axial stiffness of the cells and its hyperpolarization in response to efferent stimuli, without direct effects on the OHC prestin-based membrane motors.
Vestibular afferent neurons develop normally in the absence of quantal/glutamatergic input
Authors: Regalado Núñez Katherine , Bronson Daniel , Chang Ryan , Kalluri Radha
Published: November 2024

Introduction

The vestibular nerve is comprised of neuron sub-groups with diverse functions related to their intrinsic biophysical properties. This diversity is partly due to differences in the types and numbers of low-voltage-gated potassium channels found in the neurons’ membranes. Expression for some low-voltage gated ion channels like KCNQ4 is upregulated during early post-natal development; suggesting that ion channel composition and neuronal diversity may be shaped by hair cell activity. This idea is consistent with recent work showing that glutamatergic input from hair cells is necessary for the normal diversification auditory neurons.

Methods

To test if biophysical diversity is similarly dependent on glutamatergic input in vestibular neurons, we examined vestibular function and the maturation of the vestibular epithelium and ganglion neurons by immunohistochemistry and patch-clamp electrophysiology in Vglut3-ko mice whose hair cell synapses lack glutamate.

Results

The knockout mice showed no obvious balance deficits and crossed challenging balance beams with little difficulty. Immunolabeling of the Vglut3-ko vestibular epithelia showed normal development as indicated by an identifiable striolar zone with calyceal terminals labeled by molecular marker calretinin, and normal expression of KCNQ4 by the end of the second post-natal week. We found similar numbers of Type I and Type II hair cells in the knockout and wild-type animals, regardless of epithelial zone. Thus, the presumably quiescent Type II hair cells are not cleared from the epithelium. Patch-clamp recordings showed that biophysical diversity of vestibular ganglion neurons in the Vglut3-ko mice is comparable to that found in wild-type controls, with a similar range firing patterns at both immature and juvenile ages. However, our results suggest a subtle biophysical alteration to the largest ganglion cells (putative somata of central zone afferents); those in the knockout had smaller net conductance and were more excitable than those in the wild type.

Discussion

Thus, unlike in the auditory nerve, glutamatergic signaling is unnecessary for producing biophysical diversity in vestibular ganglion neurons. And yet, because the input signals from vestibular hair cells are complex and not solely reliant on quantal release of glutamate, whether diversity of vestibular ganglion neurons is simply hardwired or regulated by a more complex set of input signals remains to be determined.
The role and mechanism of Aβ clearance dysfunction in the glymphatic system in Alzheimer’s disease comorbidity
Authors: Li Hailang , Yao Qianqian , Huang Xueyan , Yang Xiaoyan , Yu Changyin
Published: November 2024

Alzheimer’s disease (AD) is the leading type of dementia globally, characterized by a complex pathogenesis that involves various comorbidities. An imbalance in the production and clearance of amyloid β-protein (Aβ) peptides in the brain is a key pathological mechanism of AD, with the glymphatic system playing a crucial role in Aβ clearance. Comorbidities associated with AD, such as diabetes, depression, and hypertension, not only affect Aβ production but also impair the brain’s lymphatic system. Abnormalities in the structure and function of this system further weaken Aβ clearance capabilities, and the presence of comorbidities may exacerbate this process. This paper aims to review the role and specific mechanisms of impaired Aβ clearance via the glymphatic system in the context of AD comorbidities, providing new insights for the prevention and treatment of AD. Overall, the damage to the glymphatic system primarily focuses on aquaporin-4 (AQP4) and perivascular spaces (PVS), suggesting that maintaining the health of the glymphatic system may help slow the progression of AD and its comorbidities. Additionally, given the ongoing controversies regarding the structure of the glymphatic system, this paper revisits this structure and discusses the principles and characteristics of current detection methods for the glymphatic system.
Widely targeted metabolomics and SPME-GC-MS analysis revealed the quality characteristics of non-volatile/volatile compounds in Zheng’an Bai tea
Authors: Liu Li , Qiao Dahe , Mi Xiaozeng , Yu Shirui , Jing Tingting , An Yanlin
Published: November 2024

Background

As albino tea under the geographical protection of agricultural products, Zheng’an Bai tea is not only rich in amino acids, polyphenols and other beneficial components for the human body, but also its leaf color will turn green as the temperature gradually rises, thus causing changes in the quality characteristics of tea leaves. However, these changing characteristics have not yet been revealed.

Methods

In-depth quality analysis was carried out on the fresh leaves of Zheng’an Bai tea at four different developmental stages and four samples from the processing stage through extensive targeted metabolomics and SPME-GC-MS analysis.

Results

In this study, a total of 573 non-volatile metabolites were detected from the fresh leaves and processing samples of Zheng’an Bai tea, mainly including 96 flavonoids, 75 amino acids, 56 sugars and alcohols, 48 terpenoids, 46 organic acids, 44 alkaloids, and 39 polyphenols and their derivatives. In fresh leaves, the most significant differential metabolites (VIP > 1, p < 0.05) among different samples mainly include substances such as ethyl gallate, theaflavin, isovitexin and linalool, while the main differential metabolites of samples in the processing stage include alkaloids, polyphenols and flavonoids such as zarzissine, methyl L-Pyroglutamate, theaflavin 3,3’-digallate, euscaphic acid and ethyl gallate. Overall, substances such as sugars and alcohols, alkaloids and polyphenols show the greatest differences between fresh leaves and the processing process. Meanwhile, 97 kinds of volatile metabolites were detected in these samples, most of which had a higher content in the fresh leaves. Moderate spreading is conducive to the release of the aroma of tea leaves, but fixation causes a sharp decrease in the content of most volatile metabolites. Ultimately, 9 volatile substances including geraniol, linalool, nerolidol, jasmone, octanal, 1-Nonanal, heptaldehyde, methyl salicylate and 1-Octen-3-ol were identified as the key aroma components (OAV >1) of Zheng’an Bai tea.

Conclusion

In conclusion, this study has for the first time comprehensively revealed the quality change characteristics of fresh leaves at different developmental stages and during the processing of Zheng’an Bai tea, and provided a foundation for further process improvement.
Protective effects of betaine on the early fatty liver in laying hens through ameliorating lipid metabolism and oxidative stress
Authors: Wang Chaohui , Sun Xi , Liu Xiaoying , Wang Yumeng , Luo Jiarui , Yang Xiaojun , Liu Yanli
Published: November 2024

Introduction

Fatty liver syndrome (FLS) is a prevalent nutritional and metabolic disease that mainly occurs in caged laying hens, causing substantial losses in the poultry industry. The study was carried out to explore the protective effect and potential mechanism of betaine on early FLS.

Methods

There were three groups: Con group (basal diet), FLS group (Dexamethasone injection + basal diet) and betaine group (Dexamethasone injection + basal diet with 8 g/kg betaine). Birds in FLS and betaine groups were treated with subcutaneous dexamethasone injection once a day at a dosage of 4.50 mg/kg body weight for 7 days.

Results

The results revealed that DXM treatment significantly increased the liver index, serum aspartate aminotransferase (AST), total protein (TP), total bilirubin (TBIL), total biliary acid (TBA), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), and glucose (GLU) (p < 0.05). Additionally, hepatic TC and TG levels were also elevated (p < 0.05). Meanwhile, H&E and oil red O staining showed that there were a large number of vacuoles and lipid droplets in the liver of hens in FLS group. Dietary betaine addition significantly alleviated the increasing of serum TBIL, TBA and hepatic TC caused by dexamethasone treatment (p < 0.05). There existed 1,083 up- and 996 down-regulated genes in FLS group when compared with the control, and there were 169 upregulation and 405 downregulation genes in BT group when compared with FLS group. A total of 37 differential expression genes (DEGs) were rescued by betaine addition, which were related to lipid metabolism and antioxidant functions including APOC3, APOA4, G0S2, ERG28, PLA2G3, GPX4 and SLC5A8. Serum metabolomics analysis showed that 151 differential metabolites were identified in FLS group when compared with the control. Dietary betaine addition could rescue the changes of metabolites partly such as chicoric acid, gamma-aminobutyric acid, linoleic acid, telmisartan, which were associated with anti-oxidative function. In addition, RT-PCR results showed that genes involved in lipid metabolism, such as ACC, FAS, SCD1, ELOVL6, SREBP1, GR, ATGL and MTTP were markedly upregulated at the mRNA level (p < 0.05). However, dietary supplementation with betaine can reversed the expression of these genes (p < 0.05). Importantly, dietary betaine supplementation could reverse increased lipid synthesis partly by regulating PI3K/AKT/SREBP and CEBPα pathways in the liver based on western blot results (p < 0.05).

Conclusion

Dexamethasone treatment could establish the early FLS model in laying hens with hepatic lipid accumulation and no inflammation, which could be attenuated by dietary betaine addition.
Bufonis venenum extract loaded novel cholesterol-free liposome for the treatment of hepatocellular carcinoma
Authors: Yang Siqi , Lan Jinshuai , Li Zhe , Li Ming , Wu Ya , Sun Liyan , Zhang Tong , Ding Yue
Published: November 2024

Background

This study aims to improve the solubility and the toxicity of Bufonis venenum, and finally enhance the therapeutic outcomes of hepatocellular carcinoma (HCC).

Methods

The cholesterol-free liposomes simultaneously encapsulate bufadienolides and indolealkylamines (Non-Cholesterol-Bufonis Venenum Extract-Liposome, Non-Chol-BVE-LP) was prepared by the thin-film evaporation technique. In vitro, the cytotoxicity, cell apoptosis study, cellular uptake and hemolysis studies were evaluated in HepG2 cells. In vivo, the biodistribution and anti-tumor activity studies were conducted in BALB/C mice with HepG2 cells.

Results

The liposomes showed good size distribution, encapsulation efficiency drug loading capacity and slower drug release. Non-Chol-BVE-LP had higher cytotoxicity on HepG2 cells and induced more apoptosis on HepG2 Cells compared with BVE. In addition, the liposomes could accumulate in tumor by passive targeting, thus facilitating the anti-tumor effects. In vivo, Non-Chol-BVE-LP showed equivalent anti-tumor efficacy to the first-line anti-HCC drug sorafenib.

Conclusion

The study provided new ideas for the development and clinical application of Bufonis venenum related formulation and offered new drug for the treatment of HCC.
Pregnancy-related acute kidney injury leads to hypertension, reduced kidney function and cognitive impairment in postpartum rats
Authors: Griffin Ashley , Szczepanski Jamie , Spencer Shauna-Kay , Solis Lucia , Bowles Teylor , Robinson Reanna , Williams Jan M. , Kyle Patrick B. , Wallace Kedra
Published: November 2024

Introduction

Women with hypertensive disorders of pregnancy such as HELLP (hemolysis, elevated liver enzyme, low platelet) Syndrome are affected by acute kidney injury during pregnancy (PR-AKI) at higher rates than women without hypertension. Both hypertensive disorders of pregnancy and Acute Kidney Injury (AKI) outside the context of pregnancy have been associated with an increased risk of developing Chronic Kidney Disease (CKD) and cognitive impairment. In our current study, we set out to determine if PR-AKI led to the development of CKD and impaired cognition in the postpartum period and if HELLP syndrome exacerbates the impairments.

Methods

Using timed-pregnant Sprague Dawley rats, on gestational day (GD) 12, mini-osmotic pumps infusing anti-angiogenic factors were surgically placed in the intraperitoneal cavity to induce HELLP. On GD18, AKI was induced via bilateral renal reperfusion ischemia surgery. Mean arterial pressure and birth outcomes were used to assess the global effects of AKI, and liver enzymes were used to assess HELLP. CKD was assessed by measuring glomerular filtration rate (GFR), urinary output, and renal fibrosis. Anxiety-like behaviors, object recognition memory, spatial memory, and avoidance memory were assessed via behavioral experiments.

Results

HELLP + AKI rats demonstrated more evidence of renal injury, hypertension, and behavioral deficits compared to normal pregnant animals. In addition, AKI had a negative impact on birth outcomes and maternal survival.

Conclusion

HELLP + AKI together led to evidence of persistent hypertension, progressive renal dysfunction, and cognitive impairment, which were exacerbated compared to AKI or HELLP alone. These findings suggest that PR-AKI in the presence of a hypertensive disorder of pregnancy, such as HELLP, leads to the development of CKD, cognitive dysfunction, and hypertension.
Effects of thinning on the structure of soil microbial communities in a subtropical secondary evergreen broad-leaved forest
Authors: Yao Liangjin , Jiao Jiejie , Wu Chuping , Jiang Bo , Fan Lili
Published: November 2024

Introduction

Thinning is a common practice to enhance tree growth, but its effect on rhizosphere soil microorganisms in subtropical secondary evergreen broadleaved forests remains unclear.

Methods

This study used 16S rDNA amplicon sequencing to explore soil microflora of five shrubs and five tree species.

Results

The results showed that thinning altered nutrient distribution and pH in rhizosphere soil, impacting microbial richness, which varied by tree species. The dominant bacterial phyla were Acidobacteria, Proteobacteria, Actinobacteria, and Firmicutes. Although the dominant microbial species remained largely unchanged, thinning increased the relative abundance of Firmicutes. Thinning intensity between 10-15% significantly altered the structure of soil microbial communities, demonstrating species-specific responses.

Discussion

These changes in microbial structure may influence tree growth. This study proposed the potential effects of thinning on rhizosphere soil microorganisms and suggests future research to investigate the specific microbial mechanisms affected by thinning.
Piece of Mind: knowledge translation performances for public engagement on Parkinson’s disease and dementia
Authors: Kuhlmann Naila , Thomas Aliki , Incio-Serra Natalia , Blain-Moraes Stefanie
Published: November 2024

Introduction

The subjective experience of illness is often overshadowed by the disease-and-cure focus of health research, contributing to the stigmatization of conditions such as Parkinson’s disease and dementia. This is exacerbated by the fact that traditional means of knowledge dissemination are inaccessible to non-academic audiences, hampering meaningful dialogue with and research uptake by the broader community.

Methods

Our arts-based knowledge translation project, Piece of Mind, brought together neuroscientists, people with Parkinson’s disease or dementia, care partners and artists (musicians, dancers, circus acrobats) to co-create 2 multi-media performances based on scientific research and lived experience. We investigated whether the resulting interdisciplinary, multimedia performances could (1) challenge misperceptions around Parkinson’s/dementia; and (2) render neuroscientific research accessible to a diverse audience. Prior to and immediately following virtual screenings of the feature-length Piece of Mind Parkinson’s and Dementia filmed performances, audience members were invited to complete pre-post questionnaires comprised of demographic, Likert-scale and open-ended questions.

Results

Responses indicated that both performances elicited strong emotional engagement and improved self-reported understanding and empathy towards individuals with Parkinson’s and dementia. Based on a thematic analysis on open-ended questions, we consider the barriers and facilitators to the audience’s receptiveness and discuss the performances’ potential as a knowledge translation tool.

Discussion

By presenting an emotionally engaging perspective on Parkinson’s and dementia, Piece of Mind acts as an important complement to text-based knowledge dissemination in health research.
The high energy X-ray probe (HEX-P): science overview
Authors: García Javier A. , Stern Daniel , Madsen Kristin , Smith Miles , Grefenstette Brian , Ajello Marco , Alford Jason , Annuar Adlyka , Bachetti Matteo , Baloković Mislav , Beckmann Ricarda S. , Bianchi Stefano , Biccari Daniela , Boorman Peter , Brightman Murray , Buchner Johannes , Bulbul Esra , Chen Chien-Ting , Civano Francesca , Coley Joel , Connors Riley M. T. , Del Santo Melania , Gesu Laura Di , Draghis Paul A. , Fragile P. Chris , Gúrpide Andrés , Gangi Manuele , Gezari Suvi , Harrison Fiona , Kammoun Elias , Lanzuisi Giorgio , Lehmer Bret , Lohfink Anne , Ludlam Renee , Marchesi Stefano , Marcotulli Lea , Margutti Raffaella , Masterson Megan , Merloni Andrea , Middleton Matthew , Mori Kaya , Moretti Alberto , Nandra Kirpal , Perez Kerstin , Pfeifle Ryan W. , Pinto Ciro , Piotrowska Joanna , Ponti Gabriele , Pottschmidt Katja , Predehl Peter , Puccetti Simonetta , Rau Arne , Reynolds Stephen , Santangelo Andrea , Spiga Daniele , Tomsick John A. , Torres-Albà Núria , Walton Dominic J. , Wilkins Daniel , Wilms Joern , Zhang Will , Zhao Xiurui
Published: November 2024

To answer NASA’s call for a sensitive X-ray observatory in the 2030s, we present the High Energy X-ray Probe (HEX-P) mission concept. HEX-P is designed to provide the required capabilities to explore current scientific questions and make new discoveries with a broadband X-ray observatory that simultaneously measures sources from 0.2 to 80 keV. HEX-P’s main scientific goals include: 1) understand the growth of supermassive black holes and how they drive galaxy evolution; 2) explore the lower mass populations of white dwarfs, neutron stars, and stellar-mass black holes in the nearby universe; 3) explain the physics of the mysterious corona, the luminous plasma close to the central engine of accreting compact objects that dominates cosmic X-ray emission; and 4) find the sources of the highest energy particles in the Galaxy. These goals motivate a sensitive, broadband X-ray observatory with imaging, spectroscopic, and timing capabilities, ensuring a versatile platform to serve a broad General Observer (GO) and Guest Investigator (GI) community. In this paper, we present an overview of these mission goals, which have been extensively discussed in a collection of more than a dozen papers that are part of this Research Topic volume. The proposed investigations will address key questions in all three science themes highlighted by Astro2020, including their associated priority areas. HEX-P will extend the capabilities of the most sensitive low- and high-energy X-ray satellites currently in orbit and will complement existing and planned high-energy, time-domain, and multi-messenger facilities in the next decade.
Association between tumor size and prognosis in bladder cancer: novel classifications and insights from a SEER database analysis
Authors: Jia Yige , Wu Kan , Li Xiang
Published: November 2024

Objective

Although tumor size is an essential oncologic feature, it is often underutilized in diagnosing and treating bladder cancer (BC). This study investigates the relationship between tumor size and BC prognosis, aiming to enhance clinical applications.

Methods

BC patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2015). Cox proportional hazard models were conducted to identify prognostic factors, and restricted cubic splines (RCS) were used to assess the relationship between tumor size and survival outcomes. The Kaplan-Meier method and multivariate COX models were utilized to estimate the effect of the classification scheme.

Results

A total of 69,478 patients with BC were evaluated from the SEER database. Larger tumor size, recent diagnosis, older age, high pathologic grade, variant histology, advanced T stages, positive lymph node status, and receipt of radiotherapy and chemotherapy were associated with worse overall and cancer-specific survival. RCS curves of each stage showed that the relationship between tumor size and prognosis was non-linear. Optimal cut-off points were identified based on the shape of RCS curves, suggesting new classifications of tumor size: 2.5 cm and 5 cm for Ta, 3 cm and 5 cm for T1, and 4 cm and 6 cm for T2.

Conclusions

Incorporating tumor size into prognostic evaluations can enhance bladder cancer risk stratification. Further research is needed to validate these findings and improve personalized treatment strategies.
Phenotypic variation of dairy cows’ hematic metabolites and feasibility of non-invasive monitoring of the metabolic status in the transition period
Authors: Magro Silvia , Costa Angela , Cavallini Damiano , Chiarin Elena , De Marchi Massimo
Published: November 2024

Introduction

The incidence of metabolic diseases tends to be highest during the transition period (±3 weeks around parturition) in dairy cows due to physiological changes and the onset of lactation. Although blood profile testing allows for the monitoring of nutritional and metabolic status, conducting extensive analyses in the herd is costly and stressful for cows due to invasive procedures. Therefore, mid-infrared spectroscopy (MIR) could be seen as a valid alternative.

Methods

In the present study, we used laboratory-determined reference blood data and milk spectra of 349 Holstein cows to (i) identify the non-genetic factors affecting the variability of major blood traits in healthy cows and, subsequently, (ii) test the predictive ability of milk MIR. Cows belonged to 14 Italian commercial farms and were sampled once between 5 and 38 days in milk. For β-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), cholesterol, glucose, urea, total protein, albumin, globulin, minerals, aspartate aminotransferase, gamma-glutamyl transferase, creatine kinase, total bilirubin, and cortisol, the effects of parity, days in milk, and season were investigated using a linear model.

Results and discussion

The results indicate that all fixed effects significantly affected the hematic concentration of most of the traits. Regarding MIR, the most predictable traits were BHB, NEFA, and urea, with coefficients of determination equal to 0.57, 0.62, and 0.89, respectively. These values suggest that MIR predictions of BHB and NEFA are not sufficiently accurate for precise and punctual determination of the hematic concentration, however, still the spectrum of the milk can be exploited to identify cows at risk of negative energy balance and subclinical ketosis. Finally, the predictions can be useful for herd screening, decision-making, and genetic evaluation.
Genetic characterization and clonal analysis of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae from canine and human origins
Authors: Khine Nwai Oo , Shah Asad Ali , Chatsuwan Tanittha , Yindee Jitrapa , Supimon Natthapong , Saenkankam Imporn , Hampson David John , Prapasarakul Nuvee
Published: November 2024

Introduction

Carbapenem-resistant Enterobacterales (CRE), particularly carbapenemase-producing Escherichia coli and Klebsiella pneumoniae, pose a significant global health challenge due to their resistance to last-resort antibiotics. This study investigates the genetic characteristics and clonal relationships of CRE isolated from canine and human clinical samples in Bangkok to understand potential interspecies transmission.

Methods

Fifty-two CRE isolates were collected from 477 clinical samples from dogs and humans at Chulalongkorn University between 2017–2021. Bacterial species were identified using MALDI-TOF, and antimicrobial resistance was confirmed through broth microdilution testing. Genetic analyses included plasmid replicon typing, multilocus sequence typing (MLST), whole genome sequencing (WGS), and pulsed-field gel electrophoresis (PFGE) to assess resistance genes and clonal relatedness.

Results

CRE isolates from both species exhibited genetic variability with high ARG counts, particularly in human isolates. MLST identified ST410 in most E. coli isolates from both dogs and humans, and IncFIA/IncFIB plasmids were predominant among blaNDM-positive isolates. PFGE patterns and SNP analysis showed no clonal relationship between canine and human isolates, suggesting independent acquisition pathways for CRE in the two hosts.

Discussion

The study highlights the absence of direct clonal transmission between canine and human isolates but reveals overlapping sequence types and plasmid types. The findings underscore the potential for interspecies transmission under certain conditions, emphasizing the importance of a One Health approach for monitoring CRE in both human and animal populations.
Integrated transcriptomic and metabolomic analyses reveal heterosis for meat quality of Neijiang pigs
Authors: Dan Haifeng , Liu Chengming , Zhang Huiling , Gan Mailin , Wang Yan , Chen Lei , Zhao Ye , Liu Bin , Zhu Kangping , Niu Lili , Zhu Li , Shen Linyuan
Published: November 2024

Obese pig breeds have excellent meat quality, while lean pig breeds have high lean meat percentage and feed conversion rate. However, due to their respective shortcomings, obese pig and lean pig breeds are unable to balance production and consumption needs. Therefore, this study crossbred the obese Chinese pig breed Neijiang (NJ) with lean type Large White pigs (LW) to produce Neijiang × Large White(NL) pigs. This study compared the differences in carcass and meat quality traits between NJ pigs and NL pigs, and for the first time comprehensively analyzed the longissimus dorsi muscle of NJ pigs and NL pigs using transcriptomics and metabolomics. The results of slaughter and meat quality testing indicate that the carcass performance of NL pigs was significantly higher than that of NJ pigs, and the excellent meat quality characteristics of NJ pigs were also retained on NL pigs. The results of transcriptomics and metabolomics showed that there were 635 differentially expressed genes (DEGs) and 11 significantly different metabolites (SDM) in the longissimus dorsi muscle of NJ and NL pigs. The results of multi omics joint analysis showed that betaine, uridine triphosphate, glycerol 3-phosphate, and glutathione in SDMs were enriched in the shared KEGG pathway and significantly correlated with C1QTNF12, GGA3, SLC16A6, and RXRG in DEGs. In general, it is feasible to enhance the production performance of NJ pigs through crossbreeding with LW pigs. The hybrid offspring inherit the advantages of these two varieties, maintaining excellent meat quality while also having better carcass performance.
A Design Methodology Incorporating a Sound Insulation Prediction Model, Life Cycle Assessment (LCA), and Thermal Insulation: A Comparative Study of Various Cross-Laminated Timber (CLT) and Ribbed CLT-Based Floor Assemblies
Authors: Bader Eddin Mohamad , Ménard Sylvain , Laratte Bertrand , Wu Tingting Vogt
Published: November 2024

Mass timber is increasingly being employed in constructing low- and mid-rise buildings. One of the primary reasons for using mass timber structures is their sustainability and ability to reduce environmental consequences in the building sector. One criticism of these structures is their lower subjective sound insulation quality. Therefore, acoustic treatments should be considered. However, acoustic solutions do not necessarily contribute to lower environmental impacts or improved thermal insulation performance. This paper discusses a design methodology that incorporates the development of a sound insulation prediction tool (using an artificial neural networks approach), life cycle assessment analysis, and thermal insulation study. A total of 112 sound insulation measurements (in one-third octave bands from 50 to 5000 Hz) are utilized to develop the network model and are also used for the LCA and thermal insulation study. They are lab-based measurements and are performed on 45 various CLT- and ribbed CLT-based assemblies. The acoustic model demonstrates satisfactory results with 1 dB differences in the prediction of airborne and impact sound indices (Rw and Ln,w). An acoustic sensitivity study and a statistical analysis are then conducted to validate the model’s results. Additionally, an LCA analysis is performed on the floor assemblies to calculate their environmental footprints. LCA categories are plotted against the acoustic performance of floors. No correlations are found, and the results emphasize that a wide range of sound insulation can be achieved with similar environmental impacts. Within each acoustic performance tier, the LCA results can be optimized for a floor assembly by selecting appropriate materials. The thermal insulation of floors is then calculated. Overall, a strong positive correlation is found between the total thermal resistance and heat loss against acoustic performance. Designers should be cognizant of the trade-offs between acoustic, thermal insulation, and environmental performance when choosing assemblies with favorable environmental impacts relative to acoustic and thermal insulation ratios.