bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of non-caloric artificial sweetener aspartame on female reproductive system in mice model
Authors: Naik Ab Qayoom , Zafar Tabassum , Shrivastava Vinoy K
Published: August 2023

Background

Artificial sweeteners, used as sugar substitutes have found their ways into almost all the food items due to the notion that they are non-caloric. Aspartame is used in numerous food products throughout the world. The primary users of aspartame include diabetics and calorie conscious people who intend to limit their calorie intake.

Methods

Female Swiss albino mice were divided into three groups (12 mice each) for the duration of 30 and 60 days consecutively. The treatment groups received 40 mg/kg b. w. aspartame orally. Hormone assays using ELISA and tissue histopathology have been performed along with the fertility assay to access the treatment outcomeon the fertility of treated mice in comparison to controls.

Results

Present study reports that female mice treated with aspartame for 30 and 60 days showed significant reduction in body weight, relative organ weight of (liver and kidney) and gonadosomatic index. These changes were more significantly recorded in 60 days treatment group. Aspartame treated animals for 30 and 60 days showed duration-dependent decrease gonandotropins (follicle stimulating hormone and luteinizing hormone), and steroids (estradiol and progesterone). Moreover, severe histopathological changes, reduction in number of growing follicles, degenerative changes in follicular structure, corona radiata and zonagranulosa were also observed. Besides, histomorphological changes were also observed in the uterine structure including atrophic uterine endometrial glands, contracted endometrial lining, disruption of the endometrial structure and the shapes of blood vessels were also altered.

Conclusion

Non-nutritive artificial sweeteners including aspartame negatively impact the function of ovaries and feedback mechanism of reproductive hormones by affecting the hypothalamic–pituitary–gonadal axis. In light of present findings the aspartame negatively impacted the reproductive system of female mice. More studies are required to identify the molecular mechanism and the pathways involved.
Inhibition of ERK downregulates autophagy via mitigating mitochondrial fragmentation to protect SH-SY5Y cells from OGD/R injury
Authors: Yuan Zhang-Li , Mo Yan-Zi , Li De-Li , Xie Lu , Chen Meng-Hua
Published: August 2023

Background

Cerebral ischemia-reperfusion injury (CIRI) is the main cause leading to high mortality and neurological disability in patients with cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Our previous study found that extracellular signal-regulated kinase (ERK) activation, dynamin-related protein1 (Drp1)/Mitofusin2 (Mfn2)-dependent mitochondrial dynamics imbalance, and excessive autophagy were involved in the mechanism of nerve injury after CA/CPR. However, the specific pathological signaling pathway is still unknown. This study aimed to explore the molecular function changes of ERK-Drp1/Mfn2-autophagy signaling pathway in SH-SY5Y cell oxygen-glucose deprivation/reoxygenation (OGD/R) model, to further clarify the pathophysiological mechanism of CIRI, and to provide a new strategy for cerebral protection after CIRI.

Methods

SH-SY5Y cells were pretreated with drugs 24 h before OGD/R. The Drp1 and Mfn2 knockdown were adopted small interfering RNAs. The overexpression of p-Drp1S616 and Mfn2 were used recombinant plasmids. The expression levels of mitochondrial dynamics proteins (p-Drp1, Drp1, Mfn2, Mfn1 and Opa1) and autophagy markers (LC3, Beclin1 and p62) were measured with the Western blotting. The mRNA levels after transfection were determined by PCR. Cell injury and viability were evaluated with released LDH activity and CCK8 assay kits. Mitochondria morphology and autophagosome were observed under transmission electron microscopy. Mitochondrial function was detected by the mitochondrial permeability transition pore assay kit. The co-expression of p-ERK, p-Drp1 and LC3 was assessed with multiple immunofluorescences. One-way analysis of variance followed by least significance difference post hoc analysis (for equal homogeneity) or Dunnett’s T3 test (for unequal homogeneity) were used for statistical tests.

Results

ERK inhibitor-PD98059 (PD) protects SH-SY5Y cells from OGD/R-induced injury; while ERK activator-TPA had the opposite effect. Similar to autophagy inhibitor 3-MA, PD downregulated autophagy to improve cell viability; while autophagy activator-rapamycin further aggravated cell death. PD and Drp1-knockdown synergistically attenuated OGD/R-induced Drp1 activation, mPTP opening and cell injury; overexpression of Drp1S616E or ablating Mfn2 partly abolished the protective effects of PD. Multiple immunofluorescences showed that p-ERK, p-Drp1 and LC3 were co-expressed.

Conclusion

Inhibition of ERK downregulates autophagy via reducing Drp1/Mfn2-dependent mitochondrial fragmentation to antagonize mitochondrial dysfunction and promotes cell survival in the SH-SY5Y cells OGD/R model.
PI3K/AKT signaling pathway as a critical regulator of epithelial-mesenchymal transition in colorectal tumor cells
Authors: Maharati Amirhosein , Moghbeli Meysam
Published: August 2023

Colorectal cancer (CRC) is one of the most frequent gastrointestinal malignancies that are considered as a global health challenge. Despite many progresses in therapeutic methods, there is still a high rate of mortality rate among CRC patients that is associated with poor prognosis and distant metastasis. Therefore, investigating the molecular mechanisms involved in CRC metastasis can improve the prognosis. Epithelial-mesenchymal transition (EMT) process is considered as one of the main molecular mechanisms involved in CRC metastasis, which can be regulated by various signaling pathways. PI3K/AKT signaling pathway has a key role in CRC cell proliferation and migration. In the present review, we discussed the role of PI3K/AKT pathway CRC metastasis through the regulation of the EMT process. It has been shown that PI3K/AKT pathway can induce the EMT process by down regulation of epithelial markers, while up regulation of mesenchymal markers and EMT-specific transcription factors that promote CRC metastasis. This review can be an effective step toward introducing the PI3K/AKT/EMT axis to predict prognosis as well as a therapeutic target among CRC patients.
Investigations of brain-wide functional and structural networks of dopaminergic and CamKIIα-positive neurons in VTA with DREADD-fMRI and neurotropic virus tracing technologies
Authors: Zheng Ning , Gui Zhu , Liu Xiaodong , Wu Yang , Wang Huadong , Cai Aoling , Wu Jinfeng , Li Xihai , Kaewborisuth Challika , Zhang Zhijian , Wang Qitian , Manyande Anne , Xu Fuqiang , Wang Jie
Published: August 2023

Background

The ventral tegmental area (VTA) contains heterogeneous cell populations. The dopaminergic neurons in VTA play a central role in reward and cognition, while CamKIIα-positive neurons, composed mainly of glutamatergic and some dopaminergic neurons, participate in the reward learning and locomotor activity behaviors. The differences in brain-wide functional and structural networks between these two neuronal subtypes were comparatively elucidated.

Methods

In this study, we applied a method combining Designer Receptors Exclusively Activated by Designer Drugs (DREADD) and fMRI to assess the cell type-specific modulation of whole-brain neural networks. rAAV encoding the cre-dependent hM3D was injected into the right VTA of DAT-cre or CamKIIα-cre transgenic rats. The global brain activities elicited by DREADD stimulation were then detected using BOLD-fMRI. Furthermore, the cre-dependent antegrade transsynaptic viral tracer H129ΔTK-TT was applied to label the outputs of VTA neurons.

Results

We found that DREADD stimulation of dopaminergic neurons induced significant BOLD signal changes in the VTA and several VTA-related regions including mPFC, Cg and Septum. More regions responded to selective activation of VTA CamKIIα-positive neurons, resulting in increased BOLD signals in VTA, Insula, mPFC, MC_R (Right), Cg, Septum, Hipp, TH_R, PtA_R, and ViC_R. Along with DREADD-BOLD analysis, further neuronal tracing identified multiple cortical (MC, mPFC) and subcortical (Hipp, TH) brain regions that are structurally and functionally connected by VTA dopaminergic and CamKIIα-positive neurons.

Conclusions

Our study dissects brain-wide structural and functional networks of two neuronal subtypes in VTA and advances our understanding of VTA functions.
The mitochondrial protein TSPO in Alzheimer’s disease: relation to the severity of AD pathology and the neuroinflammatory environment
Authors: Garland Emma F. , Dennett Oliver , Lau Laurie C. , Chatelet David S. , Bottlaender Michel , Nicoll James A. R. , Boche Delphine
Published: August 2023

The 18kD translocator protein (TSPO) is used as a positron emission tomography (PET) target to quantify neuroinflammation in patients. In Alzheimer’s disease (AD), the cerebellum is the pseudo-reference region for comparison with the cerebral cortex due to the absence of AD pathology and lower levels of TSPO. However, using the cerebellum as a pseudo-reference region is debated, with other brain regions suggested as more suitable. This paper aimed to establish the neuroinflammatory differences between the temporal cortex and cerebellar cortex, including TSPO expression. Using 60 human post-mortem samples encompassing the spectrum of Braak stages (I–VI), immunostaining for pan-Aβ, hyperphosphorylated (p)Tau, TSPO and microglial proteins Iba1, HLA–DR and MSR-A was performed in the temporal cortex and cerebellum. In the cerebellum, Aβ but not pTau, increased over the course of the disease, in contrast to the temporal cortex, where both proteins were significantly increased. TSPO increased in the temporal cortex, more than twofold in the later stages of AD compared to the early stages, but not in the cerebellum. Conversely, Iba1 increased in the cerebellum, but not in the temporal cortex. TSPO was associated with pTau in the temporal cortex, suggesting that TSPO positive microglia may be reacting to pTau itself and/or neurodegeneration at later stages of AD. Furthermore, the neuroinflammatory microenvironment was examined, using MesoScale Discovery assays, and IL15 only was significantly increased in the temporal cortex. Together this data suggests that the cerebellum maintains a more homeostatic environment compared to the temporal cortex, with a consistent TSPO expression, supporting its use as a pseudo-reference region for quantification in TSPO PET scans.
Biopharma innovation trends during COVID-19 and beyond: an evidence from global partnerships and fundraising activities, 2011-2022
Authors: Yu Tzu-Hui , Mei Yung-Yu , Tseng Yufeng Jane
Published: August 2023

Background

Co-development alliances and capital-raising activities are essential supports for biopharmaceutical innovation. During the initial outbreak of the COVID-19, the level of these business activities has increased greatly. Yet the magnitude, direction, and duration of the trend remain ambiguous. Real-time real-world data are needed to inform strategic redirections and industrial policies.

Methods

This observational study aims to characterize trends in global biopharma innovation activities throughout the global pandemic outbreak. Our extensive deal dataset is retrieved from the commercial database GlobalData (12,866 partnership deals and 32,250 fundraising deals announced between 2011 and 2022). We perform Chi-squared tests to examine the changes in qualitative deal attributes during and beyond the outbreak. Our deal-level sample is further aggregated into category-level panel data according to deal characteristics such as therapy area, molecule type, and development phase. We run a series of regressions to examine how the monthly investment amount raised in each category changed with the onset of the pandemic, controlling for the US Federal funds rate.

Results

The temporary surge of partnership and capital-raising activities was associated with the increase in infectious disease-related deals. Academic and government institutions played an increased role in supporting COVID-related co-development partnerships in 2020, and biopharma ventures had been securing more investments in the capital market throughout 2020 and 2021. The partnership and investment boom did not last till the later pandemic in 2022. The most significant and enduring trend was the shifting focus toward discovery-phase investments. Our regression model reveals that the discovery-phase fundraising deals did not suffer from a bounce back in the late pandemic, consistent with a persistent focus on early innovation.

Conclusions

Despite the reduced level of partnership and fundraising activities during 2022, we observe a lasting change in focus toward biopharmaceutical innovation after the pandemic outbreak. Our evidence suggests how entrepreneurs and investors should allocate resources in response to the post-pandemic tight monetary environment. We also suggest the need for policy interventions in financing private/public co-development partnerships and non-COVID-related technologies, to maintain their research capacity and generate breakthroughs when faced with unforeseen diseases.
Gut microbiota and intervertebral disc degeneration: a bidirectional two-sample Mendelian randomization study
Authors: Geng Ziming , Wang Jian , Chen Guangdong , Liu Jianchao , Lan Jie , Zhang Zepei , Miao Jun
Published: August 2023

Background

Although previous studies have suggested a close association between gut microbiota (GM) and intervertebral disc degeneration (IVDD), the causal relationship between them remains unclear. Hence, we thoroughly investigate their causal relationship by means of a two-sample Mendelian randomization (MR) study, aiming to determine the impact of gut microbiota on the risk of developing intervertebral disc degeneration.

Methods

Summary data from genome-wide association studies of GM (the MiBioGen) and IVDD (the FinnGen biobank) have been acquired. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach. Weighted median, MR-Egger regression, weighted mode, and simple mode were used as supplements. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were performed to assess horizontal pleiotropy. Cochran's Q test evaluated heterogeneity. Leave-one-out sensitivity analysis was further conducted to determine the reliability of the causal relationship. A reverse MR analysis was conducted to assess potential reverse causation.

Results

We identified nine gut microbial taxa that were causally associated with IVDD (P < 0.05). Following the Benjamini–Hochberg corrected test, the association between the phylum Bacteroidetes and a higher risk of IVDD remained significant (IVW FDR-corrected P = 0.0365). The results of the Cochrane Q test did not indicate heterogeneity (P > 0.05). Additionally, both the MR-Egger intercept test and the MR-PRESSO global test revealed that our results were not influenced by horizontal pleiotropy (P > 0.05). Furthermore, the leave-one-out analysis substantiated the reliability of the causal relationship. In the reverse analysis, no evidence was found to suggest that IVDD has an impact on the gut microbiota.

Conclusion

Our results validate the potential causal impact of particular GM taxa on IVDD, thus providing fresh insights into the gut microbiota-mediated mechanism of IVDD and laying the groundwork for further research into targeted preventive measures.
Efficacy and safety of traditional Chinese medicine in the treatment of osteonecrosis of the femoral head
Authors: Ouyang Wensi , Meng Yubo , Guo Guimei , Zhao Changwei , Zhou Xiaoling
Published: August 2023

Background

Hip joint-preserving treatment options for osteonecrosis of the femoral head (ONFH) have been a research hotspot in recent years. The combination of Chinese and Western medicine has been used in clinical practice to treat early- and mid-stage ONFH. However, there is still a lack of high-quality evidence to verify the effectiveness and safety of this approach.

Objective

To systematically evaluate the clinical efficacy and safety of the combination of traditional Chinese medicine (TCM) with Western medicine in the treatment of early- and mid-stage ONFH.

Methods

Multiple electronic databases were searched to identify the randomized controlled trials (RCTs) examining the use of TCM in the treatment of ONFH. Based on the inclusion and exclusion criteria, eligible studies were selected, and the quality of the studies was evaluated using the risk of bias assessment tool recommended by the Cochrane system Evaluator manual 5.1.0. The meta-analysis of the included data was performed using Review Manager 5.4.1 software and Stata 17.0 software.

Results

A total of 47 RCTs involving 3266 subjects were included in the meta-analysis. The results are observed: (1) Harris score: TCM + Western medicine versus Western medicine (SMD = 1.25, 95% Cl: 1.02 to 1.48, P < 0.00001), TCM + physiotherapy versus physiotherapy (SMD = 2.26, 95% Cl: 1.42 to 3.10, P < 0.00001), and TCM + hip preservation surgery versus hip preservation surgery (SMD = 1.28, 95% Cl: 1.03 to 1.53, P < 0.00001); (2) Visual analogue scale score: TCM + Western medicine versus Western medicine (SMD = −3.99, 95% Cl: −7.41 to −0.57, P = 0.02), TCM + physiotherapy versus physiotherapy (SMD = −0.99, 95% Cl: −1.44 to −0.54, P < 0.0001), and TCM + hip preservation surgery versus hip preservation surgery (SMD = −1.08, 95% Cl: −1.75 to −0.40, P = 0.002); (3) Imaging improvement: TCM + physiotherapy versus physiotherapy (RR = 1.42, 95% Cl: 1.15 to 1.76, P = 0.001) and TCM + hip preservation surgery versus hip preservation surgery (RR = 1.21, 95% Cl: 1.11 to 1.31, P < 0.0001); and (4) Occurrence of adverse reaction: TCM + Western medicine versus Western medicine (RR = 0.73, 95% Cl: 0.28 to 1.92, P = 0.53), TCM + physiotherapy versus physiotherapy (RR = 0.46, 95% Cl: 0.03 to 7.33, P = 0.58), and TCM + hip preservation surgery versus hip preservation surgery (RR = 1.11, 95% Cl: 0.36 to 3.45, P = 0.86).

Conclusion

TCM combined with Western medicine is an effective and safe approach for the treatment of ONFH. However, due to the low quality and quantity of the included studies, additional large-scale, high-quality studies are required to verify the above conclusions.

Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails, CRD42023392030.
Comparative analysis of percutaneous endoscopic interlaminar discectomy for highly downward-migrated disc herniation
Authors: Li Ran , Fu Dongming , Han Hao , Zhan Zihao , Wu Yiang , Meng Bin
Published: August 2023

Objectives

This study aimed to evaluate the clinical efficacy and safety of percutaneous endoscopic interlaminar discectomy (PEID) for treating highly downward-migrated disc herniation.

Methods

We conducted a retrospective study on 39 patients with highly downward-migrated disc herniation who underwent PEID treatment between January 2015 and October 2020. The clinical outcomes, including the preoperative and postoperative visual analogue scale (VAS) for the back and leg, Oswestry Disability Index (ODI), and MacNab criteria for surgical success, were evaluated and compared to thirty-seven patients treated with posterior lumbar interbody fusion (PLIF).

Results

The mean operation time of PEID was 93.00(77.00,110.00) min, while that of PLIF was 169.00(157.00,183.00) min. Continued improvement in both PEID and PLIF was observed in the VAS and ODI scores immediately after the surgery to the last follow‐up. The VAS and ODI scores of PEID one week after surgery were significantly different from those of PLIF. One patient with recurrent lumbar disc herniation in the same segment improved after undergoing repeat PEID, two patients had dura tears, and conservative treatment helped relieve the symptoms. The overall percentage of patients with good to excellent results of PELD according to the modified MacNab criteria was 97.43%, while that of PLIF was 94.60%.

Conclusions

PEID has reliable efficacy and safety for treating highly downward-migrated disc herniation. And the long-term efficacy of PEID is comparable to PLIF. No severe complications occurred after surgery, and most patients’ symptoms were relieved.
Current views on meningeal lymphatics and immunity in aging and Alzheimer’s disease
Authors: Rego Shanon , Sanchez Guadalupe , Da Mesquita Sandro
Published: August 2023

Alzheimer’s disease (AD) is an aging-related form of dementia associated with the accumulation of pathological aggregates of amyloid beta and neurofibrillary tangles in the brain. These phenomena are accompanied by exacerbated inflammation and marked neuronal loss, which altogether contribute to accelerated cognitive decline. The multifactorial nature of AD, allied to our still limited knowledge of its etiology and pathophysiology, have lessened our capacity to develop effective treatments for AD patients. Over the last few decades, genome wide association studies and biomarker development, alongside mechanistic experiments involving animal models, have identified different immune components that play key roles in the modulation of brain pathology in AD, affecting its progression and severity. As we will relay in this review, much of the recent efforts have been directed to better understanding the role of brain innate immunity, and particularly of microglia. However, and despite the lack of diversity within brain resident immune cells, the brain border tissues, especially the meninges, harbour a considerable number of different types and subtypes of adaptive and innate immune cells. Alongside microglia, which have taken the centre stage as important players in AD research, there is new and exciting evidence pointing to adaptive immune cells, namely T and B cells found in the brain and its meninges, as important modulators of neuroinflammation and neuronal (dys)function in AD. Importantly, a genuine and functional lymphatic vascular network is present around the brain in the outermost meningeal layer, the dura. The meningeal lymphatics are directly connected to the peripheral lymphatic system in different mammalian species, including humans, and play a crucial role in preserving a “healthy” immune surveillance of the CNS, by shaping immune responses, not only locally at the meninges, but also at the level of the brain tissue. In this review, we will provide a comprehensive view on our current knowledge about the meningeal lymphatic vasculature, emphasizing its described roles in modulating CNS fluid and macromolecule drainage, meningeal and brain immunity, as well as glial and neuronal function in aging and in AD.
Spectrum of diabetes mellitus in patients with Shwachman-Diamond syndrome: case report and review of the literature
Authors: Navasardyan Lusine V. , Furlan Ingrid , Brandt Stephanie , Schulz Ansgar , Wabitsch Martin , Denzer Christian
Published: August 2023

Background

Shwachman-Diamond syndrome (SDS) is a rare congenital disorder caused by mutations in the SBDS gene and characterized by exocrine pancreatic deficiency, hematologic dysfunction, and skeletal growth failure. Although the hematologic features and characteristics of the somatic disorders commonly associated with SDS are well known, emerging data from case reports and patient registries suggest that SDS may also be associated with an increased risk of diabetes mellitus. However, currently available data on SDS-associated diabetes are limited and do not allow conclusions regarding prevalence and incidence rates, clinical course, and outcomes.

Case presentation

Here we report the case of a 5-year-old girl with SDS who underwent bone marrow transplantation at the age of 3 months and developed autoantibody-positive type 1 diabetes mellitus at the age of 1.8 years. The manifestation and course of diabetes development were mild, complicated by concurrent spontaneous episodes of hypoglycemia even before the onset of antidiabetic treatment. Currently, adequate metabolic control can be achieved by dietary intervention.

Conclusions

Considering that the SBDS protein regulates mitosis and ribosomal biosynthesis and that its suppression may cause immunologic instability and chronic inflammation, this case provides insight into the phenotype of rare Shwachman-Diamond syndrome-associated diabetes mellitus, which may be characterized by significant age-dependent differences in clinical course.
Did the early full genome sequencing of yeast boost gene function discovery?
Authors: Tantoso Erwin , Eisenhaber Birgit , Sinha Swati , Jensen Lars Juhl , Eisenhaber Frank
Published: August 2023

Background

Although the genome of Saccharomyces cerevisiae (S. cerevisiae) was the first one of a eukaryote organism that was fully sequenced (in 1996), a complete understanding of the potential of encoded biomolecular mechanisms has not yet been achieved. Here, we wish to quantify how far the goal of a full list of S. cerevisiae gene functions still is.

Results

The scientific literature about S. cerevisiae protein-coding genes has been mapped onto the yeast genome via the mentioning of names for genomic regions in scientific publications. The match was quantified with the ratio of a given gene name’s occurrences to those of any gene names in the article. We find that ~ 230 elite genes with ≥ 75 full publication equivalents (FPEs, FPE = 1 is an idealized publication referring to just a single gene) command ~ 45% of all literature. At the same time, about two thirds of the genes (each with less than 10 FPEs) are described in just 12% of the literature (in average each such gene has just ~ 1.5% of the literature of an elite gene). About 600 genes have not been mentioned in any dedicated article. Compared with other groups of genes, the literature growth rates were highest for uncharacterized or understudied genes until late nineties of the twentieth century. Yet, these growth rates deteriorated and became negative thereafter. Thus, yeast function discovery for previously uncharacterized genes has returned to the level of ~ 1980. At the same time, literature for anyhow well-studied genes (with a threshold T10 (≥ 10 FPEs) and higher) remains steadily growing.

Conclusions

Did the early full genome sequencing of yeast boost gene function discovery? The data proves that the moment of publishing the full genome in reality coincides with the onset of decline of gene function discovery for previously uncharacterized genes. If the current status of literature about yeast molecular mechanisms can be extrapolated into the future, it will take about another ~ 50 years to complete the yeast gene function list. We found that a small group of scientific journals contributed extraordinarily to publishing early reports relevant to yeast gene function discoveries.
High-resolution melting (HRM)-based detection of polymorphisms in the malic enzyme and glucose-6-phosphate isomerase genes for Leishmania infantum genotyping
Authors: Buffi Gloria , Ceccarelli Marcello , Diotallevi Aurora , Abruzzese Michelalberto , Bruno Federica , Castelli Germano , Vitale Fabrizio , Andreoni Francesca , Bencardino Daniela , Magnani Mauro , Galluzzi Luca
Published: August 2023

Background

Leishmaniasis is a zoonotic disease endemic in the Mediterranean region where Leishmania infantum is the causative agent of human and canine infection. Characterization of this parasite at the subspecies level can be useful in epidemiological studies, to evaluate the clinical course of the disease (e.g. resistant strains, visceral and cutaneous forms of leishmaniasis) as well as to identify infection reservoirs. Multilocus enzyme electrophoresis (MLEE), a method currently recognized as the reference method for characterizing and identifying strains of Leishmania, is cumbersome and time-consuming and requires cultured parasites. These disadvantages have led to the development of other methods, such as multilocus microsatellite typing (MLMT) and multilocus sequence typing (MLST), for typing Leishmania parasites; however, these methods have not yet been applied for routine use. In this study, we first used MLST to identify informative polymorphisms on single-copy genes coding for metabolic enzymes, following which we developed two rapid genotyping assays based on high-resolution melting (HRM) analysis to explore these polymorphisms in L. infantum parasites.

Methods

A customized sequencing panel targeting 14 housekeeping genes was designed and MLST analysis was performed on nine L. infantum canine and human strains/isolates. Two quantitative real-time PCR-HRM assays were designed to analyze two informative polymorphisms on malic enzyme (ME) and glucose-6-phosphate isomerase (GPI) genes (390T/G and 1831A/G, respectively). The two assays were applied to 73 clinical samples/isolates from central/southern Italy and Pantelleria island, and the results were confirmed by DNA sequencing in a subset of samples.

Results

The MLST analysis, together with sequences available in the Genbank database, enabled the identification of two informative polymorphisms on the genes coding for ME and GPI. The fast screening of these polymorphisms using two HRM-based assays in 73 clinical samples/isolates resulted in the identification of seven genotypes. Overall, genotype 1 (sequence type 390T/1831G) was the most highly represented (45.2%) in the overall sample and correlated with the most common L. infantum zymodemes (MON-1, MON-72). Interestingly, in Pantelleria island, the most prevalent genotype (70.6%) was genotype 6 (sequence type 390T/1831A).

Conclusions

Applying our HRM assays on clinical samples allowed us to identify seven different genotypes without the need for parasite isolation and cultivation. We have demonstrated that these assays could be used as fast, routine and inexpensive tools for epidemiological surveillance of L. infantum or for the identification of new infection reservoirs.

Graphical abstract
Oral and nasal provocation test in chicken egg allergy—case report
Authors: Krzych-Fałta E. , Wojas O. , Samel-Kowalik P. , Samoliński B. , Sybilski A. , Białek S.
Published: August 2023

Introduction

Allergy to chicken egg protein is a common form of food allergy. The most common clinical presentation includes gastrointestinal, skin, and respiratory symptoms. Differential diagnosis, including provocative tests, is critical in diagnosis.

Case description

We present a case of a 21-year-old patient with egg allergy, who underwent a double-blind food provocation test with placebo (evaluating subjective complaints from the gastrointestinal tract) and a titrated nasal provocation test using dry chicken egg content. We assessed the response of the nasal mucosa in the provocation test using the visual analogue scale (VAS), acoustic and optical rhinometry, as well as measurements of nitric oxide concentration in the exhaled air. During the provocation test, we measured the changes in the transverse section of the nasal passages, which were accompanied by subjective complaints measured with the VAS scale, using objective techniques. In the nasal provocation test with a dose of 20 µg of chicken egg protein, we observed an increase in the reactivity of the nasal mucosa and a decrease in the level of nitric oxide in the exhaled air from the upper airways (920 ppb before the provocation test and up to 867 ppb during the early stage of the allergic reaction). During the provocation tests, we recorded typical symptoms associated with the early stage of the allergic reaction; including nasal obstruction (1.2 cm), leakage of watery discharge (0.8 cm) in the food test, and itchy nose (1.1 cm) in the food test vs. the nasal test: 4.6, 2.8, and 3.5 cm, respectively.

Conclusions

The nasal mucosa provides convenient conditions for evaluation of the severity of allergy to common food allergens, including chicken egg allergens.
Simulating the diameter growth responses of Larix gmelini Rupr. and Betula platyphylla Suk. to biotic and abiotic factors in secondary forests in Northeast China
Authors: Wang Tao , Xie Longfei , Miao Zheng , Dong Lihu , Hao Yuanshuo , Ma Aiyun , Li Fengri
Published: August 2023

Key message

The diameter growth of Dahurian larch (Larix gmelini Rupr.) and white birch (Betula platyphylla Suk.) species in secondary forest of Northeast China was not only influenced by biological factors such as tree size and stand characteristics, but also significantly affected by topographic and climatic factors such as temperature and precipitation. It is necessary to consider the abiotic factors in simulating the diameter growth.

Context

Climate change, such as global temperature rise, increased frequency of extreme weather events, and rising sea levels, has put forest ecosystems in an unstable state and has an impact on species composition, growth harvest, productivity and other functions of forests. And this impact varies in climate scenarios, regions and forest types.

Aims

To gain a comprehensive understanding of the adaptation for key species to their environment in secondary forests in Northeast China, the diameter growth responses of Dahurian larch and white birch to biotic and abiotic factors were simulated to assess the effects of climate on diameter growth.

Methods

China’s National Forest Continuous Inventory (NFCI) data from 2005 to 2015 were used to develop linear mixed-effects diameter growth models with plot-level random effects, and leave-one-out cross-validation was applied to evaluate the developed models. At the beginning of modeling, correlation analysis and best-subset regression were used to analyze the correlation between the diameter increment and the biotic and abiotic factors.

Results

(i) Sorting the categories of predictors in descending order based on the relative importance of the significant predictors, diameter growth of Dahurian larch was affected by competition, tree size, topographic conditions, stand attributes, diversity index, and climate factors, while the white birch species was affected by competition, tree size, stand attributes, climate factors, diversity index, and topographic conditions; (ii) the plot-level mixed-effects model, which achieved better fit and prediction performance than did basic linear models of individual-tree diameter growth in the cases of prediction calibration, was preferable for modeling individual-tree diameter growth; (iii) the prediction accuracy of the mixed-effects model increased gradually with increasing size of calibration sample, and the best sampling strategy was the use of nine random trees to calibrate and make predictions with the mixed-effects model for the larch and birch species; (iv) Dahurian larch was dominant in terms of interspecific competition, and the growth of this species was enhanced when it was grown with the birch.

Conclusion

In addition to biotic factors such as tree size and stand characteristics, the impact of climate on the growth of Dahurian larch and white birch should be considered in future management policies.
The cyclooxygenase-expressing mesenchyme resists intestinal epithelial injury by paracrine signaling
Authors: Wei Siting , Li Meng , Song Wanlu , Liu Jiaye , Yu Shicheng , Wang Yalong , Zhang Mengxian , Du Huijun , Liu Yuan , Liu Huidong , Fu Wei , Li Baojie , Chen Ye-Guang
Published: August 2023

Paracrine signals play pivotal roles in organ homeostasis. Mesenchymal stromal cells (MSCs) play a key role in regulating epithelium homeostasis in the intestine while their paracrine effects are poorly characterized. Here, we identified prostaglandin E2 (PGE2) secreted by cyclooxygenase (COX)-expressing MSCs as a vital factor to maintain the intestinal mucosal barrier. We found that MSCs-induced organoid swelling through paracrine effect in vitro, a process due to enhanced water adsorption and is mediated by the COX-PGE2-EP4 axis. To further explore the regulatory effect of this axis on the intestinal epithelial barrier in vivo, we established the conditional knockout mouse model to specifically delete COX in MSCs and found that PGE2 reduction downregulated the gene Muc2 and induced a gastric metaplasia-like phenotype. Moreover, PGE2 defects increased the susceptibility of intestinal epithelium to colitis. Our study uncovers the paracrine signaling of COX-expressing MSCs in intestinal mucosal barrier maintenance, providing a basis for understanding the role of mesenchymal cells in the pathophysiological function of the intestine.
Prefiltering-based reduced rank multiuser detection in uplink generalized spatial modulation massive MIMO system
Authors: Wu Wei-Chiang
Published: August 2023

Exploiting generalized spatial modulation in massive MIMO system, we develop an efficient uplink multiuser detection scheme. Different from the maximum likelihood detection algorithm, the spatial and temporal data in the proposed detection scheme are decoded in a sequential manner: At the front end of base station receiver, a bank of spatial filters is first employed to mitigate the multiuser interference using the benefits of large-scale antenna array. There then, a reduced rank generalized Eigen-value decomposition-based algorithm is proposed to identify the antennas activated at each user terminal. In the second stage, a least-squares-based multiuser detector is employed to decode the multiplexed temporal symbols. Both theoretical analysis and computer simulations are conducted to evaluate system performance in terms of correct identification probability and overall symbol error rate. Simulation results demonstrate that the proposed algorithm outperforms most of the existing algorithms yet the complexity is extensively reduced.
Channel and temporal-frequency attention UNet for monaural speech enhancement
Authors: Xu Shiyun , Zhang Zehua , Wang Mingjiang
Published: August 2023

The presence of noise and reverberation significantly impedes speech clarity and intelligibility. To mitigate these effects, numerous deep learning-based network models have been proposed for speech enhancement tasks aimed at improving speech quality. In this study, we propose a monaural speech enhancement model called the channel and temporal-frequency attention UNet (CTFUNet). CTFUNet takes the noisy spectrum as input and produces a complex ideal ratio mask (cIRM) as output. To improve the speech enhancement performance of CTFUNet, we employ multi-scale temporal-frequency processing to extract input speech spectrum features. We also utilize multi-conv head channel attention and residual channel attention to capture temporal-frequency and channel features. Moreover, we introduce the channel temporal-frequency skip connection to alleviate information loss between down-sampling and up-sampling. On the blind test set of the first deep noise suppression challenge, our proposed CTFUNet has better denoising performance than the champion models and the latest models. Furthermore, our model outperforms recent models such as Uformar and MTFAA in both denoising and dereverberation performance.
Causes and effects of the German energy transition in the context of environmental, societal, political, technological, and economic developments
Authors: Kappner Kai , Letmathe Peter , Weidinger Philipp
Published: August 2023

Background

As lignite mining protests and #FridaysForFuture demonstrations gained momentum in Germany and further protests have been developing over time, this paper investigates the various causes and effects of the country’s energy transition. Society and politics alongside economic, environmental, and technological developments have led to a profound and continuous transformation of the energy system, a transformation which is remarkable in terms of reach and speed for an economy of the size of Germany’s. Pressure to transform the country’s entire energy system even faster has recently been levelled due to the Russian invasion of Ukraine.

Results

From the perspective of the different pillars of sustainability and various stakeholder groups, this paper discusses the influences and their interdependencies towards the status quo of the German energy sector. We have used the cause-and-effect analysis method to answer the question of why major energy generators in Germany are still struggling with the energy transition, as well as the question of why a strategy towards more sustainability is needed to maintain Germany’s industrial strength in the long run. We found that energy transition in Germany is substantially driven by society, which pushes political decisions that lead to an economic transition, while environmental incidents are only triggers for further societal and political doings. Furthermore, technological developments fulfil only needs and do not necessarily hurry ahead of time.

Conclusions

Overall, the article creates a profound understanding of the factors influencing the German energy transition which is deeply embedded in the European energy system.
The progress of novel strategies on immune-based therapy in relapsed or refractory diffuse large B-cell lymphoma
Authors: Lu Tingxun , Zhang Jie , Xu-Monette Zijun Y. , Young Ken H.
Published: August 2023

Diffuse large B-cell lymphoma (DLBCL) can be cured with standard front-line immunochemotherapy, whereas nearly 30–40% of patients experience refractory or relapse. For several decades, the standard treatment strategy for fit relapsed/refractory (R/R) DLBCL patients has been high-dose chemotherapy followed by autologous hematopoietic stem cell transplant (auto-SCT). However, the patients who failed in salvage treatment or those ineligible for subsequent auto-SCT have dismal outcomes. Several immune-based therapies have been developed, including monoclonal antibodies, antibody–drug conjugates, bispecific T-cell engaging antibodies, chimeric antigen receptor T-cells, immune checkpoint inhibitors, and novel small molecules. Meanwhile, allogeneic SCT and radiotherapy are still necessary for disease control for fit patients with certain conditions. In this review, to expand clinical treatment options, we summarize the recent progress of immune-related therapies and prospect the future indirections in patients with R/R DLBCL.
The unique gut microbiome of giant pandas involved in protein metabolism contributes to the host’s dietary adaption to bamboo
Authors: Deng Feilong , Wang Chengdong , Li Desheng , Peng Yunjuan , Deng Linhua , Zhao Yunxiang , Zhang Zhihao , Wei Ming , Wu Kai , Zhao Jiangchao , Li Ying
Published: August 2023

Background

The gut microbiota of the giant panda (Ailuropoda melanoleuca), a global symbol of conservation, are believed to be involved in the host’s dietary switch to a fibrous bamboo diet. However, their exact roles are still largely unknown.

Results

In this study, we first comprehensively analyzed a large number of gut metagenomes giant pandas (n = 322), including 98 pandas sequenced in this study with deep sequencing (Illumina) and third-generation sequencing (nanopore). We reconstructed 408 metagenome-assembled genomes (MAGs), and 148 of which (36.27%) were near complete. The most abundant MAG was classified as Streptococcus alactolyticus. A pairwise comparison of the metagenomes and meta-transcriptomes in 14 feces revealed genes involved in carbohydrate metabolism were lower, but those involved in protein metabolism were greater in abundance and expression in giant pandas compared to those in herbivores and omnivores. Of note, S. alactolyticus was positively correlated to the KEGG modules of essential amino-acid biosynthesis. After being isolated from pandas and gavaged to mice, S. alactolyticus significantly increased the relative abundance of essential amino acids in mice jejunum.

Conclusions

The study highlights the unique protein metabolic profiles in the giant panda’s gut microbiome. The findings suggest that S. alactolyticus is an important player in the gut microbiota that contributes to the giant panda’s dietary adaptation by more involvement in protein rather than carbohydrate metabolism.
Dissection of transcriptomic and epigenetic heterogeneity of grade 4 gliomas: implications for prognosis
Authors: Zeng Chang , Song Xiao , Zhang Zhou , Cai Qinyun , Cai Jiajun , Horbinski Craig , Hu Bo , Cheng Shi-Yuan , Zhang Wei
Published: August 2023

Background

Grade 4 glioma is the most aggressive and currently incurable brain tumor with a median survival of one year in adult patients. Elucidating novel transcriptomic and epigenetic contributors to the molecular heterogeneity underlying its aggressiveness may lead to improved clinical outcomes.

Methods

To identify grade 4 glioma -associated 5-hydroxymethylcytosine (5hmC) and transcriptomic features as well as their cross-talks, genome-wide 5hmC and transcriptomic profiles of tissue samples from 61 patients with grade 4 gliomas and 9 normal controls were obtained for differential and co-regulation/co-modification analyses. Prognostic models on overall survival based on transcriptomic features and the 5hmC modifications summarized over genic regions (promoters, gene bodies) and brain-derived histone marks were developed using machine learning algorithms.

Results

Despite global reduction, the majority of differential 5hmC features showed higher modification levels in grade 4 gliomas as compared to normal controls. In addition, the bi-directional correlations between 5hmC modifications over promoter regions or gene bodies and gene expression were greatly disturbed in grade 4 gliomas regardless of IDH1 mutation status. Phenotype-associated co-regulated 5hmC–5hmC modules and 5hmC–mRNA modules not only are enriched with different molecular pathways that are indicative of the pathogenesis of grade 4 gliomas, but also are of prognostic significance comparable to IDH1 mutation status. Lastly, the best-performing 5hmC model can predict patient survival at a much higher accuracy (c-index = 74%) when compared to conventional prognostic factor IDH1 (c-index = 57%), capturing the molecular characteristics of tumors that are independent of IDH1 mutation status and gene expression-based molecular subtypes.

Conclusions

The 5hmC-based prognostic model could offer a robust tool to predict survival in patients with grade 4 gliomas, potentially outperforming existing prognostic factors such as IDH1 mutations. The crosstalk between 5hmC and gene expression revealed another layer of complexity underlying the molecular heterogeneity in grade 4 gliomas, offering opportunities for identifying novel therapeutic targets.
Aging changes in maxillary anterior teeth in untreated individuals: an observational longitudinal study
Authors: Natsumeda Gabriela , Miranda Felicia , Massaro Camila , Lauris José Roberto Pereira , Garib Daniela
Published: August 2023

Objective

The aging of the occlusion and tooth wears influence the smile design This study aimed at evaluating the aging changes of maxillary anterior teeth in nontreated subjects.

Methods

The sample comprised dental models of 23 subjects (13 male, 10 female) with normal occlusions, taken at 13 (T1), 17 (T2) and 61 (T3) years of age. The following variables were measured in the maxillary anterior teeth using digital dental models: crown width/height proportion, anterior view width, crown angulation, gingival and incisal steps between central/lateral incisors and central incisors/canines. Interphase comparisons were evaluated using repeated measures analysis of variance followed by Tukey tests or Friedman tests. Sexual differences were evaluated using t tests (P < 0.05).

Results

From 13 to 61 years of age, a decrease of crown width/height proportion (P = 0.008 and P =  < 0.001, for the lateral incisor and canines, respectively) and mesiodistal angulation (P =  < 0.001, P = 0.001 and P = 0.025 for the central incisor, lateral incisor and canines, respectively) of the maxillary anterior teeth were observed. The steps of the gingival margin and the incisal steps decreased with aging.

Conclusions

From adolescence to late adulthood, untreated individuals with normal occlusions demonstrated changes in the maxillary anterior teeth that may impair the smile esthetics and attractiveness.