bluuebunny/crossref_metadata_2025 huggingface dataset:
From lab to field: biological control of the Japanese beetle with entomopathogenic fungi
Authors: Graf Tanja , Scheibler Franziska , Niklaus Pascal A. , Grabenweger Giselher
Published: May 2023

The Japanese beetle, Popillia japonica, is an invasive scarab and listed as quarantine organism in many countries worldwide. Native to Japan, it has invaded North America, the Azores, and recently mainland Europe. Adults are gregarious and cause agricultural and horticultural losses by feeding on leaves, fruits, and flowers of a wide range of crops and ornamental plants. Larvae feed belowground and damage grassland. To date, no efficient and environmentally friendly control measure is available. Larval populations of other scarab species such as Phyllopertha horticola and Melolontha melolontha are controlled by applying spores of the entomopathogenic fungi Metarhizium brunneum and Beauveria brongniartii to larval habitats. Here, we tested this control strategy against Japanese beetle larvae in grasslands, as well as spore spray applications against adults in crops. Using both, large-scale field experiments and inoculation experiments in the laboratory, we assess the efficacy of registered fungal strains against Japanese beetle larvae and adults. Metarhizium brunneum BIPESCO 5 established and persisted in the soil of larval habitats and on the leaves of adult’s host plants after application. However, neither larval nor adult population sizes were reduced at the study sites. Laboratory experiments showed that larvae are not susceptible to M. brunneum ART 212, M. brunneum BIPESCO 5, and B. brongniartii BIPESCO 2. In contrast, adults were highly susceptible to all three strains. When blastospores were directly injected into the hemolymph, both adults and larvae showed elevated mortality rates, which suggests that the cuticle plays an important role in determining the difference in susceptibility of the two life stages. In conclusion, we do not see potential in adapting the state-of-the-art control strategy against native scarabs to Japanese beetle larvae. However, adults are susceptible to the tested entomopathogenic fungi in laboratory settings and BIPESCO 5 conidiospores survived for more than three weeks in the field despite UV-radiation and elevated temperatures. Hence, control of adults using fungi of the genera Beauveria or Metarhizium is more promising than larval control. Further research on efficient application methods and more virulent and locally adapted fungal strains will help to increase efficacy of fungal treatments for the control of P. japonica.
Influence of shallow hydrothermal fluid release on the functioning of phytoplankton communities
Authors: Tilliette Chloé , Gazeau Frédéric , Portlock Gemma , Benavides Mar , Bonnet Sophie , Guigue Catherine , Leblond Nathalie , Lory Caroline , Marie Dominique , Montanes Maryline , Pulido-Villena Elvira , Sarthou Géraldine , Tedetti Marc , Vorrath Maria-Elena , Whitby Hannah , Guieu Cécile
Published: May 2023

In the Western Tropical South Pacific (WTSP) Ocean, a hotspot of dinitrogen fixation has been identified. The survival of diazotrophs depends, among others, on the availability of dissolved iron (DFe) largely originating, as recently revealed, from shallow hydrothermal sources located along the Tonga-Kermadec arc that fertilize the Lau Basin with this element. On the opposite, these fluids, released directly close to the photic layer, can introduce numerous trace metals at concentrations that can be toxic to surface communities. Here, we performed an innovative 9-day experiment in 300 L reactors onboard the TONGA expedition, to examine the effects of hydrothermal fluids on natural plankton communities in the WTSP Ocean. Different volumes of fluids were mixed with non-hydrothermally influenced surface waters (mixing ratio from 0 to 14.5%) and the response of the communities was studied by monitoring numerous stocks and fluxes (phytoplankton biomass, community composition, net community production, N2fixation, thiol production, organic carbon and metal concentrations in exported material). Despite an initial toxic effect of hydrothermal fluids on phytoplankton communities, these inputs led to higher net community production and N2fixation rates, as well as elevated export of organic matter relative to control. This fertilizing effect was achieved through detoxification of the environment, rich in potentially toxic elements (e.g., Cu, Cd, Hg), likely by resistantSynechococcusecotypes able to produce strong binding ligands, especially thiols (thioacetamide-like and glutathione-like compounds). The striking increase of thiols quickly after fluid addition likely detoxified the environment, rendering it more favorable for phytoplankton growth. Indeed, phytoplankton groups stressed by the addition of fluids were then able to recover important growth rates, probably favored by the supply of numerous fertilizing trace metals (notably Fe) from hydrothermal fluids and new nitrogen provided by N2fixation. These experimental results are in good agreement within-situobservations, proving the causal link between the supply of hydrothermal fluids emitted at shallow depth into the surface layer and the intense biological productivity largely supported by diazotrophs in the WTSP Ocean. This study highlights the importance of considering shallow hydrothermal systems for a better understanding of the biological carbon pump.
Marine N2O cycling from high spatial resolution concentration, stable isotopic and isotopomer measurements along a meridional transect in the eastern Pacific Ocean
Authors: Bourbonnais Annie , Chang Bonnie X. , Sonnerup Rolf E. , Doney Scott C. , Altabet Mark A.
Published: May 2023

Nitrous oxide (N2O) is a potent greenhouse gas and ozone depleting substance, with the ocean accounting for about one third of global emissions. In marine environments, a significant amount of N2O is produced by biological processes in Oxygen Deficient Zones (ODZs). While recent technological advances are making surface N2O concentration more available, high temporal and spatial resolution water-column N2O concentration data are relatively scarce, limiting global N2O ocean models’ predictive capability. We present a N2O concentration, stable isotopic composition and isotopomer dataset of unprecedently large spatial coverage and depth resolution in the broader Pacific, crossing both the eastern tropical South and North Pacific Ocean ODZs collected as part of the GO-SHIP P18 repeat hydrography program in 2016/2017. We complement these data with dissolved gases (nitrogen, oxygen, argon) and nitrate isotope data to investigate the pathways controlling N2O production in relation to apparent oxygen utilization and fixed nitrogen loss. N2O yield significantly increased under low oxygen conditions near the ODZs. Keeling plot analysis revealed different N2O sources above the ODZs under different oxygen regimes. Our stable isotopic data and relationships between the N2O added by microbial processes (ΔN2O) and dissolved inorganic nitrogen (DIN) deficit confirm increased N2O production by denitrification under low oxygen conditions near the oxycline where the largest N2O accumulations were observed. The slope for δ18O-N2O versus site preference (SP, the difference between the central (α) and outer (β) N atoms in the linear N2O molecule) in the eastern tropical North Pacific ODZ was lower than expected for pure N2O reduction, likely because of the observed decrease in δ15Nβ. This trend is consistent with prior ODZ studies and attributed to concurrent production of N2O from nitrite with a low δ15N or denitrification with a SP >0‰. We estimated apparent isotope effects for N2O consumption in the ETNP ODZ of 3.6‰ for 15Nbulk, 9.4‰ for 15Nα, -2.3‰ for 15Nβ, 12.0‰ for 18O, and 11.7‰ for SP. These values were generally within ranges previously reported for previous laboratory and field experiments.
Distribution of gold derived from hydrothermal fluids on the modern seafloor and its impact on the gold budget of seawater
Authors: Huang Wei , Liang Jin , Lu Jingfang , Hou Fanghui , Li Panfeng , Cui Ruyong
Published: May 2023

The modern seafloor hydrothermal system plays a significant role in the cycling of energy and mass between the internal and external layers of the oceanic crust and upper mantle. It continues to supply hydrothermal fluids containing three to five orders of magnitude more gold into the ocean than the amount typically present in deep seawater. It has a considerable impact on the distribution and budget of gold with respect to the large geological inventory of the ocean along with other input sources such as river water. The large amount of various types of data compiled for this study reveals that only about 0.3% of the annual hydrothermal flux of gold (2618.3 kg/a) injected into the overlying seawater column as a dissolved phase is eventually trapped in sulfide deposits near vent sites on the seafloor, while about 0.8% is trapped in metalliferous sediments that fall out from the distal nonbuoyant plume. The remaining ~98.9% of gold is delivered into the depths of the global open ocean. The global budget of gold in seawater (about 1.4 × 107 kg), the annual flux of hydrothermal fluids at the seafloor (about 2.6 × 103 kg/a), the amount delivered by river water (about 7.2 × 104 kg/a), and significant estuarine removal (15%) allows us to estimate the residence time of gold in the modern ocean to be about 220 years. This value is 70% shorter than that (~1000 years) reported previously. In the future, the use of appropriate artificial means to achieve more efficient precipitation of gold from the hydrothermal system at the seafloor could increase the level of enrichment of gold to obtain gold-rich hydrothermal deposits, yielding greater economic benefits.
Thermal performance of thermoplastic polyurethane composites with microencapsulated piperazine pyrophosphate
Authors: Hu Shuang , Peng Jianwen , Tian Jianjun , Xiao Chong
Published: May 2023

This study synthesized and investigated the efficacy of a novel flame retardant, melamine formaldehyde microencapsulated piperazine pyrophosphate (MFPAPP), in improving the thermal and flame-retardant properties of thermoplastic polyurethane (TPU). When TPU was incorporated with 30wt% MFPAPP, the limiting oxygen index (LOI) value of the TPU/MFPAPP composite increased to 38.8%, achieving a V-0 rating. The thermogravimetric test (TG) results confirmed that MFPAPP significantly enhanced the thermal stability of the TPU/MFPAPP composite, as indicated by the increased char residue at 800°C, which was up to 22.4wt%. Compared with the pure TPU samples, the peak heat release rate (PHRR) and total heat release (THR) of TPU/MFPAPP30 decreased by 53% and 45%, respectively. TPU/MFPAPP10 maintained a V-0 rating after the water immersion test, whereas TPU/PAPP degraded to a V-2 rating. Scanning electron microscopy (SEM), Raman spectra, and X-ray photoelectron spectroscopy analyses revealed that MFPAPP promoted the formation of heat-resistant and dense expanded carbon layers. In summary, MFPAPP demonstrated remarkable flame retardancy and thermal stability, making it an ideal candidate for enhancing the fire safety of TPU materials.
Validation of the neuroconnective endophenotype questionnaire (NEQ): a new clinical tool for medicine and psychiatry resulting from the contribution of Ehlers–Danlos syndrome
Authors: Bulbena Antonio , Rosado Silvia , Cabaleiro Marina , Martinez María , Baeza-Velasco Carolina , Martin Luis-Miguel , Batlle Santiago , Bulbena-Cabré Andrea
Published: May 2023

Introduction

The link between anxiety disorders and joint hypermobility syndrome (now under hypermobility spectrum disorders, which include hypermobile Ehlers–Danlos syndrome) has been widely replicated over the past 30 years and has grown beyond the initial nosological limits. To integrate clinical and research progress in this field, a new neuroconnective endophenotype (NE) and its corresponding instrument, the Neuroconnective Endophenotype Questionnaire (NEQ), have been developed. This new clinical construct, created with the active participation of patients, includes both somatic and psychological dimensions and symptoms and resilience items.

Methods

The NE includes five dimensions: (1) sensorial sensitivity, (2) body signs and symptoms, (3) somatic conditions, (4) polar behavioral strategies, and (5) psychological and psychopathological dimensions. The NEQ information is collected through four self-administered questionnaires (sensorial sensitivity, body signs and symptoms, polar behavioral strategies, and psychological characteristics) and a structured diagnostic part that should be completed by a trained observer. This hetero-administered part incorporates (a) psychiatric diagnoses (using structured criteria, e.g., MINI), (b) somatic disorders diagnosis, using structured criteria, and (c) assessment of joint hypermobility criteria.

Results

In a sample of 36 anxiety cases with 36 matched controls, the NEQ obtained high scores for test–retest, inter-rater reliability, and internal consistency. As for predictive validity, cases and controls significantly differed in all five dimensions and hypermobility measurements.

Discussion

We can conclude that the NEQ has achieved acceptable reliability and validity values and, therefore, is ready to be used and tested in different samples. This original and consistent construct including somatic and mental items may improve clinical specificity, the search for more comprehensive therapies, and their genetic and neuroimaging bases.
Minimal change disease associated with thyroid cancer: a case report
Authors: Cai Xiaoyi , Wu Yuenv , Wan Qijun , Zhang Xiuli
Published: May 2023

A patient complaining of edema of the face and lower extremities was admitted to the nephrology department for nephrotic syndrome. Renal biopsy revealed findings of minimal change disease (MCD). Thyroid ultrasound showed a hypoechoic 16 × 13 mm nodule in the right lobe, suspicious of malignancy. Later, total thyroidectomy confirmed the diagnosis of papillary thyroid carcinoma (PTC). After surgery, MCD remitted rapidly and completely, strongly suggesting the diagnosis of MCD secondary to PTC. We report here the first adult case of the paraneoplastic finding of MCD secondary to PTC. Additionally, we discuss the possible role of the BRAF gene in the pathophysiology of PTC-associated MCD in this case and highlight the importance of tumor screening.
Oral voriconazole monotherapy for fungal keratitis: efficacy, safety, and factors associated with outcomes
Authors: Cai Youran , Song Shimei , Chen Yiying , Xu Xuyang , Zou Wenjin
Published: May 2023

Purpose

To provide preliminary data on the efficacy and safety of oral voriconazole (VCZ) as a primary treatment for fungal keratitis (FK).

Method

We performed a retrospective histopathological analysis of data on 90 patients with FK at The First Affiliated Hospital of Guangxi Medical University between September 2018 and February 2022. We recorded three outcomes: corneal epithelial healing, visual acuity (VA) improvement, and corneal perforation. Independent predictors were identified using univariate analysis, and multivariate logistic regression analysis was used to identify independent predictive factors associated with the three outcomes. The area under the curve was used to evaluate the predictive value of these factors.

Results

Ninety patients were treated with VCZ tablets as the only antifungal drug. Overall, 71.1% (n = 64) of the patients had extreme corneal epithelial healing, 56.7% (n = 51) showed an improvement in VA, and 14.4% (n = 13) developed perforation during treatment. Non-cured patients were more likely to have large ulcers (≥5 × 5 mm2) and hypopyon.

Conclusion

The results indicated that oral VCZ monotherapy was successful in the patients with FK in our study. Patients with ulcers larger than 5 × 5 mm2 and hypopyon were less likely to respond to this treatment.
Association of psoriasis with chronic kidney disease and end-stage renal disease: a systematic review and meta-analysis
Authors: Jing Xu , Zhuyuan Wen , Aijun Chen , Jianxia Xiong , Kun Huang , Ping Wang
Published: May 2023

Background and objective

Previous studies have shown that patients with psoriasis are at higher risk of developing chronic kidney disease (CKD) and end-stage renal disease (ESRD) compared with general population; however, data on the differences in the occurrence of CKD and ESRD between patients with psoriasis and non-psoriatic controls are limited and inconsistent. The aim of this study was to carry out a comparison of the probability of suffering CKD and ESRD in patients with or without psoriasis by conducting a meta-analysis of cohort studies.

Methods

Cohort studies on PubMed, Web of Science, Embase and Cochrane Library by March, 2023 were searched for. The studies were screened according to pre-established inclusion criteria. Hazard ratios (HRs) and a 95% confidence intervals (CIs) for the renal outcomes among patients with psoriasis were calculated using the random-effect, generic inverse variance method. Subgroup analysis was related to the severity of psoriasis.

Results

A total of seven retrospective cohort studies were included, including 738,104 psoriasis patients and 3,443,438 non-psoriasis subjects, published from 2013 to 2020. Compared to controls without psoriasis, patients with psoriasis had an increased risk of CKD and ESRD, with pooled hazard ratios of 1.65 (95% CI, 1.29–2.12) and 1.37 (95% CI, 1.14–1.64), respectively. Besides, the incidence of CKD and ESRD is positively correlated with the severity of psoriasis.

Conclusion

This study showed that compared to patients without psoriasis, patients with psoriasis, especially those with severe psoriasis, had a significantly increased risk of developing CKD and ESRD. Considering the limitations of this meta-analysis, more high-quality and well-designed studies are needed in the future to validate our findings.
Chikungunya virus infection induces ultrastructural changes and impaired neuronal differentiation of human neurospheres
Authors: de Lima Cavalcanti Thaíse Yasmine Vasconcelos , Azevedo Elisa de Almeida Neves , Lima Morganna Costa , Saraiva Karina Lidiane Alcântara , Franca Rafael Freitas Oliveira
Published: May 2023

Chikungunya virus (CHIKV) is an arthropod-borne virus recently associated with large outbreaks in many parts of the world. Infection is typically manifested as a febrile and self-limited illness, characterized by joint pain and myalgia, albeit severe neurological manifestations are also reported. Although CHIKV is not recognized as a truly neurotropic virus, neurons, astrocytes, and oligodendrocytes are susceptible to infection in vitro. Here we employed a model of 3D cell culture to obtain neurospheres from ATRA/BNDF differentiated human neuroblastoma cells. We demonstrate that CHIKV is able to establish a productive infection, resulting in ultrastructural changes in cell morphology and impaired neuronal differentiation. Ultrastructural analysis of neurospheres infected with CHIKV during neuronal differentiation revealed diminished neuron dendrite formation, accumulation of viral particles associated with the plasma membrane, numerous cell vacuoles, and swollen mitochondria. Apoptotic cells were significantly increased at 72 h post-infection. Compared to Zika virus, a well-characterized neurotropic arbovirus, CHIKV infection resulted in a more discrete, albeit detectable upregulation of IL-6 levels. Finally, we found that CHIKV infection resulted in an altered profile expression, mainly downregulation, of a group of transcription factors named Hox genes. Altogether our findings highlight important features of CHIKV in the CNS, as well as the feasibility of neurospheres as robust experimental models that can support further studies for novel pharmacological interventions.
Bifidobacterium: a probiotic for the prevention and treatment of depression
Authors: Li Jiayu , Wang Junyu , Wang Meiyu , Zheng Li , Cen Qiuyu , Wang Fangfang , Zhu Li , Pang Rizhao , Zhang Anren
Published: May 2023

Depression is a common psychological disease, which has become one of the main factors affecting human health. It has a serious impact on individuals, families, and society. With the prevalence of COVID-19, the incidence of depression has further increased worldwide. It has been confirmed that probiotics play a role in preventing and treating depression. Especially, Bifidobacterium is the most widely used probiotic and has positive effects on the treatment of depression. The mechanisms underlying its antidepressant effects might include anti-inflammation and regulation of tryptophan metabolism, 5-hydroxytryptamine synthesis, and the hypothalamus-pituitary–adrenal axis. In this mini-review, the relationship between Bifidobacterium and depression was summarized. It is hoped that Bifidobacterium-related preparations would play a positive role in the prevention and treatment of depression in the future.
Self-assembling and pH-responsive protein nanoparticle as potential platform for targeted tumor therapy
Authors: Xu Zhikun , Zhang Xiaozhan , Dong Wang , lv Huifang , Zuo Lijie , Zhu Lifei , Wang Ruining , Ma Xia
Published: May 2023

Frequent injections at high concentrations are often required for many therapeutic proteins due to their short in vivo half-life, which usually leads to unsatisfactory therapeutic outcomes, adverse side effects, high cost, and poor patient compliance. Herein we report a supramolecular strategy, self-assembling and pH regulated fusion protein to extend the in vivo half-life and tumor targeting ability of a therapeutically important protein trichosanthin (TCS). TCS was genetically fused to the N-terminus of a self-assembling protein, Sup35p prion domain (Sup35), to form a fusion protein of TCS-Sup35 that self-assembled into uniform spherical TCS-Sup35 nanoparticles (TCS-Sup35 NP) rather than classic nanofibrils. Importantly, due to the pH response ability, TCS-Sup35 NP well retained the bioactivity of TCS and possessed a 21.5-fold longer in vivo half-life than native TCS in a mouse model. As a result, in a tumor-bearing mouse model, TCS-Sup35 NP exhibited significantly improved tumor accumulation and antitumor activity without detectable systemic toxicity as compared with native TCS. These findings suggest that self-assembling and pH responding protein fusion may provide a new, simple, general, and effective solution to remarkably improve the pharmacological performance of therapeutic proteins with short circulation half-lives.
The influence of the ultrasonic treatment of working fluids on electrospun amorphous solid dispersions
Authors: Wang Haibin , Lu Yingying , Yang Haisong , Yu Deng-Guang , Lu Xuhua
Published: May 2023

Based on a working fluid consisting of a poorly water-soluble drug and a pharmaceutical polymer in an organic solvent, electrospinning has been widely exploited to create a variety of amorphous solid dispersions However, there have been very few reports about how to prepare the working fluid in a reasonable manner. In this study, an investigation was conducted to determine the influences of ultrasonic fluid pretreatment on the quality of resultant ASDs fabricated from the working fluids. SEM results demonstrated that nanofiber-based amorphous solid dispersions from the treated fluids treated amorphous solid dispersions exhibited better quality than the traditional nanofibers from untreated fluids in the following aspects: 1) a straighter linear morphology; 2) a smooth surface; and 3) a more evener diameter distribution. The fabrication mechanism associated with the influences of ultrasonic treatments of working fluids on the resultant nanofibers’ quality is suggested. Although XRD and ATR–FTIR experiments clearly verified that the drug ketoprofen was homogeneously distributed all over the TASDs and the traditional nanofibers in an amorphous state regardless of the ultrasonic treatments, the in vitro dissolution tests clearly demonstrated that the TASDs had a better sustained drug release performance than the traditional nanofibers in terms of the initial release rate and the sustained release time periods.
Sex-specific extracerebral complications in patients with aneurysmal subarachnoid hemorrhage
Authors: Bögli Stefan Y. , Beham Sabrina , Hirsbrunner Laura , Nellessen Friederike , Casagrande Francesca , Keller Emanuela , Brandi Giovanna
Published: May 2023

Background

Extracerebral complications in patients with aneurysmal subarachnoid hemorrhage (aSAH) often occur during their stay at the neurocritical care unit (NCCU). Their influence on outcomes is poorly studied. The identification of sex-specific extracerebral complications in patients with aSAH and their impact on outcomes might aid more personalized monitoring and therapy strategies, aiming to improve outcomes.

Methods

Consecutive patients with aSAH admitted to the NCCU over a 6-year period were evaluated for the occurrence of extracerebral complications (according to prespecified criteria). Outcomes were assessed with the Glasgow Outcome Scale Extended (GOSE) at 3 months and dichotomized as favorable (GOSE 5–8) and unfavorable (GOSE 1–4). Sex-specific extracerebral complications and their impact on outcomes were investigated. Based on the results of the univariate analysis, a multivariate analysis with unfavorable outcomes or the occurrence of certain complications as dependent variables was performed.

Results

Overall, 343 patients were included. Most of them were women (63.6%), and they were older than men. Demographics, presence of comorbidities, radiological findings, severity of bleeding, and aneurysm-securing strategies were compared among the sexes. More women than men suffered from cardiac complications (p = 0.013) and infection (p = 0.048). Patients with unfavorable outcomes were more likely to suffer from cardiac (p < 0.001), respiratory (p < 0.001), hepatic/gastrointestinal (p = 0.023), and hematological (p = 0.021) complications. In the multivariable analysis, known factors including age, female sex, increasing number of comorbidities, increasing World Federation of Neurosurgical Societies (WFNS), and Fisher grading were expectedly associated with unfavorable outcomes. When adding complications to these models, these factors remained significant. However, when considering the complications, only pulmonary and cardiac complications remained independently associated with unfavorable outcomes.

Conclusion

Extracerebral complications after aSAH are frequent. Cardiac and pulmonary complications are independent predictors of unfavorable outcomes. Sex-specific extracerebral complications in patients with aSAH exist. Women suffered more frequently from cardiac and infectious complications potentially explaining the worse outcomes.
Neural mechanisms of temporal and rhythmic structure processing in non-musicians
Authors: Radchenko Grigoriy , Demareva Valeriia , Gromov Kirill , Zayceva Irina , Rulev Artem , Zhukova Marina , Demarev Andrey
Published: May 2023

Music is increasingly being used as a therapeutic tool in the field of rehabilitation medicine and psychophysiology. One of the main key components of music is its temporal organization. The characteristics of neurocognitive processes during music perception of meter in different tempo variations technique have been studied by using the event-related potentials technique. The study involved 20 volunteers (6 men, the median age of the participants was 23  years). The participants were asked to listen to 4 experimental series that differed in tempo (fast vs. slow) and meter (duple vs. triple). Each series consisted of 625 audio stimuli, 85% of which were organized with a standard metric structure (standard stimulus) while 15% included unexpected accents (deviant stimulus). The results revealed that the type of metric structure influences the detection of the change in stimuli. The analysis showed that the N200 wave occurred significantly faster for stimuli with duple meter and fast tempo and was the slowest for stimuli with triple meter and fast pace.
Bioinformatic identification of hub genes Myd88 and Ccl3 and TWS-119 as a potential agent for the treatment of massive cerebral infarction
Authors: Guo Ai , Gao Bin , Zhang Mengting , Shi Xiaoyu , Jin Weina , Tian Decai
Published: May 2023

Background

Massive cerebral infarction (MCI) causes severe neurological deficits, coma and can even result in death. Here, we identified hub genes and pathways after MCI by analyzing microarray data from a murine model of ischemic stroke and identified potential therapeutic agents for the treatment of MCI.

Methods

Microarray expression profiling was performed using the GSE28731 and GSE32529 datasets from the Gene Expression Omnibus (GEO) database. Data from a sham group (n = 6 mice) and a middle cerebral artery occlusion (MCAO) group (n = 7 mice) were extracted to identify common differentially expressed genes (DEGs). After identifying gene interactions, we generated a protein-protein interaction (PPI) network with Cytoscape software. Then, the MCODE plug-in in Cytoscape was used to determine key sub-modules according to MCODE scores. Enrichment analyses were then conducted on DEGs in the key sub-modules to evaluate their biological functions. Furthermore, hub genes were identified by generating the intersections of several algorithms in the cytohubba plug-in; these genes were then verified in other datasets. Finally, we used Connectivity MAP (CMap) to identify potential agents for MCI therapy.

Results

A total of 215 common DEGs were identified and a PPI network was generated with 154 nodes and 947 edges. The most significant key sub-module had 24 nodes and 221 edges. Gene ontology (GO) analysis showed that the DEGs in this sub-module showed enrichment in inflammatory response, extracellular space and cytokine activity in terms of biological process, cellular component and molecular function, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that TNF signaling was the most enriched pathway. Myd88 and Ccl3 were identified as hub genes and TWS-119 was identified as the most potential therapeutic agent by CMap.

Conclusions

Bioinformatic analysis identified two hub genes (Myd88 and Ccl3) for ischemic injury. Further analysis identified TWS-119 as the best potential candidate for MCI therapy and that this target may be associated with TLR/MyD88 signaling.
The human brain through the lens of somatic mosaicism
Authors: Bizzotto Sara
Published: May 2023

Every cell in the human brain possesses a unique genome that is the product of the accumulation of somatic mutations starting from the first postzygotic cell division and continuing throughout life. Somatic mosaicism in the human brain has been the focus of several recent efforts that took advantage of key technological innovations to start elucidating brain development, aging and disease directly in human tissue. On one side, somatic mutation occurring in progenitor cells has been used as a natural barcoding system to address cell phylogenies of clone formation and cell segregation in the brain lineage. On the other side, analyses of mutation rates and patterns in the genome of brain cells have revealed mechanisms of brain aging and disorder predisposition. In addition to the study of somatic mosaicism in the normal human brain, the contribution of somatic mutation has been investigated in both developmental neuropsychiatric and neurodegenerative disorders. This review starts with a methodological perspective on the study of somatic mosaicism to then cover the most recent findings in brain development and aging, and ends with the role of somatic mutations in brain disease. Thus, this review underlies what we have learned and what is still possible to discover by looking at somatic mosaicism in the brain genome.
Cell-autonomous and differential endocannabinoid signaling impacts the development of presynaptic retinal ganglion cell axon connectivity in vivo
Authors: Del Rio Rodrigo , Serrano Rosa G. , Gomez Eric , Martinez Joshua C. , Edward Marina A. , Santos Rommel A. , Diaz Kenneth S. , Cohen-Cory Susana
Published: May 2023

Cannabis exposure during gestation evokes significant molecular modifications to neurodevelopmental programs leading to neurophysiological and behavioral abnormalities in humans. The main neuronal receptor for Δ9-tetrahydrocannabinol (THC) is the type-1 cannabinoid receptor CB1R, one of the most abundant G-protein-coupled receptors in the nervous system. While THC is the major psychoactive phytocannabinoid, endocannabinoids (eCBs) are the endogenous ligands of CB1R and are known to act as retrograde messengers to modulate synaptic plasticity at different time scales in the adult brain. Accumulating evidence indicates that eCB signaling through activation of CB1R plays a central role in neural development. During development, most CB1R localized to axons of projection neurons, and in mice eCB signaling impacts axon fasciculation. Understanding of eCB-mediated structural plasticity during development, however, requires the identification of the precise spatial and temporal dynamics of CB1R-mediated modifications at the level of individual neurons in the intact brain. Here, the cell-autonomous role of CB1R and the effects of CB1R-mediated eCB signaling were investigated using targeted single-cell knockdown and pharmacologic treatments in Xenopus. We imaged axonal arbors of retinal ganglion cells (RGCs) in real time following downregulation of CB1R via morpholino (MO) knockdown. We also analyzed RGC axons with altered eCB signaling following treatment with URB597, a selective inhibitor of the enzyme that degrades Anandamide (AEA), or JZL184, an inhibitor of the enzyme that blocks 2-Arachidonoylglycerol (2-AG) hydrolysis, at two distinct stages of retinotectal development. Our results demonstrate that CB1R knockdown impacts RGC axon branching at their target and that differential 2-AG and AEA-mediated eCB signaling contributes to presynaptic structural connectivity at the time that axons terminate and when retinotectal synaptic connections are made. Altering CB1R levels through CB1R MO knockdown similarly impacted dendritic morphology of tectal neurons, thus supporting both pre- and postsynaptic cell-autonomous roles for CB1R-mediated eCB signaling.
Best treatment options for occult breast cancer: A meta-analysis
Authors: Wang Rong , Yang Hong-xin , Chen Jie , Huang Jian-jun , Lv Qing
Published: May 2023

Objectives

Occult breast cancer (OBC) is a rare malignant breast tumor. Because of the rare cases and limited clinical experience, a huge therapeutic difference has existed all over the world and standardized treatments have yet been established.

Methods

A meta-analysis was conducted using MEDLINE and Embase databases to identify the choice of OBC surgical procedures in all studies: (1) patients undergoing axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB) only; (2) patients undergoing ALND with radiotherapy (RT); (3) patients undergoing ALND with breast surgery (BS); (4) patients undergoing ALND with RT and BS; and (5) patients undergoing observation or RT only. The primary endpoints were mortality rates, the second endpoints were distant metastasis and locoregional recurrence.

Results

Among the 3,476 patients, 493 (14.2%) undergo ALND or SLNB only; 632 (18.2%) undergo ALND with RT; 1483 (42.7%) undergo ALND with BS; 467 (13.4%) undergo ALND RT and BS, and 401 (11.5%) undergo observation or RT only. After comparing the multiple groups, both groups 1 and 3 have higher mortality rates than group 4 (30.7% vs. 18.6%, p < 0.0001; 25.1% vs. 18.6%, p = 0.007), and group 1 has higher mortality rates than groups 2 and 3 (30.7% vs.14.7%, p < 0.00001; 30.7 vs. 19.4%, p < 0.0001). Group (1 + 3) had a prognosis advantage over group 5 (21.4% vs. 31.0%, p < 0.00001). There was no significant difference both in the distant recurrence rates and locoregional rates between group (1 + 3) and group (2 + 4) (21.0% vs. 9.7%, p = 0.06; 12.3% vs. 6.5%, p = 0.26).

Conclusion

On the basis of this meta-analysis, our study indicates that BS including modified radical mastectomy (MRM) and breast-conserving surgery (BCS) combined RT may appear as the optimal surgical approach in patients with OBC. RT cannot prolong both the time of distant metastasis and the local recurrences.
Interval observers design for systems with ostensible Metzler system matrices
Authors: Krokavec Dušan , Filasová Anna
Published: May 2023

This paper attempts to resolve the problem concerning the interval observers design for linear systems with ostensible Metzler system matrices. Because system dynamics matrices are partially different from strictly Metzler structures, a solution is achieved by constructing a composed system matrix representation, which combines pre-compensated interval matrix structures fixed with a prescribed region of D-stability and the reconstructed strictly Metzler matrix structure, related to the original interval system matrix parameter definition. A novel design procedure is presented, which results in a strictly positive observer gain matrix and guarantees that the lower estimates of the positive state variables are non-negative when considering the given system structure and the non-negative system state initial values. The design is computationally simple since it is reduced to the feasibility of the set of linear matrix inequalities.
The burden of congenital birth defects between 1990 and 2019 in China: an observational study
Authors: Zhao Yajun , Zhang Haonan , Peng Minghui , Zhou Yemei , Cheng Xuelin , Yang Shijia , Zhang Zhaoyu , Liu Ming , Li Xiaopan , Jiang Sunfang
Published: May 2023

Background

Congenital birth defects (CBDs) are a major public health issue. This study aims to assess trends in the burden of CBDs between 1990 and 2019 across China based on the Global Burden of Disease Study 2019 (GBD 2019).

Methods

Indicators of the burden of CBDs included incidence, mortality, and disability-adjusted life years (DALYs). Metrics included number, rate, and age-standardized rate with 95% uncertainty intervals (UIs). Data were stratified by region [China, global, high-, middle-, low-socio-demographic index (SDI)], age, sex, and type of CBD. Average annual percentage changes (AAPC) and trends were evaluated.

Results

In China, between 1990 and 2019, the age-standardized incidence rate for CBDs showed an increasing trend, with an AAPC of 0.26% (0.11% to 0.41%), reaching 148.12 per 105 person-years (124.03 to 176.33) in 2019. Most CBDs were congenital heart anomalies, with an AAPC of 0.12% (−0.08% to 0.32%). The age-standardized mortality rate for CBDs showed a decreasing trend, with an AAPC of −4.57% (−4.97% to −4.17%), reaching 4.62 per 105 person-years (3.88 to 5.57) in 2019. Most mortality was associated with congenital heart anomalies, with an AAPC of −3.77% (−4.35% to −3.19%). The age-standardized DALYs rate for CBDs showed a decreasing trend, with an AAPC of −3.74% (−3.95% to −3.52%), reaching 480.95 per 105 person-years (407.69 to 570.04) in 2019.

Conclusions

Morbidity associated with CBDs increased in China between 1990 and 2019, accelerated by the adoption of the two-child policy, and ranked high globally. These findings emphasize the need for prenatal screening and primary and secondary prevention strategies.
Alterations of the Ca2+ clearing mechanisms by type 2 diabetes in aortic smooth muscle cells of Zucker diabetic fatty rat
Authors: Moreno-Salgado Adriana , Coyotl-Santiago Nayeli , Moreno-Vazquez Roberto , Lopez-Teyssier Mayte , Garcia-Carrasco Mario , Moccia Francesco , Berra-Romani Roberto
Published: May 2023

Type 2 Diabetes Mellitus (T2DM) is a rapidly rising disease with cardiovascular complications constituting the most common cause of death among diabetic patients. Chronic hyperglycemia can induce vascular dysfunction through damage of the components of the vascular wall, such as vascular smooth muscle cells (VSMCs), which regulate vascular tone and contribute to vascular repair and remodeling. These functions are dependent on intracellular Ca2+ changes. The mechanisms by which T2DM affects Ca2+ handling in VSMCs still remain poorly understood. Therefore, the objective of this study was to determine whether and how T2DM affects Ca2+ homeostasis in VSMCs. We evaluated intracellular Ca2+ signaling in VSMCs from Zucker Diabetic Fatty rats using Ca2+ imaging with Fura-2/AM. Our results indicate that T2DM decreases Ca2+ release from the sarcoplasmic reticulum (SR) and increases the activity of store-operated channels (SOCs). Moreover, we were able to identify an enhancement of the activity of the main Ca2+ extrusion mechanisms (SERCA, PMCA and NCX) during the early stage of the decay of the ATP-induced Ca2+ transient. In addition, we found an increase in Ca2+ entry through the reverse mode of NCX and a decrease in SERCA and PMCA activity during the late stage of the signal decay. These effects were appreciated as a shortening of ATP-induced Ca2+ transient during the early stage of the decay, as well as an increase in the amplitude of the following plateau. Enhanced cytosolic Ca2+ activity in VSMCs could contribute to vascular dysfunction associated with T2DM.
Improving the efficiency of phosphate rocks combined with phosphate solubilizing Actinomycetota to increase wheat growth under alkaline and acidic soils
Authors: Boubekri Kenza , Soumare Abdoulaye , Lyamlouli Karim , Ouhdouch Yedir , Hafidi Mohamed , Kouisni Lamfeddal
Published: May 2023

Low availability of phosphorus (P) in both acidic and alkaline soils is a major problem for sustainable improvement in wheat crops yield. Optimization of crops productivity can be achieved by increasing the bioavailability of P by phosphate solubilizing Actinomycetota (PSA). However, their effectiveness may vary with changing agro-climatic conditions. In this regard, a greenhouse experiment was conducted to assess the interaction inoculation of five potential PSA (P16-P18-BC3-BC10 and BC11) and RPs (RP1- RP2-RP3 and RP4) on the growth and yield of wheat crop in unsterilized P- deficient alkaline and acidic soils. Their performance was compared with single super phosphate (TSP) and reactive RP (BG4). The in-vitro tests showed that all PSA colonize wheat root and form a strong biofilm except Streptomyces anulatus strain P16. Our findings revealed that all PSA significantly improve the shoot/root dry weights, spike biomass, chlorophyll contents as well as nutrients uptake in plants fertilized with RP3 and RP4. However, the combined application of Nocardiopsis alba BC11 along with RP4 in alkaline soil, was effective in optimizing wheat yield attributes and improve the yield biomass up to 19.7% as compared to the triple superphosphate (TSP). This study supports the view that the inoculation with Nocardiopsis alba BC11 has a broad RP solubilization and could alleviate the agricultural losses due to P limitation in acidic and alkaline soils.
Investigating the impact of fungicides and mungbean genotypes on the management of pod rot disease caused by Fusarium equiseti and Fusarium chlamydosporum
Authors: Buttar Harwinder Singh , Singh Amarjit , Sirari Asmita , Anupam  , Kaur Komalpreet , Kumar Abhishek , Lal Milan Kumar , Tiwari Rahul Kumar , Kumar Ravinder
Published: May 2023

Introduction

Mungbean is a vital pulse crop in India that can thrive in dry-land conditions and is grown in three seasons, with the added benefit of being used as green manure due to its ability to fix atmospheric nitrogen. Recently, pod rot disease has emerged as a serious threat to mungbean cultivation in India.

Methods

In this study, morpho-molecular identification of associated pathogens and the bio-efficacy of systemic and non-systemic fungicides as well as genotype screening was performed during the years 2019 and 2020. The pathogens associated with this disease were confirmed on the basis of morphological and molecular characterization. For the molecular characterization, the translation elongation factor 1-alpha (tef-1) gene sequences were amplified by using primers (EF1 and EF2).

Results

Under in vitro conditions, trifloxystrobin + tebuconazole 75% WG was found to be the most effective against Fusarium equiseti (ED50 2.39 μg ml−1) and Fusarium chlamydosporum (ED50 4.23 μg ml−1) causal agents of pod rot of mungbean. Under field conditions, three applications of trifloxystrobin + tebuconazole 75% WG at 0.07% as a foliar application at fortnightly intervals starting from the last week of July proved to be the most effective against pod rot disease on mungbean cultivars, i.e., ML 2056 and SML 668. To identify the potential resistance sources, 75 interspecific derivative and mutant lines of mungbean were screened for disease reaction to pod rot under natural epiphytotic conditions for the years 2019 and 2020. Genotypic differences were observed for resistance to pod rot disease. The study revealed that among the tested genotypes, ML 2524 exhibited resistance to pod rot disease, with a disease incidence of 15.62% and disease severity of 7.69%. In addition, 41 other genotypes were found to be moderately resistant (MR) to the disease.

Conclusion

Altogether, the identified management options will offer an immediate solution to manage this disease under recent outbreak conditions and pave a path for futuristic disease management using identified resistant sources in breeding programs.
Genome diversity and highland-adaptative variation in Tibet barley landrace population of China
Authors: Dondup Dawa , Yang Yang , Xu Dongdong , Namgyal Lhundrup , Wang Zihao , Shen Xia , Dorji Tsechoe , kyi Nyima , Drolma Lhakpa , Gao Liyun , Ga Zhuo , Sang Zha , Ga Zhuo , Mu Wang , Zhuoma Pubu , Taba Xiongnu , Jiao Guocheng , Liao Wenhua , Tang Yawei , Zeng Xingquan , Luobu Zhaxi , Wu Yufeng , Wang Chunchao , Zhang Jing , Qi Zengjun , Guo Weilong , Guo Ganggang
Published: May 2023

Barley landraces accumulated variation in adapting to extreme highland environments during long-term domestication in Tibet, but little is known about their population structure and genomic selection traces. In this study, tGBS (tunable genotyping by sequencing) sequencing, molecular marker and phenotypic analyses were conducted on 1,308 highland and 58 inland barley landraces in China. The accessions were divided into six sub-populations and clearly distinguished most six-rowed, naked barley accessions (Qingke in Tibet) from inland barley. Genome-wide differentiation was observed in all five sub-populations of Qingke and inland barley accessions. High genetic differentiation in the pericentric regions of chromosomes 2H and 3H contributed to formation of five types of Qingke. Ten haplotypes of the pericentric regions of 2H, 3H, 6H and 7H were further identified as associated with ecological diversification of these sub-populations. There was genetic exchange between eastern and western Qingke but they shared the same progenitor. The identification of 20 inland barley types indicated multiple origins of Qingke in Tibet. The distribution of the five types of Qingke corresponded to specific environments. Two predominant highland-adaptative variations were identified for low temperature tolerance and grain color. Our results provide new insights into the origin, genome differentiation, population structure and highland adaptation in highland barley which will benefit both germplasm enhancement and breeding of naked barley.