Ca2+-responsive phospholipid-binding BONZAI genes confer a novel role for cotton resistance to Verticillium wilt.

Verticillium wilt which produced by the soil-borne fungus Verticillium dahliae is an important biotic threat that limits cotton (Gossypium hirsutum) growth and agricultural productivity. It is very essential to explore new genes for the generation of V. dahliae resistance or tolerance cotton varieties. Ca2+ signaling as a secondary messenger is involved in pathogen stress response. Despite Ca2+-responsive phospholipid-binding BONZAI (BON) genes have intensively been investigated in Arabidopsis, their function has not still been characterized in cotton. Here, we showed that three copies of GhBON1, two copies of GhBON2 and GhBON3 were found from the genome sequences of upland cotton. The expression of GhBON1 was inducible to V. dahliae. Knocking down of GhBON1, GhBON2 and GhBON3 using virus induced gene silencing (VIGS) each increased up-regulation of defense responses in cotton. These GhBON1, GhBON2 and GhBON3-silenced plants enhanced resistance to V. dahliae accompanied by higher burst of hydrogen peroxide and decreased cell death and had more effect on the up-regulation of defense response genes. Further analysis revealed that GhBON1 could interacts with BAK1-interacting receptor-like kinase 1 (GhBIR1) and pathogen-associated molecular pattern (PAMP) receptor regulator BAK1 (GhBAK1) at plasma membrane. Our study further reveals that plant Ca2+ -responsive phospholipid-binding BONZAI genes negatively regulate Verticillium wilt with the conserved function in response to disease resistance or plant immunity.

High temporal waveform fidelity stimulated Brillouin scattering phase conjugate mirror using Novec-7500.

A high temporal waveform fidelity stimulated Brillouin scattering phase conjugate mirror (SBS-PCM) with high energy efficiency, based on a novel medium, Novec-7500, is proposed and practically achieved in this study. A theoretical analysis reveals that the temporal-domain waveform distortion is caused by the inherent pulse duration compression effect of the SBS, and this undesirable phenomenon can be significantly suppressed by decreasing the compression coefficient (CC afterwards), which is defined as the gain coefficient divided by the phonon lifetime, which coefficient and is identified as the key parameter for high waveform-fidelity in SBS-PCM. The feasibility of this approach was demonstrated experimentally, in which a reflected pulse with waveform symmetry equals to the pump and an average pulse duration of 0.974 τp (τp is the duration of pump) with an energy efficiency of over 90% was achieved using Novec-7500.

Three New Selaginellin Derivatives from Selaginella pulvinata and Their α-Glucosidase Inhibitory Activity.

Three new selaginellin derivatives, selaginpulvilins V-X (1-3), together with seven known analogs (4-10) were isolated from whole plants of Selaginella pulvinata. Their structures were determined by extensive spectroscopic methods including 1D and 2D NMR, HR-ESI-MS and chemical derivatization method. Compound 1 represents a rare example of naturally occurring selaginellin with an alkynylphenol-trimmed skeleton. Biological evaluation showed that compounds 2, 6 and 8 displayed moderate inhibition against α-glucosidase with IC50 values of 3.71, 2.04 and 4.00 µM, respectively.

Deficiency of proline/serine-rich coiled-coil protein 1 (PSRC1) accelerates trimethylamine N-oxide-induced atherosclerosis in ApoE-/- mice.

AIMS: The main therapeutic strategies for coronary artery disease (CAD) are mainly based on the correction of abnormal cholesterol levels; however, residual risks remain. The newly proven gut microbial metabolite trimethylamine N-oxide (TMAO) linked with CAD has broadened our horizons. In this study, we determined the role of proline/serine-rich coiled-coil protein 1 (PSRC1) in TMAO-driven atherosclerosis. METHODS AND RESULTS: We first analyzed the levels of TMAO and PSRC1 in patients with or without atherosclerosis with a target LDL-C < 1.8 mmol/L. Plasma TMAO levels were increased and negatively associated with decreased PSRC1 in peripheral blood mononuclear cells. Animals and in vitro studies showed that TMAO inhibited macrophage PSRC1 expression due to DNA hypermethylation of CpG islands. ApoE-/- mice fed a choline-supplemented diet exhibited reduced PSRC1 expression accompanied by increased atherosclerotic lesions and plasma TMAO levels. We further deleted PSRC1 in apoE-/- mice and PSRC1 deficiency significantly accelerated choline-induced atherogenesis, characterized by increased macrophage infiltration, foam cell formation and M1 macrophage polarization. Mechanistically, we overexpressed and knocked out PSRC1 in cultured macrophages to explore the mechanisms underlying TMAO-induced cholesterol accumulation and inflammation. PSRC1 deletion impaired reverse cholesterol transport and enhanced cholesterol uptake and inflammation, while PSRC1 overexpression rescued the proatherogenic phenotype observed in TMAO-stimulated macrophages, which was partially attributed to sulfotransferase 2B1b (SULT2B1b) inhibition. CONCLUSIONS: Herein, clinical data provide evidence that TMAO may participate in the development of CAD beyond well-controlled LDL-C levels. Our work also suggests that PSRC1 is a negative regulator mediating the unfavorable effects of TMAO-containing diets. Therefore, PSRC1 overexpression and reduced choline consumption may further alleviate atherosclerosis.

Quarter acoustic period pulse compression using stimulated Brillouin scattering in PF-5060.

The pulse duration of the near quarter-acoustic period (τa) is demonstrated in transient stimulated Brillouin scattering (SBS) pulse compression by the suppressing Stokes trailing-edge broadening at high intensities. A theoretical analysis reveals that the difficulty in attaining the transient compression limit is caused by the broadening of the Stokes trailing edge owing to insufficient pump depletion, and this undesirable phenomenon can be significantly suppressed by a high SBS gain coefficient. An average pulse duration of ∼1.05 τa was experimentally achieved in transient compression with a high-energy efficiency of over 30%. Benefiting from energy back conversion, compression below the transient SBS limit (< τa) also occurred when the pump peak power was increased to 150 MW.

New Insight into a Fenton-like Reaction Mechanism over Sulfidated ß-FeOOH: Key Role of Sulfidation in Efficient Iron(III) Reduction and Sulfate Radical Generation.

Sulfidation can greatly improve the efficiency of utilization of reducing equivalents for contaminant removal; however, whether this method benefits Fenton-like reactions or not and the possible mechanism are not well understood. In this study, we revealed that surface sulfidation can greatly promote the heterogeneous Fenton activity of ß-FeOOH (Fe3S4@ß-FeOOH) by 40 times, in which not only the •OH formation was enhanced but also SO4•- as a new oxidation species was generated. Moreover, their contribution to metronidazole (MTZ) degradation was 52.5 and 37.1%, respectively. In comparison, almost no HO2•/O2•- was detected in the Fe3S4@ß-FeOOH/H2O2 system. These results were different from some previously reported Fenton counterparts. Based on the characterization and probe experiments, sulfur species, including S2-, S0, and Sn2-, as an electron donor and electron shuttle were responsible for efficient conversion of Fe(III) into Fe(II) other than via the Haber-Weiss mechanism, leading to excellent •OH generation via a Fenton-like mechanism. Most importantly, HSO5- can be generated from SO32- oxidized by •OH, and its scission into SO4•- was not dependent on the extra electric potential or Fe-O2-S(IV) intermediate. These findings provided new insight for utilizing sulfidation to improve the activity of iron-based Fenton catalysts.

Implications for long COVID: A systematic review and meta-aggregation of experience of patients diagnosed with COVID-19.

AIMS AND OBJECTIVES: This review aims to synthesize the available evidence of what patients experience when infected with COVID-19, both in hospital and post-discharge settings. DESIGN: This review was conducted using the Joanna Briggs Institute (JBI) methodology for qualitative systematic reviews and evidence synthesis. Reporting of results was presented according to the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) checklist. BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to be a public health crisis worldwide. Many patients diagnosed with COVID-19 have varied levels of persisting mental disorders. Previous studies have reported the degree, prevalence and outcome of psychological problems. Minimal research explored the experience of patients with long COVID. The real-life experience of patients with COVID-19 from diagnosis to post-discharge can deepen the understanding of nurses, physicians and policymakers. METHODS: All studies describing the experience of patients were included. Two authors independently appraised the methodological quality of the included studies using the JBI Critical Appraisal Checklist for Qualitative Research 2020. RESULTS: This systematic review aggregated patients' experience of being diagnosed with COVID-19 in both hospitalized and post-discharge settings. Finally, 17 studies met inclusion criteria and quality appraisal guidelines. The selected studies in the meta-synthesis resulted in 12 categories, and further were concluded as five synthesized findings: physical symptoms caused by the virus, positive and negative emotional responses to the virus, positive coping strategies as facilitators of epidemic prevention and control, negative coping strategies as obstacles of epidemic prevention and control, and unmet needs for medical resource. CONCLUSIONS: The psychological burden of patients diagnosed with COVID-19 is heavy and persistent. Social support is essential in the control and prevention of the epidemic. Nurses and other staff should pay more attention to the mental health of the infected patients both in and after hospitalization. RELEVANCE TO CLINICAL PRACTICE: Nurses should care about the persistent mental trauma of COVID-19 survivors and provide appropriate psychological interventions to mitigate the negative psychological consequences of them. Besides, nurses, as healthcare professionals who may have the most touch with patients, should evaluate the level of social support and deploy it for them. It is also needed for nurses to listen to patient's needs and treat them with carefulness and adequate patience in order to decrease the unmet needs of patients.

Sinensiols H-J, three new lignan derivatives from Selaginella sinensis (Desv.) Spring.

One new lignan sinensiol H (1) and two new bisnorlignans, sinensiols I and J (2 and 3), along with three known compounds were isolated from the whole plants of Selaginella sinensis. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopy as well as high-resolution mass spectrometry. The absolute configuration of 1 was established by ECD calculation. Compounds 2 and 3 represent rare examples of naturally occurring 9,9'-bisnorlignans. All the isolated compounds were assayed for their inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages.

SULT2B1b inhibits reverse cholesterol transport and promotes cholesterol accumulation and inflammation in lymphocytes from AMI patients with low LDL-C levels.

The current main treatment for coronary artery disease (CAD) is to reduce low-density lipoprotein cholesterol (LDL-C) by statins, which could decrease the incidence of major adverse cardiovascular events (MACEs) by 30%. However, many residual risks still remain. To clarify the mechanism involved, we studied patients with acute myocardial infarction (AMI) with low LDL-C levels. Lymphocytes were isolated, and it was found that despite no difference in plasma LDL-C level, the lymphocyte cholesterol content was higher in AMI patient than those in non-CAD patients; thus, the decrease in intracellular cholesterol content was inconsistent with that in the plasma. Additionally, [3H]-cholesterol efflux rates were lower and mRNA levels of the inflammatory factors tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) higher in AMI lymphocytes. It was found that sulphotransferase 2B1b (SULT2B1b) expression was higher in AMI lymphocytes. Further research using Jurkat T lymphocytes confirmed that SULT2B1b knockdown increased cholesterol efflux capacity and decreased mRNA levels of TNF-α and IFN-γ by increasing liver X receptor (LXR)-ß levels. Furthermore, the degree of CpG island methylation in the SULT2B1b promoter was reduced in cells from AMI patients. In conclusion, SULT2B1b up-regulation due to hypomethylation of its promoter promotes cholesterol accumulation and inflammation by inhibiting LXR-ß in lymphocytes of AMI patients with low LDL-C levels. Therefore, reducing intracellular cholesterol is also important as plasma cholesterol levels. Therapeutic approaches to decrease SULT2B1b expression might be potentially beneficial for CAD prevention by decreasing intracellular cholesterol.

PSRC1 overexpression attenuates atherosclerosis progression in apoE-/- mice by modulating cholesterol transportation and inflammation.

AIMS: Human genome-wide association studies (GWAS) have found that proline/serine-rich coiled-coil 1 (PSRC1) encodes a protein that is associated with serum lipid levels and coronary artery disease. In addition, our previous study showed that the cholesterol efflux capacity is decreased in macrophages following a treatment silencing Psrc1, indicating that PSRC1 has anti-atherosclerotic effects. However, the role of PSRC1 in the development of atherosclerosis is unknown. This study aims to explore the effect of PSRC1 on atherosclerosis and its underlying mechanisms. METHOD AND RESULTS: A recombinant adenovirus expressing Psrc1 (Ad-PSRC1) was constructed and transfected in RAW264.7 cells as well as injected intravenously into apoE-/- mice. The in vitro study showed that PSRC1 overexpression reduced the cellular cholesterol content, increased the cholesterol efflux capacity and inhibited foam cell formation by upregulating the expression of peroxisome proliferator-activated receptor γ (PPAR-γ) and liver X receptor α (LXR-α), which are key cholesterol transportation-related proteins. Infecting apoE-/- mice with Ad-PSRC1 inhibited the development of atherosclerotic lesions and enhanced atherosclerotic plaque stability. Consistent with these results, PSRC1 overexpression in apoE-/- mice decreased the plasma levels of TC, TG, LDL-C, TNF-α, IL-1ß and IL-6, increased the plasma HDL-C levels and improved HDL function. Similarly, the PPAR-γ and LXR-α expression levels were upregulated in the liver and in peritoneal macrophages of PSRC1-overexpressing apoE-/- mice. Finally, the liver and peritoneal macrophages of apoE-/- mice displayed elevated expression of ß-catenin, which is a direct downstream gene of PSRC1 and an upstream gene of PPAR-γ and LXR-α, but decreased activity of nuclear transcription factor (NF-κB), which acts as a key gene in the regulation of inflammation. CONCLUSIONS: PSRC1 protects against the development of atherosclerosis and enhances the stability of plaques by modulating cholesterol transportation and inflammation in macrophages and the liver of apoE-/- mice.

Lck Inhibits Heat Shock Protein 65-Mediated Reverse Cholesterol Transport in T Cells.

Previously, we reported that heat shock protein (HSP)65 impairs the effects of high-density lipoprotein on macrophages. We also showed that immune response activation adversely affects reverse cholesterol transport (RCT). In this study, we investigated the effects of the Src family kinase lymphocyte-specific protein tyrosine kinase (Lck) and elucidated the mechanism underlying HSP65-regulated cholesterol efflux in T cells. We evaluated cell proliferation, Lck expression, and inflammatory cytokine production in Jurkat cells and CD4+ T cells. HSP65-mediated inhibition of RCT was assessed by evaluating ABCA1, ABCG1, SR-BI, PPAR-γ, and liver X receptor-α expression. A dose-dependent relationship was found between the levels of these proteins and the suppression of cholesterol efflux. Stimulation of Lck-silenced T cells with ionomycin resulted in a decrease in intracellular calcium levels. Treatment of Jurkat cells with PP2, an inhibitor of Src family kinase, inhibited calcium-induced, but not PMA-induced, ERK phosphorylation. NF-κB activation in response to PMA was minimally inhibited in cells stimulated with PP2. HSP65 failed to trigger downstream ERK or JNK phosphorylation or to activate NF-κB or protein kinase C-γ in Lck-silenced cells. Additionally, elevation of intracellular calcium was also impaired. However, HSP65 significantly enhanced cholesterol efflux and decreased cellular cholesterol content by inducing the expression of cholesterol transport proteins in Lck-silenced cells. The treatment of Jurkat cells with PP2 also inhibited cell proliferation and promoted RCT. In conclusion, Lck is a key molecule in the TCR signaling cascade that inhibits cholesterol efflux and upregulates intracellular cholesterol ester content in T cells. Our results demonstrate that the immune response plays a previously unrecognized role in RCT.

Curcumin inhibits monocyte chemoattractant protein-1 expression and enhances cholesterol efflux by suppressing the c-Jun N-terminal kinase pathway in macrophage.

OBJECTIVE: To investigate the effect of curcumin on monocyte chemoattractant protein 1 (MCP-1) production and reverse cholesterol transport (RCT) in macrophage induced by oxidation low-density lipoprotein (ox-LDL), and to identify the signal pathways involved. METHODS: The macrophages were treated with ox-LDL and various concentrations of curcumin simultaneously. The MCP-1 expression was measured by enzyme-linked immunosorbent assay. The apoAI-mediated cholesterol efflux was measured by (3)H-cholesterol-labeled counting radioactivity. The activation of intracellular signaling pathways was studied by Western blotting. RESULTS: Curcumin decreased the production of MCP-1 induced by ox-LDL in macrophages. MCP-1 expression was restrained by the inhibition of c-Jun N-terminal kinase (JNK) pathway (SP600125) and NF-κB pathway (BAY11-7082). Curcumin suppressed the phosphorylation of JNK and activation of NF-κB. Curcumin also enhanced RCT via up-regulating the expression of liver X receptor alpha (LXRα), ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI). Additionally, the inhibition of JNK (SP600125) increased cholesterol efflux and increased the expression of ABCA1 and SR-BI, but had no effect on LXRα. CONCLUSION: Curcumin suppresses MCP-1 production induced by ox-LDL via the JNK pathway and NK-κB pathway, while enhances cholesterol efflux in macrophage via suppressing the JNK pathway and activating the LXR-ABCA1/SR-BI pathway, which indicate that the vascular protective effect of curcumin is related to anti-inflammation and anti-atherosclerosis.

[Diagnostic value of Vanderbilt ADHD Parent Rating Scale in attention deficit hyperactivity disorder].

OBJECTIVE: To study the value of the Vanderbilt ADHD Parent Rating Scale (VADPRS) in the diagnosis of attention deficit hyperactivity disorder (ADHD). METHODS: VADPRS were completed by parents of 319 children with suspected ADHD. The children were then evaluated by a specialist based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) and 196 of them were diagnosed with ADHD. The value of VADPRS in the diagnosis of attention deficit and hyperactivity was evaluated using ROC curves. Diagnostic evaluation indexes at best operating point were calculated. Kappa values were calculated to explore the consistency of items in VADPRS and corresponding items in the DSM-IV criteria. RESULTS: The area under the ROC curve for the diagnosis of attention deficit by VADPRS was 0.791. At the best operating point, its sensitivity was 0.83, specificity was 0.63, positive predictive value was 0.69 and negative predictive value was 0.79. The area under the ROC curve for the diagnosis of hyperactivity by VADPRS was 0.855. At the best operating point, its sensitivity was 0.82, specificity was 0.76, positive predictive value was 0.65, and negative predictive value was 0.88. The negative predictive value of VADPRS in general population screen was 0.99, based on the results of this study. The consistency of items in the VADPRS and corresponding items in DSM-Ⅳ criteria was poor, with the Kappa value of most items being less than 0.40. CONCLUSIONS: VADPRS is suitable for a general population screen for ADHD and it is helpful in the clinical diagnosis of ADHD, but its results can be influenced by parents' awareness and perception of children's behavior, and cannot replace the interview and judgment of professionals.

[Comorbidities and functional impairments in children with attention deficit hyperactivity disorder].

OBJECTIVE: To assess comorbidities and functional impairments in children with attention deficit hyperactivity disorder (ADHD), and to investigate their relationship with the core symptoms (attention deficit and hyperactivity) of ADHD. METHODS: A total of 319 children with suspected ADHD were included in the study. The Vanderbilt ADHD Parent Rating Scale (VADPRS) was completed by their parents. Diagnosis and classification were performed based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Comorbidities and functional impairments were evaluated according to the VADPRS. Children with various types of ADHD were compared in terms of comorbidities and functional impairments, and their relationship with the core symptoms of ADHD was analyzed. RESULTS: Of the 319 children, 196 were diagnosed with ADHD, including 84 cases of predominantly inattentive type (ADHD-I), 35 cases of predominantly hyperactive-impulsive type (ADHD-HI) and 77 cases of combined type (ADHD-C); 123 did not meet the diagnostic criteria for ADHD. At least one other psychiatric disorder (oppositional defiant disorder, conduct disorder or emotional disorder) was seen in 63.8% (125/196) of the children with ADHD, versus 37.4 % (46/123) of the children without ADHD (P<0.05). The incidence of oppositional defiant disorder and conduct disorder in the ADHD-C subgroup was significantly higher than in the ADHD-I subgroup (P<0.05). The sums of oppositional defiant disorder, conduct disorder and emotional disorder symptoms were weakly correlated with the sums of hyperactive-impulsive and inattentive symptoms (P<0.01). Up to 89.8% of children with ADHD and 74.8% of children without ADHD showed functional impairments (P<0.05). The ADHD-C subgroup had a significantly higher overall incidence of functional impairments than the ADHD-I and ADHD-HI subgroups (P<0.05). The sum of inattentive symptoms was weakly correlated with the scores of learning ability, sibling relationship and participation in organized activities (P<0.01), and the sum of hyperactive-impulsive symptoms was weakly correlated with the score of sibling relationship (P<0.01). CONCLUSIONS: The incidence of comorbidities and functional impairments among children with ADHD is high, especially in those with ADHD-C. The severity of core symptoms in children with ADHD can influence the occurrence of comorbidities and functional impairments. The incidence of psychiatric disorders and functional impairments is also high in children with suspected ADHD who do not meet the diagnostic criteria for ADHD, so attention also needs to be paid to interventions among these children.

Associated congenital anomalies and genetic anomalies in fetuses with isolated and non-isolated aberrant right subclavian artery.

OBJECTIVE: This study's aim was to determine the prevalence of chromosomal anomalies in fetuses with isolated and non-isolated aberrant right subclavian artery (ARSA) and to evaluate its association with other congenital anomalies. METHODS: From September 2018 to October 2021, 668 ARSA cases were diagnosed by prenatal ultrasound in our hospital; cases with missed visits and a lack of chromosomal findings were excluded and 363 cases were eligible for enrollment. General information, ultrasound presentation, chromosomal findings and pregnancy outcomes were retrospectively analyzed. RESULTS: Among the 363 cases, 296 were isolated, and 67 were associated with structural abnormalities or soft marker abnormalities. The proportion of fetuses with chromosomal abnormalities in the isolated ARSA group was significantly lower than that in the non-isolated ARSA group (p < .001). In the non-isolated ARSA group, 22 cases were combined with other soft marker abnormalities and 45 cases were combined with structural abnormalities. The most frequent structural abnormality coexisting with ARSA was cardiac malformations (38.81%). CONCLUSION: The most common combined malformation in ARSA is intracardiac malformation. Isolated ARSA has a low risk of chromosomal abnormalities, so invasive chromosomal testing is not recommended. Non-isolated ARSA has a high incidence of chromosomal abnormalities, so early karyotyping should be recommended.

Inhibition of EphA2 protects against atherosclerosis by synergizing with statins to mitigate macrophage inflammation.

Statins are highly prevalent in patients with coronary artery disease. Statins exert their anti-inflammatory effects on the vascular wall and circulating levels of pro-inflammatory cytokines. However, increasing attention revealed the exacerbation of macrophage inflammation induced by statins, and a clear mechanistic explanation of whether the detrimental effects of statins on macrophage inflammatory phenotypes outweigh the beneficial effects is has not yet been established. Here, RNA-sequencing and RT-qPCR analyses demonstrated that statins significantly upregulated EphA2, Nlrp3, IL-1ß and TNF-α expression in macrophages. Mechanistically, we found that atorvastatin reduced KLF4 binding to the EphA2 promoter using KLF4-chromatin immunoprecipitation, suppressed HDAC11-mediated deacetylation and subsequently led to enhanced EphA2 transcription. The 4D-label-free proteomics analysis further confirmed the upregulated EphA2 and inflammatory signals. Furthermore, the proinflammatory effect of atorvastatin was neutralized by an addition of recombinant Fc-ephrinA1, a selective Eph receptor tyrosine kinase inhibitor (ALW-II-41-27) or EphA2-silencing adenovirus (siEphA2). In vivo, EphA2 was identified a proatherogenic factor and apoE-/- mice placed on a high-fat diet following gastric gavage with atorvastatin exhibited a consistent elevation in EphA2 expression. We further observed that the transfection with siEphA2 in atorvastatin-treated mice significantly attenuated atherosclerotic plaque formation and abrogated statin-orchestrated macrophages proinflammatory genes expression as compared to that in atorvastatin alone. Increased plaque stability index was also observed following the addition of siEphA2, as evidenced by increased collagen and smooth muscle content and diminished lipid accumulation and macrophage infiltration. The data suggest that blockage of EphA2 provides an additional therapeutic benefit for further improving the anti-atherogenic effects of statins.

Corticostriatal Neurons in the Anterior Auditory Field Regulate Frequency Discrimination Behavior.

The anterior auditory field (AAF) is a core region of the auditory cortex and plays a vital role in discrimination tasks. However, the role of the AAF corticostriatal neurons in frequency discrimination remains unclear. Here, we used c-Fos staining, fiber photometry recording, and pharmacogenetic manipulation to investigate the function of the AAF corticostriatal neurons in a frequency discrimination task. c-Fos staining and fiber photometry recording revealed that the activity of AAF pyramidal neurons was significantly elevated during the frequency discrimination task. Pharmacogenetic inhibition of AAF pyramidal neurons significantly impaired frequency discrimination. In addition, histological results revealed that AAF pyramidal neurons send strong projections to the striatum. Moreover, pharmacogenetic suppression of the striatal projections from pyramidal neurons in the AAF significantly disrupted the frequency discrimination. Collectively, our findings show that AAF pyramidal neurons, particularly the AAF-striatum projections, play a crucial role in frequency discrimination behavior.

Composition-Controllable Syntheses and Property Modulations from 2D Ferromagnetic Fe5 Se8 to Metallic Fe3 Se4 Nanosheets.

Exploring new-type 2D magnetic materials with high magnetic transition temperature and robust air stability has attracted wide attention for developing innovative spintronic devices. Recently, intercalation of native metal atoms into the van der Waals gaps of 2D layered transition metal dichalcogenides (TMDs) has been developed to form 2D non-layered magnetic TMDs, while only succeeded in limited systems (e.g., Cr2 S3 , Cr5 Te8 ). Herein, composition-controllable syntheses of 2D non-layered iron selenide nanosheets (25% Fe-intercalated triclinic Fe5 Se8 and 50% Fe-intercalated monoclinic Fe3 Se4 ) are firstly reported, via a robust chemical vapor deposition strategy. Specifically, the 2D Fe5 Se8 exhibits intrinsic room-temperature ferromagnetic property, which is explained by the change of electron spin states from layered 1T'-FeSe2 to non-layered Fe-intercalated Fe5 Se8 based on density functional theory calculations. In contrast, the ultrathin Fe3 Se4 presents novel metallic features comparable with that of metallic TMDs. This work hereby sheds light on the composition-controllable synthesis and fundamental property exploration of 2D self-intercalation induced novel TMDs compounds, by propelling their application explorations in nanoelectronics and spintronics-related fields.

Linear Mixed-Effects Model to Quantify the Association between Somatic Cell Count and Milk Production in Italian Dairy Herds.

Milk production loss due to mastitis in dairy herds is economically important. Before estimating the economic impacts of mastitis, it is crucial to quantify the association between mastitis and milk production. The objective of this study was to estimate the association between somatic cell count (SCC, as an indicator of intramammary infection due to mastitis) and milk production for dairy cows in Lombardy, Italy. The test-day (TD) records data of 3816 dairy herds located in three different geographical areas of Lombardy from January 2016 to December 2018 were used. After data editing, the final dataset comprised 10,445,464 TD records from 2970 farms and 826,831 cows. The analysis was carried out by using a mixed-effects model with six fixed effects (geographical Area, Breed, Days in Milk, Parity, Season and Year) and nested random effects for each cow and herd. The results confirmed that the SCC had a negative association with milk production. On average, this study found that any two-fold increase of SCC resulted in a milk production loss of 0.830 (95% CI: -0.832, -0.828) kg/cow/day in the whole of Lombardy. These results can be used for economic calculations on the costs of mastitis.

C3/C3aR inhibition alleviates GMH-IVH-induced hydrocephalus by preventing microglia-astrocyte interactions in neonatal rats.

Activation of microglia and astrocytes following germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) plays a detrimental role in posthemorrhagic hydrocephalus (PHH). It is still unclear whether or how an interaction occurs between microglia and astrocytes in PHH. Here, we investigated the role of the C3/C3aR pathway in microglia and astrocyte interactions and whether C3/C3aR-targeted inhibition could alleviate PHH following GMH-IVH. A total of 152 Sprague-Dawley rats at postnatal day seven (P7) were enrolled in the study, and collagenase VII was used to induce GMH-IVH. Minocycline (45 mg/kg) was administered to inhibit microglial activation. Complement C3a peptide and C3aR antagonist (SB 290157, 10 mg/kg) were used to regulate the C3/C3aR pathway. As a result, the data demonstrated that periventricular C3aR+/Iba-1+ microglia and C3+/GFAP+ astrocytes were significantly increased in GMH-IVH pups at 28 days after surgery. Intranasal C3a peptide upregulated C3aR expression in microglia. Inhibition of microglia by minocycline decreased both C3+/GFAP+ astrocytes and the colocalization volume of Iba-1 and GFAP. In addition, intraperitoneally injected C3aRA alleviated the periventricular colocalization volume of microglia and astrocytes. Compared with vehicle-treated pups, the protein level of IL-1ß, IL-6 and TNF-α in cerebral spinal fluid and brain tissue at 28 days following GMH-IVH were reduced in C3aRA-treated pups. Moreover, hydrocephalus was alleviated, and long-term cognitive ability were improved in the C3aRA-treated group. Our data presented simultaneous periventricular astrogliosis and microgliosis of pups following GMH-IVH and proved their potential interaction through the C3/C3aR pathway, indicating C3aRA as a potential pharmacological treatment of PHH in neonates.