Dip2a regulates stress susceptibility in the basolateral amygdala.

JOURNAL/nrgr/04.03/01300535-202506000-00025/figure1/v/2024-08-05T133530Z/r/image-tiff Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post-traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A (Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid-associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.

Dysregulated serum concentrations of fat-soluble vitamins in dogs with chronic enteropathy.

BACKGROUND: In inflammatory bowel disease (IBD) of humans, nutrient malabsorption can result in fat-soluble vitamin deficiency, especially of vitamin D. In veterinary species, decreased concentrations of vitamin D are relatively common in dogs with chronic enteropathy (CE), but data on the status of other fat-soluble vitamins (FSVs) is lacking. OBJECTIVES: Determine the serum concentrations of retinol, vitamin D, and α-tocopherol in dogs with CE compared with healthy dogs and compare clinical, clinicopathologic variables between CE and healthy dogs to detect associations with decreased FSVs concentrations. ANIMALS: Eighteen client-owned dogs with CE and 33 healthy dogs. METHODS: Serum 25-hydroxyvitamin D (25[OH]D), serum retinol and α-tocopherol concentrations were compared between groups. Correlations and multiple regression modeling were used to examine the relationship between serum 25(OH)D, retinol, and α-tocopherol concentrations and clinical and clinicopathological variables. RESULTS: Dogs with low serum albumin concentrations were more likely to have lower 25(OH)D concentrations than dogs with normal serum albumin concentration. Dogs with CE had higher serum concentrations of retinol, and variable α-tocopherol concentrations. The cause of these dysregulated vitamin concentrations is unclear and requires further study. CONCLUSION AND CLINICAL IMPORTANCE: Dogs with severe forms of CE should be monitored for decreased concentrations of 25(OH)D. Additional studies are needed to evaluate the clinical relevance and the possible benefit of vitamin D supplementation in these patients.

Screening of Intermetallic Compounds Based on Intermediate Adsorption Equilibrium for Electrocatalytic Nitrate Reduction to Ammonia.

Electrocatalytic nitrate (NO3-) reduction reaction (NO3RR) holds great potential for the conversion of NO3- contaminants into valuable NH3 in a sustainable method. Unfortunately, the nonequilibrium adsorption of intermediates and sluggish multielectron transfer have detrimental impacts on the electrocatalytic performance of the NO3RR, posing obstacles to its practical application. Herein, we initially screen the adsorption energies of three key intermediates, i.e., *NO3, *NO, and *H2O, along with the d-band centers on 21 types of transition metal (IIIV and IB)-Sb/Bi-based intermetallic compounds (IMCs) as electrocatalysts. The results reveal that hexagonal CoSb IMCs possess the optimal adsorption equilibrium for key intermediates and exhibit outstanding electrocatalytic NO3RR performance with a Faradaic efficiency of 96.3%, a NH3 selectivity of 89.1%, and excellent stability, surpassing the majority of recently reported NO3RR electrocatalysts. Moreover, the integration of CoSb IMCs/C into a novel Zn-NO3- battery results in a high power density of 11.88 mW cm-2.

Netrin-1 Is an Important Mediator in Microglia Migration.

Microglia migrate to the cerebral cortex during early embryonic stages. However, the precise mechanisms underlying microglia migration remain incompletely understood. As an extracellular matrix protein, Netrin-1 is involved in modulating the motility of diverse cells. In this paper, we found that Netrin-1 promoted microglial BV2 cell migration in vitro. Mechanism studies indicated that the activation of GSK3ß activity contributed to Netrin-1-mediated microglia migration. Furthermore, Integrin α6/ß1 might be the relevant receptor. Single-cell data analysis revealed the higher expression of Integrin α6 subunit and ß1 subunit in microglia in comparison with classical receptors, including Dcc, Neo1, Unc5a, Unc5b, Unc5c, Unc5d, and Dscam. Microscale thermophoresis (MST) measurement confirmed the high binding affinity between Integrin α6/ß1 and Netrin-1. Importantly, activation of Integrin α6/ß1 with IKVAV peptides mirrored the microglia migration and GSK3 activation induced by Netrin-1. Finally, conditional knockout (CKO) of Netrin-1 in radial glial cells and their progeny led to a reduction in microglia population in the cerebral cortex at early developmental stages. Together, our findings highlight the role of Netrin-1 in microglia migration and underscore its therapeutic potential in microglia-related brain diseases.

Precision Treatment of Anthracycline-Induced Cardiotoxicity: An Updated Review.

OPINION STATEMENT: Anthracycline (ANT)-induced cardiotoxicity (AIC) is a particularly prominent form of cancer therapy-related cardiovascular toxicity leading to the limitations of ANTs in clinical practice. Even though AIC has drawn particular attention, the best way to treat it is remaining unclear. Updates to AIC therapy have been made possible by recent developments in research on the underlying processes of AIC. We review the current molecular pathways leading to AIC: 1) oxidative stress (OS) including enzymatic-induced and other mechanisms; 2) topoisomerase; 3) inflammatory response; 4) cardiac progenitor cell damage; 5) epigenetic changes; 6) renin-angiotensin-aldosterone system (RAAS) dysregulation. And we systematically discuss current prevention and treatment strategies and novel pathogenesis-based therapies for AIC: 1) dose reduction and change; 2) altering drug delivery methods; 3) antioxidants, dexrezosen, statina, RAAS inhibitors, and hypoglycemic drugs; 4) miRNA, natural phytochemicals, mesenchymal stem cells, and cardiac progenitor cells. We also offer a fresh perspective on the management of AIC by outlining the current dilemmas and challenges associated with its prevention and treatment.

[Research progress of chemerin in polycystic ovary syndrome].

As a multifunctional adipokine, chemerin plays a crucial role in various pathophysiological processes through endocrine and paracrine manner. It can bind to three known receptors (ChemR23, GPR1 and CCRL2) and participate in energy metabolism, glucose and lipid metabolism, and inflammation, especially in metabolic diseases. Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases, which seriously affects the normal life of women of childbearing age. Patients with PCOS have significantly increased serum levels of chemerin and high expression of chemerin in their ovaries. More and more studies have shown that chemerin is involved in the occurrence and development of PCOS by affecting obesity, insulin resistance, hyperandrogenism, oxidative stress and inflammatory response. This article mainly reviews the production, subtypes, function and receptors of chemerin protein, summarizes and discusses the research status of chemerin protein in PCOS from the perspectives of metabolism, reproduction and inflammation, and provides theoretical basis and reference for the clinical diagnosis and treatment of PCOS.

Nicotinamide N-Methyltransferase (NNMT): A New Hope for Treating Aging and Age-Related Conditions.

The complex process of aging leads to a gradual deterioration in the function of cells, tissues, and the entire organism, thereby increasing the risk of disease and death. Nicotinamide N-methyltransferase (NNMT) has attracted attention as a potential target for combating aging and its related pathologies. Studies have shown that NNMT activity increases over time, which is closely associated with the onset and progression of age-related diseases. NNMT uses S-adenosylmethionine (SAM) as a methyl donor to facilitate the methylation of nicotinamide (NAM), converting NAM into S-adenosyl-L-homocysteine (SAH) and methylnicotinamide (MNA). This enzymatic action depletes NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and generates SAH, a precursor of homocysteine (Hcy). The reduction in the NAD+ levels and the increase in the Hcy levels are considered important factors in the aging process and age-related diseases. The efficacy of RNA interference (RNAi) therapies and small-molecule inhibitors targeting NNMT demonstrates the potential of NNMT as a therapeutic target. Despite these advances, the exact mechanisms by which NNMT influences aging and age-related diseases remain unclear, and there is a lack of clinical trials involving NNMT inhibitors and RNAi drugs. Therefore, more in-depth research is needed to elucidate the precise functions of NNMT in aging and promote the development of targeted pharmaceutical interventions. This paper aims to explore the specific role of NNMT in aging, and to evaluate its potential as a therapeutic target.

Nicotinamide N-methyltransferase (NNMT): a novel therapeutic target for metabolic syndrome.

Metabolic syndrome (MetS) represents a constellation of metabolic abnormalities, typified by obesity, hypertension, hyperglycemia, and hyperlipidemia. It stems from intricate dysregulations in metabolic pathways governing energy and substrate metabolism. While comprehending the precise etiological mechanisms of MetS remains challenging, evidence underscores the pivotal roles of aberrations in lipid metabolism and insulin resistance (IR) in its pathogenesis. Notably, nicotinamide N-methyltransferase (NNMT) has recently surfaced as a promising therapeutic target for addressing MetS. Single nucleotide variants in the NNMT gene are significantly correlated with disturbances in energy metabolism, obesity, type 2 diabetes (T2D), hyperlipidemia, and hypertension. Elevated NNMT gene expression is notably observed in the liver and white adipose tissue (WAT) of individuals with diabetic mice, obesity, and rats afflicted with MetS. Knockdown of NNMT elicits heightened energy expenditure in adipose and hepatic tissues, mitigates lipid accumulation, and enhances insulin sensitivity. NNMT catalyzes the methylation of nicotinamide (NAM) using S-adenosyl-methionine (SAM) as the donor methyl group, resulting in the formation of S-adenosyl-l-homocysteine (SAH) and methylnicotinamide (MNAM). This enzymatic process results in the depletion of NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and the generation of SAH, a precursor of homocysteine (Hcy). Consequently, this cascade leads to reduced NAD+ levels and elevated Hcy levels, implicating NNMT in the pathogenesis of MetS. Moreover, experimental studies employing RNA interference (RNAi) strategies and small molecule inhibitors targeting NNMT have underscored its potential as a therapeutic target for preventing or treating MetS-related diseases. Nonetheless, the precise mechanistic underpinnings remain elusive, and as of yet, clinical trials focusing on NNMT have not been documented. Therefore, further investigations are warranted to elucidate the intricate roles of NNMT in MetS and to develop targeted therapeutic interventions.

Lipid-Encapsulated Engineered Bacterial Living Materials Inhibit Cyclooxygenase II to Enhance Doxorubicin Toxicity.

Recently, there has been increasing interest in the use of bacteria for cancer therapy due to their ability to selectively target tumor sites and inhibit tumor growth. However, the complexity of the interaction between bacteria and tumor cells evokes unpredictable therapeutic risk, which induces inflammation, stimulates the up-regulation of cyclooxygenase II (COX-2) protein, and stimulates downstream antiapoptotic gene expression in the tumor microenvironment to reduce the antitumor efficacy of chemotherapy and immunotherapy. In this study, we encapsulated celecoxib (CXB), a specific COX-2 inhibitor, in liposomes anchored to the surface of Escherichia coli Nissle 1917 (ECN) through electrostatic absorption (C@ECN) to suppress ECN-induced COX-2 up-regulation and enhance the synergistic antitumor effect of doxorubicin (DOX). C@ECN improved the antitumor effect of DOX by restraining COX-2 expression. In addition, local T lymphocyte infiltration was induced by the ECN to enhance immunotherapy efficacy in the tumor microenvironment. Considering the biosafety of C@ECN, a hypoxia-induced lysis circuit, pGEX-Pvhb-Lysis, was introduced into the ECN to limit the number of ECNs in vivo. Our results indicate that this system has the potential to enhance the synergistic effect of ECN with chemical drugs to inhibit tumor progression in medical oncology.

Retrospective evaluation of the effect of acid suppressant drugs on leukocyte ratios in dogs with mast cell tumors.

BACKGROUND: Acid suppressant drugs (ASDs) are commonly used to decrease gastric acid production, but some evidence exists that ASDs exert immunomodulatory effects. Such an effect has not been investigated in dogs for which ASDs are routinely prescribed. HYPOTHESIS: Compared to naïve subjects, dogs treated with ASDs will exhibit differences in leukocyte ratios after treatment. ANIMALS: Fifty-one dogs with mast cell tumors (MCTs). MATERIALS AND METHODS: Dogs with MCT that were either AS naïve or treated with ASDs (i.e., histamine-2-receptor antagonists [H2RA] or proton pump inhibitors [PPI]) were included in this retrospective study. Subjects were categorized into 3 treatment groups (AS naïve, H2RA treated, and PPI treated), and leukocyte ratios (neutrophil:eosinophil, lymphocyte:monocyte, and neutrophil:lymphocyte [NLR]) were calculated before and after treatment. A mixed effects analysis of variance on ranks was used to assess differences in ratios between treatments, between pre- and post-treatment time points, and between pre- and post-time points for each treatment. Concurrent administration of antihistamines, corticosteroids, and chemotherapeutic drugs was assessed as a confounding factor. RESULTS: Famotidine (n = 14/14) and omeprazole (n = 12/12) were the only H2RA and PPI used, respectively. Dogs receiving famotidine had a significant increase in median NLR from pre- to post-treatment (3.429; range, 1.417-15 to 5.631; range, 2.654-92; P < 0.01) compared to PPI treated or AS naïve dogs. No differences existed in chemotherapeutic drug or corticosteroid use between groups. CONCLUSIONS: A significant difference in NLR was identified in famotidine treated dogs compared with omeprazole treated or AS naïve dogs.

Analysis of the immunological response to antiviral therapy in patients with different subtypes of HIV/AIDS: a retrospective cohort study.

OBJECTIVE: To evaluate the effectiveness of standardised antiretroviral therapy (ART) among different HIV subtypes in people living with HIV/AIDS (PLWHA), and to screen the best ART regimen for this patient population. DESIGN: A retrospective cohort study was performed, and PLWHA residing in Huzhou, China, between 2018 and 2020, were enrolled. SETTING AND PARTICIPANTS: Data from 625 patients, who were newly diagnosed with HIV/AIDS in the AIDS Prevention and Control Information System in Huzhou between 2018 and 2020, were reviewed. ANALYSIS AND OUTCOME MEASURES: Data regarding demographic characteristics and laboratory investigation results were collected. Immune system recovery was used to assess the effectiveness of ART, and an increased percentage of CD4+ T lymphocyte counts >30% after receiving ART for >1 year was determined as immunopositive. A multiple logistic regression model was used to comprehensively quantify the association between PLWHA immunological response status and virus subtype. In addition, the joint association between different subtypes and treatment regimens on immunological response status was investigated. RESULTS: Among 326 enrolled PLWHA with circulating recombinant forms (CRFs) CRF01_AE, CRF07_BC and other HIV/AIDS subtypes, the percentages of immunopositivity were 74.0%, 65.6% and 69.6%, respectively. According to multivariate logistic regression models, there was no difference in the immunological response between patients with CRF01_AE, CRF07_BC and other subtypes of HIV/AIDS who underwent ART (CRF07_BC: adjusted OR (aOR) (95% CI) = 0.8 (0.4 to 1.4); other subtypes: aOR (95% CI) = 1.2 (0.6 to 2.3)). There was no evidence of an obvious joint association between HIV subtypes and ART regimens on immunological response. CONCLUSIONS: Standardised ART was beneficial to all PLWHA, regardless of HIV subtypes, although it was more effective, to some extent, in PLWHA with CRF01_AE.

HIV subtypes and molecular transmission characteristics among elderly HIV-infected individuals aged 50 and above: a cross-sectional study in Huzhou City, Eastern China.

OBJECTIVE: To analyse the HIV-1 subtypes and molecular transmission characteristics of HIV-infected older individuals aged 50 and above in Huzhou City, and provide a scientific basis for prevention and treatment strategies for them. DESIGN: A cross-sectional study with clustered molecular transmission network cases was performed, and basic epidemiological information was retrieved from the Chinese Centres for Disease Prevention and Control (CDC) Information System. SETTING AND PARTICIPANTS: A molecular epidemiological study was conducted in 899 newly diagnosed HIV-infected individuals from January 2019 and March 2023 in Huzhou city, Zhejiang province, Eastern China. Out of these, HIV sequences were successfully obtained from 673 individuals, including 274 who were older individuals aged 50 and above. PRIMARY AND SECONDARY OUTCOMES: Reverse transcription-polymerase chain reaction (PCR) and nested PCR were used to amplify the polymerase gene of HIV-1, and gene sequencing was performed. We used univariate and multivariate logistic regression to describe the association of clustered molecular transmission network cases. RESULTS: In total, 274 valid HIV sequences of older individuals were obtained, which revealed 14 subtypes. Circulating recombinant forms (CRF) 07_BC accounted for 55.8% and CRF01_AE accounted for 20.1% of the subtypes. Data of 150 older individuals were included in the molecular transmission network, and the proportion of elderly individuals in clustered cases is 52.26% (150/287). The results of multivariable logistic regression analysis showed that the older age group (60-82 years) and CRF07_BC subtype were associated with case clustering (transmission risk). CONCLUSIONS: The key high-risk transmission network was mainly composed of the older age group (60-82 years) and CRF07_BC subtype. It is necessary to further strengthen AIDS health promotion and education for individuals aged 60 years and above, as well as for patients with the CRF07_BC subtype, to reduce HIV transmission and clustering risk.

Heterophase Intermetallic Compounds for Electrocatalytic Hydrogen Production at Industrial-Scale Current Densities.

Heterophase nanomaterials have sparked significant research interest in catalysis due to their distinctive properties arising from synergistic effects of different components and the formed phase boundary. However, challenges persist in the controlled synthesis of heterophase intermetallic compounds (IMCs), primarily due to the lattice mismatch of distinct crystal phases and the difficulty in achieving precise control of the phase transitions. Herein, orthorhombic/cubic Ru2Ge3/RuGe IMCs with engineered boundary architecture are synthesized and anchored on the reduced graphene oxide. The Ru2Ge3/RuGe IMCs exhibit excellent hydrogen evolution reaction (HER) performance with a high current density of 1000 mA cm-2 at a low overpotential of 135 mV. The presence of phase boundaries enhances charge transfer and improves the kinetics of water dissociation while optimizing the processes of hydrogen adsorption/desorption, thus boosting the HER performance. Moreover, an anion exchange membrane electrolyzer is constructed using Ru2Ge3/RuGe as the cathode electrocatalyst, which achieves a current density of 1000 mA cm-2 at a low voltage of 1.73 V, and the activity remains virtually undiminished over 500 h.

Substance P in the medial amygdala regulates aggressive behaviors in male mice.

Behavioral and clinical studies have revealed a critical role of substance P (SP) in aggression; however, the neural circuit mechanisms underlying SP and aggression remain elusive. Here, we show that tachykinin-expressing neurons in the medial amygdala (MeATac1 neurons) are activated during aggressive behaviors in male mice. We identified MeATac1 neurons as a key mediator of aggression and found that MeATac1→ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl) projections are critical to the regulation of aggression. Moreover, SP/neurokinin-1 receptor (NK-1R) signaling in the VMHvl modulates aggressive behaviors in male mice. SP/NK-1R signaling regulates aggression by influencing glutamate transmission in neurons in the VMHvl. In summary, these findings place SP as a key node in aggression circuits.

A novel fast hybrid capture sequencing method for high-efficiency common human coronavirus whole-genome acquisition.

Rapid and accurate sequencing of the entire viral genome, coupled with continuous monitoring of genetic changes, is crucial for understanding the epidemiology of coronaviruses. We designed a novel method called micro target hybrid capture system (MT-Capture) to enable whole-genome sequencing in a timely manner. The novel design of probes used in target binding exhibits a unique and synergistic "hand-in-hand" conjugation effect. The entire hybrid capture process is within 2.5 hours, overcoming the time-consuming and complex operation characteristics of the traditional liquid-phase hybrid capture (T-Capture) system. By designing specific probes for these coronaviruses, MT-Capture effectively enriched isolated strains and 112 clinical samples of coronaviruses with cycle threshold values below 37. Compared to multiplex PCR sequencing, it does not require frequent primer updates and has higher compatibility. MT-Capture is highly sensitive and capable of tracking variants.IMPORTANCEMT-Capture is meticulously designed to enable the efficient acquisition of the target genome of the common human coronavirus. Coronavirus is a kind of virus that people are generally susceptible to and is epidemic and infectious, and it is the virus with the longest genome among known RNA viruses. Therefore, common human coronavirus samples are selected to evaluate the accuracy and sensitivity of MT-Capture. This method utilizes innovative probe designs optimized through probe conjugation techniques, greatly shortening the time and simplifying the handwork compared with traditional hybridization capture processes. Our results demonstrate that MT-Capture surpasses multiplex PCR in terms of sensitivity, exhibiting a thousandfold increase. Moreover, MT-Capture excels in the identification of mutation sites. This method not only is used to target the coronaviruses but also may be used to diagnose other diseases, including various infectious diseases, genetic diseases, or tumors.

Cat owners do not provide more reliable weight estimates for cats compared with veterinary professionals in an emergency setting.

OBJECTIVES: The aim of the present study was to assess the accuracy of weight estimation in cats provided by pet owners, veterinary technicians, house officers (interns and residents) and attending clinicians in an emergency room (ER). An additional objective was to determine whether carrying the cat contributed to a more accurate weight estimate. METHODS: A total of 72 cats presented to an ER and were enrolled in the study. Pet owners, veterinary technicians, house officers and attending clinicians were asked to record the cats' estimated weights on individual data collection cards. The actual weights of the cats were then obtained and compared with participants' estimations. RESULTS: There were no significant differences between weight estimates provided by pet owners, veterinary technicians, house officers and attending clinicians. Similarly, neither the length of experience of the veterinary staff nor carrying the cat had an effect on the provision of a more accurate weight estimate. CONCLUSIONS AND RELEVANCE: Pet owners are no better at weight estimation of cats in the ER setting compared with veterinary professionals. Carrying the cat did not improve the accuracy of weight estimation among veterinary professionals. The mean cat weight of 4.9 kg could be used as an average cat weight in an emergency situation for an adult cat.

Detection of Mycoplasma spp. and feline calicivirus in cats with ocular surface disease.

OBJECTIVE: To survey the prevalence of pathogens in shelter-housed cats with active ocular surface disease (OSD). ANIMALS STUDIED: A total of 255 shelter-housed domestic cats with evidence of active OSD. No normal, unaffected cats were sampled. PROCEDURE(S): OSD scoring was performed on cats with active OSD. Combined oropharyngeal/conjunctival swabs were submitted for rt-PCR/PCR for feline herpesvirus (FHV-1), feline calicivirus (FCV), Chlamydia spp. (CHL), Bordetella bronchiseptica (BORD), and Mycoplasma spp. (MYC). RESULTS: Pathogens were detected as follows: 76.4% (195/255) MYC, 57.6% (147/255) FHV-1, 42.7% (109/255) FCV, 26.7% (68/255) CHL, and 5.5% (14/255) BORD. Monoinfections affected 21.1% (54/255) animals, with MYC being the most common monoinfection (12.5%, 32/255), followed by FHV-1 (4.7%, 12/255), followed by CHL (2.4%, 6/255), followed by FCV (1.6%, 4/255), with no animals having a BORD monoinfection. Dual infections affected 36.4% of animals (93/255), with MYC detected in 30.1% (77/255) dual infections and FCV detected in 12.9% (33/255) dual infections. Dual infections with MYC and FCV together were detected in 9.8% (25/255) animals. Many animals (35.3%, 90/255) were found to be affected by 3 or more pathogens, and 7.1% (18/255) animals had no pathogens detected. OSD scores were not influenced by any variable assessed, including the number and type of pathogens detected. CONCLUSION: MYC, FHV-1, FCV, and CHL were commonly detected in this group of animals with OSD. Both MYC and FCV (alone or in combination with each other) were detected in multiple animals with active OSD, supporting prior evidence that either may independently act as a primary ocular surface pathogen.

Enhancing Nitrate Reduction to Ammonia Through Crystal Phase Engineering: Unveiling the Hydrogen Bonding Effect in δ-FeOOH Electrocatalysis.

Crystal phase engineering has emerged as a powerful tool for tailoring the electrocatalytic performance, yet its impact on nitrate reduction to ammonia (NRA) remains largely uncharted territory. Herein, density functional theory (DFT) calculations are performed to unravel the influence of the crystal phase of FeOOH on the adsorption behavior of *NO3. Inspiringly, FeOOH samples with four distinct crystal phases (δ, γ, α, and ß) are successfully synthesized and deployed as electrocatalysts for NRA. Remarkably, among all FeOOH samples, δ-FeOOH demonstrates the superior NRA performance, achieving a NH3 Faradic efficiency ( FE NH 3 $\rm{FE} _ {\rm{NH_3}}$ ) of 90.2% at -1.0 V versus reversible hydrogen electrode (RHE) and a NH3 yield rate ( Yield NH 3 $\rm{Yield} _ {\rm{NH_3}}$ ) of 5.73 mg h-1 cm-2 at -1.2 V. In-depth experiments and theoretical calculations unveil the existence of hydrogen bonding interaction between δ-FeOOH and *NOx, which not only enhances the adsorption of *NOx but also disrupts the linear relationships between the free energy of *NO3 adsorption and various parameters, including limiting potential, d-band center (εd) and transferred charge from FeOOH to *NO3, ultimately contributing to the exceptional NRA performance.

PRMT5-mediated homologous recombination repair is essential to maintain genomic integrity of neural progenitor cells.

Maintaining genomic stability is a prerequisite for proliferating NPCs to ensure genetic fidelity. Though histone arginine methylation has been shown to play important roles in safeguarding genomic stability, the underlying mechanism during brain development is not fully understood. Protein arginine N-methyltransferase 5 (PRMT5) is a type II protein arginine methyltransferase that plays a role in transcriptional regulation. Here, we identify PRMT5 as a key regulator of DNA repair in response to double-strand breaks (DSBs) during NPC proliferation. Prmt5F/F; Emx1-Cre (cKO-Emx1) mice show a distinctive microcephaly phenotype, with partial loss of the dorsal medial cerebral cortex and complete loss of the corpus callosum and hippocampus. This phenotype is resulted from DSBs accumulation in the medial dorsal cortex followed by cell apoptosis. Both RNA sequencing and in vitro DNA repair analyses reveal that PRMT5 is required for DNA homologous recombination (HR) repair. PRMT5 specifically catalyzes H3R2me2s in proliferating NPCs in the developing mouse brain to enhance HR-related gene expression during DNA repair. Finally, overexpression of BRCA1 significantly rescues DSBs accumulation and cell apoptosis in PRMT5-deficient NSCs. Taken together, our results show that PRMT5 maintains genomic stability by regulating histone arginine methylation in proliferating NPCs.

Tympanic membrane perforations cannot be reliably detected using computed tomography based on 15 cadaver dogs.

The integrity of the tympanic membrane is an important factor when deciding treatment and therapeutic recommendations for dogs with ear disease; however, otoscopic examination may be difficult to perform due to features of external ear canal disease or patient compliance. CT is useful for the evaluation of middle ear disease, including cases in which middle ear disease is detected incidentally. The tympanic membrane is detectable using CT, but anecdotally, apparent focal defects or discontinuities of the tympanic membrane are often seen in patients with and without ear disease. The purpose of this prospective, observer agreement study was to determine if perforations of the tympanic membrane are reliably detectable on CT. Fifteen cadaver dogs underwent CT and video otoscopy to verify the integrity of each tympanic membrane. Cadavers were randomly assigned to have the tympanic membranes left intact or to undergo a myringotomy on either the left, the right, or both sides. CT was performed immediately following the myringotomies. Four blinded evaluators evaluated the pre- and post-myringotomy scans for a total of 30 scans (60 tympanic membranes). Average accuracy was low (44%), and interobserver agreement for all four evaluators was fair. Although the tympanic membrane is visible on CT, perforations of the tympanic membrane are unlikely to be accurately detected or excluded. The appearance of an intact tympanic membrane or defect in the membrane on CT should not be used as criteria to guide clinical treatment recommendations based on this cadaver model.