Enantioselective Construction of Quaternary Stereocenters via Cooperative Photoredox/Fe/Chiral Primary Amine Triple Catalysis.

The catalytic and enantioselective construction of quaternary (all-carbon substituents) stereocenters poses a formidable challenge in organic synthesis due to the hindrance caused by steric factors. One conceptually viable and potentially versatile approach is the coupling of a C-C bond through an outer-sphere mechanism, accompanied by the realization of enantiocontrol through cooperative catalysis; however, examples of such processes are yet to be identified. Herein, we present such a method for creating different compounds with quaternary stereocenters by photoredox/Fe/chiral primary amine triple catalysis. This approach facilitates the connection of an unactivated alkyl source with a tertiary alkyl moiety, which is also rare. The scalable process exhibits mild conditions, does not necessitate the use of a base, and possesses a good functional-group tolerance. Preliminary investigations into the underlying mechanisms have provided valuable insights into the reaction pathway.

Quality of life, household income, and dietary habits are associated with the risk of sarcopenia among the Chinese elderly.

BACKGROUND: Health-related quality of life (HRQoL), which can be influenced by various aspects, especially socioeconomic status and lifestyle, has been identified as an important predictor of the prognosis of older adults. Dietary habit, a major part of lifestyle, can affect the nutritional status, which is closely correlated with the development of geriatric syndromes in the elderly. AIMS: The aim of the study was to examine the association of HRQoL, socioeconomic status, and lifestyle with the risk and severity of sarcopenia, a geriatric syndrome characterized by progressive loss of skeletal muscle mass, strength and function. METHODS: A cross-sectional retrospective study with 2877 participants aged ≥65 years was performed. HRQoL was assessed using EuroQoL Five Dimensions questionnaire. Socioeconomic status was assessed by the educational attainment, occupation, and household income. Lifestyle was assessed using 12 items closely related to Chinese living habits. The information of daily dietary habits including tea, alcohol, type of diet, and volume of drinking water were collected. The associations of HRQoL, socioeconomic status, and lifestyle with the risk of sarcopenia were examined by multivariate regression logistical analysis. The potential causal role of age, body mass index, and waist circumference in the effect of HRQoL on sarcopenia risk was analyzed by causal mediation analysis. RESULTS: High HRQoL [adjusted odds ratio (OR) =0.85, 95% confidence interval (CI) =0.69-0.95, P=0.034] and household income levels (adjusted OR =0.74, 95% CI =0.57-0.95, P=0.019) were inversely associated with the risk of sarcopenia. Meanwhile, more consumption of spicy food (adjusted OR =1.34, 95% CI =1.09-1.81, P =0.037) and occasionally drinking (adjusted OR =1.46, 95% CI =1.07-2.00, P =0.016, as compared to those never drinking) were associated with higher risk of sarcopenia, while skipping breakfast occasionally (adjusted OR =0.37, 95% CI =0.21-0.64, P <0.001, as compared to those eating breakfast every day) and less consumption of salt (adjusted OR =0.71, 95% CI =0.52-0.96, P =0.026, as compared to those consuming high amount of salt) were associated with lower risk of sarcopenia. Further causal mediation analysis aimed to explore how much age, body mass index, and waist circumference might explain the effect of HRQoL on the risk of sarcopenia showed that the estimated proportion that mediated the effect of HRQoL on the risk of sarcopenia by age was 28.0%. CONCLUSIONS: In summary, our findings demonstrate that low levels of HRQoL and household income, more intake of salt and spicy food, and occasional intake of alcohol are correlated with higher risk of sarcopenia, while skipping breakfast occasionally is associated with lower risk of sarcopenia in a Chinese population of older adults.

Case report: a special case of cryptococcal infection-related inflammatory syndrome in a non-HIV infected and non-transplant patient.

BACKGROUND: Cryptococcal meningoencephalitis (CM) is a severe infection of central nervous system with high mortality and morbidity. Infection-related inflammatory syndrome is a rare complication of CM. Herein, we report a case of CM complicated by infection-related inflammatory syndrome. CASE PRESENTATION: A 42-year-old man with chronic hepatitis B presented with a 3-day history of aphasia and left hemiparesis at an outside medical facility. The brain magnetic resonance imaging (MRI) showed symmetric and confluent hyperintense signal abnormalities mainly located in the basal ganglia, internal capsule, external capsule, periventricular, corona radiata, frontal and temporal lobes. Cerebrospinal fluid (CSF) examinations revealed elevated leukocyte and protein. India ink staining was positive for Cryptococcus. CSF culture and metagenomic next-generation sequencing (mNGS) confirmed Cryptococcus neoformans. Initial response was observed with intravenous fluconazole (400 mg per day). However, 11 days later, he developed impaired consciousness and incontinence of urine and feces. A repeat brain MRI showed the lesions were progressive and enlarged. The patient was referred to our department at this point of time. Repeat CSF analysis (India ink staining, culture and mNGS) re-confirmed Cryptococcus. However, clinical worsening after initial improvement, laboratory examinations and brain MRI findings suggested a diagnosis of infection-related inflammatory syndrome. Therefore, a combination of corticosteroids and antifungal therapy was initiated. At follow-up, a complete neurological recovery without any relapse was documented. The repeat brain MRI showed complete resolution of the previous lesions. CONCLUSIONS: This case demonstrated that cryptococcal inflammatory syndromes must be suspected in cases of CM if an otherwise unexplained clinical deterioration is observed after initial recovery. The same can happen even before the primary infection is controlled. Thus, timely identification and prompt treatment is vital to reduce the mortality and disability of CM. The administration of corticosteroids in combination with antifungal therapy is an effective strategy in such cases. Clinical course and treatment process of the patient. Hemiparalysis and aphasia improved after the initiation of antifungal treatment. However, the patient developed impaired consciousness companied by deterioration of brain MRI findings. He was treated with adjunctive glucocorticoid taper therapy consisting of dexamethasone (20 mg/day, intravenously) for 1 week followed by oral prednisone 1 mg/kg/day, tapered based on clinical and radiological response, along with amphotericin B (0.6 mg/kg/day, intravenously), voriconazole (400 mg/day in 2 divided doses, intravenously), and 5-flucytosine (100 mg/kg/day in 4 divided doses, orally). Two weeks later, his symptoms improved significantly. After discharge, he began oral voriconazole for consolidation and maintenance therapy for 8 weeks and 9 months respectively. He recovered without any neurological sequelae at 6-month follow-up. Note: MRI = magnetic resonance imaging.

Comparison of features and outcomes between HIV-negative patients with Cryptococcus gattii meningitis and Cryptococcus neoformans meningitis in South China.

OBJECTIVES: The objective of this study is to compare the epidemiologic, clinical, laboratory, and imaging features, and outcomes in patients with Cryptococcus gattii meningitis (CGM) and Cryptococcus neoformans meningitis (CNM). METHODS: We performed a retrospective study of HIV-negative patients with CGM and CNM (2015-2021) distinguished by metagenomic next-generation sequencing in cerebrospinal fluid in South China. RESULTS: A total of 81 patients (17 CGM, 64 CNM) were enrolled (72.8% male, median age 49 years, range 21-77 years), and CGM patients were younger (median, 43 vs 53 years, p = .005). Of 17 CGM, VGI and VGII accounted for 70.6% and 29.4%, respectively. CGM patients had less underlying diseases (7/17 [41.2%] vs 48/64 [75%], p = .018) and focal neurologic deficit (3/17 [17.6%] vs 35/64 [54.7%], p = .022), had higher intracranial pressure (15/17 [88.2%] vs 25/64 [39.1%], p = .002), more meningeal enhancement (14/17 [82.4%] vs 32/64 [50%], p = .034), less parenchymal involvement (median, 1 vs 3, p = .018), more lung cryptococcomas (6/12 [50%] vs 6/47 [12.8%], p = .014), faster CSF fungal clearance (p = .004), less complications (median, 1 vs 3, p < .001), and more favourable outcomes (16/17 [94.1%] vs 41/64 [64.1%], p = .035). CONCLUSIONS: This study demonstrated that species identification helps to guide therapy and predict outcomes.

Clinical ultrasound stimulating angiogenesis following drug-release from polymersomes on the ischemic zone for peripheral arterial occlusive disease.

Peripheral Arterial Occlusive Disease (PAOD) is an aging disease that affects the quality of life of many people by its intermittent claudication and critical limb ischemia presentations. Traditional treatment and management of PAOD are asking patients to make a life change and medication with antiplatelet, statins and cilostazol, which decrease the possibility of clot formation. Our strategy has employed a magnetic Fe3O4-PLGA polymersome to carry the cilostazol into the ischemic area by magnetic attraction following remote-control drug release through low-energy ultrasound exposure. In the animal studies, the cilostazol-loaded Fe3O4-PLGA polymersomes were injected and accumulated at ischemic leg through magnetic attraction. Then, using a clinical-use ultrasound machine the leg was irradiated to forward cilostazol release from the accumulated polymersomes. Dramatically, we found an observable result of bloody flux recovery in the leg after 7 days compared to the non-treated leg that showed no evidence of the blood recovery.

Formation of oligonucleotide-gated silica shell-coated Fe3O4-Au core-shell nanotrisoctahedra for magnetically targeted and near-infrared light-responsive theranostic platform.

A new multifunctional nanoparticle to perform a near-infrared (NIR)-responsive remote control drug release behavior was designed for applications in the biomedical field. Different from the previous studies in formation of Fe3O4-Au core-shell nanoparticles resulting in a spherical morphology, the heterostructure with polyhedral core and shell was presented with the truncated octahedral Fe3O4 nanoparticle as the core over a layer of trisoctahedral Au shell. The strategy of Fe3O4@polymer@Au was adopted using poly-l-lysine as the mediate layer, followed by the subsequent seeded growth of Au nanoparticles to form a Au trisoctahedral shell. Fe3O4@Au trisoctahedra possess high-index facets of {441}. To combine photothermal and chemotherapy in a remote-control manner, the trisoctahedral core-shell Fe3O4@Au nanoparticles were further covered with a mesoporous silica shell, yielding Fe3O4@Au@mSiO2. The bondable oligonucleotides (referred as dsDNA) were used as pore blockers of the mesoporous silica shell that allowed the controlled release, resulting in a NIR-responsive DNA-gated Fe3O4@Au@mSiO2 nanocarrier. Taking advantage of the magnetism, remotely triggered drug release was facilitated by magnetic attraction accompanied by the introduction of NIR radiation. DNA-gated Fe3O4@Au@mSiO2 serves as a drug control and release carrier that features functions of magnetic target, MRI diagnosis, and combination therapy through the manipulation of a magnet and a NIR laser. The results verified the significant therapeutic effects on tumors with the assistance of combination therapy consisting of magnetic guidance and remote NIR control.

Catalytic Nanoparticles in Biomedical Applications: Exploiting Advanced Nanozymes for Therapeutics and Diagnostics.

Catalytic nanoparticles (CNPs) as heterogeneous catalyst reveals superior activity due to their physio-chemical features, such as high surface-to-volume ratio and unique optical, electric, and magnetic properties. The CNPs, based on their physio-chemical nature, can either increase the reactive oxygen species (ROS) level for tumor and antibacterial therapy or eliminate the ROS for cytoprotection, anti-inflammation, and anti-aging. In addition, the catalytic activity of nanozymes can specifically trigger a specific reaction accompanied by the optical feature change, presenting the feasibility of biosensor and bioimaging applications. Undoubtedly, CNPs play a pivotal role in pushing the evolution of technologies in medical and clinical fields, and advanced strategies and nanomaterials rely on the input of chemical experts to develop. Herein, a systematic and comprehensive review of the challenges and recent development of CNPs for biomedical applications is presented from the viewpoint of advanced nanomaterial with unique catalytic activity and additional functions. Furthermore, the biosafety issue of applying biodegradable and non-biodegradable nanozymes and future perspectives are critically discussed to guide a promising direction in developing span-new nanozymes and more intelligent strategies for overcoming the current clinical limitations.

Frontiers and hotspots in comorbid epilepsy and depression: a bibliometric analysis from 2003 to 2023.

Background: Epilepsy ranks among the most common neurological disorders worldwide, frequently accompanied by depression as a prominent comorbidity. This study employs bibliometric analysis to reveal the research of comorbid epilepsy and depression over the past two decades, aiming to explore trends and contribute insights to ongoing investigations. Methods: We conducted a comprehensive search on the Web of Science Core Collection database and downloaded relevant publications on comorbid epilepsy and depression published from 2003 to 2023. VOSviewer and CiteSpace were mainly used to analyze the authors, institutions, countries, publishing journals, reference co-citation patterns, keyword co-occurrence, keyword clustering, and other aspects to construct a knowledge atlas. Results: A total of 5,586 publications related to comorbid epilepsy and depression were retrieved, with a general upward trend despite slight fluctuations in annual publications. Publications originated from 121 countries and 636 institutions, with a predominant focus on clinical research. The United States led in productivity (1,529 articles), while Melbourne University emerged as the most productive institution (135 articles). EPILEPSY & BEHAVIOR was the journal with the highest publication output (1,189 articles) and citation count. Keyword analysis highlighted emerging trends, including "recognitive impairment" and "mental health," indicating potential future research hotspots and trends. Conclusion: This study is one of the first to perform a bibliometric analysis of the 20-year scientific output of comorbid epilepsy and depression. While research has trended upwards, ambiguity in pathogenesis and the absence of standardized diagnostic guidelines remain concerning. Our analysis offers valuable guidance for researchers, informing that this might be a strong area for future collaborations.

Photo-Responsive Ascorbic Acid-Modified Ag2S-ZnS Heteronanostructure Dropping pH to Trigger Synergistic Antibacterial and Bohr Effects for Accelerating Infected Wound Healing.

Nonantibiotic approaches must be developed to kill pathogenic bacteria and ensure that clinicians have a means to treat wounds that are infected by multidrug-resistant bacteria. This study prepared matchstick-like Ag2S-ZnS heteronanostructures (HNSs). Their hydrophobic surfactants were then replaced with hydrophilic poly(ethylene glycol) (PEG) and thioglycolic acid (TGA) through the ligand exchange method, and this was followed by ascorbic acid (AA) conjugation with TGA through esterification, yielding well-dispersed PEGylated Ag2S-ZnS@TGA-AA HNSs. The ZnS component of the HNSs has innate semiconductivity, enabling the generation of electron-hole pairs upon irradiation with a light of wavelength 320 nm. These separate charges can react with oxygen and water around the HNSs to produce reactive oxygen species. Moreover, some holes can oxidize the surface-grafted AA to produce protons, decreasing the local pH and resulting in the corrosion of Ag2S, which releases silver ions. In evaluation tests, the PEGylated Ag2S-ZnS@TGA-AA had synergistic antibacterial ability and inhibited Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). Additionally, MRSA-infected wounds treated with a single dose of PEGylated Ag2S-ZnS@TGA-AA HNSs under light exposure healed significantly more quickly than those not treated, a result attributable to the HNSs' excellent antibacterial and Bohr effects.

Boosting Upconversion Efficiency in Optically Inert Shelled Structures with Electroactive Membrane through Electron Donation.

This study innovatively addresses challenges in enhancing upconversion efficiency in lanthanide-based nanoparticles (UCNPs) by exploiting Shewanella oneidensis MR-1, a microorganism capable of extracellular electron transfer. Electroactive membranes, rich in c-type cytochromes, are extracted from bacteria and integrated into membrane-integrated liposomes (MILs), encapsulating core-shelled UCNPs with an optically inactive shell, forming UCNP@MIL constructs. The electroactive membrane, tailored to donate electrons through the inert shell, independently boosts upconversion emission under near-infrared excitation (980 or 1550 nm), bypassing ligand-sensitized UCNPs. The optically inactive shell restricts energy migration, emphasizing electroactive membrane electron donation. Density functional theory calculations elucidate efficient electron transfer due to the electroactive membrane hemes' highest occupied molecular orbital being higher than the valence band maximum of the optically inactive shell, crucial for enhancing energy transfer to emitter ions. The introduction of a SiO2 insulator coating diminishes light enhancement, underscoring the importance of unimpeded electron transfer. Luminescence enhancement remains resilient to variations in emitter or sensitizing ions, highlighting the robustness of the electron transfer-induced phenomenon. However, altering the inert shell material diminishes enhancement, emphasizing the role of electron transfer. This methodology holds significant promise for diverse biological applications. UCNP@MIL offers an advantage in cellular uptake, which proves beneficial for cell imaging.

Electroactive membrane fusion-liposome for increased electron transfer to enhance radiodynamic therapy.

Dynamic therapies have potential in cancer treatments but have limitations in efficiency and penetration depth. Here a membrane-integrated liposome (MIL) is created to coat titanium dioxide (TiO2) nanoparticles to enhance electron transfer and increase radical production under low-dose X-ray irradiation. The exoelectrogenic Shewanella oneidensis MR-1 microorganism presents an innate capability for extracellular electron transfer (EET). An EET-mimicking photocatalytic system is created by coating the TiO2 nanoparticles with the MIL, which significantly enhances superoxide anions generation under low-dose (1 Gy) X-ray activation. The c-type cytochromes-constructed electron channel in the membrane mimics electron transfer to surrounding oxygen. Moreover, the hole transport in the valence band is also observed for water oxidation to produce hydroxyl radicals. The TiO2@MIL system is demonstrated against orthotopic liver tumours in vivo.

IRAK-M Ablation Promotes Status Epilepticus-Induced Neuroinflammation via Activating M1 Microglia and Impairing Excitatory Synaptic Function.

Epilepsy is one of the most common neurological disorders. The pro-epileptic and antiepileptic roles of microglia have recently garnered significant attention. Interleukin-1 receptor-associated kinase (IRAK)-M, an important kinase in the innate immune response, is mainly expressed in microglia and acts as a negative regulator of the TLR4 signaling pathway that mediates the anti-inflammatory effect. However, whether IRAK-M exerts a protective role in epileptogenesis as well as the molecular and cellular mechanisms underlying these processes are yet to be elucidated. An epilepsy mouse model induced by pilocarpine was used in this study. Real-time quantitative polymerase chain reaction and western blot analysis were used to analyze mRNA and protein expression levels, respectively. Whole-cell voltage-clamp recordings were employed to evaluate the glutamatergic synaptic transmission in hippocampal neurons. Immunofluorescence was utilized to show the glial cell activation and neuronal loss. Furthermore, the proportion of microglia was analyzed using flow cytometry. Seizure dynamics influenced the expression of IRAK-M. Its knockout dramatically exacerbated the seizures and the pathology in epilepsy and increased the N-methyl-d-aspartate receptor (NMDAR) expression, thereby enhancing glutamatergic synaptic transmission in hippocampal CA1 pyramidal neurons in mice. Furthermore, IRAK-M deficiency augmented hippocampal neuronal loss via a possible mechanism of NMDAR-mediated excitotoxicity. IRAK-M deletion promotes microglia toward the M1 phenotype, which resulted in high levels of proinflammatory cytokines and was accompanied by a visible increase in the expressions of key microglial polarization-related proteins, including p-STAT1, TRAF6, and SOCS1. The findings demonstrate that IRAK-M dysfunction contributes to the progression of epilepsy by increasing M1 microglial polarization and glutamatergic synaptic transmission. This is possibly related to NMDARs, particularly Grin2A and Grin2B, which suggests that IRAK-M could serve as a novel therapeutic target for the direct alleviation of epilepsy.

Prussian blue analog with separated active sites to catalyze water driven enhanced catalytic treatments.

Chemodynamic therapy (CDT) uses the Fenton or Fenton-like reaction to yield toxic ‧OH following H2O2 → ‧OH for tumoral therapy. Unfortunately, H2O2 is often taken from the limited endogenous supply of H2O2 in cancer cells. A water oxidation CoFe Prussian blue (CFPB) nanoframes is presented to provide sustained, external energy-free self-supply of ‧OH from H2O to process CDT and/or photothermal therapy (PTT). Unexpectedly, the as-prepared CFPB nanocubes with no near-infrared (NIR) absorption is transformed into CFPB nanoframes with NIR absorption due to the increased Fe3+-N ≡ C-Fe2+ composition through the proposed proton-induced metal replacement reactions. Surprisingly, both the CFPB nanocubes and nanoframes provide for the self-supply of O2, H2O2, and ‧OH from H2O, with the nanoframe outperforming in the production of ‧OH. Simulation analysis indicates separated active sites in catalyzation of water oxidation, oxygen reduction, and Fenton-like reactions from CFPB. The liposome-covered CFPB nanoframes prepared for controllable water-driven CDT for male tumoral mice treatments.

[Sequence analysis on drug-resistant gene of rpoB in MDR-TB among pneumoconiosis patients complicated with tuberculosis in Huainan mining district].

OBJECTIVE: To study the characteristics of drug-resistant genetic mutation of rpoB in multiple drugs resistant bacillus tuberculosis (MDR-TB) among patients of pneumoconiosis complicated with pulmonary tuberculosis. METHODS: A total of 114 clinical isolated strains of Mycobacterium tuberculosis were collected, MDR-TB were identified by conventional antimicrobial susceptibility test (AST). Their genomes DNA were extracted, the target genes were amplified by PCR, and the hot regions in the rpoB gene were analyzed by automated DNA sequenator. RESULTS: The results by AST showed that there were 31 strains of MDR-TB in the 114 clinical isolated strains, the rate of drug resistance was 27.19% (31/114). No mutation of rpoB was identified in 10 rifampicin-sensitive strains that randomly chosen, while conformation changes were found in MDR-TB strains, and the mutation rate of rpoB was 93.55% (29/31) in resistant strains, mainly concentrated in codon 531 (45.16%, 14/31) and 526 (29.03%, 9/31), happened base substitutions, including 27 unit point mutation and 2 two point mutation. CONCLUSIONS: The substitution of highly conserved amino acids encoded by rpoB gene results in the molecular mechanism responsible for RFP resistance in MDR-TB among patients of pneumoconiosis complicated with pulmonary tuberculosis. It also proves that rpoB gene is diversiform.

Riboflavin-rich agar enhances the rate of extracellular electron transfer from electrogenic bacteria inside a thin-layer system.

Numerous bacteria owe extracellular electron transport (EET) ability, and the rate enhancement of EET is critical for the emerging sensor technology to detect metabolically active pathogens. Here, the considerable enhancement of microbial current signal was firstly demonstrated in a thin layer electrolyte sandwiched between an agar substrate (AS) containing high concentration riboflavin (RF) and a screen-printed electrode. Covering cells with this AS showed a sharply current increase from 0.033 µA to 1.59 µA (47.7-folds) in EET-capable bacteria Shewanella oneidensis MR-1. Differential pulse voltammograms using gene-deletion mutant strains of S. oneidensis MR-1 revealed thin electrolyte between RF-loaded AS and electrode enhanced the rate of electron transfer via complexes between riboflavin and outer membrane c-type cytochrome. A similar effect in Streptococcus mutans UA159, a biofilm-forming pathogen, was also explored. Moreover, capturing and quantifying both metabolically active microbes from the dry solid surface are demonstrated with RF-loaded AS successfully. The considerable enhancement of the EET in the thin layer electrolyte provides a new direction for designing whole-cell biosensors and understanding a microbe/electrode interaction in a micro-sized space.

Combined effects of copper oxide and nickel oxide coated chitosan nanoparticles adsorbed to styrofoam resin beads on hydrothermal vent bacteria.

Microplastics are potential carriers of harmful contaminants but their combined effects are largely unknown. It needs intensive monitoring in order to achieve a better understanding of metal-oxide nanoparticles and their dispersion via microplastics such as styrofoam in the aquatic environment. In the present study, an effort was made to provide a preferable perception about the toxic effects of engineered nanoparticles (NPs), namely, copper oxide (CuO NPs), nickel oxide (NiO NPs), copper oxide/chitosan (CuO/CS NPs) and nickel oxide/chitosan (NiO/CS NPs). Characterizations of synthesized NPs included their morphology (SEM and EDX), functional groups (FT-IR) and crystallinity (XRD). Their combined toxic effect after adsorption to styrofoam (SF) was monitored using the hydrothermal vent bacterium Jeotgalicoccus huakuii as a model. This was done by determining MIC (minimum inhibitory concentration) through a resazurin assay measuring ELISA, growth, biofilm inhibition and making a live and dead assay. Results revealed that at high concentrations (60 mg/10 mL) of CuO, CuO/CS NPs and 60 mg of SF adsorbed CuO and CuO/CS NPs inhibited the growth of J. huakuii. However, NPs rather than SF inhibited the growth of bacteria. The toxicity of NPs adsorbed on plain SF was found to be less compared to NPs alone. This study revealed new dimensions regarding the positive impacts of SF at low concentrations. Synthesized NPs applied separately were found to affect the growth of bacteria substantially more than if coated to SF resin beads.

Astrocytes Mediate Cholinergic Regulation of Adult Hippocampal Neurogenesis and Memory Through M1 Muscarinic Receptor.

BACKGROUND: In the neurogenic niches of the adult hippocampus, new functional neurons are continuously generated throughout life, and generation of these neurons has been implicated in learning and memory. Astrocytes, as components of the neurogenic niches, are critical in the regulation of adult hippocampal neurogenesis (AHN). However, little is known about how astrocytes receive and respond to extrinsic cues to regulate AHN. METHODS: By using a transgenic strategy to conditionally delete astrocytic CRHM1 in mice and AAV (adeno-associated virus)-mediated overexpression of astrocytic CHRM1 specifically in the hippocampal dentate gyrus, we systematically investigated the role of astrocytic CHRM1 in the regulation of AHN and the underlying mechanisms using the combined approaches of immunohistochemistry, retrovirus labeling, electrophysiology, primary astrocyte cultures, immunoblotting, and behavioral assays. RESULTS: We report that genetic ablation of CHRM1 in astrocytes led to defects in neural stem cell survival, neuronal differentiation, and maturation and integration of newborn neurons in the dentate gyrus. Astrocytic CHRM1-mediated modulation of AHN was mediated by BDNF (brain-derived neurotrophic factor) signaling. Furthermore, CHRM1 ablation in astrocytes impaired contextual fear memory. These impairments in both AHN and memory were rescued by overexpression of astrocytic CHRM1 in the dentate gyrus. CONCLUSIONS: Our findings reveal a critical role for astrocytes in mediating cholinergic regulation of AHN and memory through CHRM1.

Chronic Administration of 13-cis-retinoic Acid Induces Depression-Like Behavior by Altering the Activity of Dentate Granule Cells.

Depression is a common but serious mental disorder and can be caused by the side effects of medications. Evidence from abundant clinical case reports and experimental animal models has revealed the association between the classic anti-acne drug 13-cis-retinoic acid (13-cis-RA) and depressive symptoms. However, direct experimental evidence of this mechanism and information on appropriate therapeutic rescue strategies are lacking. Herein, our data revealed that chronic administration of 13-cis-RA to adolescent mice induced depression-like behavior but not anxiety-like behavior. We next demonstrated that chronic 13-cis-RA application increased neural activity in the dentate gyrus (DG) using c-Fos immunostaining, which may be critically involved in some aspects of depression-like behavior. Therefore, we assessed electrophysiological functions by obtaining whole-cell patch-clamp recordings of dentate granule cells (DGCs), which revealed that chronic 13-cis-RA treatment shifted the excitatory-inhibitory balance toward excitation and increased intrinsic excitability. Furthermore, a pharmacogenetic approach was performed to repeatedly silence DGCs, and this manipulation could rescue depression-like behavior in chronically 13-cis-RA-treated mice, suggesting DGCs as a potential cellular target for the direct alleviation of 13-cis-RA-induced depression.

COVID-19 and liver dysfunction: What nutritionists need to know.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 has brought serious challenges for the medical field. Patients with COVID-19 usually have respiratory symptoms. However, liver dysfunction is not an uncommon presentation. Additionally, the degree of liver dysfunction is associated with the severity and prognosis of COVID-19. Prevention, diagnosis, and treatment of malnutrition should be routinely recommended in the management of patients with COVID-19, especially in those with liver dysfunction. Recently, a large number of studies have reported that nutrition therapy measures, including natural dietary supplements, vitamins, minerals and trace elements, and probiotics, might have potential hepatoprotective effects against COVID-19-related liver dysfunction via their antioxidant, antiviral, anti-inflammatory, and positive immunomodulatory effects. This review mainly focuses on the possible relationship between COVID-19 and liver dysfunction, nutritional and metabolic characteristics, nutritional status assessment, and nutrition therapy to provide a reference for the nutritionists while making evidence-based nutritional decisions during the COVID-19 pandemic.

[Differences in maxillary growth vector of skeletal class I with various vertical growth types before and after growth spurts].

OBJECTIVE: To identify the differences in maxillary growth vector with different vertical skeletal patterns of skeletal class I before and after growth spurts. METHODS: One hundred and ninety four cases with different vertical skeletal patterns of skeletal class I were selected and categorized into six groups according to their vertical skeletal patterns and cervical vertebral stages: cervical vertebral maturation stage (CVMS)1,2-horizontal pattern (n=30); CVMS1,2-average pattern (n=32); CVMS1, 2-vertical pattern (n=33); CVMS5, 6-horizontal pattern (n=34); CVMS5, 6-average pattern (n=29); and CVMS5, 6-vertical pattern (n=36). Lateral cephalograms were taken on all of the cases. The angle SN-C axis (theta) and angel PP-C axis (alpha) were measured. RESULTS: (1) The skeletal class I with a vertical growth pattern had larger angle SN-C axis than those with a horizontal or average growth pattern before growth spurts (P(average-vertical) < 0.05, P(horizontal-vertical) < 0.001). (2) The skeletal class I with a vertical growth pattern had the largest angle SN-C axis after growth spurts, followed by those with an average growth pattern. Those with a horizontal growth pattern had the smallest angle SN-C axis. The differences were statistically significant (P(horizontal-average) < 0.05, P(horizontal-vertical) < 0.001, P(average-vertical) < 0.001). (3) The skeletal class I with the same vertical growth pattern had slightly larger angle SN-C axis after growth spurts than before growth spurts, but without statistical significance. (4) The skeletal class I had relatively stable angle PP-C axis and no significant differences were found before and after growth spurts or among those with various vertical skeletal facial types. CONCLUSION: The magnitude of angle SN-C axis is closely associated with vertical growth patterns and is weakly influenced by maxillofacial growth and development.