The Mediating Role of Systemic Inflammation in the Effects of Fetal Famine Exposure on Cardiovascular Disease in Adults: A Cohort Study.

BACKGROUND: A few studies have reported the association between famine exposure during fetal development and risk of CVD, but no mechanisms have been explored. OBJECTIVES: The objective of this study was to examine risk of CVD in adulthood after exposure to famine during the fetal stage and explore the mediating role of systemic inflammation. METHODS: A total of 59,416 participants of the Kailuan Study without CVD were included. All participants were divided into 3 groups based on date of birth, including the unexposed group (1963-1974), the fetal-exposed group (1959-1962), and the childhood-exposed group (1949-1958). Systemic immune-inflammation index (SII) (neutrophils × platelets / lymphocytes) and systemic inflammatory response index (SIRI) (neutrophils × monocytes / lymphocytes) are 2 novel systemic inflammation indexes that represent the level of systemic inflammation. Time-weighted Cox regression was used to test the effect of famine exposure on risk of CVD, and a mediation model was used to calculate the role of systemic inflammation. RESULTS: During a median follow-up period of 12.36 (12.69, 13.16) y, a total of 3772 cases of CVD were documented. Compared with unexposed participants, the fetal-exposed group had an increased risk of CVD (HR: 1.19; 95% CI: 1.04, 1.38) and stroke (HR: 1.28; 95% CI: 1.09, 1.51) but not MI. No association was observed in the childhood-exposed group. In mediation analysis, SII mediated an estimated 24.43% of the association between fetal exposure and CVD (24.61% for stroke and 23.27% for MI). For SIRI, this percentage was 30.20% for CVD (29.94% for stroke and 31.25% of MI). CONCLUSIONS: Fetal exposure to famine may increase risk of CVD in adulthood. Systemic inflammation may play an intermediary role in the effect of fetal famine exposure on CVD.

Overlapping infection of Nocardia farcinica and Aspergillus fumigatus in a child with X-linked chronic granulomatous disease: a case report.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare inherited primary immunodeficiency syndrome, manifested as recurrent infections and inflammatory complications. Although prophylactic treatment with antibiotics and antifungals improved the outcome of CGD patients, infections remain the major cause of mortality. CASE PRESENTATION: A boy aged 3 years and 8 months was admitted to hospital complaining of lip swelling with fever for half a month and neck abscess for 11 days. After a thorough examination, severe pneumonia, respiratory failure, oral and maxillofacial space infection, and perianal abscess were confirmed. However, his condition didn't improve after initial comprehensive therapy. Subsequently, overlapping infections of Nocardia farcinica and Aspergillus fumigatus were identified by metagenomic next-generation sequencing. He was treated with imipenem, linezolid, and voriconazole intravenously, plus taking oral compound sulfamethoxazole. Later, his condition improved. Through whole-exome sequencing, the child was ultimately diagnosed as X-linked chronic granulomatous disease (X-CGD) caused by CYBB gene mutation. Allogeneic hematopoietic stem cell transplantation was the potential sanative approach but there were no available human leukocyte antigen compatible donors for the child. The family requested to transfer to a superior hospital for further treatment. Two months later, we followed up the child's family. Unfortunately, the child had expired due to severe infection. CONCLUSION: To our knowledge, this is the first case of overlapping infection of Nocardia farcinica and Aspergillus fumigatus identified by metagenomic next-generation sequencing in a child with X-CGD from China. For infectious pathogens that are hard to diagnosis by traditional detection methods, metagenomic next-generation sequencing is recommended as an adminicle or indispensable approach for microbial identification. Patients with X-CGD have poor prognosis, early diagnosis and intervention of X-CGD may reduce the mortality.

Iron-Catalyzed Radical Asymmetric Aminoazidation and Diazidation of Styrenes.

Asymmetric aminoazidation and diazidation of alkenes are straightforward strategies to build value-added chiral nitrogen-containing compounds from feedstock chemicals. They provide direct access to chiral organoazides and complement enantioselective diamination. Despite the advances in non-asymmetric reactions, asymmetric aminoazidation or diazidation based on acyclic systems has not been previously reported. Here we describe the iron-catalyzed intermolecular asymmetric aminoazidation and diazidation of styrenes. The method is practically useful and requires relatively low loading of catalyst and chiral ligand. With mild reaction conditions, the reaction can be completed on a 20 mmol scale. Studies of the mechanism suggest that the reaction proceeds via a radical pathway and involves stereocontrol of an acyclic free radical which probably takes place through a group transfer mechanism.

Effects of exposure to extremely low frequency electromagnetic fields on hippocampal long-term potentiation in hippocampal CA1 region.

Exposure to environmental electromagnetic fields, especially to the extremely low-frequency (ELF < 300 Hz) electromagnetic fields (EMFs) might produce modulation effects on neuronal activity. Long-term changes in synaptic plasticity such as long-term potentiation (LTP) involved in learning and memory may have contributions to a number of neurological diseases. However, the modulation effects of ELF-EMFs on LTP are not yet fully understood. In our present study, we aimed to evaluate the effects of exposure to ELF-EMFs on LTP in hippocampal CA1 region in rats. Hippocampal slices were exposed to magnetic fields generated by sXcELF system with different frequencies (15, 50, and 100 Hz [Hz]), intensities (0.5, 1, and 2 mT [mT]), and duration (10 s [s], 20 s, 40 s, 60 s, and 5 min), then the baseline signal recordings for 20 min and the evoked field excitatory postsynaptic potentials (fEPSPs) were recorded. We found that the LTP amplitudes decreased after magnetic field exposure, and the LTP amplitudes decreased in proportion to exposure doses and durations, suggesting ELF-EMFs may have dose and duration-dependent inhibition effects. Among multiple exposure duration and doses combinations, upon 5 min magnetic field exposure, 15 Hz/2 mT maximally inhibited LTP. Under 15 Hz/2 mT ELF-EMFs, LTP amplitude decreases in proportion to the length of exposure durations within 5 min time frame. Our findings illustrated the potential effects of ELF-EMFs on synaptic plasticity and will lead to better understanding of the influence on learning and memory.

The status of diagnosis and treatment to intracranial hypotension, including SIH.

Intracranial hypotension, especially spontaneous intracranial hypotension (SIH), is a well-recognized entity associated with cerebrospinal fluid (CSF) leaks, and has being recognized better in resent years, while still woefully inadequate. An increasing number of factors including iatrogenic factors are realized to involve in development and progression of intracranial hypotension. The diagnosis remains difficult due to the various clinical manifestations, some of which are nonspecific and easily to be neglected. Multiple imaging tests are optional in CSF leakage identification while clinicians are still confronted with difficulties when making selection resulting from superiorities and disadvantages of different imaging tests. Treatments for intracranial hypotension are multifarious but evidence is anecdotal. Values of autologous epidural blood patching (EBP), the mainstay of first-line interventional treatment currently, is getting more and more regards while there are no systematic review of its efficacy and risks. Hereby, the purpose of this review was to reveal the present strategy of intracranial hypotension diagnosis and treatment by reviewing literatures, coupled with our experience in clinical work.

Impact of the leucocyte immunoglobulin-like receptor A3 (LILRA3) on susceptibility and subphenotypes of systemic lupus erythematosus and Sjögren's syndrome.

BACKGROUND: Recently, our research group identified the non-deleted (functional) leucocyte immunoglobulin-like receptor A3 (LILRA3) as a new genetic risk for rheumatoid arthritis. OBJECTIVES: To further investigate whether the functional LILRA3 is a new susceptibility factor for other autoimmune diseases-for example, systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). METHODS: The LILRA3 deletion polymorphism and its tagging single nucleotide polymorphism rs103294 were genotyped for 1099 patients with SLE, 403 patients with pSS and 2169 healthy controls. Association analyses were performed in whole dataset or clinical/serological subsets. The impact of LILRA3 on SLE activity and LILRA3 expression was evaluated. RESULTS: The functional LILRA3 conferred high susceptibility to both SLE (p=3.51×10(-7), OR=2.03) and pSS (p=1.40×10(-3), OR=2.32). It was associated with almost all the clinical/serological features in SLE, especially with leucopenia (p=4.09×10(-7), OR=2.19) and thrombocytopenia (p=1.68×10(-5), OR=1.70). In pSS, functional LILRA3 was specifically associated with leucopenia (p=4.39×10(-4), OR=3.25), anti-Ro/SSA-positive subphenotypes (p=4.54×10(-3), OR=2.34) and anti-La/SSB-positive subphenotypes (p=0.012, OR=2.49). Functional LILRA3 conferred higher disease activity in patients with SLE (p=0.044) and higher LILRA3 expression in both SLE (p=5.57×10(-8)) and pSS (p=1.49×10(-7)) than in controls. CONCLUSIONS: Functional LILRA3 is a new susceptibility factor for SLE and pSS. It highly predisposes to certain phenotypes such as leucopenia and thrombocytopenia in SLE, and may confer increased disease activity in SLE and a higher risk of leucopenia and autoantibody-positive subphenotypes in pSS.

[Effects of Dickkopf-1 on synovitis of rheumatoid arthritis].

OBJECTIVE: As an important feature of rheumatoid arthritis (RA), an excessive amount of pro-inflammatory cytokines in RA synovial lesions induces the proliferation of synovial fibroblasts, cartilage erosion and systemic inflammatory immune response. Wnt inhibitor, Dkk-1, contributes to joint remodeling. This study was conducted to explore the role of Dkk-1 in the regulation of pro-inflammatory cytokine secretion. METHODS: Rheumatoid arthritis synovial fibroblasts (RASF) were cultured from surgical synovial specimens and utilized at passages 4-8. For Dkk-1 silencing assay, Dkk-1-specific siRNA and control scrambled siRNA were transfected into RASF respectively. For Dkk-1 over-expression assay, Dkk-1 plasmid and control vector were transfected into RASFs respectively. Production of pro-inflammatory cytokines, such as interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8), were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR) at pre- and post-transfection respectively. Differences between various groups were evaluated by Wilcoxon signed-rank test. RESULTS: After a treatment of Dkk-1-specific siRNA, RASF exhibited decreased production of pro-inflammatory cytokines in association with down-regulated Dkk-1 levels while Dkk-1 over-expression could up-regulate the production of pro-inflammatory cytokines. The effects were marked when RAFS was activated by TNF-α and IL-1ß after transfection. CONCLUSION: Dkk-1 promotes the production of pro-inflammatory cytokines in RASF so as to exacerbate synovitis of RA. And targeting Dkk-1 may provide a novel therapeutic strategy for RA.

Study on the influencing factors of rural residents' willingness to classify domestic waste in the context of acquaintance society: An example from Jiangsu Province in Chin.

Waste classification helps to maximize the recovery of resources, reduce environmental pollution and promote sustainable economic development. To improve the willingness of rural residents to classify waste, based on the background of a rural acquaintance society, this thesis constructed a theoretical model of waste classification cognition, willingness to classify, economic incentives, face consciousness and vernacular identity affecting the willingness of rural residents to classify waste, and put forward seven research hypotheses. With the help of 530 valid surveys of rural residents in Jiangsu Province, the seven hypotheses were verified using structural equation modeling, and the mediating effect of rural residents' willingness to classify waste was examined using the bootstrap method. The results showed that waste classification awareness, knowledge of waste classification, economic incentives, face-saving concepts and local identity all affected rural residents' willingness to classify waste, and all were significant at a 0.01 level. They also showed that face-saving concepts and local identity played partial mediating roles. Strategies to improve rural residents' willingness to classify waste have been proposed, such as multiple incentives to enhance subjective awareness, play the role of face culture in rural areas, strengthen the construction of public culture in rural areas, and improve rural residents' local identity.

An Experimental Investigation of the Precipitation Utilization of Plants in Arid Regions.

What represents a water source for the ecological restoration of a plant in an arid region is still up to debate. To address this issue, we conducted an in situ experiment in the Ulan Buh Desert of China, to study desert plants absorbing atmospheric water vapor. We selected Tamarisk, a common drought-salt-tolerant species in the desert, for ecological restoration as our research subject, used a newly designed lysimeter to monitor precipitation infiltration, and a sap flow system to track reverse sap flow that occurred in the shoot, branch, and stem during the precipitation event, and observed the precipitation redistribution process of the Tamarisk plot. The results showed that Tamarisk indeed directly absorbs precipitation water: when precipitation occurs, the main stem, lateral branch, and shoot all show the signs of reversed sap flow, and the reversed sap flow accounted for 21.5% of the annual sap flow in the shoot and branch, and 13.6% in the stem. The precipitation event in the desert was dominated by light precipitation events, which accounted for 81% of the annual precipitation events. It was found that light precipitation can be directly absorbed by the Tamarisk leaves, especially during nighttime or cloudy days. Even when the precipitation is absent, it was found that desert plants can still absorb water from the unsaturated atmospheric vapor; even the absorbed atmospheric water vapor was transported from the leaves to the stem, forming a reversed sap flow, as a reversed sap flow was observed when the atmospheric relative humidity reached 75%. This study indicated that the effect of light precipitation on desert plants was significant and should not be overlooked in terms of managing the ecological and hydrological systems in arid regions.

Study on the Role of Physical Fields in TMAS to Modulate Synaptic Plasticity in Mice.

OBJECTIVE: Transcranial magneto-acoustic stimulation (TMAS) is a composite technique combining static magnetic and coupled electric fields with transcranial ultrasound stimulation (TUS) and has shown advantages in neuromodulation. However, the role of these physical fields in neuromodulation is unclear. Synaptic plasticity is the cellular basis for learning and memory. In this paper, we varied the intensity of static magnetic, electric and ultrasonic fields respectively to investigate the modulation of synaptic plasticity by these physical fields. METHODS: There are control, static magnetic field (0.1 T/0.2 T), TUS (0.15/0.3 MPa), and TMAS (0.15 MPa + 0.2 V/m, 0.3 MPa + 0.2 V/m, 0.3 MPa + 0.4 V/m) groups. Hippocampal areas were stimulated at 5 min daily for 7 days and in vivo electrophysiological experiments were performed. RESULTS: TMAS induced greater LTP, LTD, and paired-pulse ratio (PPR) than TUS, reflecting that TMAS has a more significant modulation in both long- and short- term synaptic plasticity. In TMAS, a doubling of the electric field amplitude increases LTP, LTD and PPR to a greater extent than a doubling of the acoustic pressure. Increasing the static magnetic field intensity has no significant effect on the modulation of synaptic plasticity. CONCLUSION: This paper argues that electric fields should be the main reason for the difference in modulation between TMAS and TUS and that changing the amplitude of the electric field affected the modulation of TMAS more than changing the acoustic pressure. SIGNIFICANCE: This study elucidates the roles of the physical fields in TMAS and provides a parameterisation way to guide TMAS applications based on the dominant roles of the physical fields.

Polymorphisms of the HTR3B gene are associated with post-surgery emesis in a Chinese Han population.

WHAT IS KNOWN AND OBJECTIVES: The serotoninergic receptor 5-hydroxytryptamine (serotonin) receptor 3 (HTR3) is instrumental in the regulation of nausea and emesis (vomiting).This study investigated whether common genomic variations of the A and B subunits of HTR3 (HTR3A, HTR3B) are associated with the incidence of post-operative vomiting in a Chinese Han population. METHODS: Two hundred and thirty-one female Chinese Han patients undergoing gynaecological surgery with standardized general anaesthesia were recruited for the study. Clinical symptoms after surgery were recorded and direct DNA sequencing was performed to detect polymorphisms of HTR3A and HTR3B. RESULTS: Five single nucleotide polymorphisms (SNPs) in HTR3A and HTR3B were found, with R(2)  > 0·8 and minor allele frequency > 10%. One of these (rs3758987 in HTR3B) was statistically associated with vomiting, after adjusting for body weight, body mass index and duration of general anaesthesia in dominant and additive models (P = 0·047 and P = 0·034). WHAT IS NEW AND CONCLUSION: The HTR3B rs3758987 SNP might serve as a predictor of post-operative vomiting in Chinese Han patients undergoing gynaecological laparoscopic surgery.

Amphotericin B colloidal dispersion: an effective drug for the treatment of mucormycosis in China.

Objective: Mucormycosis has emerged as an increasingly important cause of morbidity and mortality in immunocompromised patients, but the effective drugs for the treatment are limited. Hence, the study aimed to summarize the characteristics of mucormycosis in patients with hematological malignancies, and investigate the efficacy and safety of Amphotericin B Colloidal Dispersion (ABCD) in treating mucormycosis. Methods: In this study, patients with mucormycosis complicated by hematological malignancies who received ABCD at the First Affiliated Hospital of Zhengzhou University from April 2021 to May 2022 were retrospectively enrolled. The clinical data of the enrolled patients were collected, and then, the drug response at 2 weeks, 4 weeks, and the end of treatment; the survival rate at 4, 8, and 12 weeks; and the laboratory-related indicators and adverse events (AEs) associated with ABCD were evaluated. Results: In total, 9 patients with mucormycosis complicated by hematological malignancies were enrolled. The main symptoms were fever, cough, and chest pain. In addition, reversed halo signs (RHS) were found on chest CTs. The responses to ABCD at 2 weeks, 4 weeks, and the end of treatment were 100% (9/9), 77.8% (7/9), and 77.8% (7/9), respectively. The survival rates of the patients at 4, 8, and 12 weeks were 77.8% (7/9), 66.7% (6/9), and 66.7% (6/9), respectively. Among laboratory-related indicators, white blood cell (WBC) counts were significantly increased from baseline after 1 and 2 weeks of ABCD treatment (P<0.05), whereas neutrophil counts were only increased significantly from baseline at 2 weeks post-treatment (P<0.05). The most common AEs were infusion-related AEs manifesting as fever, chills, and pruritus. Moreover, none of the patients suffered from renal injury once again. Conclusion: ABCD is a promising treatment strategy for patients with mucormycosis complicated by hematologic malignancies, showing remarkable efficacy and safety.

Case Report: Metagenomic next-generation sequencing assists in dynamic pathogen monitoring: powerful tool for progressing severe pneumonia.

Background: Severe community-acquired pneumonia (sCAP) is life-threatening and characterized by intensive care unit (ICU) admission and high mortality. And they are vulnerable to hospital-acquired infection. In such a severe condition, metagenomic next-generation sequencing (mNGS) outperforms for short turnaround time and broad detection spectrum. Case presentation: A 15-year-old male with severe influenza and methicillin-resistant Staphylococcus aureus (MRSA) pneumonia progressed rapidly, initially misdiagnosed as influenza co-infected with Aspergillus for misleading bronchoscopy manifestations. The turnaround time of mNGS is 13 h, which has the potential to expedite the clinical medication process. With the powerful support of mNGS and extracorporeal membrane oxygenation (ECMO), anti-infective therapy was adjusted accordingly, and vital signs gradually stabilized. After tortuous treatment and unremitting efforts, the patient recovered well. Conclusions: Rapid mNGS applications, timely medication adjustments, strong ECMO support and active family compliance contribute to this miracle of life. False-negative or false-positive results are alarming, anti-infective medications should be adjusted after a comprehensive review of physical status and other indicators.

Velvet Family Members Regulate Pigment Synthesis of the Fruiting Bodies of Auricularia cornea.

Color is a crucial feature to consider when breeding and improving strains of Auricularia cornea. To uncover the mechanism of white strain formation in A. cornea, this study selected parental strains that were homozygous for the color trait and analyzed the genetic laws of A. cornea color through genetic population construction, such as test-cross, back-cross, and self-cross populations, and the statistical analysis of color trait segregation. Moreover, the study developed SSR molecular markers to construct a genetic linkage map, perform the fine mapping the color-controlling genetic locus, and verify candidate genes using yeast two-hybrid, transcriptome analysis, and different light treatments. The results of the study indicated that the color trait of A. cornea is controlled by two pairs of alleles. When both pairs of loci are dominant, the fruiting body is purple, while when both pairs of loci are recessive or one pair of loci is recessive, the fruiting body is white. Based on the linkage map, the study finely mapped the color locus within Contig9_29,619bp-53,463bp in the A. cornea genome and successfully predicted the color-controlling locus gene A18078 (AcveA), which belongs to the Velvet factor family protein and has a conserved structure domain of the VeA protein. It can form a dimer with the VelB protein to inhibit pigment synthesis in filamentous fungi. Lastly, the study validated the interaction between AcVeA and VelB (AcVelB) in A. cornea at the gene, protein, and phenotype levels, revealing the mechanism of inhibition of pigment synthesis in A. cornea. Under dark conditions, dimerization occurs, allowing it to enter the nucleus and inhibit pigment synthesis, leading to a lighter fruiting body color. However, under light conditions, the dimer content is low and cannot enter the nucleus to inhibit pigment synthesis. In summary, this study clarified the mechanism of white strain formation in A. cornea, which could aid in improving white strains of A. cornea and studying the genetic basis of color in other fungi.

Association of trajectories of non-high-density lipoprotein cholesterol concentration with risk of cardiovascular disease: the Kailuan Study.

OBJECTIVES: This study aimed to assess the association between longitudinal change in non-high-density lipoprotein cholesterol (non-HDL-C) and subsequent cardiovascular disease (CVD) risk. DESIGN: A retrospective study. SETTING: Data were obtained from the Kailuan Study, a dynamic cohort study initiated in 2006 in Tangshan, China. PARTICIPANTS: The current study included 41 085 participants (mean age 53.9±11.6 years) free of CVD events in or before 2012. The non-HDL-C trajectory was developed according to the repeated measurement during 2006-2012 surveys to predict the CVD risk from 2012 to 2020. PRIMARY OUTCOME MEASURES: CVD events included myocardial infarction and stroke. RESULTS: 3 discrete non-HDL-C trajectories were identified: low-increasing (n=20 038), moderate-increasing (n=17 987) and high-increasing (n=3060). During 8 years of follow-up, 1797 CVD events were documented. Relative to the low-increasing pattern, adjusted HRs were 1.25 (95% CI: 1.13 to 1.38) for the moderate-increasing pattern and 1.46 (95% CI: 1.24 to 1.71) for the high-increasing pattern after adjustment for potential confounders such as age, sex, education background, smoking status, drinking status, physical activity, body mass index, low-density lipoprotein cholesterol, hypertension, diabetes and lipid-lowering medications. CONCLUSIONS: Changes in non-HDL-C were significantly associated with subsequent risk of CVD events, and participants with a high-increasing pattern had a higher CVD risk. Long-term monitoring of non-HDL-C could be useful to improve the prediction of CVD risk. TRIAL REGISTRATION NUMBER: ChiCTR-TNC-1100148.

Dicarboxylic Amino Acid Permease 7219 Regulates Fruiting Body Type of Auricularia heimuer.

Auricularia heimuer is a widely cultivated jelly mushroom. The fruiting bodies are categorized into cluster and chrysanthemum types. With changing consumer demands and the need to reduce bio-waste, the demand for clustered fruiting bodies is increasing. Therefore, gene mining for fruiting body types is a matter of urgency. We determined that the A. heimuer locus for fruiting body type was located at one end of the genetic linkage map. The locus was localized between the markers D23860 and D389 by increasing the density of the genetic linkage map. BlastN alignment showed that the marker SCL-18 was also located between D23860 and D389, and a total of 25 coding genes were annotated within this interval. Through parental transcriptome analysis and qRT-PCR verification, the locus g7219 was identified as the gene controlling the fruiting body type. A single-nucleotide substitution in the TATA box of g7219 was detected between the parents. By PCR amplification of the promoter region of g7219, the TATA-box sequences of the cluster- and chrysanthemum-type strains were found to be CATAAAA and TATAAAA, respectively. This study provides a foundation for the breeding of fruiting body types and strain improvement of A. heimuer.

High-quality genome assembly and multi-omics analysis of pigment synthesis pathway in Auricularia cornea.

Owing to its great market potential for food and health care, white Auricularia cornea, a rare edible fungus, has received increased attention in recent years. This study presents a high-quality genome assembly of A. cornea and multi-omics analysis of its pigment synthesis pathway. Continuous Long Reads libraries, combined with Hi-C-assisted assembly were used to assemble of white A. cornea. Based on this data, we analyzed the transcriptome and metabolome of purple and white strains during the mycelium, primordium, and fruiting body stages. Finally, we obtained the genome of A.cornea assembled from 13 clusters. Comparative and evolutionary analysis suggests that A.cornea is more closely related to Auricularia subglabra than to Auricularia heimuer. The divergence of white/purple A.cornea occurred approximately 40,000 years ago, and there were numerous inversions and translocations between homologous regions of the two genomes. Purple strain synthesized pigment via the shikimate pathway. The pigment in the fruiting body of A. cornea was γ-glutaminyl-3,4-dihydroxy-benzoate. During pigment synthesis, α-D-glucose-1P, citrate, 2-Oxoglutarate, and glutamate were four important intermediate metabolites, whereas polyphenol oxidase and other 20 enzyme genes were the key enzymes. This study sheds light on the genetic blueprint and evolutionary history of the white A.cornea genome, revealing the mechanism of pigment synthesis in A.cornea. It has important theoretical and practical implications for understanding the evolution of basidiomycetes, molecular breeding of white A.cornea, and deciphering the genetic regulations of edible fungi. Additionally, it provides valuable insights for the study of phenotypic traits in other edible fungi.

Transcranial Magneto-Acoustic Stimulation Attenuates Synaptic Plasticity Impairment through the Activation of Piezo1 in Alzheimer's Disease Mouse Model.

The neuropathological features of Alzheimer's disease include amyloid plaques. Rapidly emerging evidence suggests that Piezo1, a mechanosensitive cation channel, plays a critical role in transforming ultrasound-related mechanical stimuli through its trimeric propeller-like structure, but the importance of Piezo1-mediated mechanotransduction in brain functions is less appreciated. However, apart from mechanical stimulation, Piezo1 channels are strongly modulated by voltage. We assume that Piezo1 may play a role in converting mechanical and electrical signals, which could induce the phagocytosis and degradation of Aß, and the combined effect of mechanical and electrical stimulation is superior to single mechanical stimulation. Hence, we design a transcranial magneto-acoustic stimulation (TMAS) system, based on transcranial ultrasound stimulation (TUS) within a magnetic field that combines a magneto-acoustic coupling effect electric field and the mechanical force of ultrasound, and applied it to test the above hypothesis in 5xFAD mice. Behavioral tests, in vivo electrophysiological recordings, Golgi-Cox staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, real-time quantitative PCR, Western blotting, RNA sequencing, and cerebral blood flow monitoring were used to assess whether TMAS can alleviate the symptoms of AD mouse model by activating Piezo1. TMAS treatment enhanced autophagy to promote the phagocytosis and degradation of ß-amyloid through the activation of microglial Piezo1 and alleviated neuroinflammation, synaptic plasticity impairment, and neural oscillation abnormalities in 5xFAD mice, showing a stronger effect than ultrasound. However, inhibition of Piezo1 with an antagonist, GsMTx-4, prevented these beneficial effects of TMAS. This research indicates that Piezo1 can transform TMAS-related mechanical and electrical stimuli into biochemical signals and identifies that the favorable effects of TMAS on synaptic plasticity in 5xFAD mice are mediated by Piezo1.

Characterization, antioxidant activity, and mineral profiling of Auricularia cornea mushroom strains.

Background: Mushrooms are considered as next-generation healthy food components. Owing to their low-fat content, high-quality proteins, dietary fiber, and rich source of nutraceuticals. They are ideally preferred in formulation of low-caloric functional foods. In this view, the breeding strategies of mushroom Auricularia cornea (A. cornea) focusing on high yield and higher quality with rich nutritional values and health benefits are still needed. Materials and methods: A total of 50 strains of A. cornea were used to analyze the bio efficiency and the time required for fruiting body formation following the cultivation experiment. The calorimetric method was used to evaluate the antioxidant activity and quantify the crude polysaccharides and minerals content thereafter. Results: The results showed that the time required for fruiting body formation and biological efficiency varied significantly among the selected strains. Noticeably, the wild domesticated strain Ac13 of A. cornea mushroom showed the shortest fruit development time (80 days). Similarly, the hybrid strains including Ac3 and Ac15 possessed the highest biological efficiency (82.40 and 94.84%). Hybrid strains Ac18 (15.2%) and cultivated strains Ac33 (15.6%) showed the highest content of crude polysaccharides, while cultivated strains Ac1 and Ac33, demonstrated the highest content of total polysaccharides in the fruiting body (216 mg. g-1 and 200 mg. g-1). In the case of mineral content, the highest zinc contents were observed from the cultivated strain Ac46 (486.33 mg·kg-1). The maximum iron content was detected from the hybrid strain Ac3 (788 mg·kg-1), and the wild domesticated strain Ac28 (350 mg·kg-1). The crude polysaccharides of the A. cornea strain showed significant antioxidant potential, and the ability of Ac33 and Ac24 to scavenge DPPH radicals and ABTS, which was significantly improved compared to other strains, respectively. Principal component analysis was applied to examine the agronomic traits and chemical compounds of various strains of A. cornea mushrooms. The results revealed that cultivated, wild domesticated, and hybrid strains of A. cornea exhibited distinct characteristics in terms of growth, yield, and nutritional properties. Conclusion: The crude polysaccharides from A. cornea mushroom strains act as natural antioxidants, the wild, hybrid, and commercial A. cornea mushroom strains can achieve rapid growth, early maturation, and high yields. The evaluation of biochemical indexes and nutritional characteristics of strains with excellent traits provided a scientific basis for initiating high-quality breeding, provided germplasm resources for the production of "functional food" with real nutritional and health value.

Nontuberculous mycobacteria by metagenomic next-generation sequencing: Three cases reports and literature review.

Background: The increasing worldwide incidence of nontuberculous mycobacterial lung disease (NTM-LD) and the similarity of its manifestations to those of tuberculosis (TB) pose huge challenges in the diagnosis and treatment of NTM-LD, which is commonly misdiagnosed and mistreated as TB. Proper diagnosis and treatment at an early stage can greatly improve patient outcomes. Case presentation: Mycobacterium avium was identified by mNGS in lung tissue of case 1 and bronchioalveolar fluid from case 2 that was not identified using conventional microbiological methods. Multiple NTM species were detected in the blood mNGS samples from case 3 who had disseminated NTM infection. Although NTM was isolated from blood culture, conventional methods failed to identify the organisms to the level of species. All three patients were suffering from and being treated for myelodysplastic syndrome, rheumatoid arthritis, systemic lupus erythematosus, or acute lymphoblastic leukemia, making them immunosuppressed and susceptible to NTM infections. Case 1 and Case 2 significantly improved after anti-NTM treatment, but case 3 succumbed to the infection due to her underlying medical illness despite aggressive treatment. Conclusions: The cases in this study demonstrate the effectiveness of mNGS in facilitating and improving the clinical diagnosis of NTM infections. We propose combining mNGS with traditional diagnostic methods to identify pathogens at the early stages of the disease so that targeted treatment can be implemented.