A cingulate-hippocampal circuit mediates early depressive-like behavior in the mouse model of Alzheimer disease.

Depressive symptoms usually precede the cognitive decline in Alzheimer disease (AD) and worsen the clinical outcome. However, the neural circuitry mediating early emotional dysfunction, especially depressive symptoms in AD, remains elusive. Anterior cingulate cortex (ACC) is closely related to depression and vulnerable in AD. By quantitative whole-brain mapping and electrophysiological recording, we found that the decreased axonal calcium activity in neurons of ACC and the glutamatergic projection from ACC to the ventral hippocampal CA1 (vCA1) is significantly impaired in 3-month-old 5×FAD mice, which exhibit depressive-like phenotype before cognition defects in early stage. The activation of ACC-vCA1 circuit by chemogenetic manipulation efficiently ameliorated the early depressive-like behaviors in 5×FAD mice. We further identified the upregulated neuregulin-1 (Nrg1) in ACC impaired the excitatory synaptic transmission from the ACC to vCA1 in AD. Our work reveals the role of ACC-vCA1 circuit in regulating AD associated depression symptom in a mouse model of AD.

Loss of function variant in CIP2A associated with female infertility with early embryonic arrest and fragmentation.

BACKGROUND: Early embryonic arrest and fragmentation (EEAF) is a common cause of female infertility, but the genetic causes remain to be largely unknown. CIP2A encodes the cellular inhibitor of PP2A, playing a crucial role in mitosis and mouse oocyte meiosis. METHODS: Exome sequencing and Sanger sequencing were performed to identify candidate causative genes in patients with EEAF. The pathogenicity of the CIP2A variant was assessed and confirmed in cultured cell lines and human oocytes through Western blotting, semi-quantitative RT-PCR, TUNEL staining, and fluorescence localization analysis. FINDINGS: We identified CIP2A (c.1510C > T, p.L504F) as a novel disease-causing gene in human EEAF from a consanguineous family. L504 is highly conserved throughout evolution. The CIP2A variant (c.1510C > T, p.L504F) reduced the expression level of the mutant CIP2A protein, leading to the abnormal aggregation of mutant CIP2A protein and cell apoptosis. Abnormal aggregation of CIP2A protein and chromosomal dispersion occurred in the patient's oocytes and early embryos. We further replicated the patient phenotype by knockdown CIP2A in human oocytes. Additionally, CIP2A deficiency resulted in decreased levels of phosphorylated ERK1/2. INTERPRETATION: We first found that the CIP2A loss-of-function variant associate with female infertility characterized by EEAF. Our findings suggest the uniqueness and importance of CIP2A gene in human oocyte and early embryo development. FUNDING: This work was supported by National Key Research and Development Program of China (2023YFC2706302), the National Natural Science Foundation of China (81000079, 81170165, and 81870959), the HUST Academic Frontier Youth Team (2016QYTD02), and the Key Research of Huazhong University of Science and Technology, Tongji Hospital (2022A20).

Dense Amorphous Passivation Layer Formed on Aluminum Alloy Surfaces by Femtosecond Laser-Assisted Oxygen-Rich Doping.

Aluminum (Al) alloy surfaces are prone to serious corrosion in humid and salt-laden environments, which promotes the development of numerous protective approaches. Although the amorphous state is more conducive to improve corrosion resistance compared with the crystalline state, it still faces coating design problems like insufficient adhesive strength and flaking-off tendency. Here, we propose a strategy of femtosecond laser-assisted oxygen-rich doping to in situ create a dense high-quality passivation layer on Al alloy surfaces. With respect to the femtosecond laser processing in traditional air ambience, the material surface modifications within the oxygen-rich environment demonstrate some distinctiveness. For the ridge area of the laser ablation grooves, the oxidation surface is separated into two layers: the outer region presents a loose and porous appearance similar to the observations in the air ambience, while the inner region exhibits complete and homogeneous oxidation, especially associated with the continuous distribution of the amorphous substance, in sharp contrast to the nanoscale discrete amorphous formation in the air case. Simultaneously, the high degree of material oxidization with the amorphous phase is also developed on the wallside area of the groove valleys, which is much different from the incomplete oxidation in the air ambience. As a result, the measured corrosion current decreases by 49 times to a value of Icorr = 1.19 × 10-10 A/cm2 relative to the laser treatment in the air environment. Such a method offers the prospect for elevating the anticorrosion performance of metal surfaces.

Machine Learning for Early Prediction of Major Adverse Cardiovascular Events After First Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction: Retrospective Cohort Study.

BACKGROUND: The incidence of major adverse cardiovascular events (MACEs) remains high in patients with acute myocardial infarction (AMI) who undergo percutaneous coronary intervention (PCI), and early prediction models to guide their clinical management are lacking. OBJECTIVE: This study aimed to develop machine learning-based early prediction models for MACEs in patients with newly diagnosed AMI who underwent PCI. METHODS: A total of 1531 patients with AMI who underwent PCI from January 2018 to December 2019 were enrolled in this consecutive cohort. The data comprised demographic characteristics, clinical investigations, laboratory tests, and disease-related events. Four machine learning models-artificial neural network (ANN), k-nearest neighbors, support vector machine, and random forest-were developed and compared with the logistic regression model. Our primary outcome was the model performance that predicted the MACEs, which was determined by accuracy, area under the receiver operating characteristic curve, and F1-score. RESULTS: In total, 1362 patients were successfully followed up. With a median follow-up of 25.9 months, the incidence of MACEs was 18.5% (252/1362). The area under the receiver operating characteristic curve of the ANN, random forest, k-nearest neighbors, support vector machine, and logistic regression models were 80.49%, 72.67%, 79.80%, 77.20%, and 71.77%, respectively. The top 5 predictors in the ANN model were left ventricular ejection fraction, the number of implanted stents, age, diabetes, and the number of vessels with coronary artery disease. CONCLUSIONS: The ANN model showed good MACE prediction after PCI for patients with AMI. The use of machine learning-based prediction models may improve patient management and outcomes in clinical practice.

Climate warming has divergent physiological impacts on sympatric lizards.

Climate warming is expected to affect the vulnerability of sympatric species differentially due to their divergent traits, but the underlying physiological mechanisms of those impacts are poorly understood. We conducted field warming experiments (present climate vs. warm climate) using open-top chambers to determine the effects of climate warming on active body temperature, oxidative damage, immune competence, growth and survival in two sympatric desert-dwelling lizards, Eremias multiocellata and Eremias argus from May 2019 to September 2020. Our climate warming treatment did not affect survival of the two species, but it did increase active body temperatures and growth rate in E. multiocellata compared to E. argus. Climate warming also induced greater oxidative damage (higher malondialdehyde content and catalase activity) in E. multiocellata, but not in E. argus. Further, climate warming increased immune competence in E. multiocellata, but decreased immune competence in E. argus, with regards to white blood cell counts, bacteria killing ability and relative expression of immunoglobulin M. Our results suggest that climate warming enhances body temperature, and thereby oxidative stress, immune competence and growth in E. multiocellata, but decreases immune competence of E. argus, perhaps as a cost of thermoregulation to maintain body temperatures under climate warming. The divergent physiological effects of climate warming on sympatric species may have profound ecological consequences if it eventually leads to changes in reproductive activities, population dynamics and community structure. Our study highlights the importance of considering interspecific differences in physiological traits when we evaluate the impact of climate warming on organisms, even for those closely-related species coexisting within the same geographical area.

Rapid Diagnosis of Hemophagocytic Lymphohistiocytosis Triggered by Disseminated BCG Infection in Infants With Severe Combined Immunodeficiency: Case Report.

Hemophagocytic lymphohistiocytosis triggered by disseminated Bacillus Calmette-Guerin infection is rare. Targeted next-generation sequencing for tuberculosis can rapidly identify different strains of Mycobacterium tuberculosis complex as well as drug resistance genes. Herein we report 2 cases of hemophagocytic lymphohistiocytosis in whom targeted next-generation sequencing rapidly identified Bacillus Calmette-Guerin as the infectious trigger.

Pre- and post-pollination barriers between two exotic and five native Sagittaria species: Implications for species conservation.

Anthropogenic introduction of species has resulted in a breakdown of geographical barriers and hybridization in previously allopatric species. Thus, examining hybridization proneness of exotic species contributes to revealing its potential threat. Moreover, reproductive barriers may be strengthened or weakened due to long-term geographical isolation for these newly sympatric species. However, few studies have evaluated multiple barriers between alien and native species. In this study, we quantified the importance of four pre-pollination barriers (phenological, floral traits, pollen production, and floral constancy) and four post-pollination barriers (pollen-pistil incompatibility, seed set, seed viability, and seedling survival) between two introduced and five native Sagittaria species. Results showed that introduced S. platyphylla was cross-compatible with two native species, whereas introduced S. montevidensis was incapable of hybridizing with any native species. Different barriers were asymmetric within species pairs and multiple barriers acted in concert to maintain species boundaries. Post-pollination barriers contributed more to total reproductive isolation in native species, whereas pre-pollination barriers played a stronger role in total reproductive isolation for two introduced species. Seed set was the only barrier that was positively correlated with genetic distance. Our results provide a perspective to better understand reproductive barriers for secondary contact species. We highlight the importance of monitoring hybridization events before human introduction and the possible conservation strategies to remove invasive species with hybridization proneness.

EMD-based gray combined forecasting model - Application to long-term forecasting of wind power generation.

Wind power is the most promising renewable energy source after hydropower because of its mature technology and low price, and has great potential for carbon emission reduction. Long-term forecasts of its power generation can help power companies to develop operational plans, grid configuration and power dispatch, and can also provide a basis for the government to formulate energy and environmental policies. However, due to the characteristics of China's monsoon climate and wind power industry development, wind power generation data are characterized by nonlinear cycles and small data volume, which makes accurate prediction more difficult. To this end, this paper develops a new prediction model and applies it to the long-term prediction of wind power generation in China, and proposes some targeted policy recommendations based on the prediction results to promote the development of China's wind power industry.

Cyclic anthraquinone derivatives, unique G-quadruplex binders, selectively induce cancer cell apoptosis and inhibit tumor growth.

Cyclic anthraquinone derivatives (cAQs), which link two side chains of 1,5-disubstituted anthraquinone as a threading DNA intercalator, have been developed as G-quartet (G4) DNA-specific ligands. Among the cAQs, cAQ-mBen linked through the 1,3-position of benzene had the strongest affinity for G4 recognition and stabilization in vitro and was confirmed to bind to the G4 structure in vivo, selectively inhibiting cancer cell proliferation in correlation with telomerase expression levels and triggering cell apoptosis. RNA-sequencing analysis further indicated that differentially expressed genes regulated by cAQ-mBen were profiled with more potential quadruplex-forming sequences. In the treatment of the tumor-bearing mouse model, cAQ-mBen could effectively reduce tumor tissue and had less adverse effects on healthy tissue. These results suggest that cAQ-mBen can be a potential cancer therapeutic agent as a G4 binder.

Development of periodically concentric rings within microcavity upon femtosecond laser irradiation.

Understanding the formation mechanisms of the nanostructures and their designs has important implications for both the fundamental science and application prospects. In this study, we proposed a strategy for femtosecond laser-induced high regularity concentric rings within silicon microcavity. The morphology of the concentric rings can be flexibly modulated by the pre-fabricated structures and the laser parameters. The physics involved is deeply explored by the Finite-Difference-Time-Domain simulations, which reveals that the formation mechanism can be attributed to the near-field interference of the incident laser and the scattering light from the pre-fabricated structures. Our results provide a new method for creating the designable periodic surface structures.

Femtosecond laser upgrading the quality of bismuth films to enhance ultra-broadband photodetection.

Topological insulator bismuth has attracted considerable attention for the fabrication of room-temperature, wide bandwidth, and high-performance photodetectors due to the gapless edge state and insulating bulk state properties. However, both the photoelectric conversion and carrier transportation of the bismuth films are extremely affected by the surface morphology and grain boundaries to limit optoelectronic properties further. Here, we demonstrate a strategy of femtosecond laser treatment for upgrading the quality of bismuth films. After the treatment with proper laser parameters, the measurement of average surface roughness can be reduced from Ra = 44 nm to 6.9 nm, especially with accompany of the evident grain boundary elimination. Consequently, the photoresponsivity of the bismuth films increases approximately 2 times within an ultra-broad spectrum range from the visible to mid-infrared. This investigation suggests that the femtosecond laser treatment can help to benefit the performance of topological insulator ultra-broadband photodetectors.

A Se-enriched Grifola frondosa polysaccharide induces macrophage activation by TLR4-mediated MAPK signaling pathway.

Se-polysaccharide (Se-GFP-22) from Se-enriched Grifola frondosa has double and cooperative activities of polysaccharide and Se. To delineate the underlying mechanism and signaling cascade involved in immune-stimulatory property of Se-GFP-22, the production of cellular mediators and key proteins in signaling pathway was examined. Results showed that Se-GFP-22 exhibited no cytotoxic and had a high capacity to promote macrophage phagocytosis, up-regulate interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and nitric oxide (NO) productions, as well as the relative messenger RNA (mRNA) expressions. In Se-GFP-22-induced macrophages, intracellular superoxide dismutase (SOD) activity was significantly increased to protect cells from oxidative injury. However, Se-GFP-22 induced macrophage activation was suppressed when the toll-like receptor 4 (TLR4) signaling pathway was blocked by a specific TLR4 inhibitor. According to the western blot analysis and the use of specific inhibitors against the mitogen-activated protein kinases (MAPK) signaling pathway, we speculated that Se-GFP-22 activated RAW264.7 macrophages through the TLR4-mediated MAPK signaling pathway. This study provides a molecular basis for the potential of Se-GFP-22 as a novel immune-stimulatory agent.

Can impoverished family nurture rich sons any more? The effect of household income on intergenerational transmission of education: Evidence from China.

Family investment in education is an important variable influencing the educational attainment of children. Family investment in education is influenced by family income, and the increase in family income gap will aggravate the inequity of education and enhance the degree of intergenerational transmission of education. But the above theories need to be further tested in reality. This paper uses the 2018 China Family Panel Studies (CFPS) to verify the role of Chinese family income on intergenerational transmission of education through the education transition matrix and the mediating effect model, and examines the effect of college expansion policy on the mediating effect of family income on intergenerational transmission of education. The results show that: (1) The education level of parents has obvious transmissibility to the education level of children. The solidification rate of intergenerational transmission of education between parents and children is 25.72%, the upward mobility rate is 60.58% and the downward mobility rate is 13.70%. (2) The mediating effect model shows that the total effect of the parents' education level on children's education level is 0.279 and the direct effect is 0.272, and the family income plays a mediating effect in the intergenerational transmission of education, and the mediating degree reaches about 2.6%. (3) The expansion of higher education provides more opportunities for children of society, especially lower-middle-income families, to receive higher education, which weakens the mediating effect of family income in the intergenerational transmission of education. The findings of this paper provide support for policymakers to increase public investment in education.

Variation of Aroma Components of Pasteurized Yogurt with Different Process Combination before and after Aging by DHS/GC-O-MS.

Pasteurized yogurt is a healthy yogurt that can be stored in ambient temperature conditions. Dynamic headspace sampling (DHS) combined with gas chromatography-olfactory mass spectrometry (GC-O-MS), sensory evaluation, electronic nose (E-nose), and partial least squares discriminant analysis (PLS-DA) were used to analyze the flavor changes of pasteurized yogurt with different process combinations before and after aging. The results of odor profiles showed that the sensory descriptors of fermented, sweet, and sour were greatly affected by different process combinations. The results of odor-active compounds and relative odor activity value (r-OAV) showed that the combination of the production process affected the overall odor profile of pasteurized yogurt, which was consistent with the sensory evaluation results. A total of 15 odor-active compounds of 38 volatile compounds were detected in pasteurized yogurt samples. r-OAV results revealed that hexanal, (E)-2-octenal, 2-heptanone, and butanoic acid may be important odor-active compounds responsible for off-odor in aged, pasteurized yogurt samples. PLS-DA and variable importance of projection (VIP) results showed that butanoic acid, hexanal, acetoin, decanoic acid, 1-pentanol, 1-nonanal, and hexanoic acid were differential compounds that distinguish pasteurized yogurt before and after aging.

Clinical Characteristics of Pulmonary Tuberculosis in Children Tested by Xpert MTB/RIF Ultra.

BACKGROUND: The Xpert MTB/rifampicin Ultra (Xpert Ultra) assay improves the early diagnosis of active tuberculosis (TB) in children. Clinical evaluation is paramount for the interpretation of any positive Xpert Ultra test, especially those with low quantities of DNA. METHODS: In this study, 391 children with suspected TB who were tested with Xpert Ultra were enrolled. The clinical characteristics and Xpert Ultra results were further analyzed. RESULTS: The sensitivity and specificity of Xpert Ultra were 45.0% (149/331) and 96.7% (58/60), respectively. Children with higher semiquantitative scales of Xpert Ultra showed higher percentages of a positive MTB culture, positive acid-fast bacilli staining, severe type of disease, fever, cough and expectoration, a higher white blood cell count and higher C-reactive protein concentrations (all P < 0.01). Among 44 children with an Xpert Ultra trace result, there were no differences in clinical characteristics between confirmed cases and unconfirmed TB cases. CONCLUSIONS: The prevalence of trace is relatively high and can be considered positive in paucibacillary children. Clinical presentations are associated with bacterial load quantified by Xpert Ultra. The interpretation of Xpert Ultra trace results based on clinical information is important for the diagnosis of TB.

A novel homozygous mutation in ACTL7A leads to male infertility.

Male infertility, a global public health problem, exhibits complex pathogenic causes and genetic factors deserve further discovery and study. We identified a novel homozygous missense mutation c.224A > C (p.D75A) in ACTL7A gene in two infertile brothers with teratozoospermia by whole-exome sequencing (WES). In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) showed fertilization failure of the two affected couples. The three-dimensional (3D) models showed that a small section of α-helix transformed into random coil in the mutant ACTL7A protein and mutant amino acid lacked a hydrogen bond with Ser170 amino acid. Immunofluorescence revealed that ACTL7A protein was degraded in sperms of patients. Transmission electron microscopy (TEM) analysis of sperms from the infertile patients showed that the irregular perinuclear theca (PT) and acrosomal ultrastructural defects. Furthermore, ACTL7A mutation caused abnormal localization and reduced the expression of PLCZ1 in sperms of the patients, which may be the key reasons for the fertilization failure after ICSI. Our findings expand the spectrum of ACTL7A mutations and provide novel theoretical basis for genetic counseling.

Bacterial MazF/MazE toxin-antitoxin suppresses lytic propagation of arbitrium-containing phages.

Temperate phages dynamically switch between lysis and lysogeny in their full life cycle. Some Bacillus-infecting phages utilize a quorum-sensing-like intercellular communication system, the "arbitrium," to mediate lysis-lysogeny decisions. However, whether additional factors participate in the arbitrium signaling pathway remains largely elusive. Here, we find that the arbitrium signal induces the expression of a functionally conserved operon downstream of the arbitrium module in SPbeta-like phages. SPbeta yopM and yopR (as well as phi3T phi3T_93 and phi3T_97) in the operon play roles in suppressing phage lytic propagation and promoting lysogeny, respectively. We further focus on phi3T_93 and demonstrate that it directly binds antitoxin MazE in the host MazF/MazE toxin-antitoxin (TA) module and facilitates the activation of MazF's toxicity, which is required for phage suppression. These findings show events regulated by the arbitrium system and shed light on how the interplay between phages and the host TA module affects phage-host co-survival.

Characterization of Key Odor-Active Off-Flavor Compounds in Aged Pasteurized Yogurt by Sensory-Directed Flavor Analysis.

The purpose of this study was to determine the key odor-active compounds contributing to the off-flavor of aged pasteurized yogurt (APY) using sensory-directed flavor analysis. Additionally, different extraction methods were compared to determine their effects on the volatile compounds, including dynamic headspace sampling (DHS), solid-phase microextraction, and stir bar sorptive extraction, and DHS was found to be suitable for this study. The results showed that comprehensive two-dimensional gas chromatography-olfactometry-mass spectrometry analysis (GC × GC-O-MS) had more advantages in separating and identifying the volatile compounds than the traditional GC-O-MS. A total of 17 odor-active compounds were determined in the fresh pasteurized yogurt and APY samples by DHS coupled with GC × GC-O-MS. The dynamic headspace dilution analysis demonstrated that 2-heptanone and hexanal were the most vital components in APY with the highest flavor dilution factor. Furthermore, the spiking and omission experimental results revealed that the odor-active compounds, such as 2-heptanone, butanoic acid, pentanoic acid, hexanal, and (E)-2-heptenal, were the key odor-active off-flavor contributors in APY. Therefore, these compounds could be used as potential indicators to determine the freshness of pasteurized yogurt.

Study on the Effect of Hope Theory Combined with Psychological Intervention on the Improvement of Prognosis.

In order to evaluate the effect of the hope theory combined with psychological intervention on patients with intracranial aneurysms after surgical treatment, a total of 98 patients with intracranial aneurysm surgery admitted to our hospital from March 2019 to January 2021 were analyzed. According to the random number table method, all patients are divided into two groups: the traditional group and the experimental group. After intracranial aneurysm surgery, the patients of the traditional group and of the joint group are treated with conventional nursing and hope theory combined with psychological intervention nursing mode, respectively. The results demonstrate that the hope theory combined with psychological intervention can improve the level of postoperative patients with intracranial aneurysm life hope, self-efficacy, and postoperative quality of life.