Interaction between maternal immune activation and postpartum immune stress in neuropsychiatric phenotypes.

Epidemiological evidence has shown that maternal infection is a notable risk factor for developmental psychiatric disorders. Animal models have corroborated this link and demonstrated that maternal immune activation (MIA) induces long-term behavioural deficits and neuroimmunological responses to subsequent immune stress in offspring. However, it is unclear whether MIA offspring are more sensitive or more tolerant to immunological challenges from postnatal infections. Pregnant mice were weighed and injected with a single dose of polyinosinic-polycytidylic acid (poly I:C) or saline at gestational day 9.5, and their male offspring were exposed to poly I:C or saline again during adolescence, adulthood, and middle life. After a two-week recovery from the last exposure to poly I:C, the mice underwent behavioural and neuroendophenotypic evaluations. Finally, the mice were sacrificed, and the expression levels of inflammatory factors and the activation levels of glial cells in the cerebral cortex and hippocampus were evaluated. We found MIA mice have lifelong behavioural deficits and glial activation abnormalities. Postpartum infection exposure at different ages has different consequences. Adolescent and middle life exposure prevents sensorimotor gating deficiency, but adult exposure leads to increased sensitivity to MK-801. Moreover, MIA imposed a lasting impact on the neuroimmune profile, resulting in an enhanced cytokine-associated response and diminished microglial reactivity to postnatal infection. Our results reveal an intricate interplay between prenatal and postpartum infection in neuropsychiatric phenotypes, which identify potential windows where preventive or mitigating measures could be applied.

Anti-SFT2D2 autoantibodies alter dendrite spine and cause psychotic behavior in mice.

BACKGROUND: Autoimmunity plays an important role in schizophrenia (SCZ). Autoantibodies against SFT2D2 have been reported in patients with SCZ; however, the specific mechanism remains unclear. This study aimed to describe an autoimmune model, namely, mice immunized against SFT2D2-peptides. METHODS: ApoE-/- and WT mice (C57BL/6) were immunized four times (day 0, day 14, day 21, day 35) with SFT2D2 peptide or KLH via subcutaneous injection. Behavioral tests were conducted after the third immunization, and immunochemistry of brain tissue were performed after the sacrifice of the mice. RESULTS: Active immunization with KLH-coupled SFT2D2-derived peptides in both WT and ApoE-/- (compromised blood-brain barrier) mice led to high circulating levels of anti-SFT2D2 IgG. While there was no detectable deficit in WT mice, impaired pre-pulse inhibition, motor impairments, and reduced cognition in ApoE-/- mice, without signs of anxiety and depression were observed. In addition, immunohistochemical assays demonstrated that activated microglia and astrocytes were increased but neuronal dendritic spine densities were decreased, accompanied by increased expression of complement molecule C4 across brain regions in ApoE-/- mice. CONCLUSIONS: In model mice with compromised blood-brain barrier, endogenous anti-SFT2D2 IgG can activate glial cells and modulate synaptic plasticity, and induce a series of psychosis-like changes. These antibodies may reveal valuable therapeutic targets, which may improve the treatment strategies for a subgroup of SCZ patients.

Non-neutralizing antibodies to SARS-Cov-2-related linear epitopes induce psychotic-like behavior in mice.

Objective: An increasing number of studies have reported that numerous patients with coronavirus disease 2019 (COVID-19) and vaccinated individuals have developed central nervous system (CNS) symptoms, and that most of the antibodies in their sera have no virus-neutralizing ability. We tested the hypothesis that non-neutralizing anti-S1-111 IgG induced by the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could negatively affect the CNS. Methods: After 14-day acclimation, the grouped ApoE-/- mice were immunized four times (day 0, day 7, day 14, day 28) with different spike-protein-derived peptides (coupled with KLH) or KLH via subcutaneous injection. Antibody level, state of glial cells, gene expression, prepulse inhibition, locomotor activity, and spatial working memory were assessed from day 21. Results: An increased level of anti-S1-111 IgG was measured in their sera and brain homogenate after the immunization. Crucially, anti-S1-111 IgG increased the density of microglia, activated microglia, and astrocytes in the hippocampus, and we observed a psychomotor-like behavioral phenotype with defective sensorimotor gating and impaired spontaneity among S1-111-immunized mice. Transcriptome profiling showed that up-regulated genes in S1-111-immunized mice were mainly associated with synaptic plasticity and mental disorders. Discussion: Our results show that the non-neutralizing antibody anti-S1-111 IgG induced by the spike protein caused a series of psychotic-like changes in model mice by activating glial cells and modulating synaptic plasticity. Preventing the production of anti-S1-111 IgG (or other non-neutralizing antibodies) may be a potential strategy to reduce CNS manifestations in COVID-19 patients and vaccinated individuals.

Evolutionary artificial intelligence algorithms for the one-way road orientation planning problem with multiple venues: An example of evacuation planning in Taiwan.

INTRODUCTION: In large-scale events such as concerts and sports competitions, participants often leave the venue at the same time to return to their respective destinations. Improper traffic planning and traffic light operation usually lead to traffic congestion and road chaos near the sites. Rapid evacuation of participants has become an important issue. OBJECTIVES: In this work, a one-way road orientation planning problem with multiple venues is studied in which all roads near the venues are to be scheduled into a one-way orientation with strong connectivity to increase the evacuation efficiency of participants. METHODS: In accordance with Robbins' theorem and a random sequence of integers, an encoding scheme based on module operator is presented to construct a strongly connected graph and plan a one-way orientation for all roads. The proposed encoding scheme is further embedded into four artificial intelligence approaches, namely, grey wolf optimization, immune algorithm, genetic algorithm, and particle swarm optimization, to solve the one-way road orientation planning problem such that the total distance of all vehicles from venues to their destinations is minimized. RESULTS: Numerical results of test problems with multiple venues in Taiwan are provided and analyzed. As shown, all four algorithms can obtain the best solution for the test problems. CONCLUSIONS: The new presented encoding scheme with four algorithms can be used to effectively solve the one-way road orientation planning problem for the evacuation of participants. Moreover, grey wolf optimization is superior to the other three algorithms and particle swarm optimization is faster than the other three algorithms.

A heuristic algorithm for medical staff's scheduling problems with multiskills and vacation control.

INTRODUCTION: The main issue related to the duty schedule is to allocate medical staff to each medical department by considering personnel skills and personal vocation preferences. However, how to effectively use staff's multiskill characteristics and how to execute vocation control have not been well investigated. OBJECTIVES: This article aims to develop duty scheduling and vacation permission decisions to minimize the sum of customers' waiting costs, the overtime cost of medical staff, the cost of failing to meet medical staff' vacation requirements, and the cost of mutual support between departments. METHODS: This study formulated the problem as a multiperiod mixed integer nonlinear programming model and developed a hybrid heuristic based on evolutionary mechanism of genetic algorithm and linear programming to efficiently solve the proposed model. RESULTS: Five types of problems were solved through Lingo optimization and the proposed approach. For small-scale problems, both methods can find the optimal solutions. For a slightly larger problem, the solutions found by the proposed approach are superior those of Lingo. CONCLUSION: This research discusses the complex decision-making problem of on-duty arrangement and vacation control of medical staff in a multidepartmental medical center. This research formulates the medical staff's scheduling and vacation control problems as constrained mixed integer quadratic programming problems. Computational results indicate that the proposed approach can efficiently produce compromise solutions that outperform the solutions of the Lingo optimization software.

Scheduling the periodic delivery of liquefied petroleum gas tank with time window by using artificial intelligence approaches: An example in Taiwan.

INTRODUCTION: In Taiwan, liquefied petroleum gas tank users have to call a gas company to deliver a full liquefied petroleum gas tank when their tank is out of gas. The calls usually congest in the cooking time and the customers have to wait for a long time for a full liquefied petroleum gas tank. Additionally, allocating manpower is difficult for the gas company. OBJECTIVES: A strategy of periodic delivery for gas companies was presented to deliver liquefied petroleum gas tanks in advance and charge the gas fee based on the weight of returned tanks. Additionally, a new encoding scheme was proposed and embedded into three evolutionary algorithms to solve the nondeterministic polynomial-hard problem. The objective of the problem is to minimize the total traveling distance of the vehicle such that the delivery efficiency of tanks increases and the waiting time of customer decreases. METHODS: A new encoding scheme was presented to convert any random sequence of integers into a solution of the problem and embedded into three evolutionary algorithms, namely, immune algorithm, genetic algorithm, and particle swarm optimization, to solve the delivery problem. Additionally, the encoding scheme can be used to different frequency types of demand based on customers' requests. RESULTS: Numerical results, including a practical example in Yunlin, Taiwan, were provided to show that the adopted approaches can significantly improve the efficiency of delivery. CONCLUSIONS: The periodic delivery strategy and the new encoding scheme can effectively solve the practical problem of liquefied petroleum gas tank in Taiwan.

TBAB-Catalyzed 1,6-Conjugate Sulfonylation of para-Quinone Methides: A Highly Efficient Approach to Unsymmetrical gem-Diarylmethyl Sulfones in Water.

A highly efficient sulfonylation of para-quinone methides with sulfonyl hydrazines in water has been developed on the basis of the mode involving a tetrabutyl ammonium bromide (TBAB)-promoted sulfa-1,6-conjugated addition pathway. This reaction provides a green and sustainable method to synthesize various unsymmetrical diarylmethyl sulfones, showing good functional group tolerance, scalability, and regioselectivity. Further transformation of the resulting diarylmethyl sulfones provides an efficient route to some functionalized molecules.

NLRP3 inflammasome activation is involved in trimethyltin-induced neuroinflammation.

Trimethyltin (TMT), a neurotoxic organotin compound, is selectively localized within the limbic system. The mechanisms of TMT-induced hippocampal neurodegeneration include inflammatory responses, oxidative stress, and neuronal death. Increasing evidence shows that the inflammatory response, mediated by activated inflammasomes, is involved in apoptosis and cellular dysfunction during brain injury. This study aimed to assess the role of the nucleotide-binding oligomerization domain-like receptor pyrin-domain-containing protein 3 (NLRP3) inflammasome in TMT-induced central nervous system (CNS) injury. In addition, the mechanisms underlying TMT neurotoxicity are similar to those involved in the pathogenesis of multiple neurodegenerative diseases; hence, a study on TMT cytotoxicity may be informative for the understanding of human CNS diseases. Microglia were significantly activated in the rat hippocampal dentate gyrus after TMT treatment. The mRNA expression of pro-inflammatory cytokines, interleukin-1ß and interleukin-18, was induced both in vitro and in vivo. TMT treatment activated the NLRP3 inflammasome in the microglial cell line BV2. NLRP3 RNA interference significantly protected these cells from TMT-induced neuroinflammation. Our results demonstrate that the NLRP3 inflammasome is a key mediator of neuroinflammation and plays an important role in TMT-induced neuroinflammation.