Basolateral Amygdala Cannabinoid CB1 Receptor Controls Formation and Elimination of Social Fear Memory.

Patients with post-traumatic stress disorder (PTSD) usually manifest persistence of the traumatic memory for a long time after the event, also known as resistance to extinction learning. Numerous studies have shown that the endocannabinoid system, specifically the cannabinoid type-1 receptor (CB1R), plays an important role in traumatic memory. However, the effect of basolateral amygdala (BLA) CB1R in social fear memory formation and elimination is still unclear. Here, we built a mouse model of social avoidance induced by acute social defeat stress to investigate the role of BLA CB1R in social fear memory formation and anxiety- and depression-like behavior. Anterograde knockout of CB1R in BLA neurons facilitates social fear memory formation and manifests an anxiolytic effect but does not influence sociability and social novelty. Retrograde knockout of CB1R in BLA promotes social fear memory formation and shows an anxiogenic effect but does not affect sociability and social novelty. Moreover, intracerebral injection of the CB1R antagonist AM251 in BLA during the memory reconsolidation time window eliminates social fear memory. Our findings suggest the CB1R of BLA can be used as a novel molecular target in social fear memory formation and elimination and potential PTSD therapy with memory retrieval and AM251.

Inactivation of phage phiX174 by UV254 and free chlorine: Structure impairment and function loss.

Disinfection is widely applied in water and wastewater treatment to inactivate viruses. However, the inactivation mechanism associated with viral structural alteration during disinfection is still not clear. In this work, inactivation of bacteriophage phiX174 by ultraviolet radiation (UV254) and free chlorine (FC), two most commonly used disinfection processes, was studied at the molecular level to investigate the relationship between phiX174 genome impairment and virus inactivation, and the correlation between protein impairment and function loss. Double-layer agar technique, quantitative real-time polymerase chain reaction (qPCR), real-time reverse transcription-polymerase chain reaction (RT-qPCR), and liquid chromatography-tandem mass spectrometry techniques (LC-MS/MS), together with structure impairment and function experiments were implemented to quantitatively analyze the inactivation and damage to genome and proteins of phiX174. Results showed that UV254 and FC could effectively inactivate phiX174 at the practical doses (UV254 dose of 30 mJ/cm2, and FC of 1-3 mg/L) used in water treatment plants, accompanied with the damage to viral genome and proteins. Specifically, a UV254 irradiation dose of 9.6 mJ/cm2, and FC at an initial concentration of 1 mg/L at 4 min could lead to a 4-log10 inactivation. Nevertheless, the combination of these two methods at selected doses played no significant synergistic disinfection effect. During UV254 disinfection, the proportion of phiX174 with damaged genome was similar with that of the inactivated phiX174. In addition, UV254 and FC could disrupt proteins of phiX174 such as H protein, thereby hindering the physiological function associated with these proteins. With these findings, it is suggested that UV254 and FC disinfection could hinder the injection of the viral genome into host cells, thus resulting in the inactivation of phiX174. This work provides a comprehensive study of the inactivation mechanism of phiX174, which can enhance the applicability of UV254 and FC in water treatment plants, and facilitate the design and optimization of disinfection technologies for virus control in drinking water and wastewater worldwide to ensure the biosafety.

A study on the current state and equity level of the health promotion service demands among older adults in China.

BACKGROUND: Meeting the demands of older adults for health promotion services (DOAHPS) is essential for maintaining their health and enhancing their quality of life. The purpose of this study was to construct a model for evaluating DOAHPS to quantitatively evaluate the current state and equity level of DOAHPS in China, as well as to explore the main factors affecting DOAHPS' current state and equity level. METHODS: This study analyzed the DOAHPS data from the "Survey on Chinese Residents' Health Service Demands in the New Era", which included 1542 older adults aged 65 and older. Relationships between evaluation indicators of DOAHPS were explored using Structural Equation Modeling (SEM). The Weighted TOPSIS method and Logistic regression (LR) were used to analyze the current state and factors impacting DOAHPS. The equity level of DOAHPS' allocation among different older adult groups and its influencing factors were determined using the Rank Sum Ratio (RSR) method and T Theil index. RESULTS: The evaluation score for DOAHPS was 42.57 ± 1.51. Health status, health literacy and behavior were positively correlated with DOAHPS (r = 0.40, 0.38; P < 0.05). The LR results revealed that the most significant determinants of DOAHPS were sex, residence, education level and pre-retirement occupation (all P < 0.05). The number of older adults with very poor, poor, general, high and very high level health promotion service demands accounted for 2.27%, 28.60%, 53.05%, 15.43% and 0.65%, respectively. The total T Theil index of DOAHPS was 2.7433*10-4, and the intra-group difference contribution rate exceeded 72%. CONCLUSIONS: Compared to the maximum level, the total DOAHPS level was found to be moderate, although the demands of urban seniors with higher levels of education may be substantially greater. The observed inequities in the allocation of DOAHPS were primarily related to differences in education level and pre-retirement occupation within group. To better address health promotion services for older adults, policymakers could target older males with low education who reside in rural regions.

Molecular Hinges by Fusion of Pyrrole and Dithiin: Synthesis, Structure, Redox Chemistry and Host-Guest Complexation of Dipyrrolo-1,4-dithiins.

A series of novel hinge-like molecules, namely dipyrrolo-1,4-dithiins (PDs), were prepared and fully characterized by NMR, UV/vis, cyclic voltammogram, ESR, and single crystal X-ray diffraction (SCXRD) analysis. The lateral fusion of pyrroles with 1,4-dithiins has led to not only retained key features of a dithiin, but also enhanced redox-activity with increased susceptibility to radical cations via redox or chemical oxidation. Stabilization of their radicals are observed for the N,N-tert-butyl or N,N-triphenylmethyl PD as evidenced by ESR measurements. DFT calculations and SCXRD analysis revealed PDs are extremely flexible with adaptive molecular geometries that can be mechanically regulated via crystal packing or host-guest complexation. The excellent donor nature of PDs renders inclusion complexes with the cyclophane bluebox (cyclobis(paraquat-p-phenylene)), featuring association constants up to 104  M-1 . Additionally, a planarized transition intermediate associated with inversion dynamics of a PD has been preserved in the pseudorotaxane structure with assistances of π⋅⋅⋅π and S⋅⋅⋅π interactions. The hinged structure, excellent redox-activity, and adaptive nature of PDs could further enable accesses to exotic redox switchable host-guest chemistry and functional materials.

Recent advances in nonsurgical treatment of pulmonary ground-glass nodules.

Since the 1990s, low-dose computed tomography technology has been used in lung cancer screening. With the increase of computed tomography screening, the detection rate of ground-glass nodules (GGN) has increased dramatically. At present, the main treatment strategy for GGN is surgical resection. However, for patients with poor cardiopulmonary functions, a history of lung resection, multiple pulmonary nodules, or the age of >75 years, surgical resection is very difficult and not medically encouraged. This article reviews the applications and outcomes evaluation of nonsurgical treatments, such as chemotherapy, radiotherapy, moleculartargeted drug therapy, immunity therapy, and image-guided thermal ablation in patients with GGN.

NAc-VTA circuit underlies emotional stress-induced anxiety-like behavior in the three-chamber vicarious social defeat stress mouse model.

Emotional stress is considered a severe pathogenetic factor of psychiatric disorders. However, the circuit mechanisms remain largely unclear. Using a three-chamber vicarious social defeat stress (3C-VSDS) model in mice, we here show that chronic emotional stress (CES) induces anxiety-like behavior and transient social interaction changes. Dopaminergic neurons of ventral tegmental area (VTA) are required to control this behavioral deficit. VTA dopaminergic neuron hyperactivity induced by CES is involved in the anxiety-like behavior in the innate anxiogenic environment. Chemogenetic activation of VTA dopaminergic neurons directly triggers anxiety-like behavior, while chemogenetic inhibition of these neurons promotes resilience to the CES-induced anxiety-like behavior. Moreover, VTA dopaminergic neurons receiving nucleus accumbens (NAc) projections are activated in CES mice. Bidirectional modulation of the NAc-VTA circuit mimics or reverses the CES-induced anxiety-like behavior. In conclusion, we propose that a NAc-VTA circuit critically establishes and regulates the CES-induced anxiety-like behavior. This study not only characterizes a preclinical model that is representative of the nuanced aspect of CES, but also provides insight to the circuit-level neuronal processes that underlie empathy-like behavior.

Systematic Input-Output Mapping Reveals Structural Plasticity of VTA Dopamine Neurons-Zona Incerta Loop Underlying the Social Buffering Effects in Learned Helplessness.

A common phenomenon called social buffering (SB), communication within conspecific animals is a benefit for a stressed individual to better recover from aversive events, is crucial to all mammals. Although the dopamine reward system has been implicated in SB, it is not clear which neuronal populations are relevant and how they contribute. Here, we adopted a learned helplessness (LH) animal model of depression and found that LH subjects housed with a conspecific partner show better performance in the shuttle box test, showing that SB improves the stress-coping abilities to deal with stress. Bidirectional manipulation of ventral tegmental area (VTA) dopamine neurons by chemogenetic tools can mimic or block the SB effect in LH mice. To screen for SB-induced structure plasticity of VTA dopamine neurons, we employed viral genetic tools for mapping input and output architecture and found LH- and SB-triggered circuit-level changes in neuronal ensembles. Zona incerta (ZI), an overlapping brain region, was significantly changed in both anterograde and retrograde tracing during LH and SB. These results reveal a neural loop with structural plasticity between VTA dopamine neurons and ZI underlies the SB effects in LH and lays a foundation for studying how VTA dopamine neurons regulate SB-related neural circuits.

WITHDRAWN: Porcine reproductive and respiratory syndrome virus (PRRSV) inhibition with engineered Cas13d.

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