PVN-mPFC OT projections modulate pup-directed pup care or attacking in virgin mandarin voles.

Many species of animals exhibit caregiving or aggression toward conspecific offspring. The neural mechanisms underlying the infanticide and pup care remain poorly understood. Here, using monogamous mandarin voles (Microtus mandarinus), we found that more oxytocin (OT) neurons in the paraventricular nucleus (PVN) were activated during pup caring than infanticide. Optogenetic activation of OT neurons in the PVN facilitated pup caring in male and female mandarin voles. In infanticide voles, optogenetic activation of PVN OT cells or PVN-medial prefrontal cortex (mPFC) OT projection fibers prolonged latency to approach and attack pups, whereas inhibition of these OT neurons or projections facilitated approach and infanticide. Optogenetic activation of PVN OT neuron projections to the mPFC in males shortened the latency to approach and retrieve pups and facilitated the initiation of pup care, but produced no effects on pup-care females. In addition, OT release in the mPFC increased upon approaching and retrieving pups, and decreased upon attacking pups. Intraperitoneal injection of OT promoted pup care and inhibited infanticide behavior. It is suggested that the OT system, especially PVN OT neurons projecting to mPFC, modulates pup-directed behaviors and OT can be used to treat abnormal behavioral responses associated with some psychological diseases such as depression and psychosis.

Manganese boosts natural killer cell function via cGAS-STING mediated UTX expression.

Natural killer (NK) cells play a crucial role in both innate immunity and the activation of adaptive immunity. The activating effect of Mn2+ on cyclic GMP-AMP(cGAS)-stimulator of interferon genes (STING signaling has been well known, but its effect on NK cells remains elusive. In this study, we identified the vital role of manganese (Mn2+) in NK cell activation. Mn2+ directly boosts cytotoxicity of NK cells and promotes the cytokine secretion by NK cells, thereby activating CD8+ T cells and enhancing their antitumor activity. Furthermore, Mn2+ can simultaneously activate NK-cell intrinsic cGAS and STING and consequently augment the expression of ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX to promote the responsiveness of NK cells. Our results contribute to a broader comprehension of how cGAS-STING regulates NK cells. As a potent agonist of cGAS-STING, Mn2+ provides a promising option for NK cell-based immunotherapy of cancers.

Sexual Self-Identification Offsets and Self-Stigma Moderates: Expanding the Rejection-Identification Model to Examine Stigma's Effects on Well-Being Among Gay and Bisexual Men.

Gender and sexual minorities still face stigma-related stress from all areas of society. The rejection-identification model (RIM) proposes that some stigmatized individuals may respond to the negative effects of stigma on well-being by enhancing their self-identification. However, this does not apply to all gender and sexual minorities. Grounded in minority stress theory and the RIM, this study examined how stigma-related stressors (i.e. perceived stigma and self-stigma) and their associated mechanisms impact sexual self-identification and subjective well-being. A total of 366 Chinese gay and bisexual men were included in the study. The results showed that sexual self-identification, as a protective factor, mediated the association between perceived stigma and subjective well-being. Furthermore, the indirect effect of the mediation model was moderated by self-stigma, such that the indirect effect of perceived stigma on subjective well-being through sexual self-identification was the highest among Chinese gay and bisexual men with low self-stigma. Given that research into the mental health and well-being of Chinese gay and bisexual men is still in its infancy, our findings are important and may help in developing and improving socially and psychologically sensitive counseling services or intervention strategies for these populations.

Moderately delayed maturation of composting promotes the reduction of guild-plant pathogenic fungi within vegetable waste.

The relationships among the relative abundance of guild-plant pathogenic fungi, compost maturation index, and microbial community variation during vegetable waste composting, which are influenced by the C/N ratio, remain poorly understood. To address this, fungal communities were analyzed in composting treatments with C/N ratios of approximately 15 (CN15) and 25 (CN25), using vegetable waste as the primary raw material. The CN15 treatment showed greater microbial community variation and a better overall compost maturation index value than the CN25 treatment. However, the CN25 treatment had a greater decline in plant-pathogenic fungi than the CN15 treatment. Notably, the relative abundance of guild-plant pathogenic fungi was significantly negatively related to the compost maturity index in the CN25 treatment, while no significant relationship was observed in the CN15 treatment. This study suggests that the moderately delayed maturation of composting is beneficial for reducing guild-plant pathogenic fungi in vegetable waste.

Involvement of Serotonergic Projections from the Dorsal Raphe to the Medial Preoptic Area in the Regulation of the Pup-Directed Paternal Response of Male Mandarin Voles.

Male mammals display different paternal responses to pups, either attacking or killing the young offspring, or contrastingly, caring for them. The neural circuit mechanism underlying the between-individual variation in the pup-directed responsiveness of male mammals remains unclear. Monogamous mandarin voles were used to complete the present study. The male individuals were identified as paternal and infanticidal voles, according their behavioral responses to pups. It was found that the serotonin release in the medial preoptic area (MPOA), as well as the serotonergic neuron activity, significantly increased upon licking the pups, but showed no changes after attacking the pups, as revealed by the in vivo fiber photometry of the fluorescence signal from the 5-HT 1.0 sensor and the calcium imaging indicator, respectively. It was verified that the 5-HTergic neural projections to the MPOA originated mainly from the ventral part of the dorsal raphe (vDR). Furthermore, the chemogenetic inhibition of serotonergic projections from the vDR to the MPOA decreased the paternal behaviors and shortened the latency to attack the pups. In contrast, the activation of serotonergic neurons via optogenetics extended the licking duration and inhibited infanticide. Collectively, these results elucidate that the serotonergic projections from the vDR to the MPOA, a previously unrecognized pathway, regulate the paternal responses of virgin male mandarin voles to pups.

Oxytocin treatments or activation of the paraventricular nucleus-the shell of nucleus accumbens pathway reduce adverse effects of chronic social defeat stress on emotional and social behaviors in Mandarin voles.

Chronic social stress can cause psychological disease. Although oxytocin (OT) has been showed to modulate effects of chronic social defeat stress (CSDS) on emotional and social behaviors, however, how OT circuits mediate effects of CSDS on emotional and social abnormalities remains unclear. Here, we found that repeated intraperitoneal OT administration in the process of CSDS buffered adverse effects of CSDS on emotional and social behaviors in mandarin voles (Microtus mandarinus) of both sexes except no effect on depression-like behavior of males. Repeated OT treatments during CSDS prevented decrease of oxytocin receptors in nucleus accumbens (NAc) in females, but produced no effects on males. Furthermore, using designer receptors exclusively activated by designer drugs (DREADDs)-based chemogenetic tools, we determined that the activation of the paraventricular nucleus (PVN)-the shell of NAc (NAcs) projections before social defeat during CSDS process significantly prevented the increase of the anxiety-like behaviors and social avoidance induced by CSDS in both sexes, and reversed the depressive-like behaviors induced by CSDS only in females. Besides, optogenetic activation of PVN-NAcs projections after CSDS reduced anxiety-like behaviors and increased levels of sociality. Collectively, we suggest that PVN-NAcs projections modulate emotional and social behaviors during or after the process of CSDS sex-specifically, although AAV viruses did not specifically infect OT neurons. These findings offer potential targets for preventing or treating emotional and social disorders induced by chronic stress.

Downregulation of fatty acid oxidation led by Hilpda increases G2/M arrest/delay-induced kidney fibrosis.

Hypoxia-regulated proximal tubular epithelial cells (PTCs) G2/M phase arrest/delay was involved in production of renal tubulointerstitial fibrosis (TIF). TIF is a common pathological manifestation of progression in patients with chronic kidney disease (CKD), and is often accompanied by lipid accumulation in renal tubules. However, cause-effect relationship between hypoxia-inducible lipid droplet-associated protein (Hilpda), lipid accumulation, G2/M phase arrest/delay and TIF remains unclear. Here we found that overexpression of Hilpda downregulated adipose triglyceride lipase (ATGL) promoted triglyceride overload in the form of lipid accumulation, leading to defective fatty acid ß-oxidation (FAO), ATP depletion in a human PTC cell line (HK-2) under hypoxia and in mice kidney tissue treated with unilateral ureteral obstruction (UUO) and unilateral ischemia-reperfusion injury (UIRI). Hilpda-induced lipid accumulation caused mitochondrial dysfunction, enhanced expression of profibrogenic factors TGF-ß1, α-SMA and Collagen I elevation, and reduced expression of G2/M phase-associated gene CDK1, as well as increased CyclinB1/D1 ratio, resulted in G2/M phase arrest/delay and profibrogenic phenotypes. Hilpda deficiency in HK-2 cell and kidney of mice with UUO had sustained expression of ATGL and CDK1 and reduced expression of TGF-ß1, Collagen I and CyclinB1/D1 ratio, resulting in the amelioration of lipid accumulation and G2/M arrest/delay and subsequent TIF. Expression of Hilpda correlated with lipid accumulation, was positively associated with tubulointerstitial fibrosis in tissue samples from patients with CKD. Our findings suggest that Hilpda deranges fatty acid metabolism in PTCs, which leads to G2/M phase arrest/delay and upregulation of profibrogenic factors, and consequently promote TIF which possibly underlie pathogenesis of CKD.

Involvement of DR→mPFC 5-HTergic neural projections in changes of social exploration behaviors caused by adult chronic social isolation in mice.

Social contacts play an important role in the development and survival of social animals. Social isolation (SI) at adolescence often induces abnormalities in many kinds of behaviors. This study assessed whether five weeks of continuous SI at adulthood could alter social behaviors and whether dorsal raphe nucleus (DR) to medial prefrontal cortex (mPFC) 5-HT neural projections were involved in this alteration in C57BL/6J adult male mice. The present study found that five weeks chronic social isolation (CSI) at adulthood increased mounting and sniffing behaviors in resident-intruder test, and lengthened duration staying in interaction zone of stranger cage in the three-chamber social preference test. CSI also reduced the release of 5-HT in the mPFC detected by 5-HT 1.0 sensor and measured by in vivo fiber photometry test. Meanwhile, the c-Fos expression indicated that CSI reduced the activity of serotonergic neurons. Chemogenetic activation of DR-mPFC 5-HTergic projection reduced sniffing of CSI mice in the resident-intruder test, but didn't significantly affect mounting behavior. It also decreased the interaction time during the three-chamber social preference test. Thus, 5-HT neural projections from the DR to the mPFC are involved in changes of social exploration behaviors induced by CSI at adulthood.

Involvement of the dopamine system in paternal behavior induced by repeated pup exposure in virgin male ICR mice.

Like mothers, fathers play a vital role in the development of the brain and behavior of offspring in mammals with biparental care. Unlike mothers, fathers do not experience the physiological processes of pregnancy, parturition, or lactation before their first contact with offspring. Whether pup exposure can induce the onset of paternal behavior and the underlying neural mechanisms remains unclear. By using Slc:ICR male mice exhibiting maternal-like parental care, the present study found that repeated exposure to pups for six days significantly increased the total duration of paternal behavior and shortened the latency to retrieve and care for pups. Repeated pup exposure increased c-Fos-positive neurons and the levels of dopamine- and TH-positive neurons in the nucleus accumbens (NAc). In addition, inhibition of dopamine projections from the ventral tegmental area to the NAc using chemogenetic methods reduced paternal care induced by repeated pup exposure. In conclusion, paternal behavior in virgin male ICR mice can be initiated by repeated pup exposure via sensitization, and the dopamine system may be involved in this process.

Persistent luminescence nanorods-based autofluorescence-free biosensor for prostate-specific antigen detection.

Persistent luminescent nanoparticles (PLNPs) are a class of materials with excellent optical properties, which can continue to emit light for a long time after removing the excitation light source. This feature enables PLNPs to be used for development of biological detection modes without autofluorescence background. In this study, we prepared Zn2GeO4: Mn2+, Pr3+ (ZGOMP) nanorods through a one-pot hydrothermal method. Using the pH-responsive luminescence behavior of ZGOMP, we developed an autofluorescence-free biosensor using ZGOMP as a probe and gluconic acid as a quencher to detect prostate-specific antigen (PSA). Hybridization chain reaction (HCR) and magnetic separation system were introduced in the design to achieve efficient signal amplification. Under the optimal conditions, the as-designed autofluorescence-free sensing platform showed high selectivity, and showed a good luminescence response to PSA within the linear range of 0.001-10 ng/mL at a detection limit of 0.64 pg/mL. The excellent analytical performance shows that the current strategy provides an effective platform for clinical sample analysis.

Paraventricular Nucleus Oxytocin Subsystems Promote Active Paternal Behaviors in Mandarin Voles.

Paternal care plays a critical role in the development of brain and behaviors in offspring in monogamous species. However, the neurobiological mechanisms, especially the neuronal circuity, underlying paternal care is largely unknown. Using socially monogamous male mandarin voles (Microtus mandarinus) with high levels of paternal care, we found that paraventricular nucleus of the hypothalamus (PVN) to ventral tegmental area (VTA) or nucleus accumbens (NAc) oxytocin (OT) neurons are activated during paternal care. Chemogenetic activation/inhibition of the PVN OT projection to VTA promoted/decreased paternal care, respectively. Chemogenetic inhibition of the PVN to VTA OT pathway reduced dopamine (DA) release in the NAc of male mandarin voles during licking and grooming of pups as revealed by in vivo fiber photometry. Optogenetic activation/inhibition of the VTA to NAc DA pathway possibly enhanced/suppressed paternal behaviors, respectively. Furthermore, chemogenetic activation/inhibition of PVN to NAc OT circuit enhanced/inhibited paternal care. This finding is a first step toward delineating the neuronal circuity underlying paternal care and may have implications for treating abnormalities in paternal care associated with paternal postpartum depression or paternal abuse.SIGNIFICANCE STATEMENT Paternal behavior is essential for offspring survival and development in some mammalian species. However, the circuit mechanisms underlying the paternal brain are poorly understood. We show that manipulation of paraventricular nucleus of the hypothalamus (PVN) to ventral tegmental area (VTA) oxytocin (OT) projections as well as VTA to nucleus accumbens (NAc) DA projections promote paternal behaviors. Inhibition the PVN to VTA OT pathway reduces DA release in the NAc during pup licking and grooming. PVN to NAc OT circuit is also essential for paternal behaviors. Our findings identify two new neural circuits that modulate paternal behaviors.

Ultrasensitive photoelectrochemical immunoassay for prostate-specific antigen based on silver nanoparticle-triggered ion-exchange reaction with ZnO/CdS nanorods.

Prostate-specific antigen (PSA), a glycoprotein that is most likely to cause prostate cancer, has attracted widespread attention in recent years due to its increasing threat to people's lives and health. Herein, we developed a new signal-amplified photoelectrochemical (PEC) immunosensing method for quantitative monitoring of the target PSA based on the ion-exchange reaction for the in situ formation of ZnO/CdS/Ag2S nanohybrids triggered by the as-released silver ions (Ag+) from silver nanolabels. Initially, the introduction of a target PSA caused the formation of a sandwich immunocomplex in an anti-PSA capture antibody (cAb)-coated microplate with the help of a silver nanoparticle-labeled detection antibody (AgNPs-dAb). Thereafter, the introduced AgNPs were dissolved with acid to release numerous silver ions. In this regard, an ion-exchange reaction occurred between the silver ions and ZnO/CdS nanorods on the photosensitive electrode, thus producing ZnO/CdS/Ag2S nanohybrids to generate a relatively strong photocurrent. Under optimal conditions, the ion-exchange reaction-based PEC immunoassay exhibited a good linear range of 0.05-50 ng mL-1 and allowed the detection of the target PSA at a concentration as low as 0.018 ng mL-1. In addition, the PEC immunoassay displayed satisfactory repeatability, high specificity, and acceptable method accuracy. Importantly, the ion-exchange reaction-based PEC immunoassay provides a new perspective for the detection of other disease-related biomarkers by controlling the corresponding antibodies.

Signal-on photoelectrochemical immunoassay mediated by the etching reaction of oxygen/phosphorus co-doped g-C3N4/AgBr/MnO2 nanohybrids.

We designed a signal-on photoelectrochemical (PEC) immunoassay for the sensitive monitoring of prostate-specific antigen (PSA) based on the etching reaction of hydrogen peroxide (H2O2) toward oxygen/phosphorus co-doped graphitic C3N4/AgBr/MnO2 nanosheets (OP-g-C3N4/AgBr/MnO2). Initially, glucose oxidase (GOX)-labeled detection antibodies were introduced into the capture antibody-coated microplate with a sandwich-type immunoreaction in the presence of PSA. Then, the as-generated H2O2 from the decomposition of glucose by GOX etched the manganese dioxide (MnO2) nanosheets into manganese ions (Mn2+), thereby causing the exposure of the underlying OP-g-C3N4/AgBr. Meanwhile, H2O2 could be also used as an electron scavenger, and restrain the recombination of the electron-hole pairs of OP-g-C3N4/AgBr. Two advantages of H2O2 enhanced the photocurrent synergistically. Under optimum conditions, the PEC immunoassay showed high sensitivity toward target PSA within a dynamic working range of 0.05-50 ng mL-1 with a limit of detection of 17 pg mL-1. In addition, our system possessed high specificity, favorable selectivity, and good stability. Relative to commercialized PSA ELISA kits, the accuracy of our strategy was acceptable. More importantly, our strategy can be easily extended to screen other biomarkers by controlling the corresponding antibodies.

Dorsal raphe nucleus to anterior cingulate cortex 5-HTergic neural circuit modulates consolation and sociability.

Consolation is a common response to the distress of others in humans and some social animals, but the neural mechanisms underlying this behavior are not well characterized. By using socially monogamous mandarin voles, we found that optogenetic or chemogenetic inhibition of 5-HTergic neurons in the dorsal raphe nucleus (DR) or optogenetic inhibition of serotonin (5-HT) terminals in the anterior cingulate cortex (ACC) significantly decreased allogrooming time in the consolation test and reduced sociability in the three-chamber test. The release of 5-HT within the ACC and the activity of DR neurons were significantly increased during allogrooming, sniffing, and social approaching. Finally, we found that the activation of 5-HT1A receptors in the ACC was sufficient to reverse consolation and sociability deficits induced by the chemogenetic inhibition of 5-HTergic neurons in the DR. Our study provided the first direct evidence that DR-ACC 5-HTergic neural circuit is implicated in consolation-like behaviors and sociability.

Involvement of the dopamine system in the effect of chronic social isolation during adolescence on social behaviors in male C57 mice.

In the early stage of life, experiencing social isolation can generate long-lasting deleterious effects on behaviors and brain development. However, the effects of chronic social isolation during adolescence on social behaviors and its underlying neurobiological mechanisms remain unclear. The present study found that four weeks of social isolation during adolescence impaired social recognition ability in the three-chamber test and five-trial social recognition test, and increased aggressive-like behaviors, but reduced environmental exploration, as showed in the social interaction test. Chronic social isolation decreased levels of dopamine D2 receptor in the shell of the nucleus accumbens (NAcc) and medial prefrontal cortex. It also reduced TH in the NAcc. Using in vivo fiber photometry, it was also found that isolated mice displayed a reduction in NAcc shell activity upon exploring unfamiliar social stimuli. An injection of a 100 ng dose of the D2R agonist quinpirole into the shell of the NAcc reversed behavioral abnormalities induced by chronic social isolation. These data suggest that the dopamine system is involved in alterations in social behaviors induced by chronic social isolation. This finding sheds light on the mechanism underlying abnormalities in social behavior induced by adolescent chronic social isolation and provides a promising target to treat mental diseases relevant to social isolation.

Double ion-exchange reaction-based photoelectrochemical immunoassay for sensitive detection of prostate-specific antigen.

This work developed a double ion-exchange reaction-based photoelectrochemical (PEC) immunoassay with the split-type detection mode for sensitive detection of prostate-specific antigen (PSA, used as a model). The nanocomposite of cadmium sulfide and nickel sulfide (CdS@NiS nanocomposite), as the photoactive material, was rapidly synthesized by two-step hydrothermal treatment. In the presence of target PSA, the cupric oxide nanoparticle (CuO NP) labeled detection antibody was introduced into the detection system by sandwich immunoreaction and the copper (Cu2+) ions was released from CuO nanoparticles by acid to participate in double ion-exchange reaction. The double ion-exchange reaction on the photoelectric sensing interface between Cu2+ and CdS@NiS nanocomposites formed the weak photoactive material CuxS (x = 1, 2) to reduce the photocurrent. Under optimal conditions, the double ion-exchange reaction-based PEC immunoassay exhibited good photocurrent responses toward target PSA within the dynamic working range from 0.01 ng mL-1 to 50 ng mL-1 at a low limit of detection (LOD) of 2.9 pg mL-1. Besides, our work could achieve good reproducibility and high specificity under the split-type detection mode. Compared with human PSA ELISA kit, the accuracy obtained by our strategy was satisfactory. Importantly, this Cu2+-activated double ion-exchange reaction-based PEC immunoassay provides a promising platform for the detection of biomarkers.

Effect of gas disturbance on combustion characteristics of flammable refrigerants near LFLs.

Refrigerants with low global warming potential (GWP), will play an important role in the research of alternative refrigerants and the development of new refrigerants, but most of them are flammable. And the actual environment of the refrigeration system varies with different factors, especially gas disturbance. In this paper, the combustion characteristics of four refrigerants, i.e., isobutane (R600a), ethylene (R1150), propane (R290), and 2,3,3,3-Tetrafluoroprop-1-ene (R1234yf) under the conventional static and the gas disturbance were studied. Firstly, the flame characteristics and lower flammability limits (LFLs) of the refrigerants were investigated. Then the special combustion phenomena were observed and analyzed in the presence of the gas disturbance, and an improved method for better defining the LFLs of the flammable gases under the disturbance was proposed. Finally, the experimental results show that the LFLs of the three natural refrigerants under specific low disturbance are lower than that in normal conditions, but except for R1234yf. It was found that the specific disturbance may enhance the combustion intensity by comparing the burning time of visible flame under the two conditions. The results have guiding significance for the safe application of flammable refrigerants.

Porous Cobalt Phosphide Polyhedrons with Iron Doping as an Efficient Bifunctional Electrocatalyst.

Iron (Fe)-doped porous cobalt phosphide polyhedrons are designed and synthesized as an efficient bifunctional electrocatalyst for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). The synthesis strategy involves one-step route for doping foreign metallic element and forming porous cobalt phosphide polyhedrons. With varying doping levels of Fe, the optimized Fe-doped porous cobalt phosphide polyhedron exhibits significantly enhanced HER and OER performances, including low onset overpotentials, large current densities, as well as small Tafel slopes and good electrochemical stability during HER and OER.