First Report of Fusarium Wilt on lily (Lilium 'Tresor') Caused by Fusarium armeniacum in Jiangsu Province, China.

In June 2021, a disease of stem and leaf rot was observed on lily cultivar 'Tresor' with approximately 20% disease incidence in fields at Huaiyin District (119°04'N, 33°63'E) of Huaian County, Jiangsu Province. The roots and bulbs of symptomatic plants were brown and rotten, with sunken lesions. Symptomatic plants showed short, discolored leaves, and eventually lead to stem wilt and death of the whole plants (Fig. 1A and Fig. 3C). To isolate the pathogen, necrotized plant tissues were surface sterilized with 2% sodium hypochlorite for 2 min followed by 70% ethanol for 30 s and rinsed with sterile water. About 4 mm × 4 mm of diseased tissues were placed on potato dextrose agar (PDA) followed by incubation at 25°C in the dark for 5 days. The pure cultures were obtained by the hyphal-tip method. A total of four fungal isolates with similar colony characteristics were recovered. To determine the identity of the four isolated fungal isolates, genomic DNA was extracted using the method previously described (Khan et al. 2021), the sequences of the internal transcribed spacer (ITS), the translation elongation factor 1α (TEF1) and the RNA polymerase II beta subunit (RPB2) genes were analyzed with primers ITS1/ITS4 (White et al. 1990), EF1/ EF2 (O'Donnell et al. 1998), and 5F2/7cR (Reeb et al. 2004), respectively. The three gene sequences of four isolates showed 99.9 %-100% identities. The531 bp (ITS), 699 bp (TEF1), and 900 bp (RPB2) sequences of a representative isolate (JH-37) were deposited in GenBank with acce. nos. OR195729, OR195041 and OR195040, respectively. A phylogenetic tree was constructed using the concatenated three gene sequences of JH-37 and that of the related Fusarium species based on Maximum Likelihood (Fig.2). JH-37 was grouped together with the F. armeniacum strain CBS 485.94 (AB587001, GQ915501, GQ915485), and shared 99.9 % concatenated sequence identity. The three gene sequences of the strain JH-37 shared 100%, 99.85%, 99.89% identity to F. armeniacum strain CBS 485.94 using MEGA 7 software (Kuma et al. 2016) analysis, and with 94%, 95% and 100% coverage by BLAST analysis. The colony of JH-37 on PDA at 25°C for 5 days was white with yellow-brown pigmentation in the center (Fig. 1B-C). From 10-day-old cultures grown on Spezieller Nahrstoffarmer agar (SNA), macroconidia (n = 50) were falcate, slender, curved dorsiventrally, tapering towards both ends, 3 to 4 septate, and measured 24.2 to 50.0 × 2.6 to 4.2 µm. The microconidia (n = 50) were straight or slightly curved, septate 0 to 2, and measured 6.8 to 20.0× 2.1 to 3.7 µm (Fig.1D-F). These morphological characteristics were consistent with Fusarium spp. (Leslie and Summerell 2006). A pathogenicity test of JH-37 was performed on potted lily ('Tresor') under greenhouse conditions. Healthy lily bulbs were selected and one bulb was sown in soil of each pot. Inoculation was performed 60 days after sowing. Bulbs of the lily plants were wounded with needles and inoculated with 5 mL of conidia suspension (1×107 conidia/mL) in the soil around bulb or an equal amount of sterilized water as a control. This experiment had three replicates. After 15 days of inoculation, typical symptoms of bulb rotten, and leaf wilt, similar to the original field symptoms, appeared on the inoculated plants but not on the controls (Fig.3). The same fungus was reisolated from the diseased plants, as identified based on morphology and molecular evidence, which confirmed the Koch's postulate. To our knowledge, this is the first report that F. armeniacum caused Fusarium wilt on Lilium spp. in China. Further, our result could help to develop effective disease management strategies against lily wilt disease.

A novel heterozygous missense variant of the ARID4A gene identified in Han Chinese families with schizophrenia-diagnosed siblings that interferes with DNA-binding activity.

ARID4A plays an important role in regulating gene expression and cell proliferation. ARID4A belongs to the AT-rich interaction domain (ARID)-containing family, and a PWWP domain immediately precedes its ARID region. The molecular mechanism and structural basis of ARID4A are largely unknown. Whole-exome sequencing (WES) revealed that a novel heterozygous missense variant, ARID4A c.1231 C > G (p.His411Asp), was associated with schizophrenia (SCZ) in this study. We determined the crystal structure of the PWWP-ARID tandem at 2.05 Å, revealing an unexpected mode in which ARID4A assembles with its PWWP and ARID from a structural and functional supramodule. Our results further showed that compared with the wild type, the p.His411Asp ARID mutant protein adopts a less compact conformation and exhibits a weaker dsDNA-binding ability. The p.His411Asp mutation decreased the number of cells that were arrested in the G0-G1 phase and caused more cells to progress to the G2-M phase. In addition, the missense mutation promoted the proliferation of HEK293T cells. In conclusion, our data provide evidence that ARID4A p.His411Asp could cause a conformational change in the ARID4A ARID domain, influence the DNA binding function, and subsequently disturb the cell cycle arrest in the G1 phase. ARID4A is likely a susceptibility gene for SCZ; thus, these findings provide new insight into the role of ARID4A in psychiatric disorders.

Beneficial bacteria as biocontrol agents for American foulbrood disease in honey bees (Apis mellifera).

American foulbrood (AFB) is a cosmopolitan bacterial disease that affects honey bee (Apis mellifera) larvae and causes great economic losses in apiculture. Currently, no satisfactory methods are available for AFB treatment mainly due to the difficulties to eradicate the tenacious spores produced by the etiological agent of AFB, Paenibacillus larvae (Bacillales, Paenibacillaceae). This present review focused on the beneficial bacteria that displayed antagonistic activities against P. larvae and demonstrated potential in AFB control. Emphases were placed on commensal bacteria (genus Bacillus and lactic acid bacteria in particular) in the alimentary tract of honey bees. The probiotic roles lactic acid bacteria play in combating the pathogenic P. larvae and the limitations referring to the application of these beneficial bacteria were addressed.

A Modified Method for Transient Transformation via Pollen Magnetofection in Lilium Germplasm.

Lily (Lilium spp.) is a popular ornamental plant. Traditional genetic transformation methods have low efficiency in lily, thus development of a high-efficiency genetic transformation system is important. In this study, a novel transient transformation method involving pollen magnetofection was established and optimized pollen viability, and exogenous gene expression in magnetofected pollen and that of different germplasm were assessed. The highest germination percentage of Lilium regale pollen was 85.73% in medium containing 100 g/L sucrose, 61.5 mg/L H3BO3, and 91.5 mg/L CaCl2. A 1:4 ratio of nanomagnetic beads to DNA plasmid and transformation time of 0.5 h realized the highest transformation efficiency (88.32%). The GFP activity in transformed pollen averaged 69.66%, while that of the control pollen was 0.00%. In contrast to the control, transgenic seedlings obtained by pollination with magnetofected pollen showed strong positive GUS activity with 56.34% transformation efficiency. Among the lily germplasm tested, 'Sweet Surrender' and L. leucanthum had the highest transformation efficiency (85.80% and 54.47%), whereas L. davidii var. willmottiae was not successfully transformed. Transformation efficiency was positively correlated with pollen equatorial diameter and negatively correlated with polar axis/equatorial diameter ratio. The results suggest that pollen magnetofection-mediated transformation can be applied in Lilium but might have species or cultivar specificity.

Cloning and Functional Analysis of TaWRI1Ls, the Key Genes for Grain Fatty Acid Synthesis in Bread Wheat.

WRINKLED1 (WRI1), an APETALA2 (AP2) transcription factor (TF), critically regulates the processes related to fatty acid synthesis, storage oil accumulation, and seed development in plants. However, the WRI1 genes remain unknown in allohexaploid bread wheat (Triticum aestivum L.). In this study, based on the sequence of Arabidopsis AtWRI1, two TaWRI1Ls genes of bread wheat, TaWRI1L1 and TaWRI1L2, were cloned. TaWRI1L2 was closely related to monocotyledons and clustered in one subgroup with AtWRI1, while TaWRI1L1 was clustered in another subgroup with AtWRI3 and AtWRI4. Both were expressed highly in the developmental grain, subcellular localized in the nucleus, and showed transcriptional activation activity. TaWRI1L2, rather than TaWRI1L1, promoted oil body accumulation and significantly increased triglyceride (TAG) content in tobacco leaves. Overexpression of TaWRI1L2 compensated for the functional loss of AtWRI1 in an Arabidopsis mutant and restored the wild-type phenotypes of seed shape, generation, and fatty acid synthesis and accumulation. Knockout of TaWRI1L2 reduced grain size, 1000 grain weight, and grain fatty acid synthesis in bread wheat. Conclusively, TaWRI1L2, rather than TaWRI1L1, was the key transcriptional factor in the regulation of grain fatty acid synthesis in bread wheat. This study lays a foundation for gene regulation and genetic manipulation of fatty acid synthesis in wheat genetic breeding programs.

Transcriptome profiling reveals key genes in regulation of the tepal trichome development in Lilium pumilum D.C.

KEY MESSAGE: A number of potential genes and pathways involved in tepal trichome development were identified in a natural lily mutant by transcriptome analysis and were confirmed with trichome and trichomeless species. Trichome is a specialized structure found on the surface of the plant with an important function in survival against abiotic and biotic stress. It is also an important economic trait in crop breeding. Extensive research has investigated the foliar trichome in model plants (Arabidopsis and tomato). However, the developmental mechanism of tepal trichome remains elusive. Lilium pumilum is an edible ornamental bulb and a good breeding parent possessing cold and salt-alkali resistance. Here, we found a natural mutant of Lilium pumilum grown on a highland whose tepals are covered by trichomes. Our data indicate that trichomes of the mutant are multicellular and branchless. Notably, stomata are also developed on the tepal of the mutant as well, suggesting there may be a correlation between trichome and stomata regulation. Furthermore, we isolated 27 differentially expressed genes (DEGs) by comparing the transcriptome profiling between the natural mutant and the wild type. These 27 genes belong to 4 groups: epidermal cell cycle and division, trichome morphogenesis, stress response, and transcription factors. Quantitative real-time PCR in Lilium pumilum (natural mutant and the wild type) and other lily species (Lilium leichtlinii var. maximowiczii/trichome; Lilium davidii var. willmottiae/, trichomeless) confirmed the validation of RNA-seq data and identified several trichome-related genes.

A Case-Control Study of ABCB1, ABCB6, and ABCG1 Polymorphisms and Schizophrenia in a Han Chinese Population.

BACKGROUND: Schizophrenia (SCZ) is a complex, heritable, and devastating psychiatric disorder. Mutations in the members of ABC transporters have been associated with psychiatric illnesses. AIMS: In this study, we investigated whether 9 SNPs in ABCB1 (rs6946119, rs28401781, rs4148739, and rs3747802), ABCB6 (rs1109866, rs1109867, rs3731885, and rs3755047), and ABCG1 (rs182694) contribute to the risk of SCZ in a Han Chinese population. METHODS: We conducted a case-control study in a Han Chinese population, involving 1,034 SCZ patients and 1,034 unrelated healthy controls to genotype 9 SNPs. RESULTS: The analysis demonstrated that rs182694 of ABCG1 was significantly different between SCZ patients and controls as to allele (rs182694: p = 0.0070, χ2 = 7.27) and genotype frequencies (rs182694: p = 0.0013, χ2 = 13.35). CONCLUSIONS: Our findings support an association between ABCG1 polymorphism and SCZ in a Han Chinese population.

Metabolomic profiling on rat brain of prenatal malnutrition: implicated for oxidative stress and schizophrenia.

Schizophrenia is a kind of neurodevelopmental disease. Epidemiological data associates schizophrenia with prenatal exposure to famine. Relevant prenatal protein deprivation (PPD) rodent models support this result by observing decreasing prepulse inhibition, altered hippocampal morphology and impaired memory in offspring. All these abnormalities are highly consistent with the pathophysiology of schizophrenia. We developed a prenatal famine rat model by restricting daily diet of the pregnant rat to 50% of low protein diet. A metabolomics study of prefrontal cortex was performed to integrate GC-TOFMS and UPLC-QTOFMS. Thirteen controls and thirteen famine offspring were used to differentiate in PLS-DA (partial least squares-discriminate analysis) model. Furthermore, metabolic pathways and diseases were enriched via KEGG and HMDB databases, respectively. A total of 67 important metabolites were screened out according to the multivariate analysis. Schizophrenia was the most statistical significant disease (P = 0.0016) in our famine model. These metabolites were enriched in key metabolic pathways related to energy metabolism and glutamate metabolism. Based on these important metabolites, further discussion speculated famine group was characterized by higher level of oxidized damage compared to control group. We proposed that oxidative stress might be the pathogenesis of prenatal undernutrition which is induced schizophrenia.

SLC17A7 gene may be the indicator of selective serotonin reuptake inhibitor treatment response in the Chinese Han population.

Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for major depressive disorder (MDD), although the treatment outcomes vary in different people. The vesicular glutamate transporter 1 coded by SLC17A7 gene has been reported associated with MDD. According to its role in glutamate transmission, it is reasonable to consider it as a potential pharmacogenetic candidate in SSRI treatment. A total of 290 MDD patients who had been taking SSRIs for 6 weeks were recruited. Their genotypes were assessed for the presence of 4 single-nucleotide polymorphisms, which were selected from either the HapMap Chinese ethnic group or the literature report. Treatment effects were evaluated by the change rate of Hamilton Rating Scale for Depression. After the adjustment for the false discovery rate, 1 single-nucleotide polymorphism (rs74174284, false discovery rate; P = 0.032) demonstrated significant association with SSRI treatment response at week 6. Our results suggest that genetic variants in the SLC17A7 gene may be indicators of treatment response in MDD patients treated by SSRIs.

VPA inhibits renal cancer cell migration by targeting HDAC2 and down-regulating HIF-1α.

Cell migration plays major roles in human renal cancer-related death, but the molecular mechanisms remain unclear. Valproic acid (VPA) is a broad-spectrum inhibitor of class I and II histone deacetylases and shows great anticancer activity in a variety of human cancers. In this study, we found that VPA significantly inhibited cell migration but not proliferation of human renal cancer ACHN cells. Mechanistic studies found that VPA significantly inhibited the expression of HIF-1α. Knockdown of HIF-1α could obviously inhibited cell migration, while over-expression of HIF-1α markedly rescued the inhibition of VPA on cell migration. Further studies found that knockdown of HDAC2 completely mimicked the effects of VPA on HIF-1α and cell migration, and over-expression of HIF-1α could also rescue the effects of HDAC2 knockdown on cell migration. Collectively, these results indicated that the potential of specific inhibition of HDAC2 by small molecular chemicals may lead to future therapeutic agents in human renal cancer treatment.

Effect of Food Restriction on Food Grinding in Brandt's Voles.

Food grinding is supposed to be influenced by multiple factors. However, how those factors affecting this behavior remain unclear. In this study, we investigated the effect of food restriction on food grinding in Brandt's voles (Lasiopodomys brandtii), as well as the potential role of the gut microbiota in this process, through a comparison of the variations between voles with different food supplies. Food restriction reduced the relative amount of ground food to a greater extent than it lowered the relative food consumption, and altered the abundance of Staphylococcus, Aerococcus, Jeotgalicoccus, and Un--s-Clostridiaceae bacterium GM1. Fecal acetate content for the 7.5 g-food supply group was lower than that for the 15 g-food supply group. Our study indicated that food restriction could effectively inhibit food grinding. Further, Un--s-Clostridiaceae bacterium GM1 abundance, Aerococcus abundance, and acetate content were strongly related to food grinding. Variations in gut microbial abundance and short-chain fatty acid content induced by food restriction likely promote the inhibition of food grinding. These results could potentially provide guidance for reducing food waste during laboratory rodent maintenance.

TaMADS29 interacts with TaNF-YB1 to synergistically regulate early grain development in bread wheat.

Grain development is a crucial determinant of yield and quality in bread wheat (Triticum aestivum L.). However, the regulatory mechanisms underlying wheat grain development remain elusive. Here we report how TaMADS29 interacts with TaNF-YB1 to synergistically regulate early grain development in bread wheat. The tamads29 mutants generated by CRISPR/Cas9 exhibited severe grain filling deficiency, coupled with excessive accumulation of reactive oxygen species (ROS) and abnormal programmed cell death that occurred in early developing grains, while overexpression of TaMADS29 increased grain width and 1,000-kernel weight. Further analysis revealed that TaMADS29 interacted directly with TaNF-YB1; null mutation in TaNF-YB1 caused grain developmental deficiency similar to tamads29 mutants. The regulatory complex composed of TaMADS29 and TaNF-YB1 exercises its possible function that inhibits the excessive accumulation of ROS by regulating the genes involved in chloroplast development and photosynthesis in early developing wheat grains and prevents nucellar projection degradation and endosperm cell death, facilitating transportation of nutrients into the endosperm and wholly filling of developing grains. Collectively, our work not only discloses the molecular mechanism of MADS-box and NF-Y TFs in facilitating bread wheat grain development, but also indicates that caryopsis chloroplast might be a central regulator of grain development rather than merely a photosynthesis organelle. More importantly, our work offers an innovative way to breed high-yield wheat cultivars by controlling the ROS level in developing grains.

Personality traits as mediators in the association between SIRT1 rs12415800 polymorphism and depressive symptoms among Chinese college students.

Background: Previous research has linked polymorphisms in the SIRT1 gene to depressive symptoms, particularly in Chinese individuals. However, it is not clear how personality traits may contribute to this association. Methods: To explore the potential mediating effect of personality traits, we utilized a mediation model to examine the relationship between the SIRT1 rs12415800 polymorphism and depressive symptoms in 787 Chinese college students. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale, while personality traits were measured using the Big Five Inventory (BFI). Results: Our analysis indicated a significant association between the SIRT1 rs12415800 polymorphism and depressive symptoms, with this relationship partially mediated by the personality traits of neuroticism and conscientiousness. Specifically, individuals who were heterozygous for the rs12415800 polymorphism and had higher levels of conscientiousness were less likely to experience depressive symptoms. Conversely, those who were homozygous for the rs12415800 polymorphism and had higher levels of neuroticism were more likely to experience depressive symptoms. Conclusion: Our results suggest that personality traits, particularly neuroticism and conscientiousness, may play a critical role in the association between the SIRT1 rs12415800 polymorphism and depressive symptoms among Chinese college students. These findings highlight the importance of considering both genetic factors and personality traits when exploring the etiology of depressive symptoms in this population.

TULP4, a novel E3 ligase gene, participates in neuronal migration as a candidate in schizophrenia.

BACKGROUND: TUB-like protein 4 (TULP4) is one of the distant members of tubby family proteins, whose function remains largely unknown. In the present study, we intend to identify the role of TULP4 in schizophrenia from human samples and animal models. METHODS: Whole-exome sequencing was used to detect the four schizophrenia families collected. In different cell lines, the effects of identified variants in TULP4 gene on its expression and localization were analyzed. Knockdown models in utero and adult mice were employed to investigate the role of Tulp4 on neuronal migration and schizophrenia-related behavior. Subsequently, co-IP assays were used to search for proteins that interact with TULP4 and the effects of mutants on the molecular function of TULP4. RESULTS: For the first time, we identified five rare variants in TULP4 from schizophrenia families, of which three significantly reduced TULP4 protein expression. Knockdown the expression of Tulp4 delayed neuronal migration during embryological development and consequently triggered abnormal behaviors in adult mice, including impaired sensorimotor gating and cognitive dysfunction. Furthermore, we confirmed that TULP4 is involved in the formation of a novel E3 ligase through interaction with CUL5-ELOB/C-RNF7 and the three deleterious variants affected the binding amount of TULP4 and CUL5 to a certain extent. CONCLUSIONS: Together, we believe TULP4 plays an important role in neurodevelopment and subsequent schizophrenic-related phenotypes through its E3 ubiquitin ligase function.

Interspecific differences in sociability, social novelty preference, anxiety- and depression-like behaviors between Brandt's voles and C57BL/6J mice.

The three-chamber test has been widely used to investigate social approach/novelty preference in rodents. Most studies have used the briefly familiar and unfamiliar individuals as stimuli to examine social recognition; however, little is known about the effects of long-term familiar peers in this paradigm. In the present study, we made a slight modification to it: the first phase measured preference for a cage-mate (not a novel individual) over an identical wire cage without an individual stimulus; the later phase measured preference for a novel individual placed in the previous empty wire cage compared to the cage-mate (not the briefly familiar individual). The present study aimed to compare differences in sociability and social recognition between Brandt's voles (Lasiopodomys brandtii) and C57BL/6J mice using this modified three-chamber test. The levels of anxiety-, depression-, and anhedonia-like behaviors were also examined in both species. We found that Brandt's voles preferred the cage-mate over the empty cage in phase 1 and showed a preference for the novel individual in phase 2. In C57BL/6J mice, males showed no preference for familiar peers in phase 1, whereas females failed to show a preference for the novel individual in phase 2, showing a sex-specific difference. Furthermore, Brandt's voles displayed higher levels of locomotor activity and sociability as well as lower levels of anxiety-, depression-, and anhedonia-like behaviors than C57BL/6J mice. Interestingly, sociability and social approach correlated with depression-like behavior, whereas social novelty preference correlated with anhedonia-like behavior. Together, these data indicate that Brandt's voles and C57BL/6J mice show significant differences in sociability, social recognition, and levels of anxiety- and depression-like behaviors. Furthermore, Brandt's voles are more suitable for the study of selective social relationships.

The host genetics affects gut microbiome diversity in Chinese depressed patients.

The gut microbiome and host genetics are both associated with major depressive disorder (MDD); however, the molecular mechanisms among the associations are poorly understood, especially in the Asian, Chinese group. Our study applied linear discriminant analysis (LDA) effect size (LEfSe) and genome-wide association analysis in the cohort with both gut sequencing data and genomics data. We reported the different gut microbiota characteristics between MDD and control groups in the Chinese group and further constructed the association between host genetics and the gut microbiome. Actinobacteria and Pseudomonades were found more in the MDD group. We found significant differences in the ACE and Chao indexes of alpha diversity while no discrepancy in beta diversity. We found three associations between host genetics with microbiome features: beta diversity and rs6108 (p = 8.65 × 10-9), Actinobacteria and rs77379751 (p = 8.56 × 10-9), and PWY-5913 and rs1775633082 (p = 4.54 × 10-8). A species of the Romboutsia genus was co-associated with the species of Ruminococcus gnavus in an internetwork through four genes: METTL8, ITGB2, OTULIN, and PROSER3, with a strict threshold (p < 5 × 10-4). Furthermore, our findings suggested that the gut microbiome diversity might affect microRNA expression in the brain and influenced SERPINA5 and other spatially close genes afterward. These findings suggest new linkages between depression and gut microbiome in Asian, Chinese people, which might be mediated by genes and microRNA regulation in space distance.

Upregulation of DGCR8, a Candidate Predisposing to Schizophrenia in Han Chinese, Contributes to Phenotypic Deficits and Neuronal Migration Delay.

DiGeorge Syndrome Critical Region Gene 8 (DGCR8) is a key component of the microprocessor complex governing the maturation of most microRNAs, some of which participate in schizophrenia and neural development. Previous studies have found that the 22q11.2 locus, containing DGCR8, confers a risk of schizophrenia. However, the role of DGCR8 in schizophrenia and the early stage of neural development has remained unknown. In the present study, we try to identify the role of DGCR8 in schizophrenia from human samples and animal models. We found that the G allele and GG genotype of rs3757 in DGCR8 conferred a higher risk of schizophrenia, which likely resulted from higher expression of DGCR8 according to our test of dual-luciferase reporter system. Employed overexpression model in utero and adult mice, we also revealed that the aberrant increase of Dgcr8 delayed neuronal migration during embryological development and consequently triggered abnormal behaviors in adult mice. Together, these results demonstrate that DGCR8 may play a role in the etiology of schizophrenia through regulating neural development.

NGFR Gene and Single Nucleotide Polymorphisms, rs2072446 and rs11466162, Playing Roles in Psychiatric Disorders.

Psychiatric disorders are a class of complex disorders characterized by brain dysfunction with varying degrees of impairment in cognition, emotion, consciousness and behavior, which has become a serious public health issue. The NGFR gene encodes the p75 neurotrophin receptor, which regulates neuronal growth, survival and plasticity, and was reported to be associated with depression, schizophrenia and antidepressant efficacy in human patient and animal studies. In this study, we investigated its association with schizophrenia and major depression and its role in the behavioral phenotype of adult mice. Four NGFR SNPs were detected based on a study among 1010 schizophrenia patients, 610 patients with major depressive disorders (MDD) and 1034 normal controls, respectively. We then knocked down the expression of NGFR protein in the hippocampal dentate gyrus of the mouse brain by injection of shRNA lentivirus to further investigate its behavioral effect in mice. We found significant associations of s2072446 and rs11466162 for schizophrenia. Ngfr knockdown mice showed social and behavioral abnormalities, suggesting that it is linked to the etiology of neuropsychiatric disorders. We found significant associations between NGFR and schizophrenia and that Ngfr may contribute to the social behavior of adult mice in the functional study, which provided meaningful clues to the pathogenesis of psychiatric disorders.

College students' screening early warning factors in identification of suicide risk.

This study aimed to explore the main influencing factors of suicide risk among Chinese students and establish an early warning model to provide interventions for high-risk students. We conducted surveys of students in their first and third years from a cohort study at Jining Medical College. Logistic regression models were used to screen the early warning factors, and four machine learning models were used to establish early warning models. There were 8 factors related to suicide risk that were eventually obtained through screening, including age, having a rough father, and CES-D, OHQ, ASLEC-4, BFI-Neuroticism, BFI-Openness, and MMC-AF-C scores. A random forest model with SMOTE was adopted, and it verified that these 8 early warning signs, for suicide risk can effectively predict suicide risk within 2 years with an AUC score of 0.947. Among the factors, we constructed a model that indicated that different personality traits affected suicide risk by different paths. Moreover, the factors obtained by screening can be used to identify college students in the same year with a high risk of suicide, with an AUC score that reached 0.953. Based on this study, we suggested some interventions to prevent students going high suicide risk.

Genetic and functional analysis reveals TENM4 contributes to schizophrenia.

TENM4, encoding a member of the teneurin protein family, is a risk gene shared by many types of mental diseases and is implicated in neuronal plasticity and signaling. However, the role and the mechanisms of TENM4 in schizophrenia (SCZ) remain unclear. We identified possible pathogenic mutations in the TENM4 gene through target sequencing of TENM4 in 68 SCZ families. We further demonstrated that aberrant expression of Ten-m leads to lower learning ability, sleep reduction, and increased aggressiveness in animal models. RNA sequencing showed that aberrant expression of Ten-m was related to stimulus perception and metabolic process, and Gene Ontology enrichment terms were neurogenesis and ATPase activity. This study provides strong evidence that TENM4 contributes to SCZ, and its functional mutations might be responsible for the impaired neural circuits and behaviors observed in SCZ.