Potent human neutralizing antibodies against Nipah virus derived from two ancestral antibody heavy chains.

Nipah virus (NiV) is a World Health Organization priority pathogen and there are currently no approved drugs for clinical immunotherapy. Through the use of a naïve human phage-displayed Fab library, two neutralizing antibodies (NiV41 and NiV42) targeting the NiV receptor binding protein (RBP) were identified. Following affinity maturation, antibodies derived from NiV41 display cross-reactivity against both NiV and Hendra virus (HeV), whereas the antibody based on NiV42 is only specific to NiV. Results of immunogenetic analysis reveal a correlation between the maturation of antibodies and their antiviral activity. In vivo testing of NiV41 and its mature form (41-6) show protective efficacy against a lethal NiV challenge in hamsters. Furthermore, a 2.88 Å Cryo-EM structure of the tetrameric RBP and antibody complex demonstrates that 41-6 blocks the receptor binding interface. These findings can be beneficial for the development of antiviral drugs and the design of vaccines with broad spectrum against henipaviruses.

Mineral Chemistry and Chronology Investigation of Uraninite in the Jinguanchong Uranium Deposit in Eastern Hunan Province and the Implications for Geological Significance.

Jinguanchong deposit, a part of the Mingyuefeng ore field in eastern Hunan Province, China, is a typical perigranitic uranium deposit (a subtype of granite-related deposit) discovered recently with considerable uranium mineralization. Herein, uraninite, the primary ore mineral in the deposit, was investigated via scanning electron microscopy and electron probe microanalysis. Additionally, laser ablation-inductively coupled plasma-mass spectrometry was used for the first time to determine the in situ U-Pb age and the rare-earth element characteristics of uraninite. Uraninite mainly comprises UO2, CaO, and PbO with a low ThO2 content. Uraninite exhibits a low total content of rare-earth elements with a distinct fractionation between light and heavy rare-earth elements while displaying a negative Eu anomaly. The presence of major elements and rare-earth elements in uraninite suggests its formation within a hydrothermal environment at moderate to low temperatures below 350 °C, thereby classifying the Jinguanchong deposit as a typical hydrothermal vein-type uranium deposit. The uranium metallogenic age is determined to be 93.8 ± 1.4 Ma, falling within the midlate Cretaceous period. This age corresponds to the Mesozoic lithospheric extension and thinning events (approximately 85-95 Ma) in South China, suggesting that the formation of the Jinguanchong uranium deposit might be associated with the tectonic dynamics of lithospheric extension and thinning.

Fluorimetric determination of tetracycline antibiotics in animal derived foods using boron and nitrogen co-doped ceria-based nanoparticles.

An innovative synthesis of boron and nitrogen co-doped ceria-based nanoparticles (B/N-CeFNPs) with bright blue fluorescence emission is reported using the hydrothermal method. Based on the aggregation-induced emission enhancement (AIEE) effect between B/N-CeFNPs and chlortetracycline (CTC), a rapid detection method for CTC through fluorescence enhancement was developed. In addition, through the electron transfer process (ET), fluorescence resonance energy transfer (FRET) effect and static quenching between B/N-CeFNPs and oxytetracycline (OTC), a ratio fluorescence strategy for detecting OTC was generated. The fluorescence of B/N-CeFNPs at 410 nm can be effectively quenched by OTC, and new fluorescence emission appears at a wavelength of 500 nm. B/N-CeFNPs showed good linear responses with CTC and OTC in the range 0.1-1 µM and 1-40 µM, respectively. This system was used to simultaneously detect the CTC and OTC in milk and honey, realizing multi-residues detection of TCs in actual samples by using the same ceria-based fluorescence nanomaterial.

Eco-evolutionary dynamics of gut phageome in wild gibbons (Hoolock tianxing) with seasonal diet variations.

It has been extensively studied that the gut microbiome provides animals flexibility to adapt to food variability. Yet, how gut phageome responds to diet variation of wild animals remains unexplored. Here, we analyze the eco-evolutionary dynamics of gut phageome in six wild gibbons (Hoolock tianxing) by collecting individually-resolved fresh fecal samples and parallel feeding behavior data for 15 consecutive months. Application of complementary viral and microbial metagenomics recovers 39,198 virulent and temperate phage genomes from the feces. Hierarchical cluster analyses show remarkable seasonal diet variations in gibbons. From high-fruit to high-leaf feeding period, the abundances of phage populations are seasonally fluctuated, especially driven by the increased abundance of virulent phages that kill the Lachnospiraceae hosts, and a decreased abundance of temperate phages that piggyback the Bacteroidaceae hosts. Functional profiling reveals an enrichment through horizontal gene transfers of toxin-antitoxin genes on temperate phage genomes in high-leaf season, potentially conferring benefits to their prokaryotic hosts. The phage-host ecological dynamics are driven by the coevolutionary processes which select for tail fiber and DNA primase genes on virulent and temperate phage genomes, respectively. Our results highlight complex phageome-microbiome interactions as a key feature of the gibbon gut microbial ecosystem responding to the seasonal diet.

Small apes adjust rhythms to facilitate song coordination.

Song coordination is a universal characteristic of human music. Many animals also produce well-coordinated duets or choruses that resemble human music. However, the mechanism and evolution of song coordination have only recently been studied in animals. Here, we studied the mechanism of song coordination in three closely related species of wild Nomascus gibbons that live in polygynous groups. In each species, song bouts were dominated by male solo sequences (referred to hereafter as male sequence), and females contributed stereotyped great calls to coordinate with males. Considering the function of rhythm in facilitating song coordination in human music and animal vocalizations, we predicted that adult males adjust their song rhythm to facilitate song coordination with females. In support of this prediction, we found that adult males produced significantly more isochronous rhythms with a faster tempo in male sequences that were followed by successful female great calls (a complete sequence with "introductory" and "wa" notes). The difference in isochrony and tempos between successful great call sequences and male sequences was smaller in N. concolor compared with the other two species, which may make it difficult for females to predict a male's precise temporal pattern. Consequently, adult females of N. concolor produced more failed great call (an incomplete sequence with only introductory notes) sequences. We propose that the high degree of rhythm change functions as an unambiguous signal that can be easily perceived by receivers. In this regard, gibbon vocalizations offer an instructive model to understand the origins and evolution of human music.

ELONGATED HYPOTCOTYL5 and SPINE BASE SIZE1 together mediate light-regulated spine expansion in cucumber.

Plant trichome development is influenced by diverse developmental and environmental signals, but the molecular mechanisms involved are not well understood in most plant species. Fruit spines (trichomes) are an important trait in cucumber (Cucumis sativus L.), as they affect both fruit smoothness and commercial quality. Spine Base Size1 (CsSBS1) has been identified as essential for regulating fruit spine size in cucumber. Here, we discovered that CsSBS1 controls a season-dependent phenotype of spine base size in wild-type plants. Decreased light intensity led to reduced expression of CsSBS1 and smaller spine base size in wild-type plants, but not in the mutants with CsSBS1 deletion. Additionally, knockout of CsSBS1 resulted in smaller fruit spine base size and eliminated the light-induced expansion of spines. Overexpression of CsSBS1 increased spine base size and rescued the decrease in spine base size under low light conditions. Further analysis revealed that ELONGATED HYPOTCOTYL5(HY5), a major transcription factor involved in light signaling pathways, directly binds to the promoter of CsSBS1 and activates its expression. Knockout of CsHY5 led to smaller fruit spine base size and abolished the light-induced expansion of spines. Taken together, our study findings have clarified a CsHY5-CsSBS1 regulatory module that mediates light-regulated spine expansion in cucumber. This finding offers a strategy for cucumber breeders to develop fruit with stable appearance quality under changing light conditions.

Vocal fingerprinting reveals a substantially smaller global population of the Critically Endangered cao vit gibbon (Nomascus nasutus) than previously thought.

The cao vit gibbon (Nomascus nasutus) is one of the rarest primates on Earth and now only survives in a single forest patch of less than 5000 ha on the Vietnam-China border. Accurate monitoring of the last remaining population is critical to inform ongoing conservation interventions and track conservation success over time. However, traditional methods for monitoring gibbons, involving triangulation of groups from their songs, are inherently subjective and likely subject to considerable measurement errors. To overcome this, we aimed to use 'vocal fingerprinting' to distinguish the different singing males in the population. During the 2021 population survey, we complemented the traditional observations made by survey teams with a concurrent passive acoustic monitoring array. Counts of gibbon group sizes were also assisted with a UAV-mounted thermal camera. After identifying eight family groups in the acoustic data and incorporating long-term data, we estimate that the population was comprised of 74 individuals in 11 family groups, which is 38% smaller than previously thought. We have no evidence that the population has declined-indeed it appears to be growing, with new groups having formed in recent years-and the difference is instead due to double-counting of groups in previous surveys employing the triangulation method. Indeed, using spatially explicit capture-recapture modelling, we uncovered substantial measurement error in the bearings and distances from field teams. We also applied semi- and fully-automatic approaches to clustering the male calls into groups, finding no evidence that we had missed any males with the manual approach. Given the very small size of the population, conservation actions are now even more urgent, in particular habitat restoration to allow the population to expand. Our new population estimate now serves as a more robust basis for informing management actions and tracking conservation success over time.

Low but highly geographically structured genomic diversity of East Asian Eurasian otters and its conservation implications.

Populations of Eurasian otters Lutra lutra, one of the most widely distributed apex predators in Eurasia, have been depleted mainly since the 1950s. However, a lack of information about their genomic diversity and how they are organized geographically in East Asia severely impedes our ability to monitor and conserve them in particular management units. Here, we re-sequenced and analyzed 20 otter genomes spanning continental East Asia, including a population at Kinmen, a small island off the Fujian coast, China. The otters form three genetic clusters (one of L. l. lutra in the north and two of L. l. chinensis in the south), which have diverged in the Holocene. These three clusters should be recognized as three conservation management units to monitor and manage independently. The heterozygosity of the East Asian otters is as low as that of the threatened carnivores sequenced. Historical effective population size trajectories inferred from genomic variations suggest that their low genomic diversity could be partially attributed to changes in the climate since the mid-Pleistocene and anthropogenic intervention since the Holocene. However, no evidence of genetic erosion, mutation load, or high level of inbreeding was detected in the presumably isolated Kinmen Island population. Any future in situ conservation efforts should consider this information for the conservation management units.

A G-quadruplex-assisted target-responsive dual-mode aptasensor based on copper nanoclusters synthesized in situ in a DNA hydrogel for ultrasensitive detection of ochratoxin A.

Developing ultrasensitive sensing platforms for trace ochratoxin A (OTA) in food safety is still challenging. Herein, we presented a novel dual-mode sensing strategy for fluorescence and colorimetric detection of OTA by combining the target-responsive hemin-encapsulated and copper nanoclusters (CuNCs) functionalized DNA hydrogel. Through simple assembly and in situ synthesis methods, fluorescence CuNCs are synthesized and modified on the 3D hydrophilic network structure of DNA cross-linked. OTA specifically recognized by Apt-linker can control the collapse of hydrogel, resulting in the fluorescence quenching of CuNCs and release of coated hemin. Interestingly, OTA could trigger Apt-linker conformational changes to form G-quadruplex structures, allowing the released hemin to form G-quadruplex/hemin DNAzyme via self-assembly. Fluorescence signal amplification could be achieved through further fluorescence quenching of CuNCs caused by DNAzyme-catalyzed hydrogen peroxide (H2O2) because of the peroxidase activity of DNAzyme. Simultaneously, DNAzyme could catalyze the H2O2-mediated oxidation of TMB to provide colorimetric signal. Thereafter, the DNA-CuNCs hydrogel exhibited low detection limits of 3.49 pg/mL in fluorescence mode and 0.25 ng/mL in colorimetric modality. Real sample analyses of foodstuffs showed satisfactory results, providing prospective potential for monitoring mycotoxin contaminant.

Nitric oxide controls shoot meristem activity via regulation of DNA methylation.

Despite the importance of Nitric Oxide (NO) as signaling molecule in both plant and animal development, the regulatory mechanisms downstream of NO remain largely unclear. Here, we show that NO is involved in Arabidopsis shoot stem cell control via modifying expression and activity of ARGONAUTE 4 (AGO4), a core component of the RNA-directed DNA Methylation (RdDM) pathway. Mutations in components of the RdDM pathway cause meristematic defects, and reduce responses of the stem cell system to NO signaling. Importantly, we find that the stem cell inducing WUSCHEL transcription factor directly interacts with AGO4 in a NO dependent manner, explaining how these two signaling systems may converge to modify DNA methylation patterns. Taken together, our results reveal that NO signaling plays an important role in controlling plant stem cell homeostasis via the regulation of de novo DNA methylation.

Boosting with an aerosolized Ad5-nCoV elicited robust immune responses in inactivated COVID-19 vaccines recipients.

Introduction: The SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant and exhibits immune escape to current COVID-19 vaccines, the further boosting strategies are required. Methods: We have conducted a non-randomized, open-label and parallel-controlled phase 4 trial to evaluate the magnitude and longevity of immune responses to booster vaccination with intramuscular adenovirus vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines. Results: The aerosolized Ad5-nCoV induced the most robust and long-lasting neutralizing activity against Omicron variant and IFNg T-cell response among all the boosters, with a distinct mucosal immune response. SARS-CoV-2-specific mucosal IgA response was substantially generated in subjects boosted with the aerosolized Ad5-nCoV at day 14 post-vaccination. At month 6, participants boosted with the aerosolized Ad5-nCoV had remarkably higher median titer and seroconversion of the Omicron BA.4/5-specific neutralizing antibody than those who received other boosters. Discussion: Our findings suggest that aerosolized Ad5-nCoV may provide an efficient alternative in response to the spread of the Omicron BA.4/5 variant. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=152729, identifier ChiCTR2200057278.

Phylogenomics Reveals High Levels of Incomplete Lineage Sorting at the Ancestral Nodes of the Macaque Radiation.

The genus Macaca includes 23 species assigned into 4 to 7 groups. It exhibits the largest geographic range and represents the most successful example of adaptive radiation of nonhuman primates. However, intrageneric phylogenetic relationships among species remain controversial and have not been resolved so far. In this study, we conducted a phylogenomic analysis on 16 newly generated and 8 published macaque genomes. We found strong evidence supporting the division of this genus into 7 species groups. Incomplete lineage sorting (ILS) was the primary factor contributing to the discordance observed among gene trees; however, we also found evidence of hybridization events, specifically between the ancestral arctoides/sinica and silenus/nigra lineages that resulted in the hybrid formation of the fascicularis/mulatta group. Combined with fossil data, our phylogenomic data were used to establish a scenario for macaque radiation. These findings provide insights into ILS and potential ancient introgression events that were involved in the radiation of macaques, which will lead to a better understanding of the rapid speciation occurring in nonhuman primates.

Relationships between childhood trauma and mental health during the COVID-19 pandemic: a network analysis.

Background: Childhood trauma has been found to have an important impact on mental health. However, little is known regarding the intercorrelations between childhood trauma and mental health during the COVID-19 pandemic. This study aimed to investigate such complex interplay between childhood trauma, depression, anxiety, post-traumatic stress level during the COVID-19 pandemic, and fear of COVID-19 using network analysis. Methods: A total of 1,247 college students were recruited and were asked to complete a series of questionnaires, including the Childhood Trauma Questionnaire, Patient Health Questionnaire, Generalized Anxiety Disorder Scale, Post-traumatic Stress Checklist-Civilian version, and Fear of COVID-19 Scale. The Gaussian graphical model with the scores of the questionnaires as nodes was estimated. The partial correlations between nodes were calculated as edges. Moreover, network comparison tests were conducted to compare the network patterns between participants with high levels of childhood trauma and low levels of childhood trauma. Results: Childhood trauma was found to be connected to depression, anxiety, and post-traumatic stress level. The node of childhood trauma exhibited the strongest strength and the highest expected influence in the network. Participants with high levels of childhood trauma and participants with low levels of childhood trauma showed comparable network structure and global strength. Conclusion: Our findings revealed a complex network pattern between childhood trauma and different mental health problems, indicating that childhood trauma might be a risk factor for mental health during the COVID-19 pandemic.

Development and validation of a personalized classifier to predict the prognosis and response to immunotherapy in glioma based on glycolysis and the tumor microenvironment.

Background: Glycolysis is closely associated with cancer progression and treatment outcomes. However, the role of glycolysis in the immune microenvironment, prognosis, and immunotherapy of glioma remains unclear. Methods: This study investigated the role of glycolysis on prognosis and its relationship with the tumor microenvironment (TME). Subsequently, we developed and validated the glycolysis-related gene signature (GRS)-TME classifier using multiple independent cohorts. Furthermore, we also examined the prognostic value, somatic alterations, molecular characteristics, and potential benefits of immunotherapy based on GRS-TME classifier. Lastly, the effect of kinesin family member 20A (KIF20A) on the proliferation and migration of glioma cells was evaluated in vitro. Results: Glycolysis was identified as a significant prognostic risk factor in glioma, and closely associated with an immunosuppressive microenvironment characterized by altered distribution of immune cells. Furthermore, a personalized GRS-TME classifier was developed and validated by combining the glycolysis (18 genes) and TME (seven immune cells) scores. Patients in the GRSlow/TMEhigh subgroup exhibited a more favorable prognosis compared to other subgroups. Distinct genomic alterations and signaling pathways were observed among different subgroups, which are closely associated with cell cycle, epithelial-mesenchymal transition, p53 signaling pathway, and interferon-alpha response. Additionally, we found that patients in the GRSlow/TMEhigh subgroup exhibit a higher response rate to immunotherapy, and the GRS-TME classifier can serve as a novel biomarker for predicting immunotherapy outcomes. Finally, high expression of KIF20A is associated with an unfavorable prognosis in glioma, and its knockdown can inhibit the proliferation and migration of glioma cells. Conclusions: Our study developed a GRS-TME classifier for predicting the prognosis and potential benefits of immunotherapy in glioma patients. Additionally, we identified KIF20A as a prognostic and therapeutic biomarker for glioma.

[Application and Progress of Intelligent Assistant Diagnosis in Mental Health Assessment System].

The establishment of mental health assessment system provides a new way for the early diagnosis of mental health problems, in view of the growing population of mental diseases and problems and the uneven distribution of mental health resources. In the mental health assessment system, intelligent assistant diagnosis can assist or help psychiatrists improve their work efficiency. Intelligent assistant diagnosis provides technical support for predictive screening and auxiliary diagnosis of mental health problems. It is an intelligent diagnosis research based on big data analysis and machine learning in mental health assessment system. This article mainly reviews the application methods, the application progress in the field of mental health, as well as related technical issues and safety issues, and prospects the future research development.

Sympatric primate seed dispersers and predators jointly contribute to plant diversity in a subtropical forest.

Mutualistic and antagonistic plant-animal interactions differentially contribute to the maintenance of species diversity in ecological communities. Although both seed dispersal and predation by fruit-eating animals are recognized as important drivers of plant population dynamics, the mechanisms underlying how seed dispersers and predators jointly affect plant diversity remain largely unexplored. Based on mediating roles of seed size and species abundance, we investigated the effects of seed dispersal and predation by two sympatric primates (Nomascus concolor and Trachypithecus crepusculus) on local plant recruitment in a subtropical forest of China. Over a 26 month period, we confirmed that these primates were functionally distinct: gibbons were legitimate seed dispersers who dispersed seeds of 44 plant species, while langurs were primarily seed predators who destroyed seeds of 48 plant species. Gibbons dispersed medium-seeded species more effectively than small- and large-seeded species, and dispersed more seeds of rare species than common and dominant species. Langurs showed a similar predation rate across different sizes of seeds, but destroyed a large number of seeds from common species. Due to gut passage effects, gibbons significantly shortened the duration of seed germination for 58% of the dispersed species; however, for 54% of species, seed germination rates were reduced significantly. Our study underlined the contrasting contributions of two primate species to local plant recruitment processes. By dispersing rare species and destroying the seeds of common species, both primates might jointly maintain plant species diversity. To maintain healthy ecosystems, the conservation of mammals that play critical functional roles needs to receive further attention.

Induced PSIG expression by Herbacetin contributes to suppressing the proliferation, migration, and invasion of melanoma cells.

Melanoma is a very common malignant tumor with poor prognosis. Herbacetin is a flavonol compound with outstanding anti-tumor effects. Our work investigated the biological effects and mechanism of Herbacetin in melanoma. In our study, the mRNA and protein expressions were assessed using qRT-PCR, Western blot and IHC. MSP was performed to evaluated PGIS promoter methylation level. Cell viability, migration and invasion were examined by MTT assay, transwell migration and invasion assay, respectively. Our results revealed that DNMT3B was markedly upregulated in melanoma, while PGIS was lowly expressed. Herbacetin treatment could not only inhibit the proliferation, migration, invasion of melanoma cells and inhibit the growth of melanoma in vivo. Herbacetin could also restore the abnormal expressions of DNMT3B and PGIS in melanoma cells and tumor tissues. PGIS silencing neutralized the inhibitory effects of Herbacetin on the malignant behaviors of melanoma cells. Besides, DNMT3B knockdown promoted PGIS expression via reducing PGIS promoter methylation level in melanoma cells, thereby inhibiting malignant behaviors of melanoma cells. And as expected, the inhibitory effects of Herbacetin on malignant behaviors of melanoma cells were all abolished by DNMT3B overexpression. Collectively, Herbacetin reduced DNMT3B expression to upregulate PGIS in melanoma cells and participated in suppressing the proliferation, migration, and invasion of melanoma cells.

Insights into the coexistence of birds and humans in cropland through meta-analyses of bird exclosure studies, crop loss mitigation experiments, and social surveys.

Birds share lands with humans at a substantial scale and affect crops. Yet, at a global scale, systematic evaluations of human-bird coexistence in croplands are scarce. Here, we compiled and used meta-analysis approaches to synthesize multiple global datasets of ecological and social dimensions to understand this complex coexistence system. Our result shows that birds usually increase woody, but not herbaceous, crop production, implying that crop loss mitigation efforts are critical for a better coexistence. We reveal that many nonlethal technical measures are more effective in reducing crop loss, e.g., using scaring devices and changing sow practices, than other available methods. Besides, we find that stakeholders from low-income countries are more likely to perceive the crop losses caused by birds and are less positive toward birds than those from high-income ones. Based on our evidence, we identified potential regional clusters, particularly in tropical areas, for implementing win-win coexistence strategies. Overall, we provide an evidence-based knowledge flow and solutions for stakeholders to integrate the conservation and management of birds in croplands.

Phylogenomic analyses provide insights into primate evolution.

Comparative analysis of primate genomes within a phylogenetic context is essential for understanding the evolution of human genetic architecture and primate diversity. We present such a study of 50 primate species spanning 38 genera and 14 families, including 27 genomes first reported here, with many from previously less well represented groups, the New World monkeys and the Strepsirrhini. Our analyses reveal heterogeneous rates of genomic rearrangement and gene evolution across primate lineages. Thousands of genes under positive selection in different lineages play roles in the nervous, skeletal, and digestive systems and may have contributed to primate innovations and adaptations. Our study reveals that many key genomic innovations occurred in the Simiiformes ancestral node and may have had an impact on the adaptive radiation of the Simiiformes and human evolution.