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Molecular features are incorporated into the integrated diagnostic system for adult diffuse gliomas. Of these, copy number variation (CNV) markers, including both arm-level (1p/19q codeletion, +7/-10 signature) and gene-level (EGFR gene amplification, CDKN2A/B homozygous deletion) changes, have revolutionized the diagnostic paradigm by updating the subtyping and grading schemes. Shallow whole genome sequencing (sWGS) has been widely used for CNV detection due to its cost-effectiveness and versatility. However, the parallel detection of glioma-associated CNV markers using sWGS has not been optimized in a clinical setting. Herein, we established a model-based approach to classify the CNV status of glioma-associated diagnostic markers with a single test. To enhance its clinical utility, we carried out hypothesis testing model-based analysis through the estimation of copy ratio fluctuation level, which was implemented individually and independently and, thus, avoided the necessity for normal controls. Besides, the customization of required minimal tumor fraction (TF) was evaluated and recommended for each glioma-associated marker to ensure robust classification. As a result, with 1× sequencing depth and 0.05 TF, arm-level CNVs could be reliably detected with at least 99.5% sensitivity and specificity. For EGFR gene amplification and CDKN2A/B homozygous deletion, the corresponding TF limits were 0.15 and 0.45 to ensure the evaluation metrics were both higher than 97%. Furthermore, we applied the algorithm to an independent glioma cohort and observed the expected sample distribution and prognostic stratification patterns. In conclusion, we provide a clinically applicable algorithm to classify the CNV status of glioma-associated markers in parallel., (© 2024 The Author(s). The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Benzotriazole ultraviolet absorbers (BUVs), as emerging contaminants of extensive use, especially in plastic sports fields, have aroused increasing concern due to their potential human and environmental impacts. However, BUV exposure from plastic sports field dust is still unknown. This study compared BUVs in plastic sports field dust and indoor dust for the first time. The order of the geometric mean concentrations of the total BUVs (ΣBUVs) in plastic sports field dust was indoor badminton courts (11023 ng g -1 ) > basketball courts (4777 ng g -1 ) > plastic tracks (3779 ng g -1 ) > synthetic turf (1920 ng g -1 ) > tennis courts (689 ng g -1 ). The geometric mean concentrations of ΣBUVs in indoor dust (1150 ng g -1 ) were lower than those in most plastic sports field dust. The dominant BUV was 2-hydroxy-4-(octyloxy)benzophenone (UV-531) in plastic sports field dust, while 2,2'-methylenebis[4-(1,1,3,3-tetramethylbutyl)-6-2H-benzotriazole-2-yl)phenol] (UV-360) was the dominant BUV in indoor dust. Releases from plastic track materials, sneaker soles, and friction between them might be important BUV sources in plastic track dust. The average estimated daily intakes of ΣBUVs from plastic sports field dust for general exercisers were lower than those from indoor dust, but those for exercisers with long time or professional athletes might be higher, potentially posing health risks.

Background: Non-obstructive azoospermia is the most severe form of male infertility. A testicular biopsy is required for the diagnosis of non-obstructive azoospermia, and the causal factors for non-obstructive azoospermia remain unknown., Objectives: To reduce the risk of multiple biopsies and identify factors that contribute to non-obstructive azoospermia, we proposed an integrated approach for the preoperative diagnosis and clinical management of non-obstructive azoospermia by applying the chromosome-spreading technique and whole-exome sequencing., Materials and Methods: Between July 2020 and December 2022, after ruling out definitive obstructive azoospermia and non-obstructive azoospermia patients with testicular volume < 6 mL, 20 patients with non-obstructive azoospermia who underwent preoperative testicular diagnostic biopsy using testicular sperm aspiration were subjected to retrospective analysis., Results: Microscopic examination identified four patients with sperm cells, and 16 without sperm cells. Routine pathological analysis classified one patient as normal spermatogenesis, three as hypospermatogenesis, five as maturation arrest, nine as Sertoli cell-only, and two as unable to judge. With chromosome-spreading technology using routine cell suspension samples for microscopic examination, 18 patient diagnoses were validated, and two patients without a definitive diagnosis were supplemented. Detection of the Y chromosome and a well-organized whole-exome sequencing analysis revealed potential genetic factors., Discussion and Conclusion: The full use of testicular biopsy is beneficial for the diagnosis of azoospermia, as it avoids the risk of multiple biopsies. Moreover, in combination with whole-exome sequencing, clinicians can obtain more information regarding the pathogenesis of non-obstructive azoospermia, which may guide treatment., (© 2024 American Society of Andrology and European Academy of Andrology.)

Anoplophora glabripennis (ALB) is one of the most devastating wood boring insects of poplars. Populus deltoides 'Shalinyang (PdS), a new poplar variety, shows strong resistance to ALB infestation. However, the molecular mechanism of insect resistance in PdS is unclear. Here, we found that lignan content was much higher in PdS phloem after ALB infestation than in healthy trees, and that adding lignan to artificial diet significantly reduced: larval weight; digestive enzyme activity (cellulase [CL], polygalacturonase [PG]); detoxification enzyme activity (carboxylesterase [CarE], glutathione S-transferase [GSH-ST]); and defense enzyme activity (Catalase [CAT]). We further identified the lignan biosynthesis-related PdPLR1 gene (Pinoresinol-lariciresinol reductase, PLR) based on transcriptome analysis, and it was significantly up-regulated in the PdS phloem attacked by ALB. Overexpression of PdPLR1 in Arabidopsis increased th lignan content. In contrast, silencing PdPLR1 in PdS significantly decreased expression levels of PdPLR1 and lignan content by 82.45% and 56.85%. However, silencing PdPLR1 increased the number of adults ovipositions and eggs hatching. The activity of CL, PG, CarE, GSH-ST and CAT and the biomass of larvae fed on phloem of PdS with silenced PdPLR1 were significantly higher than in the control. Taken together, up regulation of PdPLR1 enhanced PdS resistance to ALB by regulating lignan synthesis. Our findings provide in-depth insights into the molecular mechanisms of PdS-ALB interactions, which lay the foundation for understanding of defense in poplars to pest infection., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jian feng Liu reports financial support was provided by National Natural Science Foundation of China (No. 32271891)., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

During assisted reproductive technology (ART) treatment, the aged women, especially those over 35 years old, have fewer mature oocytes and poorer quality of the oocytes comparing with the young women. In vitro maturation (IVM) technology facilitates the usage of immature oocytes, which is clinically important for the aged women. However, the maturation rate is low for the oocytes from the aged women. Human umbilical cord mesenchymal stem cells derived exosomes (HUCMSCs-exosomes), as important mediators of intercellular communication, have been widely used to restore ovarian function and improve female fertility. In this study, we isolated HUCMSCs-exosomes and collected the immature germinal vesicle oocytes from the naturally aged mouse model. And we added these HUCMSCs-exosomes to the conventional IVM culture system. The effects of HUCMSCs-exosomes on IVM oocytes were observed and analyzed from multiple aspects including maturation rate, spindle morphology, mitochondria function, and development potential. We found the quality of oocytes was improved by HUCMSCs-exosomes. Based on the results, we propose that HUCMSCs-exosomes may provide a novel and cell free strategy in the improvement of the IVM in elderly infertile women in the future., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Rheumatoid arthritis (RA) is an autoimmune disease featured by chronic synovitis and progressive joint damage. Early treatment before the onset of clinical symptoms (also known as the pre-RA stage) may slow or stop the progression of the disease. We sought to discover the dynamic metabolic changes during the evolution of collagen-induced arthritis (CIA) to better characterize the disease stages. Untargeted metabolomics analysis using gas chromatography-mass spectrometry revealed that the metabolic profiles of CIA mice gradually differed from that of the control group with the progression of the disease. During the induction phase, the CIA group showed some metabolic alterations in galactose metabolism, arginine biosynthesis, tricarboxylic acid cycle (TCA cycle), pyruvate metabolism, and starch/sucrose metabolism. During the early inflammatory phase, no joint swelling was observed in CIA mice, and metabolites changed mainly involving amino acid metabolism (arginine biosynthesis, arginine/proline metabolism, phenylalanine/tyrosine/tryptophan biosynthesis), and glutathione metabolism. During the peak inflammatory phase, severe arthritis symptoms were observed in CIA mice, and there were more extensive metabolic alterations in valine/leucine/isoleucine biosynthesis, phenylalanine/tyrosine/tryptophan biosynthesis, TCA cycle, galactose metabolism, and arginine biosynthesis. Moreover, the reduction of specific amino acids, such as glycine, serine, and proline, during the early stages may result in an imbalance in macrophage polarization and enhance the inflammatory response in CIA mice. Our study confirmed that specific perturbations in amino acid metabolism have occurred in CIA mice prior to the onset of joint symptoms, which may be related to autoimmune disorders. The findings could provide insights into the metabolic mechanism and the diagnosis of pre-RA., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Depression is defined by a persistent low mood and disruptions in sleep patterns, with the WHO forecasting that major depression will rank as the third most prevalent contributor to the global burden of disease by the year 2030. Sleep deprivation serves as a stressor that triggers inflammation within the central nervous system, a process known as neuroinflammation. This inflammatory response plays a crucial role in the development of depression by upregulating the expression of inflammatory mediators that contribute to symptoms such as anxiety, hopelessness, and loss of pleasure., Methods: In this study, sleep deprivation was utilized as a method to induce anxiety and depressive-like behaviors in mice. The behavioral changes in the mice were then evaluated using the EZM, EPM, TST, FST, and SPT. H&E staining and Nissl staining was used to detect morphological changes in the medial prefrontal cortical (mPFC) regions. Elisa to assess serum CORT levels. Detection of mRNA levels and protein expression of clock genes, high mobility genome box-1 (Hmgb1), silent message regulator 6 (Sirt6), and pro-inflammatory factors by RT-qPCR, Western blotting, and immunofluorescence techniques., Results: Sleep deprivation resulted in decreased exploration of unfamiliar territory, increased time spent in a state of despair, and lower sucrose water intake in mice. Additionally, sleep deprivation led to increased secretion of serum CORT and upregulation of clock genes, IL6, IL1β, TNFα, Cox-2, iNOS, Sirt6, and Hmgb1. Sleep., Conclusions: Sleep deprivation induces anxiety-depressive-like behaviors and neuroinflammation in the brain. Transcription of clock genes and activation of the Sirt6/Hmgb1 pathway may contribute to inflammatory responses in the mPFC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Metal halide perovskites (MHPs) have demonstrated considerable promise for a range of photoelectronic applications owing to their prominent photophysical properties. However, MHPs suffer from remarkable ion migration under illumination and bias voltage, which generally poses operational instability of MHP-based devices and restricts their practicality. While numerous chemical strategies have been proposed for manipulating ion migration dynamics, the relevant mechanistic research relatively lags behind, which is nevertheless imperative for guiding ion migration engineering. In this perspective, we first review the well-established experimental techniques for characterizing ion migration in MHP films and photovoltaic devices. For the sake of gaining insights into the underlying mechanism, we also present a series of physical models that elucidate the dynamics of ion migration and the coupling interaction between ions and charge carriers in MHP photovoltaics. Finally, we identify several crucial areas for future investigation, with the aim of advancing both the fundamental and applied research on high-efficiency and high-stability MHP materials and devices.

Background: Niraparib, a poly ADP-ribose polymerase inhibitors (PARPi), has been widely applied in the intervention of epithelial ovarian, fallopian tube, or primary peritoneal cancer. Nevertheless, as of the present moment, there are limited instances demonstrating favorable outcomes stemming from niraparib therapy in patients with clear cell renal cell carcinoma (ccRCC)., Case Presentation: Here, we report a case of a 50-year-old patient with ccRCC who subsequently developed distant metastasis. The patient received monotherapy with pazopanib and combination therapy with axitinib and tislelizumab, demonstrating limited efficacy. Liquid biopsy revealed missense mutations in the CDK12 and RAD51C of the homologous recombination repair (HRR) pathway, suggesting potential sensitivity to PARPi. Following niraparib treatment, the patient's condition improved, with no significant side effects., Conclusion: In summary, patients with ccRCC harboring HRR pathway gene mutation may potentially benefit from niraparib. This will present more options for ccRCC patients with limited response to conventional treatments., Competing Interests: CY and DC were employed by Genetron Health (Beijing) Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yue, Yang, Cao and Li.)

Ion migration activated by illumination is a critical factor responsible for the performance decline and stability degradation of perovskite solar cells (PSCs). While ion migration has been widely believed to be much slower than charge transport, recent research suggests that, despite the lack of understanding of the mechanism, it may also be involved in a series of rapid photoelectric responses of PSCs. Here, we report an improved circuit-switched transient photoelectric technique with nanosecond temporal resolution, which enables quantitative characterization of ion migration dynamics in PSCs across a fairly broad time window. Specifically, ion migration occurring within microseconds after illumination (corresponding to a diffusion length of ∼10-7 cm) is unambiguously identified. In conjunction with the composition engineering protocol, we justify that it arises from the short-range migration of halide anions and organic cations around the contact/perovskite interface. The rapid ion migration kinetics revealed in this work strongly complement the well-established ion migration model, which offers new insights into the mechanism of ion-carrier interaction in PSC devices., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

The purpose of the study is to investigate the metabolic characteristics of placental tissue in patients diagnosed with gestational diabetes mellitus (GDM). Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was employed to qualitatively and quantitatively analyze the metabolites in placental tissues obtained from 25 healthy pregnant women and 25 pregnant women diagnosed with GDM. Multilevel statistical methods are applied to process intricate metabolomics data. Meanwhile, we applied machine learning techniques to identify biomarkers that could potentially predict the risk of long-term complications in patients with GDM as well as their offspring. We identified 1902 annotated metabolites, out of which 212 metabolites exhibited significant differences in GDM placentas. In addition, the study identifies a set of risk biomarkers that effectively predict the likelihood of long-term complications in both pregnant women with GDM and their offspring. The accuracy of this panel was measured by the area under the receiver operating characteristic curve (ROC), which was found to be 0.992 and 0.960 in the training and validation sets, respectively. This study enhances our understanding of GDM pathogenesis through metabolomics. Furthermore, the panel of risk markers identified could prove to be a valuable tool in predicting potential long-term complications for both GDM patients and their offspring., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Dynamic chromosome remodeling and nuclear compartmentalization take place during mammalian meiotic prophase I. We report here that the crucial roles of male pachynema-specific protein (MAPS) in pachynema progression might be mediated by its liquid-liquid phase separation in vitro and in cellulo. MAPS forms distinguishable liquid phases, and deletion or mutations of its N-terminal amino acids (aa) 2-9 disrupt its secondary structure and charge properties, impeding phase separation. Maps -/- pachytene spermatocytes exhibit defects in nucleus compartmentalization, including defects in forming sex bodies, altered nucleosome composition, and disordered chromatin accessibility. Maps Δ2-9/Δ2-9 male mice expressing MAPS protein lacking aa 2-9 phenocopy Maps -/- mice. Moreover, a frameshift mutation in C3orf62, the human counterpart of Maps, is correlated with nonobstructive azoospermia in a patient exhibiting pachynema arrest in spermatocyte development. Hence, the phase separation property of MAPS seems essential for pachynema progression in mouse and human spermatocytes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity., (Copyright © 2025 Copyright: © 2025 Neural Regeneration Research.)

The toxicity of microplastics (MPs) to aquatic organisms has been extensively studied recently. However, few studies have investigated the effects of MPs in sediments on aquatic ecosystem functioning. In the present study, we conducted an in situ experiment to explore the concentration-dependent effects (0.025%, 0.25%, 2.5%) and size-dependent effects (150-300 μm and 500-1000 μm) of polypropylene microplastics (PP MPs) on Vallisneria natans litter decomposition dynamics, in particular, the process associated with macroinvertebrates, microorganisms, as well as microalgae and/or cyanobacteria. The results showed that exposure to high concentrations and large sizes of PP MPs can accelerate leaf litter biomass loss and nutrition release. Moreover, microbial respiration, microalgal and/or cyanobacteria chlorophyll-a were also significantly affected by PP MPs. However, PP MPs have no effect on the abundance of associated macroinvertebrate during the experiment, despite the collection of five macroinvertebrate taxa from two functional feeding groups (i.e., collectors and scrapers). Therefore, our experiment demonstrated that PP MPs may enhance leaf litter decomposition through effected microbial metabolic activity, microalgal and/or cyanobacteria biomass in the sedimentary lake. Overall, our findings highlight that PP MPs have the potential to interfere with the basic ecological functions such as plant litter decomposition in aquatic environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Terpenoids emitted from plants are important for regulating plant-insect interaction. However, it is still unclear how terpenoids affect the host defense system. There are few reports of terpenoids' involvement in the mechanisms that regulate woody plants' insect resistance., Results: The (E)-β-ocimene of terpenes was only found in RBO-resist leaves, and its content was higher than that of other type terpenes. Further, we also found (E)-β-ocimene had a significant avoidance effect on RBO and reached 87.5% of the highest avoidance rate. Meanwhile, overexpression of HrTPS12 in Arabidopsis increased the HrTPS12 expression level, (E)-β-ocimene content, and enhanced the defense against RBO. However, silencing HrTPS12 in sea buckthorn revealed that the expression levels of HrTPS12 and (E)-β-ocimene significantly decreased, causing the attraction effect on RBO., Conclusion: HrTPS12 was an up-regulator, which improves sea buckthorn resistance to RBO by regulating the synthesis of volatile (E)-β-ocimene. These results provide in-depth information about the interaction between RBO and sea buckthorn and provide a theoretical basis for developing plant-based insect repellents that can be used to manage RBO. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

The giant panda ( Ailuropoda melanoleuca ) is the flagship species of animal conservation worldwide, and the number of captive pandas reached 673 in 2021. According to the Fourth National Survey Report on the Giant Panda, there are 1864 wild pandas, segregated into 33 local populations, and 25 of these populations are too small to be self-sustaining. In addition to the conservation and restoration of panda habitats, conservation translocations, an approach that has been shown to be effective in slowing or reversing biodiversity loss, are highly desirable for panda conservation. The captive-bred panda population has grown rapidly, laying the foundation for releasing captive-bred pandas into the wild. This paper reviews the scientific advances in conservation translocations of pandas. Studies have shown that before translocation conservation programs are implemented, we should determine what factors are causing the depletion of the original population at the release site. The selection of suitable release sites and individuals will help to improve the survival rate of released individuals in the wild. Pre-release training and post-release monitoring are essential to ensure successful releases. We also see the great potential for increasing applications of Adaptive Management to improve the success of giant panda conservation translocation programs. This review provides theoretical guidance for improvement of the success rate in conservation translocations for captive pandas, and uses the panda as a model species to provide a global reference for the conservation translocations of rare and endangered species.

Ankylosing spondylitis (AS) is a type of chronic rheumatic immune disease, and the crucial point of AS treatment is identifying the correct stage of the disease. However, there is a lack of effective diagnostic methods for AS staging. The primary objective of this study was to perform an untargeted metabolomic approach in AS patients in an effort to reveal metabolic differences between patients in remission and acute stages. Serum samples from 40 controls and 57 AS patients were analyzed via gas chromatography-mass spectrometry (GC-MS). Twenty-four kinds of differential metabolites were identified between the healthy controls and AS patients, mainly involving valine/leucine/isoleucine biosynthesis and degradation, phenylalanine/tyrosine/tryptophan biosynthesis, glutathione metabolism, etc. Furthermore, the levels of fatty acids (linoleate, dodecanoate, hexadecanoate, and octadecanoate), amino acids (serine and pyroglutamate), 2-hydroxybutanoate, glucose, etc., were lower in patients in the acute stage than those in the remission stage, which may be associated with the aggravated inflammatory response and elevated oxidative stress in the acute stage. Multiple stage-specific metabolites were significantly correlated with inflammatory indicators (CRP and ESR). In addition, the combination of serum 2-hydroxybutanoate and hexadecanoate plays a significant role in the diagnosis of AS stages. These metabolomics-based findings provide new perspectives for AS staging, treatment, and pathogenesis studies.

Background: The Asian longhorned beetle (ALB), Anoplophora glabripennis, is a serious wood borer of hardwood trees. Populus deltoides 'Shalinyang' (PdS) is attractive to ALB adults for oviposition but highly resistant to their offspring. Investigation of the chemicals regulating ALB oviposition is scarce in previous studies until now. To determine which chemicals emitted by PdS were attractive and induced oviposition behavior by ALB on non-host poplar tree species, we first: collected and identified the bio-active volatiles produced by PdS using coupled gas chromatography-mass spectrometry (GC-MS) and coupled gas chromatography-electroantennographic detector (GC-EAD); then evaluated which chemicals were attractive in a Y-tube olfactometer bioassay; and finally screened key compounds affecting ALB oviposition using a 'chemical-stimulated oviposition on non-host tree' bioassay., Results: (E)-2-Hexenal, hexyl acetate, (Z)-3-hexenol acetate, 1-hexanol, (Z)-3-hexenol, β-caryophyllene, and salicylaldehyde emitted from PdS were attractive to ALB. When (E)-2-hexenal, 1-hexanol, (Z)-3-hexenol acetate, and (Z)-3-hexenol were applied to the non-host tree Populus tomentosa, oviposition by ALB females was significantly increased. Furthermore, the mean number of oviposition pits increased as the (Z)-3-hexenol concentrations increased. Further tests on synergy between pairs of chemicals showed that (Z)-3-hexenol stimulated production of the most oviposition pits, but that the percentage of effective oviposition pits (those containing an egg and larva and not empty) decreased., Conclusion: (Z)-3-Hexenol is the main chemical component inducing ALB oviposition. These results increase understanding about the oviposition behavior of ALB and could help improve management strategies that regulate ALB behavior by planting mixed-species forests resistant to ALB. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Neuroinflammation is a critical feature in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Hesperetin can exert anti-inflammatory, antioxidant and other neuroprotective effects. In this study, the scopolamine (SCOP)-induced cognitive dysfunction in mice model was used to evaluate the neuroprotective effects of hesperetin. Behavioral tests (Morris water maze, open field, and novel object recognition tests) were conducted to evaluate the effect of hesperetin on cognitive dysfunction behaviors. Nissl staining and Immunofluorescence were used to evaluate hippocampal neuronal damage and microglial activation in mice. The levels of proinflammatory factors, oxidant stress, and the cholinergic neurotransmitter were detected by real-time quantitative fluorescence PCR (RT-qPCR) or biochemical reagent kits. Western blotting was used to detect the relative protein expression of the sirtuin 6 (SIRT6) / NOD-like receptor thermal protein domain associated protein 3 (NLRP3) pathway. Results showed that hesperetin could ameliorate SCOP-induced cognitive impairment and neuronal damage, and regulate the levels of cholinergic neurotransmitters in the hippocampal of AD mice. Hesperetin could also enhance antioxidant defense by regulating the levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). Hesperetin exerted anti-neuroinflammation effects through inhibiting of microglia activation and down-regulating the mRNA transcript levels of inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Meanwhile, hesperetin could attenuate the expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), thioredoxin-interacting protein (TXNIP), and caspase-1 p20 and upregulate the expression of SIRT6 in SCOP-induced mice. Overall, our study suggested that hesperetin might ameliorate SCOP-induced cognitive dysfunction by improving cholinergic system dysfunction and suppressing oxidative stress and attenuating neuroinflammation via SIRT6/NLRP3 pathway in mice., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Astrocytoma and glioblastoma (GB) are reclassified subtypes of adult diffuse gliomas based on distinct isocitrate dehydrogenase (IDH) mutation in the fifth edition of the WHO Classification of Tumors of the Central Nervous System. The recurrence of gliomas is a common and inevitable challenge, and analyzing the distinct genomic alterations in astrocytoma and GB could provide insights into their progression. This study conducted a longitudinal investigation, utilizing whole-exome sequencing, on 65 paired primary/recurrent gliomas. It examined chromosome arm aneuploidies, copy number variations (CNVs) of cancer-related genes and pathway enrichments during the relapse. The veracity of these findings was verified through the integration of our data with multiple public resources and by corroborative immunohistochemistry (IHC). The results revealed a greater prevalence of aneuploidy changes and acquired CNVs in recurrent lower grade astrocytoma than in relapsed grade 4 astrocytoma and GB. Larger aneuploidy changes were predictive of an unfavorable prognosis in lower grade astrocytoma (P < 0.05). Further, patients with acquired gains of 1q, 6p or loss of 13q at recurrence had a shorter overall survival in lower grade astrocytoma (P < 0.05); however, these prognostic effects were confined in grade 4 astrocytoma and GB. Moreover, acquired gains of 12 genes (including VEGFA) on 6p during relapse were associated with unfavorable prognosis for lower grade astrocytoma patients. Notably, elevated VEGFA expression during recurrence corresponded to poorer survival, validated through IHC and CGGA data. To summarize, these findings offer valuable insights into the progression of gliomas and have implications for guiding therapeutic approaches during recurrence., (© 2023. Nature Publishing Group UK.)

Minimal residual disease (MRD) is termed as the small numbers of remnant tumor cells in a subset of patients with tumors. Liquid biopsy is increasingly used for the detection of MRD, illustrating the potential of MRD detection to provide more accurate management for cancer patients. As new techniques and algorithms have enhanced the performance of MRD detection, the approach is becoming more widely and routinely used to predict the prognosis and monitor the relapse of cancer patients. In fact, MRD detection has been shown to achieve better performance than imaging methods. On this basis, rigorous investigation of MRD detection as an integral method for guiding clinical treatment has made important advances. This review summarizes the development of MRD biomarkers, techniques, and strategies for the detection of cancer, and emphasizes the application of MRD detection in solid tumors, particularly for the guidance of clinical treatment., (© 2023. Higher Education Press.)

A distinct population of skeletal stem/progenitor cells (SSPCs) has been identified that is indispensable for the maintenance and remodeling of the adult skeleton. However, the cell types that are responsible for age-related bone loss and the characteristic changes in these cells during aging remain to be determined. Here, we established models of premature aging by conditional depletion of Zmpste24 (Z24) in mice and found that Prx1-dependent Z24 deletion, but not Osx-dependent Z24 deletion, caused significant bone loss. However, Acan-associated Z24 depletion caused only trabecular bone loss. Single-cell RNA sequencing (scRNA-seq) revealed that two populations of SSPCs, one that differentiates into trabecular bone cells and another that differentiates into cortical bone cells, were significantly decreased in Prx1-Cre; Z24 f/f mice. Both premature SSPC populations exhibited apoptotic signaling pathway activation and decreased mechanosensation. Physical exercise reversed the effects of Z24 depletion on cellular apoptosis, extracellular matrix expression and bone mass. This study identified two populations of SSPCs that are responsible for premature aging-related bone loss. The impairment of mechanosensation in Z24-deficient SSPCs provides new insight into how physical exercise can be used to prevent bone aging., (© 2023. The Author(s).)

Problem: The phenotypes and functions of B and CD4 + T-helper cell subsets during chronic inflammation of the endometria remain largely unexplored. This study aimed to investigate the characteristics and functions of follicular helper T (Tfh) cells to understand the pathological mechanisms of chronic endometritis (CE)., Method of Study: Eighty patients who underwent hysteroscopic and histopathological examinations for CE were divided into three groups-those with positive results for hysteroscopy and CD138 staining (DP), negative results for hysteroscopy but positive CD138 staining (SP), and negative results for hysteroscopy and CD138 staining (DN). The phenotypes of B cells and CD4 + T-cell subsets were analyzed using flow cytometry., Results: CD38 + and CD138 + cells were mainly expressed in the non-leukocyte population of the endometria, and the endometrial CD19 + CD138 + B cells were fewer than the CD3 + CD138 + T cells. The percentage of Tfh cells increased with chronic inflammation in the endometria. Additionally, the elevated percentage of Tfh cells correlated with the number of miscarriages., Conclusions: CD4 + T cells, particularly Tfh cells, may be critical in chronic endometrial inflammation and affect its microenvironment, thereby regulating endometrial receptivity, compared to B cells., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pregnancy involves a wide range of adaptations in the maternal body. Maternal immune tolerance toward the foreign fetus is critical for a successful pregnancy. Decidual macrophages are the primary antigen-presenting and phagocytic cells responsible for antigen presentation and apoptotic cell removal. Their phenotype changes dynamically during pregnancy. Placenta-derived exosomes are small vesicles carrying active biological molecules such as microRNAs, proteins, and lipids. The placenta-derived exosomes have been implicated in endothelial cell activation, smooth muscle cell migration, and T-cell apoptosis, but it is unknown whether placenta-derived exosomes would affect the development and functions of decidual macrophages. In this study, we reported that placenta-derived exosomes stimulated macrophage polarization into alternatively activated (M2) macrophages. Mechanistically, miRNA-30d-5p from the placenta-derived exosomes induced macrophage polarization to the M2 phenotype by targeting histone deacetylase 9. Furthermore, the conditioned medium of placenta-derived exosome-treated macrophages promoted trophoblast migration and invasion. By contrast, the conditioned medium impaired the ability of endothelial cell tube formation and migration. Placenta-derived exosome-treated macrophages had no impact on T-cell proliferation. Together, we demonstrated that placenta-derived exosomes polarize macrophages to acquire a decidua-like macrophage phenotype to modulate trophoblast and endothelial cell functions., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hematopoietic stem cell (HSC) self-renewal and aging are tightly regulated by paracrine factors from the bone marrow niche. However, whether HSC rejuvenation could be achieved by engineering a bone marrow niche ex vivo remains unknown. Here, we show that matrix stiffness fine-tunes HSC niche factor expression by bone marrow stromal cells (BMSCs). Increased stiffness activates Yap/Taz signaling to promote BMSC expansion upon 2D culture, which is largely reversed by 3D culture in soft gelatin methacrylate hydrogels. Notably, 3D co-culture with BMSCs promotes HSC maintenance and lymphopoiesis, reverses aging hallmarks of HSCs, and restores their long-term multilineage reconstitution capacity. In situ atomic force microscopy analysis reveals that mouse bone marrow stiffens with age, which correlates with a compromised HSC niche. Taken together, this study highlights the biomechanical regulation of the HSC niche by BMSCs, which could be harnessed to engineer a soft bone marrow niche for HSC rejuvenation., Competing Interests: Declaration of interests R.Y. has submitted a patent application related to 3D co-culture of BMSCs and HSCs in GelMA hydrogel reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Human expanded potential stem cells (hEPSC) have been derived from human embryonic stem cells and induced pluripotent stem cells. Here direct derivation of hEPSC from human pre-implantation embryos is reported. Like the reported hEPSC, the embryo-derived hEPSC (hEPSC-em) exhibit a transcriptome similar to morula, comparable differentiation potency, and high genome editing efficiency. Interestingly, the hEPSC-em show a unique H3 lysine-4 trimethylation (H3K4me3) open chromatin conformation; they possess a higher proportion of H3K4me3 bound broad domain (>5 kb) than the reported hEPSC, naive, and primed embryonic stem cells. The open conformation is associated with enhanced trophoblast differentiation potency with increased trophoblast gene expression upon induction of differentiation and success in derivation of trophoblast stem cells with bona fide characteristics. Hippo signaling is specifically enriched in the H3K4me3 broad domains of the hEPSC-. Knockout of the Hippo signaling gene, YAP1 abolishes the ability of the embryo-derived EPSC to form trophoblast stem cells., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Successful placentation requires delicate communication between the endometrium and trophoblasts. The invasion and integration of trophoblasts into the endometrium during early pregnancy are crucial to placentation. Dysregulation of these functions is associated with various pregnancy complications, such as miscarriage and preeclampsia. The endometrial microenvironment has an important influence on trophoblast cell functions. The precise effect of the endometrial gland secretome on trophoblast functions remains uncertain. We hypothesized that the hormonal environment regulates the miRNA profile and secretome of the human endometrial gland, which subsequently modulates trophoblast functions during early pregnancy. Human endometrial tissues were obtained from endometrial biopsies with written consent. Endometrial organoids were established in matrix gel under defined culture conditions. They were treated with hormones mimicking the environment of the proliferative phase (Estrogen, E2), secretory phase (E2+Progesterone, P4), and early pregnancy (E2+P4+Human Chorionic Gonadotropin, hCG). miRNA-seq was performed on the treated organoids. Organoid secretions were also collected for mass spectrometric analysis. The viability and invasion/migration of the trophoblasts after treatment with the organoid secretome were determined by cytotoxicity assay and transwell assay, respectively. Endometrial organoids with the ability to respond to sex steroid hormones were successfully developed from human endometrial glands. By establishing the first secretome profiles and miRNA atlas of these endometrial organoids to the hormonal changes followed by trophoblast functional assays, we demonstrated that sex steroid hormones modulate aquaporin (AQP)1/9 and S100A9 secretions through miR-3194 activation in endometrial epithelial cells, which in turn enhanced trophoblast migration and invasion during early pregnancy. By using a human endometrial organoid model, we demonstrated for the first time that the hormonal regulation of the endometrial gland secretome is crucial to regulating the functions of human trophoblasts during early pregnancy. The study provides the basis for understanding the regulation of early placental development in humans., Competing Interests: Conflict of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Myocardial infarction (MI) elicits cardiac fibroblast activation and extracellular matrix (ECM) deposition to maintain the structural integrity of the heart. Recent studies demonstrate that Fap (fibroblast activation protein)-a prolyl-specific serine protease-is an important marker of activated cardiac fibroblasts after MI., Methods: Left ventricle and plasma samples from patients and healthy donors were used to analyze the expression level of FAP and its prognostic value. Echocardiography and histological analysis of heart sections were used to analyze cardiac functions, scar formation, ECM deposition and angiogenesis after MI. RNA-Sequencing, biochemical analysis, cardiac fibroblasts (CFs) and endothelial cells co-culture were used to reveal the molecular and cellular mechanisms by which Fap regulates angiogenesis., Results: We found that Fap is upregulated in patient cardiac fibroblasts after cardiac injuries, while plasma Fap is downregulated and functions as a prognostic marker for cardiac repair. Genetic or pharmacological inhibition of Fap in mice significantly improved cardiac function after MI. Histological and transcriptomic analyses showed that Fap inhibition leads to increased angiogenesis in the peri-infarct zone, which promotes ECM deposition and alignment by cardiac fibroblasts and prevents their overactivation, thereby limiting scar expansion. Mechanistically, we found that BNP (brain natriuretic peptide) is a novel substrate of Fap that mediates postischemic angiogenesis. Fap degrades BNP to inhibit vascular endothelial cell migration and tube formation. Pharmacological inhibition of Fap in Nppb (encoding pre-proBNP) or Npr1 (encoding the BNP receptor)-deficient mice showed no cardioprotective effects, suggesting that BNP is a physiological substrate of Fap., Conclusions: This study identifies Fap as a negative regulator of cardiac repair and a potential drug target to treat MI. Inhibition of Fap stabilizes BNP to promote angiogenesis and cardiac repair.

Purpose: Implantation is a limiting factor for treatment success in assisted reproduction. Both embryonic and endometrial factors contribute to implantation. Embryonic factors have often been ignored in previous studies about the role of endometrium in implantation. In this study, we sought to identify the endometrial genes associated with negative pregnancy outcomes following the transfer of a single euploid blastocyst., Methods: Computational analyses of the transcriptomes of mid-secretory endometria from nine pregnant and seven non-pregnant patients in a cycle preceding the transfer of a single euploid blastocyst in a vitrified-warmed cycle were performed., Results: Principal component analysis of two reported endometrial receptivity gene sets showed close clustering of the pregnant and non-pregnant samples. Differential gene expression analysis and co-expression module analysis identified 131 genes associated with the pregnancy status. The endometrial signatures identified highlight the importance of immune and metabolic regulation in pregnancy outcome. Network analysis identified 20 hub genes that could predict pregnancy outcomes with 88.9% sensitivity and 85.7% specificity. Single-cell gene expression analysis highlighted the regulation of endometrial natural killer (NK) cells, T cells, and macrophages during embryo implantation. Immune cell abundance analysis supported the dysregulation of cytotoxic immune cells in the endometria of non-pregnant women., Conclusions: We reported the first endometrial gene signature associated with pregnancy after elimination of embryo aneuploidy and highlighted the importance of the endometrial immune microenvironment and metabolic status in pregnancy outcomes., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Recently, food safety has received considerable attention, and various analytical techniques have been employed to monitor food quality. One of the promising techniques in this domain is the surface-enhanced Raman scattering (SERS) technique. This study developed a facile, cost-effective SERS method by supporting a wipe-type substrate with a small-head cotton swab. We fabricated Au-nanoparticle (NP)-decorated cotton swabs (CS-Au NP) via the dropwise addition of gold colloid on the cotton fibers. These swabs exhibit reduced gold colloid consumption and a compact fiber structure, allowing for the uniform distribution of Au NPs and easy capture of molecular signals. Experiments were conducted to obtain a CS-Au NP wiper performance optimized for cotton swab selection, NaCl concentration, and Au NP layers. The Raman reporter molecule 4-mercaptopyridine was detected at a concentration of 1 × 10 -8 M and a relative standard deviation of ≤10%. The proposed SERS platform enables the facile and reliable detection of food-safety-related molecules such as malachite green on the surface of fruits and vegetables. This paper describes the development of an easy, cost-effective, and environment-friendly method of detecting food-safety-related molecules on various food surfaces through SERS., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The removal and recovery of uranium (VI) from water solutions are critical for energy and environmental security. In this study, hydrochar at 100, 150, and 190 °C (HC100, HC150, and HC190) and pyrochar at 250 °C (BC250) were prepared from residual sludge (RS). The uranium (VI) adsorption behavior, recovery, and heavy metal risk of RS and its biochars were assessed. The sorption distribution coefficient of RS was higher than those of its biochars within the tested concentration range. The maximum adsorption capacity of uranium (VI) by HC190 was 121.26 mg/g at acidic pH (pH 4.5), which was higher than those of other tested biochars, previously reported unmodified biochars, and activated carbon. The zeta potential, FTIR, and XPS results implied that the adsorption of uranium (VI) by RS and its biochars was regulated by electrostatic attraction and the complexation with oxygen- and phosphorus-containing functional groups. Besides, partial reduction of uranium (VI) into uranium (IV) happened during the process of adsorption. More than 86% of the adsorbed uranium (VI) was recovered by 0.01 M hydrochloric acid and 100% by 0.01 M sodium carbonate. The leaching amount of heavy metals was greatly reduced after the sludge was converted to biochar, indicating that hydrothermal carbonization and pyrolysis can promote the stabilization of heavy metals. This work demonstrates that RS and its biochars can be implemented as low-cost, environment-friendly, and high-efficient materials for the purification of uranium (VI)-containing solutions by means of adsorption and desorption., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Insulin-like growth factor I (IGF-1) is a key regulator of tissue growth and development in response to growth hormone stimulation. In the skeletal system, IGF-1 derived from osteoblasts and chondrocytes are essential for normal bone development; however, whether bone marrow (BM)-resident cells provide distinct sources of IGF-1 in the adult skeleton remains elusive. Here, we show that BM stromal cells (BMSCs) and megakaryocytes/platelets (MKs/PLTs) express the highest levels of IGF-1 in adult long bones. Deletion of Igf1 from BMSCs by Lepr-Cre leads to decreased bone formation, impaired bone regeneration, and increased BM adipogenesis. Importantly, reduction of BMSC-derived IGF-1 contributes to fasting-induced marrow fat accumulation. In contrast, deletion of Igf1 from MKs/PLTs by Pf4-Cre leads to reduced bone formation and regeneration without affecting BM adipogenesis. To our surprise, MKs/PLTs are also an important source of systemic IGF-1. Platelet-rich plasma (PRP) from Pf4-Cre; Igf1 f/f mice showed compromised osteogenic potential both in vivo and in vitro, suggesting that MK/PLT-derived IGF-1 underlies the therapeutic effects of PRP. Taken together, this study identifies BMSCs and MKs/PLTs as two important sources of IGF-1 that coordinate to maintain and regenerate the adult skeleton, highlighting reciprocal regulation between the hematopoietic and skeletal systems.

Fibroblast activation protein (Fap) is a serine protease that degrades denatured type I collagen, α2-antiplasmin and FGF21. Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin (Oln). Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis (RA). However, whether Fap plays a critical role in osteoarthritis (OA) remains poorly understood. Here, we found that Fap is significantly elevated in osteoarthritic synovium, while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice. Mechanistically, we found that Fap degrades denatured type II collagen (Col II) and Mmp13-cleaved native Col II. Intra-articular injection of rFap significantly accelerated Col II degradation and OA progression. In contrast, Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA. Genetic deletion of Oln significantly exacerbated OA progression, which was partially rescued by Fap deletion or inhibition. Intra-articular injection of rOln significantly ameliorated OA progression. Taken together, these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation., (© 2023. The Author(s).)

The decidualization of endometrial stromal cells (ESCs) is an essential process facilitating embryo implantation. However, the roles of non-decidualized and decidualized ESCs in regulating the microenvironment of a receptive endometrium remain unclear. We investigated single-cell transcriptomic changes in the uterus of a CD-1 mouse model at the post-implantation stage. The implantation and inter-implantation sites of the uteruses of pregnant mice at 4.5 and 5.5 days post-coitum were dissected for single-cell RNA sequencing. We identified eight cell types: epithelial cells, stromal cells, endothelial cells, mesothelial cells, lymphocytes, myocytes, myeloids, and pericytes. The ESC transcriptome suggests that the four ESC subtypes are involved in the extracellular remodeling during implantation. The trajectory plot of ESC subtypes indicates embryo implantation that involves a differentiation pathway from undifferentiated ESCs (ESC 1) to decidualized ESCs (DEC ESCs), with distinct signaling pathways between the ESC subtypes. Furthermore, the ligand-receptor analysis suggests that ESCs communicate with epithelial cells and immune cells through nectin and ICAM signaling. Collectively, both decidualized and non-decidualized ESCs may regulate the endometrial microenvironment for optimal endometrial receptivity and immune tolerance. This study provides insights on the molecular and cellular characteristics of mouse ESCs in modulating the epithelial and lymphocyte functions during early embryo implantation.

A feature of the camel is its tolerance to osmotic stress. However, few studies of osmotic stress in vivo or comparative analyses between different tissues of the camel have been performed. Here, we report the roles of Krüppel-associated box domain containing zinc-finger repressor proteins (KRAB-ZFPs) in transcriptional networks under osmotic stress in camels by analyzing transcriptomes of four different tissues under various osmotic conditions. We found that 273 of 278 KRAB-ZFPs were expressed in our data set, being involved in all of the 65 identified networks and exhibiting their extensive functional diversity. We also found that 110 KRAB-ZFPs were hub genes involved in more than half of the networks. We demonstrated that the osmotic stress response is involved in network shifts and that KRAB-ZFPs mediate this process. Finally, we presented the diverse mechanisms of osmotic stress responses in different tissues. These results revealed the genetic architecture of systematic physiological response in vivo to osmotic stress in camels. Our work will lead to new directions for studying the mechanism of osmotic stress response in anti-arid mammals., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

One objective of human genetics is to unveil the variants that contribute to human diseases. With the rapid development and wide use of next-generation sequencing (NGS), massive genomic sequence data have been created, making personal genetic information available. Conventional experimental evidence is critical in establishing the relationship between sequence variants and phenotype but with low efficiency. Due to the lack of comprehensive databases and resources which present clinical and experimental evidence on genotype-phenotype relationship, as well as accumulating variants found from NGS, different computational tools that can predict the impact of the variants on phenotype have been greatly developed to bridge the gap. In this review, we present a brief introduction and discussion about the computational approaches for variant impact prediction. Following an innovative manner, we mainly focus on approaches for non-synonymous variants (nsSNVs) impact prediction and categorize them into six classes. Their underlying rationale and constraints, together with the concerns and remedies raised from comparative studies are discussed. We also present how the predictive approaches employed in different research. Although diverse constraints exist, the computational predictive approaches are indispensable in exploring genotype-phenotype relationship., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Yeung, Chiu and Cao.)

The ternary CdS/Ag/TiO 2 NTs photocatalysts with indirect Z-scheme heterojunctions were synthesized by the photoreduction deposition of Ag and successive ionic layer adsorption and reaction (SILAR) of CdS on TiO 2 nanotube arrays (TiO 2 NTs). The elemental composition, microstructure, photoresponse and photoelectrochemical property of the photocatalyst were systematically characterized. The results proved that compared with binary heterojunction, the light absorption range of the ternary CdS/Ag/TiO 2 NTs photocatalyst was significantly extended, and the photoelectron transportation efficiency was improved. Under sunlight irradiation, the photocatalytic capacity was verified by investigating the photodegradation of MB and RhB dyes. The CdS/Ag/TiO 2 NTs exhibited the optimal photocatalytic performance with the degradation efficiency of 82.24% for RhB and 100% for MB. The synthesized CdS/Ag/TiO 2 NTs had high photocatalytic hydrogen evolution capacity and stability, and the hydrogen production reached 806.33 μmol·cm -2 . Based on the results of electron spin resonance spectroscopy (ESR) and free radical trapping, the photocatalytic reaction mechanism was explained. The synthesis of ternary CdS/Ag/TiO 2 NTs provides a practical reference and guidance for designing high-efficient photocatalysts with Z-scheme heterojunctions toward solar energy development for H 2 generation, pollutant remediation and photoelectric conversion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Testis size determination is an important question of reproductive biology. Sertoli cells are known to be a key determinant of mammalian testis size but the underlying molecular mechanisms remain incompletely understood. Previously we showed that highly conserved germ cell RNA-binding proteins, PUMILIO1(PUM1) and PUMILIO2 (PUM2), control mouse organ and body size through translational regulation, but how different cell types of the organs contribute to their organ size regulation has not been established. Here, we report a somatic role of PUM in gonad size determination. PUM1 is highly expressed in the Sertoli cells of the developing testis from embryonic and postnatal mice as well as in germ cells. Removal of Sertoli cell, but not germ cell, Pum1 gene, led to reduced testis size without significantly affecting sperm number or fertility. Knockout of PUM1 target, Cdkn1b, rescued the phenotype of reduced testis size, supporting a key role of Sertoli cell PUM1 mediated Cdkn1b repression in the testis size control. Furthermore, removal of Pum2 or both Pum1 and Pum2 in the Sertoli cells also only affected the testis size, not sperm development, with the biggest size reduction in Pum1/2 double knockout mice. We propose that PUM1 and PUM2 modulate the testis size through their synergistic translational regulation of cell cycle regulators in the Sertoli cell. Further investigation of the ovary or other organs could reveal if PUM-mediated translational control of cell proliferation of the supporting cell represents a general mechanism for organ size modulation., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Chronic epididymitis (CE) refers to a long-lasting inflammatory condition of the epididymis, which is considered the most common site of intrascrotal inflammation and an important aetiological factor of male infertility. Recent studies demonstrate that small RNAs secreted from epididymal epithelium modulate embryo development and offspring phenotypes via sperm transmission, and the resulting modifications may lead to transgenerational inheritance. However, to date, the genome-wide analysis of small RNA together with the transcriptomic expression profiles of human epididymis and CE is still lacking. In this study, we facilitated next-generation sequencing and bioinformatics to comprehensively analyze the small RNA and mRNA in an integrative way and identified signatures associated with CE. Both of the small RNA and mRNA expression data demonstrated relatively larger molecular differences among the segmental region of the epididymides, including caput, corpus, and cauda, than that of the inflammatory conditions. By comparing the inflamed caputs to the controls, a total of 1727 genes (1220 upregulated and 507 downregulated; 42 most significant genes, adjusted P < 0.05) and 34 miRNAs (23 upregulated and 11 downregulated) were identified as differentially expressed. In silico functional enrichment analysis showed their roles in regulating different biological activities, including leukocyte chemotaxis, extracellular milieu reconstruction, ion channel and transporter-related processes, and nervous system development. Integrative analysis of miRNA and mRNA identified a regulatory network consisting of 22 miRNAs and 31 genes (miRNA-mRNA) which are strong candidates for CE. In addition, analysis about other species of small RNA, including (miRNA), piwi-interacting RNA (piRNA), tRNA-derived small RNA (tsRNA), Y RNA, and rsRNA identified the distinct expression pattern of tsRNA in CE. In summary, our study performed small RNA and miRNA profiling and integrative analysis in human CE. The findings will help to understand the role of miRNA-mRNA in the pathogenesis of CE and provide molecular candidates for the development of potential biomarkers for human CE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gong, Wang, Liu, Li, Zeng, Yang, Li, Yu, Cao and Duan.)

Aims: Metastatic cervical carcinoma is hard to cure using traditional treatment and new therapeutic approaches are needed. However, the process of clonal evolution and the molecular alterations that contribute to tumor progression from primary to metastatic carcinoma remain unclear. It is currently difficult to distinguish between the primary pulmonary squamous cell carcinoma (PPSCC) and metastatic cervical squamous cell carcinoma (CSCC). Methods: Paired primary CSCC and lung/lymph nodes metastatic lesions from eight patients were analyzed by whole-exome sequencing (WES). WES data of matched specimens and normal samples were aligned to the human reference genome and analyzed to identify somatic mutations in primary and metastatic lesions. Results: A total of 1,254 somatic variants were identified. All the primary lesions and metastatic lesions shared mutations, the percentage of shared mutations between primary lesions and corresponding metastatic lesions varied significantly, ranging from 6% to 70%. In other words, all the metastatic lesions are clonally related to primary lesions, confirming WES could prove they are metastatic from the cervix but not PPSCC. We tried to apply a gene panel to help distinguish PPSCC and metastatic CSCC but failed because the mutations were widely distributed in CSCC. Interestingly, lymph nodes metastasis (LNM) harbored fewer cancer driver mutations than primary CSCC specimens with a significant difference. Besides this, there was no significant difference in somatic mutations and copy number variation (CNV) between primary and metastatic CSCC. Conclusion: Our data demonstrate that WES is an additional helpful tool in distinguishing PPSCC and metastatic CSCC, especially for certain difficult cases., Competing Interests: QS and DC were employed by the Genetron Health (Beijing) Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Song, Cao, Jiao, Yuan and Song.)

Translational control is a fundamental mechanism regulating animal germ cell development. Gonadal somatic cells provide support and microenvironment for germ cell development to ensure fertility, yet the roles of translational control in gonadal somatic compartment remain largely undefined. We found that mouse homolog of conserved fly germline stem cell factor Pumilio, PUM1, is absent in oocytes of all growing follicles after the primordial follicle stage, instead, it is highly expressed in somatic compartments of ovaries. Global loss of Pum1, not oocyte-specific loss of Pum1, led to a significant reduction in follicular number and size as well as fertility. Whole-genome identification of PUM1 targets in ovarian somatic cells revealed an enrichment of cell proliferation pathway, including 48 key regulators of cell phase transition. Consistently granulosa cells proliferation is reduced and the protein expression of the PUM-bound Cell Cycle Regulators (PCCR) were altered accordingly in mutant ovaries, and specifically in granulosa cells. Increase in negative regulator expression and decrease in positive regulators in the mutant ovaries support a coordinated translational control of somatic cell cycle program via PUM proteins. Furthermore, postnatal knockdown, but not postnatal oocyte-specific loss, of Pum1 in Pum2 knockout mice reduced follicular growth and led to similar expression alteration of PCCR genes, supporting a critical role of PUM-mediated translational control in ovarian somatic cells for mammalian female fertility. Finally, expression of human PUM protein and its regulated cell cycle targets exhibited significant correlation with ovarian cancer and prognosis for cancer survival. Hence, PUMILIO-mediated cell cycle regulation represents an important mechanism in mammalian female reproduction and human cancer biology., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Aromia bungii (Coleoptera: Cerambycidae) is an economically important wood-boring insect pest of stone fruit trees, particularly Prunus persica , in China. It has entered Japan and several European countries as an invasive species in recent years. It is difficult to control because of the cryptic feeding behaviour of larvae beneath the bark. Identification of repellent constituents from non-host plants has potential for use in management strategies against this beetle. Mentha spicata is cultivated extensively in Hebei Province (China) as a medicinal plant. Firstly, antennal responses of female A. bungii to M. spicata volatiles were evaluated by coupled gas chromatography-electroantennograms (GC-EAD), and then the EAD-active components were tested in semi-field trials. The results showed that A. bungii females were significantly repelled by myrcene, ( S )-(+)-carvone, ( E )-β-caryophyllene, and borneol compared with the control. The presence of myrcene (100 µL; 90% purity), ( S )-(+)-carvone (200 µL; 96% purity), ( E )-β-caryophyllene (500 µL; 98.5% purity), and borneol (800 µL; 80% purity) significantly reduced the perching rates of A. bungii females on both peach logs and leaves. Considering cost and commercial availability, we suggest that myrcene, ( S )-(+)-carvone, and ( E )-β-caryophyllene could be promising repellents against A. bungii females in the field.

Background: The maternal immune system needs to tolerate the semi-allogeneic fetus in pregnancy. The adaptation occurs locally at the maternal-fetal interface as well as systemically through the maternal circulation. Failure to tolerate the paternal antigens may result in pregnancy complications, such as pregnancy loss and pre-eclampsia. However, the mechanism that regulates maternal immune tolerance, especially at the systemic level, is still an enigma. Here we report that the first-trimester placenta-derived exosomes (pEXOs) contribute to maternal immune tolerance by reprogramming the circulating monocytes., Results: pEXOs predominantly target monocytes and pEXO-educated monocytes exhibit an immunosuppressive phenotype as demonstrated by reduced expression of marker genes for monocyte activation, T-cell activation and antigen-process/presentation at the transcriptomic level. They also have a greater propensity towards M2 polarization when compared to the monocytes without pEXO treatment. The inclusion of pEXOs in a monocyte-T-cell coculture model significantly reduces proliferation of the T helper cells and cytotoxic T cells and elevates the expansion of regulatory T cells. By integrating the microRNAome of pEXO and the transcriptomes of pEXO-educated monocytes as well as various immune cell functional assays, we demonstrate that the pEXO-derived microRNA miR-29a-3p promotes the expression of programmed cell death ligand-1, a well-known surface receptor that suppresses the adaptive immune system, by down-regulation of phosphatase and tensin homolog in monocytes., Conclusions: This is the first report to show how human pEXO directly regulates monocyte functions and its molecular mechanism during early pregnancy. The results uncover the importance of pEXO in regulating the maternal systemic immune response during early pregnancy by reprogramming circulating monocytes. The study provides the basis for understanding the regulation of maternal immune tolerance to the fetal allograft., (© 2022. The Author(s).)

Leptin receptor (LepR)-positive cells are key components of the bone marrow hematopoietic microenvironment, and highly enrich skeletal stem and progenitor cells that maintain homeostasis of the adult skeleton. However, the heterogeneity and lineage hierarchy within this population has been elusive. Using genetic lineage tracing and single-cell RNA sequencing, we found that Lepr-Cre labels most bone marrow stromal cells and osteogenic lineage cells in adult long bones. Integrated analysis of Lepr-Cre-traced cells under homeostatic and stress conditions revealed dynamic changes of the adipogenic, osteogenic, and periosteal lineages. Importantly, we discovered a Notch3 + bone marrow sub-population that is slow-cycling and closely associated with the vasculatures, as well as key transcriptional networks promoting osteo-chondrogenic differentiation. We also identified a Sca-1 + periosteal sub-population with high clonogenic activity but limited osteo-chondrogenic potential. Together, we mapped the transcriptomic landscape of adult LepR + stem and progenitor cells and uncovered cellular and molecular mechanisms underlying their maintenance and lineage specification., (© 2021 The Authors.)

Nonobstructive azoospermia (NOA) and diminished ovarian reserve (DOR) are two disorders that can lead to infertility in males and females. Genetic factors have been identified to contribute to NOA and DOR. However, the same genetic factor that can cause both NOA and DOR remains largely unknown. To explore the candidate pathogenic gene that causes both NOA and DOR, we conducted whole-exome sequencing (WES) in a non-consanguineous family with two daughters with DOR and a son with NOA. We detected one pathogenic frameshift variant (NM&#95;007068:c.28delG, p. Glu10Asnfs*31) following a recessive inheritance mode in a meiosis gene DMC1 (DNA meiotic recombinase 1). Clinical analysis showed reduced antral follicle number in both daughters with DOR, but metaphase II oocytes could be retrieved from one of them. For the son with NOA, no spermatozoa were found after microsurgical testicular sperm extraction. A further homozygous Dmc1 knockout mice study demonstrated total failure of follicle development and spermatogenesis. These results revealed a discrepancy of DMC1 action between mice and humans. In humans, DMC1 is required for spermatogenesis but is dispensable for oogenesis, although the loss of function of this gene may lead to DOR. To our knowledge, this is the first report on the homozygous frameshift mutation as causative for both NOA and DOR and demonstrating that DMC1 is dispensable in human oogenesis., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Posttranscriptional regulation of cancer gene expression programs plays a vital role in carcinogenesis; identifying the critical regulators of tumorigenesis and their molecular targets may provide novel strategies for cancer diagnosis and therapeutics. Highly conserved RNA-binding protein Pumilio-1 (PUM1) regulates mouse growth and cell proliferation, propelling us to examine its role in cancer. We found human PUM1 is highly expressed in a diverse group of cancer, including prostate cancer; enhanced PUM1 expression is also correlated with reduced survival among prostate cancer patients. Detailed expression analysis in twenty prostate cancer tissues showed enhanced expression of PUM1 at mRNA and protein levels. Knockdown of PUM1 reduced prostate cancer cell proliferation and colony formation, and subcutaneous injection of PUM1 knockdown cells led to reduced tumor size. Downregulation of PUM1 in prostate cancer cells consistently elevated cyclin-dependent kinase inhibitor 1B (CDKN1B) protein expression through increased translation but did not impact its mRNA level, while overexpression of PUM1 reduced CDKN1B protein level. Our finding established a critical role of PUM1 mediated translational control, particularly the PUM1-CDKN1B axis, in prostate cancer cell growth and tumorigenesis. We proposed that PUM1-CDKN1B regulatory axis may represent a novel mechanism for the loss of CDKN1B protein expression in diverse cancers and potential targets for therapeutics development.

Background: Endometrial mesenchymal-like stromal/stem cells (eMSCs) have been proposed as adult stem cells contributing to endometrial regeneration. One set of perivascular markers (CD140b&CD146) has been widely used to enrich eMSCs. Although eMSCs are easily accessible for regenerative medicine and have long been studied, their cellular heterogeneity, relationship to primary counterpart, remains largely unclear., Methods: In this study, we applied 10X genomics single-cell RNA sequencing (scRNA-seq) to cultured human CD140b + CD146 + endometrial perivascular cells (ePCs) from menstrual and secretory endometrium. We also analyzed publicly available scRNA-seq data of primary endometrium and performed transcriptome comparison between cultured ePCs and primary ePCs at single-cell level., Results: Transcriptomic expression-based clustering revealed limited heterogeneity within cultured menstrual and secretory ePCs. A main subpopulation and a small stress-induced subpopulation were identified in secretory and menstrual ePCs. Cell identity analysis demonstrated the similar cellular composition in secretory and menstrual ePCs. Marker gene expression analysis showed that the main subpopulations identified from cultured secretory and menstrual ePCs simultaneously expressed genes marking mesenchymal stem cell (MSC), perivascular cell, smooth muscle cell, and stromal fibroblast. GO enrichment analysis revealed that genes upregulated in the main subpopulation enriched in actin filament organization, cellular division, etc., while genes upregulated in the small subpopulation enriched in extracellular matrix disassembly, stress response, etc. By comparing subpopulations of cultured ePCs to the publicly available primary endometrial cells, it was found that the main subpopulation identified from cultured ePCs was culture-unique which was unlike primary ePCs or primary endometrial stromal fibroblast cells., Conclusion: In summary, these data for the first time provides a single-cell atlas of the cultured human CD140b + CD146 + ePCs. The identification of culture-unique relatively homogenous cell population of CD140b + CD146 + ePCs underscores the importance of in vivo microenvironment in maintaining cellular identity.

In order to improve the effect of human motion rehabilitation, a design model of human motion rehabilitation based on object-oriented technology is proposed. The entire model design process includes the following steps. First, a visual dynamic tracking model for human motion rehabilitation is established, and then a fuzzy PID (Proportion Integration Differentiation) superheterodyne control method is used to design the bone training control for human motion rehabilitation. The bone tracking control and adaptive training are under the control of object-oriented technology; it is analyzed by collecting human activity data during training. The 6-DOF kinematics problem of human movement rehabilitation is decomposed into the bone training control problem in the subspace. Combining object-oriented technology, visual blur recognition of human sports rehabilitation training, and adopting an adaptive kinematics model to design sports rehabilitation can improve the control convergence and global stability of the human sports rehabilitation process. The simulation results show that the method has a good overall steady state and the sports rehabilitation training effect is obvious., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Dandan Cao et al.)