FANCM promotes PARP inhibitor resistance by minimizing ssDNA gap formation and counteracting resection inhibition.

Poly(ADP-ribose) polymerase inhibitors (PARPis) exhibit remarkable anticancer activity in tumors with homologous recombination (HR) gene mutations. However, the role of other DNA repair proteins in PARPi-induced lethality remains elusive. Here, we reveal that FANCM promotes PARPi resistance independent of the core Fanconi anemia (FA) complex. FANCM-depleted cells retain HR proficiency, acting independently of BRCA1 in response to PARPis. FANCM depletion leads to increased DNA damage in the second S phase after PARPi exposure, driven by elevated single-strand DNA (ssDNA) gap formation behind replication forks in the first S phase. These gaps arise from both 53BP1- and primase and DNA directed polymerase (PRIMPOL)-dependent mechanisms. Notably, FANCM-depleted cells also exhibit reduced resection of collapsed forks, while 53BP1 deletion restores resection and mitigates PARPi sensitivity. Our results suggest that FANCM counteracts 53BP1 to repair PARPi-induced DNA damage. Furthermore, FANCM depletion leads to increased chromatin bridges and micronuclei formation after PARPi treatment, elucidating the mechanism underlying extensive cell death in FANCM-depleted cells.

A synthetic position decoding technology for rotary transformers based rotor position measurement system.

This article proposes a rotary transformer position decoding scheme for motor drive control. In this scheme, a simple analog circuit is used to design the excitation circuit and signal conditioning circuit. Demodulate the modulated sine/cosine signal through software and decode it through a phase locked loop (PLL) to obtain the implemented position signal. This scheme completely avoids the use of traditional, specialized decoding chips. At the same time, in order to make the position decoding scheme applicable to different motor drive control platforms, a single-cycle partition average based pulse signal estimation method is proposed for converting the angle position into pulse signals similar to the output of an encoder's phases A, B, and Z, which are referred to as A/B/Z signals in the paper. In order to experimentally validate the proposed scheme, a software decoding platform based on the STM32F407 was built and compared with the decoding results of the chip. The effectiveness and accuracy of the proposed scheme were verified, and it can be effectively applied in the field of motor drive control.

Using organic fertilizer to mitigate organic-inorganic fouling in agricultural saline wastewater irrigation systems.

Recycling saline wastewater for agricultural irrigation offer a promising solution to address both water scarcity and anthropogenic pollution. However, organic-inorganic fouling in saline wastewater irrigation systems (SWIS) poses significant technical and economic challenges. Traditional chemical biocides are currently insufficient for controlling composite organic-inorganic fouling and may pose environmental hazards. This study proposed a greener approach using organic acid (OA) fertilizers to alleviate organic-inorganic fouling in agricultural SWIS. The treatment performances were assessed employing four types of OA fertilizers (i.e., humic acid, alginic acid, nucleotide, and ammonia acid) and a negative control. Results showed that three types of OA, i.e., alginic acid, nucleotide, and ammonia acid, effectively reduced the total SWIS fouling content by 11.2%-57.4%, whereas humic acid exacerbated fouling by 11.2%-57.4%. Specifically, all types of OA significantly mitigated the content of inorganic fouling (precipitates and silicates) by 10.7%-42.3% by forming loosed and sparser structures. However, OA exhibited minimum effects on controlling silica fouling. Meanwhile, except the humic acid, other types of OA decreased the total content of organic fouling by 17.2%-39.5% by reducing the content of humic substances and building block fractions. In addition, the significant binary interactions of organic-inorganic fouling indicated the active role of calcium silica and biomineralization fouling. These findings provide insight into the development of appropriate and eco-friendly antifouling strategies for SWIS, with implications for recycling and reusing saline wastewater.

Combination of magnetic field and ultraviolet for fouling control in saline wastewater distribution systems.

Fouling is a significant challenge for recycling and reusing saline wastewaters for industrial, agricultural or municipal applications. In this study, we propose a novel approach of magnetic field (MaF) and ultraviolet (UV) combined application for fouling mitigation. Results showed, combination of MaF and UV (MaF-UV) significantly decreased the content of biofouling and reduced the complexity of microbial networks, compared to UV and MaF alone treatments. This was due to MaF as pretreatment effectively reduced the water turbidity, improve the influent water quality of UV disinfection and increases UV transmittance, eliminating the adverse impacts of UV scattering and shielding, hence increased the inactivation effectiveness of UV disinfection process. MaF assisted UV also reduced the abundance of UV-resistant bacteria and inhibited the risk of bacterial photoreactivation and dark repair. Meanwhile, MaF-UV drastically reduced the contents of precipitates and particulate fouling by accelerating the transformation rate of CaCO3 crystal from compact calcite to loosen hydrated amorphous CaCO3, and enhancing the flocculation process. These findings demonstrated that MaF-UV is an effective anti-fouling strategy, and provide insights for sustainable application of saline wastewaters.

Decoding the spatiotemporal regulation of transcription factors during human spinal cord development.

The spinal cord is a crucial component of the central nervous system that facilitates sensory processing and motor performance. Despite its importance, the spatiotemporal codes underlying human spinal cord development have remained elusive. In this study, we have introduced an image-based single-cell transcription factor (TF) expression decoding spatial transcriptome method (TF-seqFISH) to investigate the spatial expression and regulation of TFs during human spinal cord development. By combining spatial transcriptomic data from TF-seqFISH and single-cell RNA-sequencing data, we uncovered the spatial distribution of neural progenitor cells characterized by combinatorial TFs along the dorsoventral axis, as well as the molecular and spatial features governing neuronal generation, migration, and differentiation along the mediolateral axis. Notably, we observed a sandwich-like organization of excitatory and inhibitory interneurons transiently appearing in the dorsal horns of the developing human spinal cord. In addition, we integrated data from 10× Visium to identify early and late waves of neurogenesis in the dorsal horn, revealing the formation of laminas in the dorsal horns. Our study also illuminated the spatial differences and molecular cues underlying motor neuron (MN) diversification, and the enrichment of Amyotrophic Lateral Sclerosis (ALS) risk genes in MNs and microglia. Interestingly, we detected disease-associated microglia (DAM)-like microglia groups in the developing human spinal cord, which are predicted to be vulnerable to ALS and engaged in the TYROBP causal network and response to unfolded proteins. These findings provide spatiotemporal transcriptomic resources on the developing human spinal cord and potential strategies for spinal cord injury repair and ALS treatment.

Relationship Between CD8+ T Cells and Prognosis of Esophageal Cancer Patients: A Systematic Review and Meta-analysis.

Tumor infiltrating lymphocytes (TILs), especially CD8+ T cells, play an important role in the process of anti-tumor immune response and are significantly correlated with the prognosis of esophageal cancer (EC), but there are also inconsistent conclusions. This study aimed to comprehensively evaluate the relationship between invasive CD8+ T cells and the prognosis in patients with EC through meta-analysis, and to provide a basis for prognosis and immunotherapy for EC. Articles related to CD8+ T cells and EC prognosis in PubMed, Cochrane Library, Embase, and CNKI were searched. Cancer specific survival (CSS), overall survival (OS) and disease-free survival (DFS) served as endpoint events. Besides, Stata15.0 was adopted for meta-analysis, and hazard ratio (HR) and 95% confidence interval (95%CI) for calculation of combined effect sizes. Total 547 articles were retrieved and 27 articles were finally enrolled, including 3988 cases of EC patients. Meta-analysis showed that high CD8 expression levels in tumor tissues, especially those in cancer nests, were associated with longer OS (HR = 0.74, 95% CI 0.67-0.81) and DFS (HR = 0.90, 95% CI 0.85-0.95) in EC patients (P < 0.05). CD8+ T cells play an important role in the prognosis of EC patients and are indispensable components for the immune score of EC.

Optimizing the development of contaminated land in China: Exploring machine-learning to identify risk markers.

Often available for use, previously developed land, which includes residential and commercial/industrial areas, presents a significant challenge due to the risk to human health. China's 2018 release of health risk assessment standards for land reuse aimed to bridge this gap in soil quality standards. Despite this, the absence of representative indicators strains risk managers economically and operationally. We improved China's land redevelopment approach by leveraging a dataset of 297,275 soil samples from 352 contaminated sites, employing machine learning. Our method incorporating soil quality standards from seven countries to discern patterns for establishing a cost-effective evaluative framework. Our research findings demonstrated that detection costs could be curtailed by 60% while maintaining consistency with international soil standards (prediction accuracy = 90-98%). Our findings deepen insights into soil pollution, proposing a more efficient risk assessment system for land redevelopment, addressing the current dearth of expertise in evaluating land development in China.

The chromatin remodeller MdRAD5B enhances drought tolerance by coupling MdLHP1-mediated H3K27me3 in apple.

RAD5B belongs to the Rad5/16-like group of the SNF2 family, which often functions in chromatin remodelling. However, whether RAD5B is involved in chromatin remodelling, histone modification, and drought stress tolerance is largely unclear. We identified a drought-inducible chromatin remodeler, MdRAD5B, which positively regulates apple drought tolerance. Transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) analysis showed that MdRAD5B affects the expression of 466 drought-responsive genes through its chromatin remodelling function in response to drought stress. In addition, MdRAD5B interacts with and degrades MdLHP1, a crucial regulator of histone H3 trimethylation at K27 (H3K27me3), through the ubiquitin-independent 20S proteasome. Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis revealed that MdRAD5B modulates the H3K27me3 deposition of 615 genes in response to drought stress. Genetic interaction analysis showed that MdRAD5B mediates the H3K27me3 deposition of drought-responsive genes through MdLHP1, which causes their expression changes under drought stress. Our results unravelled a dual function of MdRAD5B in gene expression modulation in apple in response to drought, that is, via the regulation of chromatin remodelling and H3K27me3.

Casticin induces apoptosis and cytoprotective autophagy while inhibiting stemness involving Akt/mTOR and JAK2/STAT3 pathways in glioblastoma.

Glioblastoma (GBM) is the most common malignant glioma. However, the current systemic drugs cannot completely cure GBM. Casticin is a methoxylated flavonol compound isolated from a traditional Chinese medicine Vitex rotundifolia L.f. and exhibits a strong antitumor activity in multiple human malignancies. This study was aimed to explore the effects and underlying mechanisms of casticin in GBM. The MTT assay and colony formation was used to evaluate the casticin-induced cell viability in GBM cells. Apoptosis was assessed by ANNEXIV/PI staining assay. Autophagy was analyzed by transmission electron microscopy and immunofluorescence assays. GBM stem cell (GSC) was analyzed by tumor-sphere formation assay and ALDEFLUOR assay. The anti-GBM effect of casticin was also determined by the U87MG xenograft model. Casticin inhibited tumor cell growth in vitro and in vivo, as well as significantly induced apoptosis and autophagy. Autophagy inhibition augmented casticin-induced apoptosis. Casticin also reduced the GSC population by suppressing Oct4, Nanog, and Sox2. Mechanistically, casticin inhibited Akt/mTOR and JAK2/STAT3 signal pathways. The antitumor effect of casticin in GBM was demonstrated by inducing apoptosis, autophagy, and reducing population of GSCs; thus, it may be a potential GBM therapeutic agent for future clinical usage.

Co-drivers of Air Pollutant and CO2 Emissions from On-Road Transportation in China 2010-2020.

Co-controlling the emissions of air pollutants and CO2 from automobiles is crucial for addressing the intertwined challenges of air pollution and climate change in China. Here, we analyze the synergetic characteristics of air pollutant and CO2 emissions from China's on-road transportation and identify the co-drivers influencing these trends. Using detailed emission inventories and employing index decomposition analysis, we found that despite notable progress in pollution control, minimizing on-road CO2 emissions remains a formidable task. Over 2010-2020, the estimated sectoral emissions of VOCs, NOx, PM2.5, and CO declined by 49.9%, 25.9%, 75.2%, and 63.5%, respectively, while CO2 emissions increased by 46.1%. Light-duty passenger vehicles and heavy-duty trucks have been identified as the primary contributors to carbon-pollution co-emissions, highlighting the need for tailored policies. The driver analysis indicates that socioeconomic changes are primary drivers of emission growth, while policy controls, particularly advances in emission efficiency, can facilitate co-reductions. Regional disparities emphasize the need for policy refinement, including reducing dependency on fuel vehicles in the passenger subsector and prioritizing co-reduction strategies in high-emission provinces in the freight subsector. Overall, our study confirms the effectiveness of China's on-road control policies and provides valuable insights for future policy makers in China and other similarly positioned developing countries.

On the Chemistry of Aqueous Ammonium Acetate Droplets during Native Electrospray Ionization Mass Spectrometry.

Ammonium acetate (NH4Ac) is a widely used solvent additive in native electrospray ionization (ESI) mass spectrometry. NH4Ac can undergo proton transfer to form ammonia and acetic acid (NH4+ + Ac- → NH3 + HAc). The volatility of these products ensures that electrosprayed ions are free of undesired adducts. NH4Ac dissolution in water yields pH 7, providing "physiological" conditions. However, NH4Ac is not a buffer at pH 7 because NH4+ and Ac- are not a conjugate acid/base pair (Konermann, L. J. Am. Soc. Mass Spectrom. 2017, 28, 1827-1835.). In native ESI, it is desirable that analytes experience physiological conditions not only in bulk solution but also while they reside in ESI droplets. Little is known about the internal milieu of NH4Ac-containing ESI droplets. The current work explored the acid/base chemistry of such droplets, starting from a pH 7 analyte solution. We used a two-pronged approach involving evaporation experiments on bulk solutions under ESI-mimicking conditions, as well as molecular dynamics simulations using a newly developed algorithm that allows for proton transfer. Our results reveal that during droplet formation at the tip of the Taylor cone, electrolytically generated protons get neutralized by Ac-, making NH4+ the net charge carriers in the weakly acidic nascent droplets. During the subsequent evaporation, the droplets lose water as well as NH3 and HAc that were generated by proton transfer. NH3 departs more quickly because of its greater volatility, causing the accumulation of HAc. Together with residual Ac-, these HAc molecules form an acetate buffer that stabilizes the average droplet pH at 5.4 ± 0.1, as governed by the Henderson-Hasselbalch equation. The remarkable success of native ESI investigations in the literature implies that this pH drop by ∼1.6 units relative to the initially neutral analyte solution can be tolerated by most biomolecular analytes on the short time scale of the ESI process.

Interfering small ubiquitin modifiers (SUMO) improves the thermotolerance of apple by facilitating the activity of MdDREB2A.

Heat stress, which is caused by global warming, threatens crops yield and quality across the world. As a kind of post-translation modification, SUMOylation involves in plants heat stress response with a rapid and wide pattern. Here, we identified small ubiquitin modifiers (SUMO), which affect drought tolerance in apple, also participated in thermotolerance. Six isoforms of SUMOs located on six chromosomes in apple genome, and all the SUMOs were up-regulated in response to heat stress condition. The MdSUMO2 RNAi transgenic apple plants exhibited higher survival rate, lower ion leakage, higher catalase (CAT) activity, and Malondialdehyde (MDA) content under heat stress. MdDREB2A, the substrate of MdSUMO2 in apple, was accumulated in MdSUMO2 RNAi transgenic plants than the wild type GL-3 at the protein level in response to heat stress treatment. Further, the inhibited SUMOylation level of MdDREB2A in MdSUMO2 RNAi plants might repress its ubiquitination, too. The accumulated MdDREB2A in MdSUMO2 RNAi plants further induced heat-responsive genes expression to strengthen plants thermotolerance, including MdHSFA3, MdHSP26.5, MdHSP18.2, MdHSP70, MdCYP18-1 and MdTLP1. In summary, these findings illustrate that interfering small ubiquitin modifiers (SUMO) in apple improves plants thermotolerance, partly by facilitating the stability and activity of MdDREB2A.

Achromatopsia Showing Compound Heterozygous Mutations in ATF6 by Whole Exome Sequencing: A Rare Case Report.

Achromatopsia, inherited in an autosomal recessive manner, is a rare condition featured by dysfunction of cone photoreceptors responsible for high-acuity vision in daylight. To date, its pathogenesis and genetic mechanism are still not well defined due to the rarity of cases. In this study, the authors describe a patient with achromatopsia who was diagnosed based on the combination of whole exome sequencing, ocular examination, fundus photography, and fundus fluorescein angiography. A 1-year-old girl presented due to absence of the foveal reflex, severe photophobia, and pigment mottling. Fundus photography and fundus fluorescein angiography were performed on admission. Blood samples were extracted from the proband and her parents. Whole exome sequencing detected two ATF6 variants (c.533C>A and c.82+1G>T), which were confirmed through Sanger sequencing. According to the American College of Medical Genetics guidelines, both c.533C>A and c.82+1G>T variants in ATF6 were predicted as pathogenic mutations (PVS1, PM2, PM3). The patient was diagnosed as having achromatopsia with pathogenicity of ATF6 variants (c.533C>A and c.82+1G>T). [J Pediatr Ophthalmol Strabismus. 2023;60(5):e65-e69.].

Identification and verification of aging-related lncRNAs for prognosis prediction and immune microenvironment in patients with head and neck squamous carcinoma.

Aging is highly associated with tumor formation and progression. However, little research has explored the association of aging-related lncRNAs (ARLs) with the prognosis and tumor immune microenvironment (TIME) of head and neck squamous cell carcinoma (HNSCC). RNA sequences and clinicopathological data of HNSCC patients and normal subjects were downloaded from The Cancer Genome Atlas. In the training group, we used Pearson correlation, univariate Cox regression, least absolute shrinkage/selection operator regression analyses, and multivariate Cox regression to build a prognostic model. In the test group, we evaluated the model. Multivariate Cox regression was done to screen out independent prognostic factors, with which we constructed a nomogram. Afterward, we demonstrated the predictive value of the risk scores based on the model and the nomogram using time-dependent receiver operating characteristics. Gene set enrichment analysis, immune correlation analysis, and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno- and chemo-therapeutic responses. The most important LINC00861 in the model was examined in HNE1, CNE1, and CNE2 nasopharyngeal carcinoma cell lines and transfected into the cell lines CNE1 and CNE2 using the LINC00861-pcDNA3.1 construct plasmid. In addition, CCK-8, Edu, and SA-ß-gal staining assays were conducted to test the biofunction of LINC00861 in the CNE1 and CNE2 cells. The signature based on nine ARLs has a good predictive value in survival time, immune infiltration, immune checkpoint expression, and sensitivity to multiple drugs. LINC00861 expression in CNE2 was significantly lower than in the HNE1 and CNE1 cells, and LINC00861 overexpression significantly inhibited the proliferation and increased the senescence of nasopharyngeal carcinoma cell lines. This work built and verified a new prognostic model for HNSCC based on ARLs and mapped the immune landscape in HNSCC. LINC00861 is a protective factor for the development of HNSCC.

The single-cell and spatial transcriptional landscape of human gastrulation and early brain development.

The emergence of the three germ layers and the lineage-specific precursor cells orchestrating organogenesis represent fundamental milestones during early embryonic development. We analyzed the transcriptional profiles of over 400,000 cells from 14 human samples collected from post-conceptional weeks (PCW) 3 to 12 to delineate the dynamic molecular and cellular landscape of early gastrulation and nervous system development. We described the diversification of cell types, the spatial patterning of neural tube cells, and the signaling pathways likely involved in transforming epiblast cells into neuroepithelial cells and then into radial glia. We resolved 24 clusters of radial glial cells along the neural tube and outlined differentiation trajectories for the main classes of neurons. Lastly, we identified conserved and distinctive features across species by comparing early embryonic single-cell transcriptomic profiles between humans and mice. This comprehensive atlas sheds light on the molecular mechanisms underlying gastrulation and early human brain development.

Health impacts under different ozone mitigation pathways in Beijing-Tianjin-Hebei and its surroundings.

To evaluate the effects of the various ozone (O3) control approaches on environmental health and health inequalities, 121 reduction scenarios for nitrogen oxides (NOx) and volatile organic compounds (VOCs) were developed, and their environmental health impacts were calculated. With the target of achieving the 90th percentile of the daily maximum 8 h mean O3 concentration (MDA8-90th) of 160 µg/m3 in Beijing-Tianjin-Hebei and its surroundings ("2 + 26" cities), three typical scenarios namely, High-NOx reduction ratio (HN, NOx/VOCs = 6:1), High-VOCs reduction ratio (HV, NOx/VOCs = 3:7), and Balanced reduction ratio (Balanced, NOx/VOCs = 1:1) were investigated. The results show that O3 formation is currently NOx-limited at the regional scale, while some developed cities are VOC-limited, indicating that NOx mitigation should be the core for achieving the targeted concentration (160 µg/m3) at the regional scale, whereas cities such as Beijing in the short term should focus on VOCs mitigation. The population-weighted O3 concentrations in the HN, Balanced, and HV scenarios were 159.19, 159.19, and 158.44 µg/m3, respectively. In addition, the O3-related premature mortality was 41,320 in "2 + 26" cities; control measures under HN, Balanced, and HV could potentially decrease O3-related premature deaths by 59.94 %, 60.25 %, and 71.48 %, respectively. The HV scenario has been found to be more advantageous in lowering the O3-related environmental health impacts than the HN and Balanced scenarios. It was further found that premature deaths avoided by the HN scenario were mainly concentrated in economically unadvanced regions, whereas those prevented by the HV scenario were mainly concentrated in developed cities. This may lead to geographical inequities in environmental health. As ozone pollution in large cities with high population density is primarily VOC-limited, decrease in VOCs should be focused on in the short term to avoid more O3-related premature deaths, whereas NOx control may be more important in decreasing ozone concentrations and ozone-related mortality in the future.

Ferrodifferentiation regulates neurodevelopment via ROS generation.

Iron is important for life, and iron deficiency impairs development, but whether the iron level regulates neural differentiation remains elusive. In this study, with iron-regulatory proteins (IRPs) knockout embryonic stem cells (ESCs) that showed severe iron deficiency, we found that the Pax6- and Sox2-positive neuronal precursor cells and Tuj1 fibers in IRP1-/-IRP2-/- ESCs were significantly decreased after inducing neural differentiation. Consistently, in vivo study showed that the knockdown of IRP1 in IRP2-/- fetal mice remarkably affected the differentiation of neuronal precursors and the migration of neurons. These findings suggest that low intracellular iron status significantly inhibits neurodifferentiation. When supplementing IRP1-/-IRP2-/- ESCs with iron, these ESCs could differentiate normally. Further investigations revealed that the underlying mechanism was associated with an increase in reactive oxygen species (ROS) production caused by the substantially low level of iron and the down-regulation of iron-sulfur cluster protein ISCU, which, in turn, affected the proliferation and differentiation of stem cells. Thus, the appropriate amount of iron is crucial for maintaining normal neural differentiation that is termed ferrodifferentiation.

Microplastic Removal from Drinking Water Using Point-of-Use Devices.

The occurrence of microplastics in drinking water has drawn increasing attention due to their ubiquity and unresolved implications regarding human health. Despite achieving high reduction efficiencies (70 to >90%) at conventional drinking water treatment plants (DWTPs), microplastics remain. Since human consumption represents a small portion of typical household water use, point-of-use (POU) water treatment devices may provide the additional removal of microplastics (MPs) prior to consumption. The primary objective of this study was to evaluate the performance of commonly used pour-through POU devices, including those that utilize combinations of granular activated carbon (GAC), ion exchange (IX), and microfiltration (MF), with respect to MP removal. Treated drinking water was spiked with polyethylene terephthalate (PET) and polyvinyl chloride (PVC) fragments, along with nylon fibers representing a range of particle sizes (30-1000 µm) at concentrations of 36-64 particles/L. Samples were collected from each POU device following 25, 50, 75, 100 and 125% increases in the manufacturer's rated treatment capacity, and subsequently analyzed via microscopy to determine their removal efficiency. Two POU devices that incorporate MF technologies exhibited 78-86% and 94-100% removal values for PVC and PET fragments, respectively, whereas one device that only incorporates GAC and IX resulted in a greater number of particles in its effluent when compared to the influent. When comparing the two devices that incorporate membranes, the device with the smaller nominal pore size (0.2 µm vs. ≥1 µm) exhibited the best performance. These findings suggest that POU devices that incorporate physical treatment barriers, including membrane filtration, may be optimal for MP removal (if desired) from drinking water.

The temporal and spatial signature of microglial transcriptome in neuropathic pain.

Microglial activation following peripheral nerve injury is crucial for neuropathic pain (NP) development; however, studies on time-specific and spatial characteristics of microglial transcriptome are scarce. Firstly, we comparatively analysed microglial transcriptome of different brain regions and multiple timepoints after nerve injury by analysing the gene expression profile of GSE180627 and GSE117320. Then, we performed a mechanical pain hypersensitivity test on 12 rat neuropathic pain models using von Frey fibres at various timepoints after nerve injury. To further explore the key gene clusters closely related to the neuropathic pain phenotype, we conducted a weighted gene co-expression network analysis (WGCNA) on the GSE60670 gene expression profile. Lastly, we performed a single-cell sequencing analysis on GSE162807 for identifying microglia subpopulations. We found that the trend of microglia's transcriptome changes after nerve injury was that mRNA expression changes mainly occur early after injury, which is also consistent with phenotypic changes (NP progression). We also revealed that in addition to spatial specificity, microglia are also temporally specific in NP progression following nerve injury. The WGCNA findings revealed that the functional analysis of the key module genes emphasized the endoplasmic reticulum's (ER's) crucial role in NP. In our single-cell sequencing analysis, microglia were clustered into 18 cell subsets, of which we identified specific subsets of two timepoints (D3/D7) post-injury. Our study further revealed the temporal and spatial gene expression specificity of microglia in neuropathic pain. These results contribute to our comprehensive understanding of the pathogenic mechanism of microglia in neuropathic pain.

Worldwide research trends on femur head necrosis (2000-2021): a bibliometrics analysis and suggestions for researchers.

Background: Osteonecrosis of the femoral head (ONFH) is a common and stubborn disease. The main causes are venous stasis of the femoral head, arterial blood supply damage, bone cell and bone marrow death, and bone tissue necrosis and subsequent repair obstacles. Over the past 22 years, the number of papers on ONFH has, overall, continued to increase. Methods: Using bibliometrics, we investigated the trends, frontiers, and hotspots of global scientific output in the past 22 years. We searched Science Citation Index Expanded (SCIE) of the Web of Science Core Collection (WoSCC) and retrieved information associated with papers and records published between 2000 and 2021. We used VOSviewer and CiteSpace to conduct bibliometric analysis and visual analysis on the overall distribution of annual output, major countries, active institutions, journals, authors, commonly cited literature, and keywords. The impact and quality of the papers were assessed using the global citation score (GCS). Results: We retrieved a total of 2006 articles and reviews. Over the past 22 years, the number of publications (NP) increased. China ranked first in terms of NP, while the United States had the highest h-index and the highest number of citations (NC). Shanghai Jiao Tong University and International Orthopaedics were the institution and periodical, respectively. The paper written by Mont et al. in 2006 had the highest total GCS score, at 379. The top three keywords were "ischemic necrosis", "osteonecrosis", and "hip joint". Although there was a fluctuation in publications associated with ONFH, overall, the NP increased. China was the most prolific in this area, while the United States was the most influential country. The top 3 authors in terms of NP were Zhang, Motomura, and Zhao. Areas of focus in ONFH over recent years include signal pathway, genetic differentiation, glucocorticoid-induced osteogenesis, induced ischemic necrosis and osteogenesis. Conclusions: Our bibliometrics analysis revealed the research hotspots and rapid development trends of ONFH research in the past 22 years. The most critical indicators [researchers, countries, research institutions, and journals publishing osteonecrosis of the femoral head (ONFH) research] relevant to the research hotspots in the field of ONFH research were analyzed.