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Abstract IDH1 and IDH2 mutational status is a critical biomarker with diagnostic, prognostic, and treatment implications in glioma. Although IDH1 p.R132H-specific immunohistochemistry is available, it is unable to identify other mutations in IDH1/2. Next-generation sequencing can accurately determine IDH1/2 mutational status but suffers from long turnaround time when urgent treatment planning and initiation is medically necessary. The Idylla assay can detect IDH1/2 mutational status from unstained formalin-fixed paraffin-embedded (FFPE) slides in as little as a few hours. In a clinical validation, we demonstrate clinical accuracy of 97% compared to next-generation sequencing. Sensitivity studies demonstrated a limit of detection of 2.5-5% variant allele frequency, even at DNA inputs below the manufacturer’s recommended threshold. Overall, the assay is an effective and accurate method for rapid determination of IDH1/2 mutational status.

In order to explore the antioxidant ability of different solvent extracts of Ge-riched Auricularia auricular mycelium in vitro, the Ge-riched A. auricular mycelium was extracted by water, 70% ethanol and ethyl acetate. The scavenging ability of different extracts on superoxide anion free radical, hydroxyl free radical and DPPH free radical were compared. The comprehensive antioxidant capacity of different solvent extracts was evaluated by subordinate function value, and the correlation between substance content and antioxidant capacity were analyzed. The results showed that the content of organic Ge in Ge-riched A. auricular mycelium was 542.83 μg/g. The extraction rate and substance content of different solvent extracts were different, the extraction rate of water extract and ethanol extract was higher, the polysaccharide content of water extract was the highest, and the polyphenol and flavonoid content of ethyl acetate extract was the highest. Different solvent extracts had certain scavenging ability on free radicals，and the extract concentration increased with the increase. Water extract had the strongest scavenging rate of superoxide anion free radical，when the extract concentration was 9 mg/mL, the highest clearance rate was 43.32%. 70% ethanol extract had the best scavenging effect on hydroxyl free radical and DPPH free radical. When the extract concentration was 9 mg/mL, the scavenging rate was 70.10% and 76.99%, respectively. Polysaccharides, polyphenols and flavonoids all played different roles in scavenging free radicals, and ethanol extract had the strongest comprehensive antioxidant capacity. The contents of polysaccharides, polyphenols and flavonoids were significant (P

Carbon black nanoparticles (CBNPs) have been demonstrated to induce DNA damage in epithelial cells. However, the potential of the damage to initiate carcinogenesis and the underlying mechanism remain poorly understood. Therefore, we constructed an in vitro model of malignant transformation of human bronchial epithelial cells (16HBE-T) by treating 40 μg/mL CBNPs for 120 passages. We observed tumor-like transformation and sustained DNA damage. Using transcriptome sequencing and RIP-seq, we identified the overexpression of the critical DNA mismatch repair genes MutS homolog 2 (MSH2) and its related circular RNA, circ_0025373, in the 16HBE-T cells. Mechanistically, circ_0025373 was found to inhibit DNA damage by binding to MSH2, thereby modifying its expression and influencing its nuclear and cytoplasmic distribution, which lead to inhibition of CBNP-induced malignant transformation of human bronchial epithelial cells. Our findings provide novel evidence on the carcinogenicity of CBNPs, and offer biological insights into the potential epigenetic regulation and potential therapeutic targets for lung carcinogenesis.

Recycled aggregate concrete has received much attention in recent years. Using tailings sand in concrete can save natural resources and create environmentally friendly building materials. Simultaneously, adding iron tailings can compensate for the loss of strength caused by recycled aggregates and enhance performance. The mechanical properties of recycled aggregate concrete with iron tailings and prepared concrete specimens with iron tailings sand content of 0%, 25%, 50%, 75%, and 100% were studied. Mechanical tests are conducted to evaluate the performance with the assistance of PVA fibers. The patterns of change in numerical values such as compressive strength, flexural strength, and peak strain of recycled concrete specimens are tested and analyzed, and the experiment's effectiveness is demonstrated through finite element numerical simulation. The results show that when the TRAC content is 50%, the working performance of recycled concrete reaches its peak; When the TRAC content exceeds 50%, the positive effect of tailings sand on the performance of concrete decreases; The strength of TRAC concrete increases with the increase of PVA fiber content; Improving the replacement rate of recycled iron tailings aggregate can increase the peak strain of the specimen under cyclic loading, and the stress-strain curve calculated by finite element software is consistent with the experimental results.

Abstract This study investigated the effect of replacing a portion of fish meal with unfermented and/or fermented soybean meal in juvenile coho salmon (Oncorhynchus kisutch). Four groups of juveniles (initial weight 110.31 ± 3.12 g) in triplicate were fed for 90 days on four different iso‐nitrogen and iso‐lipid diets. The G0 diet comprised 28% fish meal protein (control group). In the other three diets (G1, G2, and G3), 10% of the fish meal protein was replaced with unfermented and/or fermented soybean meal protein. The main results were: Compared with G0, the WGR, SGR, CF; the contents of GLU, TP, ALB, T‐CHO, and T‐AOC, the activities of AKP, CAT, SOD, GST, GSH‐PX, O2·‐CR, OH·‐CR, and GSH and the expressions of SOD, GSH‐PX, GST, CAT, and Nrf2 genes of juvenile coho salmon in G3 were significantly (p 0.05) of diet on their survival rate (SR). In conclusion, the fermented soybean meal in the juvenile coho salmon diet can replace 10% of the fish meal protein.

Goupi plaster, a representative preparation of black plaster, has demonstrated promising effects in treating knee osteoarthritis. However, high temperature used in traditional frying extraction may cause decomposition of its effective components, thus limiting the efficacy. This study aimed to explore the scientific nature of the traditional preparation technology of Goupi plaster, and to compare the effects of different extraction methods on the types of chemical components and the content of index components. The UPLC-Q-Exactive-MS and UPLC-MS/MS technologies which have high efficiency, sensitivity and accuracy, were used to qualitatively and quantitatively analyze the chemical components of Goupi plaster under different preparation processes. The results show that the extraction solvent approach is different from the traditional frying extraction method, and has a positive effect. However, the mechanism of action of Goupi plaster is complex and its pharmacological effects are diverse. Future studies should explore whether it necessary to change the frying extraction method. This experiment provides a theoretical basis that will guide further scientific discussion and research into the frying extraction of Goupi plaster.

Poly(ADP-ribosyl)ation (PARylation), catalyzed by poly(ADP-ribose) polymerases (PARPs) and hydrolyzed by poly(ADP-ribose) glycohydrolase (PARG), is a kind of post-translational protein modification that is involved in various cellular processes in fungi, plants, and mammals. However, the function of PARPs in plant pathogenic fungi remains unknown. The present study investigated the roles and mechanisms of FonPARP1 in watermelon Fusarium wilt fungus Fusarium oxysporum f. sp. niveum (Fon). Fon has a single PARP FonPARP1 and one PARG FonPARG1. FonPARP1 is an active PARP and contributes to Fon pathogenicity through regulating its invasive growth within watermelon plants, while FonPARG1 is not required for Fon pathogenicity. A serine/threonine protein kinase, FonKin4, was identified as a FonPARP1-interacting partner by LC–MS/MS. FonKin4 is required for vegetative growth, conidiation, macroconidia morphology, abiotic stress response and pathogenicity of Fon. The S_TKc domain is sufficient for both enzyme activity and pathogenicity function of FonKin4 in Fon. FonKin4 phosphorylates FonPARP1 in vitro to enhance its poly(ADP-ribose) polymerase activity; however, FonPARP1 does not PARylate FonKin4. These results establish the FonKin4-FonPARP1 phosphorylation cascade that positively contributes to Fon pathogenicity. The present study highlights the importance of PARP-catalyzed protein PARylation in regulating the pathogenicity of Fon and other plant pathogenic fungi.

Sweet-waxy maize is a new type of fresh maize pioneered in China. It combines the advantages of sweet maize and waxy maize. The sweet and waxy grains arranged randomly on one ear, therefore the taste is both sweet and waxy. In recent years, sweet-waxy maize has been hotly sought after by the market and has become the trend and focus of the development of fresh maize. Chinese breeders created sweet and waxy double (multiple) recessive inbred lines by polymerizing key sweet and waxy genes in the starch synthesis pathway of maize endosperm, and then crossed with waxy maize inbred lines or for hybridized combination with each other. The recessive genes were separated in the hybrid offspring so that sweet and waxy grains appeared on the same ear at the same time. The breeding of sweet-waxy maize has developed rapidly. At present, a breeding system of sweet and waxy maize combining traditional breeding methods (sweet and waxy maize hybrid combination method and sweet and waxy maize bicyclic breeding method) + modern breeding methods (molecular marker-assisted selection technology and haploid breeding technology) has been established, and the bred varieties are developing towards a diversified, high-quality, featured and functional direction. Sweet-waxy maize has high value-added, short production cycle, and can be flexibly matched with aspects of stubble, therefore, its market demand and planting area are increasing year by year. However, due to the limited genetic background of germplasm resources, high cost of inbred lines reproduction and seed production, imperfect quality evaluation system, and the urgent need for innovation in fresh-keeping and processing technology, the challenges it faces are becoming more prominent, hindering the future development of the sweet-waxy maize industry. In the study, the theoretical basis of sweet-waxy maize breeding, breeding development history, variety certification, planting distribution, planting mode and market overview were discussed, the core bottlenecks and constraints were discussed, and corresponding countermeasures were put forward, with an aims to provide theoretical basis for breeding research and industrial development of sweet-waxy maize.

Abstract Genomic profiling of hematologic malignancies has augmented our understanding of variants that contribute to disease pathogenesis and supported development of prognostic models that inform disease management in the clinic. Tumor only sequencing assays are limited in their ability to identify definitive somatic variants, which can lead to ambiguity in clinical reporting and patient management. Here, we describe the MSK-IMPACT Heme cohort, a comprehensive data set of somatic alterations from paired tumor and normal DNA using a hybridization capture-based next generation sequencing platform. We highlight patterns of mutations, copy number alterations, and mutation signatures in a broad set of myeloid and lymphoid neoplasms. We also demonstrate the power of appropriate matching to make definitive somatic calls, including in patients who have undergone allogeneic stem cell transplant. We expect that this resource will further spur research into the pathobiology and clinical utility of clinical sequencing for patients with hematologic neoplasms.

In recent years, wind energy has begun to receive a significant amount of attention as clean energy is utilised and demanded in large quantities, resulting in a sharp increase in the use of wind turbines. The demand for wind turbines has gradually risen due to the clean and recyclable nature of wind energy. The current blade life of wind turbines in China is about 20 years, which means that the disposal of obsolete used blades can become a difficult problem in the future. Therefore, this study is of great significance to explore the regeneration performance of the blades after recycling and disposal. In this paper, wind turbine blades were mechanically recycled into recycled macrofibres, which were added to concrete as a reinforcing material to make wind impeller fibre concrete (WIC), and the three proportion ratios of 1%, 1.5%, and 2% were explored to compare the performance. The performance of WIC was also evaluated and its performance was compared to that of glass fibre concrete (GC). In addition, the material physical properties of second-generation recycled aggregate concrete (RAC) based on WIC were explored. The strength and peak strain variations and their causal mechanisms were analysed both macroscopically and microscopically by means of the classical mechanical tests (compression and bending tests), SEM, and XRD. The results show that the compressive strength of WIC was negatively correlated with the fibre content and increased by 6.04–18.12% compared to that of ordinary concrete (OG), with a maximum of 19.25 MPa; the flexural strength was positively correlated with the fibre content, with an increase of 5.37–18.5%. The microstructural analysis confirmed the macroscopic results and the intrinsic model better validated the experimental results.

Nasal administration is a non-invasive method of drug delivery that offers several advantages, including rapid onset of action, ease of use, no first-pass effect, and fewer side effects. On this basis, nose-to-brain delivery technology offers a new method for drug delivery to the brain and central nervous system, which has attracted widespread attention. In this paper, the development status and trends of nasal drug delivery and nose-to-brain delivery technology are deeply analyzed through multiple dimensions: literature research, questionnaire surveys, and patent analysis. First, FDA-approved nasal formulations for nose-to-brain delivery were combed. Second, we collected a large amount of relevant information about nasal drug delivery through a questionnaire survey of 165 pharmaceutical industry practitioners in 28 provinces and 161 different organizations in China. Third, and most importantly, we conducted a patent analysis of approximately 700+ patents related to nose-to-brain delivery, both domestically and internationally. This analysis was conducted in terms of patent application trends, technology life cycle, technology composition, and technology evolution. The LDA topic model was employed to identify technological topics in each time window (1990–2023), and the five key major evolution paths were extracted. The research results in this paper will provide useful references for relevant researchers and enterprises in the pharmaceutical industry, promoting the further development and application of nasal drug delivery and nose-to-brain delivery technology.

Sphingolipids (SPLs) represent a highly diverse and structurally complex lipid class. The discussion of SPL metabolism-related issues is of importance in understanding the neuropathological progression of Alzheimer's disease (AD). AD is characterized by the accumulation of extracellular deposits of the amyloid β-peptide (Aβ) and intraneuronal aggregates of the microtubule-associated protein tau. Critical roles of Aβ oligomer deposited and ganglioside GM1 could be formed as “seed” from insoluble GAβ polymer in initiating the pathogenic process, while tau might also mediate SPLs and their toxicity. The interaction between ceramide and α-Synuclein (α-Syn) accelerates the aggregation of ferroptosis and exacerbates the pathogenesis of AD. For instance, reducing the levels of SPLs can mitigate α-Syn accumulation and inhibit AD progression. Meanwhile, loss of SPLs may inhibit the expression of APOE4 and confer protection against AD, while the loss of APOE4 expression also disrupts SPLs homeostasis. Moreover, the heightened activation of sphingomyelinase promotes the ferroptosis signaling pathway, leading to exacerbated AD symptoms. Ferroptosis plays a vital role in the pathological progression of AD by influencing Aβ, tau, APOE, and α-Syn. Conversely, the development of AD also exacerbates the manifestation of ferroptosis and SPLs. We are compiling the emerging techniques (Derivatization and IM-MS) of sphingolipidomics, to overcome the challenges of AD diagnosis and treatment. In this review, we examined the intricate neuro-mechanistic interactions between SPLs and Aβ, tau, α-Syn, APOE, and ferroptosis, mediating the onset of AD. Furthermore, our findings highlight the potential of targeting SPLs as underexplored avenue for devising innovative therapeutic strategies against AD.

Abstract Background Recent studies have demonstrated that glioma-associated mesenchymal stem cells (GA-MSCs) are implicated in the regulation of glioma malignant progression. However, the prognostic value of GA-MSCs has not been comprehensively explored in glioma. Methods We extracted GA-MSCs from glioma tissues, established intracranial xenograft models in nude mice, and obtained GA-MSC-related genes (GA-MSCRGs) by using microarrays. The transcriptome data and clinical information of glioma patients were obtained from the CGGA and TCGA databases. We screened 8 prognostic GA-MSCRGs to construct a prognostic index by using the multivariate Cox regression method. The validity of the GA-MSCRGPI was verified in the training (CGGA693) and validation (TCGA and CGGA325) cohorts. The expression patterns of these 8 GA-MSCRGs were validated in 78 glioma tissue specimens by using a qRT‒PCR assay. Results GA-MSCs were successfully isolated from glioma tissues. Based on intracranial xenograft models and transcriptome microarray screening, 8 genes (MCM7, CDK6, ORC1, CCL20, TNFRSF12A, POLA1, TRAF1 and TIAM1) were selected for the construction of a GA-MSC-related gene prognostic index (GA-MSCRGPI). In both the training and validation cohorts, high GA-MSCRGPI patients showed an inferior survival outcome compared with low GA-MSCRGPI patients. A nomogram was established based on independent prognostic indicators (age, WHO grade and GA-MSCRGPI) and exhibited a strong forecasting ability for overall survival (OS). Moreover, we found that the GA-MSCRGPI could evaluate the prognosis of glioma patients undergoing chemoradiotherapy. The high GA-MSCRGPI group exhibited higher immune, stromal and ESTIMATE scores; lower tumor purity; higher infiltration of Tregs and M2-type macrophages; fewer activated NK cells; and higher expression of immune checkpoints. Tumor Immune Dysfunction and Exclusion (TIDE) showed that the high GA-MSCRGPI group had more responders to ICI therapy. The results of the genetic mutation profile and tumor mutation burden (TMB) in different GA-MSCRGPI subgroups further supplement GA-MSCRGPI-related mechanisms. Finally, the expression patterns of 8 selected GA-MSCRGs in GA-MSCRGPI were correlated with glioma WHO grades to a certain extent. Conclusion The constructed GA-MSCRGPI could predict prognosis and guide individualized therapy in glioma patients.

Summary: Studies using stool samples suggest that non-sugar sweetener (NSS) consumption affects gut microbiome composition. However, stool does not represent the entire gut. We analyzed the duodenal luminal microbiome in subjects consuming non-aspartame non-sugar sweeteners (NANS, N = 35), aspartame only (ASP, N = 9), and controls (CON, N = 55) and the stool microbiome in a subset (N = 40). Duodenal alpha diversity was decreased in NANS vs. CON. Duodenal relative abundance (RA) of Escherichia, Klebsiella, and Salmonella (all phylum Proteobacteria) was lower in both NANS and ASP vs. CON, whereas stool RA of Escherichia, Klebsiella, and Salmonella was increased in both NANS and ASP vs. CON. Predicted duodenal microbial metabolic pathways altered in NANS vs. CON included polysaccharides biosynthesis and D-galactose degradation, whereas cylindrospermopsin biosynthesis was significantly enriched in ASP vs. CON. These findings suggest that consuming non-sugar sweeteners may significantly alter microbiome composition and function in the metabolically active small bowel, with different alterations seen in stool.

Intestinal mucositis (IM) is a common adverse effect of chemotherapy, limiting its clinical application. Codonopsis pilosula-derived CP-A (an inulin-type fructan) is an edible Chinese medicine with anti-inflammatory and gastrointestinal protective effects, which may be useful for treating IM. Here, we explored CP-A’s role in ameliorating IM induced by 5-fluorouracil (5-FU) and investigated the underlying mechanism using in vitro experiments and rat models. Western blotting, immunohistochemistry (IHC), and real-time PCR (RT-PCR) analyses were used to assess protein expression related to the extracellular-regulated protein kinases (ERK)/myosin light chain kinase (MLCK)/myosin light chain 2 (MLC2) signaling pathway and tight junction proteins. Inflammatory factors were quantified using enzyme-linked immunosorbent assays (ELISAs), and 16S rRNA amplicon sequencing was employed for cecum content analysis. The results indicated that CP-A restored body weight and food intake and reversed histopathological changes in IM rats. Further, abnormal MLCK activation induced by 5-FU was attenuated by CP-A via the ERK/MLCK/MLC2 pathway. CP-A treatment improved tight junction protein levels and reduced inflammatory factor expression. Moreover, CP-A intervention regulated the intestinal microbiota community structure, increasing the abundance of Lactobacillus and decreasing the abundance of Shigella. In conclusion, CP-A mitigates 5-FU-induced IM by inhibiting the ERK/MLCK/MLC2 pathway, reducing the expression of inflammatory factors, improving the intestinal mucosal barrier, and regulating the intestinal microbial community. This study highlights CP-A’s therapeutic potential in IM treatment and provides insights for future research.

Choroidal vascular diseases, such as age-related macular degeneration, are the leading cause of vision impairment and are characterized by pathological angiogenesis. Verteporfin-mediated photodynamic therapy is a current strategy that selectively occludes choroidal neovasculature. However, the clinically used large-dose systemic administration increases the risk of systemic adverse events, such as phototoxicity to superficial tissues. In this study, we developed an in situ verteporfin delivery system with a photoswitching synergistic function that disassembles in response to intraocular inflammatory enzymes. Under light-on conditions, verteporfin-mediated photodynamic therapy effectively occurs and this leads to vascular occlusion. Under light-off conditions, non-photoactive verteporfin negatively regulates vascular endothelial growth factor-induced angiogenesis as a yes-associated protein inhibitor. Taken together, our system serves as an intraocular verteporfin reservoir to improve the bioavailability of verteporfin by innovatively exploiting its photochemical and biological functions. This work provides a promising strategy with synergistic antiangiogenic effects for the treatment of choroidal vascular diseases.

ABSTRACT Fusarium oxysporum f. sp. niveum (Fon), a soilborne phytopathogenic fungus, causes watermelon Fusarium wilt, resulting in serious yield losses worldwide. However, the underlying molecular mechanism of Fon virulence is largely unknown. The present study investigated the biological functions of six FonPUFs, encoding RNA binding Pumilio proteins, and especially explored the molecular mechanism of FonPUF1 in Fon virulence. A series of phenotypic analyses indicated that FonPUFs have distinct but diverse functions in vegetative growth, asexual reproduction, macroconidia morphology, spore germination, cell wall, or abiotic stress response of Fon. Notably, the deletion of FonPUF1 attenuates Fon virulence by impairing the invasive growth and colonization ability inside the watermelon plants. FonPUF1 possesses RNA binding activity, and its biochemical activity and virulence function depend on the RNA recognition motif or Pumilio domains. FonPUF1 associates with the actin-related protein 2/3 (ARP2/3) complex by interacting with FonARC18, which is also required for Fon virulence and plays an important role in regulating mitochondrial functions, such as ATP generation and reactive oxygen species production. Transcriptomic profiling of ΔFonPUF1 identified a set of putative FonPUF1-dependent virulence-related genes in Fon, possessing a novel A-rich binding motif in the 3′ untranslated region (UTR), indicating that FonPUF1 participates in additional mechanisms critical for Fon virulence. These findings highlight the functions and molecular mechanism of FonPUFs in Fon virulence. IMPORTANCE Fusarium oxysporum is a devastating plant-pathogenic fungus that causes vascular wilt disease in many economically important crops, including watermelon, worldwide. F. oxysporum f. sp. nievum (Fon) causes serious yield loss in watermelon production. However, the molecular mechanism of Fusarium wilt development by Fon remains largely unknown. Here, we demonstrate that six putative Pumilio proteins-encoding genes (FonPUFs) differentially operate diverse basic biological processes, including stress response, and that FonPUF1 is required for Fon virulence. Notably, FonPUF1 possesses RNA binding activity and associates with the actin-related protein 2/3 complex to control mitochondrial functions. Furthermore, FonPUF1 coordinates the expression of a set of putative virulence-related genes in Fon by binding to a novel A-rich motif present in the 3′ UTR of a diverse set of target mRNAs. Our study disentangles the previously unexplored molecular mechanism involved in regulating Fon virulence, providing a possibility for the development of novel strategies for disease management.

Abstract Tobacco use is the leading preventable cause of cancer, and affects the respiratory, oral, fecal, and duodenal mucosa-associated microbiota. However, the effects of smoking on the duodenal luminal microbiome have not been studied directly. We aimed to compare the duodenal luminal microbiome in never-smokers, current smokers, and ex-smokers who quit ≥ 10 years ago. In a cross-sectional study, current smokers (CS, n = 24) were identified and matched to never-smokers (NS, n = 27) and ex-smokers (XS, n = 27) by age (± 5 years), body mass index (BMI, ± 3 kg/m2), and sex. Current antibiotic users were excluded. The duodenal luminal microbiome was analysed in 1 aspirate sample per subject by 16S rRNA gene sequencing. Relative abundances (RA) of families associated with increased duodenal microbial diversity, Prevotellaceae, Neisseriaceae, and Porphyromonadaceae, were significantly lower in CS vs. NS. This was driven by lower RA of unknown Prevotella and Porphyromonas species, and Neisseria subflava and N. cinerea, in CS. In contrast, RA of Enterobacteriaceae and Lactobacillaceae (associated with decreased diversity), were significantly higher in CS, due to higher RA of Escherichia-Shigella, Klebsiella and Lactobacillus species. Many of these changes were absent or less pronounced in XS, who exhibited a duodenal luminal microbiome more similar to NS. RA of taxa previously found to be increased in the oral and respiratory microbiota of smokers were also higher in the duodenal luminal microbiome, including Bulledia extructa and an unknown Filifactor species. In conclusion, smoking is associated with an altered duodenal luminal microbiome. However, ex-smokers have a duodenal luminal microbiome that is similar to never-smokers.

Malignant glioma is the most frequent primary tumor of the central nervous system. PDCL3 is a member of the phosducin-like protein family, and its imbalance has been shown to be associated with several human diseases. However, the underlying role of PDCL3 in human malignant cancers, especially in malignant gliomas, is unclear. In this study, we combined public database analysis and experimental verification to explore the differential expression, prognostic value and potential functions and mechanisms of PDCL3. The results revealed that PDCL3 is upregulated in multiple cancers and acts as a potential prognostic biomarker of glioma. Mechanistically, PDCL3 expression is associated with epigenetic modifications and genetic mutations. PDCL3 may directly interact with the chaperonin-containing TCP1 complex, regulating cell malignancy, cell communication and the extracellular matrix. More importantly, the association of PDCL3 with the infiltration of immune cells, immunomodulatory genes, immune checkpoints, cancer stemness and angiogenesis suggested that PDCL3 may regulate the glioma immune landscape. Furthermore, PDCL3 interference also decreased the proliferation, invasion and migration of glioma cells. In conclusion, PDCL3 is a novel oncogene and can be adopted as a biomarker with value in assisting clinical diagnosis, predicting patient outcomes and assessing the immune landscape of the tumor microenvironment in glioma.

ObjectiveMicroelectrode recording (MER) guided subthalamic nucleus deep brain stimulation (STN-DBS) under local anesthesia (LA) is widely applied in the management of advanced Parkinson's disease (PD). Whereas, awake DBS under LA is painful and burdensome for PD patients. We analyzed the influence of general anesthesia (GA) on intraoperative MER, to assess the feasibility and effectiveness of GA in MER guided STN-DBS.MethodsRetrospective analysis was performed on the PD patients, who underwent bilateral MER guided STN-DBS in Wuhan Union Hospital from July 2019 to December 2021. The patients were assigned to LA or GA group according to the anesthetic methods implemented. Multidimensional parameters, including MER signals, electrode implantation accuracy, clinical outcome and adverse events, were analyzed.ResultsA total of 40 PD patients were enrolled in this study, including 18 in LA group and 22 in GA group. There were no statistically significant differences in patient demographics and baseline characteristics between two groups. Although, the parameters of MER signal, including frequency, inter-spike interval (ISI) and amplitude, were obviously interfered under GA, the waveforms of MER signals were recognizable and shared similar characteristics with LA group. Both LA and GA could achieve effective electrode implantation accuracy and clinical outcome. They also shared similar adverse events postoperatively.ConclusionGA is viable and comparable to LA in MER guided STN-DBS for PD, regarding electrode implantation accuracy, clinical outcome and adverse events. Notably, GA is more friendly and acceptable to the patients who are incapable of enduring intraoperative MER under LA.

ABSTRACT Protein palmitoylation, one of posttranslational modifications, is catalyzed by a group of palmitoyl transferases (PATs) and plays critical roles in the regulation of protein functions. However, little is known about the function and mechanism of PATs in plant pathogenic fungi. The present study reports the function and molecular mechanism of FonPATs in Fusarium oxysporum f. sp. niveum (Fon), the causal agent of watermelon Fusarium wilt. The Fon genome contains six FonPAT genes with distinct functions in vegetative growth, conidiation and conidial morphology, and stress response. FonPAT1, FonPAT2, and FonPAT4 have PAT activity and are required for Fon virulence on watermelon mainly through regulating in planta fungal growth within host plants. Comparative proteomics analysis identified a set of proteins that were palmitoylated by FonPAT2, and some of them are previously reported pathogenicity-related proteins in fungi. The FonAP-2 complex core subunits FonAP-2α, FonAP-2β, and FonAP-2μ were palmitoylated by FonPAT2 in vivo. FonPAT2-catalyzed palmitoylation contributed to the stability and interaction ability of the core subunits to ensure the formation of the FonAP-2 complex, which is essential for vegetative growth, asexual reproduction, cell wall integrity, and virulence in Fon. These findings demonstrate that FonPAT1, FonPAT2, and FonPAT4 play important roles in Fon virulence and that FonPAT2-catalyzed palmitoylation of the FonAP-2 complex is critical to Fon virulence, providing novel insights into the importance of protein palmitoylation in the virulence of plant fungal pathogens. IMPORTANCE Fusarium oxysporum f. sp. niveum (Fon), the causal agent of watermelon Fusarium wilt, is one of the most serious threats for the sustainable development of the watermelon industry worldwide. However, little is known about the underlying molecular mechanism of pathogenicity in Fon. Here, we found that the palmitoyl transferase (FonPAT) genes play distinct and diverse roles in basic biological processes and stress response and demonstrated that FonPAT1, FonPAT2, and FonPAT4 have PAT activity and are required for virulence in Fon. We also found that FonPAT2 palmitoylates the core subunits of the FonAP-2 complex to maintain the stability and the formation of the FonAP-2 complex, which is essential for basic biological processes, stress response, and virulence in Fon. Our study provides new insights into the understanding of the molecular mechanism involved in Fon virulence and will be helpful in the development of novel strategies for disease management.

The Peiligang culture (ca. 9000–7000 cal. BP) represents the first Neolithic settlements in the middle Yellow River Valley, marking the beginning of millet and rice farming in the region. While previous studies have focused primarily on identifying cultivated cereals, less attention has been given to plant harvesting and processing practices or environmental conditions. To address this gap, we present new phytolith data from the Peiligang site (8000–7600 cal. BP) to make three key contributions. First, we show that the Peiligang people utilized two microhabitats: hillslopes for dryland millet cultivation and alluvial plain for wetland resources. Second, we combine our findings with other archaeological evidence to reconstruct the environmental conditions of the Peiligang site, suggesting that it was a water-rich habitat. Finally, by analyzing phytolith remains of plant processing waste in middens, we reconstruct how people harvested and processed millets and rice at the site. This study sheds light on the plant-based subsistence strategies employed by the Peiligang people and offers insights into the environmental factors that contributed to the development of early farming in the middle Yellow River Valley.

A correct preoperative diagnosis is essential for the treatment and prognosis of necrotic glioblastoma and brain abscess, but the differentiation between them remains challenging. We constructed a diagnostic prediction model with good performance and enhanced clinical applicability based on data from 86 patients with necrotic glioblastoma and 32 patients with brain abscess that were diagnosed between January 2012 and January 2020. The diagnostic values of three regions of interest based on contrast-enhanced T1 weighted images (including whole tumor, brain-tumor interface, and an amalgamation of both regions) were compared using Logistics Regression and Random Forest. Feature reduction based on the optimal regions of interest was performed using principal component analysis with varimax rotation. The performance of the classifiers was assessed by receiver operator curves. Finally, clinical predictors were utilized to detect the diagnostic power. The mean area under curve (AUC) values of the whole tumor model was significantly higher than other two models obtained from Brain-Tumor Interface (BTI) and combine regions both in training (AUC mean = 0.850) and test/validation set (AUC mean = 0.896) calculated by Logistics Regression and in the testing set (AUC mean = 0.876) calculated by Random Forest. Among these three diagnostic prediction models, the combined model provided superior discrimination performance and yielded an AUC of 0.993, 0.907, and 0.974 in training, testing, and combined datasets, respectively. Compared with the brain-tumor interface and the combined regions, features obtained from the whole tumor showed the best differential value. The radiomic features combined with the peritumoral edema/tumor volume ratio provided the prediction model with the greatest diagnostic performance.

Gummy stem blight (GSB), which is caused by three related species of Stagonosporopsis, is a worldwide devastating disease of cucurbit crops including watermelon. Previously S. cucurbitacearum was reported to be the major fungal cause of watermelon GSB in Southern China, where it causes a significant decrease in watermelon yield. Here, we present the draft whole genome sequence, gene prediction and annotation of S. cucurbitacearum strain DBTL4, isolated from diseased watermelon plants. To our knowledge, this is the first publicly available genome sequence of this species, and knowledge of this genome sequence will help further understand the pathogenic mechanism of S. cucurbitacearum to cucurbit plants.[Graphic: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Introduction Primary pontine haemorrhage (PPH) is the most devastating subtype of intracerebral haemorrhage and is associated with poor prognosis, especially for the severe patients. Although medical treatment (MT) is widely accepted, a large number of studies have shown surgical haematoma evacuation (HE) might dramatically reduce mortality and improve prognosis outcome in severe PPH (sPPH). However, evidence to clarify the safety of HE remains insufficient.Methods and analysis The Safety of surgical Treatment In severe primary Pontine haemorrhage Evacuation study is a multi-centre, randomised, controlled, open-label trial, conducted from January 2022 to November 2024 in 20 tertiary hospitals in China. A total of 64 patients with sPPH will be randomly assigned to MT or HE group. Eligible patients will receive the corresponding treatment according to the result of randomisation. The primary outcomes are related to the safety of surgery including rate of symptomatic rebleeding at 3 days and rate of mortality and intracranial infection at 30 days. The secondary outcomes are the neurological function indexes following up at 30 days, 90 days, 180 days and 365 days.Ethics and dissemination The clinical trial has been approved by the Biomedical Research Ethics Committee of West China Hospital of Sichuan University (unique identifiers: No. 2020-894). All results of the trial will be published in international peer-reviewed scientific journals and will be disseminated through scientific conferences. Academic dissertation will be published in a peer-reviewed journal.Trial registration numbers NCT04647162, ChiCTR2000039679.

BackgroundVogt-Koyanagi-Harada (VKH) disease is an autoimmune inflammatory disorder characterized by bilateral granulomatous uveitis. The objective of this study was to identify immune hub genes involved in the pathogenesis and progression of VKH disease.MethodsHigh throughput sequencing data were downloaded from the Gene Expression Omnibus (GEO) and an immune dataset was downloaded from ImmPort. Immune differentially expressed genes (DEGs) were obtained from their intersection in the GEO and ImmPort datasets. Immune hub genes for VKH disease were selected through differential expression analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO), protein-protein interaction (PPI) network, and clustering analyses. Confidence in the immune hub genes was subsequently validated using box plots and receiver operating characteristic (ROC) curves.ResultsA total of 254 DEGs were screened and after the intersection with ImmPort, 20 genes were obtained as immune DEGs. Functional enrichment analysis indicated that the key genes were mainly involved in several types of immune pathways (such as the lymphocyte mediated and leukocyte mediated immune responses, natural killer cell mediated cytotoxicity, and antigen binding) and immunodeficiency diseases. Following PPI network analysis, the top seven genes in cluster 1 were selected as potential immune hub genes in VKH. After evaluating the accuracy of the hub genes, one gene (GNLY) was excluded because its expression level was statistically similar in VKH patients and healthy controls. Finally, six immune hub genes, namely KLRC2, KLRC3 SH2D1B, GZMB, KIR2DL3, and KIR3DL2 were identified as playing important roles in the occurrence and development of VKH disease.ConclusionSix immune hub genes (KLRC2, KLRC3 SH2D1B, GZMB, KIR2DL3, and KIR3DL2) identified by our bioinformatics analyses may provide new diagnostic and therapeutic targets for VKH disease.

BackgroundManagement of menopausal dyslipidemia is the main measure to reduce the incidence of cardiovascular disease in postmenopausal women. Tonifying Kidney and Removing Dampness Formula (TKRDF) is a traditional Chinese medicine (TCM) formula that ameliorates dyslipidemia in postmenopausal women. This study applied network pharmacology, molecular docking, and in vitro and in vitro experiments to investigate the underlying mechanism of TKRDF against postmenopausal dyslipidemia.MethodsNetwork pharmacology research was first conducted, and the active compounds and targets of TKRDF, as well as the targets of postmenopausal dyslipidemia, were extracted from public databases. Protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to identify the potential targets and signaling pathways of TKRDF in postmenopausal dyslipidemia. Molecular docking was then performed to evaluate the combination of active compounds with principal targets. Finally, an ovariectomized rat model was used for the in vivo experiment and alpha mouse liver 12 (AML12) cells treated with palmitic acid were used for the in vitro experiments to provide further evidence for the research.ResultsBased on network pharmacology analysis, we obtained 78 active compounds from TKRDF that acted on 222 targets of postmenopausal dyslipidemia. The analysis results indicated that IL6, TNF, VEGFA, AKT1, MAPK3, MAPK1, PPARG and PIK3CA, etc., were the potentially key targets, and the PI3K/AKT signaling pathway was the possibly crucial pathway for TKRDF to treat postmenopausal dyslipidemia. Molecular docking suggested that the active compounds have good binding activity with the core targets. The in vivo and in vitro experiments demonstrated that TKRDF ameliorates postmenopausal dyslipidemia by regulating hormone levels, inhibiting inflammation, promoting angiogenesis and inhibiting lipid synthesis, which appear to be related to TKRDF’s regulation of the ERK1/2 and PI3K/AKT signaling pathways.ConclusionThis study clarified the active ingredients, potential targets, and molecular mechanisms of TKRDF for treating postmenopausal dyslipidemia. It also provided a feasible method to uncover the scientific basis and therapeutic mechanism for prescribing TCM in the treatment of diseases.

Cotton (Gossypium spp.) is one of the most important cash crops worldwide. At present, new cotton varieties are mainly produced through conventional cross breeding, which is limited by available germplasm. Although the genome of cotton has been fully sequenced, research on the function of specific genes lags behind due to the lack of sufficient genetic material. Therefore, it is very important to create a cotton mutant library to create new, higher-quality varieties and identify genes associated with the regulation of key traits. Traditional mutagenic strategies, such as physical, chemical, and site-directed mutagenesis, are relatively costly, inefficient, and difficult to perform. In this study, we used a radiation mutation method based on linear electron acceleration to mutate cotton variety ‘TM-1’, for which a whole-genome sequence has previously been performed, to create a high throughput cotton mutant library. Abundant phenotypic variation was observed in the progeny population for three consecutive generations, including cotton fiber color variation, plant dwarfing, significant improvement of yield traits, and increased sensitivity to Verticillium wilt. These results show that radiation mutagenesis is an effective and feasible method to create plant mutant libraries.

Retinal degeneration is a main class of ocular diseases. So far, retinal progenitor cell (RPC) transplantation has been the most potential therapy for it, in which promoting RPCs neuronal differentiation remains an unmet challenge. To address this issue, innovatively designed L/d-phenylalanine based chiral nanofibers (LPG and DPG) are employed and it finds that chirality of fibers can efficiently regulate RPCs differentiation. qPCR, western blot, and immunofluorescence analysis show that right-handed helical DPG nanofibers significantly promote RPCs neuronal differentiation, whereas left-handed LPG nanofibers decrease this effect. These effects are mainly ascribed to the stereoselective interaction between chiral helical nanofibers and retinol-binding protein 4 (RBP4, a key protein in the retinoic acid (RA) metabolic pathway). The findings of chirality-dependent neuronal differentiation provide new strategies for treatment of neurodegenerative diseases via optimizing differentiation of transplanted stem cells on chiral nanofibers.

ObjectiveThis study aims to evaluate the impact of the inferior petrosal veins (IPVs) on operational exploration and to analyze related anatomic features.MethodsA total of 317 patients were retrospectively studied. Surgical outcomes and postoperative complications were analyzed, and patients were divided into two groups according to whether the IPV was sacrificed or preserved. The diameter of the IPV was also recorded during operation. Furthermore, the position where the IPV drained into the jugular bulb was recorded in each patient, and the influence of different injection points on the operation was analyzed.ResultsIPVs were conclusively identified in 242/317 (76.3%) of patients, with 110/242 (45.5%) of patients categorized as “IPV sacrifice” versus 132/242 (54.5%) categorized as “IPV preservation.” IPV diameter was observed to be 1 mm in 39 cases (16.2%). The position of IPV drainage into the jugular bulb was at the level of the accessory nerve in 163 cases (67.3%), the level of the vagus nerve in 42 cases (17.4%), and the level of the glossopharyngeal nerve or above in 37 cases (15.3%). The diameters of IPV in the sacrifice group were mainly less than 1 mm (94.5% vs. 75%, P 1 mm.

ObjectiveTo explore the impact of the COVID-19 pandemic on hospital business and the contribution of Internet healthcare to hospital operations during the epidemic by analyzing the degree of impact on major business indicators.MethodsThe three-year period from 2019 to 2021 was compared and analyzed, and the main medical business indicators such as outpatient and emergency visits, inpatients, operations, patient improvement rate, cure rate and fatality rate in tertiary hospitals were compared and analyzed, and the impact of the epidemic on medical services and hospital operation was analyzed. degree and the impact of Internet medical development on medical service capacity.ResultsDuring the outbreak of COVID-19, the number of hospital outpatient and emergency visits, inpatients, and operations decreased significantly; after the normalization of the epidemic, the main medical business indicators such as outpatient and emergency visits, inpatients, and operations gradually returned to pre-epidemic levels; patient improvement rate, the cure rate and mortality rate and other indicators did not change significantly. During the epidemic period, the number of visits to the Internet outpatient clinic has increased significantly, which has significantly improved the hospital's medical service capacity.ConclusionWith the normalization of epidemic prevention and control, the main business indicators of Tianjin tertiary hospitals have gradually recovered. The operation of Internet medical care during the epidemic has changed the management and operation mode of the hospital to a certain extent, improved the main business indicators of the hospital, and eased the pressure on the hospital's economic operation.

Importance: The incidence of dyslipidemia increases after menopause. Menopause hormone therapy (MHT) is recommended for menopause related disease. However, it is benefit for lipid profiles is inconclusive.Objective: To conduct a systematic review and meta-analysis of randomized controlled trials to evaluate the effects of MHT on lipid profile in postmenopausal women.Evidence Review: Related articles were searched on PubMed/Medline, EMBASE, Web of Science, and Cochrane Library databases from inception to December 2020. Data extraction and quality evaluation were performed independently by two reviewers. The methodological quality was assessed using the “Cochrane Risk of Bias checklist”.Results: Seventy-three eligible studies were selected. The results showed that MHT significantly decreased the levels of TC (WMD: −0.43, 95% CI: −0.53 to −0.33), LDL-C (WMD: −0.47, 95% CI: −0.55 to −0.40) and LP (a) (WMD: −49.46, 95% CI: −64.27 to −34.64) compared with placebo or no treatment. Oral MHT led to a significantly higher TG compared with transdermal MHT (WMD: 0.12, 95% CI: 0.04–0.21). The benefits of low dose MHT on TG was also concluded when comparing with conventional-dose estrogen (WMD: −0.18, 95% CI: −0.32 to −0.03). The results also showed that conventional MHT significantly decreased LDL-C (WMD: −0.35, 95% CI: −0.50 to −0.19), but increase TG (WMD: 0.42, 95%CI: 0.18–0.65) compared with tibolone. When comparing with the different MHT regimens, estrogen (E) + progesterone (P) regimen significantly increased TC (WMD: 0.15, 95% CI: 0.09 to 0.20), LDL-C (WMD: 0.12, 95% CI: 0.07–0.17) and Lp(a) (WMD: 44.58, 95% CI:28.09–61.06) compared with estrogen alone.Conclusion and Relevance: MHT plays a positive role in lipid profile in postmenopausal women, meanwhile for women with hypertriglyceridemia, low doses or transdermal MHT or tibolone would be a safer choice. Moreover, E + P regimen might blunt the benefit of estrogen on the lipid profile.Clinical Trial Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018092924], identifier [No. CRD42018092924].

Induced pluripotent stem cells (iPSCs) have become the leading research object in the clinical application of restorative medicine. They are easily generated from diverse cell sources and functionally indistinguishable from embryonic stem cells without the accompanying ethical issues. To date, the use of iPSC-derived neural stem cells and their progeny in the treatment of neurodegenerative and injurious diseases has achieved good results, with great potential in cell drug development. However, because of some unique biological properties and differences from traditional drug production processes, cell drug research and development has many problems that can hinder clinical applications. Given this situation, the Chinese Association of Neurorestoratology (Preparatory) and China Committee of the International Association of Neurorestoratology have organized relevant professional experts to formulate the standard presented here. Overall, the aim was to promote the clinical application of neural stem cells (NSCs) and their further derived neural cells from iPSC sources and promote cell drugs’ production and development. This standard refers to the latest research results, quality evaluation criteria for traditional medicines, and the regulatory framework for cellular treatments. The standard considers general biological properties of cells, including cell morphology, cell cycle, karyotype, and cell viability. The specific biological properties of NSCs, such as cell surface markers and differentiation ability, general drug standards, such as aseptic testing, endotoxins, human virus detection, and cell-related drug standards, such as telomerase activity and tumorigenicity, are also considered. This standard will serve as a reference for physicians and scientists who focus on clinical nervous cell applications and studies related to iPSCs.

This study aims to investigate the effects of partial dietary replacement of fish meal with unfermented and/or fermented soybean meal (fermented by Bacillus cereus) supplemented on the growth performance, whole-body composition, antioxidant and immunity capacity, and their related gene expression of juvenile coho salmon (Oncorhynchus kisutch). Four groups of juveniles (initial weight 159.63 ± 9.54 g) at 6 months of age in triplicate were fed for 12 weeks on four different iso-nitrogen (about 41% dietary protein) and iso-lipid (about 15% dietary lipid) experimental diets. The main results were: Compared with the control diet, the diet with replaced 10% fish meal protein with fermented soybean meal protein supplementation can significantly (p < 0.05) influence the expression of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, nuclear factor erythroid 2-related factor 2, tumor necrosis factor α and interleukin-6 genes, the growth performance, the serum biochemical indices, and the activity of antioxidant and immunity enzymes. However, there was no significant effect (p > 0.05) on the survival rate (SR) and whole-body composition in the juveniles among the experimental groups. In conclusion, the diet with replaced 10% fish meal protein with fermented soybean meal protein supplementation could significantly increase the growth performance, antioxidant and immunity capacity, and their related gene expression of juveniles.

SUMOylation is an essential protein modification process that regulates numerous crucial cellular and biochemical processes in phytopathogenic fungi, and thus plays important roles in multiple biological functions. The present study characterizes the SUMOylation pathway components, including SMT3 (SUMO), AOS1 (an E1 enzyme), UBC9 (an E2 enzyme), and MMS21 (an E3 ligase), in Fusarium oxysporum f. sp. niveum (Fon), the causative agent of watermelon Fusarium wilt, in terms of the phylogenetic relationship, gene/protein structures, and basic biological functions. The SUMOylation components FonSMT3, FonAOS1, FonUBC9, and FonMMS21 are predominantly located in the nucleus. FonSMT3, FonAOS1, FonUBC9, and FonMMS21 are highly expressed in the germinating macroconidia, but their expression is downregulated gradually in infected watermelon roots with the disease progression. The disruption of FonUBA2 and FonSIZ1 seems to be lethal in Fon. The deletion mutant strains for FonSMT3, FonAOS1, FonUBC9, and FonMMS21 are viable, but exhibit significant defects in vegetative growth, asexual reproduction, conidial morphology, spore germination, responses to metal ions and DNA-damaging agents, and apoptosis. The disruption of FonSMT3, FonAOS1, FonUBC9, and FonMMS21 enhances sensitivity to cell wall-perturbing agents, but confers tolerance to digestion by cell wall-degrading enzymes. Furthermore, the disruption of FonSMT3, FonAOS1, and FonUBC9 negatively regulates autophagy in Fon. Overall, these results demonstrate that the SUMOylation pathway plays vital roles in regulating multiple basic biological processes in Fon, and, thus, can serve as a potential target for developing a disease management approach to control Fusarium wilt in watermelon.

Soybean is a source of edible oil for humans and provides a third of the vegetable oil consumed worldwide. Increasing seed oil content in seeds is thus a key objective in soybean breeding. In the present study, a four-way recombinant inbred line (FW-RIL) population comprising 144 lines, planted in 10 environments, and a germplasm panel of 455 accessions, planted in two environments, were used to collect oil-content phenotypes. First, 59 quantitative trait loci (QTL) were detected in the FW-RIL population by inclusive complete interval mapping on a linkage map consisting of 2232 single-nucleotide polymorphism (SNP) markers. Also in the FW-RILs, 44 quantitative trait nucleotides (QTNs) were detected by association analysis using 109,676 SNP markers and five methods of multi-locus genome-wide association study. Second, 77 QTN were detected by association analysis in the germplasm panel using 63,306 markers. Comparison of the QTL and QTN suggested four QTN controlling oil content. Pathway analysis was performed on genes in attenuation regions of these four QTN, and two candidate genes involved in the synthesis or metabolism of soybean oil were identified. These findings provide useful information about the genetics of oil content and may contribute to its genetic improvement by marker-assisted selection.

Retinal progenitor cells (RPCs) transplantation has become a promising therapy for retinal degeneration, which is a major kind of ocular diseases causing blindness. Since RPCs have limited proliferation and differentiation abilities toward retinal neurons, it is urgent to resolve these problems. MicroRNAs have been reported to have vital effects on stem cell fate. In our study, the data showed that overexpression of miR-381-3p repressed Hes1 expression, which promoted RPCs differentiation, especially toward neuronal cells, and inhibited RPCs proliferation. Knockdown of endogenous miR-381-3p increased Hes1 expression to inhibit RPCs differentiation and promote proliferation. In addition, a luciferase assay demonstrated that miR-381-3p directly targeted the Hes1 3’ untranslated region (UTR). Taken together, our study demonstrated that miR-381-3p regulated RPCs proliferation and differentiation by targeting Hes1, which provides an experimental basis of RPCs transplantation therapy for retinal degeneration.

The Lower Yangtze River of China has been identified as an independent center of rice domestication, but tracing the earliest evidence for rice cultivation practices has been challenging. Here we report the first evidence for rice harvesting, based on use-wear and phytolith residue analyses of 52 flaked stone tools (10000-7000 BP) from the Shangshan and Hehuashan sites. The tools reflect two harvesting methods: reaping the panicles at the top and cutting the stalk near the base. Thus, our research provides a new method for investigating prehistoric cereal cultivation, and the data lend support to the evidence of rice domestication in the early Holocene. The results also show the complexity of rice harvesting strategies several millennia before the emergence of full-fledged agriculture in the Lower Yangtze.

Soybean is an important global crop for edible protein and oil, and plant height is a main breeding goal which is closely related to its plant shape and yield. In this research, a high-density genetic linkage map was constructed by 1996 SNP-bin markers on the basis of a recombinant inbred line population derived from Dongnong L13 × Henong 60. A total of 33 QTL related to plant height were identified, of which five were repeatedly detected in multiple environments. In addition, a 455-germplasm population with 63,306 SNP markers was used for multi-locus association analysis. A total of 62 plant height QTN were detected, of which 26 were detected repeatedly under multiple methods. Two candidate genes, Glyma.02G133000 and Glyma.05G240600, involving in plant height were predicted by pathway analysis in the regions identified by multiple environments and backgrounds, and validated by qRT-PCR. These results enriched the soybean plant height regulatory network and contributed to molecular selection-assisted breeding.

Objective: The aim of the current study was to investigate the alterations in the neural networks of patients with temporal lobe epilepsy (TLE) during working memory (WM) encoding.Methods: Patients with TLE (n = 52) and healthy volunteers (n = 35) completed a WM task, during which 34-channel electroencephalogram signals were recorded. The neural networks during WM encoding were calculated in TLE patients with (TLE-WM) and without (TLE-N) WM deficits.Results: Functional connectivity strength decreased, and the theta network was altered in the TLE-WM group, although no significant differences in clinical features were observed between the TLE-N and TLE-WM groups.Conclusions: Not all patients with TLE present with cognitive impairments and alterations in the theta network were identified in TLE patients with functional cognitive deficits.Significance: The theta network may represent a sensitive measure of cognitive impairment and could predict cognitive outcomes among patients with TLE.

To keep plant height (PH) stable in various densities, mapping QTL underlying te response of PH to density is of importance for soybean breeding. In this study, two soybean RIL populations were planted under two densities in two environments and PH at the pod-bearing stage (PBS), seed-filling stage (SFS) and maturity stage (MS) were measured to identify QTL controlling PH and its response to density increment. Expression of QTL controlling PH varied due to the change of seeding density, and the response to density (RD) of PH at SFS and MS surpassed that at PBS in both populations. Total 25 PH QTL and 8 RD QTL were identified which functioned on PH at three developmental stages. Of 25 PH QTL, 14, 8 and 8 were detected at PBS, SFS and MS, respectively. Three QTL could be expressed at two stages, and thirteen, seven and six QTL played roles separately at PDS, SFS and MS, respectively. Four QTL were expressed in the two seeding densities, and twelve and ten QTL showed effects specifically at low and high seeding density, respectively. Among eight RD QTL, five, two and one acted on PH at PBS, SFS and MS, and five and three QTL functioned in two environments, respectively. The information found in the present research lays the foundation for molecular design breeding on improving PH with stability in multiple densities in soybean.

Number of pods per plant and number of seeds per pod are quantitative, multigenic traits and important components of yield in soybean [Glycine max (L.) Merr.]. Pods are distributed unevenly in the upper, middle, and lower segments of the plant and this distribution is affected by sowing date (SD). A population of four-way recombinant inbred lines (FW-RIL), containing 160 F2:8 individuals, was generated from the cross (Kenfeng 14 × Kenfeng 15) × (Heinong 48 × Kenfeng 19). A linkage map consisting of 275 simple sequence repeat (SSR) markers was used to map quantitative trait loci (QTL) associated with the production of one, two, three, and four seeds per pod in the upper, middle, and lower segments of plants at two SDs, totaling 12 measurements per SD. A wide range of variation in the twelve characteristics was observed among the four parental lines and the FW-RIL population at the two SDs. The effect of SD2 (May 17, 2016) on pod number was stronger than that of SD1 (May 7, 2016) because the heritability of each trait in the SD1 experiment was generally greater than that of SD2. The study identified 76 QTL controlling pod number, with the phenotypic variation explained by each QTL ranging from 1.86% to 13.71%. The numbers of QTL controlling one, two, three, and four seeds per pod were 28, 23, 23, and 23, respectively. There were 30, 28, and 28 QTL controlling the pod number in the upper, middle, and lower segments of the plant, respectively. Forty-five QTL were identified at SD1 and 38 QTL were identified at SD2. Seventeen QTL were associated with pod-number traits. The QTL qPN-A1–3 was associated with the number of pods containing one seed in the middle segment of the plant at both SDs. Sixty-three QTL were published QTL (common areas existed when integrating on a map GmComposite2003 of Wm82 based on left and right markers). and 13 QTL related to pod number were newly discovered. These results provide a reference for breeders to improve soybean yield by combining advantageous alleles for these QTL. Future studies may reveal candidate genes for these QTL and identify causal alleles for marker-assisted selection. Keywords: Soybean, Pod number, QTL, Sowing date, Vertical distribution

The rice NAC transcriptional factor family harbors 151 members, and some of them play important roles in rice immunity. Here, we report the function and molecular mechanism of a pathogen-inducible NAC transcription factor, ONAC096, in rice immunity against Magnaprothe oryzae and Xanthomonas oryzae pv. oryzae. Expression of ONAC096 was induced by M. oryzae and by abscisic acid and methyl jasmonate. ONAC096 had the DNA binding ability to NAC recognition sequence and was found to be a nucleus-localized transcriptional activator whose activity depended on its C-terminal. CRISPR/Cas9-mediated knockout of ONAC096 attenuated rice immunity against M. oryzae and X. oryzae pv. oryzae as well as suppressed chitin- and flg22-induced reactive oxygen species burst and expression of PTI marker genes OsWRKY45 and OsPAL4; by contrast, overexpression of ONAC096 enhanced rice immunity against these two pathogens and strengthened chitin- or flg22-induced PTI. RNA-seq transcriptomic profiling and qRT-PCR analysis identified a small set of defense and signaling genes that are putatively regulated by ONAC096, and further biochemical analysis validated that ONAC096 could directly bind to the promoters of OsRap2.6, OsWRKY62, and OsPAL1, three known defense and signaling genes that regulate rice immunity. ONAC096 interacts with ONAC066, which is a positive regulator of rice immunity. These results demonstrate that ONAC096 positively contributes to rice immunity against M. oryzae and X. oryzae pv. oryzae through direct binding to the promoters of downstream target genes including OsRap2.6, OsWRKY62, and OsPAL1.

NAC transcriptional factors constitute a large family in rice and some of them have been demonstrated to play crucial roles in rice immunity. The present study investigated the function and mechanism of ONAC066 in rice immunity. ONAC066 shows transcription activator activity that depends on its C-terminal region in rice cells. ONAC066-OE plants exhibited enhanced resistance while ONAC066-Ri and onac066-1 plants showed attenuated resistance to Magnaporthe oryzae. A total of 81 genes were found to be up-regulated in ONAC066-OE plants, and 26 of them were predicted to be induced by M. oryzae. Four OsWRKY genes, including OsWRKY45 and OsWRKY62, were up-regulated in ONAC066-OE plants but down-regulated in ONAC066-Ri plants. ONAC066 bound to NAC core-binding site in OsWRKY62 promoter and activated OsWRKY62 expression, indicating that OsWRKY62 is a ONAC066 target. A set of cytochrome P450 genes were found to be co-expressed with ONAC066 and 5 of them were up-regulated in ONAC066-OE plants but down-regulated in ONAC066-Ri plants. ONAC066 bound to promoters of cytochrome P450 genes LOC_Os02g30110, LOC_Os06g37300, and LOC_Os02g36150 and activated their transcription, indicating that these three cytochrome P450 genes are ONAC066 targets. These results suggest that ONAC066, as a transcription activator, positively contributes to rice immunity through modulating the expression of OsWRKY62 and a set of cytochrome P450 genes to activate defense response.

Summary: Gut microbial diversity decreases with aging, but existing studies have used stool samples, which do not represent the entire gut. We analyzed the duodenal microbiome in 251 subjects aged 18–35 (n = 32), 36–50 (n = 41), 51–65 (n = 96), and 66–80 (n = 82). Decreased duodenal microbial diversity in older subjects is associated with combinations of chronological age, number of concomitant diseases, and number of medications used, and also correlated with increasing coliform numbers (p < 0.0001). Relative abundance (RA) of phylum Proteobacteria increases in older subjects, with increased RA of family Enterobacteriaceae and coliform genera Escherichia and Klebsiella, and is associated with alterations in the RA of other duodenal microbial taxa and decreased microbial diversity. Increased RA of specific genera are associated with chronological age only (Escherichia, Lactobacillus, and Enterococcus), number of medications only (Klebsiella), or number of concomitant diseases only (Clostridium and Bilophila). These findings indicate the small intestinal microbiome changes significantly with age and the aging process.

Background: Vertebrobasilar dolichoectasia (VBD) is one of the rare causes of trigeminal neuralgia (TN). The common surgical treatments for patients with TN caused by VBD (VBD-TN) are microvascular decompression (MVD) and Gamma Knife radiosurgery (GKRS). However, the therapeutic effects of the two methods have not been clinically compared, so this study was performed to evaluate the treatment outcomes of MVD and GKRS for patients with VBD-TN.Methods: The retrospective study was performed from March 2011 to March 2019 in Wuhan Union Hospital. A total of 80 patients diagnosed with VBD-TN were included in this study, and they were divided into the MVD group (n = 46) and GKRS group (n = 34) according to the surgical methods. The imaging data, intraoperative findings, treatment outcomes, and complications of the two groups were analyzed and compared. Meanwhile, the influencing factors of the treatment effect are also explored on the two groups.Results: Patients who underwent MVD were younger than patients who underwent GKRS (median ages were 61.1 and 65.4 years old, respectively, p = 0.03). The median follow-up was 61.1 months for the MVD group and 56.8 months for the GKRS group. The favorable outcomes [Barrow Neurological Institute (BNI) pain score, BNI scores I–II] occurred in 97.8% of patients treated with MVD and in 78.9% of patients treated with GKRS (p = 0.009). The favorable outcomes in the percentage of patients after MVD 1, 3, 5, and 7 years were 95.7, 85.1, 74.2, and 74.2%, respectively, whereas the corresponding percentages after GKRS were 76.5, 66.2, 56.6, and 47.2%, respectively (p = 0.031). The postoperative complications (except facial numbness) in the MVD group were higher than those in the GKRS group (p = 0.036), but the incidence of new and worsening facial numbness was lower in the GKRS group (p < 0.001).Conclusions: MVD is superior to GKRS in obtaining and maintaining favorable outcomes for patients with VBD-TN, but it also comes with more complications other than facial numbness. Thus, the treatment program can be tailored to a patient's unique condition and wishes.

Soybean is valued in foods, animal feed and some industrial applications, and agronomic traits are important targets for soybean breeding. In this study, two sets of recombinant inbred line (RIL) populations were used to map yield and quality trait quantitative trait loci (QTLs) across three environments. In total, we detected 37 QTLs in two RIL populations grown in three locations. In the 3613 RIL population, three QTLs related to quality traits and 13 related to yield traits were identified among the 16 QTLs. In the 6013 population, we identified six QTLs related to quality traits and 15 related to yield traits. Among these QTLs, some genomic regions showed pleiotropic effects on yield and quality traits. We further identified candidate genes from these regions. Our results lay the foundation for producing high-yielding soybean with excellent quality traits via molecular breeding.

Aiming at the geomorphological and geometrical features of the basin, a recognition approach combined with a landform classification and discriminant analysis is presented. First, a k-means algorithm is applied to the digital elevation model data. The basic types of landforms with elevation, slope, and relief amplitude are clustered, and the landform regions of plains, mountains, and hills have been separated. Focusing on the plain and its neighboring region, a measurement function is defined to analyze the cases of the plain surrounded by mountains and hills. Finally, a discrimination model for basin recognition is presented with parameters of the surrounded state, area of the plain, and difference of its elevation. The approach is applied to the DEM of the Shuttle Radar Topography Mission of China. The experiments show that the results are the same as those of real terrains.

Alcoholic beverages played an essential role in rituals in ancient societies. Here we report the first evidence for beer drinking in the context of burial ritual in early Holocene southern China. Recent archaeological investigations at Qiaotou (9,000-8,700 cal. BP) have revealed a platform mound containing human burials and high concentrations of painted pottery, encircled by a human-made ditch. By applying microfossil (starch, phytolith, and fungi) residue analysis on the pottery vessels, we found that some of the pots held beer made of rice (Oryza sp.), Job's tears (Coix lacryma-jobi), and USOs. We also discovered the earliest evidence for using mold saccharification-fermentation starter in beer making, predating written records by 8,000 years. The beer at Qiaotou was likely served in rituals to commemorate the burial of the dead. Ritualized drinking probably played an integrative role in maintaining social relationships, paving the way for the rise of complex farming societies four millennia later.