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Seeds are important microbial vectors, and seed-associated pathogens can be introduced into a country through trade, resulting in yield and quality losses in agriculture. The aim of this study was to characterize the microbial communities associated with barley seeds, and based on which, to develop technical approaches to trace their geographical origins, and to inspect and identify quarantine pathogens. Our analysis defined the core microbiota of barley seed and revealed significant differences in the barley seed-associated microbial communities among different continents, suggesting a strong geographic specificity of the barley seed microbiota. By implementing a machine learning model, we achieved over 95% accuracy in tracing the origin of barley seeds. Furthermore, the analysis of co-occurrence and exclusion patterns provided important insights into the identification of candidate biocontrol agents or microbial inoculants that could be useful in improving barley yield and quality. A core pathogen database was developed, and a procedure for inspecting potential quarantine species associated with barley seed was established. These approaches proved effective in detecting four fungal and three bacterial quarantine species for the first time in the port of China. This study not only characterized the core microbiota of barley seeds but also provided practical approaches for tracing the regional origin of barley and identifying potential quarantine pathogens.

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BACKGROUND: HIV notification and testing integrated into partner service (PS) practices among HIV-positive individuals have been proven to be an efficient approach for case finding, although it remains a weak link in China. Although nonmarital sexual activities accounted for a large proportion of newly diagnosed HIV-positive cases in China, little is known about PS uptake and associated factors within nonmarital partnerships. OBJECTIVE: This study aimed to describe HIV PS utilization and its associated factors among HIV-positive individuals with nonmarital sexual partners. METHODS: We recruited newly diagnosed HIV-positive individuals who had nonmarital sexual partners in 2022 in Zhejiang Province and offered them PS. We described the PS uptake cascade within sexual partner categories and analyzed the associated factors with 3 primary outcomes from the participants' perspective: nonmarital partner enumeration, HIV testing, and HIV positivity. RESULTS: In this study, 3509 HIV-positive individuals were recruited as participants, and they enumerated 2507 nonmarital sex partners (2507/14,556, 17.2% of all nonmarital sex partners) with contact information. Among these, 43.1% (1090/2507) underwent an HIV test, with an HIV-positive rate of 28.3% (309/1090). Heterosexual commercial partners were the least likely of being enumerated (441/4292, 10.3%) and had the highest HIV-positive rate (40/107, 37.4%). At the participant level, 48.1% (1688/3509) of the participants enumerated at least one nonmarital sex partner with contact information, 52.7% (890/1688) had a sex partner tested for HIV, and 31% (276/890) had at least one nonmarital sex partner who tested positive. Multivariate analysis indicated that gender and transmission route were associated with both nonmarital sex partner enumeration and HIV testing. Age and occupation were associated with nonmarital sex partner enumeration and HIV positivity. Compared with participants who had no regular nonmarital sex partner, those who had a regular nonmarital sex partner were more likely to enumerate nonmarital sex partners (adjusted odds ratio [aOR] 3.017, 95% CI 2.560-3.554), have them get tested for HIV (aOR 1.725, 95% CI 1.403-2.122), and have an HIV-positive nonmarital sex partner (aOR 1.962, 95% CI 1.454-2.647). CONCLUSIONS: The percentage of partner enumeration was low, and HIV testing rate was moderate among nonmarital partnerships of HIV-positive individuals. More efforts should be made to improve PS practices among HIV-positive individuals and address the gap in partner enumeration, especially for heterosexual commercial nonmarital partnerships. Additionally, enhancing PS operational skills among health care personnel could increase the overall efficiency of PS uptake in China.

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BACKGROUND: Health problems associated with shift work and night shift work are gaining increasing public attention. OBJECTIVE: To investigate the association between night shift work and the hazard of mortality. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 283,579 individuals with paid employment or self-employment aged 37-73 years were included from the UK Biobank with a median follow-up period of 14.0 years. MAIN MEASURES: Participants were divided into day workers and shift workers, including the frequency of night shifts, to evaluate the association between baseline work schedules and all-cause and cause-specific mortality using the Cox proportional hazards model. Additionally, 75,760 participants with work histories were assessed for the association between average frequency and cumulative years of exposure to night shift work and all-cause and cause-specific mortality. KEY RESULTS: Compared with that of day workers, the adjusted hazard of all-cause mortality was increased by 12.0% (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.07-1.18) in shift workers, particularly in those with no or rare night shifts (approximately 16.1%; HR, 1.16; 95% CI, 1.08-1.25) and those with irregular night shifts (approximately 9.2%; HR, 1.09; 95% CI, 1.00-1.19). Moreover, a non-linear relationship was identified between cumulative night shift years and all-cause and cause-specific mortality. Only individuals who worked night shifts for 20-30 years exhibited a substantially increased hazard of all-cause (HR, 1.52; 95% CI, 1.15-2.00) and cardiovascular disease (CVD; HR, 2.08; 95% CI, 1.16-3.71) mortality. CONCLUSIONS: Shift workers, particularly those with rare or irregular night shifts, exhibited an increased hazard of mortality. Additionally, participants who worked night shifts for 20-30 years exhibited a substantially increased hazard of all-cause and CVD mortality.

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Cognitive abilities of primates, including humans, continue to improve through adolescence 1,2. While a range of changes in brain structure and connectivity have been documented 3,4, how they affect neuronal activity that ultimately determines performance of cognitive functions remains unknown. Here, we conducted a multilevel longitudinal study of monkey adolescent neurocognitive development. The developmental trajectory of neural activity in the prefrontal cortex accounted remarkably well for working memory improvements. While complex aspects of activity changed progressively during adolescence, such as the rotation of stimulus representation in multidimensional neuronal space, which has been implicated in cognitive flexibility, even simpler attributes, such as the baseline firing rate in the period preceding a stimulus appearance had predictive power over behavior. Unexpectedly, decreases in brain volume and thickness, which are widely thought to underlie cognitive changes in humans 5 did not predict well the trajectory of neural activity or cognitive performance changes. Whole brain cortical volume in particular, exhibited an increase and reached a local maximum in late adolescence, at a time of rapid behavioral improvement. Maturation of long-distance white matter tracts linking the frontal lobe with areas of the association cortex and subcortical regions best predicted changes in neuronal activity and behavior. Our results provide evidence that optimization of neural activity depending on widely distributed circuitry effects cognitive development in adolescence.

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OBJECTIVES: To explore the factors associated with poor prognosis in critically ill patients with Electroencephalogram (EEG) patterns exhibiting stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs), and to construct a prognostic prediction model. METHODS: This study included a total of 53 critically ill patients with EEG patterns exhibiting SIRPIDs who were admitted to the First Affiliated Hospital of Chongqing Medical University from May 2023 to March 2024. Patients were divided into two groups based on their Modified Rankin Scale (mRS) scores at discharge: good prognosis group (0-3 points) and poor prognosis group (4-6 points). Retrospective analyses were performed on the clinical and EEG parameters of patients in both groups. Logistic regression analysis was applied to identify the risk factors related to poor prognosis in critically ill patients with EEG patterns exhibiting SIRPIDs; a risk prediction model for poor prognosis was constructed, along with an individualized predictive nomogram model, and the predictive performance and consistency of the model were evaluated. RESULTS: Multivariate logistic regression analysis revealed that APACHE II score (OR=1.217, 95 %CI=1.030∼1.438), slow frequency bands or no obvious brain electrical activity (OR=8.720, 95 %CI=1.220∼62.313), and no sleep waveforms (OR=9.813, 95 %CI=1.371∼70.223) were independent risk factors for poor prognosis in patients. A regression model established based on multivariate logistic regression analysis had an area under the curve of 0.902. The model's accuracy was 90.60 %, with a sensitivity of 92.86 % and a specificity of 89.70 %. The nomogram model, after internal validation, showed a concordance index of 0.904. CONCLUSIONS: A high APACHE II score, EEG patterns with slow frequency bands or no obvious brain electrical activity, and no sleep waveforms were independent risk factors for poor prognosis in patients with SIRPIDs. The nomogram model constructed based on these factors had a favorably high level of accuracy in predicting the risk of poor prognosis and held certain reference and application value for clinical neurofunctional assessment and prognostic determination.

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OBJECTIVE: To assess the feasibility, efficacy, and safety of microwave ablation in treating follicular thyroid neoplasms and suspicious follicular thyroid neoplasms. METHODS: In this retrospective study, the data of patients treated with microwave ablation for follicular neoplasms from December 2016 to January 2024 were summarized. The changes in nodule size, volume, technical success rate, disease progression, complete tumor resolution, thyroid function, and complications post-ablation were evaluated. RESULTS: Seventy-four patients (15 men, 59 women; mean age 46.3 ± 15.2 years) with follicular neoplasms were included. Over a median follow-up of 13 months, complete ablation was achieved, giving a 100% technical success rate. At the first month post-ablation, the maximum diameter of nodules showed no significant change (p = 0.287). From the third month, both maximum diameter and volume significantly decreased (p < 0.005 for all). Volume reduction rates remained stable at one and three months (p = 0.389 and 0.06, respectively) but increased significantly thereafter (p < 0.005 for all). By 24 months, the median maximum diameter had reduced from 2.3 cm to 0 cm, achieving a median volume reduction rate of 100%. Nodules disappeared completely in 20.3% (15/74). Local recurrence was noted in 2.7% of cases (2/74), with no metastasis or neoplasm-related deaths reported. Thyroid function remained unchanged post-treatment (p > 0.05). The complication and side effect rates were 8.1% and 4.1%, respectively. CONCLUSIONS: Initial findings suggest microwave ablation is an effective and safe treatment for follicular neoplasms, with low incidences of disease progression and complications, while maintaining thyroid function.

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Rationale: Understanding the immune mechanisms associated with liver transplantation (LT), particularly the involvement of tissue-resident memory T cells (TRMs), represents a significant challenge. Methods: This study employs a multi-omics approach to analyse liver transplant samples from both human (n = 17) and mouse (n = 16), utilizing single-cell RNA sequencing, bulk RNA sequencing, and immunological techniques. Results: Our findings reveal a comprehensive T cell-centric landscape in LT across human and mouse species, involving 235,116 cells. Notably, we found a substantial increase in CD8+ TRMs within rejected grafts compared to stable ones. The elevated presence of CD8+ TRMs is characterised by a distinct expression profile, featuring upregulation of tissue-residency markers (CD69, CXCR6, CD49A and CD103+/-,), immune checkpoints (PD1, CTLA4, and TIGIT), cytotoxic markers (GZMB and IFNG) and proliferative markers (PCNA and TOP2A) during rejection. Furthermore, there is a high expression of transcription factors such as EOMES and RUNX3. Functional assays and analyses of cellular communication underscore the active role of CD8+ TRMs in interacting with other tissue-resident cells, particularly Kupffer cells, especially during rejection episodes. Conclusions: These insights into the distinctive activation and interaction patterns of CD8+ TRMs suggest their potential utility as biomarkers for graft rejection, paving the way for novel therapeutic strategies aimed at enhancing graft tolerance and improving overall transplant outcomes.

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Blinatumomab has emerged as a promising component of first-line therapy for acute B-cell precursor lymphoblastic leukemia (BCP-ALL), bolstering treatment efficacy. To mitigate CD19 selection pressure and reduce the incidence of blinatumomab-associated toxicities, pre-treatment chemotherapy is recommended before administering blinatumomab. From September 2022 to December 2023, we conducted a single-arm, multicenter, phase 2 trial (NCT05557110) in newly diagnosed Philadelphia chromosome-negative BCP-ALL (Ph-negative BCP-ALL) patients. Participants received induction treatment with reduced-dose chemotherapy (RDC), comprising idarubicin, vindesine, and dexamethasone over 7 days, followed by 2 weeks of blinatumomab. Those failing to achieve composite complete remission (CRc) received an additional 2 weeks of blinatumomab. The primary endpoint was the CRc rate post initial induction treatment. Of the 35 enrolled patients, 33 (94%) achieved CRc after 2 weeks of blinatumomab, with 30 (86%) achieving measurable residual disease (MRD) negativity. Two patients extended blinatumomab to 4 weeks. With either 2 or 4 weeks of blinatumomab treatment, all patients achieved CR (35/35) and 89% (31/35) were MRD negativity. The median time to CR was 22 days. Immune effector cell-associated neurotoxicity syndrome was limited (14%, all grade 1). Non-hematological adverse events of grade 3 or higher included pneumonia (17%), sepsis (6%), and cytokine release syndrome (9%). With a median follow-up of 11.5 months, estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%, respectively. These findings affirm that RDC followed by blinatumomab is an effective and well-tolerated induction regimen for newly diagnosed Ph-negative BCP-ALL, supporting a shift towards less intensive and more targeted therapeutic approaches. Trial registration: https://www.clinicaltrials.Gov . Identifier NCT05557110.

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Genomic copy number changes are associated with antifungal drug resistance and virulence across diverse fungal pathogens, but the rate and dynamics of these genomic changes in the presence of antifungal drugs are unknown. Here we optimized a dual-fluorescent reporter system in the diploid pathogen Candida albicans to quantify haplotype-specific copy number variation (CNV) and loss of heterozygosity (LOH) at the single-cell level with flow cytometry. We followed the frequency and dynamics of CNV and LOH at two distinct genomic locations in the presence and absence of antifungal drugs in vitro and in a murine model of candidiasis. Copy number changes were rapid and dynamic during adaptation to fluconazole and frequently involved competing subpopulations with distinct genotypes. This study provides quantitative evidence for the rapid speed at which diverse genotypes arise and undergo dynamic population-level fluctuations during adaptation to antifungal drugs in vitro and in vivo.

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Background: Microbial community dynamics have been involved in numerous diseases, including cancer. The diversity of intertumoral microbiota in human papillomavirus independent endocervical adenocarcinoma (HPVI ECA) is not well-characterized. Objective: Our objective is to delineate the intratumoral microbiota profile in HPVI ECA and investigate its potential influence on oncogenesis. Methods: We analyzed 45 HPVI ECA cases, comprising 36 gastric-type ECA (GEA) and 9 clear cell carcinomas (CCC). We compared the microbial composition within cancerous and adjacent noncancerous tissue samples using 5R-16S ribosomal DNA sequencing. Further, we investigated the correlation between specific microbes and clinical-pathological metrics as well as patient outcomes. Results: Our findings demonstrate notable differences in the microbial spectra between cancerous and adjacent noncancerous tissues. Amongst HPVI ECA subtypes, GEAs exhibit more microbial variations compared to CCCs. Using the Random Forest algorithm, we identified two distinct microbial signatures that could act as predictive biomarkers for HPVI ECA and differentiate between GEA and CCC. Varied microbial abundances was related to clinical characteristics of HPVI ECA patients. In addition, high levels of Micrococcus and low levels of unknown genus75 from the Comamonadaceae family were associated with poorer outcomes in HPVI ECA patients. Similarly, an abundance of Microbacterium correlated with reduced overall survival (OS), and a high presence of Streptococcaceae family microbes was linked to reduced recurrence-free survival (RFS) in GEA patients. Intriguingly, a high abundance of Micrococcus was also associated with a worse OS in GEA patients. Conclusion: The study reveals distinct microbial signatures in HPVI ECA, which have potential as biomarkers for disease prognosis. The correlation between these tumor-associated microbiota features and clinicopathological characteristics underscores the possibility of microbiome-based interventions. Our research provides a foundation for more in-depth studies into the cervical microbiome's role in HPVI ECA.

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Human-based modelling and simulation offer an ideal testbed for novel medical therapies to guide experimental and clinical studies. Myocardial infarction (MI) is a common cause of heart failure and mortality, for which novel therapies are urgently needed. Although cell therapy offers promise, electrophysiological heterogeneity raises pro-arrhythmic safety concerns, where underlying complex spatio-temporal dynamics cannot be investigated experimentally. Here, after demonstrating credibility of the modelling and simulation framework, we investigate cell therapy in acute versus chronic MI and the role of cell heterogeneity, scar size and the Purkinje system. Simulations agreed with experimental and clinical recordings from ionic to ECG dynamics in acute and chronic infarction. Following cell delivery, spontaneous beats were facilitated by heterogeneity in cell populations, chronic MI due to tissue depolarisation and slow sinus rhythm. Subsequent re-entrant arrhythmias occurred, in some instances with Purkinje involvement and their susceptibility was enhanced by impaired Purkinje-myocardium coupling, large scars and acute infarction. We conclude that homogeneity in injected ventricular-like cell populations minimises their spontaneous beating, which is enhanced by chronic MI, whereas a healthy Purkinje-myocardium coupling is key to prevent subsequent re-entrant arrhythmias, particularly for large scars.

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Citrus aurantium L., sometimes known as "sour orange," is an important Chinese herb with young, immature fruits, or "zhishi," that are high in synephrine. Synephrine is a commonly utilized natural chemical with promising applications in effectively increasing metabolism, heat expenditure, energy level, oxidative fat, and weight loss. However, little is known about the genes and pathways involved in synephrine production during the critical developmental stages of C. aurantium L., which limits the development of the industry. According to this study, the concentration of synephrine gradually decreased as the fruit developed. Transcriptome sequencing was used to examine the DEGs associated with synephrine connections and served as the foundation for creating synephrine-rich C. aurantium L. Comparisons conducted between different developmental stages to obtain DEGs, and the number of DEGs varied from 690 to 3,019. Tyrosine and tryptophan biosynthesis, glycolysis/gluconeogenesis, pentose phosphate pathway, phenylalanine, and tyrosine metabolism were the main KEGG pathways that were substantially enriched. The results showed that 25 genes among these KEGG pathways may be related to synephrine synthesis. The WGCNA and one-way ANOVA analysis adoption variance across the groups suggested that 11 genes might play a crucial role in synephrine synthesis and should therefore be further analyzed. We also selected six DEGs at random and analyzed their expression levels by RT-qPCR, and high repeatability and reliability were demonstrated by our finished RNA-seq study results. These results may be useful in selecting or modifying genes to increase the quantity of synephrine in sour oranges.

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This study presents the identification of four novel Xylaria species, discovered in the karst region of China. The discovery was facilitated by a rigorous analysis that encompassed both morpho-anatomical features and multi-locus phylogenetics utilizing sequences from the ITS, rpb2, and TUB2 loci. The newly identified species are designated as Xylariajichuanii sp. nov., X.nanningensis sp. nov., X.orientalis sp. nov., and X.taiyangheensis sp. nov. The distinction of these species from their known counterparts was verified through comparison of morphological features and phylogenetic analysis. The study further provides detailed morphological descriptions, illustrative representations, and a phylogenetic tree, all of which contribute to the taxonomic positioning of these novel species.

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Molecular phylogeny and morphological characteristics of collections of diatrypaceous fungi from Guizhou Province, China, lead to the establishment of a new genus, Stromatolinea, and the identification of four new species and two new combinations. The taxa were found growing on the dead culms of Phyllostachys bamboo. The new genus is distinguished by its well-developed, discrete linear stromata with yellow interior tissue and allantoid subhyaline ascospores. The newly described species are Stromatolineagrisea, S.guizhouensis, S.hydei, and S.xishuiensis. Additionally, two new combinations, Stromatolinealinearis and S.phaselina, are proposed based on comparative analysis and morphology. Phylogenetic analyses were conducted using ITS and TUB2 sequences. The study includes comprehensive morphological descriptions, illustrations, and a phylogenetic tree depicting the placement of the new taxa.

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BACKGROUND: Despite growing applications of backward walking (BW) in assessing and rehabilitating neuromuscular conditions, its effects on gait in chronic ankle instability (CAI) remain unclear. Moreover, linking patient-reported and clinically generated measures is imperative for understanding CAI. HYPOTHESES: Patients with CAI will exhibit worse and compensatory spatio-temporal and kinetic gait parameters during BW, and patient-reported outcomes (PROs) will be correlated significantly with gait parameters. STUDY DESIGN: Case-control study. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 46 volunteers participated (23 per group). Patients filled out scales for pain, functions, and fear-avoidance beliefs before testing. All participants walked 6 times each in both forward and backward conditions, and gait was recorded using the Win-Track system. A 2-way mixed analysis of variance was performed to compare gait parameters. The relationship between PRO and gait outcomes was assessed through the Pearson product correlation coefficient. RESULTS: The CAI group demonstrated prolonged support and swing phases, increased walk-off angle, and plantar pressure area, but decreased step length and plantar pressure versus controls (P < 0.05). The CAI group had a smaller right walk-off angle during BW than FW; the control group showed the opposite (P < 0.05). The left single stance duration was greater in the CAI group, while the right was not (P < 0.05). PRO correlated significantly with gait parameters, particularly spatial parameters (P < 0.05). CONCLUSION: The CAI group exhibited worse gait parameters during BW. The CAI group exhibited a characteristic compensatory gait pattern. Linking the self-reported scores provides a better representation of gait changes in CAI. CLINICAL RELEVANCE: These results suggest that BW may be an effective strategy for identifying and evaluating CAI. It may be feasible to apply BW to the rehabilitation of CAI.

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Introduction: The incidence of knee osteoarthritis (KOA) is moderately correlated with age and body weight and increases with life span and weight gain, associated with tearing and wearing the knee joints. KOA can adjust the force through the human lower limbs, redistribute the load of the knee joint, reduce the pain, and restore mobility when the arthritis changes are mild. However, most of the existing knee orthosis cannot be adjusted adaptively according to the needs of patients. Methodology: This study establishes a biomechanical model of the knee joint to analyze the medial and lateral forces acting on the joint. The new adjustable knee orthosis is designed. It applies the principle of four-point bending to apply pressure to both sides of the knee joint, thereby adjusting the varus angle and modifying the medial and lateral forces on the knee joint. Through structural optimization, the prototype of the knee orthosis weighs only 324 g. Utilizing three-dimensional scanning technology, discrete point cloud data of the leg surface is obtained, reconstructed, and processed to create a 3D model of the human leg surface. The design ensures a close fit to the human leg surface, offering comfortable wear. A pressure sensing film system is employed to build a pressure sensing test system, where the knee orthosis is worn on a prosthesis for pressure testing to evaluate its ability to adjust knee joint forces. Results: The pressure test results demonstrate that the knee orthosis can stably provide an adjustment angle of 0-7° and sustain a maximum force of 10N on both sides of the knee joint over extended periods. A self-developed 8-channel plantar pressure sensing insole is calibrated against commercial plantar pressure sensors. Human wear tests on 15 subjects show that during the operation of the knee orthosis, it significantly adjusts plantar pressures, reducing lateral foot pressures by 22% overall, with more pronounced corrective effects observed in lighter participants. Discussion: In this study, a wedge-shaped adaptive knee orthosis was provided for KOA patients. The four-point force principle was used to balance the force between femurs and tibia and adjust the meniscus contact gap. The orthotic appliance has the advantages of simple mechanical structure, adjustable correction Angle and good wearing comfort.

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The rapid identification of bacterial Gram types and their viability, as well as efficient bacterial elimination are crucial for managing bacterial infections yet present important challenges. In this research, we utilized long-chain-tailed BODIPY derivatives to address these hurdles. Our data indicated that these derivatives can distinguish bacteria types and their viability in aqueous solutions through a concise turn-on fluorescent response. Among them, B-8 stained both live and dead bacteria, and B-14 offered a wash-free staining. B-18 demonstrated the highest affinity to selectively fluorescent label viable gram-positive bacteria with a 53.2-fold fluorescent enhancement. Confocal imaging confirmed that B-18 can serve as an effective membrane-specific probe for facilitating the typing between gram-negative and gram-positive bacteria in a wash-free manner. Additionally, B-18 displayed selective photodynamic inactivation at 1 µM toward gram-positive bacteria. In vivo studies variformed the ideal photodynamic therapeutic efficacy of B-18 against methicillin-resistant Staphylococcus aureus in mice wound infections.

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Our study aims to explore the effects of neoadjuvant chemotherapy (NACT) on tumour cells and immune cells in the immune microenvironment of patients with high-grade serous ovarian cancer (HGSOC). Single-cell RNA sequencing data of paired ovarian cancer tissues were analysed before and after NACT in 11 patients with HGSOC. The effect of NACT on two major cell components of the tumour microenvironment, epithelial cells and CD8+T cells, was investigated. The mechanisms of epithelial cell evasion by NACT and immune killing were explored from the perspectives of gene expression, functional characteristics, transcriptional regulation, and cell communication. Key targets for reversing NACT resistance were identified and possible therapeutic strategies proposed. While NACT improved the de novo differentiation of anti-tumour CD8+T cells, enhancing their anti-tumour function, it increased the proportion of cancer cells with high HSP90B1 expression. Thus, the potential reasons for NACT resistance were identified as: 1) high levels of endoplasmic reticulum stress (ERS) characteristics, 2) high expression of the MDK-NCL ligand-receptor pair between them and exhausted CD8+T cells before NACT, and 3) high expression of the NECTIN2-TIGIT immune ligand-receptor pair between them and exhausted CD8+T cells after NACT. Thus, our study reveals the mechanisms underlying NACT resistance in patients with HGSOC from the perspective of the independent and interactive roles of cancer cells and CD8+T cells. We propose therapeutic strategies targeting the ERS marker HSP90B1 and the immune escape marker MDK before or during NACT, while targeting NECTIN2 blockade after NACT. This approach may offer new insights into combination treatments for patients with HGSOC displaying NACT resistance.

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A recent study has introduced a recombinant fusion protein, consisting of the extracellular domain (ECD) of p75 and the Fc fragment of human immunoglobulin IgG1 (p75ECD-Fc), as a multifaceted agent within the nervous system. This research aimed to assess the effects of p75ECD-Fc on neuronal growth and the restoration of neurological functions in rats afflicted with neonatal hypoxic-ischemic encephalopathy (NHIE). In vitro analyses revealed that 1 µM p75ECD-Fc treatment markedly increased cell viability and facilitated neurite outgrowth in neurons exposed to oxygen-glucose deprivation (OGD). Subsequent in vivo studies determined that a dose of 78.6 µg/3 µl of p75ECD-Fc significantly mitigated brain damage and both acute and long-term neurological impairments, outperforming the therapeutic efficacy of hypothermia, as evidenced through behavioral assessments. Additionally, in vivo immunostaining showed that p75ECD-Fc administration enhanced neuronal survival and regeneration, and reduced astrocytosis and microglia activation in the cortex and hippocampus of NHIE rats. A noteworthy shift from A1 to A2 astrocyte phenotypes and from M1 to M2 microglia phenotypes was observed after p75ECD-Fc treatment. Furthermore, a co-expression of the p75 neurotrophin receptor (p75NTR) and Nestin was identified, with an overexpression of Nestin alleviating the neurological dysfunction induced by NHIE. Mechanistically, the neuroprotective effects of p75ECD-Fc, particularly its inhibition of neuronal apoptosis post-OGD, may be attributed to Nestin. Taken together, these results highlight the neuroprotective and anti-inflammatory effects of p75ECD-Fc treatment through the modulation of glial cell phenotypes and the Nestin-mediated inhibition of neuronal apoptosis, positioning it as a viable therapeutic approach for NHIE.

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Southeast Asia is a biodiversity hotspot characterized by a complex paleogeography, and its Polypodiopsida flora is particularly diverse. While hybridization is recognized as common in ferns, further research is needed to investigate the relationship between hybridization events and fern diversity. Lecanopteris s.s., an ant-associated fern, has been subject to debate regarding species delimitations primarily due to limited DNA markers and species sampling. Our study integrates 22 newly generated plastomes, 22 transcriptomes, and flow cytometry of all native species along with two cultivated hybrids. Our objective is to elucidate the reticulate evolutionary history within Lecanopteris s.s. through the integration of phylobiogeographic reconstruction, gene flow inference, and genome size estimation. Key findings of our study include: (1) An enlarged plastome size (178-187 Kb) in Lecanopteris, attributed to extreme expansion of the Inverted Repeat (IR) regions; (2) The traditional 'pumila' and 'crustacea' groups are paraphyletic; (3) Significant cytonuclear discordance attributed to gene flow; (4) Natural hybridization and introgression in the 'pumila' and 'darnaedii' groups; (5) L. luzonensis is the maternal parent of L. 'Yellow Tip', with L. pumila suggested as a possible paternal parent; (6) L. 'Tatsuta' is a hybrid between L. luzonensis and L. crustacea; (7) Lecanopteris first diverged during the Neogene and then during the middle Miocene climatic optimum in the Indochina and Sundaic regions. In conclusion, the biogeographic history and speciation of Lecanopteris have been profoundly shaped by past climate changes and geodynamics of Southeast Asia. Dispersals, hybridization and introgression between species act as pivotal factors in the evolutionary trajectory of Lecanopteris. This research provides a robust framework for further exploration and understanding of the complex dynamics driving the diversification and distribution patterns within Polypodiaceae subfamily Microsoroideae.