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Abstract Background Cereal diseases caused by insect-transmitted viruses are challenging to forecast and control because of their intermittent outbreak patterns, which are usually attributed to increased population densities of vector insects due to cereal crop rotations and indiscriminate use of pesticides, and lack of resistance in commercial varieties. Root microbiomes are known to significantly affect plant health, but there are significant knowledge gaps concerning epidemics of cereal virus diseases at the microbiome-wide scale under a variety of environmental and biological factors. Results Here, we characterize the diversity and composition of rice (Oryza sativa) root-associated bacterial communities after infection by an insect-transmitted reovirus, rice black-streaked dwarf virus (RBSDV, genus Fijivirus, family Spinareoviridae), by sequencing the bacterial 16S rRNA gene amplified fragments from 1240 samples collected at a consecutive 3-year field experiment. The disease incidences gradually decreased from 2017 to 2019 in both Langfang (LF) and Kaifeng (KF). BRSDV infection significantly impacted the bacterial community in the rice rhizosphere, but this effect was highly susceptible to both the rice-intrinsic and external conditions. A greater correlation between the bacterial community in the rice rhizosphere and those in the root endosphere was found after virus infection, implying a potential relationship between the rice-intrinsic conditions and the rhizosphere bacterial community. The discrepant metabolites in rhizosphere soil were strongly and significantly correlated with the variation of rhizosphere bacterial communities. Glycerophosphates, amino acids, steroid esters, and triterpenoids were the metabolites most closely associated with the bacterial communities, and they mainly linked to the taxa of Proteobacteria, especially Rhodocyclaceae, Burkholderiaceae, and Xanthomonadales. In addition, the greenhouse pot experiments demonstrated that bulk soil microbiota significantly influenced the rhizosphere and endosphere communities and also regulated the RBSDV-mediated variation of rhizosphere bacterial communities. Conclusions Overall, this study reveals unprecedented spatiotemporal dynamics in rhizosphere bacterial communities triggered by RBSDV infection with potential implications for disease intermittent outbreaks. The finding has promising implications for future studies exploring virus-mediated plant-microbiome interactions. Video Abstract

Lung cancer is the main cause of cancer-related deaths worldwide. Due to lack of obvious clinical symptoms in the early stage of the lung cancer, it is hard to distinguish between malignancy and pulmonary nodules. Understanding the immune responses in the early stage of malignant lung cancer patients may provide new insights for diagnosis. Here, using high-through-put sequencing, we obtained the TCRβ repertoires in the peripheral blood of 100 patients with Stage I lung cancer and 99 patients with benign pulmonary nodules. Our analysis revealed that the usage frequencies of TRBV, TRBJ genes, and V-J pairs and TCR diversities indicated by D50s, Shannon indexes, Simpson indexes, and the frequencies of the largest TCR clone in the malignant samples were significantly different from those in the benign samples. Furthermore, reduced TCR diversities were correlated with the size of pulmonary nodules. Moreover, we built a backpropagation neural network model with no clinical information to identify lung cancer cases from patients with pulmonary nodules using 15 characteristic TCR clones. Based on the model, we have created a web server named “Lung Cancer Prediction” (LCP), which can be accessed at http://i.uestc.edu.cn/LCP/index.html.

Abstract Background Postoperative thirst is one of the most intense, common and easily ignored subjective discomforts in patients after gynecological surgery. This study aimed to investigate whether early oral hydration on demand in the postanesthesia care unit (PACU) after gynecological laparoscopy under general anesthesia can appease postoperative thirst and increase patient comfort. Methods Participants were randomized into the intervention and control groups. Patients in the intervention group were allowed to achieve early oral hydration on demand in the PACU if they were evaluated as fully conscious, with stable vital signs, grade 5 muscle strength, and well-recovered cough and swallowing reflex. However, the total amount of water intake throughout the entire study should not exceed 0.5mL/kg. During the study, the frequency of water intake, the total amount of water intake and adverse events were accurately recorded. The control group was managed according to the routine procedures and began to drink water 2 h after anesthesia. The intensity of thirst and subjective comfort in patients were assessed using the visual analog scale (VAS) when they entered and left the PACU. Results No statistically significant differences were identified in age, height, weight, body mass index, pre-operative fasting time, duration of surgery, intraoperative fluid intake, intraoperative blood loss, intraoperative urine volume, and thirst intensity and subjective comfort scores between the groups before intervention (P > 0.05). After intervention, the VAS score for thirst intensity in the intervention group significantly decreased (P

Mesenchymal stem cell (MSC) migration determines the healing capacity of bone and is crucial in promoting bone regeneration. Migration of MSCs is highly dependent on degradation of extracellular matrix by proteolytic enzymes. However, the underlying mechanisms of how enzymolysis paves the way for MSCs to migrate from their niche to the defect area is still not fully understood. Here, this study shows that high-temperature requirement A3 (HtrA3) overcomes the physical barrier and provides anchor points through collagen IV degradation, paving the way for MSC migration. HtrA3 is upregulated in MSCs at the leading edge of bone defect during the early stage of healing. HtrA3 degrades the surrounding collagen IV, which increases the collagen network porosity and increases integrin β1 expression. Subsequently, integrin β1 enhances the mechanotransduction of MSCs, thus remodeling the cytoskeleton, increasing cellular stiffness and nuclear translocation of YAP, eventually promoting the migration and subsequent osteogenic differentiation of MSCs. Local administration of recombinant HtrA3 in rat cranial bone defects significantly increases new bone formation and further validates the enhancement of MSC migration. This study helps to reveal the novel roles of HtrA3, explore potential targets for regenerative medicine, and offer new insights for the development of bioactive materials.

Alfalfa (Medicago sativa. L.) is a globally significant autotetraploid legume forage crop. However, despite its importance, establishing efficient gene editing systems for cultivated alfalfa remains a formidable challenge. In this study, we pioneered the development of a highly effective ultrasonic-assisted leaf disc transformation system for Gongnong 1 alfalfa, a variety widely cultivated in Northeast China. Subsequently, we created a single transcript CRISPR/Cas9 (CRISPR_2.0) toolkit, incorporating multiplex gRNAs, designed for gene editing in Gongnong 1. Both Cas9 and gRNA scaffolds were under the control of the Arabidopsis ubiquitin-10 promoter, a widely employed polymerase II constitutive promoter known for strong transgene expression in dicots. To assess the toolkit’s efficiency, we targeted PALM1, a gene associated with a recognizable multifoliate phenotype. Utilizing the CRISPR_2.0 toolkit, we directed PALM1 editing at two sites in the wild-type Gongnong 1. Results indicated a 35.1% occurrence of editing events all in target 2 alleles, while no mutations were detected at target 1 in the transgenic-positive lines. To explore more efficient sgRNAs, we developed a rapid, reliable screening system based on Agrobacterium rhizogenes-mediated hairy root transformation, incorporating the visible reporter MtLAP1. This screening system demonstrated that most purple visible hairy roots underwent gene editing. Notably, sgRNA3, with an 83.0% editing efficiency, was selected using the visible hairy root system. As anticipated, tetra-allelic homozygous palm1 mutations exhibited a clear multifoliate phenotype. These palm1 lines demonstrated an average crude protein yield increase of 21.5% compared to trifoliolate alfalfa. Our findings highlight the modified CRISPR_2.0 system as a highly efficient and robust gene editing tool for autotetraploid alfalfa.

Abstract Asynchronous nuclear and cytoplasmic maturation in human oocytes is believed to cause morphological anomalies after controlled ovarian hyperstimulation. Vacuolar protein sorting 34 (VPS34) is renowned for its pivotal role in regulating autophagy and endocytic trafficking. To investigate its impact on oocyte development, oocyte‐specific knockout mice (ZcKO) are generated, and these mice are completely found infertile, with embryonic development halted at 2‐ to 4‐cell stage. This infertility is related with a disruption on autophagic/mitophagic flux in ZcKO oocytes, leading to subsequent failure of zygotic genome activation (ZGA) in derived 2‐cell embryos. The findings further elucidated the regulation of VPS34 on the activity and subcellular translocation of RAS‐related GTP‐binding protein 7 (RAB7), which is critical not only for the maturation of late endosomes and lysosomes, but also for initiating mitophagy via retrograde trafficking. VPS34 binds directly with RAB7 and facilitates its activity conversion through TBC1 domain family member 5 (TBC1D5). Consistent with the cytoplasmic vacuolation observed in ZcKO oocytes, defects in multiple vesicle trafficking systems are also identified in vacuolated human oocytes. Furthermore, activating VPS34 with corynoxin B (CB) treatment improved oocyte quality in aged mice. Hence, VPS34 activation may represent a novel approach to enhance oocyte quality in human artificial reproduction.

Abstract Mammalian cochlea spiral ganglion neurons (SGNs) are crucial for sound transmission, they can be damaged by chemotherapy drug cisplatin and lead to irreversible sensorineural hearing loss (SNHL), while such damage can also render cochlear implants ineffective. However, the mechanisms underlying cisplatin‐induced SGNs damage and subsequent SNHL are still under debate and there is no currently effective clinical treatment. Here, this study demonstrates that ferroptosis is triggered in SGNs following exposure to cisplatin. Inhibiting ferroptosis protects against cisplatin‐induced SGNs damage and hearing loss, while inducing ferroptosis intensifies these effects. Furthermore, cisplatin prompts nuclear receptor coactivator 4 (NCOA4)‐mediated ferritinophagy in SGNs, while knocking down NCOA4 mitigates cisplatin‐induced ferroptosis and hearing loss. Notably, the upstream regulator of NCOA4 is identified and transcription factor forkhead box O1 (FOXO1) is shown to directly suppress NCOA4 expression in SGNs. The knocking down of FOXO1 amplifies NCOA4‐mediated ferritinophagy, increases ferroptosis and lipid peroxidation, while disrupting the interaction between FOXO1 and NCOA4 in NCOA4 knock out mice prevents the cisplatin‐induced SGN ferroptosis and hearing loss. Collectively, this study highlights the critical role of the FOXO1‐NCOA4 axis in regulating ferritinophagy and ferroptosis in cisplatin‐induced SGNs damage, offering promising therapeutic targets for SNHL mitigation.

Abstract The pursuit of pharmacological interventions in aging aims focuses on maximizing safety and efficacy, prompting an exploration of natural products endowed with inherent medicinal properties. Subsequently, this work establishes a unique library of plant extracts sourced from Yunnan Province, China. Screening of this herbal library herein revealed that Salsola collina (JM10001) notably enhances both lifespan and healthspan in C. elegans. Further analysis via network pharmacology indicates that the p53 signaling pathway plays a crucial role in mediating the anti‐aging effects of JM10001. Additionally, this work identifies that a composition, designated as JM10101 and comprising three chemical constituents of JM10001, preserves the original lifespan‐extending activity in C. elegans. Both JM10001 and JM10101 mitigate aging symptoms in senescence‐accelerated mice treated with doxorubicin and in naturally aged mice. Notably, JM10101 exhibits a more sophisticated senomorphlytic role encompassing both senomorphic and senolytic functions than JM10001 in the modulation of senescent cells, offering a promising strategy for the discovery of combination drugs in the rational development of anti‐aging therapies.

BackgroundTo improve perioperative frailty status in patients undergoing laparoscopic colorectal cancer surgery (LCCS), we explored a new intensive prehabilitation program that combines prehabilitation exercises with standard enhanced recovery after surgery (ERAS) and explored its impact.MethodsWe conducted a prospective randomized controlled trial. Between April 2021 to August 2021, patients undergoing elective LCCS were randomized into the standardized ERAS (S-ERAS) group or ERAS based on prehabilitation (group PR-ERAS). Patients in the PR-ERAS group undergoing prehabilitation exercises in the perioperative period in addition to standard enhanced recovery after surgery. We explored the effects of this prehabilitation protocol on frailty, short-term quality of recovery (QoR), psychological status, postoperative functional capacity, postoperative outcomes, and pain.ResultsIn total, 125 patients were evaluated, and 95 eligible patients were enrolled and randomly allocated to the S-ERAS (n = 45) and PR-ERAS (n = 50) groups. The Fried score was higher in the PR-ERAS group on postoperative day (7 (2(2,3) vs. 3(2,4), P = 0.012). The QoR-9 was higher in the PR-ERAS group than in the S-ERAS group on the 1st, 2nd, 3rd, and 7th postoperative days. The PR-ERAS group had an earlier time to first ambulation (P < 0.050) and time to first flatus (P < 0.050).ConclusionPrehabilitation exercises can improve postoperative frailty and accelerate recovery in patients undergoing LCCS but may not improve surgical safety. Therefore, better and more targeted prehabilitation recovery protocols should be explored.Clinical trial registrationwww.clinicaltrials.org, identifier NCT04964856.

BackgroundThe study aims to assess the efficacy and safety of the recently approved S1PR modulator etrasimod in adults with ulcerative colitis during the induction phase through meta-analysis.MethodsA systemic search was performed for randomized controlled trials evaluating the efficacy and safety of the S1PR modulator etrasimod using electronic databases PubMed, Embase, the Cochrane Library, Clinical Trials, and the International Clinical Trials Registry Platform. Three studies with 943 patients met the inclusion criteria and were included in this analysis. The study’s primary endpoint was the proportion of patients who achieved clinical remission at week 12. Key secondary endpoints included the proportion of patients with clinical response, endoscopic improvement, and histologic remission. The incidence of adverse effects (AEs), serious AEs (SAEs), and AE-related treatment discontinuation were statistically analyzed to determine the safety of etrasimod.ResultsThis study revealed that etrasimod is superior to placebo at the primary endpoint clinical remission (OR = 3.09, 95% CI: 2.04–4.69), as well as at the secondary endpoints clinical response (OR = 2.56, 95% CI: 1.91–3.43), endoscopic improvement (OR = 2.15, 95% CI: 1.51–3.05), and histologic remission (OR = 3.39, 95% CI: 2.03–5.68). The proportion of patients with TEAE (OR = 1.34, 95% CI: 1.01–1.78) and SAE (OR = 0.77, 95% CI: 0.41–1.43) was similar between the etrasimod and placebo groups. Patients receiving etrasimod had slightly higher odds of experiencing headache (OR = 2.07, 95% CI: 1.01–4.23), and nausea (OR = 1.84, 95% CI: 0.72–4.72). The incidences of upper respiratory tract infection (OR = 0.79, 95% CI: 0.27–2.32), nasopharyngitis (OR = 0.40, 95% CI: 0.15–1.07), and urinary tract infection (OR = 1.82, 95% CI: 0.59–5.60) were generally lower in the etrasimod groups and no treatment-related serious infections were reported.ConclusionThis study demonstrates that etrasimod is effective in treating moderately to severely active ulcerative colitis with a favorable benefit-risk profile at week 12. Etrasimod shows promise as a potential first-line oral therapy for individuals suffering from this disease. Additional RCTs with larger sample sizes and longer observation periods are needed to confirm the sustained efficacy of etrasimod beyond the initial phase.

Phage-immunoprecipitation sequencing (PhIP-Seq) technology is an innovative, high-throughput antibody detection method. It enables comprehensive analysis of individual antibody profiles. This technology shows great potential, particularly in exploring disease mechanisms and immune responses. Currently, PhIP-Seq has been successfully applied in various fields, such as the exploration of biomarkers for autoimmune diseases, vaccine development, and allergen detection. A variety of bioinformatics tools have facilitated the development of this process. However, PhIP-Seq technology still faces many challenges and has room for improvement. Here, we review the methods, applications, and challenges of PhIP-Seq and discuss its future directions in immunological research and clinical applications. With continuous progress and optimization, PhIP-Seq is expected to play an even more important role in future biomedical research, providing new ideas and methods for disease prevention, diagnosis, and treatment.

Abstract Background Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of lung cancer patients with mutated EGFR. However, the efficacy of EGFR-TKIs in wild-type EGFR tumors has been shown to be marginal. Methods that can sensitize EGFR-TKIs to EGFR wild-type NSCLC remain rare. Hence, we determined whether combination treatment can maximize the therapeutic efficacy of EGFR-TKIs. Methods We established a focused drug screening system to investigate candidates for overcoming the intrinsic resistance of wild-type EGFR NSCLC to EGFR-TKIs. Molecular docking assays and western blotting were used to identify the binding mode and blocking effect of the candidate compounds. Proliferation assays, analyses of drug interactions, colony formation assays, flow cytometry and nude mice xenograft models were used to determine the effects and investigate the molecular mechanism of the combination treatment. Results Betulinic acid (BA) is effective at targeting EGFR and synergizes with EGFR-TKIs (gefitinib and osimertinib) preferentially against wild-type EGFR. BA showed inhibitory activity due to its interaction with the ATP-binding pocket of EGFR and dramatically enhanced the suppressive effects of EGFR-TKIs by blocking EGFR and modulating the EGFR-ATK-mTOR axis. Mechanistic studies revealed that the combination strategy activated EGFR-induced autophagic cell death and that the EGFR-AKT-mTOR signaling pathway was essential for completing autophagy and cell cycle arrest. Activation of the mTOR pathway or blockade of autophagy by specific chemical agents markedly attenuated the effect of cell cycle arrest. In vivo administration of the combination treatment caused marked tumor regression in the A549 xenografts. Conclusions BA is a potential wild-type EGFR inhibitor that plays a critical role in sensitizing EGFR-TKI activity. BA combined with an EGFR-TKI effectively suppressed the proliferation and survival of intrinsically resistant lung cancer cells via the inhibition of EGFR as well as the induction of autophagy-related cell death, indicating that BA combined with an EGFR-TKI may be a potential therapeutic strategy for overcoming the primary resistance of wild-type EGFR-positive lung cancers. Graphical abstract

Abstract Background Facioscapulohumeral muscular dystrophy (FSHD) is a high-prevalence autosomal dominant neuromuscular disease characterized by significant clinical and genetic heterogeneity. Genetic diagnosis of FSHD remains a challenge because it cannot be detected by standard sequencing methods and requires a complex diagnosis workflow. Methods We developed a comprehensive genetic FSHD detection method based on Oxford Nanopore Technologies (ONT) whole-genome sequencing. Using a case–control design, we applied this procedure to 29 samples and compared the results with those from optical genome mapping (OGM), bisulfite sequencing (BSS), and whole-exome sequencing (WES). Results Using our ONT-based method, we identified 59 haplotypes (35 4qA and 24 4qB) among the 29 samples (including a mosaic sample), as well as the number of D4Z4 repeat units (RUs). The pathogenetic D4Z4 RU contraction identified by our ONT-based method showed 100% concordance with OGM results. The methylation levels of the most distal D4Z4 RU and the double homeobox 4 gene (DUX4) detected by ONT sequencing are highly consistent with the BSS results and showed excellent diagnostic efficiency. Additionally, our ONT-based method provided an independent methylation profile analysis of two permissive 4qA alleles, reflecting a more accurate scenario than traditional BSS. The ONT-based method detected 17 variations in three FSHD2-related genes from nine samples, showing 100% concordance with WES. Conclusions Our ONT-based FSHD detection method is a comprehensive method for identifying pathogenetic D4Z4 RU contractions, methylation level alterations, allele-specific methylation of two 4qA haplotypes, and variations in FSHD2-related genes, which will all greatly improve genetic testing for FSHD.

In this paper, we propose an analytical approach to estimate the largest Lyapunov exponent (LLE) of a Rössler chaotic system, leveraging the synchronization method. This research focuses on establishing an analytical criterion for the synchronization of two identical Rössler chaotic systems through the linear coupling of state variables. This is crucial because the LLE of such systems can be estimated based on the critical coupling required for synchronization. Unlike previous studies, we first transform the synchronization error system between two identical Rössler chaotic systems into a set of Volterra integral equations by using the Laplace transform and convolution theorem. The critical coupling for synchronization is analytically derived using integral equation theory to solve the error system. As compared to the numerical results of the Rössler chaotic system's LLE, our analytical estimates demonstrate high accuracy. Our findings suggest that the challenge of estimating the Rössler chaotic system's LLE can be simplified to solving a cubic algebraic equation, offering a novel perspective on the analysis of how parameters influence the LLE's value in the Rössler chaotic system.

Abstract Background Studies have shown that chemotherapy and radiotherapy can cause premature ovarian failure and loss of fertility in female cancer patients. Ovarian cortex cryopreservation is a good choice to preserve female fertility before cancer treatment. Following the remission of the disease, the thawed ovarian tissue can be transplanted back and restore fertility of the patient. However, there is a risk to reintroduce cancer cells in the body and leads to the recurrence of cancer. Given the low success rate of current in vitro culture techniques for obtaining mature oocytes from primordial follicles, an artificial ovary with primordial follicles may be a good way to solve this problem. Methods In the study, we established an artificial ovary model based on the participation of mesenchymal stem cells (MSCs) to evaluate the effect of MSCs on follicular development and oocyte maturation. P2.5 mouse ovaries were digested into single cell suspensions and mixed with bone marrow derived mesenchymal stem cells (BM-MSCs) at a 1:1 ratio. The reconstituted ovarian model was then generated by using phytohemagglutinin. The phenotype and mechanism studies were explored by follicle counting, immunohistochemistry, immunofluorescence, in vitro maturation (IVM), in vitro fertilization (IVF), real-time quantitative polymerase chain reaction (RT-PCR), and Terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) assay. Results Our study found that the addition of BM-MSCs to the reconstituted ovary can enhance the survival of oocytes and promote the growth and development of follicles. After transplanting the reconstituted ovaries under kidney capsules of the recipient mice, we observed normal folliculogenesis and oocyte maturation. Interestingly, we found that BM-MSCs did not contribute to the formation of follicles in ovarian aggregation, nor did they undergo proliferation during follicle growth. Instead, the cells were found to be located around growing follicles in the reconstituted ovary. When theca cells were labeled with CYP17a1, we found some overlapped staining with green fluorescent protein(GFP)-labeled BM-MSCs. The results suggest that BM-MSCs may participate in directing the differentiation of theca layer in the reconstituted ovary. Conclusions The presence of BM-MSCs in the artificial ovary was found to promote the survival of ovarian cells, as well as facilitate follicle formation and development. Since the cells didn’t proliferate in the reconstituted ovary, this discovery suggests a potential new and safe method for the application of MSCs in clinical fertility preservation by enhancing the success rate of cryo-thawed ovarian tissues after transplantation.

Abstract Background Brain metastasis (BM) is common among cases of advanced non-small cell lung cancer (NSCLC) and is the leading cause of death for these patients. Mesothelin (MSLN), a tumor-associated antigen expressed in many solid tumors, has been reported to be involved in the progression of multiple tumors. However, its potential involvement in BM of NSCLC and the underlying mechanism remain unknown. Methods The expression of MSLN was validated in clinical tissue and serum samples using immunohistochemistry and enzyme-linked immunosorbent assay. The ability of NSCLC cells to penetrate the blood-brain barrier (BBB) was examined using an in vitro Transwell model and an ex vivo multi-organ microfluidic bionic chip. Immunofluorescence staining and western blotting were used to detect the disruption of tight junctions. In vivo BBB leakiness assay was performed to assess the barrier integrity. MET expression and activation was detected by western blotting. The therapeutic efficacy of drugs targeting MSLN (anetumab) and MET (crizotinib/capmatinib) on BM was evaluated in animal studies. Results MSLN expression was significantly elevated in both serum and tumor tissue samples from NSCLC patients with BM and correlated with a poor clinical prognosis. MSLN significantly enhanced the brain metastatic abilities of NSCLC cells, especially BBB extravasation. Mechanistically, MSLN facilitated the expression and activation of MET through the c-Jun N-terminal kinase (JNK) signaling pathway, which allowed tumor cells to disrupt tight junctions and the integrity of the BBB and thereby penetrate the barrier. Drugs targeting MSLN (anetumab) and MET (crizotinib/capmatinib) effectively blocked the development of BM and prolonged the survival of mice. Conclusions Our results demonstrate that MSLN plays a critical role in BM of NSCLC by modulating the JNK/MET signaling network and thus, provides a potential novel therapeutic target for preventing BM in NSCLC patients.

Summary: Although autosomal-dominant inheritance is believed an important cause of familial clustering Alzheimer’s disease (FAD), it covers only a small proportion of FAD incidence, and so we investigated epigenetic memory as an alternative mechanism to contribute for intergenerational AD pathogenesis. Our data in vivo showed that mys-2 of Caenorhabditis elegans that encodes a putative MYST acetyltransferase responsible for H4K16 acetylation modulated AD occurrence. The phenotypic improvements in the parent generation caused by mys-2 disfunction were passed to their progeny due to epigenetic memory, which resulted in similar H4K16ac levels among the candidate target genes of MYS-2 and similar gene expression patterns of the AD-related pathways. Furthermore, the ROS/CDK-5/ATM pathway functioned as an upstream activator of MYS-2. Our study indicated that MYS-2/MOF could be inherited intergenerationally via epigenetic mechanisms in C. elegans and mammalian cell of AD model, providing a new insight into our understanding of the etiology and inheritance of FAD.

Abstract Patients who have non‐small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations are more prone to brain metastasis (BM) and poor prognosis. Previous studies showed that the tumor microenvironment of BM in these patients is immunosuppressed, as indicated by reduced T‐cell abundance and activity, although the mechanism of this immunosuppression requires further study. This study shows that reactive astrocytes play a critical role in promoting the immune escape of BM from EGFR‐mutated NSCLC by increasing the apoptosis of CD8+ T lymphocytes. The increased secretion of interleukin 11(IL11) by astrocytes promotes the expression of PDL1 in BM, and this is responsible for the increased apoptosis of T lymphocytes. IL11 functions as a ligand of EGFR, and this binding activates EGFR and downstream signaling to increase the expression of PDL1, culminating in the immune escape of tumor cells. IL11 also promotes immune escape by binding to its intrinsic receptor (IL11Rα/glycoprotein 130 [gp130]). Additional in vivo studies show that the targeted inhibition of gp130 and EGFR suppresses the growth of BM and prolongs the survival time of mice. These results suggest a novel therapeutic strategy for treatment of NSCLC patients with EGFR mutations.

Abstract Plant's life history can evolve in response to variation in climate spatio‐temporally, but numerous multiple‐species studies overlook species‐specific (especially a foundation species) ecological effects and genetic underpinnings. For a species to successfully invade a region, likely to become a foundation species, life‐history variation of invasive plants exerts considerable ecological and evolutionary impacts on invaded ecosystems. We examined how an invasive foundation plant, Spartina alterniflora, varied in its life history along latitudinal gradient using a common gardens experiment. Two common gardens were located at range boundary in tropical zone and main distribution area of S. alterniflora in temperate zone in China. Within each population/garden, we measured the onset time of three successive phenological stages constituting the reproductive phase and a fitness trait. In the low‐latitude garden with higher temperature, we found that reproductive phase was advanced and its length prolonged compared to the high‐latitude garden. This could possibly due to lower plasticity of maturity time. Additionally, plasticity in the length of the reproductive phase positively related with fitness in the low‐latitude garden. Marginal population from tropic had the lowest plasticity and fitness, and the poor capacity to cope with changing environment may result in reduction of this population. These results reflected genetic divergence in life history of S. alterniflora in China. Our study provided a novel view to test the center–periphery hypothesis by integration across a plant's life history and highlighted the significance in considering evolution. Such insights can help us to understand long‐term ecological consequences of life‐history variation, with implications for plant fitness, species interaction, and ecosystem functions under climate change.

Summary: Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3–5 or infarct core volume 70–100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18–2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06–2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].

Abstract Background Necrotizing enterocolitis (NEC) is a multifactorial gastrointestinal disease with high morbidity and mortality among premature infants. However, studies with large samples on the factors of NEC in China have not been reported. This meta-analysis aims to systematically review the literature to explore the influencing factors of necrotizing enterocolitis in premature infants in China and provide a reference for the prevention of NEC. Methods PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), Wanfang and VIP databases were systematically searched from inception to February 2023. We used Stata14.0 software to perform the systematic review and meta-analysis. We used fixed or random effects models with combined odds ratios (ORs) and 95% confidence intervals (CIs), and quality was evaluated using the Newcastle‒Ottawa Scale (NOS). Results The total sample was 8616 cases, including 2456 cases in the intervention group and 6160 cases in the control group. It was found that 16 risk factors and 3 protective factors were related to necrotizing enterocolitis in premature infants. Septicemia (OR = 3.91), blood transfusion (OR = 2.41), neonatal asphyxia (OR = 2.46), pneumonia (OR = 6.17), infection (OR = 5.99), congenital heart disease (OR = 4.80), intrahepatic cholestasis of pregnancy (ICP) (OR = 2.71), mechanical ventilation (OR = 1.44), gestational diabetes mellitus (GDM) (OR = 3.08), respiratory distress syndrome (RDS) (OR = 3.28), hypoalbuminemia (OR = 2.80), patent ductus arteriosus (PDA) (OR = 3.10), respiratory failure (OR = 7.51), severe anemia (OR = 2.86), history of antibiotic use (OR = 2.12), and meconium-stained amniotic fluid (MSAF) (OR = 3.14) were risk factors for NEC in preterm infants in China. Breastfeeding (OR = 0.31), oral probiotics (OR = 0.36), and prenatal use of glucocorticoids (OR = 0.38) were protective factors for NEC in preterm infants. Conclusions Septicemia, blood transfusion, neonatal asphyxia, pneumonia, infection, congenital heart disease, ICP, GDM, RDS, hypoproteinemia, PDA, respiratory failure, severe anemia, history of antibiotic use and MSAF will increase the risk of NEC in premature infants, whereas breastfeeding, oral probiotics and prenatal use of glucocorticoids reduce the risk. Due to the quantity and quality of the included literature, the above findings need to be further validated by more high-quality studies.

In an extensive fungal investigation conducted in southern China, a large number of fungal strains were isolated by collecting and treating diseased and decayed leaves. Using internal transcribed spacer regions (ITSs) sequence data for a BLAST search to screen for suspected strains of Daldinia, followed by phylogenetic analysis using internal transcribed spacer regions, partial sequences of the large subunit of the rDNA (LSU), RNA polymerase II (rpb2), and beta tubulin (tub2) sequence data, combined with morphological characteristics of anamorphic species, ninety-four strains of Daldinia were identified. Furthermore, their geographical distribution and host specificity of the genus were thoroughly analyzed and summarized. Additionally, seven new anamorphic species of the genus Daldinia were also detected, Daldinia ehretiae sp. nov., D. jianfengensis sp. nov., D. ledongensis sp. nov., D. menghaiensis sp. nov., D. rhododendri sp. nov., D. spatholobi sp. nov., and D. thunbergiae sp. nov.

Traditional cancer treatment modalities such as surgery, chemotherapy, and radiation therapy have seen significant advancements in the past. However, inherent drawbacks, including systemic toxicity and high recurrence rates. Consequently, The nanoparticles, with their targeting and multifunctionality, have captured significant attention. This work synthesizes HMNPs-C60-N-GQDs-SS-PEI (HMNPs:Fe3O4@SiO2@mSiO2-C18) nanoparticles, integrating diverse functionalities for enhanced cancer therapy. The inclusion of SiO2 and C60 significantly improves the loading efficiency of gallic acid (GA). The magnetic properties of HMNPs enable efficient targeting to cancer sites under external magnetic fields. The -SS- linkage ensures drug release exclusively in tumor cells over-expressing glutathione (GSH), minimizing adverse effects on normal tissues. Introduction of Polyethyleneimine (PEI) imparts positive charge to facilitate accumulation on negatively charged tumor surfaces and enhances biocompatibility. Additionally, the fluorescence properties of N-doped graphene quantum dots (N-GQDs) facilitate real-time monitoring of material distribution in vivo during mouse and clinical therapy. Furthermore, the nano-magnetic targeting material demonstrates efficient drug loading and precise control over drug release, addressing issues such as the poor biocompatibility and high biotoxicity associated with traditional materials. This study not only achieves effective tumor treatment but also offers a promising direction for developing efficient multifunctional nano-targeting materials.

Abstract Hereditary deafness is a common neurosensory disorder, and 148 non‐syndromic deafness genes have been identified to date. Gene therapy has been used to treat a variety of genetic diseases, but no gene therapy drug for hereditary deafness has been approved for clinical use. At present, several clinical trials of gene therapy for hereditary deafness are underway. However, few normative documents have been issued to guide the standardization of gene therapy for hearing loss, and this document is the first global gene therapy guideline for hereditary hearing loss. The guidelines were jointly developed and drafted by experienced audiologists, virologists and biologists who are vigorously involved in inner ear gene therapy research in the Hearing, Speech and Communication Subsociety of Biophysical Society of China, Audiology Development Foundation Of China and Audiology Subsociety of Jiangsu Medical Association. These guidelines cover preclinical research and clinical practice of gene therapy for hereditary deafness, including indications, key points of pre‐clinical research, patient selection criteria, pre‐clinical preparation, drug efficacy, drug safety evaluation criteria, ethical review, etc. We hope that the guidelines will promote the standardization of clinical practice related to gene therapy for hereditary deafness in China and around the world.

Summary Background Autoimmune enteropathy (AIE) defined by intractable diarrhoea and nonceliac enteropathy with villous atrophy, is a rare digestive disease. Case reports of this disease are sporadic and the clinical characteristics of AIE is seldom discussed. Purpose We evaluate the clinical, laboratory, histopathological features, response to therapy and outcome of AIE in children. Method We conducted a retrospective analysis of five children with AIE in our hospital. A comprehensive search of MEDLINE was performed using PubMed, through keywords of “autoimmune enteropathy, pediatric or children”. The clinical manifestations, endoscopic results, pathological results, and medication therapy of these children were collected and the cases were divided into two groups, infants (≤ 1 year old) and children (> 1 year old). Results Five cases treated in our department: one case took eight years to make the final diagnosis; one case was positive for anti-intestinal epithelial cell (AE) antibody; three cases showed crypt apoptosis in histopathology; and two cases showed celiac-like changes. All cases were responsive to glucocorticoid therapy in the early stage of treatment, while three cases required immunosuppressant maintenance. After reviewing the literature, we performed a statistical analysis of 50 cases with a male-to-female ratio of 31:19. Among them, 35 patients (70%) were within 1 year of age, and their clinical manifestations were mainly watery stool (43 cases, 86%), weight loss (28 cases, 56%), abdominal distension (3 cases, 6%), serum AE or anti-goblet cell (AG) antibody positivity (32 cases, 64%), other immune-related antibodies (21 cases, 42%), gene mutations (9 cases, 18%), and family history (21 cases, 42%). All the children showed different degrees of intestinal villous atrophy. Thirty-seven (74%) of the children were treated early, and their clinical symptoms were relieved. Comparing the cases between different age groups, it was found that the mortality rate of children with onset in infancy was higher (P 0.05) through analysis of mortality and clinical remission cases. Conclusion Endoscopic examination and mucosal pathological examination should be performed to diagnose AIE in children with watery stool and weight loss who fail to be treated with diet therapy. Immunotherapy is the core of medical management of AIE and can improve prognosis. Children with a poor prognosis in infancy should be actively treated to reduce mortality rates associated with AIE.

Abstract Background Infantile cholestasis (IC) is the most common hepatobiliary disease in infants, resulting in elevated direct bilirubin levels. Indeed, hepatointestinal circulation impacts bile acid and bilirubin metabolism. This study evaluates changes in the gut microbiota composition in children with IC and identifies abnormal metabolite profiles associated with microbial alterations. Results The gut microbiota in the IC group exhibits the higher abundance of Veillonella, Streptococcus and Clostridium spp. (P

Strawflower (Helichrysum bracteatum) capitula have papery bracts and thus have the qualities of a naturally dried flower. The involucral bract cells have a secondary cell wall (SCW) of which a crucial component is lignin. Although the constituents of SCWs have been studied extensively in plants, little is known of the mechanism regulating SCW formation, especially lignin biosynthesis in the involucral bracts of strawflower. In this study, a homolog of NAC SECONDARY WALL THICKENING PROMOTING FACTOR 1, designated HbNST1, was identified as a positive regulator of lignin biosynthesis in strawflower. The transcript level of HbNST1 was the highest in the involucral bracts. Subcellular localization analysis indicated that HbNST1 was localized to the nucleus. Overexpression of HbNST1 in Chrysanthemum indicum promoted the expression of a gene related to lignin biosynthesis, a homolog of cinnamyl alcohol dehydrogenase, designated CiCAD, suggesting that HbNST1 was associated with the accumulation of lignin in the SCW of the involucral bracts. Taken together, the results suggested that HbNST1 positively regulated lignin accumulation in the involucral bracts and mediated the expression of lignin biosynthesis-related genes in strawflower.

This paper proposes a road crack detection method based on residual and attention mechanisms to address the issues of difficult detection of small cracks on road surfaces in complex backgrounds and inaccurate crack detection edges. This method introduces residual modules in the encoder stage to better extract crack detail features and introduces attention mechanism modules in the skip connection structure of the network to better locate crack positions. Training and testing on public datasets have shown that compared with existing partial detection methods, our method has improved segmentation accuracy and generalization, and is more precise in segmenting small cracks, thus verifying the superiority of the proposed method in this paper.

Abstract Background Resistance to pemetrexed (PEM), a rare chemotherapeutic agent that can efficiently cross the blood-brain barrier, limits the therapeutic efficacy for patients with lung cancer brain metastasis (BM). Aldo-keto reductase family 1 B10 (AKR1B10) was recently found to be elevated in lung cancer BM. The link between AKR1B10 and BM-acquired PEM is unknown. Methods PEM drug-sensitivity was assessed in the preclinical BM model of PC9 lung adenocarcinoma cells and the BM cells with or without AKR1B10 interference in vitro and in vivo. Metabolic reprogramming of BM attributed to AKR1B10 was identified by chromatography-mass spectrometry (GC-MS) metabolomics, and the mechanism of how AKR1B10 mediates PEM chemoresistance via a way of modified metabolism was revealed by RNA sequencing as well as further molecular biology experimental approaches. Results The lung cancer brain metastatic subpopulation cells (PC9-BrM3) exhibited significant resistance to PEM and silencing AKR1B10 in PC9-BrM3 increased the PEM sensitivity in vitro and in vivo. Metabolic profiling revealed that AKR1B10 prominently facilitated the Warburg metabolism characterized by the overproduction of lactate. Glycolysis regulated by AKR1B10 is vital for the resistance to PEM. In mechanism, AKR1B10 promoted glycolysis by regulating the expression of lactate dehydrogenase (LDHA) and the increased lactate, acts as a precursor that stimulates histone lactylation (H4K12la), activated the transcription of CCNB1 and accelerated the DNA replication and cell cycle. Conclusions Our finding demonstrates that AKR1B10/glycolysis/H4K12la/CCNB1 promotes acquired PEM chemoresistance in lung cancer BM, providing novel strategies to sensitize PEM response in the treatment of lung cancer patients suffering from BM.

Abstract For bone defect repair under co-morbidity conditions, the use of biomaterials that can be non-invasively regulated is highly desirable to avoid further complications and to promote osteogenesis. However, it remains a formidable challenge in clinical applications to achieve efficient osteogenesis with stimuli-responsive materials. Here, we develop polarized CoFe2O4@BaTiO3/poly(vinylidene fluoridetrifluoroethylene) [P(VDF-TrFE)] core-shell particle-incorporated composite membranes with high magnetoelectric conversion efficiency for activating bone regeneration. An external magnetic field force conduct on the CoFe2O4 core can increase charge density on the BaTiO3 shell and strengthens the β-phase transition in the P(VDF-TrFE) matrix. This energy conversion increases the membrane surface potential, which hence activates osteogenesis. Skull defect experiments on male rats showed that repeated magnetic field applications on the membranes enhanced bone defect repair, even when osteogenesis repression is elicited by dexamethasone or lipopolysaccharide-induced inflammation. This study provides a strategy of utilizing stimuli-responsive magnetoelectric membranes to efficiently activate osteogenesis in situ.

Fhb7 is a major gene that was transferred from Thinopyrum ponticum to chromosome 7D of wheat (Triticum aestivum) and confers resistance to both Fusarium head blight (FHB) and Fusarium crown rot (FCR). However, Fhb7 is tightly linked to the PSY-E2 gene, which causes yellow flour, limiting its application in breeding. To break this linkage, marker K-PSY was developed for tagging PSY-E2 and used with Fhb7 markers to identify recombination between the two genes. Screening 21,000 BC1F2 backcross progeny (Chinese Spring ph1bph1b*2/SDAU 2028) revealed two Fhb7+ wheat-Tp7el2L lines, Shannong 2–16 and Shannong 16–1, that carry a desired truncated Fhb7+ translocation segment without PSY-E2. The two lines show levels of resistance to FHB and FCR similar to those of the original translocation line SDAU 2028, but have white flour. To facilitate Fhb7 use in wheat breeding, STS markers were developed and used to isolate Fhb7 on a truncated Tp7el2 translocation segment. Near-isogenic lines carrying the Fhb7+ segment were generated in the backgrounds of three commercial cultivars, and Fhb7+ lines showed increased FHB and FCR resistance without yield penalty. The breakage of the tight linkage between Fhb7 and PSY-E2 via homoeologous recombination provides genetic resources for improvement of wheat resistance to FHB and FCR and permit the large-scale deployment of Fhb7 in breeding using marker-assisted selection.

Abstract Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy, resulting in abnormal sensation in lower lip. It is generally believed that spontaneous sensory recovery in this nerve injury is difficult. However, during our follow-up, patients with inferior alveolar nerve sacrifice showed different degrees of lower lip sensory recovery. In this study, a prospective cohort study was conducted to demonstrate this phenomenon and analyze the factors influencing sensory recovery. A mental nerve transection model of Thy1-YFP mice and tissue clearing technique were used to explore possible mechanisms in this process. Gene silencing and overexpression experiments were then conducted to detect the changes in cell morphology and molecular markers. In our follow-up, 75% of patients with unilateral inferior alveolar nerve neurectomy had complete sensory recovery of the lower lip 12 months postoperatively. Patients with younger age, malignant tumors, and preservation of ipsilateral buccal and lingual nerves had a shorter recovery time. The buccal nerve collateral sprouting compensation was observed in the lower lip tissue of Thy1-YFP mice. ApoD was demonstrated to be involved in axon growth and peripheral nerve sensory recovery in the animal model. TGF-β inhibited the expression of STAT3 and the transcription of ApoD in Schwann cells through Zfp423. Overall, after sacrificing the inferior alveolar nerve, the collateral compensation of the ipsilateral buccal nerve could innervate the sensation. And this process was regulated by TGF-β-Zfp423-ApoD pathway.

Summary: The titer of viruses that persist and propagate in their insect vector must be high enough for transmission yet not harm the insect, but the mechanism of this dynamic balance is unclear. Here, expression of inosine monophosphate dehydrogenase (LsIMPDH), a rate-limiting enzyme for guanosine triphosphate (GTP) synthesis, is shown to be downregulated by increased levels of N6-methyladenosine (m6A) on LsIMPDH mRNA in rice stripe virus (RSV)-infected small brown planthoppers (SBPHs; Laodelphax striatellus), the RSV vector, which decreases GTP content, thus limiting viral proliferation. Moreover, planthopper methyltransferase-like protein 3 (LsMETTL3) and m6A reader protein LsYTHDF3 are found to catalyze and recognize the m6A on LsIMPDH mRNA, respectively, and cooperate in destabilizing LsIMPDH transcripts. Co-silencing assays show that negative regulation of viral proliferation by both LsMETTL3 and LsYTHDF3 is partially dependent on LsIMPDH. This distinct mechanism limits virus replication in an insect vector, providing a potential gene target to block viral transmission.

Abstract Development and regeneration in biological tissues are fundamentally affected by stem‐cell‐fate commitment. Bioelectricity is heterogeneous between different tissues and crucially regulates cell behaviors, including cell differentiation. However, the effects of heterogeneous bioelectricity on stem‐cell differentiation remain poorly understood. Herein, it is shown that providing stem cells with electrical stimulation matching the endogenous membrane potentials of cells derived from different tissues (osteogenic‐related: −55.05 ± 4.22 mV, neurogenic‐related: −84.8 ± 7.48 mV) can induce their osteogenic or neurogenic lineage commitment. Molecular dynamics simulations indicated that the osteogenic‐related surface potential favors the adsorption of fibronectin, while the neurogenic‐related surface potential enhances the adsorption of FGF‐2. These different protein adsorptions trigger either downstream Wnt or Erk signaling, which direct stem‐cell differentiation. Surface‐potential‐mediated lineage‐specification of stem cells using bioelectrical intensity has enormous potential application value in tissue regenerative therapy.

Spiral ganglion neurons (SGNs) in the mammalian cochleae are essential for the delivery of acoustic information, and damage to SGNs can lead to permanent sensorineural hearing loss as SGNs are not capable of regeneration. Cochlear glial cells (GCs) might be a potential source for SGN regeneration, but the neuronal differentiation ability of GCs is limited and its properties are not clear yet. Here, we characterized the cochlear Sox10-positive (Sox10+) GCs as a neural progenitor population and developed a basement membrane extract-based three-dimensional (BME-3D) culture system to promote its neuronal generation capacity in vitro. Firstly, the purified Sox10+ GCs, isolated from Sox10-creER/tdTomato mice via flow cytometry, were able to form neurospheres after being cultured in the traditional suspension culture system, while significantly more neurospheres were found and the expression of stem cell-related genes was upregulated in the BME-3D culture group. Next, the BME-3D culture system promoted the neuronal differentiation ability of Sox10+ GCs, as evidenced by the increased number, neurite outgrowth, area of growth cones, and synapse density as well as the promoted excitability of newly induced neurons. Notably, the BME-3D culture system also intensified the reinnervation of newly generated neurons with HCs and protected the neurospheres and derived-neurons against cisplatin-induced damage. Finally, transcriptome sequencing analysis was performed to identify the characteristics of the differentiated neurons. These findings suggest that the BME-3D culture system considerably promotes the proliferation capacity and neuronal differentiation efficiency of Sox10+ GCs in vitro, thus providing a possible strategy for the SGN regeneration study.

BackgroundPreterm infants have imperfect neurological development, uncoordinated sucking-swallowing-breathing, which makes it difficult to realize effective oral feeding after birth. How to help preterm infants achieve complete oral feeding as soon as possible has become an important issue in the management of preterm infants. Non-nutritive sucking (NNS), as a useful oral stimulation, can improve the effect of oral feeding in preterm infants. This review aimed to explore the effect of NNS on oral feeding progression through a meta-analysis.MethodsWe systematically searched PubMed, CINHAL, Web of Science, Embase, Cochrane databases, China's National Knowledge Infrastructure (CNKI), Wanfang and VIP database from inception to January 20, 2024. Search terms included 'non-nutritive sucking' 'oral feeding' and 'premature.' Eligibility criteria involved randomized controlled studies in English or Chinese. Studies were excluded if they were reviews, case reports, or observational studies from which valid data could not be extracted or outcome indicators were poorly defined. The meta-analysis will utilize Review Manager 5.3 software, employing either random-effects or fixed-effects models based on observed heterogeneity. We calculated the mean difference (MD) and 95% confidence interval (CI) for continuous data, and estimated pooled odds ratios (ORs) for dichotomous data. Sensitivity and publication bias analyses were conducted to ensure robust and reliable findings. We evaluated the methodological quality of randomized controlled trials (RCTs) utilizing the assessment tool provided by the Cochrane Collaboration.ResultsA total of 23 randomized controlled trials with 1461 preterm infants were included. The results of the meta-analysis showed that NNS significantly shortened time taken to achieve exclusive oral feeding (MD = -5.37,95%CI = -7.48 to-3.26, pConclusionNNS improves oral feeding outcomes in preterm infants and reduces the time to reach full oral feeding and hospitalization length. However, this study was limited by the relatively small sample size of included studies and did not account for potential confounding factors. There was some heterogeneity and bias between studies. More studies are needed in the future to validate the effects on weight gain and growth in preterm infants. Nevertheless, our meta-analysis provides valuable insights, updating existing evidence on NNS for improving oral feeding in preterm infants and promoting evidence-based feeding practices in this population.

BackgroundLiver hepatocellular carcinoma (LIHC) is a prevalent form of primary liver cancer. Research has demonstrated the contribution of tumor stem cells in facilitating tumor recurrence, metastasis, and treatment resistance. Despite this, there remains a lack of established cancer stem cells (CSCs)-associated genes signatures for effectively predicting the prognosis and guiding the treatment strategies for patients diagnosed with LIHC.MethodsThe single-cell RNA sequencing (scRNA-seq) and bulk RNA transcriptome data were obtained based on public datasets and computerized firstly using CytoTRACE package and One Class Linear Regression (OCLR) algorithm to evaluate stemness level, respectively. Then, we explored the association of stemness indicators (CytoTRACE score and stemness index, mRNAsi) with survival outcomes and clinical characteristics by combining clinical information and survival analyses. Subsequently, weighted co-expression network analysis (WGCNA) and Cox were applied to assess mRNAsi-related genes in bulk LIHC data and construct a prognostic model for LIHC patients. Single-sample gene-set enrichment analysis (ssGSEA), Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Tumor Immune Estimation Resource (TIMER) analysis were employed for immune infiltration assessment. Finally, the potential immunotherapeutic response was predicted by the Tumor Immune Dysfunction and Exclusion (TIDE), and the tumor mutation burden (TMB). Additionally, pRRophetic package was applied to evaluate the sensitivity of high and low-risk groups to common chemotherapeutic drugs.ResultsA total of four genes (including STIP1, H2AFZ, BRIX1, and TUBB) associated with stemness score (CytoTRACE score and mRNAsi) were identified and constructed a risk model that could predict prognosis in LIHC patients. It was observed that high stemness cells occurred predominantly in the late stages of LIHC and that poor overall survival in LIHC patients was also associated with high mRNAsi scores. In addition, pathway analysis confirmed the biological uniqueness of the two risk groups. Personalized treatment predictions suggest that patients with a low risk benefited more from immunotherapy, while those with a high risk group may be conducive to chemotherapeutic drugs.ConclusionThe current study developed a novel prognostic risk signature with genes related to CSCs, which provides novel ideas for the diagnosis, prognosis and treatment of LIHC.

In the evolving landscape of robotics and visual navigation, event cameras have gained important traction, notably for their exceptional dynamic range, efficient power consumption, and low latency. Despite these advantages, conventional processing methods oversimplify the data into 2 dimensions, neglecting critical temporal information. To overcome this limitation, we propose a novel method that treats events as 3D time-discrete signals. Drawing inspiration from the intricate biological filtering systems inherent to the human visual apparatus, we have developed a 3D spatiotemporal filter based on unsupervised machine learning algorithm. This filter effectively reduces noise levels and performs data size reduction, with its parameters being dynamically adjusted based on population activity. This ensures adaptability and precision under various conditions, like changes in motion velocity and ambient lighting. In our novel validation approach, we first identify the noise type and determine its power spectral density in the event stream. We then apply a one-dimensional discrete fast Fourier transform to assess the filtered event data within the frequency domain, ensuring that the targeted noise frequencies are adequately reduced. Our research also delved into the impact of indoor lighting on event stream noise. Remarkably, our method led to a 37% decrease in the data point cloud, improving data quality in diverse outdoor settings.

Inner ear cell regeneration from stem/progenitor cells provides potential therapeutic strategies for the restoration of sensorineural hearing loss (SNHL), however, the efficiency of regeneration is low and the functions of differentiated cells are not yet mature. Biomaterials have been used in inner ear cell regeneration to construct a more physiologically relevant 3D culture system which mimics the stem cell microenvironment and facilitates cellular interactions. Currently, these biomaterials include hydrogel, conductive materials, magneto-responsive materials, photo-responsive materials, etc. We analyzed the characteristics and described the advantages and limitations of these materials. Furthermore, we reviewed the mechanisms by which biomaterials with different physicochemical properties act on the inner ear cell regeneration and depicted the current status of the material selection based on their characteristics to achieve the reconstruction of the auditory circuits. The application of biomaterials in inner ear cell regeneration offers promising opportunities for the reconstruction of the auditory circuits and the restoration of hearing, yet biomaterials should be strategically explored and combined according to the obstacles to be solved in the inner ear cell regeneration research.

Abstract Background Meiotic recombination is initiated by Spo11-dependent programmed DNA double-strand breaks (DSBs) that are preferentially concentrated within genomic regions called hotspots; however, the factor(s) that specify the positions of meiotic DSB hotspots remain unclear. Results Here, we examined the frequency and distribution of R-loops, a type of functional chromatin structure comprising single-stranded DNA and a DNA:RNA hybrid, during budding yeast meiosis and found that the R-loops were changed dramatically throughout meiosis. We detected the formation of multiple de novo R-loops in the pachytene stage and found that these R-loops were associated with meiotic recombination during yeast meiosis. We show that transcription-replication head-on collisions could promote R-loop formation during meiotic DNA replication, and these R-loops are associated with Spo11. Furthermore, meiotic recombination hotspots can be eliminated by reversing the direction of transcription or replication, and reversing both of these directions can reconstitute the hotspots. Conclusions Our study reveals that R-loops may play dual roles in meiotic recombination. In addition to participation in meiotic DSB processing, some meiotic DSB hotspots may be originated from the transcription-replication head-on collisions during meiotic DNA replication.

Achondroplasia is a rare disease leading to growth and developmental disorders in children, mainly manifested as skeletal dysplasia and disproportionate short stature, which can lead to respiratory abnormalities, hearing loss, spinal involvement, limb joint deformity and other problems, thus making patients encounter a variety of treatment and rehabilitation issues throughout their life, with greatly impaired quality of life. However, the clinical treatment and care pathways of achondroplasia are still not completely unified. To facilitate the standardization of clinical treatment of achondroplasia, the International Consensus Statement on the Diagnosis, Multidisciplinary Management and Lifelong Care of Individuals with Achondroplasia was developed by a group of international experts. We interpreted the key points of the consensus, mainly involving lifelong care and multidisciplinary clinical management, aiming to promote the standardization of care for individuals with achondroplasia in order to improve their clinical outcomes and quality of life as well as reduce their mortality.

To investigate the effects of different packaging methods for preservation on the quality of Chinese flowering cabbages, kitchen towel (ZJ), common plastic bags (CPE), and modified atmosphere bags (EFB and JG) were used to keep them fresh, with untreated ones as the control (CK). The Chinese flowering cabbages were stored at room temperature (18～23 ℃) or low temperature (4～6 ℃) for 5 days and 25 days, respectively. Then, they were evaluated for commerciality in appearance, rotting rate, etiolation rate, weight loss, and changes in the content of chlorophyll, water, soluble sugar and vitamin C. The results showed that the fresh-keeping effect of modified atmosphere bags (EFB and JG) was better than that of CPE and CK, and ZJ exhibited the worst effect. Compared with other methods, Chinese flowering cabbages packed with EFB and JG showed higher commerciality in appearance and maintain higher nutritional quality. Among them, JG had an even better fresh-keeping effect, with a rotting rate of 0.03%, an etiolation rate of 0.42%, a weight loss of 1.55%, and a minor decrease in chlorophyll content and water content (5.01% and 1.26%, respectively) after 25 days of low temperature storage; on the other hand, when compared with day 1, there was no significant difference in the content of soluble sugar after 15 days of low temperature storage (P>0.05). In addition, the content of vitamin C only decreased by 11.43%, a value significantly lower than that of any other methods (P

Heat treatment effectively inhibits the water absorption recovery of compressed wood. To elucidate this phenomenon, we prepared compressed pine and thermally compressed pine (heartwood and sapwood) using the hot pressing method at 160 °C, 180 °C, 200 °C, and 220 °C. The effects of chemical components, swelling stresses, and monosaccharides on modified wood recovery were investigated using regression analyses. Notably, the recovery of both compressed heartwood and sapwood during water absorption declined from 18.89% to 2.66% and from 58.40% to 1.60%, respectively, after heat treatment. Similarly, the swelling stresses of the compressed heartwood and sapwood at 220 °C, respectively, ranged from 0.693 MPa to 0.275 MPa and from 0.783 MPa to 0.330 MPa. These were close to the values of untreated heartwood (0.175 MPa) and sapwood (0.225 MPa). Regression functions indicated that the recovery of compressed wood is chemically dependent on hemicellulose and mechanically related to swelling stress. For monosaccharides, regression functions indicated that modified heartwood recovery primarily relied on mannose, whereas modified sapwood recovery was remarkably affected by mannose and xylose. This confirmed that the pyrolytic monosaccharides in hemicellulose promoted stress relaxation, which induced the deformation fixation of thermally compressed wood.