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The residual bone tumor and defects which is caused by surgical therapy of bone tumor is a major and important problem in clinicals. And the sequential treatment for irradiating residual tumor and repairing bone defects has wildly prospects. In this study, we developed a general modification strategy by gallic acid (GA)-assisted coordination chemistry to prepare black calcium-based materials, which combines the sequential photothermal therapy of bone tumor and bone defects. The GA modification endows the materials remarkable photothermal properties. Under the near-infrared (NIR) irradiation with different power densities, the black GA-modified bone matrix (GBM) did not merely display an excellent performance in eliminating bone tumor with high temperature, but showed a facile effect of the mild-heat stimulation to accelerate bone regeneration. GBM can efficiently regulate the microenvironments of bone regeneration in a spatial-temporal manner, including inflammation/immune response, vascularization and osteogenic differentiation. Meanwhile, the integrin/PI3K/Akt signaling pathway of bone marrow mesenchymal stem cells (BMSCs) was revealed to be involved in the effect of osteogenesis induced by the mild-heat stimulation. The outcome of this study not only provides a serial of new multifunctional biomaterials, but also demonstrates a general strategy for designing novel blacked calcium-based biomaterials with great potential for clinical use.

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Bone marrow biopsy depends on tissue morphology, immunohistochemical staining, and moleculardetection. Tissue pretreatment is required for bone marrow samples, from clinical specimen acquisition to pathological reporting, but during the process, proteins and nucleic acids are often altered because of the acid in fixation and decalcification solutions. In our study, we present an easy and effective pretreatment protocol and compared this novel pretreatment protocol (Set 2) with an existing traditional pretreatment process (Set 1) using tissue morphology, IHC staining, and molecular pathological analyses. Granulocytic IHC markers showed more intensive staining in samples of Set 2 than in those of Set 1. The Set 2 protocol provided a higher DNA yield and less fragmentation; moreover, samples processed with the Set 2 protocol could be subsequently used in FISH and DNA sequencing assays. Our optimized novel pretreatment protocol could better protect proteins and DNA molecules while maintaining good cell morphology compared to traditional pretreatment The novel pretreatment reagents could role as a reference by more laboratories for pretreating bone marrow biopsy samples and scientific research.

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This study aimed to investigate how varying concentrations (0.01-0.5 %, w/v) and molecular weights (50, 500, 1500 kDa) of hyaluronic acid (HA) affect the physicochemical properties of heat-induced ginkgo seed protein isolate (GSPI)-HA composite gel. Incorporating HA increased viscosity (up to 14 times) and charge (up to 23 %) of GSPI-HA aggregates, while reducing particle size (up to 31 %) and improving gel texture, particularly with high molecular weight HA. However, high concentrations (0.5 %, w/v) of HA weakened gel texture. Non-covalent bonds primarily drive the formation of a continuous gel network between HA and GSPI, resulting in small pores and enhanced hydration properties. With increasing HA molecular weight, non-covalent interactions between GSPI and HA increased, leading to improved gel thermal stability. Overall, the study suggests that manipulating the molecular weight and concentration of HA can enhance the gelling properties of GSPI, leading to the development of a diverse array of GSPI-HA composite gels with varied properties.

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Skull defect repair is a complex and critical medical challenge, and there is an urgent need to develop multifunctional tissue engineering scaffolds for skull regeneration. The success of bone tissue engineering depends on the construction of scaffolds that can regulate the immune microenvironment of bone regeneration and mimic the liquid crystal and viscoelastic properties of natural bone extracellular matrix. Hence, a smart hydrogel (PEGDA5/AM15/CLC-BMP-4@MBG) with good biocompatibility and the ability to modulate the wound immune microenvironment has been developed for the repair of skull defects. The hydrogel consists of chitin liquid crystal hydrogel (PEGDA5/AM15/CLC) and mesoporous bioactive glasses (MBGs) loaded with bone morphogenetic protein-4 (BMP-4). The liquid crystal hydrogel not only offers the necessary biological support and mechanical properties but also maintains the stability of the liquid crystal state, facilitating adhesion and regeneration of surrounding bone tissue. In addition, BMP-4@MBG intelligently regulates the release rate of BMP-4 in response to changes in wound microenvironment, thus effectively promoting the transformation of macrophages from M1 to M2 macrophages. At the same time, Ca2+ and Si4+ released by MBG degradation and BMP-4 synergically promote bone repair process. The PEGDA5/AM15/CLC-BMP-4@MBG hydrogel shows excellent immunomodulatory and osteogenic properties of bone microenvironment and is a promising scaffold material for bone tissue engineering.

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BACKGROUND: Construction of meat analogs based on pea protein isolate (PPI) alone by high moisture extrusion (HME) is diffocult as a result of the lack of anisotropic structures. In the present study, 0%-15% of whey protein (WP) was introduced to PPI to make hybrid blends, which were used to construct HME extrudates. RESULTS: WP enhanced the hardness, adhesive, cohesiveness and gumminess of the extrudates and facilitated the formation of a distinct anisotropic structure of PPI. The fibrous degrees of the extrudates containing 10% and 15% WP were around 1.50. The addition of WP, which has more -SH groups, increased the disulfide bonds and hydrogen bonding in the extrudates, leading to a denser cross-linked structure. Particle size distribution and Fourier transform infrared analysis showed that WP induced more compact structured aggregates and more ß-sheet structures in the extrudates. Furthermore, the higher hydration capacity of WP may also help form a dilute melt and generate a more pronounced plug flow, assisting the formation of fiber structures of PPI. CONCLUSION: The present study demonstrates that WP is a potential modifier, which could be used to improve the structure of PPI-based meat analogs. © 2024 Society of Chemical Industry.

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PURPOSE: To investigate whether personalized embryo transfer (pET) predicted by a modified RNA-sequencing-based endometrial receptivity test (rsERT) model can improve intrauterine pregnancy rate (IPR) in patients with a receptive window of implantation (WOI). DESIGN: A retrospective pilot study was conducted in the Center for Reproductive Medicine, Central South University, from January 2018 to December 2023. A total of 524 patients with receptive WOI results from rsERT were assigned into two groups based on whether they underwent conventional embryo transfer (conventional ET) or pET. Patients in the conventional ET were matched with those in the pET group at a 1:1 ratio using propensity score matching (PSM). RESULTS: Before PSM, the IPR (55.73% vs. 46.19%, P = 0.032) and implantation rate (IR) (47.51% vs. 34.03%, P = 0.000) in the pET group were significantly higher than that in the conventional ET group. However, the number and types of transferred embryos differed significantly between the two groups. After adjusting for confounding factors, IPR (57.38% vs. 44.81, P = 0.016) and IR (46.81% vs. 33.10%, P = 0.001) remained significantly higher in the pET group compared to the conventional ET group. The implantation failure rate was significantly lower in the pET group compared to controls (42.62% vs. 55.19%, P = 0.016). Additionally, the multiple-pregnancy rate was significantly higher in the pET group compared to the conventional ET group (10.29% vs. 1.68%, P = 0.001). CONCLUSIONS: Women with receptive WOI results could benefit from the receptivity-timed pET predicted by the newly refined rsERT. These findings provide a basis for future research in precision medicine for embryo transfer.

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While forward osmosis (FO) and reverse osmosis (RO) processes have been proven effective in rejecting organic pollutants, the rejection rate is highly dependent on compound and membrane characteristics, as well as operating conditions. This study aims to establish machine learning (ML) models for predicting the rejection of organic pollutants by FO and RO and providing insights into the underlying rejection mechanisms. Among the 14 ML models established, the random forest model (R2 = 0.85) and extreme gradient boosting model (R2 = 0.92) emerged as the best-performing models for FO and RO, respectively. Shapley additive explanations (SHAP) analysis identified the length of the compound, water flux, and hydrophobicity as the top three variables contributing to the FO model. For RO, in addition to the length of the compound and operating pressure, advanced variables including four molecular descriptors (e.g., ATSC2m and Balaban J) and three fingerprints (e.g., C=C double bond and carbonyl group) significantly contributed to the prediction. Besides, the associations between these highly ranked variables and their SHAP values shed light on the rejection mechanisms, such as size exclusion, adsorption, hydrophobic interaction, and electrostatic interaction, and illustrate the role of the operating parameters, such as the FO permeate water flux and RO operating pressure, in the rejection process. These findings provide interpretable predictive models for the removal of organic pollutants and advance the mechanistic understanding of the rejection mechanisms in the FO and RO processes.

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The G-quadruplex (GQ) formed by guanine-rich DNA strands exhibits superior thermal stability and electric properties, which have generated substantial interest in applying GQ DNA to bioelectric interfaces. However, single G-wires formed by GQs have not yet surpassed the µm length due to the lack of an optimal assembly protocol and understanding of assembly mechanisms that limit application. Herein, we optimized a self-assembly protocol for a short 4-nt oligonucleotide (dG4) to achieve micrometer lengths of G-wires, including the buffer composition, incubation process and surface assembly. Furthermore, both theoretical modeling and chemical modifications were applied to unveil the atomic-level detail of GQ monomer interfaces and indicated that the assembly process follows a stepwise mechanism from nucleation to grow into oligomers and nanowires.

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Humans can be exposed to multiple pollutants in the air and surface water. These environments are non-static, trans-boundary and correlated, creating a complex network, and significant challenges for research on environmental hazards, especially in real-world cancer research. This article reports on a large study (377 million people in 30 provinces of China) that evaluated the combined impact of air and surface water pollution on cancer. We formulate a spatial evaluation system and a common grading scale for co-pollution measurement, and validate assumptions that air and surface water environments are spatially connected and that cancers of different types tend to cluster in areas where these environments are poorer. We observe "dose-response" relationships in both the number of affected cancer types and the cancer incidence with an increase in degree of co-pollution. We estimate that 62,847 (7.4%) new cases of cancer registered in China in 2016 were attributable to air and surface water pollution, and the majority (69.7%) of these excess cases occurred in areas with the highest level of co-pollution. The findings clearly show that the environment cannot be considered as a set of separate entities. They also support the development of policies for cooperative environmental governance and disease prevention.

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Brain-computer interface (BCI) based on steady-state visual evoked potential (SSVEP) have attracted much attention in the field of intelligent robotics. Traditional SSVEP-based BCI systems mostly use synchronized triggers without identifying whether the user is in the control or non-control state, resulting in a system that lacks autonomous control capability. Therefore, this paper proposed a SSVEP asynchronous state recognition method, which constructs an asynchronous state recognition model by fusing multiple time-frequency domain features of electroencephalographic (EEG) signals and combining with a linear discriminant analysis (LDA) to improve the accuracy of SSVEP asynchronous state recognition. Furthermore, addressing the control needs of disabled individuals in multitasking scenarios, a brain-machine fusion system based on SSVEP-BCI asynchronous cooperative control was developed. This system enabled the collaborative control of wearable manipulator and robotic arm, where the robotic arm acts as a "third hand", offering significant advantages in complex environments. The experimental results showed that using the SSVEP asynchronous control algorithm and brain-computer fusion system proposed in this paper could assist users to complete multitasking cooperative operations. The average accuracy of user intent recognition in online control experiments was 93.0%, which provides a theoretical and practical basis for the practical application of the asynchronous SSVEP-BCI system.

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Reperfusion injury represents a significant impediment to recovery after recanalization in an ischemic stroke and can be alleviated by neuroprotectants. However, inadequate drug delivery to ischemic lesions impairs the therapeutic effects of neuroprotectants. To address this issue, an ischemic microenvironment-targeted bioinspired lipoprotein system encapsulating lipoic acid (LA@PHDL) is herein designed to sequentially penetrate ischemic lesions and be readily taken up by neurons and microglia. In transient middle cerebral artery occlusion (tMCAO) mouse models, LA@PHDL accumulates rapidly and preferentially in the ischemic brain, with a 2.29-fold higher than the nontargeted nanoplatform in the early stage. Furthermore, LA@PHDL effectively restores neurological function, reduces infarct volume to 17.70%, prevents brain cell necrosis and apoptosis, and attenuates inflammation in tMCAO mouse models. This design presents new opportunities for delivering neuroprotectants to cerebral ischemic lesions to improve the outcome of an ischemic stroke.

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Objective: Up to now there is a lack of research to summarize the relevant evidence for radiation dermatitis (RD) management in patients with breast cancer. Therefore, this study aimed to summarize the best evidence for the prevention and management of RD in patients with breast cancer. Methods: According to the "6S" evidence pyramid model, all major databases were searched from January 2018 to February 2024: UpToDate, BMJ Best Practice, National Guideline Clearinghouse, Guidelines International Network, MedSci, Yi Maitong Guidelines, National Comprehensive Cancer Network, Oncology Nursing Society, Radiology Assistant database, Society and College of Radiographers, Australian JBI Evidence-Based Health Care Center database, Cochrane Library, PubMed, CINAHL, Embase, Web of Science, China National Knowledge Infrastructure, Wangfang Data, Chinese Science and Technology Journal Database, Chinese Biology Medicine, etc. Results: A total of 22 articles which met the inclusion criteria were included in the study, comprising six guidelines, nine systematic reviews, four evidence summaries, one clinical decision, one expert consensus, and one randomized controlled trial. We summarized 35 pieces of evidence across four aspects: influence factor, evaluation and monitoring, prevention and treatment, care and health education. Conclusions: This study provides a comprehensive summary of the best evidence for the prevention and management of RD in patients with breast cancer. It is recommended that subsequent evidence transformation should be conducted based on specific clinical circumstances to standardize the process of clinical prevention and management of RD. Systematic review registration: This study was registered at the Fudan University Center for Evidence-Based Nursing (Registration No. ES20244311).

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OBJECTIVE: To assess the efficacy and safety of combining Programmed Death-1/Programmed Death-Ligand 1 (PD-1/L1) inhibitors with platinum-containing chemotherapy for treating late-stage Non-Small Cell Lung Cancer (NSCLC) patients who have developed resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs). METHODS: A retrospective analysis was conducted at Baoji Traditional Chinese Medicine Hospital involving 133 patients with advanced NSCLC who had shown resistance to EGFR-TKIs and were treated from October 2018 to May 2021. The cohort was categorized into two groups: one treated with immune checkpoint inhibitors (ICIs) plus chemotherapy and antiangiogenic agents (ICIs+BCP group), and the other treated with ICIs alone (ICIs group). Baseline data collected included demographic factors, smoking status, PD-L1 Tumor Proportion Score (TPS), EGFR mutation, Eastern Cooperative Oncology Group (ECOG) score, and routine blood markers prior to second-line therapy. Computed Tomography (CT) scans were performed every two treatment courses to evaluate the treatment efficacy. RESULTS: The ICIs+BCP group exhibited a statistically significant improvement in Overall Survival (OS) compared to the ICIs group (P=0.001). Cox survival analysis uncovered age (P=0.012), PD-L1 TPS expression (P<0.001), treatment regimen (P=0.006), Neutrophil-to-Lymphocyte Ratio (NLR) (P=0.024), and Platelet-to-Lymphocyte Ratio (PLR) (P=0.005) as independent factors influencing OS in patients with advanced NSCLC resistant to primary-line EGFR-TKI therapy. The nomogram model, based on these prognostic factors, exhibited Area Under the Curve (AUC) values of 0.823 and 0.769, indicating its predictive accuracy for 1-year and 2-year survival, respectively. CONCLUSION: Combining ICIs with BCP prolongs OS in patients with NSCLC resistant to EGFR-TKIs. This study underscores the importance of personalized treatment plans and biomarker evaluations to improve outcomes in drug-resistant cases.

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In this study, we combined two distinct extraction and separation techniques with the aim of comprehensively collecting metabolite features in sprouts, particularly hydrophilic compounds. By synergistically analyzing the data using MS-DIAL and MetaboAnalystR, we obtained a greater number of annotated metabolites and explored differences in annotation across analytical tools. We found that this approach significantly increased the number of detected metabolite features and the final identification counts. Furthermore, we explored the functional component characteristics of four sprout types. This study provides data supporting the potential of sprouts as nutritious vegetables and functional food ingredients, emphasizing their value in the development of functional foods.

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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.

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In this study, hydrolysates were obtained from salmon milts using four proteases (neutrase, papain, trypsin and novozym 11028). The effects of protease type and enzymolysis time (30, 60, 90, and 120 min) on the structural characteristics and functional properties of the hydrolysates were assessed. The fluorescence intensity of all hydrolysates increased as the extension of enzymolysis time, accompanied by an increase in solubility, emulsifying and foaming ability. Trypsin-hydrolysates showed the highest protein recovery and degree of hydrolysis (DH). The electrophoresis indicated that papain-hydrolysates contained more aggregates (>60 kDa), which was confirmed by larger particle size and lower DH. Neutrase-hydrolysate exhibited the smallest particle size and the highest emulsifying and foaming ability, while the highest emulsifying stability appeared in papain-hydrolysates. Neutrase-hydrolysate displayed the strongest antioxidant potential while papain-hydrolysate possessed the weakest. Results demonstrated that the salmon milt protein hydrolysates can be utilized as nutraceutical and functional food ingredients.

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Two sulfur-containing heterodimers of a cytochalasan and a macrolide, sucurchalasins A and B (1 and 2), and four known cytochalasan monomers (3-6), as well as four known macrolide derivatives (7-10), were obtained from the endophytic fungus Aspergillus spelaeus GDGJ-286. Sucurchalasins A and B (1 and 2) are the first cytochalasan heterodimers formed via a thioether bridge between cytochalasan and curvularin macrolide units. Their structures were elucidated by detailed analysis of NMR, LC-MS/MS, and X-ray crystallography. In bioassays, 1 and 2 exhibited cytotoxic effects on A2780 cells, with IC50 values of 3.9 and 8.3 µM, respectively. They also showed antibacterial activities against E. faecalis and B. subtilis with MIC values of 3.1 and 6.3 µg/mL, respectively.

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Background: Immunotherapy has become the standard treatment for driving gene-negative advanced non-small cell lung cancer (NSCLC). However, compared to PD-L1-positive patients, the efficacy of Anti-PD-(L)1 monotherapy is suboptimal in PD-L1-negative advanced NSCLC. In this study, we aim to analyze the optimal immunotherapy approach for PD-L1-negative NSCLC patients and develop a new nomogram to enhance the clinical predictability of immunotherapy for NSCLC patients. Methods: In this study, we retrieved clinical information and genomic data from cBioPortal for NSCLC patients undergoing immunotherapy. Cox regression analyses were utilized to screen the clinical information and genomic data that related to survival. The prognostic-relate genes function was studied by comprehensive bioinformatics analyses. The Kaplan-Meier plot method was employed for survival analysis. Results: A total of 199 PD-L1-negative NSCLC patients were included in this study. Among them, 165 patients received Anti-PD-(L)1 monotherapy, while 34 patients received Anti-PD-(L)1+Anti-CTLA-4 combination therapy. The Anti-PD-(L)1+Anti-CTLA-4 combination therapy demonstrated significantly higher PFS compared to the Anti-PD-(L)1 monotherapy. The mutation status of KRAS, ANO1, COL14A1, LTBP1. ERBB4 and PCSK5 were found to correlate with PFS. Utilizing the clinicopathological parameters and genomic data of the patients, a novel nomogram was developed to predict the prognosis of Anti-PD-(L)1+Anti-CTLA-4 combination therapy. Conclusion: Our study revealed that KRAS, ANO1, COL14A1, LTBP1. ERBB4 and PCSK5 mutation could serve as predictive biomarkers for patients with Anti-PD-(L)1+Anti-CTLA-4 combination therapy. Our systematic nomogram demonstrates significant potential in predicting the prognosis for NSCLC patients with responsive to dual PD-1/CTLA-4 blockade.

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Hypoxic-ischemic encephalopathy (HIE) poses a significant challenge in neonatal medicine, often resulting in profound and lasting neurological deficits. Current therapeutic strategies for hypoxia-ischemia brain damage (HIBD) remain limited. Ferroptosis has been reported to play a crucial role in HIE and serves as a potential therapeutic target. However, the mechanisms underlying ferroptosis in HIBD remain largely unclear. In this study, we found that elevated lysyl oxidase (LOX) expression correlates closely with the severity of HIE, suggesting LOX as a potential biomarker for HIE. LOX expression levels and enzymatic activity were significantly increased in HI-induced neuronal models both in vitro and in vivo. Notably, we discovered that HI-induced brain tissue injury results in increased stiffness and observed a selective upregulation of the mechanosensitive ion channel Piezo1 in both brain tissue of HIBD and primary cortex neurons. Mechanistically, LOX increases its catalytic substrates, the Collagen I/III components, promoting extracellular matrix (ECM) remodeling and possibly mediating ECM cross-linking, which leads to increased stiffness at the site of injury and subsequent activation of the Piezo1 channel. Piezo1 senses these stiffness stimuli and then induces neuronal ferroptosis in a GPX4-dependent manner. Pharmacological inhibition of LOX or Piezo1 ameliorated brain neuronal ferroptosis and improved learning and memory impairments. Furthermore, we identified traumatic acid (TA) as a novel LOX inhibitor that effectively suppresses LOX enzymatic activity, mitigating neuronal ferroptosis and promoting synaptic plasticity. In conclusion, our findings elucidate a critical role for LOX-mediated ECM mechanical stress-induced Piezo1 activation in regulating ferroptotic cell death in HIBD. This mechanistic insight provides a basis for developing targeted therapies aimed at ameliorating neurological outcomes in neonates affected by HIBD.

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BACKGROUND: Plastic bronchitis (PB) is an uncommon and severe acute respiratory ailment characterized by the formation of casts in the trachea or bronchial tree. Some instances have been linked to human bocavirus (HBoV) infections. CASE PRESENTATION: In this report, we present a case of PB secondary to HBoV1 infection in a previously healthy pediatric patient. A 17-month-old male was admitted due to respiratory distress following 2 days of cough and fever. A preadmission chest X-ray revealed atelectasis of the left lung. Emergency electronic bronchoscopy and foreign body forceps were employed to remove casts, leading to improved breathing. High-throughput next-generation sequencing detected only HBoV1. A subsequent electronic bronchoscopy 2 days later showed no casts. CONCLUSIONS: PB associated with HBoV1 infection should be considered in children experiencing acute respiratory distress, and a second bronchoscopy intervention may not be necessary in cases related to HBoV1.

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