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Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.

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PURPOSE: To evaluate the diagnostic accuracy of machine learning (ML) in detecting vertebral fractures, considering varying fracture classifications, patient populations, and imaging approaches. METHOD: A systematic review and meta-analysis were conducted by searching PubMed, Embase, Cochrane Library, and Web of Science up to December 31, 2023, for studies using ML for vertebral fracture diagnosis. Bias risk was assessed using QUADAS-2. A bivariate mixed-effects model was used for the meta-analysis. Meta-analyses were performed according to five task types (vertebral fractures, osteoporotic vertebral fractures, differentiation of benign and malignant vertebral fractures, differentiation of acute and chronic vertebral fractures, and prediction of vertebral fractures). Subgroup analyses were conducted by different ML models (including ML and DL) and modeling methods (including CT, X-ray, MRI, and clinical features). RESULTS: Eighty-one studies were included. ML demonstrated a diagnostic sensitivity of 0.91 and specificity of 0.95 for vertebral fractures. Subgroup analysis showed that DL (SROC 0.98) and CT (SROC 0.98) performed best overall. For osteoporotic fractures, ML showed a sensitivity of 0.93 and specificity of 0.96, with DL (SROC 0.99) and X-ray (SROC 0.99) performing better. For differentiating benign from malignant fractures, ML achieved a sensitivity of 0.92 and specificity of 0.93, with DL (SROC 0.96) and MRI (SROC 0.97) performing best. For differentiating acute from chronic vertebral fractures, ML showed a sensitivity of 0.92 and specificity of 0.93, with ML (SROC 0.96) and CT (SROC 0.97) performing best. For predicting vertebral fractures, ML had a sensitivity of 0.76 and specificity of 0.87, with ML (SROC 0.80) and clinical features (SROC 0.86) performing better. CONCLUSIONS: ML, especially DL models applied to CT, MRI, and X-ray, shows high diagnostic accuracy for vertebral fractures. ML also effectively predicts osteoporotic vertebral fractures, aiding in tailored prevention strategies. Further research and validation are required to confirm ML's clinical efficacy.

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BACKGROUND: Inflammatory bowel disease (IBD) is a chronic and relapsing disease marked by chronic tissue inflammation that alters the integrity and function of the gut, seriously impacting patient health and quality of life. Aucklandiae Radix (AR), known as Mu Xiang in Chinese, is a traditional Chinese medicine documented in Chinese Pharmacopoeia with effects of strengthening the intestine and stopping diarrhea. However, the potential of AR in treating intestinal inflammation and its underlying mechanism have yet to be further elucidated. PURPOSE: The objective of this study was to explore the protective effect and the potential mechanism attributable to AR for treating ulcerative colitis (UC). STUDY DESIGN AND METHODS: A murine model of UC was constructed using dextran sulfate sodium (DSS) to examine the therapeutic potential of AR in alleviating inflammation and modulating the immune response. Advanced techniques such as photocrosslinking target fishing technique, click chemistry, Western blot analysis, real-time quantitative PCR, flow cytometry, immunofluorescence, and immunohistochemistry were employed to unveil the therapeutic mechanism of AR for treating IBD. RESULTS: AR decreased disease activity index (DAI) score to alleviate the course of IBD through ameliorating intestinal barrier function in DSS-induced mice. Furthermore, AR suppressed NF-κB and NLRP3 pathways to reduce the release of pro-inflammatory factors interleukin-6 and 1ß (IL-6 and IL-1ß) and tumor necrosis factor α (TNF-α), allowing to alleviate the inflammatory response. Flow cytometry revealed that AR could reduce the accumulation of intestinal macrophages and neutrophils, maintaining intestinal immune balance by regulating the ratio of Treg to Th17 cells. It was worth noting that pyruvate kinase isozyme type M2 (PKM2) served as a potential target of AR using the photocrosslinking target fishing technology, which was further supported by cellular thermal shift assay (CETSA), drug affinity target stability (DARTS), and PKM2 knockdown experiments. CONCLUSION: AR targeted PKM2 to inhibit NF-κB and NLRP3 pathways, thereby modulating the inflammatory response and immunity to alleviate DSS-induced UC. These findings suggested the potential of AR in the treatment of UC and AR as a candidate for developing PKM2 regulators.

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Currently, developing nonantibiotic growth promoters is a broad consensus in broiler industry, which is one of the effective ways to reduce drug-resistant strains. Chuanminshen violaceum is a traditional Chinese medicinal herb that is commonly used for its roots, while the stems and leaves are often discarded, resulting in a huge amount of waste. This study optimized the preparation process of water extract of Chuanminshen violaceum stems and leaves (CVSLE) by response surface analysis based on the yields of polysaccharide and protein. The CVSLE and herbal powder (CVSL) were then processed into granules before being used as feed additives. The Macleaya cordata powder was used as positive control. The results showed that the addition of CVSLE (0.5% of the feed) showed the highest growth-promoting activity than other CVSLE groups (0.2% and 1%), 1% CVSL group and positive control (0.05%). CVSLE at the dosage of 0.5% could significantly increase the ADG and reduce the FCR from d 21 to 42, d 0 to 42. The HI antibody titers against Newcastle disease virus and avian influenza virus were significantly enhanced at 21, 28 and 42 d. CVSLE did not affect the slaughtering performances, but could significantly elevate the spleen, thymus and bursa of Fabricius indices and the transcriptional levels of IL-2, IL-4, IL-10 and IFN-γ in spleen. The intestinal barrier function of broilers was significantly enhanced by increased levels of immune barrier (sIgA), physical barrier (ZO-1, OCL and Muc-2) and flora barrier (Lactobacillus and Bifidobacterium). These results suggest that CVSLE was a promising herbal additive candidate for broilers.

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Statins are well-tolerated and widely available lipid-lowering medications with neuroprotective effects against traumatic brain injury (TBI). However, whether delayed statin therapy starting in the subacute phase promotes recovery after TBI is unknown. Elongation of the very long-chain fatty acid protein 1 (ELOVL1) is involved in astrocyte-mediated neurotoxicity, but its role in TBI and the relationship between ELOVL1 and statins are unclear. We hypothesized that delayed simvastatin treatment promotes neurological functional recovery after TBI by regulating the ELOVL1-mediated production of very long-chain fatty acids (VLCFAs). ICR male mice received daily intragastric administration of 1, 2 or 5mg/kg simvastatin on Days 1-14, 3-14, 5-14, or 7-14 after cryogenic TBI (cTBI). The results showed that simvastatin promoted motor functional recovery in a dose-dependent manner, with a wide therapeutic window of at least 7 days postinjury. Meanwhile, simvastatin inhibited astrocyte and microglial overactivation and glial scar formation, and increased total dendritic length, neuronal complexity and spine density on day 14 after cTBI. The up-regulation of ELOVL1 expression and saturated VLCFAs concentrations in the cortex surrounding the lesion caused by cTBI was inhibited by simvastatin, which was related to the inhibition of the mTOR signaling. Overexpression of ELOVL1 in astrocytes surrounding the lesion using HBAAV2/9-GFAP-m-ELOVL1-3xFlag-EGFP partially attenuated the benefits of simvastatin. These results showed that delayed simvastatin treatment promoted functional recovery and brain tissue repair after TBI through the downregulation of ELOVL1 expression by inhibiting mTOR signaling. Astrocytic ELOVL1 may be a potential target for rehabilitation after TBI.

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

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Exosomes are small membrane vesicles that are released by cells into the extracellular environment. Tumor-associated exosomes (TAEs) are extracellular vesicles that play a significant role in cancer progression by mediating intercellular communication and contributing to various hallmarks of cancer. These vesicles carry a cargo of proteins, lipids, nucleic acids, and other biomolecules that can be transferred to recipient cells, modifying their behavior and promoting tumor growth, angiogenesis, immune modulation, and drug resistance. Several potential therapeutic targets within the TAEs cargo have been identified, including oncogenic proteins, miRNAs, tumor-associated antigens, immune checkpoint proteins, drug resistance proteins, and tissue factor. In this review, we will systematically summarize the biogenesis, composition, and function of TAEs in cancer progression and highlight potential therapeutic targets. Considering the complexity of exosome-mediated signaling and the pleiotropic effects of exosome cargoes has challenge in developing effective therapeutic strategies. Further research is needed to fully understand the role of TAEs in cancer and to develop effective therapies that target them. In particular, the development of strategies to block TAEs release, target TAEs cargo, inhibit TAEs uptake, and modulate TAEs content could provide novel approaches to cancer treatment.

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CONTEXT: All types of caloric restriction are preventive against cardiovascular risk factors, but the best restriction method and most affected factors have not been identified. OBJECTIVE: The objective of this study was to explore the effects of different caloric restriction methods on various cardiovascular risk factors by horizontally comparing program advantages and disadvantages via network meta-analysis. DATA SOURCES: The PubMed, Web of Science, Cochrane Library, and Embase literature databases were searched (October 2013 to October 2023). DATA EXTRACTION: Eligible randomized controlled trials involving participants who underwent caloric restriction and systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and high-density lipoprotein (HDL) cholesterol level measurements were included. DATA ANALYSIS: Thirty-six of 13 208 records (0.27%) were included. Two researchers reviewed the articles, extracted data, and assessed article quality. RESULTS: Alternate-day fasting (ADF) reduced SBP (4.88 mmHg; CI, 2.06-7.15) and DBP (5.10 mmHg; CI, 2.44-7.76). Time-restricted eating reduced SBP (2.46 mmHg; CI, 0.16-4.76) but not DBP. Continuous energy restriction (CER) significantly reduced BMI (1.11 kg/m2; CI = 0.16, 2.06) and waist circumference (3.28 cm; CI, 0.62-5.94). CONCLUSIONS: This meta-analysis confirmed the preventive effect of CER and ADF on various cardiovascular risk factors. Additionally, CER is more likely to reduce obesity, and ADF is more likely to reduce blood pressure (BP). Based on this meta-analysis, CER is recommended to control obesity only for people who are obese and do not have elevated BP or other abnormal indicators. Additionally, ADF for early control or prevention is recommended for patients who have abnormal BP or other cardiovascular risk factors. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023455889.

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A molten-salt-induced structural heterogeneity strategy was developed to construct molecular heterostructured carbon nitride with intimately connected heptazine and triazine units, which effectively accelerate charge transport and suppress carrier recombination. Consequently, the prepared CN-2 exhibits significantly enhanced photocatalytic H2O2 production, about 143 times that of traditional carbon nitride.

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Improving the efficiency of tin-based perovskite solar cells (TPSCs) is significantly hindered by energy level mismatch and weak interactions at the interface between the tin-based perovskite and fullerene-based electron transport layers (ETLs). In this study, four well-defined multidentate fullerene molecules with 3, 4, 5, and 6 diethylmalonate groups, labeled as FM3, FM4, FM5, and FM6 are synthesized, and employed as interfacial layers in TPSCs. It is observed that increasing the number of functional groups in these fullerenes leads to shallower lowest unoccupied molecular orbital (LUMO) energy levels and enhance interfacial chemical interactions. Notably, FM5 exhibits a suitable energy level and robust interaction with the perovskite, effectively enhancing electron extraction and defect passivation. Additionally, the unique molecular structure of FM5 allows the exposed carbon cage to be tightly stacked with the upper fullerene cage after interaction with the perovskite, facilitating efficient charge transfer and protecting the perovskite from moisture and oxygen damage. As a result, the FM5-based device achieves a champion efficiency of 15.05%, significantly surpassing that of the PCBM-based (11.77%), FM3-based (13.54%), FM4-based (14.34%), and FM6-based (13.75%) devices. Moreover, the FM5-based unencapsulated device exhibits excellent stability, maintaining over 90% of its initial efficiency even after 300 h of air exposure.

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Effectively controlling the selective conversion of CO2 photoreduction to C2 products presents a significant challenge. Here, we develop a heterojunction photocatalyst by controllably implanting Au nanoparticles and single atoms into unsaturated Mo atoms of edge-rich MoS2, denoted as Aun/Au1-CMS. Photoreduction of CO2 results in the production of CH3COOH with a selectivity of 86.4%, which represents a 6.4-fold increase compared to samples lacking single atoms, and the overall selectivity for C2 products is 95.1%. Furthermore, the yield of CH3COOH is 22.4 times higher compared to samples containing single atoms and without nanoparticles. Optical experiments demonstrate that the single atoms domains can effectively capture photoexcited electrons by the Au nanoparticles, or the local electric field generated by the nanoparticles promotes the transfer of photogenerated electrons in MoS2 to Au single atoms, prolonging the relaxation time of photogenerated electrons. Mechanistic investigations reveal that the orbital coupling of Au5d and Mo4d strengthens the oxygen affinity of Mo and carbon affinity of Au. The hybridized orbitals reduce energy splitting levels of CO molecular orbitals, aiding C-C coupling. Moreover, the Mo-Au dual-site stabilize the crucial oxygen-associated intermediate *CH2CO, thereby enhancing the selectivity towards CH3COOH. The cross-scale heterojunctions provide an effective strategy to simultaneously address the kinetical and thermodynamical limitations of CO2-to-CH3COOH conversion.

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Arsenic is a toxic metal-like element widely used in the pesticide, preservative and semiconductor industries. However, accumulation of arsenic through the food chain can cause serious damage to animal and human health. However, the toxic mechanism of arsenic-induced hepatotoxicity in chickens is not clear, and the present study aimed to investigate the potential role of cGAS-STING and NF-κB pathways on inflammatory injury in chicken liver. In this study, 75 white-feathered broilers were divided into a control group, a low-dose arsenic group (4 mg/kg) and a high-dose arsenic group (8 mg/kg) to investigate the toxic effects of arsenic on chicken liver. In this study, we found that pathological changes such as inflammatory cell infiltration and vesicular degeneration occurred in the liver when exposed to ATO. Crucially, exposure to ATO triggered the cGAS-STING pathway and markedly raised the levels of mRNA and protein expression of cGAS, STING, TBK1, and IRF7. The type I interferon response was also triggered. Simultaneously, STING induced the activation of the conventional NF-κB signaling pathway and stimulated the expression of genes associated with inflammation, such as IL-6, TNF-α and IL-1ß. In summary, the induction of inflammatory responses via cGAS-STING and NF-κB signaling pathways under high ATO exposure provides new ideas for further studies on the toxicological mechanisms of arsenic.

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The emergence of lysosome-targeting chimeras (LYTACs), which represents a promising strategy for membrane protein degradation based on lysosomal pathways, has attracted much attention in disease intervention and treatment. However, the expression level of commonly used lysosome-targeting receptors (LTRs) varies in different cell lines, thus limiting the broad applications of LYTACs. To overcome this difficulty, we herein report the development of integrin α3ß1 (ITGA3B1)-facilitated bispecific aptamer chimeras (ITGBACs) as a platform for the degradation of membrane proteins. ITGBACs consist of two aptamers, one targeting ITGA3B1 and another binding to the membrane-associated protein of interest (POI), effectively transporting the POI into lysosomes for degradation. Our findings demonstrate that ITGBACs effectively eliminate pathological membrane proteins, such as CD71 and PTK7, inducing significant cell-cycle arrest and apoptosis and markedly inhibiting tumor growth in tumor-bearing mice models. Therefore, this work provides a novel and versatile membrane protein degradation platform, offering a promising targeted therapy based on tumor-specific LTRs.

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OBJECTIVE: The aim of this study was to develop a cone beam computed tomography (CBCT) radiomics-based model that differentiates between conventional and unicystic ameloblastoma (AB). METHODS: In this retrospective study, CBCT images were collected from 100 patients who had ABs that were diagnosed histopathologically as conventional or unicystic AB after surgical treatment. The patients were randomly divided into training (70) and validation (30) cohorts. Radiomics features were extracted from the images, and the optimal features were incorporated into 5 models: Logistic Regression, Support Vector Machine, Linear Discriminant Analysis, Random Forest, and XGBoost for prediction of tumor type. Model performance was evaluated using the area under the curve (AUC) from receiver operating characteristic analysis, sensitivity, specificity, accuracy, calibration curves, and decision curve analysis (DCA). RESULTS: The 20 optimal radiomics features were incorporated into the Logistic Regression (LR) model, which exhibited the best overall performance with AUC = 0.936 (95% confidence interval [CI] = 0.877-0.996) for the training cohort and AUC = 0.929 (95% CI = 0.832-1.000) for the validation cohort. The nomogram combined the clinical features and the radiomics signature and resulted in the best predictive performance. CONCLUSIONS: The LR model demonstrated the ability of radiomics and the nomogram to distinguish between the 2 types of AB and may have the potential to replace biopsies under noninvasive conditions.

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On December 15, 2023, the FDA granted traditional approval to enfortumab vedotin-ejfv plus pembrolizumab (EV + Pembro) for patients with locally advanced or metastatic urothelial carcinoma (la/mUC). Substantial evidence of effectiveness was obtained from EV-302/KEYNOTE-A39 (NCT04223856), an open-label, randomized, trial evaluating EV + Pembro versus cisplatin or carboplatin plus gemcitabine (Plat + Gem) in patients with previously untreated la/mUC. A total of 886 patients were randomized (1:1) to receive EV 1.25 mg/kg intravenously on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity plus pembrolizumab 200 mg intravenously on day 1 of each 21-day cycle for up to 35 cycles, or Plat + Gem for up to 6 cycles. Dual primary endpoints were progression-free survival (PFS) determined by blinded independent central review and overall survival (OS). Median PFS was 12.5 months (95% CI: 10.4, 16.6) in the EV + Pembro arm and 6.3 months (95% CI: 6.2, 6.5) in the Plat + Gem arm (HR 0.450 [95% CI: 0.377, 0.538]; p-value < 0.0001). Median OS was 31.5 months (95% CI: 25.4, NE) in the EV + Pembro arm and 16.1 months (95% CI: 13.9, 18.3) in the Plat + Gem arm (HR 0.468 [95% CI: 0.376, 0.582]; p-value < 0.0001). The safety profile of EV + pembrolizumab was similar to that observed in EV-103/KEYNOTE-869 in cisplatin-ineligible patients with la/mUC. This article summarizes the data and the FDA thought process supporting traditional approval of EV + pembrolizumab, as well as additional exploratory analyses conducted by FDA.

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Objective: The effects of Pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) in primiparas remain unclear. This study examines the associations of pre-pregnancy BMI and GWG with cesarean delivery after induction (CDaI) in primiparous women. Methods: This prospective cohort study included 3,054 primiparous women. We recorded pre-pregnancy BMI, first, second, and third trimester weight values, as well as instances of CDaI and other pregnancy outcomes. We analyzed the associations of pre-pregnancy BMI and GWG with CDaI by conducting a multivariate logistic regression analysis after adjusting for covariates, and adjusted risk ratios (aRR) and 95% confidence intervals were reported. Results: We recorded 969 CDaIs. In the vaginal delivery group, each increase of 1 standard deviation in the pre-pregnancy BMI was correlated with a 6% increase in the CDaI risk [aRR (95% CI), 1.06 (1.01-1.11)]. Each increase of 1 standard deviation in the rate of weight gain during the entire pregnancy was correlated with a 21% increase in the CDaI risk [aRR (95% CI), 1.21 (1.14-1.29)]. Compared to women with a normal weekly GWG in the second and third trimester, those with slow GWG had a 19% increased risk of CDaI [aRR (95% CI), 1.19 (1.01-1.37)]. The subgroup analysis results showed that increases in pre-pregnancy BMI could increase the CDaI risk regardless of the induction method. Conclusion: High pre-pregnancy BMI, excessive GWG, and rapid first trimester weight gain are risk factors for CDaI in primiparous women. Excessive first trimester weight gain, may associated with increased risks of CDaI in primiparous women.

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Mining is a major threat to vegetation and soil in the tropical forests. Reforestation of degraded surface mines is critically dependent on the recovery of soil health, where the nematodes play an important role. However, the key determinants of community assembly of soil nematodes during mine-restoration remain unknown in the tropical rainforests. Here, the recovery of taxonomic diversity of nematode communities and their trophic groups during reforestation of an extremely degraded tropical open-mining area is studied. The factors that may impact their recovery, such as root traits (length, area and tissue density), soil properties (pH and soil organic matter content (SOM)), and taxonomic diversities of soil bacterial and fungal communities are investigated. Differences in these parameters were evaluated in the three soil types: (i) mined soil - the erstwhile soil that was removed during mining and stock-piled for 10 years at the foot of an extremely degraded open-mining area; (ii) reforested soil, sampled from a 10-year successful restoration, which used the mined soil for reforestation; and (iii) undisturbed soil, collected from an adjacent undisturbed/not-mined tropical rainforest. A total of 11, 34 and 29 nematode-genera were identified in mined-, undisturbed-, and reforested soils, respectively. The taxonomic diversities of the 5 nematode groups in the mined soil were 1.5-5.2 times lower than in the undisturbed soil, but were similar in the restored and undisturbed soils. Taxonomic diversities of phytophagous and predator nematodes were correlated to restored root traits; whereas of bacterivores, fungivores, and omnivores were correlated to pH, SOM, soil bacterial and fungal communities. Consequently, complete loss of roots during mining likely severely reduced the nematodes, but their recovery after reforestation led to the restoration of taxonomic diversity of nematode communities. The mix-planting fast-growing tree species may be appropriate for recovering soil health, including nematode diversity, during reforestation of open tropical mines.

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Background and aim: A surplus of glucocorticoids (GC) is a main cause of non-traumatic osteonecrosis of the femoral head (ONFH), and Jintiange (JTG), as one of the traditional Chinese medicines (TCM), also plays an instrumental role in the alleviation of bone loss simultaneously. Therefore, JTG was thought to be able to reverse GC-induced ONFH (GC-ONFH) to a certain extent. Experimental procedure: In vivo, the effect of JTG on trabeculae in the subchondral bone of the femoral head was investigated using micro-computed tomography (micro-CT), TdT-mediated dUTP nick end labeling (TUNEL) and histological staining; in vitro, proliferation, viability, apoptosis, and senescence of purified bone mesenchymal stem cells (BMSCs) were examined to demonstrate the direct impact of JTG on these cells. Meanwhile after using a series of interventions, the function of JTG on BMSC differentiation could be assessed by measuring of osteogenic and adipogenic markers at levels of protein and mRNA. Results: Our final results demonstrated that with the involvement of Wnt/ß-catenin pathway, JTG was able to significantly promote osteogenesis, restrain adipogenesis, delay senescence in BMSCs, reduce osteoclast number, weaken apoptosis, and enhance proliferation of osteocytes, all of which could mitigate the progression of subchondral osteonecrosis. Conclusion: According to the results of experiments in vitro and vivo, JTG was deemed to relieve the early GC-ONFH using the prevention of destruction of subchondral bone, which was contributed to regulating the differentiation of BMSCs and the number of osteoclasts.

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Although the silicon (Si) anode has a high theoretical capacity, large volume-expansion would lead to rapid capacity decay. Here, a core-nest structured Si@SnS0.5Se0.5/carbon (Si@SnS0.5Se0.5/C) is developed using silicon as the core and SnS0.5Se0.5/carbon as a binary nest. Both the core-nest structure and carbon matrix enable a stable hybrid structure during charge and discharge. The binary nest Si@SnS0.5Se0.5/C nanospheres as a lithium-ion battery anode display good capacity, recoverable rate-performance, and enhanced electron and ion transfer properties. A capacity of 1318 mA h g-1 and a high coulombic efficiency of 98.9% after 50 cycles at 0.1 A g-1 are achievable, and the capacity remains 887 mA h g-1 after 150 cycles at 0.5 A g-1. A high capacity at 50 °C is also retained, showing a high initial specific capacity. It is found that the reaction resistance of Si@SnS0.5Se0.5/C is significantly lower than that of the pure components, and the stress-strain relationship of the Li-Si system is demonstrated by density functional theory (DFT) calculations. The engineering of the binary-nest structure should be able to provide some new ideas for developing many other high-performance energy-storage hybrids.

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Background: Intervertebral disc degeneration (IDD) can lead to disc herniation and spinal instability, sometimes requiring surgical intervention. Currently, estrogen has a potential protective effect on IDD, and estrogen is associated with an increased risk of some cancers, such as breast and endometrial cancer. Therefore, it is important to identify natural compounds that estrogen analogues treat IDD while reducing the risk of tumor development. Objective: This study aims to explore a natural metabolic treatment strategy by targeting CRISP2 with the natural compound Hesperidin to mimic the protective effects of estrogen on IDD and reduce the risk of tumor development. Methods: Microarray data from healthy volunteers and IDD patients were extracted from the Gene Expression Omnibus (GEO) database, and RNA sequencing and clinical data from various cancer types were analyzed. Differentially expressed genes (DEGs) were identified using the Bioconductor Limma package, followed by principal component analysis, volcano plot, and heatmap visualization. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, CIBERSORT and ssGSEA immune cell infiltration assessments, survival analysis, metabolite enrichment analysis, and molecular docking were performed. Hesperidin's interaction with CRISP2 was further validated through molecular docking and experimental studies. Results: Hesperidin significantly reduced the expression of CRISP2, iNOS, and COX2 in IDD models, decreased reactive oxygen species (ROS) and apoptosis, and diminished inflammatory markers. CIBERSORT and ssGSEA analyses revealed a correlation between CRISP2 and immune cell infiltration. Survival analysis demonstrated that CRISP2 expression levels were associated with patient survival across various cancer types. Hesperidin was found to mimic estrogen's effects on IDD and reduce tumor progression. Cell culture and experimental validation confirmed Hesperidin's protective effects on nucleus pulposus cells (NPCs). Conclusion: Hesperidin, as a potential natural metabolic regulator, not only has therapeutic effects on IDD but may also synergize with estrogen therapy to promote spinal health without increasing cancer risk. This study presents a new clinical approach for IDD treatment and lays the foundation for further drug development and experimental research.