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The tumor suppressor breast cancer 1 (BRCA1) complexed with BRCA1-associated RING domain 1 (BARD1), a RING-type E3 ligase, facilitates the attachment of ubiquitin onto the substrate protein. Here, we present a protocol for evaluating the E3 ligase activity of BRCA1-BARD1 and its variants by nucleosomal histone ubiquitylation. We describe steps for isolating 147 bp Widom 601 DNA and assembling nucleosome core particles (NCPs). We then detail procedures for the in vitro ubiquitylation of nucleosome histone H2A by BRCA1-BARD1 and its variants. For complete details on the use and execution of this protocol, please refer to Wang et al.1.

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AIM: This study aimed to investigate the association of periodontitis with biological aging and to assess potential causality using Mendelian randomization (MR). METHODS: A cross-sectional study with 9558 participants from the National Health and Nutrition Examination Survey (2009-2014) was conducted. Age acceleration (BioAgeAccel and PhenoAgeAccel) was calculated from clinical biomarkers and their discrepancies with chronological age. Two-sample MR analysis was performed using data from a large-scale genome-wide association study and UK Biobank. RESULTS: Periodontitis was associated with increased biological aging, with 0.57-year (95% CI: 0.28-0.86, p < .001) increases in BioAgeAccel and 0.41-year (95% CI: 0.04-0.78, p = .034) increases in PhenoAgeAccel. Subgroup analysis found significantly stronger associations in males for BioAgeAccele (PINTERACTION = .006), and pronounced associations in young adults (pinteraction = .023), individuals with normal body mass index (pinteraction = .015), and current smokers (pinteraction = .016) for PehonAgeAccel. MR analysis did not provide strong evidence for a causal effect of periodontitis on biological aging (BioAgeAccel: IVW ß = 0.008, 95% CI: -0.018 to 0.034, p = .553 and PhenoAgeAccel: IVW ß = 0.016, 95% CI: -0.042 to 0.074, p = .585). CONCLUSION: This study identified the association of periodontitis and its severity with accelerated aging, suggesting periodontal health could be a possible method in personalized preventive and therapeutic strategies of biological aging.

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Immunotherapy has emerged as a pivotal modality in cancer treatment, with immune checkpoint inhibitors effectively combating malignancies by impeding crucial pathways within the immune system and stimulating patients' immune responses. Soluble forms of immune checkpoints exhibit a remarkable diversity and can be readily tracked in circulation, holding immense potential as biomarkers for cancer treatment. An increasing number of studies focused on soluble immune checkpoints in cancer have emerged thanks to technological advancements. In this systematic review, we comprehensively summarized the recent studies on soluble immune checkpoints in human cancer risk prediction, outcome prediction, therapeutic applications, and potential molecular mechanisms, which demonstrated the promising future of soluble immune checkpoints in clinical applications. The clinical relevance of soluble immune checkpoints has been recognized in multiple cancers, yet the therapeutic applications and mechanisms remain obscure. Interpreting the impacts and mechanisms of soluble immune checkpoints could shed a light on the novel strategies of cancer screening, treatments, and outcome prediction.

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Purpose: The use of multi-source precursor data to predict the epidemic risk level would aid in the early and timely identification of the epidemic risk of infectious diseases. To achieve this, a new comprehensive big data fusion assessment method must be developed. Methods: With the help of the Functional Resonance Analysis Method (FRAM) model, this paper proposes a risk portrait for the whole process of a pandemic spreading. Using medical, human behaviour, internet and geo-meteorological data, a hierarchical multi-source dataset was developed with three function module tags, ie, Basic Risk Factors (BRF), the Spread of Epidemic Threats (SET) and Risk Influencing Factors (RIF). Results: Using the dynamic functional network diagram of the risk assessment functional module, the FRAM portrait was applied to pandemic case analysis in Wuhan in 2020. This new-format FRAM portrait model offers a potential early and rapid risk assessment method that could be applied in future acute public health events.

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Antiferroelectric (AFE) has emerged as a promising branch of electroactive materials, due to their intriguing physical attributes stemming from the electric field-induced antipolar-to-polar phase transformation. However, the requirement of an extremely high electric field strength to switch adjacent sublattice polarization poses great challenges for exploiting molecular AFE system. Although photoirradiation is striking as a noncontact and nondestructive manipulation tool to optimize physical properties, the optical control of antiferroelectricity is still unexplored. Here, by adopting light-sensitive triiodide I3- anion into the 2D perovskite family, we have designed the first I3--intercalated molecular AFE of (t-ACH)2EA2Pb3I10(I3)0.5·((H3O)(H2O))0.5 (1, t-ACH = trans-4-aminomethyl-1-cyclohexanecarboxylate, EA = ethylammonium). The I3--intercalating gives an ultra-narrow bandgap of 1.65 eV with strong absorption. In terms of AFE structure, the anti-parallel alignment of electric dipoles results in a spontaneous polarization of 4.3 µC/cm2. Strikingly, 1 merely shows AFE behaviour in the dark even under ultrahigh voltage, while the field-induced ferroelectric state can be facilely obtained upon visible illumination. Such unprecedented photo-assisted phase switching ascribes to the incorporation of photoactive I3- anions, which reduce the AFE-to-ferroelectric switching barrier for 1. This pioneering work on the photo-assisting transformation of ferroic orders paves a new way to develop future photoactive materials with significant potential applications.

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Microbial communities in desert riparian forest ecosystems have developed unique adaptive strategies to thrive in harsh habitats shaped by prolonged exposure to abiotic stressors. However, the influence of drought stress on the functional and metabolic characteristics of soil rhizosphere microorganisms remains unknown. Therefore, this study aimed to investigate the effects of drought stress on soil biogeochemistry and metabolism and analyze the relationship between the biogeochemical cycle processes and network of differentially-expressed metabolites. Using metagenomics and metabolomics, this study explored the microbial functional cycle and differential metabolic pathways within desert riparian forests. The predominant biogeochemical cycles in the study area were the Carbon and Nitrogen cycles, comprising 78.90 % of C, N, Phosphorus, Sulfur and Iron cycles. Drought led to increased soil C fixation, reduced C degradation and methane metabolism, weakened denitrification, and decreased N fixation. Furthermore, drought can disrupt iron homeostasis and reduce its absorption. The differential metabolic pathways of drought stress include flavonoid biosynthesis, arachidonic acid metabolism, steroid hormone biosynthesis, and starch and sucrose degradation. Network analysis of functional genes and metabolism revealed a pronounced competitive relationship between the C cycle and metabolic network, whereas the Fe cycle and metabolic network promoted each other, optimizing resource utilization. Partial least squares analysis revealed that drought hindered the expression and metabolic processes and functional genes, whereas the rhizosphere environment facilitated metabolic expression and the functional genes. The rhizosphere effect primarily promoted metabolic processes indirectly through soil enzyme activities. The integrated multi-omics analysis further revealed that the effects of drought and the rhizosphere play a predominant role in shaping soil functional potential and the accumulation of metabolites. These insights deepen our comprehension of desert riparian forest ecosystems and offer strong support for the functionality of nutrient cycling and metabolite dynamics.

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The licensing step of DNA double-strand break repair by homologous recombination entails resection of DNA ends to generate a single-stranded DNA template for assembly of the repair machinery consisting of the RAD51 recombinase and ancillary factors1. DNA end resection is mechanistically intricate and reliant on the tumour suppressor complex BRCA1-BARD1 (ref. 2). Specifically, three distinct nuclease entities-the 5'-3' exonuclease EXO1 and heterodimeric complexes of the DNA endonuclease DNA2, with either the BLM or WRN helicase-act in synergy to execute the end resection process3. A major question concerns whether BRCA1-BARD1 directly regulates end resection. Here, using highly purified protein factors, we provide evidence that BRCA1-BARD1 physically interacts with EXO1, BLM and WRN. Importantly, with reconstituted biochemical systems and a single-molecule analytical tool, we show that BRCA1-BARD1 upregulates the activity of all three resection pathways. We also demonstrate that BRCA1 and BARD1 harbour stand-alone modules that contribute to the overall functionality of BRCA1-BARD1. Moreover, analysis of a BARD1 mutant impaired in DNA binding shows the importance of this BARD1 attribute in end resection, both in vitro and in cells. Thus, BRCA1-BARD1 enhances the efficiency of all three long-range DNA end resection pathways during homologous recombination in human cells.

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Trophoblast cell surface antigen 2 expressed in several malignant cancers promotes tumor growth and metastasis via several signal transduction pathways. Trop2 is reputed as a prospective biomarker and therapeutic target. Trophoblast cell surface antigen 2-targeted agents, including antibodies, antibody conjugates and therapeutic combinations, could be utilized to fight cancers. To develop an effective drug targeting strategy, we resorted to a new trophoblast cell surface antigen 2-targeted anticancer treatment through aptamer conjugated with chemotherapeutic drug. This study identified trophoblast cell surface antigen 2-specific ssDNA aptamers using engineered trophoblast cell surface antigen 2 overexpression cells for cell-SELEX. The obtained ssDNA aptamer bound to trophoblast cell surface antigen 2 overexpressed cells with nanomolar affinity and was specific for several tumor cell types which express trophoblast cell surface antigen 2 abundantly. Significant cytotoxicity against HT29 cell by the conjugate of trophoblast cell surface antigen 2 aptamer and Emtansine was observed while resulting negligible therapeutic effect on human normal intestinal epithelial cell line HIEC in vitro, indicating that the conjugate shows potential as a promising therapeutic agent. Furthermore, the isolated aptamer demonstrated the ability for the targeted delivery, resulting excellent therapeutic effectiveness of aptamer-drug conjugate for xenograft tumor model of mice with human colorectal cancer.

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BACKGROUND: Hua-Shi-Bai-Du decoction (HSBD) exerts significant effects on the prevention and treatment of COVID-19 in China. The activation of the NLRP3 inflammasome of macrophages plays a vital role in COVID-19 pathology. However, no previous studies have focused on this pathological process to explore the effect of HSBD. PURPOSE: Our aim is to uncover the effect of HSBD on NLRP3 inflammasome activation and the underlying mechanisms. METHODS: The NLRP3-activated J774A.1 cells primed by LPS and activated by nigericin/ATP/MSU were used to evaluate NLRP3 activation in vitro. ASC oligomerization and speck formation were assessed by western blot and immunofluorescence imaging. Intracellular K+ levels were determined by the colorimetric assay. Mitochondrial ROS (mtROS) level was detected by the flow cytometry and the fluorescence spectrophotometry. The intracellular cAMP level was determined by chemiluminescence method and ELISA, while phosphodiesterase (PDE) activity was measured using the fluorescent substrate MANT-cAMP. siRNA was applied to knockdown PDE4B. Two in vivo mouse models, MSU-induced peritonitis and LPS-induced acute lung injury (ALI), were used to evaluate the effects of HSBD on IL-1ß and other inflammatory cytokines. Pathological changes in lung tissue were observed by histopathological examination. RESULTS: HSBD not only decreased supernatant IL-1ß, caspase-1 p20, and cleaved gasdermin D (GSDMD) in NLRP3-activated J774A.1 cells, but also reduced IL-1ß in the peritoneal lavage fluid of mice with MSU-induced peritonitis, demonstrating the suppressive effect on NLRP3 inflammasome activation. The mechanism study showed that HSBD blocked ASC oligomerization and speck formation without affecting K+ efflux or mtROS production. Furthermore, it prevented the decrease of intracellular cAMP by inhibiting PDE4B activity. And in the PDE4B-deficient cells, its suppressive effect on IL-1ß release was abolished. In LPS-induced ALI mice, oral administration of HSBD decreased several proinflammatory cytokines (IL-1ß, IL-6, TNF-α, and CXCL-1) and attenuated the pathological damage to the lung. CONCLUSION: HSBD suppresses the activation of NLRP3 inflammasome by inhibiting PDE4B activity to counteract the decrease of intracellular cAMP, thereby blocking ASC oligomerization in macrophages. Our findings may provide new insight into the clinical effets of HSBD for the treatment of COVID-19.

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KEY MESSAGE: A critical gene for leaf prickle development (LPD) in eggplant was mapped on chromosome E06 and was confirmed to be SmARF10B through RNA interference using a new genetic transformation technique called SACI developed in this study Prickles on eggplant pose challenges for agriculture and are undesirable in cultivated varieties. This study aimed to uncover the genetic mechanisms behind prickle formation in eggplant. Using the F2 and F2:3 populations derived from a cross between the prickly wild eggplant, YQ, and the prickle-free cultivated variety, YZQ, we identified a key genetic locus (LPD, leaf prickle development) on chromosome E06 associated with leaf prickle development through BSA-seq and QTL mapping. An auxin response factor gene, SmARF10B, was predicted as the candidate gene as it exhibited high expression in YQ's mature leaves, while being significantly low in YZQ. Downregulating SmARF10B in YQ through RNAi using a simple and efficient Agrobacterium-mediated genetic transformation method named Seedling Apical Cut Infection (SACI) developed in this study substantially reduced the size and density of leaf prickles, confirming the role of this gene in prickle development. Besides, an effective SNP was identified in SmARF10B, resulting in an amino acid change between YQ and YZQ. However, this SNP did not consistently correlate with prickle formation in eight other eggplant materials examined. This study sheds light on the pivotal role of SmARF10B in eggplant prickle development and introduces a new genetic transformation method for eggplant, paving the way for future research in this field.

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Cartilage defects are frequently caused by trauma, illness and degradation of the cartilage. If these defects are not sufficiently treated, the joints will degrade irreversibly, possibly resulting in disability. Articular cartilage lacks blood vessels and nerves and is unable to regenerate itself, so the repair of cartilage defects is extremely challenging in clinical treatment. Tissue engineering technology is an emerging technology in cartilage repair and cartilage regeneration. 3D-printed hydrogels show great potential in cartilage tissue engineering for the fabrication of 3D cell culture scaffolds to mimic extracellular matrix. In this study, we construct a 3D-printed hydrogel loaded with nanoparticles by electrostatic interaction and photo cross-linking for the regeneration of cartilage, which has adaptable and drug-continuous release behavior. A photopolymerizable bioink was prepared using recombinant collagen, chitosan, nanoclay Laponite-XLG and nanoparticles loaded with Kartogenin (KGN). This bioink was added with KGN, a small molecule drug that promotes cartilage differentiation, and as a result, the 3D-printed CF/CM/3%LAP/KGN scaffolds obtained by extrusion printing is expected to be used for cartilage repair. It was shown that the 3D-printed scaffolds had good cytocompatibility for human bone marrow mesenchymal stem cells (hBMSCs) and exhibited excellent antimicrobial properties, the continuous release of KGN in the scaffold induced the hBMSCs differentiation into chondrocytes, which significantly enhanced the expression of collagen II and glycosaminoglycan. In vivo studies have shown that implantation of KGN-loaded scaffolds into cartilage-injured tissues promoted cartilage tissue regeneration. This study demonstrated that 3D-printed CF/CM/3%LAP/KGN scaffolds can be used for cartilage repair, which is expected to lead to new healing opportunities for cartilage injury-based diseases.

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OBJECTIVES: The occurrence of infection in the ankle and hindfoot presents a formidable surgical challenge. Currently, there is a lack of consensus regarding its treatment strategies. The purpose of this study was to investigate the outcomes of one-stage arthroscopic ankle and tibiotalocalcaneal (TTC) arthrodesis with external fixation in the treatment of septic ankle and hindfoot arthritis. METHODS: A retrospective consecutive case-series study was conducted involving six patients diagnosed with acute or chronic septic ankle or hindfoot arthritis, who underwent operative intervention entailing thorough debridement, arthroscopically assisted one-stage ankle or TTC fusion, and external fixation. The American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score and visual analog scale (VAS) pain score were determined preoperatively and at the final follow-up. Demographic and clinical data, inclusive of perioperative and postoperative complications, were recorded. Comparisons of AOFAS ankle-hindfoot score and VAS pain score between preoperative measures and those at the final follow-up were conducted using paired t-tests or paired Wilcoxon rank-sum tests. RESULTS: The study cohort comprised two males and four females, with a mean age of 48.7 years (range, 26-75) at the time of surgical intervention. At the final follow-up (mean, 26.5 months; range, 16-48), the AOFAS scores exhibited a significant improvement, ascending from an initial mean of 38.8 (range, 12-57) to 80.0 (range, 54-92) (p = 0.007). VAS scores indicated a substantial reduction in pain, decreasing from 6.5 (range, 4-9) to 0 (range, 0-5) (p = 0.046). All patients had achieved osseous consolidation, with a hindfoot infection control rate of 100%. CONCLUSION: One-stage arthroscopic ankle and TTC arthrodesis with external fixation is as an effective therapeutic choice for septic ankle or hindfoot arthritis. This approach yields favorable outcomes characterized by effective infection control, favorable osseous consolidation, and significant functional restoration of the affected limb.

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The hybrid brain-computer interface (BCI) is verified to reduce disadvantages of conventional BCI systems. Transcranial electrical stimulation (tES) can also improve the performance and applicability of BCI. However, enhancement in BCI performance attained solely from the perspective of users or solely from the angle of BCI system design is limited. In this study, a hybrid BCI system combining MI and SSVEP was proposed. Furthermore, transcranial alternating current stimulation (tACS) was utilized to enhance the performance of the proposed hybrid BCI system. The stimulation interface presented a depiction of grabbing a ball with both of hands, with left-hand and right-hand flickering at frequencies of 34 Hz and 35 Hz. Subjects watched the interface and imagined grabbing a ball with either left hand or right hand to perform SSVEP and MI task. The MI and SSVEP signals were processed separately using filter bank common spatial patterns (FBCSP) and filter bank canonical correlation analysis (FBCCA) algorithms, respectively. A fusion method was proposed to fuse the features extracted from MI and SSVEP. Twenty healthy subjects took part in the online experiment and underwent tACS sequentially. The fusion accuracy post-tACS reached 90.25% ± 11.40%, which was significantly different from pre-tACS. The fusion accuracy also surpassed MI accuracy and SSVEP accuracy respectively. These results indicated the superior performance of the hybrid BCI system and tACS would improve the performance of the hybrid BCI system.

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DSS1, essential for BRCA2-RAD51 dependent homologous recombination (HR), associates with the helical domain (HD) and OB fold 1 (OB1) of the BRCA2 DSS1/DNA-binding domain (DBD) which is frequently targeted by cancer-associated pathogenic variants. Herein, we reveal robust ss/dsDNA binding abilities in HD-OB1 subdomains and find that DSS1 shuts down HD-OB1's DNA binding to enable ssDNA targeting of the BRCA2-RAD51 complex. We show that C-terminal helix mutations of DSS1, including the cancer-associated R57Q mutation, disrupt this DSS1 regulation and permit dsDNA binding of HD-OB1/BRCA2-DBD. Importantly, these DSS1 mutations impair BRCA2/RAD51 ssDNA loading and focus formation and cause decreased HR efficiency, destabilization of stalled forks and R-loop accumulation, and hypersensitize cells to DNA-damaging agents. We propose that DSS1 restrains the intrinsic dsDNA binding of BRCA2-DBD to ensure BRCA2/RAD51 targeting to ssDNA, thereby promoting optimal execution of HR, and potentially replication fork protection and R-loop suppression.

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In this work, a proton-conductive inorganic filler based on polyoxovanadate (NH4)7[MnV13O38] (AMV) and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide (EMIM TFSI) was synthesized for hybridization with sulfonated poly(aryl ether ketone sulfone) (SPAEKS) to address the "trade-off" between high proton conductivity and mechanical strength. The novel inorganic filler AMV-EMIM TFSI (AI) was uniformly dispersed and stable within the polymer matrix due to the enhanced ionic interaction. AI provided additional proton transport sites, leading to an elevated ion exchange capacity (IEC) and improved proton conductivity, even at low swelling ratios. The optimized SPAEKS-50/AI-5 (50 for degree of sulfonation of SPAEKS and 5 for weight percentage of AI filler) membrane exhibited the highest proton conductivity of 0.188 S·cm-1 at 80 °C with an IEC of 2.38 mmol·g-1. The enhancement of intermolecular forces improved the mechanical strength from 35 to 55 MPa and improved the elongation at break from 17 to 45%, indicating excellent mechanical properties. The hybrid membrane also demonstrated reinforced methanol resistance due to the hydrogen bonding network and blocking effect, making it suitable for direct methanol fuel cell (DMFC) applications, which exhibited a power density of 15.1 mW·cm-2 at 80 °C. The possibility of further functionalizing these hybrid membranes to tailor their properties for specific applications presents exciting new avenues for research and development. By modification of the type and distribution of fillers or incorporation of additional functional groups, the membranes could be customized to meet the unique demands of various energy storage and conversion systems, enhancing their performance and broadening their application scope. This work provides new insights into the design of polymer electrolyte membranes through inorganic filler hybridization.

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IMPORTANCE: Identifying pediatric eye diseases at an early stage is a worldwide issue. Traditional screening procedures depend on hospitals and ophthalmologists, which are expensive and time-consuming. Using artificial intelligence (AI) to assess children's eye conditions from mobile photographs could facilitate convenient and early identification of eye disorders in a home setting. OBJECTIVE: To develop an AI model to identify myopia, strabismus, and ptosis using mobile photographs. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted at the Department of Ophthalmology of Shanghai Ninth People's Hospital from October 1, 2022, to September 30, 2023, and included children who were diagnosed with myopia, strabismus, or ptosis. MAIN OUTCOMES AND MEASURES: A deep learning-based model was developed to identify myopia, strabismus, and ptosis. The performance of the model was assessed using sensitivity, specificity, accuracy, the area under the curve (AUC), positive predictive values (PPV), negative predictive values (NPV), positive likelihood ratios (P-LR), negative likelihood ratios (N-LR), and the F1-score. GradCAM++ was utilized to visually and analytically assess the impact of each region on the model. A sex subgroup analysis and an age subgroup analysis were performed to validate the model's generalizability. RESULTS: A total of 1419 images obtained from 476 patients (225 female [47.27%]; 299 [62.82%] aged between 6 and 12 years) were used to build the model. Among them, 946 monocular images were used to identify myopia and ptosis, and 473 binocular images were used to identify strabismus. The model demonstrated good sensitivity in detecting myopia (0.84 [95% CI, 0.82-0.87]), strabismus (0.73 [95% CI, 0.70-0.77]), and ptosis (0.85 [95% CI, 0.82-0.87]). The model showed comparable performance in identifying eye disorders in both female and male children during sex subgroup analysis. There were differences in identifying eye disorders among different age subgroups. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, the AI model demonstrated strong performance in accurately identifying myopia, strabismus, and ptosis using only smartphone images. These results suggest that such a model could facilitate the early detection of pediatric eye diseases in a convenient manner at home.

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The achievement of RTP in hybrid organic-inorganic perovskites (HIOPs) via molecular engineering remains relatively uncommon. Here, a series of novel 2D HIOPs composed of mixed organic cations such as naphthalene methylamine (NMA) and 2-(4-methylphenyl) ethanamine (4MPEA) are reported. Efficient RTP and tunable emissions ranging from green to yellow to orange, depending on the doping ratio, are activated in the organic cation-mixed 2D HIOPs system. It has been certified that the triplet excitons of NMA primarily stem from the Wannier excitons of the inorganic layer through an energy transfer process. By gradually altering the halide composition from Br to Cl, the NMA substituted chlorine-based 2D HIOPs show an outstandingly long lifetime of 176 ms. Moreover, potential applications in multiple information encryption and displays have been demonstrated. Our study confirms the effectiveness of strategically hybridizing organic cations with inorganic matrices at the molecular level to achieve high performance RTP.

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BACKGROUND: HHLA2 (human endogenous retrovirus-H long terminal repeat-associating protein 2) represents a recently identified member of the B7 immune checkpoint family, characterized by limited expression in normal tissues but notable overexpression in various cancer types. Nevertheless, the precise function and interaction with immune cells remain poorly understood, particularly in laryngeal squamous cell carcinoma (LSCC). This investigation endeavored to elucidate the biological significance of HHLA2 within the tumor microenvironment of human LSCC tissues and delineate the clinical relevance and functional roles of HHLA2 in LSCC pathogenesis. METHODS: Through multiplexed immunohistochemistry analyses conducted on tissue microarrays sourced from LSCC patients (n = 72), the analysis was executed to assess the expression levels of HHLA2, density and spatial patterns of CD68+HLA-DR+CD163- (M1 macrophages), CTLA-4+CD4+FoxP3+ (CTLA-4+Treg cells), CTLA-4+CD4+FoxP3- (CTLA-4+Tcon cells), exhausted CD8+T cells, and terminally exhausted CD8+T cells in LSCC tissues. Survival analysis was conducted to evaluate the prognostic significance of HHLA2 and these immune checkpoints or immune cell populations, employing COX regression analysis to identify independent prognostic factors. RESULTS: Kaplan-Meier (K-M) survival curves revealed a significant association between HHLA2 expression and overall survival (OS) in LSCC. Elevated levels of HHLA2 were linked to reduced patient survival, indicating its potential as a prognostic marker (HR: 3.230, 95%CI 0.9205-11.34, P = 0.0067). Notably, increased infiltration of CD68+ cells (total macrophages), STING+CD68+HLA-DR+CD163- (STING+M1 macrophages), CTLA-4+CD4+FoxP3+, CTLA-4+CD4+FoxP3-, PD-1+LAG-3+CD8+T cells, and PD-1+LAG-3+TIM-3+CD8+T cells strongly linked to poorer survival outcomes (P < 0.05). A discernible trend was observed between the levels of these immune cell populations, STING+CD68+ (STING+ total macrophages), CD68+HLA-DR+CD163-, STING+CD68+CD163+HLA-DR- (STING+M2 macrophages), PD-1+LAG-3-CD8+T cells, PD-1+TIM-3+CD8+T cells, and PD-1+LAG-3+TIM-3-CD8+T cells and prognosis. Importantly, multivariate COX analysis identified HHLA2 as an independent predictive factor for OS in LSCC patients (HR = 3.86, 95% CI 1.08-13.80, P = 0.038). This underscored the potential of HHLA2 as a critical marker for predicting patient outcomes in LSCC. CONCLUSIONS: HHLA2 emerged as a detrimental prognostic biomarker for assessing OS in LSCC patients. Relative to other immune checkpoints, HHLA2 exhibited heightened predictive efficacy for the prognosis of LSCC patients.

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It's currently a challenge to design a drug delivery system for chemotherapy with high drug contents and minimal side effects. Herein, we constructed a novel one-dimensional binary-drug delivery system for cancer treatment. In this drug delivery system, drugs (doxorubicin (DOX) and resveratrol (RES)) self-assemble on bacterial cellulose nano-whiskers (BCW) and are subsequently encapsulated by polydopamine (PDA) with high encapsulation efficiencies (DOX: 81.53 %, RES: 70.32 %) and high drug loading efficiencies (DOX: 51.54 %, RES: 36.93 %). The cumulative release efficiencies can reach 89.27 % for DOX and 80.05 % for RES in acidic medium within 96 h. The BCW/(DOX + RES)/PDA can enter tumor cells easily through endocytosis and presents significant anti-cancer effects. Furthermore, the released-RES plays a protective role in normal cells through up-regulation of antioxidant enzymes activities and scavenging of reactive oxygen species. Taken together, the one-dimensional BCW/(DOX + RES)/PDA binary-drug delivery system can be used for the anticancer treatment along with slight side effects.

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How to develop contrast agents for cancer theranostics is a meaningful and challenging endeavor, and rare earth nanoparticles (RENPs) may provide a possible solution. In this study, we initially modified RENPs through the application of photodynamic agents (ZnPc) and targeted the bevacizumab antibody for cancer theranostics, which was aimed at improving the therapeutic targeting and efficacy. Subsequently, we amalgamated anthocyanin with the modified RENPs, creating a potential cancer diagnosis platform. When the spectral data were obtained from the composite of cells, the crucial information was extracted through a competitive adaptive reweighted sampling feature algorithm. Then, we employed a machine learning classification model and classified both the individual spectral data and fused spectral data to accurately predict distinctions between breast cancer and normal tissue. The results indicate that the amalgamation of fusion techniques with machine learning algorithms provides highly precise predictions for molecular-level breast cancer detection. Finally, in vitro and in vivo experiments were carried out to validate the near-infrared luminescence and therapeutic effectiveness of the modified nanomedicine. This research not only underscores the targeted effects of nanomedicine but also demonstrates the potent synergy between optical spectral technology and machine learning. This innovative approach offers a comprehensive strategy for the integrated treatment of breast cancer.

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