Altered excitation energy transfer between phycobilisome and photosystems in the absence of ApcG, a small linker peptide, in Synechocystis sp. PCC 6803, a cyanobacterium.

Phycobilisome (PBS) is a large pigment-protein complex in cyanobacteria and red algae responsible for capturing sunlight and transferring its energy to photosystems (PS). Spectroscopic and structural properties of various PBSs have been widely studied, however, the nature of so-called complex-complex interactions between PBS and PSs remains much less explored. In this work, we have investigated the function of a newly identified PBS linker protein, ApcG, some domain of which, together with a loop region (PB-loop in ApcE), is possibly located near the PBS-PS interface. Using Synechocystis sp. PCC 6803, we generated an ApcG deletion mutant and probed its deletion effect on the energetic coupling between PBS and photosystems. Steady-state and time-resolved spectroscopic characterization of the purified ΔApcG-PBS demonstrated that ApcG removal weakly affects the photophysical properties of PBS for which the spectroscopic properties of terminal energy emitters are comparable to those of PBS from wild-type strain. However, analysis of fluorescence decay imaging datasets reveals that ApcG deletion induces disruptions within the allophycocyanin (APC) core, resulting in the emergence (splitting) of two spectrally diverse subgroups with some short-lived APC. Profound spectroscopic changes of the whole ΔApcG mutant cell, however, emerge during state transition, a dynamic process of light scheme adaptation. The mutant cells in State I show a substantial increase in PBS-related fluorescence. On the other hand, global analysis of time-resolved fluorescence demonstrates that in general ApcG deletion does not alter or inhibit state transitions interpreted in terms of the changes of the PSII and PSI fluorescence emission intensity. The results revealed yet-to-be discovered mechanism of ApcG-docking induced excitation energy transfer regulation within PBS or to Photosystems.

Clean Transfer of Two-Dimensional Materials: A Comprehensive Review.

The growth of two-dimensional (2D) materials through chemical vapor deposition (CVD) has sparked a growing interest among both the industrial and academic communities. The interest stems from several key advantages associated with CVD, including high yield, high quality, and high tunability. In order to harness the application potentials of 2D materials, it is often necessary to transfer them from their growth substrates to their desired target substrates. However, conventional transfer methods introduce contamination that can adversely affect the quality and properties of the transferred 2D materials, thus limiting their overall application performance. This review presents a comprehensive summary of the current clean transfer methods for 2D materials with a specific focus on the understanding of interaction between supporting layers and 2D materials. The review encompasses various aspects, including clean transfer methods, post-transfer cleaning techniques, and cleanliness assessment. Furthermore, it analyzes and compares the advances and limitations of these clean transfer techniques. Finally, the review highlights the primary challenges associated with current clean transfer methods and provides an outlook on future prospects.

Unlocking growth potential in Halomonas bluephagenesis for enhanced PHA production with sulfate ions.

The mutant strain Halomonas bluephagenesis (TDH4A1B5P) was found to produce PHA under low-salt, non-sterile conditions, but the yield was low. To improve the yield, different nitrogen sources were tested. It was discovered that urea was the most effective nitrogen source for promoting growth during the stable stage, while ammonium sulfate was used during the logarithmic stage. The growth time of H. bluephagenesis (TDH4A1B5P) and its PHA content were significantly prolonged by the presence of sulfate ions. After 64 hr in a 5-L bioreactor supplemented with sulfate ions, the dry cell weight (DCW) of H. bluephagenesis weighed 132 g/L and had a PHA content of 82%. To promote the growth and PHA accumulation of H. bluephagenesis (TDH4A1B5P), a feeding regimen supplemented with nitrogen sources and sulfate ions with ammonium sodium sulfate was established in this study. The DCW was 124 g/L, and the PHA content accounted for 82.3% (w/w) of the DCW, resulting in a PHA yield of 101 g/L in a 30-L bioreactor using the optimized culture strategy. In conclusion, stimulating H. bluephagenesis (TDH4A1B5P) to produce PHA is a feasible and suitable strategy for all H. bluephagenesis.

Metabolomic reveals the responses of sludge properties and microbial communities to high nitrite stress in denitrifying phosphorus removal systems.

Nitrite, as an electron acceptor, plays a good role in denitrifying phosphorus removal (DPR); however, high nitrite concentration has adverse affects on sludge performance. We investigated the precise mechanisms of responses of sludge to high nitrite stress, including surface characteristics, intracellular and extracellular components, microbial and metabolic responses. When the nitrite stress reached 90 mg/L, the sludge settling performance was improved, but the activated sludge was aging. FTIR and XPS analysis revealed a significant increase in the hydrophobicity of the sludge, resulting in improve settling performance. However, the intracellular carbon sources synthesis was inhibited. In addition, the components in the tightly bound extracellular polymeric substances (TB-EPS) of sludge were significantly reduced and indicated the disturb of metabolism. Notably, Exiguobacterium emerged as a new genus when face high nitrite stress that could maintaining survival in hostile environments. Moreover, metabolomic analysis demonstrated strong biological response to nitrite stress further supported above results that include the inhibited of carbohydrate and amino acid metabolism. More importantly, some lipids (PS, PA, LysoPA, LysoPC and LysoPE) were significantly upregulated that related enhanced membrane lipid remodeling. The comprehensive analyses provide novel insights into the high nitrite stress responses mechanisms in activated sludge systems.

Multi-Modal Enhancement Transformer Network for Skeleton-Based Human Interaction Recognition.

Skeleton-based human interaction recognition is a challenging task in the field of vision and image processing. Graph Convolutional Networks (GCNs) achieved remarkable performance by modeling the human skeleton as a topology. However, existing GCN-based methods have two problems: (1) Existing frameworks cannot effectively take advantage of the complementary features of different skeletal modalities. There is no information transfer channel between various specific modalities. (2) Limited by the structure of the skeleton topology, it is hard to capture and learn the information about two-person interactions. To solve these problems, inspired by the human visual neural network, we propose a multi-modal enhancement transformer (ME-Former) network for skeleton-based human interaction recognition. ME-Former includes a multi-modal enhancement module (ME) and a context progressive fusion block (CPF). More specifically, each ME module consists of a multi-head cross-modal attention block (MH-CA) and a two-person hypergraph self-attention block (TH-SA), which are responsible for enhancing the skeleton features of a specific modality from other skeletal modalities and modeling spatial dependencies between joints using the specific modality, respectively. In addition, we propose a two-person skeleton topology and a two-person hypergraph representation. The TH-SA block can embed their structural information into the self-attention to better learn two-person interaction. The CPF block is capable of progressively transforming the features of different skeletal modalities from low-level features to higher-order global contexts, making the enhancement process more efficient. Extensive experiments on benchmark NTU-RGB+D 60 and NTU-RGB+D 120 datasets consistently verify the effectiveness of our proposed ME-Former by outperforming state-of-the-art methods.

PSE-Net: Channel pruning for Convolutional Neural Networks with parallel-subnets estimator.

Channel Pruning is one of the most widespread techniques used to compress deep neural networks while maintaining their performances. Currently, a typical pruning algorithm leverages neural architecture search to directly find networks with a configurable width, the key step of which is to identify representative subnet for various pruning ratios by training a supernet. However, current methods mainly follow a serial training strategy to optimize supernet, which is very time-consuming. In this work, we introduce PSE-Net, a novel parallel-subnets estimator for efficient channel pruning. Specifically, we propose a parallel-subnets training algorithm that simulate the forward-backward pass of multiple subnets by droping extraneous features on batch dimension, thus various subnets could be trained in one round. Our proposed algorithm facilitates the efficiency of supernet training and equips the network with the ability to interpolate the accuracy of unsampled subnets, enabling PSE-Net to effectively evaluate and rank the subnets. Over the trained supernet, we develop a prior-distributed-based sampling algorithm to boost the performance of classical evolutionary search. Such algorithm utilizes the prior information of supernet training phase to assist in the search of optimal subnets while tackling the challenge of discovering samples that satisfy resource constraints due to the long-tail distribution of network configuration. Extensive experiments demonstrate PSE-Net outperforms previous state-of-the-art channel pruning methods on the ImageNet dataset while retaining superior supernet training efficiency. For example, under 300M FLOPs constraint, our pruned MobileNetV2 achieves 75.2% Top-1 accuracy on ImageNet dataset, exceeding the original MobileNetV2 by 2.6 units while only cost 30%/16% times than BCNet/AutoAlim.

Functional analyses of TRAF6 gene in Argopecten scallops.

The tumor necrosis factor (TNF) receptor-associated factor (TRAF) family has been reported to be involved in many immune pathways. In a previous study, we identified 5 TRAF genes, including TRAF2, 3, 4, 6, and 7, in the bay scallop (Argopecten irradians, Air) and the Peruvian scallop (Argopecten purpuratus, Apu). Since TRAF6 is a key molecular link in the TNF superfamily, we conducted a series of studies targeting the TRAF6 gene in the Air and Apu scallops as well as their hybrid progeny, Aip (Air ♀ × Apu ♂) and Api (Apu ♀ × Air ♂). Subcellular localization assay showed that the Air-, Aip-, and Api-TRAF6 were widely distributed in the cytoplasm of the human embryonic kidney cell line (HEK293T). Additionally, dual-luciferase reporter assay revealed that among TRAF3, TRAF4, and TRAF6, only the overexpression of TRAF6 significantly activated NF-κB activity in the HEK293T cells in a dose-dependent manner. These results suggest a crucial role of TRAF6 in the immune response in Argopecten scallops. To investigate the specific immune mechanism of TRAF6 in Argopecten scallops, we conducted TRAF6 knockdown using RNA interference. Transcriptomic analyses of the TRAF6 RNAi and control groups identified 1194, 2403, and 1099 differentially expressed genes (DEGs) in the Air, Aip, and Api scallops, respectively. KEGG enrichment analyses revealed that these DEGs were primarily enriched in transport and catabolism, amino acid metabolism, peroxisome, lysosome, and phagosome pathways. Expression profiles of 28 key DEGs were confirmed by qRT-PCR assays. The results of this study may provide insights into the immune mechanisms of TRAF in Argopecten scallops and ultimately benefit scallop breeding.

Comparative impact of bacitracin and select feed additives in the feeding program of Lohmann LSL-Lite pullets at the onset of lay through to 31 weeks of age.

There are limited investigations on the role of feed additives in easing transition of pullets to egg production phase. We investigated the effects of supplementation of bacitracin methylene disalicylate (BMD) and select feed additives (myristic acid [MA], benzoic acid [BA], and Aspergillus niger probiotic [PRO]) in feeding program for pullets from the onset of lay through to 31 weeks of age (woa). Parameters measured included hen-day egg production (HDEP), feed intake (FI), feed conversion ratio (FCR), egg quality characteristics, ceca microbial activity, apparent retention of components, and plasma metabolites. A total of 1,200 Lohmann LSL Lite pullets were procured at 18 woa and placed in enriched cages (30 birds/cage) based on body weight (BW) and allocated to five diets. The diets were a basal diet formulated to meet specifications or basal mixed with either BMD, MA, BA, or PRO. Birds had free access to feed and water throughout the experiment. Between 18 and 20 woa, birds fed BMD ate a similar (P > 0.05) amount of feed to BA birds, but more (P = 0.0003) than birds fed basal, MA, or PRO diets. Basal birds had lower HDEP (P = 0.001) and lighter eggs (P < 0.0001) than birds fed any of the feed additives between 21 and 31 woa. The basal hens had a higher (P = 0.009) abundance of Escherichia coli than birds fed BMD, BA, and PRO diets. Consequently, BMD, BA, and PRO birds had a higher (P = 0.011) Lactobacilli: E. coli ratio (LER) than hens fed the basal diet. Specifically, relative to basal-fed hens, the LER of the BMD, MA, BA, and PRO hens was higher by 37%, 21%, 26%, and 45%, respectively. Moreover, birds fed PRO tended to have a higher concentration of ceca digesta acetic acid (P = 0.072) and a lower concentration of isobutyric acid (P = 0.096). In conclusion, supplementing pullet diets with broad-spectrum antibiotics or feed additives (MA, BA, and PRO) had a positive impact on FI, and egg production linked to modulation of indices of gut health. The results suggested supplementing feed additives in feeding programs for pullets at the onset of lay can bolster productivity outcomes.

The estrogen receptor and metabolism.

Across the globe, metabolic syndrome, hyperuric acid, and their related diseases, such as cardiovascular disease, diabetes, and insulin resistance, are increasing in incidence due to metabolic imbalances. Due to the pathogenesis, women are more prone to these diseases than men. As estrogen levels decrease after menopause, obesity and metabolic disorders are more likely to occur. Men are also affected by hyperuric acid. To provide ideas for the prevention and treatment of metabolic syndrome and hyperuricemia, this article reviews and analyzes the relationship between estrogen receptors, metabolic syndrome, and hyperuricemia.

Influence of estrogen receptor on metabolic syndrome and hyperuricemiaA narrative review discusses the mechanism of estrogen and estrogen receptors for metabolic syndrome and hyperuric acid, and highlights the important for prevention and treatment of metabolic balances.

Oncolytic Peptide-Nanoplatform Drives Oncoimmune Response and Reverses Adenosine-Induced Immunosuppressive Tumor Microenvironment.

The application of oncolytic peptides has become a powerful approach to induce complete and long-lasting remission in multiple types of carcinomas, as affirmed by the appearance of tumor-associated antigens and adenosine triphosphate (ATP) in large quantities, which jumpstarts the cancer-immunity cycle. However, the ATP breakdown product adenosine is a significant contributor to forming the immunosuppressive tumor microenvironment, which substantially weakens peptide-driven oncolytic immunotherapy. In this study, a lipid-coated micelle (CA@TLM) loaded with a stapled oncolytic peptide (PalAno) and an adenosine 2A receptor (A2AR) inhibitor (CPI-444) is devised to enact tumor-targeted oncolytic immunotherapy and to overcome adenosine-mediated immune suppression simultaneously. The CA@TLM micelle accumulates in tumors with high efficiency, and the acidic lysosomal environment prompts the rapid release of PalAno and CPI-444. Subsequently, PalAno induces swift membrane lysis of tumor cells and the release of antigenic materials. Meanwhile, CPI-444 blocks activation of the immunosuppressive adenosine-A2AR signaling pathway. This combined approach exhibit pronounced synergy at stalling tumor growth and metastasis in animal models for triple-negative breast cancer (TNBC) and melanoma, providing a novel strategy for enhanced oncolytic immunotherapy. This article is protected by copyright. All rights reserved.

Rheumatoid arthritis with pulmonary accelerated rheumatoid nodules treated by baricitinib: a case-based review.

Pulmonary accelerated rheumatoid nodules (ARN) represent a rare occurrence within the context of rheumatoid arthritis (RA), with conventional treatment typically involving corticosteroids. In this report, we present a unique case of pulmonary ARN managed with baricitinib, a Janus kinase inhibitor. The patient, a 46-year-old woman diagnosed with RA, initially displayed no evident pulmonary nodules upon pulmonary imaging. Her treatment regimen encompassed corticosteroids, methotrexate, and leflunomide. Nevertheless, a chest computed tomography (CT) scan conducted after a year unveiled the presence of multiple bilateral pulmonary nodules. A thoracoscopic biopsy of these nodules confirmed the presence of rheumatoid nodules. Treatment with baricitinib, a Janus kinase inhibitor or synthetic disease-modifying antirheumatic drug (DMARD), effectively reduced the size of the nodules. Our review of 45 articles on ARN published since 1986 found that nine of them reported 13 cases of pulmonary ARN. These nodules may be caused by certain synthetic and biological DMARDs and often present with respiratory symptoms. CT scans typically reveal multiple solid nodules or ground-glass opacities, some of which may have cavities. Treatment customarily involves discontinuing the suspected drugs and administering corticosteroids. This case suggests that Janus kinase inhibitors may be an effective treatment option for ARN.

Bimetallic metal-organic framework-derived bamboo-like N-doped carbon nanotube-encapsulated Ni-doped MoC nanoparticles for water oxidation.

Molybdenum carbide materials with unique electronic structures have received special attention as water-splitting catalysts, but their structural stability in the alkaline water electrolysis process is not satisfactory. This study reports an in situ pyrolysis method for preparing NiMo-based metal-organic framework (MOF)-derived chain-mail oxygen evolution reaction (OER) electrocatalysts and bamboo-like N-doped carbon nanotube (NCNT)-encapsulated Ni-doped MoC nanoparticles (NiMoC-NCNTs). The NCNTs can provide chain mail shells to protect the inner highly reactive Ni-doped MoC cores from electrochemical corrosion by the alkaline electrolyte and regulate their catalytic properties through charge redistribution. Benefiting from high N-doping with abundant pyridinic moieties and abundant active sites of the periodic bamboo-like nodes, the as-prepared NiMoC-NCNTs display an outstanding activity for the OER with an overpotential of 310 mV at 10 mA cm-2 and a superior long-term stability of 50 h. Density functional theory calculations reveal that the excellent electrocatalytic activity of NiMoC-NCNTs comes from the electron transfer from NiMoC nanoparticles to NCNTs, resulting in a decrease in the local work function at the carbon surface and optimized free efficiencies of OER intermediates on C sites. This work provides an effective approach to improve the structural stability of fragile catalysts by equipping them with carbon-based chain.

Heritability of chronic thermal tolerance and genetic correlations with growth traits in the Pacific oyster (Crassostrea gigas).

The increasing seawater temperature during summer months frequently results in severe mortalities in the Pacific oyster Crassostrea gigas around the world, becoming one of the most significant problems challenging the oyster farming industry. In northern China, significant recurrent summer losses of C. gigas have occurred, and its impact on oyster aquaculture has increased in recent years. Selective breeding for improved oyster resistance to high temperature could help to reduce this massive mortality, but the extent of genetic variation underlying this trait is currently unknown. In this study, we constructed 38 full-sib families using the wild C. gigas and estimated the genetic parameters by performing two month-long high-temperature challenge experiments (30 ℃). Experiment 1 was performed in March 2022 followed by experiment 2 in June 2022 (spawning season). In both challenge experiments, there were significant differences in survival among families, suggesting that C. gigas has a different ability to survive under heat stress. Notably, significantly greater mortality was observed for experiment 2, which related to reproductive status and may contribute to additional stress. Thermal tolerance was defined using both binary test survival and time of death traits. Heritability estimates for thermal tolerance were low to moderate (0.16-0.36 for experiment 1 and 0.16-0.33 for experiment 2) using both a Bayesian (MCMCglmm) and a likelihood-based (ASReml-R) approach and estimated heritability of the threshold animal model using ASReml-R (0.16) appeared to be lower compared to MCMCglmm (0.31-0.32). Notably, the genetic and phenotypic correlations for thermal tolerance between two experiments were 0.463 (BS) to 0.491 (TD) and 0.510 (family survival), respectively, which suggested a significant re-ranking of the family breeding values in different time periods. Finally, the genetic and phenotypic correlations were low between growth traits (shell height, shell length, and shell width) and thermal tolerance, suggesting that selection for these traits should be conducted separately. This study reports the first estimation of genetic parameters for chronic thermal tolerance in C. gigas and indicates that this trait is heritable and selective breeding for thermal tolerance is a feasible and promising approach to reduce summer mortality.

A rare presentation of primary cardiac diffuse large B­cell lymphoma: A case report.

Primary cardiac lymphomas display a low frequency, sudden onset, swift progression of illness and elevated mortality rates. The current study presents a unique instance of primary cardiac diffuse large B-cell lymphoma and examines its clinical manifestations, pathological characteristics and differential diagnosis. A 64-year-old male patient sought medical attention due to cardiac debility and exertional dyspnea persisting for >10 days. Chest enhanced computed tomography revealed a moderately enhancing irregular mass in the ventricular area, exhibiting limited demarcation from the pericardium and left atrium, accompanied by irregular thickening of the interventricular septum. The postoperative specimen showed the presence of yellow fish-like tumor tissue. Immunohistochemical analysis revealed the presence of lymphocytes positive for CD20, BCL-2, BCL-6, c-Myc-binding protein, mutated melanoma-associated antigen 1 and CD79a, along with a high Ki-67 proliferation index of 80%. Conversely, CD10, CD30, CD3, pan cytokeratin, cyclin D1, desmin and vimentin marker results were found to be negative. Additionally, in situ hybridization demonstrated a lack of Epstein-Barr virus-encoded small RNA expression. The present case report emphasizes the significance of conducting a thorough analysis of the clinical manifestations of diffuse large B-cell lymphoma to assist clinicians in establishing a diagnosis and determining an effective treatment approach, thereby enhancing the patient's prognosis.

The Role of PKM2 in Multiple Signaling Pathways Related to Neurological Diseases.

Pyruvate kinase M2 (PKM2) is a key rate-limiting enzyme in glycolysis. It is well known that PKM2 plays a vital role in the proliferation of tumor cells. However, PKM2 can also exert its biological functions by mediating multiple signaling pathways in neurological diseases, such as Alzheimer's disease (AD), cognitive dysfunction, ischemic stroke, post-stroke depression, cerebral small-vessel disease, hypoxic-ischemic encephalopathy, traumatic brain injury, spinal cord injury, Parkinson's disease (PD), epilepsy, neuropathic pain, and autoimmune diseases. In these diseases, PKM2 can exert various biological functions, including regulation of glycolysis, inflammatory responses, apoptosis, proliferation of cells, oxidative stress, mitochondrial dysfunction, or pathological autoimmune responses. Moreover, the complexity of PKM2's biological characteristics determines the diversity of its biological functions. However, the role of PKM2 is not entirely the same in different diseases or cells, which is related to its oligomerization, subcellular localization, and post-translational modifications. This article will focus on the biological characteristics of PKM2, the regulation of PKM2 expression, and the biological role of PKM2 in neurological diseases. With this review, we hope to have a better understanding of the molecular mechanisms of PKM2, which may help researchers develop therapeutic strategies in clinic.

Role of Oxidative Stress in the Occurrence and Development of Cognitive Dysfunction in Patients with Obstructive Sleep Apnea Syndrome.

Obstructive sleep apnea syndrome (OSAS) causes recurrent apnea and intermittent hypoxia at night, leading to several complications such as cognitive dysfunction. However, the molecular mechanisms underlying cognitive dysfunction in OSAS are unclear, and oxidative stress mediated by intermittent hypoxia is an important mechanism. In addition, the improvement of cognitive dysfunction in patients with OSAS varies by different treatment regimens; among them, continuous positive airway pressure therapy (CPAP) is mostly recognized for improving cognitive dysfunction. In this review, we discuss the potential mechanisms of oxidative stress in OSAS, the common factors of affecting oxidative stress and the Links between oxidative stress and inflammation in OSAS, focusing on the potential links between oxidative stress and cognitive dysfunction in OSAS and the potential therapies for neurocognitive dysfunction in patients with OSAS mediated by oxidative stress. Therefore, further analysis on the relationship between oxidative stress and cognitive dysfunction in patients with OSAS will help to clarify the etiology and discover new treatment options, which will be of great significance for early clinical intervention.

Characterization of Higher Order Structural Changes of a Thermally Stressed Monoclonal Antibody via Mass Spectrometry Footprinting and Other Biophysical Approaches.

Characterizing changes in the higher order structure (HOS) of monoclonal antibodies upon stressed conditions is critical to gaining a better understanding of the product and process. One single biophysical approach may not be best suited to assess HOS comprehensively; thus, the synergy from multiple, complementary approaches improves characterization accuracy and resolution. In this study, we employed two mass spectrometry (MS )-based footprinting techniques, namely, fast photochemical oxidation of proteins (FPOP)-MS and hydrogen-deuterium exchange (HDX)-MS, supported by dynamic light scattering (DLS), differential scanning calorimetry (DSC), circular dichroism (CD), and nuclear magnetic resonance (NMR) to study changes to the HOS of a mAb upon thermal stress. The biophysical techniques report a nuanced characterization of the HOS in which CD detects no changes to the secondary or tertiary structure, yet DLS measurements show an increase in the hydrodynamic radius. DSC indicates that the stability decreases, and chemical or conformational changes accumulate with incubation time according to NMR. Furthermore, whereas HDX-MS does not indicate HOS changes, FPOP-MS footprinting reveals conformational changes at residue resolution for some amino acids. The local phenomena observed with FPOP-MS indicate that several residues show various patterns of degradation during thermal stress: no change, an increase in solvent exposure, and a biphasic response to solvent exposure. All evidences show that FPOP-MS efficiently resolves subtle structural changes and novel degradation pathways upon thermal stress treatment at residue-level resolution.

Nanosensitizer-mediated augmentation of sonodynamic therapy efficacy and antitumor immunity.

The dense stroma of desmoplastic tumor limits nanotherapeutic penetration and hampers the antitumor immune response. Here, we report a denaturation-and-penetration strategy and the use of tin monosulfide nanoparticles (SnSNPs) as nano-sonosensitizers that can overcome the stromal barrier for the management of desmoplastic triple-negative breast cancer (TNBC). SnSNPs possess a narrow bandgap (1.18 eV), allowing for efficient electron (e-)-hole (h+) pair separation to generate reactive oxygen species under US activation. More importantly, SnSNPs display mild photothermal properties that can in situ denature tumor collagen and facilitate deep penetration into the tumor mass upon near-infrared irradiation. This approach significantly enhances sonodynamic therapy (SDT) by SnSNPs and boosts antitumor immunity. In mouse models of malignant TNBC and hepatocellular carcinoma (HCC), the combination of robust SDT and enhanced cytotoxic T lymphocyte infiltration achieves remarkable anti-tumor efficacy. This study presents an innovative approach to enhance SDT and antitumor immunity using the denaturation-and-penetration strategy, offering a potential combined sono-immunotherapy approach for the cancer nanomedicine field.

[Clinical application study of multiple small-diameter drilling combined with extracorporeal shock wave therapy (ESWT) under C-arm positioning in the treatment of early femoral head necrosis].

OBJECTIVE: To explore the therapeutic effect of multiple small diameter drilling combined with extracorporeal shock wave therapy (ESWT) under C-arm X-raylocalization in patients with early osteonecrosis of the femoral head (ONFH). METHODS: A total of 106 cases of early ONFH patients admitted from May 2015 to May 2017 were retrospectively selected as the study subjects. According to different treatment methods, the patients were divided into observation group and control group, 53 cases in each group. The observation group was treated with multiple small-diameter drilling combined with ESWT under C-arm positioning in the observation group, including 41 males and 12 females with an age of (45.85±6.01) years old (22 to 70 years old);and the control group was treated with ESWT, including 34 males and 19 females with an age of (45.12±5.83) years old(20 to 68 years old) in the control group. The modified Harris hip scores(mHHS), visual analog scale(VAS), hip flexion range, hip abduction and adduction range, ONFH area ratio and clinical efficacy were compared between twe groups before and after treatment. Kaplan-Meier method was used to draw a survival curve to compare the femoral head survival rate between two groups during the 3-year follow-up period after treatment. RESULTS: There were no complications such as poor wound healing and infection. All of 106 patients were followed up for 28 to 36 months with an average of (31.06±4.28) months. MHHS score, hip flexion range and hip abduction and adduction range in the observation group were increased from (63.85±5.42) scores, (23.79±2.21) °, (32.40±4.19) ° before treatment to (85.51±5.69) scores, (34.65±2.73)°, (43.32±5.71)° at 2 years after treatment, respectively(P<0.05). The above indicators in the control group increased from (64.73±5.64)°, (23.82±2.18)°, (32.45±4.13)° before treatment to (81.65±5.48) scores, (32.79±2.87)°, (39.75±5.68)°at two years after treatment, respectively(P<0.05). VAS score and ONFH area ratio in the observation group decreased from (5.76±1.41) scores and (35.07±4.96)% before treatment to (3.39±1.02) scores and (22.04±3.23)% at 2 years after treatment, respectively(P<0.05). The above indicatiors in control group decreased from (5.73±1.45) scores and (35.24±5.18)% before treatment to (4.43±1.21) scores and (28.32±3.76)% at 2 years after treatment, respectively(P<0.05), and the improvement in the observation group was significantly higher than that in the control group(P<0.05). At 3 years after treatment, the femoral head survival rate in the observation group was higher than that in the control group (P<0.05). CONCLUSION: Multiple small diameter drilling combined with ESWT under C-arm positioning can significantly improve the clinical symptoms of patients with early ONFH, relieve pain and improve clinical efficacy.

Tumor-derived exosomal linc00881 induces lung fibroblast activation and promotes osteosarcoma lung migration.

Osteosarcoma (OS) commonly metastasizes to the lung, yet the underlying molecular mechanisms remain poorly understood. Exosomes play a crucial role in tumor migration, including OS lung migration. However, the underlying mechanism by which exosome-derived long non-coding RNAs (lncRNAs) contribute to lung migration in osteosarcoma (OS) remains unclear. This study presents a newly discovered lncRNA, linc00881, derived from OS exosomes. Our study shows that linc00881 promotes the migration of OS cells to the lung and induces the conversion of normal lung fibroblasts into cancer-associated fibroblasts (CAFs). Subsequently, we found that exosomal linc00881 secreted by OS cells can regulate the expression of matrix metalloproteinase 2 (MMP2) in HFL-1 cells by sponging miR-29c-3p, thereby activating the NF-κB signaling in lung fibroblasts. Finally, we discovered that pro-inflammatory cytokines, namely IL-1ß, IL-6, and IL-8, were secreted through the linc00881/miR-29c-3p/MMP2 axis. These results suggest that OS-derived exosomes can mediate the intercellular crosstalk between OS cells and lung fibroblasts, ultimately impacting OS lung migration. Our study provides a potential target for the treatment of OS lung migration.