Evaluating the efficacy of standardized pressure ulcer management protocols in the prevention of pressure injuries among patients undergoing neurosurgical procedures.

Pressure injuries are a significant concern for patients undergoing neurosurgical procedures due to prolonged immobility and the complexity of care. This study evaluates the efficacy of standardized pressure ulcer management protocols in preventing pressure injuries and enhancing patient care in a neurosurgical context. A comprehensive retrospective analysis was conducted at a single institution from December 2020 to December 2023, comparing 50 patients who received standardized pressure ulcer management (intervention group) with 50 patients who received conventional care (control group). The study assessed the incidence of pressure ulcers, patient comfort levels using the Kolcaba Comfort Scale and sleep quality using the Richards-Campbell Sleep Questionnaire (RCSQ). Statistical analysis was performed using SPSS software, version 27.0, applying t-tests and chi-square tests as appropriate. The intervention group exhibited a significantly lower incidence of pressure ulcers at all measured time points post-surgery compared to the control group. Patient comfort levels in the intervention group were consistently higher across psychological, environmental, physiological and socio-cultural domains. Sleep quality metrics, including sleep depth, latency to sleep onset and overall sleep quality, were significantly improved in the intervention group. The implementation of standardized pressure ulcer management protocols in neurosurgical care significantly reduces the incidence of pressure injuries, enhances patient comfort and improves sleep quality. These findings highlight the importance of adopting structured care protocols to improve postoperative outcomes and patient well-being in neurosurgical settings.

Spatiotemporal-Controlled NIR-II Immune Agonist Sensitizes Cancer Immunotherapy.

The integration of nanomedicine and immunotherapy has presented a promising opportunity for the treatment of cancer and diverse diseases. However, achieving spatiotemporal controllable immunotherapy with excellent efficacy and safety performances remains a significant challenge. This study develops a biodegradable near-infrared II (NIR-II) photothermal response polymer nanoparticle (PTEQ) system. This platform exhibits intrinsic immunostimulatory properties while concurrently delivering siRNA for Programmed Death-Ligand 1 (siPD-L1), leveraging enhanced immune responses and immune checkpoint blockade for safe and effective cancer therapy. In the CT26 tumor-bearing mouse model, PTEQ, as an immune stimulant, significantly boosts the infiltration of CD4+ and CD8+ T cells within the tumor microenvironment (TME). The PTEQ/siPD-L1+laser group not only initiates NIR-II photothermal therapy but also promotes the activation and infiltration of T cells, M1 macrophage polarization, and maturation of dendritic cells in the TME, resulting in the complete elimination of tumors in 7/10 cases, achieving a 100% survival rate. In another in vivo vaccine experiment, all tumors on the right side are completely eliminated in the PTEQ/siPD-L1+laser group, reaching a 100% tumor eradication rate. These findings underscore the potential of this strategy to overcome the current immunotherapeutic limitations and achieve immune therapy normalization.

Hierarchical Sea Urchin-like Fe-doped Heazlewoodite for High-Efficient Oxygen Evolution.

Electrochemical water-splitting to produce hydrogen is potential to substitute the traditional industrial coal gasification, but the oxygen evolution kinetics at the anode remains sluggish. In this paper, sea urchin-like Fe doped Ni3S2 catalyst growing on nickel foam (NF) substrate is constructed via a simple two-step strategy, including surface iron activation and post sulfuration process. The NF-Fe-Ni3S2 obtains at temperature of 130 °C (NF-Fe-Ni3S2-130) features nanoneedle-like arrays which are vertically grown on the particles to form sea urchin-like morphology, features high electrochemical surface area. As oxygen evolution catalyst, NF-Fe-Ni3S2-130 exhibits excellent oxygen evolution activities, fast reaction kinetics, and superior reaction stability. The excellent OER performance of sea urchin-like NF-Fe-Ni3S2-130 is mainly ascribed to the high-vertically dispersive of nanoneedles and the existing Fe dopants, which obviously improved the reaction kinetics and the intrinsic catalytic properties. The simple preparation strategy is conducive to establish high-electrochemical-interface catalysts, which shows great potential in renewable energy conversion.

A patient with multiple primary malignant neoplasms with high variant allele frequencies of RB1, TP53, and TERT.

Multiple primary malignant neoplasms are a rare disease with tumors of different histology or morphology arising in various sites. Next-generation sequencing is essential in the etiology, diagnosis, treatment, and surveillance of this disease. No eight primary malignant neoplasm cases with high variant allele frequencies of RB1, TP53, and TERT have been reported. Herein, we report a 65-year-old male who exhibited eight primary malignancies of the vocal cord, pharynx, kidney, mouth floor, esophagus, and urinary bladder with different pathological types. The first seven tumors were early-stage tumors; the last tumor, small cell carcinoma of urinary bladder, showed liver metastasis at diagnosis. Next-generation sequencing results revealed extremely high somatic variant allele frequencies of RB1 c.1472 T > C, TP53 c.576A > G, and TERT c.-58-u66C > T (95.5%, 95.1%, and 51.0%, respectively). No germline mutations were detected. These findings denoted a heavy tumor burden and poor prognosis. This is the first report of eight primary malignant neoplasm cases with high variant allele frequencies of RB1, TP53, and TERT.

Non-volatile 2 × 2 optical switch using multimode interference in an Sb2Se3-loaded waveguide.

We propose a non-volatile 2 × 2 photonic switch based on multimode interference in an Sb2Se3-loaded waveguide. The different modal symmetries of the TE0 and TE1 modes supported in the multimode region change their propagation constants distinctly upon the Sb2Se3 phase transition. Through careful optical design and FDTD optimization of the multimode waveguide dimensions, efficient switching is achieved despite the modest index contrast of Sb2Se3 relative to Ge2Sb2Te5. The fabricated optical switch demonstrates favorable characteristics, including low insertion loss of ∼1 dB, a compact length of ∼27 µm, and small cross talk below -15 dB across a 35 nm bandwidth. Such non-volatile and broadband components will be critical for future high-density programmable photonic-integrated circuits for optical communications and signal processing.

Nucleic-acid-triggered NADase activation of a short prokaryotic Argonaute.

Argonaute (Ago) proteins mediate RNA- or DNA-guided inhibition of nucleic acids1,2. Although the mechanisms used by eukaryotic Ago proteins and long prokaryotic Ago proteins (pAgos) are known, that used by short pAgos remains elusive. Here we determined the cryo-electron microscopy structures of a short pAgo and the associated TIR-APAZ proteins (SPARTA) from Crenotalea thermophila (Crt): a free-state Crt-SPARTA; a guide RNA-target DNA-loaded Crt-SPARTA; two Crt-SPARTA dimers with distinct TIR organization; and a Crt-SPARTA tetramer. These structures reveal that Crt-SPARTA is composed of a bilobal-fold Ago lobe that connects with a TIR lobe. Whereas the Crt-Ago contains a MID and a PIWI domain, Crt-TIR-APAZ has a TIR domain, an N-like domain, a linker domain and a trigger domain. The bound RNA-DNA duplex adopts a B-form conformation that is recognized by base-specific contacts. Nucleic acid binding causes conformational changes because the trigger domain acts as a 'roadblock' that prevents the guide RNA 5' ends and the target DNA 3' ends from reaching their canonical pockets; this disorders the MID domain and promotes Crt-SPARTA dimerization. Two RNA-DNA-loaded Crt-SPARTA dimers form a tetramer through their TIR domains. Four Crt-TIR domains assemble into two parallel head-to-tail-organized TIR dimers, indicating an NADase-active conformation, which is supported by our mutagenesis study. Our results reveal the structural basis of short-pAgo-mediated defence against invading nucleic acids, and provide insights for optimizing the detection of SPARTA-based programmable DNA sequences.

Near-Infrared-II Nanoparticles for Vascular Normalization Combined with Immune Checkpoint Blockade via Photodynamic Immunotherapy Inhibit Uveal Melanoma Growth and Metastasis.

Photodynamic therapy (PDT) has been widely employed in tumor treatment due to its effectiveness. However, the tumor hypoxic microenvironment which is caused by abnormal vasculature severely limits the efficacy of PDT. Furthermore, the abnormal vasculature has been implicated in the failure of immunotherapy. In this study, a novel nanoparticle denoted as Combo-NP is introduced, composed of a biodegradable NIR II fluorescent pseudo-conjugate polymer featuring disulfide bonds within its main chain, designated as TPA-BD, and the vascular inhibitor Lenvatinib. Combo-NP exhibits dual functionality by not only inducing cytotoxic reactive oxygen species (ROS) to directly eliminate tumor cells but also eliciting immunogenic cell death (ICD). This ICD response, in turn, initiates a robust cascade of immune reactions, thereby augmenting the generation of cytotoxic T lymphocytes (CTLs). In addition, Combo-NP addresses the issue of tumor hypoxia by normalizing the tumor vasculature. This normalization process enhances the efficacy of PDT while concurrently fostering increased CTLs infiltration within the tumor microenvironment. These synergistic effects synergize to potentiate the photodynamic-immunotherapeutic properties of the nanoparticles. Furthermore, when combined with anti-programmed death-ligand 1 (PD-L1), they showcase notable inhibitory effects on tumor metastasis. The findings in this study introduce an innovative nanomedicine strategy aimed at triggering systemic anti-tumor immune responses for the treatment of Uveal melanoma.

CLIP-Driven Prototype Network for Few-Shot Semantic Segmentation.

Recent research has shown that visual-text pretrained models perform well in traditional vision tasks. CLIP, as the most influential work, has garnered significant attention from researchers. Thanks to its excellent visual representation capabilities, many recent studies have used CLIP for pixel-level tasks. We explore the potential abilities of CLIP in the field of few-shot segmentation. The current mainstream approach is to utilize support and query features to generate class prototypes and then use the prototype features to match image features. We propose a new method that utilizes CLIP to extract text features for a specific class. These text features are then used as training samples to participate in the model's training process. The addition of text features enables model to extract features that contain richer semantic information, thus making it easier to capture potential class information. To better match the query image features, we also propose a new prototype generation method that incorporates multi-modal fusion features of text and images in the prototype generation process. Adaptive query prototypes were generated by combining foreground and background information from the images with the multi-modal support prototype, thereby allowing for a better matching of image features and improved segmentation accuracy. We provide a new perspective to the task of few-shot segmentation in multi-modal scenarios. Experiments demonstrate that our proposed method achieves excellent results on two common datasets, PASCAL-5i and COCO-20i.

Herpes Simplex Virus Type 1 Infection Induces the Formation of Tunneling Nanotubes.

Herpes simplex virus type 1 (HSV-1) is human specific virus. The intercellular transmission of HSV-1 is essential in its pathogenesis. The tunneling nanotube (TNT), a new mode connecting distant cells, has been found to play an important role in the spread of various viruses like human immunodeficiency virus (HIV) and influenza virus. However, whether HSV-1 can be transmitted through TNTs has not been confirmed. The purpose of this study was to clarify this, and further to determine the effect of inhibiting the actin-related protein 2/3 (Arp2/3) complex on the intercellular transmission of HSV-1. A scanning electron microscope and fluorescence microscope detected the formation of TNTs between HSV-1 infected cells. Envelope glycoprotein D (gD) and envelope glycoprotein E (gE) of HSV-1 and viral particles were observed in TNTs. Treatment with CK666, an inhibitor of the Arp2/3 complex, reduced the number of TNTs by approximately 40-80%. At the same time, the DNA level of HSV-1 in cells and the number of plaque formation units (PFU) were also reduced by nearly 30%. These findings indicated that TNT contributes to HSV-1 transmission and that the inhibition of the Arp2/3 complex could impair HSV-1 transmission, which not only provides a novel insight into the transmission mode of HSV-1, but also a putative new antiviral target.

Hypertension and cystatin C account for sex differences in serum homocysteine levels in acute coronary syndrome subjects with normal serum creatinine.

BACKGROUND: Hyperhomocysteinemia is one of cardiovascular disease risk factors and fasting homocysteine levels are significantly elevated in male compared to female acute coronary syndrome (ACS) patients with normal renal function. However, it is not known the sex related determinants of plasma homocysteine levels in ACS subjects without renal dysfunction. METHODS: A total of 165 ACS participants with normal plasma creatinine who underwent coronary angiography were included in the present study. Clinical parameters, homocysteine, fasting glucose and lipid profile, hemoglobin, white blood cell, platelets, creatinine, cystatin C, blood urea nitrogen, uric acid (UA), and albumin were measured. Multivariate linear regression analyses were used to recognize the predictive factors for homocysteine. RESULTS: The levels of plasma homocysteine were significantly higher in men than in women (P < 0.0001). In males, homocysteine (log10) was positively associated with hypertension (r = 0.569, P < 0.001), creatinine (r = 0.367, P < 0.001) and cystatin C (log10) (r = 0.333, P = 0.001). In females, homocysteine (log10) was positively correlated with age (r = 0.307, P = 0.107), hypertension (r = 0.456, P < 0.001), creatinine (r = 0.341, P = 0.008), cystatin C (log10) (r = 0.429, P = 0.001) and UA (r = 0.569, P < 0.001) whereas was negatively associated with LDL-C (r = - 0.298, P = 0.021) and ApoB (r = - 0.273, P = 0.033). Parameters up to statistical significance in males or females were incorporated into the stepwise linear regression models. In men, hypertension (P < 0.001) and creatinine (P = 0.031) were independently related to homocysteine. Most of the variability of homocysteine levels in males were only determined by hypertension. In women, cystatin C (log10) (P = 0.004) and hypertension (P = 0.005) were independently related to homocysteine (log10). Plasma cystatin C had a higher explanatory value than hypertension in females. CONCLUSIONS: Hypertension and cystatin C could explain most of the sex differences in serum homocysteine levels in ACS subjects with normal serum creatinine. This finding suggested the importance of making different strategies in males and females to manage hyperhomocysteinemia effectively in ACS subjects without renal dysfunction.

Abnormal chromatin remodeling caused by ARID1A deletion leads to malformation of the dentate gyrus.

ARID1A, an SWI/SNF chromatin-remodeling gene, is commonly mutated in cancer and hypothesized to be a tumor suppressor. Recently, loss-of-function of ARID1A gene has been shown to cause intellectual disability. Here we generate Arid1a conditional knockout mice and investigate Arid1a function in the hippocampus. Disruption of Arid1a in mouse forebrain significantly decreases neural stem/progenitor cells (NSPCs) proliferation and differentiation to neurons within the dentate gyrus (DG), increasing perinatal and postnatal apoptosis, leading to reduced hippocampus size. Moreover, we perform single-cell RNA sequencing (scRNA-seq) to investigate cellular heterogeneity and reveal that Arid1a is necessary for the maintenance of the DG progenitor pool and survival of post-mitotic neurons. Transcriptome and ChIP-seq analysis data demonstrate that ARID1A specifically regulates Prox1 by altering the levels of histone modifications. Overexpression of downstream target Prox1 can rescue proliferation and differentiation defects of NSPCs caused by Arid1a deletion. Overall, our results demonstrate a critical role for Arid1a in the development of the hippocampus and may also provide insight into the genetic basis of intellectual disabilities such as Coffin-Siris syndrome, which is caused by germ-line mutations or microduplication of Arid1a.

ASH2L regulates postnatal neurogenesis through Onecut2-mediated inhibition of TGF-ß signaling pathway.

The ability of neural stem/progenitor cells (NSPCs) to proliferate and differentiate is required through different stages of neurogenesis. Disturbance in the regulation of neurogenesis causes many neurological diseases, such as intellectual disability, autism, and schizophrenia. However, the intrinsic mechanisms of this regulation in neurogenesis remain poorly understood. Here, we report that Ash2l (Absent, small or homeotic discs-like 2), one core component of a multimeric histone methyltransferase complex, is essential for NSPC fate determination during postnatal neurogenesis. Deletion of Ash2l in NSPCs impairs their capacity for proliferation and differentiation, leading to simplified dendritic arbors in adult-born hippocampal neurons and deficits in cognitive abilities. RNA sequencing data reveal that Ash2l primarily regulates cell fate specification and neuron commitment. Furthermore, we identified Onecut2, a major downstream target of ASH2L characterized by bivalent histone modifications, and demonstrated that constitutive expression of Onecut2 restores defective proliferation and differentiation of NSPCs in adult Ash2l-deficient mice. Importantly, we identified that Onecut2 modulates TGF-ß signaling in NSPCs and that treatment with a TGF-ß inhibitor rectifies the phenotype of Ash2l-deficient NSPCs. Collectively, our findings reveal the ASH2L-Onecut2-TGF-ß signaling axis that mediates postnatal neurogenesis to maintain proper forebrain function.

Clearance of intracellular bacterial infections by hyaluronic acid-based ROS responsive drug delivery micelles.

Pathogenic bacteria residing inside cells could cause disruption of cellular metabolic balance. Therefore, basing on high oxidative stress response of the intracellular bacteria infected micro-environment, a novel amphipathic micelle (HATAD-TCS) was developed consisting of hyaluronic acid-derivative and reactive oxygen species (ROS) - responsive group and antibacterial agent triclosan (TCS). ROS-generating cinnamaldehyde (CA) was incorporated into ROS-cleavable linkages which are future linked to the 1-decylamine to form hydrophobicity. The cinnamaldehyde released did not just killed bacteria however, also maintained intracellular ROS levels. In this study, the HATAD-TCS micelles have been characterized by scanning electron microscopy (SEM) and dynamic light scattering (DLS). The HATAD-TCS micelles could release drug gradually upon exposure to endogenous ROS being caused by infected intracellular bacteria. Furthermore, the more promising therapeutic effect of the HATAD-TCS micelles was observed in a mouse pneumonia model. These results might highlight a ROS-responsive hyaluronic acid-based nanoparticle, which could effectively treat intracellular bacterial infections.

Cancer Risk and its Association With Diabetes Mellitus in Patients With Acromegaly: A Two Center-based Study.

OBJECTIVE: To compare the incidence of cancer in patients with acromegaly with that of the local population in China and explore possible risk factors. METHODS: Data from 117 patients diagnosed with acromegaly at 2 centers between 2011 and 2022 were analyzed, and their cancer diagnoses were recorded. The cancer standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated by comparison with those of the local population. The patients were divided into 2 groups, having cancer diagnosis or not. The relationships between cancer and sex, body mass index, age, growth hormone levels, diagnosis delay, tumor size, disease duration, treatment, disease status, and other comorbidities were analyzed. RESULTS: Eight (6.8%) of 117 patients were diagnosed with cancer. The incidence of overall (SIR = 3.29, 95% CI = 1.42-6.94), colorectal (SIR = 16.67, 95% CI = 4.45-42.67), and thyroid cancers (SIR = 14.29, 95% CI = 1.73-51.60) was increased, but that of lung cancer (SIR = 4.17, 95% CI = 0.50-15.05) was not. Diagnostic delay (10.1[8.6-14.3] vs 3.8[1.3-9.0]; P = .005) and duration of acromegaly (12.8[8.9-16.4] vs 5.6[2.3-10.9]; P = .008) were prolonged in the cancer group. Diabetes mellitus (odds ratio = 7.01, 95% CI = 1.23-39.99) was an independent risk factor for acromegaly with cancer. CONCLUSION: Acromegaly patients are at a higher risk of cancer and its association with diabetes mellitus. Considering the rarity of the disease, an Acromegaly Cancer Registry Center should be established in China as soon as possible.

Immune-enhancing activity of polysaccharides and flavonoids derived from Phellinus igniarius YASH1.

Introduction: Phellinus igniarius (P. igniarius) (Sanghuang) is a widely used traditional Chinese medicine fungus, and its natural products have great potential for clinical application in immune enhancement. This study aimed to explore the immune-enhancing activity and underlying mechanisms of the polysaccharides and flavonoids derived from Phellinus igniarius (P. igniarius) and to provide a theoretical and experimental basis for the development of novel drugs. Methods: Wild P. igniarius YASH1 from the Loess Plateau in Yan'an region was collected, and polysaccharides and total flavonoids were extracted, isolated and identified from mycelium and sporophore. In vitro antioxidant activity was detected through the scavenging activity of hydroxyl radicals and total antioxidant capacity. Cell Counting Kit-8 and trypan blue detection kit were used to detect the effect of extract polysaccharides and flavonoids on the proliferation and phagocytosis ability of immune cells. To assess the effect of the drugs on cytokine secretion by immune cells and immune recovery in immunocompromised mice, the expression of interleukin (IL)-2, IL-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were examined at the cellular and animal levels. The species composition, abundance of gut microbiota and the altered content of short-chain fatty acids in the feces were analyzed to elucidate the possible mechanisms of drugs by 16S ribosomal RNA (rRNA) amplifiers sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Both polysaccharides and flavonoids derived from mycelium or sporophore had antioxidant activity and may stimulate the expression and secretion of IL-2, IL-6, and IFN-γ in immune cells while inhibiting TNF-α expression and secretion and increasing IL-2, IL-6, and IFN- γ expression levels in mice. Furthermore, polysaccharides and flavonoids from mycelium and sporophore showed different effects on the metabolic response of intestinal short-chain fatty acids (SCFAs) in mice, and the use of these drugs remarkably changed the species composition and abundance of intestinal flora in mice. Discussion: Polysaccharides and flavonoids from P. igniarius YASH1 mycelium and sporophore have in vitro antioxidant activity, and they affect the promotion of cell proliferation, stimulation of IL-2, IL-6, and IFN-γ secretion, and inhibition of TNF-α expression in immune cells. Polysaccharides and flavonoids from P. igniarius YASH1 may enhance immunity in immunocompromised mice and remarkably affect the intestinal flora and content of SCFAs.

3-Methyladenine ameliorates surgery-induced anxiety-like behaviors in aged mice by inhibiting autophagy-induced excessive oxidative stress.

BACKGROUND: Postoperative anxiety is a common surgical complication in older patients. Research has recently linked excessive autophagy to several neurological disorders, including anxiety. This study aimed to determine whether 3-Methyladenine (3-MA) administration reduced anxiety-like behaviors in a mouse model following abdominal exploratory laparotomy. METHODS: An abdominal exploratory laparotomy model of postoperative anxiety was established using male C57BL/6 mice aged 20 months. 3-MA (6, 30, and 150 mg/ml) was administered via intracerebroventricular immediately following surgery. The mice were assessed 14 days after surgery using the marble burying, elevated plus maze tests, and local field potential recording in the amygdala. The levels of expression of phosphorylated-Akt, Beclin-1, LC3B, nuclear factor erythroid 2-related factor 2 (Nrf2)-occupied regions in NeuN-positive cells, superoxide dismutase (SOD) activity, malondialdehyde (MDA), and glutathione (GSH) were measured at 24 h after surgery. RESULTS: The injection of 3-MA reversed the increased number of marbles buried, decreased time spent in the open arm, and enhanced θ oscillation power after 14 days of abdominal exploratory laparotomy. In addition, administration of 3-MA reduced the ratio of phosphorylated- to total-Akt, decreased expression in Beclin-1 and LC3B, attenuated MDA levels, and increased the ratio of Nrf2-occupied areas in NeuN-positive cells, SOD activity, and GSH levels under abdominal exploratory laparotomy conditions. CONCLUSIONS: 3-MA improved anxiety-like behaviors in aged mice undergoing abdominal exploratory laparotomy by inhibiting excessive autophagy-induced oxidative stress. These results suggest that 3-MA could be an effective treatment for postoperative anxiety.

SLC27A2 mediates FAO in colorectal cancer through nongenic crosstalk regulation of the PPARs pathway.

BACKGROUND: Peroxisome proliferator activated receptors (PPARs) are a nuclear hormone receptors superfamily that is closely related to fatty acid (FA) metabolism and tumor progression. Solute carrier family 27 member 2 (SLC27A2) is important for FA transportation and metabolism and is related to cancer progression. This study aims to explore the mechanisms of how PPARs and SLC27A2 regulate FA metabolism in colorectal cancer (CRC) and find new strategies for CRC treatment. METHODS: Biological information analysis was applied to detect the expression and the correlation of PPARs and SLC27A2 in CRC. The protein-protein interaction (PPI) interaction networks were explored by using the STRING database. Uptake experiments and immunofluorescence staining were used to analyse the function and number of peroxisomes and colocalization of FA with peroxisomes, respectively. Western blotting and qRT‒PCR were performed to explore the mechanisms. RESULTS: SLC27A2 was overexpressed in CRC. PPARs had different expression levels, and PPARG was significantly highly expressed in CRC. SLC27A2 was correlated with PPARs in CRC. Both SLC27A2 and PPARs were closely related to fatty acid oxidation (FAO)‒related genes. SLC27A2 affected the activity of ATP Binding Cassette Subfamily D Member 3 (ABCD3), also named PMP70, the most abundant peroxisomal membrane protein. We found that the ratios of p-Erk/Erk and p-GSK3ß/GSK3ß were elevated through nongenic crosstalk regulation of the PPARs pathway. CONCLUSIONS: SLC27A2 mediates FA uptake and beta-oxidation through nongenic crosstalk regulation of the PPARs pathway in CRC. Targeting SLC27A2/FATP2 or PPARs may provide new insights for antitumour strategies.

Disulfide-containing polymer delivery of C527 and a Platinum(IV) prodrug selectively inhibited protein ubiquitination and tumor growth on cisplatin resistant and patient-derived liver cancer models.

USP1 (Ubiquitin-specific protease 1) is closely related to the prognosis of patients with liver cancer and plays an important role in DNA damage repair. C527 is a selective USP1 inhibitor (USP1i), which can regulate the protein ubiquitination to effectively inhibit the proliferation of cancer cells. However, its clinical application is hindered due to the poor water solubility and lack of tumor targeting. Moreover, the efficacy of single use of USP1i is still limited. Herein, a glutathione (GSH) sensitive amphiphilic polymer (poly (2-HD-co-HPMDA)-mPEG, PHHM) with disulfide bonds in the main chain was designed to encapsulate the USP1i as well as platinum (IV) prodrug (Pt (IV)-C12), resulting in the formation of composite nanoparticles, i.e., NP-Pt-USP1i. NP-Pt-USP1i can inhibit the DNA damage repair by targeting USP1 by the encapsulated USP1i, which ultimately increases the sensitivity of tumor cells to cisplatin and enhances the anti-cancer efficacy of cisplatin. Finally, an intraperitoneal tumor mice model and a patient-derived xenograft (PDX) of liver cancer mice model were established to prove that NP-Pt-USP1i could effectively inhibit the tumor growth. This work further validated the possibility of therapeutically target USP1 by USP1i in combination with DNA damaging alkylating agents, which could become a promising cancer treatment modality in the future.

Soil copper concentration map in mining area generated from AHSI remote sensing imagery.

Hyperspectral remote sensing has the advantages to predict and map soil heavy metal concentration over conventional monitoring methods and multispectral remote sensing. In quantitative applications of hyperspectral remote sensing imagery, the contribution of hyperspectral bands is different, and abnormal prediction values resulted from incorrectly classified bare soil images are a major problem. In this study, a variable weighting method was proposed to weight the hyperspectral bands, and a probability threshold was used to improve the classification to mitigate the problem of abnormal prediction values. The variable weighting was conducted by using the absorption depths obtained by continuum removal. Soil samples were collected from a mining area in southwestern China. Hyperspectral remote sensing imagery was acquired by the Advanced Hyperspectral Imager (AHSI) abroad on Geofen-5 (GF-5) satellite. Genetic algorithm and partial least squares regression (PLSR) were adopted to calibrate prediction models. In prediction of soil copper (Cu) concentration, root mean square error (RMSE) and coefficient of determination (R2) were 21.59 mg kg-1 and 0.60 for the prediction using raw reflectance spectra, and the values were improved to 18.33 mg kg-1 and 0.71 by using the weighted reflectance spectra. The developed prediction model was applied to the AHSI imagery to predict Cu concentration in bare soil areas. In prediction of Cu concentration using the AHSI imagery, negative prediction values were eliminated by using the bare soil image extracted by the improved classification. Based on the prediction, soil Cu concentration map was generated by kriging spatial interpolation. The result indicates that the proposed variable weighting method is effective and the problem of abnormal prediction values could be mitigated by using improved bare soil images. Further analysis indicates that some indices with proper thresholds also could be used to get improved bare soil images.

Glutathione-Responsive Nanoparticles of Camptothecin Prodrug for Cancer Therapy.

Camptothecin (CPT) is a potent chemotherapeutic agent for various cancers, but the broader application of CPT is still hindered by its poor bioavailability and systemic toxicity. Here, a prodrug that releases CPT in response to glutathione (GSH), which is commonly overexpressed by cancer cells is reported. Through assembling with PEGylated lipids, the prodrug is incorporated within as-assembled nanoparticles, affording CPT with a prolonged half-life in blood circulation, enhanced tumor targetingability, and improved therapeutic efficacy. Furthermore, such prodrug nanoparticles can also promote dendritic cell maturation and tumor infiltration of CD8+ T cells, providing a novel strategy to improve the therapeutic efficacy of CPT.