Regulating Catalytic Oxidation Enantiomers Behavior by Imparting Chiral Microenvironment in Zr-Based Metal-Organic Frameworks.

Chiral inversions of enantiomers have significantly different biological activities, so it is important to develop simple and effective methods to efficiently identify optically pure compounds. Inspired by enzyme catalysis, the construction of chiral microenvironments resembling enzyme pockets in the pore space structure of metal-organic frameworks (MOFs) to achieve asymmetric enantioselective recognition and catalysis has become a new research hotspot. Here, a super-stable porphyrin-containing material PCN-224 is constructed by solvothermal method and a chiral microenvironment around the existing catalytic site of the material is created by post-synthesis modifications of the histidine (His) enantiomers. Experimental and theoretical calculations results show that the modulation of chiral ligands around Zr oxide clusters produces different spatial site resistances, which can greatly affect the adsorption and catalytic level of the enantiomeric molecules of tryptophan guests, resulting in a good enantioselective property of the material. It provides new ideas and possibilities for future chiral recognition and asymmetric catalysis.

Defect-engineered chiral metal-organic frameworks.

Chirality has an important impact on chemical and biological research, as most active substances are chiral. In recent decades, metal-organic frameworks (MOFs), which are assembled from metal ions or clusters and organic linkers via metal-ligand bonding, have attracted considerable scientific interest due to their high crystallinity, exceptional porosity and tunable pore sizes, high modularity, and diverse functionalities. Since the discovery of the first functional chiral metal-organic frameworks (CMOFs), CMOFs have been involved in a variety of disciplines such as chemistry, physics, optics, medicine, and pharmacology. The introduction of defect engineering theory into CMOFs allows the construction of a class of defective CMOFs with high hydrothermal stability and multi-stage pore structure. The introduction of defects not only increases the active sites but also enlarges the pore sizes of the materials, which improves chiral recognition, separation, and catalytic reactions, and has been widely investigated in various fields. This review describes the design and synthesis of various defective CMOFs, their characterization, and applications. Finally, the development of the materials is summarized, and an outlook is given. This review should provide researchers with an insight into the design and study of complex defective CMOFs.

Supramolecular Anchored Copper Nanoclusters for a Multipath Electrochemiluminescence Probe.

Copper nanoclusters (Cu NCs) are highly promising nanomaterials in the field of electrochemiluminescence (ECL). Nevertheless, their limited stability and efficiency have impeded their practical applications. Here, we introduced a novel supramolecular anchoring strategy resulting in the creation of exceptionally stable Cu NCs (CET-Cu NCs) with remarkable ECL properties. Specifically, CET-Cu NCs exhibited a relative ECL efficiency (ΦECL) of 62% based on the annihilation ECL efficiency of [Ru(bpy)3]2+ (100%), with tripropylamine employed as a coreactant. Moreover, CET-Cu NCs can generate ECL emission through multiple different paths, which enables them to serve as signal probes in a wider range of testing scenarios, thereby enhancing the reliability and robustness of sensing and analytical systems. To demonstrate the practical utility, CET-Cu NCs were selected as an ECL signal probe for a sensing platform that facilitated ultrasensitive detection of progesterone via oriented immobilization technology and antibody/aptamer sandwich assays. This study surmounted the barriers to the practical application of Cu NCs through the implementation of a supramolecular anchoring strategy, thereby providing enhanced utility of Cu NCs in ECL sensing and analysis.

Uptake, accumulation, and degradation of dibutyl phthalate by three wetland plants.

The uptake and degradation mechanisms of dibutyl phthalate (DBP) by three wetland plants, namely Lythrum salicaria, Thalia dealbata, and Canna indica, were studied using hydroponics. The results revealed that exposure to DBP at 0.5 mg/L had no significant effect on the growth of L. salicaria and C. indica but inhibited the growth of T. dealbata. After 28 days, DBP concentrations in the roots of L. salicaria, T. dealbata, and C. indica were 8.74, 5.67, and 5.46 mg/kg, respectively, compared to 2.03-3.95 mg/kg in stems and leaves. Mono-n-butyl phthalate concentrations in L. salicaria tissues were significantly higher than those in the other two plants at 23.1, 15.0, and 13.6 mg/kg in roots, stems, and leaves, respectively. The roots of L. salicaria also had the highest concentration of phthalic acid, reaching 2.45 mg/kg. Carboxylesterase, polyphenol oxidase, and superoxide dismutase may be the primary enzymes involved in DBP degradation in wetland plants. The activities of these three enzymes exhibited significant changes in plant tissues. The findings suggest L. salicaria as a potent plant for phytoremediation and use in constructed wetlands for the treatment of DBP-contaminated wastewater.

Thoracic Endovascular Aortic Repair of Highly Tapered Type B Aortic Dissection with Proximal Tapered Stent Grafts and Distal Restrictive Stent Grafts.

BACKGROUND: This study evaluated aortic remodeling in highly tapered type B aortic dissection (TBAD) patients who underwent thoracic endovascular aortic repair (TEVAR) with a proximal tapered stent graft plus a distal restrictive stent graft to maximize thoracic coverage while avoiding distal excessive oversizing. METHODS: Thirty-four patients presenting with highly tapered TABD were randomized to restricted TEVAR (r-TEVAR) and standard TEVAR groups. Highly tapered TBAD was defined as the maximal diameter of the true lumen at proximal and distal thoracic aorta landing zone tapers greater than 8 mm or taper ratio greater than 20%. Patients in the r-TEVAR group underwent proximal tapered stent grafts plus distal restrictive stent grafts, to match the taper ratio of the descending thoracic aorta (DTA) and extend the length of stent coverage. Patients in the standard TEVAR group underwent proximal tapered stent grafts implantation without distal restrictive stent grafts. Aortic remodeling was estimated by computed tomography angiography (CTA) during the follow-up. RESULTS: In total, 16 patients underwent r-TEVAR, and 18 patients underwent standard TEVAR. The taper ratio of the stent graft matched the DTA in the r-TEVAR group (24.7 ± 3.4% vs. 27.3 ± 4.2%, P = 0.068), but did not match that in the standard TEVAR group (13.5 ± 3.3% vs. 30.5 ± 9.6%, P < 0.001). The length of stent graft coverage in the r-TEVAR group was longer than that in the standard TEVAR group (220.4 ± 21.1 mm vs. 175.3 ± 17.8 mm, P < 0.001). Compared with the standard TEVAR group, the r-TEVAR group had better complete remodeling of the DTA at 6 months (40% vs. 5.6%, P = 0.03), 12 months (60% vs. 16.7%, P = 0.027), and 24 months (78.6% vs. 41.2%, P = 0.036) after the operation. There was no difference in the cumulative survival rate between the r-TEVAR and standard TEVAR groups (P = 0.166). CONCLUSIONS: The r-TEVAR with overlapping proximal tapered stent grafts and distal restrictive stent grafts can match the taper of highly tapered TABD, extend the length of stent graft coverage, and lead to better remodeling of the DTA than standard TEVAR.

Combined Detection of Plasma Tumor Necrosis Factor-α Converting Enzyme and Notch1 is Valuable in Screening Endoleak After Endovascular Abdominal Aortic Aneurysms Repair.

OBJECTIVES: Endoleaks may be present in up to 25% of patients after endovascular abdominal aortic aneurysm repair (EVAR) and there is no clear consensus on valuable biomarkers to determine endoleak presence. The aim of this study was to examine the potential value of plasma tumor necrosis factor-α converting enzyme (TACE) and Notch1 concentrations in determining endoleak presence after EVAR. METHODS: A total of 110 patients with abdominal aortic aneurysm who underwent EVAR were enrolled in our study, and plasma TACE and Notch1 concentrations were measured prior to and 6 months after EVAR. Logistic regression was performed to assess the association of postoperative plasma TACE and Notch1 concentrations with endoleak after adjusting for potential confounders. The ability of plasma TACE and Notch1 concentrations to determine endoleak presence was assessed using receiver operating characteristic curves and area under the curve (AUC). RESULTS: Twenty-four patients developed endoleaks 6 months after EVAR. Both postoperative plasma TACE and Notch1 concentrations were higher in patients with endoleak than in those without endoleak (2376.4 ± 28.1 pg/ml vs. 2094.1 ± 27.3 pg/ml, P < 0.01; 218.6 ± 1.9 pg/ml vs. 195.0 ± 2.1 pg/ml, P < 0.01, respectively). The AUCs from receiver operating characteristic curve analysis of plasma TACE and Notch1 concentrations in determining endoleak presence were 0.844 (95% CI 0.771 to 0.918, P < 0.01) and 0.860 (95% CI 0.791 to 0.930, P < 0.01), respectively. Combining the detection of plasma Notch1 and TACE concentrations could improve the accuracy in determining endoleak presence (AUC 0.930, 95% CI 0.883 to 0.978, P < 0.01). The predicted probability cutoff of 0.22 yielded a sensitivity of 95.8% and a specificity of 82.6% for endoleak presence. CONCLUSIONS: Plasma TACE and Notch1 levels can discriminate patients with and without endoleak 6 months after EVAR, and have a potential role in screening patients requiring computed tomography angiography.

Predisposing Factors for Migration of the Iliac Limb and Reintervention after Endovascular Abdominal Aortic Aneurysm Repair.

BACKGROUND: Migration of the iliac limb after endovascular abdominal aortic aneurysm repair (EVAR) can result in type 1b and 3 endoleaks, which are relatively common causes of reintervention after EVAR. The aim of the present study was to investigate the factors influencing migration of the iliac limb and methods of treatment. METHODS: From April 2012 to September 2017, 4 patients experienced migration of the iliac limb, requiring additional iliac stent graft implantation intraoperatively or at follow-up at our institute. Patient 1 was a 74-year-old man in whom preoperative computed tomography angiography (CTA) revealed a large aneurysm. The patient underwent EVAR with a bifurcated stent graft, and the left iliac stent graft migrated into the aneurysm sac. Patient 2 was a 53-year-old man in whom CTA revealed a large abdominal aortic aneurysm (AAA) involving the bilateral common iliac artery (CIA), with occlusion of the left hypogastric artery. An iliac stent graft was deployed to the right CIA to preserve the hypogastric artery. CTA, at 5 years of follow-up, showed migration of the right iliac limb and impending rupture. Patient 3 was a 61-year-old man with a ruptured AAA, and CTA revealed a large AAA and dilated CIA. The patient underwent EVAR with a bifurcated stent graft. Three years after EVAR, CTA showed that the right iliac limb migrated and kinked, with rupture of the stent graft. Patient 4 was an 80-year-old man with a ruptured AAA and aortocaval fistula. CTA revealed a large aneurysm involving the bilateral CIA. The patient underwent urgent EVAR with a bifurcated stent graft, and a cuff was deployed to seal the landing zone of the left CIA to preserve the hypogastric artery. Type 3 endoleak occurred because of the migration and detachment of the left iliac limb. All 4 patients underwent additional iliac stent graft implantation to connect or reline the iliac limb. RESULTS: The mean diameter of the aneurysms was 85.3 ± 18.9 mm, and 2 patients were diagnosed with ruptured AAAs. The mean diameter, length, and proportional engagement rate of the CIA that experienced migration of the iliac limb were 25.50 ± 11.1 mm, 32.8 ± 6.6 mm, and 72.75% ± 17.88%, respectively. Oversizing of the iliac stent graft was 10-20% in 2 patients and was less than 10% in the other 2 patients. The migrated iliac limbs were bell-bottom stent grafts. All patients underwent additional iliac stent graft implantation successfully, and there were no deaths or complications perioperatively. The patients were followed up from 7 months to 3 years and remained in good condition. CONCLUSIONS: Migration of the iliac limb after EVAR was influenced by a complex combination of several factors including a large aneurysm (>60 mm in diameter), dilated or aneurysmal CIA (>18 mm in diameter), short length of fixation (<70%), lower degree of iliac limb oversizing (<10-20%), and bell-bottom of the iliac limb. Patients with these factors require more vigorous surveillance after EVAR. The implantation of an additional stent graft is effective and is the most common reintervention procedure.

Effect of phosphate amendments on improving the fertilizer efficiency and reducing the mobility of heavy metals during sewage sludge composting.

Composting has been globally applied as an effective and cost-efficient process to manage and reuse sewage sludge. In the present study, four different phosphates as well as a mixture of ferrous sulfate and monopotassium phosphate were used in sewage sludge composting. The results showed that these phosphate amendments promoted an increase in temperature and the degradation of organic matter as well as reduction on nitrogen loss during 18 days of composting. In addition, ferrous sulfate and phosphate had a synergistic effect on reducing nitrogen loss. The contents of total phosphorus and available phosphorus in the compost with addition of 1% phosphate were 40.9% and 66.1% higher than the compost with control treatment. Using the BCR (Community Bureau of Reference) sequential extraction procedure, the addition of calcium magnesium phosphate significantly reduced the mobility factor of Cd, Zn and Cu by 24.2%, 1.7% and 18.8%, respectively. The mobility factors of Pb were increased in all samples, but the monopotassium phosphate treated sample exhibited the greatest Pb passivation ability with the lowest mobility factor increase (1.8%) among all treatments. The X-ray diffraction patterns of compost samples indicated that the passivation mechanism of Cu and Zn may be the forming CuFeS2 and ZnCu(P2O7) crystals during sewage sludge composting. The germination index showed that the compost of all treatments was safe for agricultural application; the germination index of the calcium magnesium phosphate treatment was 99.9 ±â€¯11.8%, which was the highest among all treatments.

Oxygen Monitoring Equipment for Sewage-Sludge Composting and Its Application to Aeration Optimization.

Oxygen is an important parameter for organic-waste composting, and continuous control of the oxygen in a composting pile may be beneficial. The oxygen consumption rate can be used to measure the degree of biological oxidation and decomposition of organic matter. However, without having a real-time online device to monitor oxygen levels in the composting pile, the adjustment and optimization of the composting process cannot be directly implemented. In the present study, we researched and developed such a system, and then tested its stability, reliability, and characteristics. The test results showed that the equipment was accurate and stable, and produced good responses with good repeatability. The equilibrium time required to detect oxygen concentration in the composting pile was 50 s, and the response time for oxygen detection was less than 2 s. The equipment could monitor oxygen concentration online and in real time to optimize the aeration strategy for the compost depending on the concentration indicated by the oxygen-measuring equipment.

Genetic analysis and clinicopathological features of ALK-rearranged renal cell carcinoma in a large series of resected Chinese renal cell carcinoma patients and literature review.

AIMS: Anaplastic lymphoma kinase (ALK)-rearranged renal cell carcinoma (RCC) is a rare subtype of RCC reported in recent years, with eight cases so far. The aims of the present study were to screen ALK-rearranged cases from a large cohort of RCCs in China to determine the frequency of ALK rearrangement and investigate the clinicopathological features and outcomes. METHODS AND RESULTS: Tissues from a total of 477 RCC patients in China were embedded into tissue microarrays for immunostaining. Fluorescence in-situ hybridization (FISH) and fluorescence quantitative reverse transcription polymerase chain reaction (RT-PCR) were applied to identify and confirm the rearrangement of ALK, and to identify the genes fused with ALK. ALK expression was identified in two of 477 RCCs. By FISH analysis, the two tumours showed either a 1R1G1F or a 2R2G signal pattern, indicating rearrangement involving ALK. Fluorescence quantitative RT-PCR detected the TPM3-ALK fusion and EML4-ALK fusion transcripts in the two tumours, respectively. Follow-up data were analyzed for the two cases and eight other ALK-rearranged RCCs reported in the literature. Two patients died from RCCs, on the 16th month and 48th month after surgery, respectively. The 5-year cancer-specific survival rate of patients with the 10 ALK-rearranged RCCs was lower than that of patients with International Society of Urological Pathology (ISUP) G1, G2 and G3 clear cell RCC (CCRCC) and papillary RCC (PRCC), but higher than that of patients with G4 CCRCC and PRCC. CONCLUSIONS: ALK-rearranged RCC is a rare subtype of adult RCC and is associated with distinct histological features and a poor prognosis. Identification of ALK-rearranged RCC has important clinical significance, because patients might benefit from ALK inhibitor therapy as used in lung adenocarcinoma.

Distinct immunophenotypes and prognostic factors in renal cell carcinoma with sarcomatoid differentiation: a systematic study of 19 immunohistochemical markers in 42 cases.

BACKGROUND: Renal cell carcinoma (RCC) with sarcomatoid differentiation is a relatively rare tumor containing both carcinoma and sarcomatoid components. However, there has not been a systemic study on immunophenotypes of renal cell carcinoma with sarcomatoid differentiation, especially using some renal specific immunohistochemical markers. In this study, we aimed to comprehensively investigate the distinct immunophenotypes of RCC with sarcomatoid differentiation to analyze the pathogenesis of sarcomatoid differentiation and identify new prognostic factors in RCC with sarcomatoid differentiation. METHODS: A total of 42 cases of RCCs with sarcomatoid differentiation were enrolled into the study. Immunohistochemistry study was performed on tissue microarrays to evaluate the expressions of 19 immunohistochemical markers including a series of epithelial, mesenchymal markers and RCC specific markers. Kaplan-Meier method was applied to assess the prognostic values of CD10, CAIX, p53 and Bcl-2. RESULTS: Histologically, 42 cases of RCCs with sarcomatoid differentiation presented with different proportions of carcinoma and sarcomatoid components. The cohort contained 35 cases of clear cell renal cell carcinoma (CCRCC) and 7 cases of chromophobe renal cell carcinoma (ChRCC) based on the carcinoma components. Immunohistochemically, all cases were positive for vimentin, and 80% of cases showed immunostaining for at least one epithelial marker, such as CK, EMA, CK7 and CK18. Notably, the expression rates of CAIX, CD10 and PAX8 in sarcomatoid cells were 76%, 76% and 64%, respectively. The carcinoma component of the tumors showed differentient labeling for CAIX, CD10, vimentin, CK7 and CD117 in CCRCC vs ChRCC, but the sarcomatoid component lost the specificity for these markers ( p < 0.05). Patients with positive expressions of CAIX, p53 and Bcl-2 had a poor prognosis. CONCLUSIONS: The sarcomatoid cells in RCC with sarcomatoid differentiation express both epithelial and mesenchymal markers, supporting their epithelial origin. PAX8, CAIX and CD10 could be used as the reliable and useful markers to determine the renal origin of sarcomatoid cells such as in fine needle aspiration cases and metastatic RCC with sarcomatoid differentiation. CAIX, p53 and Bcl-2 might play important roles in the transformation from renal cell carcinoma to high malignant sarcomatoid differentiation, and these three immunohistochemical markers are adverse prognostic factors for the survival of patients with RCC with sarcomatoid differentiation.

[Change of Serum Angiopoietin-related Growth Factor in Patients with Abdominal Aortic Aneurysm and Its Clinical Significance].

OBJECTIVE: To investigate the changes and value of plasma angiopoietin-related growth factor (AGF) in patients with abdominal aortic aneurysm (AAA). METHODS: Serum AGF level was analyzed in 50 AAA patients and in 56 healthy subjects. AGF and adiponectin were quantified by enzyme-linked immunosorbent assay. Routine testing of blood biochemistry and high-sensitivity C-reactive protein were performed. RESULTS: The plasma AGF level was significantly higher in AAA patients than in the controls [(87.91±96.87) µg/L vs. (56.89±41.32) µg/L, P=0.040],while serum adiponectin level showed no significant difference between these two groups. The plasma AGF level in patients with an AAA>5 cm and those with AAA between 3 cm and 5 cm were (96.08±68.61) µg/L and (75.27±46.05) µg/L. CONCLUSIONS: Plasma AGF is highly expressed in AAA patients. Higher serum AGF level is associates with larger AAA. Thus, AGF may be a potential serum biomarker for AAA.

Single-cell network analysis reveals gene expression programs for Arabidopsis root development and metabolism.

Single-cell RNA-sequencing datasets of Arabidopsis roots have been generated, but related comprehensive gene co-expression network analyses are lacking. We conducted a single-cell gene co-expression network analysis with publicly available scRNA-seq datasets of Arabidopsis roots using a SingleCellGGM algorithm. The analysis identified 149 gene co-expression modules, which we considered to be gene expression programs (GEPs). By examining their spatiotemporal expression, we identified GEPs specifically expressed in major root cell types along their developmental trajectories. These GEPs define gene programs regulating root cell development at different stages and are enriched with relevant developmental regulators. As examples, a GEP specific for the quiescent center (QC) contains 20 genes regulating QC and stem cell niche homeostasis, and four GEPs are expressed in sieve elements (SEs) from early to late developmental stages, with the early-stage GEP containing 17 known SE developmental regulators. We also identified GEPs for metabolic pathways with cell-type-specific expression, suggesting the existence of cell-type-specific metabolism in roots. Using the GEPs, we discovered and verified a columella-specific gene, NRL27, as a regulator of the auxin-related root gravitropism response. Our analysis thus systematically reveals GEPs that regulate Arabidopsis root development and metabolism and provides ample resources for root biology studies.

Succinate dehydrogenase A deficient renal cell carcinoma: A rare renal tumor distinct from typical Succinate dehydrogenase deficient renal cell carcinoma.

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare subtype of RCC classified as a molecularly defined RCC in the fifth edition of the WHO. Most gene alterations in patients with SDH-deficient RCC involve the SDHB subunit, with less involvement of the SDHC, SDHA, and SDHD subunits. Four cases of SDHA-deficient RCC have been reported in the literature, of which one case was associated with an NF2 gene mutation. Herein, we report six novel SDHA-deficient RCC cases, including two cases with NF2 gene mutations. In contrast to the typical morphology of SDH-deficient RCC, the six tumors mainly displayed glandular, sheet-like, or papillary growth patterns with prominent nucleoli (Grades 2-3), among which two cases with NF2 mutations had prominent nucleoli (Grade 3), large transparent vacuoles in the cytoplasm, and a large number of lymphocytes in the stroma. Six tumors showed negative immunohistochemical staining for SDHA and SDHB, and three cases presented with high expression of PD-L1. Second-generation sequencing revealed novel pathogenic somatic SDHA gene mutation and NF2 gene mutations in six and two tumors, respectively. Follow-up data were collected for the six patients with a follow-up time ranging from 7 to 268 months, and all six patients have survived to date. One patient received targeted therapy for tumor metastasis to the lungs after seven months, and another patient with an NF2 gene mutation received immunotherapy for lymph node metastasis revealed during surgery. SDHA-deficient RCCs with NF2 gene mutations have the ability to metastasize but might respond well to immunotherapy. For the first time, we report the largest number of SDHA-deficient RCC cases and comprehensively investigate their clinicopathological and molecular features to provide important guidance for diagnosis and clinical immunotherapy.

A novel tumor metastasis suppressor gene LASS2/TMSG1 interacts with vacuolar ATPase through its homeodomain.

LASS2/TMSG1 was a novel tumor metastasis suppressor gene, which was first cloned by our laboratory from non-metastatic and metastatic cancer cell variants of human prostate carcinoma PC-3M using mRNA differential display in 1999. LASS2/TMSG1 could interact with the C subunit of vacuolar ATPase (V-ATPase, ATP6V0C) and regulate V-ATPase activity. In an attempt to provide molecular mechanism of the interaction between LASS2/TMSG1 and V-ATPase, we constructed four variant transfectants containing different functional domain of LASS2/TMSG1 and stably transfected the variants to human prostate cancer cell line PC-3M-1E8 cell with high metastatic potential. Results showed that there were no obvious differences of V-ATPase expression among different transfected cells and the control. However, V-ATPase activity and intracellular pH was significantly higher in the variant transfectants with Homeodomain of LASS2/TMSG1 than that in the control using the pH-dependent fluorescence probe BECEF/AM. Immunoprecipitation, immunofluorescence and immuno-electron microscope alone or in combination demonstrated the direct interaction of Homeodomain of LASS2/TMSG1 and ATP6V0C. Loss of Homeodomain markedly enhanced the proliferation ability but weakened the apoptotic effect of LASS2/TMSG1 in PC-3M-1E8 cells. These lines of results for the first time contribute to the conclusion that LASS2/TMSG1 could regulate V-ATPase activity and intracellular pH through the direct interaction of its Homeodomain and the C subunit of V-ATPase. Their interaction could play important roles in the apoptosis of tumor cells.

Cyber-physical oil spill monitoring and detection for offshore petroleum risk management service.

Petroleum industry has started to embrace the advanced petroleum cyber-physical system (CPS) technologies. Offshore petroleum CPS is particularly hard to build, mainly due to the difficulty in detecting and preventing offshore oil leaking. During the oil exploration and transportation process, the remote multi-sensing technology is typically employed for emerging service. It can be utilized for leak detection by enabling the underwater modeling of an offshore petroleum CPS. However, such a technology suffers from insufficient remote sensing resources and expensive computational overhead. In this work, a cross-entropy based leak detection technique is proposed to detect the oil leak, which facilitates the understanding of the oil leak induced marine pollution. Furthermore, a hierarchical parallel approach is proposed on the super computer Tianhe-2 to improve the efficiency of the proposed leak detection technique. Experimental results on Penglai oil spill events demonstrate that the proposed method can effectively identify the sources of oil spilling with accuracy up to [Formula: see text].

Living Cells and Cell-Derived Vesicles: A Trojan Horse Technique for Brain Delivery.

Brain diseases remain a significant global healthcare burden. Conventional pharmacological therapy for brain diseases encounters huge challenges because of the blood-brain barrier (BBB) limiting the delivery of therapeutics into the brain parenchyma. To address this issue, researchers have explored various types of drug delivery systems. Cells and cell derivatives have attracted increasing interest as "Trojan horse" delivery systems for brain diseases, owing to their superior biocompatibility, low immunogenicity, and BBB penetration properties. This review provided an overview of recent advancements in cell- and cell-derivative-based delivery systems for the diagnosis and treatment of brain diseases. Additionally, it discussed the challenges and potential solutions for clinical translation.

Targeting lactate metabolism and immune interaction in breast tumor via protease-triggered delivery.

Lactate is abundant in cancer tissues due to active glycolysis (aka Warburg effect) and mediates crosstalk between tumor cells and the immune microenvironment (TIME) to promote the progression of breast cancer. Quercetin (QU) is a potent monocarboxylate transporters (MCT) inhibitor, which can reduce lactate production and secretion of tumor cells. Doxorubicin (DOX) can induce immunogenic cell death (ICD), which promotes tumor-specific immune activation. Thus, we propose a combination therapy of QU&DOX to inhibit lactate metabolism and stimulate anti-tumor immunity. To enhance tumor-targeting efficiency, we developed a legumain-activatable liposome system (KC26-Lipo) with modification of KC26 peptide for co-delivery of QU&DOX for modulation of tumor metabolism and TIME in breast cancer. The KC26 peptide is a legumain-responsive, hairpin-structured cell-penetrating peptide (polyarginine) derivative. Legumain is a protease overexpressed in breast tumors, allowing selective activation of the KC26-Lipo to subsequently facilitate intra-tumoral and intracellular penetration. The KC26-Lipo effectively inhibited 4T1 breast cancer tumor growth through chemotherapy and anti-tumor immunity. Besides, inhibition of lactate metabolism suppressed the HIF-1α/VEGF pathway and angiogenesis and repolarized the tumor-associated macrophages (TAM). This work provides a promising breast cancer therapy strategy by regulating lactate metabolism and TIME.

Natural products as potential lead compounds to develop new antiviral drugs over the past decade.

Virus infection has been one of the main causes of human death since the ancient times. Even though more and more antiviral drugs have been approved in clinic, long-term use can easily lead to the emergence of drug resistance and side effects. Fortunately, there are many kinds of metabolites which were produced by plants, marine organisms and microorganisms in nature with rich structural skeletons, and they are natural treasure house for people to find antiviral active substances. Aiming at many types of viruses that had caused serious harm to human health in recent years, this review summarizes the natural products with antiviral activity that had been reported for the first time in the past ten years, we also sort out the source, chemical structure and safety indicators in order to provide potential lead compounds for the research and development of new antiviral drugs.

The spatial pattern and influencing factors of tourism eco-efficiency in Inner Mongolia, China.

Background: Tourism eco-efficiency is a performance basis for evaluating green total factor productivity and sustainable development. Objective: The objective of this study was to measure tourism eco-efficiency in Inner Mongolia and explore its influencing factors. The aim was to provide an accurate reference for improving the quality and efficiency of tourism in Inner Mongolia and promoting the sustainable development of the regional economy and society. Methods: Tourism eco-efficiency in Inner Mongolia from 2009 to 2019 was calculated using a super-slacks-based measure (SBM) model with an undesirable output. The spatial variation function was used to explore the spatial evolution pattern of tourism eco-efficiency in Inner Mongolia, and the influencing factors of the spatial evolution were analyzed by geographically weighted regression. Results: Tourism eco-efficiency in Inner Mongolia is relatively low. Eco-efficiency values among cities in Inner Mongolia vary, and their distribution is not balanced. The structural eco-efficiency of tourism in Inner Mongolia has been consistent from 2009 to 2019. The degree of homogenization in the overall direction is relatively good. Furthermore, its spatial distribution form and internal structure evolution show a certain regularity and continuity. The pattern evolution of tourism eco-efficiency in Inner Mongolia is jointly driven by the economic level, environmental regulation, industrial structure, traffic conditions, resource endowment, and tourism reception facilities. These influencing factors show obvious spatial heterogeneity. Conclusion: From the perspective of Inner Mongolia, the difference in the tourism eco-efficiency value from 2009 to 2019 was relatively large, but the number of effective areas in the efficiency frontier generally showed a fluctuating growth trend. The range parameters of tourism eco-efficiency showed a decreasing trend, and the spatial correlation effect of tourism eco-efficiency in Inner Mongolia showed a decreasing trend under the influence of structural and spatial differentiation.