Dual-mode photoelectrochemical radar based on CdS quantum dot and Ce-MOF for detection of low-abundance disease-associated proteins.

Herein, we developed a convenient and versatile dual-mode electrochemiluminescence (ECL) and photoelectrochemistry (PEC) sensing radar for the detection of Prostate-specific antigen (PSA), which has important implications for detection of low-abundance disease-associated proteins. Cerium-based metal-organic framework (Ce-MOFs) were firstly modified on the electrode, showing well ECL and PEC property. In particular, a unique multifunctional Au@CdS quantum dots (QDs) probe loaded numerous QDs and antibody was fabricated, not only displaying strong ECL and PEC signals, but also having specific recognition to PSA. After the signal probe was linked to the electrode by immune reaction, much amplified signals of ECL and PEC were generated for double-mode detection of PSA. Therefore, this work proposed a multifunctional Au@CdS QDs signal probe with excellent ECL and PEC performance, and developed an ultrasensitive photoelectric biosensing platform for dual-mode detection, which provides an effective method for health monitoring of cancer patients.

Investigating the Impact of Irrigation on Malaria Vector Larval Habitats and Transmission Using a Hydrology-Based Model.

A combination of accelerated population growth and severe droughts has created pressure on food security and driven the development of irrigation schemes across sub-Saharan Africa. Irrigation has been associated with increased malaria risk, but risk prediction remains difficult due to the heterogeneity of irrigation and the environment. While investigating transmission dynamics is helpful, malaria models cannot be applied directly in irrigated regions as they typically rely only on rainfall as a source of water to quantify larval habitats. By coupling a hydrologic model with an agent-based malaria model for a sugarcane plantation site in Arjo, Ethiopia, we demonstrated how incorporating hydrologic processes to estimate larval habitats can affect malaria transmission. Using the coupled model, we then examined the impact of an existing irrigation scheme on malaria transmission dynamics. The inclusion of hydrologic processes increased the variability of larval habitat area by around two-fold and resulted in reduction in malaria transmission by 60%. In addition, irrigation increased all habitat types in the dry season by up to 7.4 times. It converted temporary and semi-permanent habitats to permanent habitats during the rainy season, which grew by about 24%. Consequently, malaria transmission was sustained all-year round and intensified during the main transmission season, with the peak shifted forward by around 1 month. Lastly, we evaluated the spatiotemporal distribution of adult vectors under the effect of irrigation by resolving habitat heterogeneity. These findings could help larval source management by identifying transmission hotspots and prioritizing resources for malaria elimination planning.

A sequential scheme including PTT and 2'3'-cGAMP/CQ-LP reveals the antitumor immune function of PTT through the type I interferon pathway.

Photothermal therapy (PTT) is a promising antitumor treatment that is easy to implement, minimally invasive, and precisely controllable, and evokes strong antitumor immunity. We believe that a thorough elucidation of its underlying antitumor immune mechanisms would contribute to the rational design of combination treatments with other antitumor strategies and consequently potentiate clinical use. In this study, PTT using indocyanine green (ICG) induced STING-dependent type I interferon (IFN) production in macrophages (RAW264.7 and bone marrow-derived macrophages (BMDMs)), as proven by the use of a STING inhibitor (C178), and triggered STING-independent type I IFN generation in tumor cells (CT26 and 4T1), which was inhibited by DNase pretreatment. A novel liposome coloaded with the STING agonist 2'3'-cGAMP (cGAMP) and chloroquine (CQ) was constructed to achieve synergistic effect with PTT, in which CQ increased cGAMP entrapment efficiency and prevented STING degradation after IFN signaling activation. The sequential combination treatment caused a significant increase in tumor cell apoptosis, probably due to interferon stimulating gene products 15 and 54 (ISG15 and ISG 54), and achieved a more striking antitumor inhibition effect in the CT26 tumor model than the 4T1 model, likely due to higher STAT1 expression and consequently more intense IFN signal transduction. In the tumor microenvironment, the combination treatment increased infiltrating CD8+T cells (4-fold) and M1-like TAMs (10-fold), and decreased M-MDSCs (over 2-fold) and M2-like TAMs (over 4-fold). Above all, in-depth exploration of the antitumor mechanism of PTT provides guidance for selecting sensitive tumor models and designing reasonable clinical schemes.

Topographic hydro-conditioning to resolve surface depression storage and ponding in a fully distributed hydrologic model.

Land surface depressions play a central role in the transformation of rainfall to ponding, infiltration and runoff, yet digital elevation models (DEMs) used by spatially distributed hydrologic models that resolve land surface processes rarely capture land surface depressions at spatial scales relevant to this transformation. Methods to generate DEMs through processing of remote sensing data, such as optical and light detection and ranging (LiDAR) have favored surfaces without depressions to avoid adverse slopes that are problematic for many hydrologic routing methods. Here we present a new topographic conditioning workflow, Depression-Preserved DEM Processing (D2P) algorithm, which is designed to preserve physically meaningful surface depressions for depression-integrated and efficient hydrologic modeling. D2P includes several features: (1) an adaptive screening interval for delineation of depressions, (2) the ability to filter out anthropogenic land surface features (e.g., bridges), (3) the ability to blend river smoothing (e.g., a general downslope profile) and depression resolving functionality. From a case study in the Goodwin Creek Experimental Watershed, D2P successfully resolved 86% of the ponds at a DEM resolution of 10 m. Topographic conditioning was achieved with minimum impact as D2P reduced the number of modified cells from the original DEM by 51% compared to a conventional algorithm. Furthermore, hydrologic simulation using a D2P processed DEM resulted in a more robust characterization on surface water dynamics based on higher surface water storage as well as an attenuated and delayed peak streamflow.

Potential of extracellular vesicles for early prediction of severity and potential risk stratification in critical inflammatory diseases.

Some acute inflammatory diseases are often exacerbated during or after hospitalization, leading to some severe manifestations like systemic inflammatory response syndrome, multiple organ failure, and high mortality. Early clinical predictors of disease severity are urgently needed to optimize patient management for better prognosis. The existing clinical scoring system and laboratory tests cannot circumvent the problems of low sensitivity and limited specificity. Extracellular vesicles (EVs) are heterogeneous nanosecretory vesicles containing various biomolecules related to immune regulation, inflammation activation, and inflammation-related complications. This review provides an overview of EVs as inflammatory mediators, inflammatory signaling pathway regulators, promoters of inflammatory exacerbation, and markers of severity and prognosis. Currently, although relevant biomarkers are clinically available or are in the preclinical research stage, searching for new markers and detection methods is still warranted, as the problems of low sensitivity/specificity, cumbersome laboratory operation and high cost still plague clinicians. In-depth study of EVs might open a door in the search for novel predictors.

Source apportionment of suspended sediment using grain-size end-member analysis.

End-members mixing analysis (EMMA) was performed on in situ suspended sediment grain-size distribution (GSD) data from Haizhou Bay to estimate suspended sediment provenance and the relative contributions of different sediment sources to total seawater suspended sediment. The results show that the suspended sediment in Haizhou Bay can be expressed as a mixture of three EMs. End-member 1 represents fine-grained suspended sediment that was transported over long distances by advection; this shows a genetic connection with the old Huanghe River delta. End-member 2 represents resuspension of local sediment, while EM3 represents riverine suspended sediment. On average, advection, resuspension, and riverine input contributed 41.92%, 37.83%, and 20.25% of the total suspended sediment, respectively. Temporal changes in advection and resuspension caused considerable variability in these relative contributions. The application of EMMA herein demonstrates that it is a feasible approach to explore suspended sediment sources and their mixing processes using suspended sediment GSD data.

Impact of Environmental Modifications on the Ecology, Epidemiology, and Pathogenesis of Plasmodium falciparum and Plasmodium vivax Malaria in East Africa.

Food insecurity, recurrent famine, and poverty threaten the health of millions of African residents. Construction of dams and rural irrigation schemes is key to solving these problems. The sub-Saharan Africa International Center of Excellence for Malaria Research addresses major knowledge gaps and challenges in Plasmodium falciparum and Plasmodium vivax malaria control and elimination in malaria-endemic areas of Kenya and Ethiopia where major investments in water resource development are taking place. This article highlights progress of the International Center of Excellence for Malaria Research in malaria vector ecology and behavior, epidemiology, and pathogenesis since its inception in 2017. Studies conducted in four field sites in Kenya and Ethiopia show that dams and irrigation increased the abundance, stability, and productivity of larval habitats, resulting in increased malaria transmission and a greater disease burden. These field studies, together with hydrological and malaria transmission modeling, enhance the ability to predict the impact of water resource development projects on vector larval ecology and malaria risks, thereby facilitating the development of optimal water and environmental management practices in the context of malaria control efforts. Intersectoral collaborations and community engagement are crucial to develop and implement cost-effective malaria control strategies that meet food security needs while controlling malaria burden in local communities.

Nanoparticle encapsulated CQ/TAM combination harmonizes with MSCs in arresting progression of severity in AP mice through iNOS (IDO) signaling.

Background: Sever acute pancreatitis (SAP) is a critical disease with high mortality, and lack of clinically available treatments with specificity and effectiveness. Bone marrow derived mesenchymal stem cells (BMSCs) exhibited moderate effect on AP which needs further improvement. Methods: Pancreatic infiltrating lymphocytes were analyzed to demonstrate the intervention of BMSCs on inflammatory cell infiltration of AP. Gene silencing with siRNA and small molecule inhibitor were utilized to determine the key effector molecule of BMSCs on AP. Pharmacological regulation and nanotechnology were introduced to further ameliorate BMSCs action. Results: It was revealed that BMSCs prevent the progression of acute pancreatitis (AP) by reducing recruitment of macrophages, neutrophils and CD4+T cells in the lesion site. The pivotal role of chemokine-iNOS-IDO axis for BMSCs to intervene AP was confirmed. Compared with any single drug, Chloroquine/Tamoxifen combination together with IFN-γ pronouncedly up-regulated the transcription of several MSC immune regulators such as COX-2, PD-L1, HO-1 especially iNOS/IDO. As expected, BMSCs and human umbilical cord mesenchymal stem cells (UMSCs) pretreated with CQ/TAM/IFN-γ exerted enhanced intervention in AP and SAP mice. Moreover, pretreatment with CQ-LPs/TAM-NPs combination not only counteracted MSCs proliferation inhibition induced by free drugs but also enhanced their efficacy. Conclusion: Under the background of rapid progress in MSCs clinical translation, this study focuses on the urgent clinical issue and initiates an original mechanism-based strategy to promote intervention on severity progression of SAP, which promises its clinical translation in future.

Adoptive CD8+T-cell grafted with liposomal immunotherapy drugs to counteract the immune suppressive tumor microenvironment and enhance therapy for melanoma.

The immunosuppressive tumor microenvironment has become a formidable obstacle to the treatment of tumors using adoptive T cell therapy, in particular solid tumors. For the purposes of addressing this issue, effector OT-1 CD8+T cells conjugated with liposomal immune regulators (CD8-T-LP-CpG/CD8-T-LP-BMS-202) were developed. An anionic liposome formulation was employed to avoid T cell aggregation and prevent unfavorable side-effects. The inclusion of EGCG in the LP-CpG formulation facilitated the formation of compact complexes with poly lysine (PLL) and is thus expected to increase the stability. CD8-T-LP-CpG administered with a median dose of CpG (20 µg per mouse) markedly reduced the frequency of tumor infiltrating polymorphonuclear leukocyte myeloid-derived suppressor cells (PMN-MDSCs) (20-folds), M2-like macrophages (8-folds), regulatory T-cells (Treg) (2.7-folds), and consequently increased the frequency of cytotoxic CD8+T cells in tumor-infiltrating lymphocytes (TILs) (2-folds) and splenic effector memory CD8+T cells (3-folds) relative to the phosphate buffered saline (PBS) control group. Furthermore, the absolute number of tumor infiltrating lymphocyte subtypes altered followed a consistent trend. The difference remained significant compared to the OT-1 CD8+T cells and the drug-loaded liposome combination group. According to in vivo imaging of CD8-T-LP-DiD, we assumed that the improvement in regulation of the tumor microenvironment of LP-CpG/LP-BMS-202 was attributed to the enhanced drug transportation to the tumor site aided by tumor-specific OT-1 CD8+T cells. In addition, CD8-T-LP-BMS-202 administered with a low dose of BMS-202 (1.5 mg per kg body weight) exerted a dramatically improved therapeutic effect by reducing the tumor infiltrating PMN-MDSCs and M2-like macrophages and the corresponding promoted cytotoxic CD8+T cell recruitment in the TILs and effector memory CD8+T cells mediated anti-tumor immunity. In summary, immune therapy drugs backpacked onto adoptive T cell therapy provides a feasible strategy to improve the therapeutic effect and could result in future clinical translation.

Predicting distribution of malaria vector larval habitats in Ethiopia by integrating distributed hydrologic modeling with remotely sensed data.

Larval source management has gained renewed interest as a malaria control strategy in Africa but the widespread and transient nature of larval breeding sites poses a challenge to its implementation. To address this problem, we propose combining an integrated high resolution (50 m) distributed hydrological model and remotely sensed data to simulate potential malaria vector aquatic habitats. The novelty of our approach lies in its consideration of irrigation practices and its ability to resolve complex ponding processes that contribute to potential larval habitats. The simulation was performed for the year of 2018 using ParFlow-Common Land Model (CLM) in a sugarcane plantation in the Oromia region, Ethiopia to examine the effects of rainfall and irrigation. The model was calibrated using field observations of larval habitats to successfully predict ponding at all surveyed locations from the validation dataset. Results show that without irrigation, at least half of the area inside the farms had a 40% probability of potential larval habitat occurrence. With irrigation, the probability increased to 56%. Irrigation dampened the seasonality of the potential larval habitats such that the peak larval habitat occurrence window during the rainy season was extended into the dry season. Furthermore, the stability of the habitats was prolonged, with a significant shift from semi-permanent to permanent habitats. Our study provides a hydrological perspective on the impact of environmental modification on malaria vector ecology, which can potentially inform malaria control strategies through better water management.

Perioperative Nursing of Diffuse Pulmonary Ossification.

This study aims to describe the clinical manifestations of diffuse pulmonary ossification, explore the diagnostic methods to reduce the misdiagnosis rate, and discuss its nursing treatment in the perioperative period. In The Fifth Central Hospital of Tianjin, one patient with diffuse pulmonary ossification, confirmed by surgical lung biopsy, was reported; and the clinical features and effective nursing methods are analysed. The patient was a 16-year teenager, who developed sudden convulsions without obvious cause with limited respiration. After the mental state was restored, the patient presented with chest tightness, shortness of breath, cough and expectoration. Hence, the subject was admitted in our hospital. Routine and imaging examinations failed to draw a definite diagnosis. Then, lung biopsy was performed, and a diagnosis of diffuse pulmonary ossification was made. Diffuse pulmonary ossification is very rare in clinical practice. The clinical manifestations are nonspecific, and imaging features are characterised by diffuse lung damages. Therefore, it is easily misdiagnosed as other interstitial lung diseases. Lung biopsy can be used to confirm this disease. Sequential acupoint stimulation by tapping the back can relieve cough and help patients recover quickly.

Versatile cationic liposomes for RIP3 overexpression in colon cancer therapy and RIP3 downregulation in acute pancreatitis therapy.

Because the induction of strong host antitumor responses plays a very important role in antitumor therapy, identifying effective approaches to elicit immunogenic cell death could have important implications. RIP3-dependent necroptotic cancer cells have been reported to release damage-associated molecular patterns and enhance antitumor immunity. In this study, hyaluronic acid-conjugated cationic liposomes (DOTAP/DOPE/PEG-DSPE/CHOL) (HA-P-LP) were prepared as a vector for mRIP3-pDNA overexpression in tumours. Compared with standard cationic liposomes, this vector markedly increased cellular gene internalisation in vitro, enhanced the tumour-targeting effect in vivo and exhibited a significant antitumor effect in combination with adjuvant chloroquine. Considering the dramatic increase in RIP3 under the pathological condition of pancreatitis and the correlation between pancreatitis and necroptosis, non-HA-conjugated liposomes with the same formulation loaded with shRNA mRIP3-pDNA effectively controlled the disease by decreasing the serum amylase concentration and inflammatory cell infiltration. The versatile cationic liposomes loaded with plasmids with opposing functions in this study provide a new concept and method for both tumour therapy and pancreatitis therapy.

Protective Effects of Ligustroflavone, an Active Compound from Ligustrum lucidum, on Diabetes-Induced Osteoporosis in Mice: A Potential Candidate as Calcium-Sensing Receptor Antagonist.

Ligustroflavone is one major compound contained in active fraction from Fructus Ligustri Lucidi (the fruit of Ligustrum lucidum), which could regulate parathyroid hormone (PTH) levels and improve calcium balance by acting on calcium-sensing receptors (CaSR). This study aimed to explore the potency of ligustroflavone as a CaSR antagonist and its protective effects against diabetic osteoporosis in mice. LF interacted well with the allosteric site of CaSR shown by molecular docking analysis, increased PTH release of primary parathyroid gland cells and suppressed extracellular calcium influx in HEK-293 cells. The serum level of PTH attained peak value at 2 h and maintained high during the period of 1 h and 3 h than that before treatment in mice after a single dose of LF. Treatment of diabetic mice with LF inhibited the decrease in calcium level of serum and bone and the enhancement in urinary calcium excretion as well as elevated circulating PTH levels. Trabecular bone mineral density and micro-architecture were markedly improved in diabetic mice upon to LF treatment for 8 weeks. LF reduced CaSR mRNA and protein expression in the kidneys of diabetic mice. Taken together, ligustroflavone could transiently increase PTH level and regulate calcium metabolism as well as prevent osteoporosis in diabetic mice, suggesting that ligustroflavone might be an effective antagonist on CaSR.

A randomized study on the effect of sequential acupoint stimulation on pulmonary function of patients with spontaneous pneumothorax during VATS perioperative period.

This study aims to explore the effect of sequential acupoint stimulation on the postoperative pulmonary function of patients with spontaneous pneumothorax who underwent video-assisted thoracoscopic surgery (VATS).Using a random number table, the patients were randomly divided into 2 groups: routine nursing group and sequential acupoint stimulation group. Patients in the routine nursing group received standard nursing care of thoracic surgery, while patients in the acupoint group received sequential acupoint stimulation on Shenshu (BL23), Gaohuang (BL43), Feishu (BL13), and Tiantu (CV22). Then, the maximal ventilatory volume (MVV), oxygen saturation (SpO2), postoperative drainage volume, postoperative drainage time, postoperative hospitalization days, and procalcitonin (PCT) were observed on the first, third, fifth and 30th day after VATS operation.On the fifth day after spontaneous pneumothorax was treated with VATS, MVV, and SpO2 of the sequential acupoint stimulation group were significantly higher than those of the routine nursing group (P < .05). On both the third day and fifth day after VATS, PCT of the sequential acupoint stimulation group was significantly lower than that of the routine nursing group (P < .01). Furthermore, the difference in postoperative drainage volume between the 2 groups was not statistically significant (P > .05), while chest tube drainage time (P < .01) and postoperative hospitalization days (P < .05) of the sequential acupoint stimulation group were significantly lower than those of the routine nursing group.In spontaneous pneumothorax patients who underwent VATS, sequential acupoint stimulation nursing was significantly more effective than routine postoperative nursing in promoting postoperative recovery of lung function, alleviating inflammatory response and shortening hospitalization days.