Origin and Characteristics of the Crude Oils and Condensates in the Callovian-Oxfordian Carbonate Reservoirs of the Amu Darya Right Bank Block, Turkmenistan

AbstractThe Amu Darya Right Bank Block is located northeast of the Amu Darya basin, a large petroliferous sedimentary basin, with abundant natural gas resources in carbonate rocks under the ultra-thick gypsum-salt layer. Oil fields producing crude oils have recently been found around large gas fields. Unraveling the origins of the crude oils is crucial for effective petroleum exploration and exploitation. The origin of gas condensates and crude oils was unraveled through the use of comprehensively analytical and interpretative geochemical approaches. Based on oil-source correlation, the reservoir forming process has been restored. The bulk geochemical parameters of the local source rocks of the ADRBB indicated that the local sources have hydrocarbon generation and accumulation potential. The middle-lower Jurassic coal-bearing mudstone is gas prone, while the mudstone of the Callovian-Oxfordian gap layer is oil prone, and the organic matter type of Callovian-Oxfordian carbonate rocks is the mixed type between the two previous source rocks. The interpretation schemes for compositions of n-alkanes, pristane and phytane, C27–C28–C29 sterane distributions, C19+C20–C21–C23 tricyclic terpane distributions, extended tricyclic terpane ratio, and δ13C indicated that crude oil is likely from marine organic matter, while condensates mainly originate from terrestrial organic matter. However, from the perspective of the 18α-trisnorneohopane/17α-trisnorhopane and isomerization ratio of C29 sterane, condensates are too mature to have originated in the local source rocks of the ADRBB, whose maturity is well comparable with that of crude oils. The geochemical, geologic, and tectonic evolutions collectively indicate that the crude oils were most likely generated and migrated from the relatively shallow, lowly mature gap layer and Callovian-Oxfordian carbonate rocks of the ADRBB, while the condensates mostly originated from the relatively deep and highly mature middle-lower coal-bearing mudstone and Callovian-Oxfordian carbonate rocks in the Murgab depression in the southeast of the basin. Basement faults are the key factors affecting the types of oil and gas reservoirs. During the periods of oil and gas migration, traps with basement faults mainly captured natural gas and condensates and traps without basement faults were enriched with crude oils generated from local source rocks

Multiple-Clade H5N1 Influenza Split Vaccine Elicits Broad Cross Protection against Lethal Influenza Virus Challenge in Mice by Intranasal Vaccination

Background: The increase in recent outbreaks and unpredictable changes of highly pathogenic avian influenza (HPAI) H5N1 in birds and humans highlights the urgent need to develop a cross-protective H5N1 vaccine. We here report our development of a multiple-clade H5N1 influenza vaccine tested for immunogenicity and efficacy to confer cross-protection in an animal model. Methodology/Principal Findings: Mice received two doses of influenza split vaccine with oil-in-water emulsion adjuvant SP01 by intranasal administration separated by two weeks. Single vaccines (3 mg HA per dose) included rg-A/Vietnam/1203/ 2004(Clade 1), rg-A/Indonesia/05/2005(Clade 2.1), and rg-A/Anhui/1/2005(Clade 2.3.4). The trivalent vaccine contained 1 mg HA per dose of each single vaccine. Importantly, complete cross-protection was observed in mice immunized using trivalent vaccine with oil-in-water emulsion adjuvant SP01 that was subsequently challenged with the lethal A/OT/SZ/097/03 influenza strain (Clade 0), whereas only the survival rate was up to 60 % in single A/Anhui/1/2005 vaccine group. Conclusion/Significance: Our findings demonstrated that the multiple-clade H5N1 influenza vaccine was able to elicit a cross-protective immune response to heterologous HPAI H5N1 virus, thus giving rise to a broadly cross-reactive vaccine to potential prevention use ahead of the strain-specific pandemic influenza vaccine in the event of an HPAI H5N1 influenza outbreak. Also, the multiple-clade adjuvanted vaccine could be useful in allowing timely initiation of vaccination agains

Development of smart optical imaging agents for disease diagnosis

Optical imaging has become an indispensable tool in disease diagnosis and treatment. As compared to other imaging modalities, it exhibits high-throughput capacity, high sensitivity with detection at molecular and cellular levels, avoidance of radiative toxicity, and relatively low instrumentation costs. In the clinical settings, optical instrumentations such as endoscopy, microscopy and photoacoustic tomography, has facilitated both pre-clinical and clinical optical imaging applications. Encouraged by preclinical results and the translational potential of optical imaging, a variety of optical imaging agents have been developed, which could be classified into inorganic nanoparticles and organic fluorophores, based on the material of construction. Organic fluorophores show high structural versatility with clear structure-property relationships. These optical agents feature modifiable groups, which enables the combination of different functional moieties to achieve desired biochemical properties in biomarker detection, targeting and even therapy. Particularly, biomarker-activatable optical imaging agents that specifically turn on the optical signals in the presence of disease biomarkers at the molecular and cellular level have the potential for disease detection at an incipient stage. This thesis aims to discuss the application of biomarker-activatable molecular fluorophore for disease diagnosis via both real-time in vivo imaging and in vitro urinalysis. In the real-time imaging approach, both attempts to improve probe design for clinical translation and explore different diseases will be reported. The probe design could be improved from two different aspects: i) tuning optical properties to improve penetration depth and signal-to-noise ratio; ii) tuning pharmacokinetic properties to accelerate body excretion and minimize organ toxicity. Such activatable fluorophores are utilized to detect malignant skin diseases, drug-induced liver injury, drug-induced kidney injury in living mice models. Last but not least, the application of activatable optical probes for in vitro urinalysis is introduced. The in vitro application liberates the stringent requirement of biocompatibility and pharmacokinetic properties on molecular fluorophores. Therefore, the emphasize is on finding appropriate disease biomarkers that are both urinary-secreted and disease-specific. Multiplex urinalysis reporters that specifically emit optical signals in the presence of three different biomarkers are developed and they are applied for disease detection in drug-induced kidney injury model.Doctor of Philosoph

Rational engineering of yeast to develop biosensors

The yeast, Saccharomyces cerevisiae, is widely used to produce high value-added chemicals and food ingredients. Typically, genes are either deleted from or added to the yeast to produce a compound-of-interest. However, in doing so, we perturb cellular networks and affect the metabolism of the cell. It will be useful if we can readily determine the concentrations of various chemicals in the cell and dynamically regulate metabolic pathways, so that the cells can cope better. Thus, there is a need to develop biosensors for various chemicals for the yeast cells. [2nd Award

Recent advances in cell membrane-camouflaged nanoparticles for cancer phototherapy

Phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) employs phototherapeutic agents to generate heat or cytotoxic reactive oxygen species (ROS), and has therefore garnered particular interest for cancer therapy. However, the main challenges faced by conventional phototherapeutic agents include easy recognition by the immune system, rapid clearance from blood circulation, and low accumulation in target sites. Cell-membrane coating has emerged as a potential way to overcome these limitations, owing to the abundant proteins on the surface of cell membranes that can be inherited to the cell membrane-camouflaged nanoparticles. This review summarizes the recent advances in the development of biomimetic cell membrane-camouflaged nanoparticles for cancer phototherapy. Different sources of cell membranes can be used to coat nanoparticles uisng different coating approaches. After cell-membrane coating, the photophysical properties of the original phototherapeutic nanoparticles remain nearly unchanged; however, the coated nanoparticles are equipped with additional physiological features including immune escape, in vivo prolonged circulation time, or homologous targeting, depending on the cell sources. Moreover, the coated cell membrane can be ablated from phototherapeutic nanoparticles under laser irradiation, leading to drug release and thus synergetic therapy. By combining other supplementary agents to normalize tumor microenvironment, cell-membrane coating can further enhance the therapeutic efficacy against cancer.MOE (Min. of Education, S’pore)Accepted versio

Activatable near-infrared probes for the detection of specific populations of tumour-infiltrating leukocytes in vivo and in urine

Tracking the immune microenvironment of tumours is essential for understanding the mechanisms behind the effectiveness of cancer immunotherapies. Molecular imaging of tumour-infiltrating leukocytes (TILs) can be used to non-invasively monitor the tumour immune microenvironment, but current imaging agents do not distinguish TILs from leukocytes resident in other tissues. Here we report a library of activatable molecular probes for the imaging, via near-infrared fluorescence, of specific TILs (including M1 macrophages, cytotoxic T lymphocytes and neutrophils) in vivo in real time and also via excreted urine, owing to the probes' renal clearance. The fluorescence of the probes is activated only in the presence of both tumour and leukocyte biomarkers, which allows for the imaging of populations of specific TILs in mouse models of cancers with sensitivities and specificities similar to those achieved via flow-cytometric analyses of biopsied tumour tissues. We also show that the probes enable the non-invasive evaluation of the immunogenicity of different tumours, the dynamic monitoring of responses to immunotherapies and the accurate prediction of tumour growth under various treatments.Ministry of Education (MOE)National Research Foundation (NRF)K.P. thanks the Singapore Ministry of Education, Academic Research Fund Tier 1 (RG125/19; RT05/20), Academic Research Fund Tier 2 (MOE2018-T2-2-042; MOE-T2EP30220-0010) and the Singapore National Research Foundation (NRF-NRFI07-2021-0005) for financial support

Synthesis of PEGylated semiconducting polymer amphiphiles for molecular photoacoustic imaging and guided therapy

Semiconducting polymer nanoparticles (SPNs) have been used as a new class of photonic materials with great potential in biomedical applications, but their synthetic method is limited to nanoprecipitation. Semiconducting polymer amphiphiles (SPAs) that can spontaneously self-assemble into nanoparticles are ideal alternatives for SPNs. Depending on their backbone structures, SPAs with different optical properties can be developed into nanoprobes for molecular imaging applications such as photoacoustic (PA) and fluorescence imaging as well as photothermal therapy. In this Concept, recent studies on the synthesis of SPAs for PA imaging and guided cancer therapy are summarized. The effect of grafting density on the optical properties of SPAs is discussed, and the nanoparticle sizes of SPAs can be reduced by utilization of a short semiconducting oligomer. Moreover, SPAs can be developed into PA theranostic platform and activatable PA nanoprobes. These studies demonstrate that SPAs are promising for advanced molecular imaging and therapy applications.MOE (Min. of Education, S’pore

Recent progress in the development of near-infrared organic photothermal and photodynamic nanotherapeutics

Phototherapies including photothermal therapy (PTT) and photodynamic therapy (PDT) have gained considerable attention due to their high tumor ablation efficiency, excellent spatial resolution and minimal side effects on normal tissue. In contrast to inorganic nanoparticles, near-infrared (NIR) absorbing organic nanoparticles bypass the issue of metal-ion induced toxicity and thus are generally considered to be more biocompatible. Moreover, with the guidance of different kinds of imaging methods, the efficacy of cancer phototherapy based on organic nanoparticles has shown to be optimizable. In this review, we summarize the synthesis and application of NIR-absorbing organic nanoparticles as phototherapeutic nanoagents for cancer phototherapy. The chemistry, optical properties and therapeutic efficacies of organic nanoparticles are firstly described. Their phototherapy applications are then surveyed in terms of therapeutic modalities, which include PTT, PDT and PTT/PDT combined therapy. Finally, the present challenges and potential of imaging guided PTT/PDT are discussed.MOE (Min. of Education, S’pore)Accepted versio

A dual-locked tandem fluorescent probe for imaging of pyroptosis in cancer chemo-immunotherapy

Real-time imaging of programmed cancer cell death (PCD) is imperative to monitor cancer therapeutic efficacy and tailor therapeutic regimens; however, specific in vivo detection of intratumoral pyroptosis remains challenging. Herein, a dual-locked and tandem activatable probe (DTAP) is reported for near-infrared fluorescence (NIRF) imaging of intratumoral pyroptosis during cancer chemo-immunotherapy in living mice. The probe comprises a hemicyanine dye dual-locked with an enzyme-responsive moiety that can be tandemly cleaved by pyroptosis-related biomarker (Caspase-1) and cancer biomarker (GGT) to turn on its NIRF signal. As pyroptosis plays a vital role in triggering anti-tumor immune responses, the activated signal of DTAP correlates well with the population of tumor-infiltrating cytotoxic T lymphocytes and tumor growth inhibition, consequently permitting the prediction of cancer therapeutic efficacy. This study also provides a non-invasive technique to study the regulatory mechanism of pyroptosis in cancer therapy and to optimize cancer chemo-immunotherapies for precision medicine.Ministry of Education (MOE)National Research Foundation (NRF)Submitted/Accepted versionK.P. thanks Singapore National Research Foundation (NRF) (NRF-NRFI07-2021-0005), and Singapore Ministry of Education, Academic Research Fund Tier 1 (2019-T1-002-045, RG125/19, and RT05/20), and Academic Research Fund Tier 2 (MOE-T2EP30220-0010; MOE-T2EP30221-0004), for the financial support

A tandem-locked fluorescent NETosis reporter for the prognosis assessment of cancer immunotherapy

NETosis, the peculiar type of neutrophil death, plays important roles in pro-tumorigenic functions and inhibits cancer immunotherapy. Non-invasive real-time imaging is thus imperative for prognosis of cancer immunotherapy yet remains challenging. Herein, we report a Tandem-locked NETosis Reporter 1 (TNR1 ) that activates fluorescence signals only in the presence of both neutrophil elastase (NE) and cathepsin G (CTSG) for the specific imaging of NETosis. In the aspect of molecular design, the sequence of biomarker-specific tandem peptide blocks can largely affect the detection specificity towards NETosis. In live cell imaging, the tandem-locked design allows TNR1 to differentiate NETosis from neutrophil activation, while single-locked reporters fail to do so. The near-infrared signals from activated TNR1 in tumor from living mice were consistent with the intratumoral NETosis levels from histological results. Moreover, the near-infrared signals from activated TNR1 negatively correlated with tumor inhibition effect after immunotherapy, thereby providing prognosis for cancer immunotherapy. Thus, our study not only demonstrates the first sensitive optical reporter for noninvasive monitoring of NETosis levels and evaluation of cancer immunotherapeutic efficacy in tumor-bearing living mice, but also proposes a generic approach for tandem-locked probe design.Ministry of Education (MOE)National Research Foundation (NRF)K.P. thanks Singapore National Research Foundation (NRF) (NRF‐NRFI07‐2021‐0005), and Singapore Ministry of Education, Academic Research Fund Tier 1 (2019‐T1‐002‐045, RG125/19, RT05/20), Academic Research Fund Tier 2 (MOE‐T2EP30220‐0010; MOE‐T2EP30221‐0004), for the financial support