Publications by authors named "Fan Xia"

645 Publications

Synergistic Effect of Bio-Inspired Nanochannels: Hydrophilic DNA Probes at Inner Wall and Hydrophobic Coating at Outer Surface for Highly Sensitive Detection.

Small 2022 Aug 18:e2201925. Epub 2022 Aug 18.

Key Laboratory of Bio-Inspired Smart Interfacial Science and Technology of the Ministry of Education, School of Chemistry and Environment, Beihang University, Beijing, 100191, P. R. China.

During the past few decades, bio-inspired nanochannels have been well developed and applied in biosensing, energy transfer, separation, and so on. Here, inspired by the synergistic effect of biological nanopores, biomimetic solid-state nanochannels with hydrophilic DNA probes at the inner wall ([email protected] ) and hydrophobic coating at the outer surface ([email protected] ) are designed. To demonstrate their prompted sensing properties, Hg and its specific probe are selected as target and hydrophilic DNA probes, respectively. Compared with the traditional solid-state nanochannels with hydrophilic probes distributed on both the inner wall and outer surface, the nanochannels with [email protected] [email protected] significantly decrease the limit of detection (LOD) by 10 -fold. The obvious improvement of sensitivity (with LOD of 1 nM) is attributed to the synergistic effect: [email protected] results in the nanochannel's effective diameter decrease and [email protected] induces a specific sensing target. Meanwhile, nanomolar detection of Hg in human serum and in vivo fish muscle are achieved. Through molecular dynamics simulation, the synergistic effect can be confirmed by ion fluxes increasement; the relative carbon nanotube increases from 135.64% to 135.84%. This work improves the understanding of nanochannels' synergistic effect and provides a significant insight for nanochannels with improved sensitivity.
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http://dx.doi.org/10.1002/smll.202201925DOI Listing
August 2022

An epidermal electronic system for physiological information acquisition, processing, and storage with an integrated flash memory array.

Sci Adv 2022 Aug 17;8(33):eabp8075. Epub 2022 Aug 17.

Key Laboratory for the Physics and Chemistry of Nanodevices, School of Electronics and Center for Carbon-Based Electronics, Peking University, Beijing 100871, China.

Epidermal electronic systems that simultaneously provide physiological information acquisition, processing, and storage are in high demand for health care/clinical applications. However, these system-level demonstrations using flexible devices are still challenging because of obstacles in device performance, functional module construction, or integration scale. Here, on the basis of carbon nanotubes, we present an epidermal system that incorporates flexible sensors, sensor interface circuits, and an integrated flash memory array to collect physiological information from the human body surface; amplify weak biosignals by high-performance differential amplifiers (voltage gain of 27 decibels, common-mode rejection ratio of >43 decibels, and gain bandwidth product of >22 kilohertz); and store the processed information in the memory array with performance on par with industrial standards (retention time of 10 seconds, program/erase voltages of ±2 volts, and endurance of 10 cycles). The results shed light on the great application potential of epidermal electronic systems in personalized diagnostic and physiological monitoring.
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http://dx.doi.org/10.1126/sciadv.abp8075DOI Listing
August 2022

A pH-independent electrochemical aptamer-based biosensor supports quantitative, real-time measurement .

Chem Sci 2022 Aug 27;13(30):8813-8820. Epub 2022 Jun 27.

Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Complutense de Madrid 28040 Madrid Spain.

The development of biosensors capable of achieving accurate and precise molecular measurements in the living body in pH-variable biological environments ( subcellular organelles, biological fluids and organs) plays a significant role in personalized medicine. Because they recapitulate the conformation-linked signaling mechanisms, electrochemical aptamer-based (E-AB) sensors are good candidates to fill this role. However, this class of sensors suffers from a lack of a stable and pH-independent redox reporter to support their utility under pH-variable conditions. Here, in response, we demonstrate the efficiency of an electron donor π-extended tetrathiafulvalene (exTTF) as an excellent candidate (due to its good electrochemical stability and no proton participation in its redox reaction) of pH-independent redox reporters. Its use has allowed improvement of E-AB sensing performance in biological fluids under different pH conditions, achieving high-frequency, real-time molecular measurements in biological samples both and in the bladders of living rats.
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http://dx.doi.org/10.1039/d2sc02021aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9350589PMC
August 2022

Fujian cytoplasmic male sterility and the fertility restorer gene provide a promising breeding system for hybrid rice.

Proc Natl Acad Sci U S A 2022 Aug 15;119(34):e2208759119. Epub 2022 Aug 15.

National Key Laboratory of Crop Genetic Improvement, Hubei Hongshan Laboratory, Huazhong Agricultural University, 430070 Wuhan, China.

Cytoplasmic male sterility (CMS) determined by mitochondrial genes and restorer of fertility () controlled by nuclear-encoded genes provide the breeding systems of many hybrid crops for the utilization of heterosis. Although several CMS/ systems have been widely exploited in rice, hybrid breeding using these systems has encountered difficulties due to either fertility instability or complications of two-locus inheritance or both. In this work, we characterized a type of CMS, Fujian Abortive cytoplasmic male sterility (CMS-FA), with stable sporophytic male sterility and a nuclear restorer gene that completely restores hybrid fertility. CMS is caused by the chimeric open reading frame that specifically occurs in the mitochondrial genome of CMS-FA rice. The restorer gene encodes a pentatricopeptide repeat (PPR) protein targeted to mitochondria, where it mediates the cleavage of transcripts, thus restoring male fertility. Comparative sequence analysis revealed that originated through a recent duplication in wild rice relatives, sharing a common ancestor with /, a fertility restorer gene for Boro II and Hong-Lian CMS. We developed six restorer lines by introgressing into parental lines of elite CMS-WA hybrids; hybrids produced from these lines showed equivalent or better agronomic performance relative to their counterparts based on the CMS-WA system. These results demonstrate that CMS-FA/ provides a highly promising system for future hybrid rice breeding.
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http://dx.doi.org/10.1073/pnas.2208759119DOI Listing
August 2022

Role of Eryptosis in Hemorrhagic Stroke.

Front Mol Neurosci 2022 28;15:932931. Epub 2022 Jul 28.

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.

Erythrocytes undergo certain morphological changes resembling apoptosis during senescence or in an abnormal state/site, which is termed eryptosis. This process is characterized by phosphatidylserine (PS) exposure, membrane blebbing, and cell shrinkage. Eryptotic erythrocytes are subsequently removed macrophage-mediated efferocytosis. In hemorrhagic stroke (HS), blood within an artery rapidly bleeds into the brain tissue or the subarachnoid space, resulting in severe neurological deficits. A hypoxic, over-oxidative, and pro-inflammatory microenvironment in the hematoma leads to oxidative stress, hyperosmotic shock, energy depletion, and Cl removal in erythrocytes, which eventually triggers eryptosis. In addition, eryptosis following intracerebral hemorrhage favors hematoma clearance, which sheds light on a common mechanism of intrinsic phagocytosis. In this review, we summarized the canonical mechanisms of eryptosis and discussed its pathological conditions associated with HS. Understanding the role of eryptosis in HS may uncover additional potential interventions for further translational clinical research.
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http://dx.doi.org/10.3389/fnmol.2022.932931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9371462PMC
July 2022

Simultaneous Determination of 21 Sulfonamides in Poultry Eggs Using Ionic Liquid-Modified Molecularly Imprinted Polymer SPE and UPLC-MS/MS.

Molecules 2022 Aug 4;27(15). Epub 2022 Aug 4.

Institute of Quality Standards and Testing Technology for Agricultural Products, Chinese Academy of Agricultural Science, Beijing 100081, China.

An ionic liquid-modified molecularly imprinted polymer (IL-MIP) composite with sulfamethazine as a template molecule and methyl acrylic acid and 1-aminopropyl-3-methylimidazolium bromide as functional monomers was successfully synthesized. The achieved IL-MIP was characterized and evaluated in detail and utilized in the extraction and cleanup of sulfonamides (SAs) in poultry egg samples. The results demonstrated that the IL-MIP possessed a broad reorganization toward SAs and could selectively adsorb 21 kinds of SA compounds. Furthermore, the solid-phase extraction column based on the IL-MIP was used in the extraction and cleanup of 21 SAs in eggs, and the confirmatory detection of SAs was performed using ultraperformance liquid chromatography-tandem mass spectrometry. Under optimum conditions, the limits of detection (LODs) for all SAs ranged from 0.1 ng·g to 1.5 ng·g, and the LOD of this method was better than those of the existing methods. The recoveries of SA compounds spiked in egg samples ranged from 84.3% to 105.8%, with low relative standard deviations (<15%). The developed method based on the IL-MIP extraction and cleanup was successfully used in the detection of 21 SAs in more than 100 real poultry egg samples. The results indicated that the proposed method was suitable for detecting 21 SAs in poultry eggs.
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http://dx.doi.org/10.3390/molecules27154953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9370267PMC
August 2022

Sandwich fluorometric method for dual-role recognition of Listeria monocytogenes based on antibiotic-affinity strategy and fluorescence quenching effect.

Anal Chim Acta 2022 Aug 14;1221:340085. Epub 2022 Jun 14.

College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China. Electronic address:

In this work, a sandwich fluorometric method for dual-role recognition of L. monocytogenes was developed based on antibiotic-affinity strategy and fluorescence quenching effect for sensitive and rapid detection of L. monocytogenes in ham samples. Vancomycin (Van) was conjugated with magnetic nanoparticles (MNPs) to recognize and capture target bacteria. Biotinylated aptamers were used to bind specifically to L. monocytogenes through the cell wall. The two agents recognized target bacteria at different binding sites showing satisfied specificity. The upconversion fluorescence response signal could be enlarged by using the inner filter effect (IFE) between the colored products produced by enzyme-catalyzing substrate and upconversion nanoparticles (UCNPs). The change in fluorescence intensity could represent the concentration of target bacteria over 10-2 × 10 CFU mL. The developed sandwich fluorimetric method achieved a low detection limit (LOD) of 2.8 × 10 CFU mL. Overall, the constructed fluorometric sensor could provide a simple and reliable method for the detection of L. monocytogenes.
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http://dx.doi.org/10.1016/j.aca.2022.340085DOI Listing
August 2022

Icetexane diterpenoids as Ca3.2 T-type calcium channel inhibitors from Salvia prattii and analgesic effect of their Semi-synthesized derivatives.

Bioorg Chem 2022 Aug 1;128:106059. Epub 2022 Aug 1.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, People's Republic of China. Electronic address:

Ten new icetexane diterpenoids, salpratins E-N (1-10) and a known analogue (11) were characterized from Salvia prattii Hemsl. Structurally, 1 is the first 19(4 → 3)-abeo-icetexane diterpenoid featuring with a 6/7/6 ring system. The structures of isolated compounds were determined by comprehensive analyses of spectroscopic data, ECD calculation, and single-crystal X-ray diffraction. Biological studies initially revealed that 1, 7, 10, and 11 are notable Ca3.2 T-type Ca channel (TTCC) inhibitors with IC values of 2.9, 5.1, 2.3, and 3.2 μM, respectively. Five icetexane related derivatives (13-17) were synthesized from an abietane type precursor, (+)-carnosic acid (12), for the purpose of overcoming the poor water solubility of aforementioned active compounds and further investigating diverse diterpenes with valuable activity. Among them, 13 and 14 showed potent inhibitions on Ca3.2, having IC values of 6.7 and 2.4 μM, respectively. Significantly, they exhibited dose-dependent (1, 3, and 10 mg/kg) and comparable analgesic effects as that of Z944, a TTCCs inhibitor under clinical trial for pain management, in the mouse acetic acid writhing test. These findings further enrich structural diversity and bioactivity of Salvia diterpenoids, as well as provide promising structural templates for the development of Ca3.2 analgesics.
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http://dx.doi.org/10.1016/j.bioorg.2022.106059DOI Listing
August 2022

Antibacterial Theranostic Agents with Negligible Living Cell Invasiveness: AIE-Active Cationic Amphiphiles Regulated by Alkyl Chain Engineering.

ACS Nano 2022 Aug 2. Epub 2022 Aug 2.

State Key Laboratory of Luminescent Materials and Devices, Key Laboratory of Luminescence from Molecular Aggregates of Guangdong Province, South China University of Technology, Guangzhou 510640, China.

To address the threat of bacterial infection in the following post-antibiotic era, developing effective antibacterial approaches is of utmost urgency. Theranostic medicine integrating diagnosis and therapy is a promising protocol to fight against pathogenic bacteria. But numerous reported antibacterial theranostic materials are disclosed to be trapped in the excessive invasiveness to living mammal cells, leading to false positives and possible biosafety risks. Herein, a series of cationic pyridinium-substituted phosphindole oxide derivatives featuring aggregation-induced emission are designed, and alkyl chain engineering is conducted to finely tune their hydrophobicity and investigate their bioaffinity preference for living mammal cells and pathogenic bacteria. Most importantly, an efficient theranostic agent (PyBu-PIO) is acquired that is free from living cell invasiveness with negligible cytotoxicity and yet holds a good affinity for Gram-positive bacteria, including drug-resistant strains, with a superior inactivating effect. Externally applying PyBu-PIO onto Gram-positive bacteria-infected skin wounds can achieve creditable imaging effects and successfully accelerate the healing processes with reliable biosafety. This work proposes living cell invasiveness as a criterion for antibacterial theranostic materials and provides important enlightenment for the design of antibacterial theranostic materials.
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http://dx.doi.org/10.1021/acsnano.2c01721DOI Listing
August 2022

Lifetime-Based Responsive Probes: Design and Applications in Biological Analysis.

Chem Asian J 2022 Aug 2:e202200563. Epub 2022 Aug 2.

State Key Laboratory of Biogeology and Environmental Geology, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, China.

With the development of modern biomedicine, biological analysis and detection are very important in disease diagnosis, detection of curative effect, prognosis and prediction of tumor recurrence. Compared with the currently widely used optical probes based on intensity signals, the lifetime signal does not depend on the influence of conditions such as the concentration of luminophore, tissue penetration depth and measurement method. Therefore, biological detection methods based on lifetime-based responsive probes have attracted great attention from the scientific community. Here, we briefly review the key advances in lifetime-based responsive probes in recent years (2017-2022). The review focuses on the design strategies of lifetime-based responsive probes and the research progress of their applications in the field of bioanalysis, and discusses the challenges they face. We hope it will further promote the development of lifetime-based responsive probes in the field of bioanalysis.
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http://dx.doi.org/10.1002/asia.202200563DOI Listing
August 2022

Aggregation-induced emission photosensitizer-based photodynamic therapy in cancer: from chemical to clinical.

J Nanobiotechnology 2022 Jul 26;20(1):344. Epub 2022 Jul 26.

State Key Laboratory of Biogeology and Environmental Geology, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, China.

Cancer remains a serious threat to human health owing to the lack of effective treatments. Photodynamic therapy (PDT) has emerged as a promising non-invasive cancer treatment that consists of three main elements: photosensitizers (PSs), light and oxygen. However, some traditional PSs are prone to aggregation-caused quenching (ACQ), leading to reduced reactive oxygen species (ROS) generation capacity. Aggregation-induced emission (AIE)-PSs, due to their distorted structure, suppress the strong molecular interactions, making them more photosensitive in the aggregated state instead. Activated by light, they can efficiently produce ROS and induce cell death. PS is one of the core factors of efficient PDT, so proceeding from the design and preparation of AIE-PSs, including how to manipulate the electron donor (D) and receptor (A) in the PSs configuration, introduce heavy atoms or metal complexes, design of Type I AIE-PSs, polymerization-enhanced photosensitization and nano-engineering approaches. Then, the preclinical experiments of AIE-PSs in treating different types of tumors, such as ovarian cancer, cervical cancer, lung cancer, breast cancer, and its great potential clinical applications are discussed. In addition, some perspectives on the further development of AIE-PSs are presented. This review hopes to stimulate the interest of researchers in different fields such as chemistry, materials science, biology, and medicine, and promote the clinical translation of AIE-PSs.
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http://dx.doi.org/10.1186/s12951-022-01553-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327335PMC
July 2022

The Validity of Virtual Courage for Trainees in High-Risk Occupations.

Psychol Res Behav Manag 2022 14;15:1783-1796. Epub 2022 Jul 14.

Department of Developmental Psychology of Armyman, School of Psychology, Army Medical University, Chongqing, People's Republic of China.

Background: Employees in high-risk occupations are exposed to tremendous work stress that hinders organizational effectiveness and personal mental health. Based on positive psychology, courage can be considered a protective factor that buffers the adverse effect of high-risk surroundings on employees. However, little is known about the way courage is simulated or evaluated in response to safety concerns. Virtual reality (VR) is an accessible tool for courage simulation due to its immersive qualities, presence and interactive features and may provide a promising pathway to achieve a scientific, accurate and ecologically valid evaluation of high-risk employees.

Methods: The sample consisted of 51 high-risk employees who were recruited voluntarily. Before and after experiencing the VR courage scenarios, the participants completed the VR features questionnaire, the Physical Courage at Work Scale (PCWS), the Courage Measure (CM), and the Positive and Negative Affect Scale (PANAS). During the process of watching the VR courage scenarios, the participants' heart rate and skin conductance at resting-state baseline and during virtual courage scenarios were recorded through HTC VIVE Pro Eye and BioGraph Infiniti 8.

Results: The results support the hypothesis and reveal that the interaction, immersion and presence scores of the scenarios were all significantly higher than the median 4 points. The score for the CM in the posttest was significantly higher than that in the pretest. The scared and afraid scores for the posttest were significantly higher than those for the pretest. The heart rate and skin conductance of each scenario showed an increase compared with the baseline. The Pearson's correlation between physiological indicators and the score of the PCWS was 0.28~0.54.

Conclusion: This study developed virtual courage for high-risk occupations based on well-established theory and VR technology. Experimental data revealed that the paradigm conformed to the requirements of VR features and was able to activate fear and evoke the quality of courage. Thus, the virtual courage paradigms have good validity in simulating scenarios for high-risk employees, which might accelerate organizational effectiveness while buffering working stress.
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http://dx.doi.org/10.2147/PRBM.S371653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9292066PMC
July 2022

Dual epigenetic agents plus rituximab-gemcitabine-oxaliplatin as salvage treatment in relapsed/refractory diffuse large B-cell lymphoma patients failure of salvage chemotherapy.

Hematol Oncol 2022 Jul 20. Epub 2022 Jul 20.

Department of Hematology, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou, China.

Refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL) patients' failure of salvage chemotherapy had extremely worse prognoses. Herein, 14 R/R DLBCL patients failed to salvage chemotherapy were exposed to dual epigenetic agents (Chidamide 30 mg biw*2w and Decitabine 10 mg/m qd*d1-d5) and sequential R-GemOx (rituximab 375 mg/m qd d6; gemcitabine 1 g/m d7, d14; and oxaliplatin 100 mg/m d7) for further salvage chemotherapy. Finally, 11/14(78.6%) patients achieved overall response with 6/14(42.9%) achieving complete remission and 2-year overall survival (OS)/progression free survival (PFS) rate was 42.7%, extremely higher than reported previously. Further subgroup analysis demonstrated that 2-year OS/PFS rate was significantly higher in patients achieved complete/partial remission or with low international prognosis index (IPI 0-2) than that in patients with steady disease or high IPI (3-5). Common grade 3-4 adverse events were hematological toxicities. All toxicities were transient and reversible. Our report implicates that combination of dual epigenetic agents and R-GemOx is a safe and promising alternative for R/R DLBCL patients.
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http://dx.doi.org/10.1002/hon.3052DOI Listing
July 2022

Universal and Stable Slippery Coatings: Chemical Combination Induced Adhesive-Lubricant Cooperation.

Small 2022 Aug 17;18(32):e2203057. Epub 2022 Jul 17.

Key Laboratory of Bio-inspired Materials and Interfacial Science, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Liquid lubricant of low affinity makes slippery coatings widely used in lubricating, anti-biofouling, anti-icing, fluid guiding, and drag reduction. Two critical challenges, however, remain in the practical application of slippery coatings consisting of liquid lubricants: (1) universality regardless of roughness and chemical composition of substrates, (2) stability of surface lubricity against evaporation. Herein, a chemical method is reported to create a universal and stable slippery lubricant-adhesive cooperated coating (SLACC) through acid catalyzed dehydration reaction between the phenolic hydroxyl of polydopamine (PDA), with universal (for challenge-1) and strong (for challenge-2) adhesion properties, and liquid-like polydimethylsiloxane (PDMS), with lubricant properties. Through overlying PDMS on PDA, a spatial gradient interpenetration of chemical combined PDA and PDMS leaving lubricant PDMS at the outermost of coating is achieved. This structure contributes to the following performances of SLACC: nearly universality suitable for 100 different abiotic or biotic substrates and stability sustainable for long-term usages, UV radiating, refrigerating, hot air drying, freeze drying, knife scratch and abrasion. This proposed strategy is envisioned anti-fouling from plane to tube and exhibits drag reduction in confined space.
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http://dx.doi.org/10.1002/smll.202203057DOI Listing
August 2022

Adenosine triphosphate-based tumor chemosensitivity assay may predict the clinical outcomes of gastric cancer patients receiving taxane-based post-operative adjuvant chemotherapy.

Chin Med J (Engl) 2022 Jul 18. Epub 2022 Jul 18.

Department of Clinical Pharmacology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.

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http://dx.doi.org/10.1097/CM9.0000000000002210DOI Listing
July 2022

Efficacy and safety of radiotherapy combined with raltitrexed and irinotecan for treating unresectable recurrent colorectal cancer: a single-arm phase II trial.

J Gastrointest Oncol 2022 Jun;13(3):1112-1120

Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.

Background: Local recurrence of colorectal cancer is associated with poor prognosis and quality of life. For patients not eligible for curative surgery, chemoradiation could be a promising therapeutic option, but there is no consensus yet for the concurrent chemotherapy regimen. This study evaluated the effects and safety of intensity-modulated radiation therapy (IMRT) when administered concurrently with raltitrexed and irinotecan to patients with unresectable recurrent colorectal cancer.

Methods: Eligible patients developed unresectable recurrent colorectal cancer, and were refractory to, or intolerant of, chemotherapy with fluoropyrimidine and oxaliplatin. IMRT was delivered (total dose: 50-60 Gy in 25-30 fractions) concurrently with irinotecan and raltitrexed (200 and 3 mg/m, respectively, on days 1 and 22). After treatment completion, patients underwent surgery or continued the same regimen of chemotherapy and were assessed by a multidisciplinary team. The primary endpoint was the objective response rate, defined as the proportion of patients with a confirmed complete response or partial response, assessed by radiologist and investigator after the completion of radiotherapy and reconfirmed a month later, in accordance with the Response Evaluation Criteria in Solid Tumors version 1.1.

Results: All 30 patients enrolled in this study between January 2019 and July 2020 completed radiotherapy and received a median of five chemotherapy cycles (range, 2-10 cycles). Twelve patients (40.0%) experienced an objective response (two complete responses and ten partial responses) and 17 patients exhibited stable disease [disease control rate (DCR): 96.7%]. The median follow-up was 22 months (range, 4-35 months), by the end of follow-up, six (20.0%) patients had local failure in the irradiation field, four (13.3%) had regional progression outside the irradiation field, 13 (43.3%) had distant metastasis or metastatic progression and nine (30.0%) died. The median progression-free survival (PFS) and local PFS (LPFS) were 13.5 and 23 months, respectively. The incidence of grade 3 or 4 adverse events was 26.7%, the most common of which was neutropenia (13.3%).

Conclusions: IMRT with concurrent raltitrexed and irinotecan is a feasible treatment for unresectable recurrent colorectal cancer, which allows good tumor response and local control with acceptable toxicity profile.
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http://dx.doi.org/10.21037/jgo-22-308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274057PMC
June 2022

Alisol B 23-Acetate Ameliorates Lipopolysaccharide-Induced Intestinal Barrier Dysfunction by Inhibiting TLR4-NOX1/ROS Signaling Pathway in Caco-2 Cells.

Front Pharmacol 2022 14;13:911196. Epub 2022 Jun 14.

Department of Pharmacy, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.

Alisol B 23-Acetate (AB23A) is a naturally occurring triterpenoid, which can be indicated in the rhizome of medicinal and dietary plants from Alisma species. Previous studies have demonstrated that AB23A could inhibit intestinal permeability by regulating tight junction (TJ)-related proteins. Even so, the AB23A protective mechanism against intestinal barrier dysfunction remains poorly understood. This investigation seeks to evaluate the AB23A protective effects on intestinal barrier dysfunction and determine the mechanisms for restoring intestinal barrier dysfunction in LPS-stimulated Caco-2 monolayers. According to our findings, AB23A attenuated the inflammation by reducing pro-inflammatory cytokines production like IL-6, TNF-α, IL-1β, and prevented the paracellular permeability by inhibiting the disruption of TJ in LPS-induced Caco-2 monolayers after treated with LPS. AB23A also inhibited LPS-induced TLR4, NOX1 overexpression and subsequent ROS generation in Caco-2 monolayers. Transfected with NOX1-specific shRNA diminished the up-regulating AB23A effect on ZO-1 and occludin expression. Moreover, transfected with shRNA of TLR4 not only enhanced ZO-1 and occludin expression but attenuated NOX1 expression and ROS generation. Therefore, AB23A ameliorates LPS-induced intestinal barrier dysfunction by inhibiting TLR4-NOX1/ROS signaling pathway in Caco-2 monolayers, suggesting that AB23A may have positive impact on maintaining the intestinal barrier's integrity.
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http://dx.doi.org/10.3389/fphar.2022.911196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237229PMC
June 2022

Analysis of stepped wedge cluster randomized trials in the presence of a time-varying treatment effect.

Stat Med 2022 Jun 30. Epub 2022 Jun 30.

Department of Biostatistics, University of Washington, Seattle, Washington, USA.

Stepped wedge cluster randomized controlled trials are typically analyzed using models that assume the full effect of the treatment is achieved instantaneously. We provide an analytical framework for scenarios in which the treatment effect varies as a function of exposure time (time since the start of treatment) and define the "effect curve" as the magnitude of the treatment effect on the linear predictor scale as a function of exposure time. The "time-averaged treatment effect" (TATE) and "long-term treatment effect" (LTE) are summaries of this curve. We analytically derive the expectation of the estimator resulting from a model that assumes an immediate treatment effect and show that it can be expressed as a weighted sum of the time-specific treatment effects corresponding to the observed exposure times. Surprisingly, although the weights sum to one, some of the weights can be negative. This implies that may be severely misleading and can even converge to a value of the opposite sign of the true TATE or LTE. We describe several models, some of which make assumptions about the shape of the effect curve, that can be used to simultaneously estimate the entire effect curve, the TATE, and the LTE. We evaluate these models in a simulation study to examine the operating characteristics of the resulting estimators and apply them to two real datasets.
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http://dx.doi.org/10.1002/sim.9511DOI Listing
June 2022

Methane dynamics in the Hailuogou Glacier forefield, Southwest China.

Environ Res 2022 Jun 27;214(Pt 1):113767. Epub 2022 Jun 27.

State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, CAS, Guiyang 550081, China.

Soils in glacier forefields have a significant capacity for atmospheric CH uptake, but this pattern could be changed by high soil water content (SWC). The Hailuogou Glacier in SW China is a typical temperate monsoon glacier on siliceous bedrock, where a forefield soil chronosequence has developed with progressive glacier recession. To understand CH dynamics and their potential regulatory factors, we measured the concentrations and stable carbon (C) isotope compositions of CH and CO soil physicochemical properties, and perfromed a high-throughput sequencing. Among nine sampling sites, soil CH concentrations of six sites were below atmospheric levels and δC-CH values were similar to atmospheric levels. The average value was approximately -48.6‰ and without obvious fractionation. The soil CH concentrations exceeded atmospheric levels for the remaining three sites, and the δC-CH values were more enriched with increasing soil CH concentration. We calculated the soil-atmosphere CH flux (J) using the concentration gradient method based on the soil CH concentration, sampling depth, and soil porosity. J ranges from -0.08 to -0.52 mg m d, acting as an atmospheric CH sink. It also shows that the correlation with soil exposure age or vegetation succession was insignificant. But the CH emission shows a larger variation changing from 0.05 to 1.8 mg m d, which could result from local CH production differences catalyzed by aceticlastic methanogens. The results showed that not all sites acted as a net CH sink. SWC may have an important influence on CH dynamics in the Hailuogou Glacier forefield (HGF).
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http://dx.doi.org/10.1016/j.envres.2022.113767DOI Listing
June 2022

A study protocol of a randomized phase II trial of perioperative chemoimmunotherapy verses perioperative chemoimmunotherapy plus preoperative chemoradiation for locally advanced gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma: the NeoRacing study.

BMC Cancer 2022 Jun 28;22(1):710. Epub 2022 Jun 28.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, People's Republic of China.

Background: Perioperative chemotherapy (ChT) and preoperative chemoradiation (CRT) are both the standard treatments for locally advanced gastric cancer (LAGC). CRT can achieve a higher pathological complete regression (pCR) rate, but whether this higher pCR rate can be transformed into a long-term survival benefit remains inconclusive. Therefore, relevant studies are in progress. On the other hand, immunotherapy has been established for the first-line treatment of advanced gastric cancer (AGC) and has been widely explored in the perioperative setting. The combination of chemotherapy/radiotherapy and immunotherapy may have a synergistic effect, which will lead to a better antitumor effect. The preliminary reports of ongoing studies show promising results, including a further improved pCR rate. However, the preferred treatment combination for LAGC is still not established. To solve this problem, we are carrying out this randomized phase II trial, which aims to evaluate the efficacy and safety of perioperative chemotherapy plus the use of PD-1 antibody with or without preoperative chemoradiation for LAGC.

Methods: Eligible patients with LAGC or gastroesophageal junction (GEJ) adenocarcinoma were randomized to receive perioperative ChT, PD-1 antibody, surgery with (Arm A) or without preoperative CRT (Arm B), and PD-1 antibody maintenance until one year after surgery. The primary endpoint of this study is that the pCR rate of Arm A will be significantly higher than that of Arm B. The secondary endpoints include the pathological partial regression (pPR) rate, R0 resection rate, objective response rate (ORR), event-free survival (EFS), overall survival (OS), safety and surgical complications. Moreover, several explorative endpoints will be evaluated to find and validate the predictive biomarkers of immunotherapy.

Discussion: The results of the NeoRacing study will provide important information concerning the application of PD-1 antibody in LAGC patients during the perioperative setting. Meanwhile, the two treatment protocols will be compared in terms of efficacy and safety.

Trial Registration: ClinicalTrials.gov , NCT05161572 . Registered 17 December 2021 - Retrospectively registered.
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http://dx.doi.org/10.1186/s12885-022-09786-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238164PMC
June 2022

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors.

J Vis Exp 2022 06 8(184). Epub 2022 Jun 8.

Division of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University;

Lysophospholipids (LPLs) are bioactive lipids that include sphingosine 1-phosphate (S1P), lysophosphatidic acid, etc. S1P, a metabolic product of sphingolipids in the cell membrane, is one of the best-characterized LPLs that regulates a variety of cellular physiological responses via signaling pathways mediated by sphingosine 1-phosphate receptors (S1PRs). This implicated that the S1P-S1PRs signaling system is a remarkable potential therapeutic target for disorders, including multiple sclerosis (MS), autoimmune disorders, cancer, inflammation, and even COVID-19. S1PRs, a small subset of the class A G-protein coupled receptor (GPCR) family, are composed of five subtypes: S1PR1, S1PR2, S1PR3, S1PR4, and S1PR5. The lack of detailed structural information, however, impedes the drug discovery targeting S1PRs. Here, we applied the cryo-electron microscopy method to solve the structure of the S1P-S1PRs complex, and elucidated the mechanism of activation, selective drug recognition, and G-protein coupling by using cell-based functional assays. Other lysophospholipid receptors (LPLRs) and GPCRs can also be studied using this strategy.
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http://dx.doi.org/10.3791/64054DOI Listing
June 2022

Phased small RNA-mediated systemic signaling in plants.

Sci Adv 2022 Jun 24;8(25):eabm8791. Epub 2022 Jun 24.

Department of Plant Pathology, University of Kentucky, Lexington, KY 40546, USA.

Systemic acquired resistance (SAR) involves the generation of systemically transported signal that arms distal plant parts against secondary infections. We show that two phased 21-nucleotide (nt) RNAs (tasi-RNA) derived from and synthesized within 3 hours of pathogen infection are the early mobile signal in SAR. undergoes alternate polyadenylation, resulting in the generation of 555- and 367-nt transcripts. The 555-nt transcripts likely serves as the sole precursor for tasi-RNAs D7 and D8, which cleave () , , and to induce SAR. Conversely, increased expression of represses SAR. Knockout mutations in or RNA silencing components required for tasi-RNA biogenesis compromise SAR without altering levels of known SAR-inducing chemicals. Both tasi-ARFs and the 367-nt transcripts are mobile and transported via plasmodesmata. Together, we show that tasi-ARFs are the early mobile signal in SAR.
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http://dx.doi.org/10.1126/sciadv.abm8791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9232115PMC
June 2022

Ultrasmall Ruthenium Nanoparticles with Boosted Antioxidant Activity Upregulate Regulatory T Cells for Highly Efficient Liver Injury Therapy.

Small 2022 Jul 24;18(29):e2201558. Epub 2022 Jun 24.

Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.

Nanozymes exhibiting antioxidant activity are beneficial for the treatment of oxidative stress-associated diseases. Ruthenium nanoparticles (RuNPs) with multiple enzyme-like activities have attracted growing attention, but the relatively low antioxidant enzyme-like activities hinder their practical biomedical applications. Here, a size regulation strategy is presented to significantly boost the antioxidant enzyme-like activities of RuNPs. It is found that as the size of RuNPs decreases to ≈2.0 nm (sRuNP), the surface-oxidized Ru atoms become dominant, thus possessing an unprecedentedly boosted antioxidant activity as compared to medium-sized (≈3.9 nm) or large-sized counterparts (≈5.9 nm) that are mainly composed of surface metallic Ru atoms. Notably, based on their antioxidant enzyme-like activities and ultrasmall size, sRuNP can not only sustainably ameliorate oxidative stress but also upregulate regulatory T cells in late-stage acetaminophen (APAP)-induced liver injury (ALI). Consequently, sRuNPs perform highly efficient therapeutic efficiency on ALI mice even when treated at 6 h after APAP intoxication. This strategy is insightful for tuning the catalytic performances of nanozymes for their extensive biomedical applications.
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http://dx.doi.org/10.1002/smll.202201558DOI Listing
July 2022

Effect of Thermal Processing on the Metabolic Components of Black Beans on Ultra-High-Performance Liquid Chromatography Coupled with High-Field Quadrupole-Orbitrap High-Resolution Mass Spectrometry.

Molecules 2022 Jun 18;27(12). Epub 2022 Jun 18.

College of Food, Heilongjiang Bayi Agricultural University, Xinfeng Lu 5, Daqing 163319, China.

An ultra-high-performance liquid chromatography coupled with high-field quadrupole-orbitrap mass spectrometry (UHPLC-QE-MS) histological platform was used to analyze the effects of two thermal processing methods (cooking and steaming) on the nutritional metabolic components of black beans. Black beans had the most amino acids, followed by lipids and polyphenols, and more sugars. Multivariate statistical analysis indicated that heat processing significantly affected the metabolic component content in black beans, with effects varying among different components. Polyphenols, especially flavonoids and isoflavones, were highly susceptible. A total of 197 and 210 differential metabolites were identified in both raw black beans and cooked and steamed black beans, respectively. Cooking reduced the cumulative content of amino acids, lipids, polyphenols, sugars, and nucleosides, whereas steaming reduced amino acid and lipid content, slightly increased polyphenol content, and significantly increased sugar and nucleoside content. Our results indicated that metabolic components were better retained during steaming than cooking. Heat treatment had the greatest impact on amino acids, followed by polyphenols, fatty acids, sugars, and vitamins, indicating that cooking promotes the transformation of most substances and the synthesis of a few. The results of this study provide a basis for further research and development of nutritional products using black beans.
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http://dx.doi.org/10.3390/molecules27123919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227771PMC
June 2022

Carbon Nanotube-Based Flexible Ferroelectric Synaptic Transistors for Neuromorphic Computing.

ACS Appl Mater Interfaces 2022 Jul 23;14(26):30124-30132. Epub 2022 Jun 23.

Key Laboratory for the Physics and Chemistry of Nanodevices, Center for Carbon-Based Electronics, and School of Electronics, Peking University, Beijing 100871, China.

Biological nervous systems evolved in nature have marvelous information processing capacities, which have great reference value for modern information technologies. To expand the function of electronic devices with applications in smart health monitoring and treatment, wearable energy-efficient computing, neuroprosthetics, etc., flexible artificial synapses for neuromorphic computing will play a crucial role. Here, carbon nanotube-based ferroelectric synaptic transistors are realized on ultrathin flexible substrates via a low-temperature approach not exceeding 90 °C to grow ferroelectric dielectrics in which the single-pulse, paired-pulse, and repetitive-pulse responses testify to well-mimicked plasticity in artificial synapses. The long-term potentiation and long-term depression processes in the device demonstrate a dynamic range as large as 2000×, and 360 distinguishable conductance states are achieved with a weight increase/decrease nonlinearity of no more than 1 by applying stepped identical pulses. The stability of the device is verified by the almost unchanged performance after the device is kept in ambient conditions without additional passivation for 240 days. An artificial neural network-based simulation is conducted to benchmark the hardware performance of the neuromorphic devices in which a pattern recognition accuracy of 95.24% is achieved.
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http://dx.doi.org/10.1021/acsami.2c07825DOI Listing
July 2022

Impact of the Grain for Green Project on water resources and ecological water stress in the Yanhe River Basin.

PLoS One 2022 16;17(6):e0259611. Epub 2022 Jun 16.

College of Water Resources, North China University of Water Resources and Electric Power, Zhengzhou, Henan, China.

The Grain for Green project (GGP), initialized by the Chinese government in 1999, has achieved substantial achievements accompanied by a decrease in surface runoff on the Loess Plateau, but the impacts of large-scale afforestation on regional water resources are uncertain. Hence, the objective of this study was to explore the impact of land use change on generalized water resources and ecological water stress using the blue and green water concepts, taking the Yanhe River Basin as the case study. The Soil and Water Assessment Tool (SWAT) was applied to quantify the green water and blue water, which are defined as generalized water resources. The ecological water requirement of vegetation (forest and grass), agricultural water footprint and virtual water flow are considered regional water requirements. The land use types of 1980 (Scenario I) and 2017 (Scenario II) were entered into the SWAT model while keeping the other parameters constant to isolate the influence of land use changes. The results show that the average annual differences in blue, green and generalized water resources were -72.08 million m3, 24.34 million m3, and -47.74 million m3, respectively, when the simulation results of Scenario II were subtracted from those of Scenario I, which shows that land use change caused by the GGP led to a decrease in blue and generalized water resources and an increase in green water resources. Surface runoff in Scenario I was more than that in Scenario II in all of the years of the study period from 1980-2017, and green water storage in Scenario I was more than that in Scenario II in all of the years of the study period except in 1998; although lateral flow in Scenario I was less than that in Scenario II except in 2000 and 2015, as was groundwater runoff in 1992, 2000 and 2015, and green water flow in 1998. Blue water flow, green water storage and green water flow in Scenario II were less than those in Scenario I in the whole basin, 12.89 percent of the basin and 99.21 percent of the basin, respectively. The total water footprint increased from 1995 to 2010 because the forest water footprint increased significantly in this period, although the agricultural water footprint and grass water footprint decreased. The ecological water stress index values had no obvious temporal change trends in either land use scenario, but the ecological water stress index in Scenario II was greater than that in Scenario I, which illustrates that the GGP led to an increase in ecological water stress from the perspective of generalized water resources.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0259611PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202897PMC
June 2022

High stability of autochthonous dissolved organic matter in karst aquatic ecosystems: Evidence from fluorescence.

Water Res 2022 Jul 7;220:118723. Epub 2022 Jun 7.

State Key Laboratory of Environmental Geochemistry, CAS, Institute of Geochemistry, Guiyang 550081, China.

Biological carbon pump (BCP) in karst areas has received intensive attention for years due to their significant contribution to the global missing carbon sink. The stability of autochthonous dissolved organic matter (Auto-DOM) produced by BCP in karst aquatic ecosystems may play a critical role in the missing carbon sink. However, the source of dissolved organic matter (DOM) in inland waters and its consumption by planktonic bacteria have not been thoroughly examined. Recalcitrant dissolved organic matter (RDOM) may exist in karst aquatic ecosystem as in the ocean. Through the study of the chromophoric dissolved organic matter (CDOM) and the interaction between CDOM and the planktonic bacterial community under different land uses at the Shawan Karst Water-carbon Cycle Test Site, SW China, we found that C2, as the fluorescence component of Auto-DOM mineralised by planktonic bacteria, may have some of the characteristics of RDOM and is an important DOM source in karst aquatic ecosystems. The stability ratio (Fmax) of Auto-DOM reached 89.6 ± 6.71% in winter and 64.1 ± 7.19% in spring. Moreover, correlation-based network analysis determined that the planktonic bacterial communities were controlled by different fluorescence types of CDOM, of which C1 (fresh Auto-DOM), C3 (conventional allochthonous DOM (Allo-DOM)) and C4 (the Allo-DOM mineralised by bacteria) were clustered in one module together with prevalent organic-degrading planktonic bacteria; C2 was clustered in another tightly combined module, suggesting specific microbial utilization strategies for the C2 component. In addition, some important planktonic bacterium and functional genes (including chemotrophic heterotrophs and photosynthetic bacteria) were found to be affected by high Ca and dissolved inorganic carbon (DIC) concentrations in karst aquatic ecosystems. Our research showed that Auto-DOM may be as an important carbon sink as the Allo-DOM in karst ecosystems, the former generally being neglected based on a posit that it is easily and first mineralized by planktonic bacteria.
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http://dx.doi.org/10.1016/j.watres.2022.118723DOI Listing
July 2022

Erythrocyte membrane-camouflaged nanoparticles as effective and biocompatible platform: Either autologous or allogeneic erythrocyte-derived.

Mater Today Bio 2022 Jun 5;15:100279. Epub 2022 May 5.

State Key Laboratory of Biogeology and Environmental Geology, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, China.

Erythrocytes are often used for the development of cell membrane camouflaged nanoparticles (NPs) due to their wide range of sources. However, whether the difference between autologous and allogeneic sources for the erythrocyte membranes have an influence on the performance of camouflaged NPs, which is still inconclusive. To this end, we developed two aggregation-induced emission (AIE) photosensitizers camouflaged with erythrocyte membranes (E-M), named [email protected] and [email protected], which were prepared using autologous- and allogeneic-derived erythrocytes, respectively. In vivo, [email protected] photodynamic therapy (PDT) effectively inhibited tumor growth, and this therapeutic effect did not differ between [email protected] and [email protected] Importantly, there were no differences between [email protected] and [email protected] treated mice in terms of general condition, organ function or immune system. Both [email protected] and [email protected] have been shown not to cross the placental barrier and do not affect the development of the embryo, which could be a good platform for the treatment of pregnancy-related disorders. These findings provided more detailed evidences for erythrocyte membrane camouflaged NPs as a promising therapeutic platform, since there is no difference in efficacy or biosafety of either autologous or allogeneic erythrocyte-derived NPs.
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http://dx.doi.org/10.1016/j.mtbio.2022.100279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119842PMC
June 2022

New rapid detection method of total chlorogenic acids in plants using SERS based on reusable CuO-Ag substrate.

Talanta 2022 Sep 14;247:123552. Epub 2022 May 14.

College of Engineering, China Agricultural University, Beijing, 100083, PR China.

A new method for rapidly detecting of total chlorogenic acids (CGAs) in plants by surface-enhanced Raman spectroscopy (SERS) based on reusable CuO-Ag substrate was developed in this study. The CuO-Ag substrate prepared by the in-situ growth method had high uniformity with peak intensity relative standard deviation (RSD) of 5.27%, repeatability with peak intensity RSD of 3.58%, and sensitivity with an analytical enhancement factor of 1.27 × 10 for detecting CGAs. Furthermore, the substrate had excellent reusability, after it was reused for seven cycles, the signal strength of CGAs was still above 80% of initial. Compared with the standard method of high-performance liquid chromatography (HPLC), the SERS method can successfully analyze the contents of total CGAs in plants, such as Stevia rebaudiana leaves, coffee beans, Lonicera japonica leaves, and Eucommia ulmoides flowers, with recovery rate from 93.26% to 112.65%, and the limit of detection was 0.13 μg/mL. The total CGAs content of Stevia rebaudiana leaves samples detected by HPLC and SERS have good consistency with R = 0.9760 and RMSE = 3286 mg/kg. Furthermore, the SERS method only needed less than 1 min, one standard and reusable substrate in this study to analyze, which can further reduce the cost of method analysis. Therefore, the SERS method with the appropriate substrate can provide a rapid, accurate, and economic way to detect the total CGAs in plants.
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http://dx.doi.org/10.1016/j.talanta.2022.123552DOI Listing
September 2022

Endocytosis Pathway Self-Regulation for Precise Image-Guided Therapy through an Enzyme-Responsive Modular Peptide Probe.

Anal Chem 2022 06 20;94(22):7960-7969. Epub 2022 May 20.

State Key Laboratory of Biogeology and Environmental Geology, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430078, China.

Before arriving at the intracellular destinations, probes might be trapped in the lysosomes, reducing the amount of cargos, which compromises the therapeutic outcomes. The current methods are based on the fact that probes enter the lysosomes and then escape from them, which do not fundamentally solve the degradation by lysosomal hydrolases. Here, an enzyme-responsive modular peptide probe named PKP that can be divided into two parts, Pal-part and KP-part, by matrix metalloproteinase-2 (MMP-2) overexpressed in tumor microenvironments is designed. Pal-part quickly enters the cells and forms nanofibers in the lysosomes, decreasing protein phosphatase 2A (PP2A), which transforms the endocytic pathway of KP-part from clathrin-mediated endocytosis (CME) into caveolae-mediated endocytosis (CvME) and allows KP-part to directly reach the mitochondria sites without passing through the lysosomes. Finally, through self-regulating intracellular delivery pathways, the mitochondrial delivery efficiency of KP-part is greatly improved, leading to an optimized image-guided therapeutic efficiency. Furthermore, this system also shows great potential for the delivery of siRNA and doxorubicin to achieve precise cancer image-guided therapy, which is expected to significantly expand its application and facilitate the development of personalized therapy.
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http://dx.doi.org/10.1021/acs.analchem.2c00776DOI Listing
June 2022
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