Publications by authors named "Jing Lin"

1,355 Publications

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Combination of continuous wavelet transform and genetic algorithm-based Otsu for efficient mass spectrometry peak detection.

Biochem Biophys Res Commun 2022 Aug 1;624:75-80. Epub 2022 Aug 1.

Zhejiang Engineering Research Center of Advanced Mass Spectrometry and Clinical Application, Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis of Zhejiang Province, Institute of Mass Spectrometry, School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, PR China. Electronic address:

Mass spectrometry (MS) data is susceptible to random noises and alternating baseline, posing great challenges to spectral peak detection, especially for weak peaks and overlapping peaks. Herein, an efficient peak detection algorithm combining continuous wavelet transform (CWT) and genetic algorithm-based threshold segmentation (denoted as WSTGA) for mass spectrometry was proposed. Firstly, Mexican Hat wavelet was selected as the mother wavelet by comparing the matching degree between the difference of Gaussian (DOG) and different wavelets. Subsequently, the ridges and valleys were identified from 2D wavelet coefficient matrix. Afterward, an improved threshold segmentation method, Otsu method based on genetic algorithm, was introduced to find optimal segmentation threshold and achieve better image segmentation, overcoming the deficiency of traditional Otsu method that cannot handle long-tailed unimodal histograms. Finally, the characteristic peaks were successfully identified by utilizing the ridge-valley lines in wavelet space and original spectrum. Receiver operating characteristic (ROC) curve, area under curve (AUC) and F₁ measure are used as criterions to evaluate performance of peak detection algorithms. Compared with multi-scale peak detection (MSPD) and CWT and image segmentation (CWT-IS) methods, all the results showed that WSTGA can achieve better peak detection. More importantly, the experimental results from MALDI-TOF spectra demonstrated that WSTGA can effectively detect more weak peaks and overlapping peaks while maintaining a lower false peak detection rate than MSPD and CWT-IS methods, indicating its great advantages in characteristic peak identification.
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http://dx.doi.org/10.1016/j.bbrc.2022.07.083DOI Listing
August 2022

Identification and mapping of genetic locus conferring resistance to multiple plant viruses in soybean.

Theor Appl Genet 2022 Aug 6. Epub 2022 Aug 6.

Institute of Cereal and Oil Crops, The Key Laboratory of Crop Genetics and Breeding of Hebei, Hebei Academy of Agricultural and Forestry Sciences, Shijiazhuang, 050035, China.

Key Message: A reliable locus confers broad-spectrum resistance to multiple plant viruses in soybean under field conditions. Soybean mosaic disease (SMD) can be caused by a variety of viruses, most of which have been largely overlooked in breeding programs. Effective mitigation of the adverse of SMD might result from breeding cultivars with broad-spectrum resistance. However, reports on broad-spectrum resistance to multiple virus have been limited. To catalog viral community members behind SMD, virus samples were collected from symptomatic field plots, and pathogenicity of component strains was assessed. Preliminary ELISA and PCR detection revealed that 39.58% and 66.67% of samples contained two or more virus strains, respectively. Only three soybean accessions were completely asymptomatic, while 42% exhibited moderate or severe susceptibility, indicating that co-infection of multiple virus remains a significant threat in current soybean production systems. Further, a RIL population consisting of 150 F strains derived from two soybean genotypes with contrasting reactions to virus infection was constructed and explored for significant markers and resistance genes. QTL analysis returned a reliable locus, named GmRmv, on chromosome 13. Significance of GmRmv in imparting resistance to SMD was further confirmed in NIL lines and delimited into a 157-kb interval that contains 17 annotated genes. Among these genes, three, Glyma.13G190000, Glyma.13G190300 and Glyma.13G190400, each contained LRR domains, as well as significant variation in coding sequences between resistant and susceptible parents. Hence, these three genes are considered strong candidate genes for explaining GmRmv significance. In summary, this research opens a new avenue for formulating strategies to breed soybean varieties with broad-spectrum resistance to multiple virus associated with SMD.
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http://dx.doi.org/10.1007/s00122-022-04187-9DOI Listing
August 2022

Drug-loaded mesoporous carbon with sustained drug release capacity and enhanced antifungal activity to treat fungal keratitis.

Biomater Adv 2022 May 23;136:212771. Epub 2022 Mar 23.

Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao 266003, PR China. Electronic address:

Fungal keratitis is a severe infectious corneal disease with a high rate of incidence and blindness. Since traditional treatments natamycin (NATA) eye drops, exhibit poor dissolution and bioavailability, and the efficacy of current therapeutic approaches remains limited. In this study, we innovatively utilized mesoporous carbon (Meso-C) and microporous carbon (Micro-C) as nanocarriers loaded with the antifungal drug NATA and silver nanoparticles (Ag-NPs). Porous carbon loaded with NATA and Ag-NPs has not previously been studied in fungal keratitis. Due to the mesoporous structure, high surface area and larger pore volume of Meso-C, it displayed greater superiority in sustained drug release and drug dispersity than Micro-C. Moreover, Meso-C could adsorb inflammatory cytokines during fungal infection. In vitro, Meso-C/NATA/Ag showed excellent antifungal effects. In vivo, compared with pure NATA treatment, Meso-C/NATA/Ag exhibited significantly improved therapeutic effects and reduced dosing frequency when treating fungal keratitis. Our study is the first to report the sustained drug release and improved drug dispersity of Meso-C/NATA and demonstrates that NATA and Ag-NPs-loaded Meso-C has therapeutic effects against fungal keratitis.
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http://dx.doi.org/10.1016/j.bioadv.2022.212771DOI Listing
May 2022

Molecularly imprinted polymers based on magnetic metal-organic frameworks for surface-assisted laser desorption/ionization time-of-flight mass spectrometry analysis and simultaneous luteolin enrichment.

J Chromatogr A 2022 Jul 26;1678:463377. Epub 2022 Jul 26.

School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China. Electronic address:

UiO-66(NH), a metal-organic framework, exhibits excellent UV absorption and energy transfer performance and can be used as a substrate for surface-assisted laser desorption/ionization (SALDI) analysis of small molecules. Molecularly imprinted polymers (MIPs) exhibit outstanding selectivity toward certain targets. The complexes of UiO-66(NH) and MIPs can be applied as both an adsorbent and substrate for SALDI-time-of-flight mass spectrometry (SALDI-TOF MS) analysis of small molecules. Herein, magnetic UiO-66(NH)-molecularly imprinted polymers (MUMIPs) were prepared for the selective enrichment and detection of luteolin via SALDI-TOF MS. The amino group on UiO-66(NH) were used as functional monomer to prepare MIPs that interact with luteolin via hydrogen bonding. The surface functional monomer can effectively control the coating thickness of the MIPs to avoid embedding template molecules and enhance adsorption performance. In addition, FeO particles were introduced for rapid magnetic separation. The physicochemical properties of the MUMIPs were characterized via scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, thermal gravimetric analysis, vibrating sample magnetometry, Brunauer-Emmett-Teller analysis, and X-ray photoelectron spectroscopy. Adsorption experiments and selectivity studies indicated that MUMIPs exhibited good adsorption capacity, fast adsorption rates, and excellent luteolin selectivity. MUMIPs are efficient substrates for the SALDI analysis of luteolin and its structural analogs. In addition, the MUMIPs-SALDI-TOF MS method successfully detected luteolin in rat plasma and urine after administration of oral Chrysanthemum morifolium Ramat extracts. This method possessed high sensitivity with a limit of detection of 0.5 ng/mL. The traditional precipitation method combined with high-performance liquid chromatography-mass spectrometry was also used to analyze luteolin in biological samples. Compared with the traditional method, the novel MUMIP-SALDI-TOF MS method can more effectively detect the target compounds in complex samples. Ultimately, the MUMIP-SALDI-TOF MS method was applied to detect luteolin and its metabolites in rat liver after oral luteolin treatment. Three luteolin metabolites (apigenin, chrysoeriol, and diosmetin) were analyzed using the newly developed MUMIP-SALDI-TOF MS method.
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http://dx.doi.org/10.1016/j.chroma.2022.463377DOI Listing
July 2022

NADPH oxidase 2 plays a protective role in experimental keratitis in mice through killing fungi and limiting the degree of inflammation.

Int J Ophthalmol 2022 18;15(7):1044-1052. Epub 2022 Jul 18.

Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China.

Aim: To explore whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) is expressed in fungal keratitis in mice and investigate its role in this disease.

Methods: NOX2 expression was detected in C57BL/6 mice. After testing the inhibitory effect of diphenyleneiodonium chloride (DPI) on NOX2, its impact on clinical performance, myeloperoxidase levels, the number of colonies forming units, the level of H3, the generation of reactive oxygen species (ROS) and the release of cytokines [NF-κB, interleukin-17A (IL-17A), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), Nrf2, IL-10, and TGF-β] were compared. A one-way ANOVA and an unpaired, two-tailed Student's -test was used to determine the statistical significance.

Results: NOX2 expression was significantly increased after injection in corneas and that this increase could be reduced by treatment with DPI. DPI treatment produced more severe inflammation and resulted in higher clinical scores, more neutrophils infiltration, a weakened ability to clear fungi, the release of fewer ROS and the formation of neutrophil extracellular traps. Treatment with DPI increased the expression of the proinflammatory cytokines NF-κB, IL-17A, IL-6, and TNF-α and decreased the expression of the anti-inflammatory cytokines Nrf2, IL-10 and TGF-β compared to their expression levels without DPI treatment.

Conclusion: NOX2 plays an important role against in the mouse cornea through killing fungi and limiting the degree of inflammation.
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http://dx.doi.org/10.18240/ijo.2022.07.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318084PMC
July 2022

The discovery of potentially active diterpenoids to inhibit the pyroptosis from Callicarpa arborea.

Bioorg Chem 2022 Jul 20;128:106022. Epub 2022 Jul 20.

KeyLaboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Research & Development Center for Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming 650091, People's Republic of China; StateKey Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming 650091, People's Republic of China. Electronic address:

Pyroptosis is a programmed-inflammatory cell death, which leads to release of inflammatory cellular contents and formation of inflammation. Uncontrollable pyroptosis can result in serious immune diseases, such as cytokine release syndrome (CRS), sepsis, disseminated intravascular coagulation (DIC), and acute organ damage, including acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). Members of the Callicarpa genus are significant raw materials for traditional Chinese medicine, widely used for analgesia, hemostasis, and anti-inflammation. Previously, we have reported some ent-clerodane diterpenoids from Callicarpa arborea, shown potent inhibitory effects against pyroptosis. In this study, we went on investigating this kind of diterpenoids, and yielded 66 ent-clerodane diterpenoids, including 52 new compounds, from Callicarpa arborea. Their structures featured with a 5/6- (1-25) or a 6/6- (26-66)-fused double-ring scaffolds, were elucidated using spectroscopic data, electrostatic circular dichroism (ECD) and X-ray diffraction analyses. Screening for the inhibitory activity against pyroptosis by detecting of IL-1β secretion in J771A.1 cells, revealed 28 compounds with an IC below 10.5 μM. Compound 1 was the most potent with an IC of 0.68 μM and inhibited the J774A.1 macrophage pyroptosis by blocking the NLR pyrin domain containing 3 (NLRP3) inflammasome activation. An in vivo study further revealed that compound 1 decreased infiltration of CD11b + F4/80 + macrophages into lung and attenuated the lipopolysaccharide (LPS)-induced lung injury. Taken together, this study indicated the potential of compound 1 as a candidate for pyroptosis-related inflammation treatment, as well as provided the chemical and pharmacological basis for the further development of Callicarpa genus as a herbal medicine.
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http://dx.doi.org/10.1016/j.bioorg.2022.106022DOI Listing
July 2022

The Effect of Correlated Colour Temperature on Physiological, Emotional and Subjective Satisfaction in the Hygiene Area of a Space Station.

Int J Environ Res Public Health 2022 Jul 27;19(15). Epub 2022 Jul 27.

School of Design, University of Leeds, Leeds LS2 9JT, UK.

The hygiene area is one of the most important facilities in a space station. If its environmental lighting is appropriately designed, it can significantly reduce the psychological pressure on astronauts. This study investigates the effect of correlated colour temperature (CCT) on heart rate, galvanic skin response, emotion and satisfaction in the hygiene area of a space station. Forty subjects participated in experiments in a hygiene area simulator with a controlled lighting environment. The lighting conditions included 2700 K, 3300 K, 3600 K, 5000 K and 6300 K; physiological responses (heart rate, galvanic skin response), as well as emotion and satisfaction, were recorded. The results showed that CCT significantly influenced the participants' physiological and subjective responses in the space station hygiene area. 6300 K led to the best emotion and satisfaction levels, the highest galvanic skin response and the lowest heart rate. The opposite was true for 2700 K.
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http://dx.doi.org/10.3390/ijerph19159090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332769PMC
July 2022

Transcriptional Repression of Aerobic Glycolysis by OVOL2 in Breast Cancer.

Adv Sci (Weinh) 2022 Jul 27:e2200705. Epub 2022 Jul 27.

Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Collaborative Innovation Center for Cancer Medicine, Beijing, 100850, China.

Aerobic glycolysis (Warburg effect), a hallmark of cancer, plays a critical role in cancer cell growth and metastasis; however, direct inhibition of the Warburg effect remains largely unknown. Herein, the transcription factor OVO-like zinc finger 2 (OVOL2) is demonstrated to directly repress the expression of several glycolytic genes, blocking the Warburg effect and breast tumor growth and metastasis in vitro and in vivo. OVOL2 inhibits glycolysis by recruiting the nuclear receptor co-repressor (NCoR) and histone deacetylase 3 (HDAC3). The tumor suppressor p53, a key regulator of cancer metabolism, activates OVOL2 by binding to the oncoprotein mouse double minute 2 homolog (MDM2) and inhibiting MDM2-mediated ubiquitination and degradation of OVOL2. OVOL2 expression is negatively correlated with glycolytic gene expression and can be a good predictor of prognosis in patients with breast cancer. Therefore, targeting the p53/MDM2/OVOL2 axis provides a potential avenue for cancer treatment, especially breast cancer.
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http://dx.doi.org/10.1002/advs.202200705DOI Listing
July 2022

Identification and Characterization of Specific Nanobodies against Trop-2 for Tumor Targeting.

Int J Mol Sci 2022 Jul 19;23(14). Epub 2022 Jul 19.

Research Institute of Public Health, School of Medicine, Nankai University, Tianjin 300071, China.

Trophoblast cell-surface antigen 2 (Trop-2) is a tumor-associated antigen that is connected with the development of various tumors and has been identified as a promising target for tumor immunotherapy. To date, the immunotherapy against Trop-2 mainly relies on the specific targeting by monoclonal antibody in antibody-drug conjugate (ADC). Alternatively, the single domain antibodies of nanobodies (Nbs) possesses unique properties such as smaller size, better tissue penetration, etc., to make them good candidates for tumor targeting. Thus, it was proposed to develop anti-Trop-2 Nbs for tumor targeting in this study. Generally, three consecutive rounds of bio-panning were performed against immobilized recombinant Trop-2, and yielded three Nbs (Nb60, Nb65, and Nb108). The affinity of selected Nbs was determined in the nanomolar range, especially the good properties of Nb60 were verified as a promising candidate for tumor labeling. The binding to native Trop-2 was confirmed by flow cytometry against tumor cells. The inhibitory effects of the selected Nbs on tumor cell proliferation and migration were confirmed by wound healing and Transwell assay. The clear localization of the selected Nbs on the surface of tumor cells verified the potent labeling efficiency. In conclusion, this study provided several Nbs with the potential to be developed as targeting moiety of drug conjugates.
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http://dx.doi.org/10.3390/ijms23147942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316174PMC
July 2022

Enhanced Water Resistance and Catalytic Performance of Ru/TiO by Regulating Brønsted Acid and Oxygen Vacancy for the Oxidative Removal of 1,2-Dichloroethane and Toluene.

Environ Sci Technol 2022 Jul 25. Epub 2022 Jul 25.

Beijing Key Laboratory for Green Catalysis and Separation, Key Laboratory of Beijing on Regional Air Pollution Control, Key Laboratory of Advanced Functional Materials, Education Ministry of China, Laboratory of Catalysis Chemistry and Nanoscience, Department of Environmental Chemical Engineering, College of Environmental and Chemical Engineering, Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China.

The compositions of volatile organic compounds (VOCs) under actual industrial conditions are often complex; especially, the interaction of intermediate products easily leads to more toxic emissions that are harmful to the atmospheric environment and human health. Herein, we report a comparative investigation on 1,2-dichloroethane (1,2-DCE) and (1,2-DCE + toluene) oxidation over the Ru/TiO, phosphotungstic acid (HPW)-modified Ru/TiO, and oxygen vacancy-rich Ru/TiO catalysts. The doping of HPW successfully introduced the 1,2-DCE adsorption sites to promote its oxidation and exhibited outstanding water resistance. For the mixed VOCs, Ru/HPW-TiO promoted the preferential and superfluous adsorption of toluene and resulted in the inhibition of 1,2-DCE degradation. Therefore, HPW modification is a successful strategy in catalytic 1,2-DCE oxidation, but Brønsted acid sites tend to adsorb toluene in the mixed VOC oxidation. The Ru/TiO catalyst exhibited excellent activity and stability in the oxidation of mixed VOCs and could inhibit the generation of byproducts and Cl compared with the Ru/HPW-TiO catalyst. Compared with the Brønsted acid modification, the oxygen vacancy-rich catalysts are significantly suitable for the oxidation of multicomponent VOCs.
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http://dx.doi.org/10.1021/acs.est.2c03336DOI Listing
July 2022

Magnesium Lithospermate B Protects Against Cisplatin-Induced Acute Kidney Injury via Alleviating Mitochondrial Dysfunction.

Drug Des Devel Ther 2022 15;16:2293-2304. Epub 2022 Jul 15.

Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

Purpose: Apoptosis plays a critical role in cisplatin-induced acute kidney injury (AKI) and is related to mitochondrial dysfunction. Magnesium lithospermate B (Mlb), one of the most important components of Bunge, is mainly used to treat cardiovascular diseases because of its anti-apoptotic effects. The mechanism underlying the protective effect of Mlb against cisplatin-induced AKI remains unclear. In this study, we investigated the protective effect of Mlb on mitochondrial function against apoptosis caused by cisplatin-induced renal injury.

Methods: Renal injury induced by cisplatin in mouse renal tubular epithelial cells (mTECs) was measured by quantifying serum creatinine levels, mitochondrial morphology, cell viability, apoptosis, Dynamin-related protein 1(Drp1) expression, etc. The cells were then administered Mlb to determine its protective effects against cisplatin-induced AKI.

Results: Mlb treatment significantly reduced serum creatinine levels and pathological injury of renal, inhibited the production of malondialdehyde, and reduced the depletion of superoxide dismutase. In addition, Mlb reduced Bax/Bcl2, cleaved caspase-3/caspase-3, and maintained mitochondrial integrity after AKI. Mlb administration also improved cell viability and reduced the percentage of apoptotic cells in vitro. Furthermore, Mlb reduced mitochondrial reactive oxygen species, improved mitochondrial membrane potential, and ameliorated mitochondrial morphological abnormalities by downregulating Drp1 expression.

Conclusion: These results indicated that Mlb could protect the kidneys against cisplatin-induced apoptosis by alleviating mitochondrial dysfunction.
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http://dx.doi.org/10.2147/DDDT.S358830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296868PMC
July 2022

Morphology of the anterior mesorectum: a new predictor for local recurrence in patients with rectal cancer.

Chin Med J (Engl) 2022 Jul 22. Epub 2022 Jul 22.

Department of Colorectal Surgery, Union Hospital, Fujian Medical University, Fuzhou, Fujian 350001, China.

Background: Pre-operative assessment with high-resolution magnetic resonance imaging (MRI) is useful for assessing the risk of local recurrence (LR) and survival in rectal cancer. However, no studies have explored the clinical importance of the morphology of the anterior mesorectum, especially in patients with anterior cancer. Hence, the study aimed to investigate the impact of the morphology of the anterior mesorectum on LR in patients with primary rectal cancer.

Methods: A retrospective study was performed on 176 patients who underwent neoadjuvant treatment and curative-intent surgery. Patients were divided into two groups according to the morphology of the anterior mesorectum on sagittal MRI: (1) linear type: the anterior mesorectum was thin and linear; and (2) triangular type: the anterior mesorectum was thick and had a unique triangular shape. Clinicopathological and LR data were compared between patients with linear type anterior mesorectal morphology and patients with triangular type anterior mesorectal morphology.

Results: Morphometric analysis showed that 90 (51.1%) patients had linear type anterior mesorectal morphology, while 86 (48.9%) had triangular type anterior mesorectal morphology. Compared to triangular type anterior mesorectal morphology, linear type anterior mesorectal morphology was more common in females and was associated with a higher risk of circumferential resection margin involvement measured by MRI (35.6% vs. 16.3%, P  = 0.004) and a higher 5-year LR rate (12.2% vs. 3.5%, P  = 0.030). In addition, the combination of linear type anterior mesorectal morphology and anterior tumors was confirmed as an independent risk factor for LR (odds ratio = 4.283, P = 0.014).

Conclusions: The classification established in this study was a simple way to describe morphological characteristics of the anterior mesorectum. The combination of linear type anterior mesorectal morphology and anterior tumors was an independent risk factor for LR and may act as a tool to assist with LR risk stratification and treatment selection.
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http://dx.doi.org/10.1097/CM9.0000000000002024DOI Listing
July 2022

Management of fluorescent organic/inorganic nanohybrids for biomedical applications in the NIR-II region.

Chem Soc Rev 2022 Jul 21. Epub 2022 Jul 21.

Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore, 119074, Singapore.

Biomedical fluorescence imaging in the second near-infrared (NIR-II, 100-1700 nm) window provides great potential for visualizing physiological and pathological processes, owing to the reduced tissue absorption, scattering, and autofluorescence. Various types of NIR-II probes have been reported in the past decade. Among them, NIR-II organic/inorganic nanohybrids have attracted widespread attention due to their unique properties by integrating the advantages of both organic and inorganic species. Versatile organic/inorganic nanohybrids provide the possibility of realizing a combination of functions, controllable size, and multiple optical features. This tutorial review summarizes the reported organic and inorganic species in nanohybrids, and their biomedical applications in NIR-II fluorescence and lifetime imaging. Finally, the challenges and outlook of organic/inorganic nanohybrids in biomedical applications are discussed.
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http://dx.doi.org/10.1039/d2cs00131dDOI Listing
July 2022

Biocatalytic Depletion of Tumorigenic Energy Sources Driven by Cascade Reactions for Efficient Antitumor Therapy.

Angew Chem Int Ed Engl 2022 Jul 19. Epub 2022 Jul 19.

Shenzhen University, 3688 Nanhai Ave, Nanshan, 518060, Shenzhen, CHINA.

Glucose and lactate play important roles for tumor growth. How to simultaneously deprive glucose and lactate of tumors is a big challenge. Herein, we developed a cascade catalytic system (denoted as FPGLC) based on fluorinated polymer (FP) with co-loading of glucose oxidase (GOx), lactate oxidase (LOx) and catalase (CAT). GOx and LOx deprive glucose and lactate, respectively, resulting in abundant hydrogen peroxide (H2O2) generation. Meanwhile, CAT catalyzes H2O2 into O2, which not only promotes catalytic reactions of GOx and LOx for consuming more glucose and lactate, but also alleviates tumor hypoxia. Benefiting from the excellent cross-membrane and transmucosal penetration capacities of FP, FPGLC rapidly accumulated in tumors and subsequently mediated enhanced cascade catalytic therapy under the guidance of photoacoustic imaging. These results demonstrate that the dual-depletion of glucose and lactate with O2 supply is a promising strategy for efficient antitumor starvation therapy.
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http://dx.doi.org/10.1002/anie.202204584DOI Listing
July 2022

Antineoplastic Enzyme as Drug Carrier with Activatable Catalytic Activity for Efficient Combined Therapy.

Angew Chem Int Ed Engl 2022 Jul 18:e202208583. Epub 2022 Jul 18.

Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060, China.

The delivery of glucose oxidase (GOx) requires extra carriers, which suffers from early leakage and exposure of GOx. These issues will be of less concern if GOx itself acts as a drug carrier. However, the catalytic activity of GOx in the blood still needs to be inhibited. Herein, we found that GOx could self-assemble with hydrophobic molecules into uniform and stable nanoparticles (NPs), including sorafenib, 4'-(amino-methyl phenyl)-2,2' : 6',2''-terpyridine modified cyanin and paclitaxel. The catalytic activity of GOx in NPs was significantly inhibited due to the binding of small molecules with its hydrophobic pockets. After dissociation in the tumor acidic microenvironment, the enzyme activity of GOx could be largely recovered. This acidity-triggered "OFF-to-ON" process ensured safe intravenous administration of GOx-based NPs. In vivo experiments showed that the combined starvation therapy and ferroptosis/photothermal therapy/chemotherapy effectively inhibited 4T1 breast tumor growth.
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http://dx.doi.org/10.1002/anie.202208583DOI Listing
July 2022

The predictive value of tumor volume reduction ratio on three-dimensional endorectal ultrasound for tumor response to chemoradiotherapy for locally advanced rectal cancer.

Ann Transl Med 2022 Jun;10(12):666

Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Preoperative chemoradiotherapy remains part of the standard treatment for patients with locally advanced rectal cancer. Subsequent treatment individualization requires accurate prediction of tumor response to chemoradiotherapy. Three-dimensional endorectal ultrasound (3D-ERUS) can automatically capture and store the images of the rectal wall and rectal cancer with high resolution. In this study, we aimed to assess the correlation and predictive value between tumor volume changes measured on 3D-ERUS and the histopathological tumor response after chemoradiotherapy for patients with locally advanced rectal cancer.

Methods: A total of 54 patients with locally advanced rectal cancer who underwent chemoradiotherapy and had complete 3D-ERUS data pre-and post-chemoradiotherapy were enrolled in the study. The tumor volume pre-and post-chemoradiotherapy was measured manually on 3D-ERUS, and the tumor volume reduction ratio was calculated. The histopathological tumor regression grade (TRG) was used to assess tumor response. The differences in volumetry parameters were compared between groups with varying tumor response. The diagnostic efficacy of the tumor volume reduction ratio was evaluated by the receiver operating characteristic (ROC) curve.

Results: The mean age of all patients was 55.19±12.46 years. The relative proportions of TRG 0-3 were 29.6% (16/54), 16.6% (9/54), 50% (27/54), and 3.8% (2/54), respectively. The median tumor volumes post-chemoradiotherapy in good responders (TRG 0-1, median tumor volume =3.26 cm) and the complete response group (TRG 0, median tumor volume =2.61 cm) were smaller than those in poor responders (TRG 2-3, median tumor volume =5.43 cm) and the partial response group (TRG 1-3, median tumor volume =4.00 cm), while tumor volume reduction ratios were higher than those of poor responders (79.32% 59.67%) and the partial response group (82.22% 61.64%), with significant differences (all P values <0.05). The ROC curves showed that the cut-off values of the tumor volume reduction ratio to predict good responders and complete response were 67.77% and 72.02%, respectively. The corresponding areas under the curve in the prediction of good responders and complete response were 0.830 and 0.829, respectively.

Conclusions: The tumor volume reduction ratio measured on 3D-ERUS might be a helpful indicator for tumor response in patients with locally advanced rectal cancer.
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http://dx.doi.org/10.21037/atm-22-2418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279805PMC
June 2022

Enhanced Anti-Inflammatory Effects of Silibinin and Capsaicin Combination in Lipopolysaccharide-Induced RAW264.7 Cells by Inhibiting NF-κB and MAPK Activation.

Front Chem 2022 30;10:934541. Epub 2022 Jun 30.

School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China.

Silibinin and capsaicin both are natural product molecules with diverse biological activities. In this article, we investigated the anti-inflammatory effects of silibinin combined with capsaicin in lipopolysaccharide (LPS)-induced RAW264.7 cells. The results showed that silibinin combined with capsaicin strongly inhibited LPS-induced nitric oxide (NO), tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), and COX-2. Moreover, silibinin combined with capsaicin potently inhibited nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. The results of the present study indicate that silibinin combined with capsaicin effectively inhibits inflammation.
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http://dx.doi.org/10.3389/fchem.2022.934541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279934PMC
June 2022

Amplification Profiling Identifies a Subtype of Melanoma Associated With Poor Survival and an Immunosuppressive Tumor Microenvironment.

Front Immunol 2022 1;13:725679. Epub 2022 Jul 1.

Department of Medical Oncology, Fujian Medical University Cancer Hospital and Fujian Cancer Hospital, Fuzhou, China.

Background: Although melanoma is generally regarded as an immunogenic cancer that will respond to immune checkpoint inhibitors (ICIs), melanomas with amplification respond poorly to these therapies. Further understanding how amplification impacts the effectiveness of ICI therapy is important for the design of future clinical trials.

Methods: We used data from tumor samples taken from Chinese patients with melanoma analyzed at the Geneplus Institute (=302), as well as data from the Cancer Genome Atlas (TCGA) database (=367) and the Memorial Sloan Kettering Cancer Center (MSKCC) database (=350) to estimate the prevalence of amplification in melanoma, interrogate the relationship between amplification and survival in patients with melanoma, and explore the molecular mechanisms of amplification. We also established a murine model of melanoma harboring amplification and utilized RNA-seq to verify the findings from human tissue samples.

Results: Data from all three sources revealed a low frequency of amplification co-occurring with , , , and mutations. Data from TCGA did not show a statistically significant correlation between amplification and prognosis, irrespective of ICI use. In contrast, the MSKCC cohort showed that amplification was an unfavorable prognostic factor for patients with melanoma, especially for patients who received ICIs and had a high tumor mutation burden (TMB). The TCGA data showed that amplification was associated with a higher proportion of immunosuppressive cells (Treg cells and M2 macrophages) and a lower proportion of immune boosting cells (follicular helper T cells naïve B cells, CD8 T cells). Murine models supported the association between a suppressive immune microenvironment and amplification; tumors with amplification had reduced mRNA expression of CD8, Gzm, B2m and Tap1, significantly higher proportions of resting CD4 memory T cells and significantly lower proportions of plasma cells, CD8 T cells, and T follicular helper cells. Furthermore, a Gene Set Enrichment Analysis (GSEA) analysis of data from the TCGA database suggested that signaling pathways involved in oxidative phosphorylation, reactive oxygen species, adipogenesis, fatty acid metabolism, DNA repair, and Myc targets were differentially enriched in melanoma tumors with amplification. Finally, we observed a notable reduction in levels of angiogenesis-related molecules (encoded by , , , , and ) in a high amplification group from the TCGA database.

Conclusions: Melanoma with amplification is an independent genomic subtype associated with a poor prognosis, an immunosuppressive TME, activated oxidative and lipid metabolism, and down-regulated angiogenesis. Therefore, avoiding ICIs and antiangiogenic agents, while employing CDK4/6 inhibitors alone or in combination with ICIs, and targeting oxidative and lipid metabolism pathways, may be effective therapeutic strategies for melanoma patients harboring amplification.
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http://dx.doi.org/10.3389/fimmu.2022.725679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285001PMC
July 2022

Whole-Blood MicroRNA Sequence Profiling and Identification of Specific miR-21 for Adolescents With Postural Tachycardia Syndrome.

Front Neurosci 2022 30;16:920477. Epub 2022 Jun 30.

Department of Pediatrics, The Third Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China.

Objective: The aim of the study was to establish whether whole-blood microRNA (miRNA) profiles differ between postural tachycardia syndrome (POTS) sufferers and control subjects and to identify the miRNA that regulates plasma HS.

Study Design: High-throughput sequencing was used to obtain whole-blood miRNA expression profiles for 20 POTS sufferers and 20 normal children.The thresholds for defining differentially expressed miRNAs (DEmiRNAs) were an adjusted DESeq of <0.05 and a log2 fold variation of ≥3. The DEmiRNA target genes were identified using RNAhybrid and miRanda, and only those identified by both were considered. The combined effects of the DEmiRNAs were determined using KEGG pathway analysis. Another 40 POTS and 20 normal patients were used as validation subjects. Plasma HS was determined with a sulfide electrode, and flow-mediated vasodilation (FMD) was performed with a color Doppler ultrasound system. miRNAs were analyzed using qRT-PCR.

Results: Totally, 13 DEmiRNAs were identified through high-throughput sequencing. In the 60-member validation group, the 13 miRNAs were verified again, and it turned out that miR-21 was significantly elevated and could diagnose POTS with a 100% specificity and 92.5% sensitivity. Overall, 198 and 481 genes, respectively, were shown to be targeted by the 13 DEmiRNAs when values of 0.01 and 0.05 were used. The target gene of hsa-miR-21-5p was SP1 when the -value is <0.01. DEmiRNAs were significantly enriched in 36 pathways ( < 0.05), in which PI3K/Akt signaling was closely related to vascular function. In the validation subjects, the plasma HS and FMD were higher in the POTS sufferers ( < 0.05).

Conclusion: Elevated whole-blood miR-21 levels serve as an indicator for POTS and may explain the increased plasma HS observed in POTS sufferers.
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http://dx.doi.org/10.3389/fnins.2022.920477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281551PMC
June 2022

Omega-3 polyunsaturated fatty acid biomarkers and risk of type 2 diabetes, cardiovascular disease, cancer, and mortality.

Clin Nutr 2022 Aug 30;41(8):1798-1807. Epub 2022 Jun 30.

School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an, China. Electronic address:

Background & Aims: Considerable attention has focused on the role of omega-3 polyunsaturated fatty acids (PUFA) in the prevention of cardiometabolic diseases, which has led to dietary recommendations to increase omega-3 fatty acid intake. A meta-analysis was conducted to summarize evidence from prospective studies regarding associations between omega-3 PUFA biomarkers and risk of developing major chronic diseases.

Methods: Four electronic databases were searched for articles from inception to March 1, 2022. Random-effects model was used to estimate the pooled relative risk (RR) and 95% confidence intervals (CIs) for the association of omega-3 PUFAs, including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), with risk of developing type 2 diabetes (T2D), cardiovascular disease (CVD), including coronary heart disease (CHD) and stroke, cancer, and mortality. The Grades of Recommendation, Assessment, Development and Evaluation assessment tool was used to rates the confidence in estimates.

Results: A total of 67 prospective studies comprised of 310,955 participants were identified. Individual omega-3 PUFAs showed divergent associations with the study outcomes of interest. A significant inverse association with T2D risk was observed across categories of ALA (relative risk [RR]: 0.89, 95% confidence interval [CI]: 0.82-0.96), EPA (RR: 0.85, 95% CI: 0.72-0.99) and DPA (RR: 0.84, 95% CI: 0.73-0.96) biomarkers. The marine-origin omega-3 fatty acids biomarkers but not ALA was significantly associated with lower risks of total CVD, CHD, and overall mortality, with RRs ranging from 0.70 for DHA-CHD association to 0.85 for EPA-CHD association. A lower risk of colorectal cancer was observed at higher levels of DPA (RR: 0.76, 95% CI: 0.59-0.98) and DHA (RR: 0.80; 95% CI: 0.65-0.99), whereas no association was noted for other outcomes. In addition, a dose-response relationship was observed between an increasing level of EPA, DPA, or DHA biomarker and lower risk of CVD.

Conclusions: Higher concentrations of marine-derived omega-3 PUFA biomarkers were associated with a significantly reduced risk of total CVD, CHD, and total mortality. Levels of ALA were inversely associated with a lower risk of T2D but not CVD-related outcomes. These data support the dietary recommendations advocating the role of omega-3 PUFAs in maintaining an overall lower risk of developing cardiovascular disease and premature deaths.
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http://dx.doi.org/10.1016/j.clnu.2022.06.034DOI Listing
August 2022

Lelliottia steviae sp. nov. isolated from Stevia rebaudiana Bertoni.

Arch Microbiol 2022 Jul 12;204(8):475. Epub 2022 Jul 12.

College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, People's Republic of China.

A Gram-negative, aerobic, chemoheterotrophic, rod-shaped, and motile bacterium, designated as LST-1, was isolated from wild Stevia rebaudiana Bertoni and subjected to a polyphasic taxonomic analysis. The LST-1 strain grew optimally at 37 °C and pH 6.0-7.0 in the presence of 0.5% (w/v) NaCl. Phylogenetic analysis based on the 16S rDNA sequence indicated that LST-1 is closely related to Lelliottia jeotgali PFL01 (99.85%), Lelliottia nimipressuralis LMG10245 (98.82%), and Lelliottia amnigena LMG2784 (98.54%). Multi-locus sequence typing of concatenated partial atpD, infB, gyrB, and rpoB genes was performed to improve the resolution, and clear distinctions between the closest related type strains were observed. The results of average nucleotide identify analyses and DNA-DNA hybridization with four species (16S rDNA similarity > 98.65%) were less than 90 and 40%, respectively, verifying the distinct characteristics from other species of Lelliottia. The cellular fatty acid profile of the strain consisted of C16:0, Summed Feature3, and Summed Feature8 (possibly 16:1 w6c/16:1 w7c and 18:1 w6c) as major components. The major polar lipids included phosphatidylethanolamine, phosphatidylglycerol, an aminophospholipid, three non-characteristic phospholipids, and a non-characteristic lipid. The genome of LST-1 was 4,611,055 bp in size, with a G + C content of 55.02%. The unique combination of several phenotypic, chemotaxonomic, and genomic characteristics proved that strain LST-1 belongs to a novel species, for which the name Lelliottia steviae sp. nov. is proposed. The type strain is LST-1 (= CGMCC 1.19175 = JCM 34938).Repositories: The genbank accession numbers for the 16S rRNA gene and genome sequences of strain LST-1T are MZ497264 and CP063663, respectively.
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http://dx.doi.org/10.1007/s00203-022-03033-2DOI Listing
July 2022

A prospective study using an individualized nomogram to predict the success rate of external cephalic version.

Sci Rep 2022 Jul 12;12(1):11795. Epub 2022 Jul 12.

International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910 Hengshan Road, Shanghai, 200030, China.

To establish a clinical-based nomogram for predicting the success rate of external cephalic version (ECV) through a prospective study. This was a single-center prospective study that collected eligible breech pregnant women. 152 participants were enrolled in the training cohort, who received ECV procedures performed by a single operator. We used the training cohort to establish regression equations and prediction models. These variables include maternal factors (age, operation gestational age, pre-pregnancy BMI (Body Mass Index), operation BMI, BMI increase, multipara), ultrasound factors (fetal weight estimation, amniotic fluid index, placental location, type of breech presentation, spinal position), and anesthesia. Univariate and multivariable analyses were used to screen the factors affecting the success of ECV. A nomogram scoring model was established based on these factors. And C-index, DCA (Decision Curve Analysis) and calibration curve, Hosmer-Lemeshow test was used to verify the prediction effect of the model. Finally, 33 participants were enrolled in the testing cohort who received ECV with an unrestricted operator. We used C-index, DCA (decision curve analysis), and Hosmer-Lemeshow to verify the application value of the prediction model. The calibration curves and ROC curves of both the training cohort and testing cohort are plotted for internal and external validation of the model. The ECV success rate of the training cohort was 62.5%. Univariate analysis showed that the predictors related to the success rate of ECV were age, BMI increase value, AFI (amniotic fluid index), breech type, placental location, spinal position, anesthesia, and multipara. The prediction thresholds of the corresponding indexes were calculated according to the Youden index. Multivariate logistic regression analysis showed that BMI increase ≥ 3.85 kg/m, AFI ≥ 10.6 cm, anesthesia, multipara, and non-anterior placenta were independent predictors of ECV success. Through the internal and external validation, it is confirmed that the model has a good calibration and prediction ability. Our nomogram has a good ability to predict the success rate of ECV.
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http://dx.doi.org/10.1038/s41598-022-16112-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276686PMC
July 2022

Versatile Application of Nanobodies for Food Allergen Detection and Allergy Immunotherapy.

J Agric Food Chem 2022 Jul 12;70(29):8901-8912. Epub 2022 Jul 12.

Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China.

The unique characteristics of camelid heavy-chain only antibody (HCAb) derived nanobodies (Nbs) have facilitated their employment as tools for research and application in extensive fields including food safety inspection, diagnosis and therapy of diseases, etc., to develop immune detecting techniques or alternative candidates of conventional antibodies as diagnostic and therapeutic reagents. The wide application in the fields of food allergen inspection and immunotherapy has not been addressed as not much results published in the literature. The robust properties and straightforward selecting strategy of Nbs impel the advantageous employment compared with monoclonal antibodies (mAbs) to establish immunoassay and serve as blocking antibodies to compete immunoglobulin E (IgE) binding epitopes on food allergens. More and more efforts have been invested to develop specific Nbs against food allergen proteins, such as macadamia allergen of Mac i 1, peanut allergen of Ara h 3, and lupine allergen of Lup an 1, which demonstrated the potential of Nbs for research and application in food allergen surveillance. Meanwhile, the paratopes of Nbs preferably targeting the unique epitopes of food allergens can provide more possibilities to serve as blocking antibodies to shield IgE binding epitopes for food allergy immunotherapy. Regardless, the research and application of Nbs in the field of food allergen and allergic reactions are expected to attract dramatic focus and produce promising research outputs.
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http://dx.doi.org/10.1021/acs.jafc.2c03324DOI Listing
July 2022

Synthesis and Biological Evaluation of 5-Fluoro-2-Oxindole Derivatives as Potential α-Glucosidase Inhibitors.

Front Chem 2022 23;10:928295. Epub 2022 Jun 23.

School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China.

α-Glucosidase inhibitors are known to prevent the digestion of carbohydrates and reduce the impact of carbohydrates on blood glucose. To develop novel α-glucosidase inhibitors, a series of 5-fluoro-2-oxindole derivatives ( ∼ ) were synthesized, and their α-glucosidase inhibitory activities were investigated. Biological assessment results showed that most synthesized compounds presented potential inhibition on α-glucosidase. Among them, compounds , , and exhibited much better inhibitory activity with IC values of 49.89 ± 1.16 μM, 35.83 ± 0.98 μM, and 56.87 ± 0.42 μM, respectively, which were about 10 ∼ 15 folds higher than acarbose (IC = 569.43 ± 43.72 μM). A kinetic mechanism study revealed that compounds , , and inhibited the α-glucosidase in a reversible and mixed manner. Molecular docking was carried out to simulate the affinity between the compound and α-glucosidase.
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http://dx.doi.org/10.3389/fchem.2022.928295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261963PMC
June 2022

Mechanism of antifungal activity and therapeutic action of β-ionone on Aspergillus fumigatus keratitis via suppressing LOX1 and JNK/p38 MAPK activation.

Int Immunopharmacol 2022 Jul 7;110:108992. Epub 2022 Jul 7.

Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China. Electronic address:

Purpose: To investigate the anti-inflammatory and antifungal role of β-ionone (BI) in fungal keratitis (FK).

Methods: In vitro antifungal activity of BI against Aspergillus fumigatus (A. fumigatus) was evaluated by using minimum inhibitory concentration (MIC), crystal violet staining, biofilm biomass measurement, propidium iodide uptake test, and adherence assay. And RT-PCR was carried out to measure the levels of RodA, RodB, Rho, FKs, CshA-D, RlmA, Cyp51A-B and Cdr1B. Network pharmacology analysis was applied to predict the relationship between BI and FK. Cell Count Kit-8 (CCK8) assay was utilized to detect the cytotoxicity of BI to RAW264.7 and immortalized human corneal epithelial cells (HCECs). The underlying mechanism of BI at regulating the level of inflammatory factors in FK was assessed by RT-PCR, ELISA and Western blot in vitro and in vivo. The therapeutic effect of BI has investigated in A. fumigatus keratitis by employing the clinical score, pathological examination, plate count, immunofluorescence and myeloperoxidase (MPO) assay. We also used the slit-lamp microscopy, clinical scores, and HE staining to assess the effect of natamycin compared with BI treatment in vivo.

Results: BI suppressed the growth of A. fumigatus and had a significant effect on A. fumigatus biofilms and membrane permeability. RT-PCR demonstrated that exposure of A. fumigatus to BI inhibited the expression of genes that function in hydrophobin (RodA, RodB), cell wall integrity (Rho, FKs, CshA-D, RlmA), azole susceptibility (Cyp51A-B, Cdr1B). Network pharmacology showed that the effects of BI in FK implicate with C-type lectin receptor signaling pathway. In vivo, after A. fumigatus infection, BI treatment markedly reduced the severity of FK by decreasing clinical score, neutrophil recruitment, and fungal load. And BI treatment also obviously reduced the expression of inflammatory cytokines, Lectin-like oxidized LDL receptor (LOX-1), phosphorylation of p38MAPK and p-JNK versus the DMSO-treated group. BI and natamycin both significantly increased corneal transparency and decreased inflammatory cell recruitment in the FK in the mice model.

Conclusion: These results indicated that BI had fungicidal activities against A. fumigatus. It also ameliorated FK in mice by reducing inflammation, which was regulated by LOX-1, p-p38MAPK and p-JNK.
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http://dx.doi.org/10.1016/j.intimp.2022.108992DOI Listing
July 2022

Iminyl radical-triggered relay annulation for the construction of bridged aza-tetracycles bearing four contiguous stereogenic centers.

Chem Sci 2022 Jun 30;13(24):7283-7288. Epub 2022 May 30.

School of Chemistry and Chemical Engineering, Southwest University Chongqing 400715 China

Bridged tetracyclic nitrogen scaffolds are found in numerous biologically active molecules and medicinally relevant structures. Traditional methods usually require tedious reaction steps, and/or the use of structurally specific starting materials. We report an unprecedented, iminyl radical-triggered relay annulation from oxime-derived peresters and azadienes, which shows good substrate scope and functional group compatibility, and can deliver various bridged aza-tetracyclic compounds with complex molecular topology and four contiguous stereogenic centers (dr > 19 : 1) in a single operation. This transformation represents the first example of trifunctionalization of iminyl radicals through simultaneous formation of one C-N and two C-C bonds. DFT calculation studies were conducted to obtain an in-depth insight into the reaction pathways, which revealed that the reactions involved an interesting 1,6-hydrogen atom transfer process.
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http://dx.doi.org/10.1039/d2sc01548jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214848PMC
June 2022

Magnetic porous cellulose surface-imprinted polymers synthetized with assistance of deep eutectic solvent for specific recognition and purification of bisphenols.

Int J Biol Macromol 2022 Jul 5;216:374-387. Epub 2022 Jul 5.

School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China. Electronic address:

Magnetic porous cellulose molecularly imprinted polymers-based bisphenols have been developed using FeO as the magnetic material, a deep eutectic solvent as the assisted solvent, and N-isopropylacrylamide as the functional monomer. The resulting magnetic porous cellulose molecularly imprinted polymers were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, vibrating sample magnetometry, thermal gravimetric analysis, and Brunauer-Emmett-Teller analysis. Moreover, the adsorption properties of the magnetic porous cellulose molecularly imprinted polymers toward bisphenol A, bisphenol F, and bisphenol AF were investigated using static, dynamic, and selective adsorption experiments. The introduction of porous cellulose materials significantly improves the capabilities of the material. The adsorption capacity, mass transfer efficiency, and selectivity of the magnetic porous cellulose molecularly imprinted polymers toward bisphenol A were 5.9, 4.0, and 4.4 times those of traditional molecularly imprinted polymers. Moreover, the adsorption stability of the magnetic porous cellulose molecularly imprinted polymers was investigated under different temperature and pH conditions. The adsorption characteristics of the magnetic porous cellulose molecularly imprinted polymers toward the target molecules were investigated using adsorption isotherm, kinetic, and thermodynamic models. Hydrogen bonding is the main interaction formed between the magnetic porous cellulose molecularly imprinted polymers and the target molecules. Magnetic porous cellulose molecularly imprinted polymers have great application value with excellent stability and reusability. Finally, the combination of the magnetic porous cellulose molecularly imprinted polymers and high-performance liquid chromatography or ultra-performance liquid chromatography-mass spectrometry was successfully used for the purification and detection of bisphenols in milk (1.349 ng/mL bisphenol F and 3.014 ng/mL bisphenol AF), canned fruits (1129 ng/mL bisphenol A, 10.11 ng/mL bisphenol F, and 91.87 ng/mL bisphenol AF), and fish (11.91 ng/mL bisphenol AF) samples. Furthermore, the magnetic porous cellulose molecularly imprinted polymer method is more selective, sensitive, and accurate than the traditional precipitation method.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.06.187DOI Listing
July 2022

Stereotactic body radiotherapy extends the clinical benefit of PD-1 inhibitors in refractory recurrent/metastatic nasopharyngeal carcinoma.

Radiat Oncol 2022 Jul 5;17(1):117. Epub 2022 Jul 5.

Cancer Bio-Immunotherapy Center, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, No. 420 Fuma Road, Fuzhou, 350014, Fujian Province, China.

Purpose: Emerging evidence shows that immune checkpoint inhibitors lead to durable responses in a variety of cancers, including nasopharyngeal carcinoma (NPC), however, combination approaches (i.e., stereotactic body radiation therapy, SBRT) are required to extend this benefit beyond a subset of patients. This study retrospectively evaluated eight recurrent/metastatic NPC patients, to investigate how radiation could potentiate PD-1 checkpoint inhibition therapy.

Methods: Between September 2016 and July 2017, eight consecutive cases with histologically confirmed PDL1-positive status, for which prior standard therapy had been ineffective (five patients), were treated at our institution and Macao Clinics and two patients had disease progression within 6 months of completion of definitive chemoradiation, or one patient refused to receive chemoradiotherapy. All received PD-1 inhibitors first, seven of them accepted SBRT with an unmodified PD-1 inhibitors regimen after first evaluation as they were unresponsive to PD-1 inhibitors alone. Treatment was discontinued as long as patients were experiencing a clinical benefit in the opinion of the physicians and at least five cycles were given before stoppage.

Results: Median follow-up time was 56.7 months. The confirmed objective response rate based on RECIST-v1.1 at first evaluation was 12.5% (1/8). For the seven cases who received SBRT, six of them experience an objective response (6/7, 85.7%) after SBRT. Only one patient showed rapid progress and die within 95 days after the initiation of SBRT intervention. Three patients who did not have all lesions exposed to irradiation were available to evaluate the incidence of an abscopal effect, however, it did not occur as expected. Median PFS and OS for the seven patients were 8.0 and 30.8 months after SBRT intervention, respectively. Two-year OS as indicated was 71.0%.

Conclusions: PD-1 inhibitors combined with SBRT demonstrated promising antitumor activity in patients with PD-L1 positive RM-NPC. Patients may benefit from continue immunotherapy beyond disease progression when SBRT was introduced.
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http://dx.doi.org/10.1186/s13014-022-02073-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254565PMC
July 2022

The Role of Incubation Conditions on the Regulation of Muscle Development and Meat Quality in Poultry.

Front Physiol 2022 15;13:883134. Epub 2022 Jun 15.

Laboratory of Quality and Safety Risk Assessment for Animal Products on Feed Hazards (Beijing) of the Ministry of Agriculture and Rural Affairs, Research Institute of Feed, Chinese Academy of Agricultural Sciences, Beijing, China.

Muscle is the most abundant edible tissue in table poultry, which serves as an important source of high protein for humans. Poultry myofiber originates in the early embryogenic stage, and the overall muscle fiber number is almost determined before hatching. Muscle development in the embryonic stage is critical to the posthatch muscle growth and final meat yield and quality. Incubation conditions including temperature, humidity, oxygen density, ventilation and lighting may substantially affect the number, shape and structure of the muscle fiber, which may produce long-lasting effect on the postnatal muscle growth and meat quality. Suboptimal incubation conditions can induce the onset of myopathies. Early exposure to suitable hatching conditions may modify the muscle histomorphology posthatch and the final muscle mass of the birds by regulating embryonic hormone levels and benefit the muscle cell activity. The elucidation of the muscle development at the embryonic stage would facilitate the modulation of poultry muscle quantity and meat quality. This review starts from the physical and biochemical characteristics of poultry myofiber formation, and brings together recent advances of incubation conditions on satellite cell migration, fiber development and transformation, and subsequent muscle myopathies and other meat quality defects. The underlying molecular and cellular mechanisms for the induced muscle growth and meat quality traits are also discussed. The future studies on the effects of external incubation conditions on the regulation of muscle cell proliferation and meat quality are suggested. This review may broaden our knowledge on the regulation of incubation conditions on poultry muscle development, and provide more informative decisions for hatchery in the selection of hatching parameter for pursuit of more large muscle size and superior meat quality.
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http://dx.doi.org/10.3389/fphys.2022.883134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240787PMC
June 2022

Synthesis and Biological Activity Evaluation of 2-Cyanopyrrole Derivatives as Potential Tyrosinase Inhibitors.

Front Chem 2022 17;10:914944. Epub 2022 Jun 17.

School of Pharmacy and State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, China.

In order to find potential inhibitors of tyrosinase, two series of pyrrole derivatives A (1-17) and B (1-8) were synthesized and screened for their inhibitory activities on tyrosinase. Most of the 2-cyanopyrrole derivatives exhibited effective inhibitory activities. In particular, A12 exhibited the strongest inhibitory activities, with the IC values of 0.97 μM, which is ∼30 times stronger than the reference inhibitor kojic acid (IC: 28.72 μM). The inhibitory mechanism analysis results revealed that A12 was a reversible and mixed-type inhibitor. Molecular docking experiments clarified the interaction between A12 with tyrosinase. Furthermore, A12 (100 μM) presented effective inhibitory effect on tyrosinase in B16 melanoma cells with inhibition of 33.48%, which was equivalent to that of Kojic acid (39.81%). Accordingly, compound A12 may serve as the lead structure for the further design of potent tyrosinase inhibitors. Molecular docking studies confirmed the interaction between the compound and tyrosinase.
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http://dx.doi.org/10.3389/fchem.2022.914944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247258PMC
June 2022
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