Publications by authors named "Shuai Wang"

2,137 Publications

  • Page 1 of 1

Arabinosyltransferase C Mediates Multiple Drugs Intrinsic Resistance by Altering Cell Envelope Permeability in Mycobacterium abscessus.

Microbiol Spectr 2022 Aug 10:e0276321. Epub 2022 Aug 10.

State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Healthgrid.428926.3, Chinese Academy of Sciences, Guangzhou, China.

Mycobacterium abscessus is an emerging human pathogen leading to significant morbidity and even mortality, intrinsically resistant to almost all the antibiotics available and so can be a nightmare. Mechanisms of its intrinsic resistance remain not fully understood. Here, we selected and confirmed an M. abscessus transposon mutant that is hypersensitive to multiple drugs including rifampin, rifabutin, vancomycin, clofazimine, linezolid, imipenem, levofloxacin, cefoxitin, and clarithromycin. The gene encoding a putative arabinosyltransferase C was found to be disrupted, using a newly developed highly-efficient strategy combining next-generation sequencing and multiple PCR. Furthermore, selectable marker-free deletion of recapitulated the hypersensitive phenotype. Disruption of resulted in an inability to synthesize lipoarabinomannan and markedly enhanced its cell envelope permeability. Complementing or M. tuberculosis restored the resistance phenotype. Importantly, treatment of M. abscessus with ethambutol, a first-line antituberculosis drug targeting arabinosyltransferases of M. tuberculosis, largely sensitized M. abscessus to multiple antibiotics . We finally tested activities of six selected drugs using a murine model of sustained M. abscessus infection and found that linezolid, rifabutin, and imipenem were active against the deletion strain. These results identified MAB_0189 as a crucial determinant of intrinsic resistance of M. abscessus, and optimizing inhibitors targeting MAB_0189 might be a strategy to disarm the intrinsic multiple antibiotic resistance of M. abscessus. Mycobacterium abscessus is intrinsically resistant to most antibiotics, and treatment of its infections is highly challenging. The mechanisms of its intrinsic resistance remain not fully understood. Here we found a transposon mutant hypersensitive to a variety of drugs and identified the transposon inserted into the (orthologous coding arabinosyltransferase, EmbC) gene by using a newly developed rapid and efficient approach. We further verified that the gene played a significant role in its intrinsic resistance by decreasing the cell envelope permeability through affecting the production of lipoarabinomannan in its cell envelope. Lastly, we found the arabinosyltransferases inhibitor, ethambutol, increased activities of nine selected drugs . Knockout of made M. abscessus become susceptible to 3 drugs in mice. These findings indicated that potential powerful M. abscessus EmbC inhibitor might be used to reverse the intrinsic resistance of M. abscessus to multiple drugs.
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http://dx.doi.org/10.1128/spectrum.02763-21DOI Listing
August 2022

Antibiofilm Activity of Essential Fatty Acids Against from Vulvovaginal Candidiasis and Bloodstream Infections.

Infect Drug Resist 2022 3;15:4181-4193. Epub 2022 Aug 3.

Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.

Purpose: The biofilm formation of is an important virulence factor as it can increase tolerance to conventional antifungal drugs and the host immune system. The study aimed to assess the effect of essential fatty acids (EFAs) against biofilm formation and mature biofilms of strains, which were isolated from vulvovaginal candidiasis and candidemia.

Methods: The biofilm formation ability of and antifungal activities of fluconazole were determined. Additionally, the effects of six EFAs [α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LOA), γ-linolenic acid (GLA), and arachidonic acid (AA)] against under planktonic and biofilm conditions were evaluated.

Results: 94.1% of exhibited biofilm formation capacity, and 98.5% of were susceptible to fluconazole. The biofilms of were highly resistant to fluconazole with minimum biofilm eradication concentration values ≥ 64 µg/mL. The EFAs attenuated biofilm formation in a dose-dependent manner, and GLA displayed a remarkable inhibitory activity against biofilm formation of . In addition, EPA, DHA, and GLA at 0.1 mM could inhibit the biofilm formation of without affecting the planktonic growth rate. Notably, EPA and AA at 1 mM had both inhibitory and eradication activities on biofilms.

Conclusion: This is the first study to directly compare different EFAs for their capacity to affect biofilm formation as well as biofilm eradication. These results suggest EPA and AA could serve as potential new antifungal agents for the treatment of clinical infections caused by biofilms.
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http://dx.doi.org/10.2147/IDR.S373991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357398PMC
August 2022

Durable Superoleophobic Janus Fabric with Oil Repellence and Anisotropic Water-Transport Integration toward Energetic-Efficient Oil-Water Separation.

ACS Appl Mater Interfaces 2022 Aug 7. Epub 2022 Aug 7.

Key Laboratory of Micro-Systems and Micro-Structures Manufacturing, Ministry of Education and School of Mechatronics Engineering, Harbin Institute of Technology, Harbin 150001, China.

Porous materials with opposing superwettability toward oil and water have aroused widespread interest for their selective-wetting advantage in oil-water separation. The separation process, however, requires constant energy input to maintain the driving force. Further reducing the external energy consumption or accelerating the liquid transport during separation is still a challenge. The Janus membrane is an emerging porous material with opposing wettability toward a specific liquid on each side. The asymmetric wettability distribution leads to a surface energy gradient-driven liquid-transport behavior through the thickness, which significantly facilitates liquid transportation. It is conceived that porous materials possessing both Janus features and selective superwettability would reduce energy consumption and strengthen the efficiency in oil-water separation. Herein, a novel durable superoleophobic (SOHB) Janus fabric which possesses oil-repellent and surface energy gradient-driven water-transport properties was developed through one-side superoleophobic/superhydrophilic modification of the superamphiphobic fabric. The SOHB Janus fabric exhibits high mechanical durability and significant superior capacity than the homogeneous superoleophobic/superhydrophilic fabric in separating various oil-water mixtures. Moreover, the SOHB Janus fabric repels oil contaminants and pumps perspiration from the human skin, exhibiting prospects in physical moisture regulation and comfort improvement. Our novel Janus fabric, along with the fabrication principle, provides a feasible solution for energetic-efficient oil-water remediations and would have implications for the fabrication of advanced separation membranes and intelligent functional clothing.
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http://dx.doi.org/10.1021/acsami.2c09545DOI Listing
August 2022

Conspecific pollen advantage mediated by the extragynoecial compitum and its potential to resist interspecific reproductive interference between two species.

Front Plant Sci 2022 22;13:956193. Epub 2022 Jul 22.

College of Life Sciences, Wuhan University, Wuhan, China.

The extragynoecial compitum formed by the incomplete fusion of carpel margins, while allowing intercarpellary growth of pollen tubes in apocarpous angiosperms, may also increase the risk of reproductive interference caused by heterospecific pollen (HP) deposition. In , congeneric HP tubes grow via different paths and enter the ovules later than conspecific pollen (CP) tubes. However, it is unclear how the growth advantage of the CP tube helps ensure reproductive success when HP is deposited on the stigmas. We performed molecular characterization of interspecies-pollinated seeds to examine the consequences of interspecific pollen deposition between and . We also conducted CP-HP (1:1) mixed pollination and delayed CP pollination treatments to explore the seed-siring abilities of CP and HP. Our results showed that although HP could trigger the development of fruits, the interspecies-pollinated seeds contained partially developed embryos and could not germinate. More than 70% of the embryos in these seeds were molecularly identified as hybrids of both species, suggesting that HP tubes could enter the ovules and fertilize the egg cells. Moreover, CP could sire more offspring (≥70%) after the CP-HP (1:1) mixed pollination treatment, even when HP reached the stigma 0.5-1 h earlier than CP (≥50%). Following adequate CP vs. HP (1:1) pollination on carpels on two sides of the apocarpous gynoecium, both species produced > 70% conspecific seeds, indicating that the CP tubes could occupy ovules that should be occupied by HP via the extragynoecial compitum. Our results reveal that in , pollen deposition from co-existing congeneric heterospecies leads to interspecific seed discounting. However, the CP advantage mediated by the extragynoecial compitum is an effective strategy to mitigate the effects of interspecific pollen deposition. This study improves our understanding of how apocarpous angiosperms with an extragynoecial compitum can maintain species stability and mitigate the negative reproductive interference effect from sympatrically distributed related species.
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http://dx.doi.org/10.3389/fpls.2022.956193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354020PMC
July 2022

The isotopic composition of organic carbon, nitrogen and provenance of organic matter in surface sediment from the Jiangsu tidal flat, southwestern Yellow Sea.

Mar Pollut Bull 2022 Aug 4;182:114010. Epub 2022 Aug 4.

College of Earth Sciences and Engineering, Hohai University, Nanjing 211100, China. Electronic address:

The Jiangsu tidal flat is a significant organic matter reservoir, but quantitative studies of organic matter sources are scarce. In this study, total organic carbon (TOC) and total nitrogen (TN) concentrations and δC and δN values of surface sediment from Jiangsu tidal flat were investigated for their distributions, influencing factors, and sources of organic matter. TOC and TN were high in the center of study area and correlated well with grain size, indicating hydrodynamic influence on organic matter. High TOC/TN and low δC and δN in estuaries were characteristic of C plants, soil, and fertilizer sources, suggesting source effect on the distribution of organic matter. The MixSIAR model revealed that marine sources were dominant with a contribution reaching 56.9 %, followed by uniform of C plants, soil and fertilizer, while domestic sewage was least prominent. This study enriched theories of the biogeochemical cycle and ecological protection in the southwestern Yellow Sea.
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http://dx.doi.org/10.1016/j.marpolbul.2022.114010DOI Listing
August 2022

Identification of arsenic spatial distribution by hydrogeochemical processes represented by different ion ratios in the Hohhot Basin, China.

Environ Sci Pollut Res Int 2022 Aug 6. Epub 2022 Aug 6.

Henan Institute of Geological Environmental Monitoring, Zhengzhou, 450016, China.

The Hohhot Basin, a typical inland basin of the Yellow River Basin in China, has high concentrations of arsenic (As) in its shallow groundwater, while the factors dominating the distribution of high arsenic levels remain to be further identified. An analysis of the ratio of hydrogeochemical compositions can help to reveal the spatial characteristics of the shallow groundwater environmental conditions and the distribution of high-arsenic water (As >10 μg/L). In this study, a total of 170 samples of shallow groundwater in the Hohhot Basin were collected and water samples with As >10 μg/L accounted for 29.4% of the total. Based on the slope changes of the cumulative frequency curves of (HCO + CO)/SO, Ca/(HCO + CO), Ca/Mg, and Na/Ca, the groundwater in the study area can be categorized into six different zones according to the environmental characteristics including redox condition, water recharge intensity, and cation exchange level. The result shows that the groundwater in the front of the piedmont alluvial plain and platform is in a weak reducing condition with high lateral recharge intensity, fast runoff, and weak cation exchange. In the Dahei River alluvial plain, which serves as the groundwater discharge zone, the groundwater runoff is sluggish with poor lateral recharge, sufficient exchange between cations in the groundwater and the aquifer matrix, and enhanced reducibility. The degree of oxidation increased in the groundwater near the Hasuhai Lake and the drainage canal, which adverse to the arsenic enrichment. High-arsenic groundwater is mainly distributed in aquifers of (HCO + CO)/SO > 10, Na/Ca > 13, and Ca/(HCO + CO) < 0.1, which represent the strong reducing condition, low surface water recharge intensity, and strong cation exchange condition. Reductive dissolution of iron oxide, strong evaporation and concentration process, and competition from phosphate in aquifers jointly lead to the release of arsenic into groundwater.
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http://dx.doi.org/10.1007/s11356-022-22311-6DOI Listing
August 2022

Facile Synthesis of Conductive Metal-Organic Frameworks Nanotubes for Ultrahigh-Performance Flexible NO Sensors.

Small Methods 2022 Aug 5:e2200581. Epub 2022 Aug 5.

Laboratory of Molecular Materials and Devices, Department of Materials Science, Fudan University, Shanghai, 200433, P. R. China.

Cu-benzenehexathiol (Cu-BHT) has attracted significant attention due to its record high electrical conductivity and crystal defects Cu . However, the nonporous structure and small specific surface area of Cu-BHT with two-dimensional kagome lattice invariably limit its practical application in sensing and catalysis. In this work, Cu-BHT nanotubes (Cu-BHT-NTs) are designed and prepared via a facile homogeneous reaction to solve these problems. Compared with the traditional nanorod-like structure, the Cu-BHT-NTs not only have a higher specific surface area but also possess a higher proportion of crystal defects (66.6%). The successfully configured DPPTT/Cu-BHT-NTs heterostructure organic field-effect transistor (OFET)-based sensor exhibits excellent sensitivity as high as 13 610%, a minimum detection limits down to 5 ppb, and exceptional selectivity to nitric oxide (NO) toxic gases. Theoretical analysis systematically shows that Cu sites in the Cu-BHT-NTs increase the number of electrons transferred from the heterostructure to NO molecules, confirming that the high sensitivity and selectivity result from the high binding between Cu-BHT-NTs and NO molecules. Furthermore, a fully flexible device based on the heterojunction OFET sensor is prepared to ensure the convenience of wearing and carrying gas sensors, opening up a new avenue for the next generation of wearable intelligent electronics.
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http://dx.doi.org/10.1002/smtd.202200581DOI Listing
August 2022

Enhanced self-cleaning performance of bio-inspired micropillar arrayed surface by shear.

Bioinspir Biomim 2022 Aug 5. Epub 2022 Aug 5.

Beijing Institute of Technology, No. 5 South Street Zhongguancun, Haidian District, Beijing, 100081, CHINA.

Inspired by the sliding behavior of gecko feet during climbing, the contribution of shear effect to the self-cleaning performance of a bio-inspired micropillar arrayed surface is studied through a load-shear-pull contact process. It is found that the self-cleaning efficiency can be enhanced significantly by shear, which also depends on the microparticle sizes. For the case of relatively large and small microparticles, the self-cleaning efficiency increases first and then almost keeps a constant with the increase of the shear distance at different preload. For medium microparticles, shear can effectively improve self-cleaning efficiency only when the preload is small. The mechanical mechanism under such the enhancement is mainly due to the varying contact states between microparticles and micropillars with the shear distance. When the shear distance is large enough, the final self-cleaning efficiency is not sensitive to shear distance anymore because the contact state reaches dynamic equilibrium. Based on such the self-cleaning mechanism of large microparticles, a simple and effective manipulator which can efficiently transfer solid particles is further proposed.
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http://dx.doi.org/10.1088/1748-3190/ac877bDOI Listing
August 2022

[email protected](Fe-Cu) as a sorbent for the extraction of benzoylurea pesticides from irrigation water and fruit juices.

Anal Methods 2022 Aug 5. Epub 2022 Aug 5.

CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.

The [email protected](Fe-Cu) solid-phase extraction material was prepared by growing MOF-919(Fe-Cu) on three-dimensional radial TiO microspheres by a simple solvothermal method. This combination drew on both the resources of good single dispersion and extraction rate, which made it a better extraction material. It was accompanied with high-performance liquid chromatography (SPE-HPLC) for the separation and determination of four benzoylurea pesticides (triflumuron, chlorbenzuron, teflubenzuron and diflubenzuron) in afforestation irrigation water and juice samples (grape, peach and apple juices). Under the optimal conditions, the linearity of the method ranged from 1 to 400 μg L with a correlation coefficient () ≥ 0.9994, while the detection limit was in the range of 0.40-0.56 μg L for the four pesticides. The adopted material showed good reusability and can be used no less than 10 times. The intra-day and inter-day precision were in the range of 1.78-3.24% and 4.06-5.08%, respectively. The proposed method was then successfully applied for the detection of benzoylurea pesticides in the spiked samples with good recoveries (72.3-108.4%) and good precision (5.15%) due to π-π and hydrophobic interactions between the analytes and adsorbent. The results show that the composite had the potential to be used as a SPE adsorbent for the enrichment and extraction of benzene ring structures containing imide groups in actual samples.
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http://dx.doi.org/10.1039/d2ay00842dDOI Listing
August 2022

DCBLD2 regulates vascular hyperplasia by modulating the platelet derived growth factor receptor-β endocytosis through Caveolin-1 in vascular smooth muscle cells.

FASEB J 2022 Sep;36(9):e22488

Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang, China.

DCBLD2 is a neuropilin-like transmembrane protein that is up-regulated during arterial remodeling in humans, rats, and mice. Activation of PDGFR-β via PDGF triggers receptor phosphorylation and endocytosis. Subsequent activation of downstream signals leads to the stimulation of phenotypic conversion of VSMCs and arterial wall proliferation, which are common pathological changes in vascular remodeling diseases such as atherosclerosis, hypertension, and restenosis after angioplasty. In this study, we hypothesized that DCBLD2 regulates neointimal hyperplasia through the regulation of PDGFR-β endocytosis of vascular smooth muscle cells (VSMCs) through Caveolin-1 (Cav-1). Compared with wild-type (WT) mice or control littermate mice, the germline or VSMC conditional deletion of the Dcbld2 gene resulted in a significant increase in the thickness of the tunica media in the carotid artery ligation. To elucidate the underlying molecular mechanisms, VSMCs were isolated from the aorta of WT or Dcbld2 mice and were stimulated with PDGF. Western blotting assays demonstrated that Dcbld2 deletion increased the PDGF signaling pathway. Biotin labeling test and membrane-cytosol separation test showed that after DCBLD2 was knocked down or knocked out, the level of PDGFR-β on the cell membrane was significantly reduced, while the amount of PDGFR-β in the cytoplasm increased. Co-immunoprecipitation experiments showed that after DCBLD2 gene knock-out, the binding of PDGFR-β and Cav-1 in the cytoplasm significantly increased. Double immunofluorescence staining showed that PDGFR-β accumulated Cav-1/lysosomes earlier than for control cells, which indicated that DCBLD2 gene knock-down or deletion accelerated the endocytosis of PDGF-induced PDGFR-β in VSMCs. In order to confirm that DCBLD2 affects the relationship between Cav-1 and PDGFR-β, proteins extracted from VSMCs cultured in vitro were derived from WT and Dcbld2 mice, whereas co-immunoprecipitation suggested that the combination of DCBLD2 and Cav-1 reduced the bond between Cav-1 and PDGFR-β, and DCBLD2 knock-out was able to enhance the interaction between Cav-1 and PDGFR-β. Therefore, the current results suggest that DCBLD2 may inhibit the caveolae-dependent endocytosis of PDGFR-β by anchoring the receptor on the cell membrane. Based on its ability to regulate the activity of PDGFR-β, DCBLD2 may be a novel therapeutic target for the treatment of cardiovascular diseases.
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http://dx.doi.org/10.1096/fj.202200156RRDOI Listing
September 2022

Maternal Methamphetamine Exposure Influences Behavioral Sensitization and Nucleus Accumbens DNA Methylation in Subsequent Generation.

Front Pharmacol 2022 19;13:940798. Epub 2022 Jul 19.

College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, China.

The deleterious effects of methamphetamine (METH) exposure extend beyond abusers, and may potentially impact the vulnerability of their offspring in developing addictive behaviors. Epigenetic signatures have been implicated in addiction, yet the characteristics to identify prenatal METH abuse to offspring addiction risk remains elusive. Here, we used escalating doses of METH-exposed mouse model in F0 female mice before and during pregnancy to simulate the human pattern of drug abuse and generated METH-induced behavioral sensitization to investigate the addictive behavior in offspring mice. We then utilized whole genome-bisulfite sequencing (WGBS) to investigate the methylation signature of nucleus accumbens (NAc) in male METH-sensitized mice. Interestingly, male but not female offspring exhibited an enhanced response to METH-induced behavioral sensitization. Additionally, the METH-exposed group of male mice underwent a more comprehensive wave of epigenome remodeling over all genomic elements compared with unexposed groups due to drug exposure history. 104,219 DMCs (METH-SAL vs SAL-SAL) induced by prenatal METH-exposure were positively correlated with that of postnatal METH-exposure (38,570, SAL-METH vs SAL-SAL). Moreover, 4,983 DMCs induced by pre- and postnatal METH exposure (METH-METH vs SAL-METH) were negatively correlated with that of postnatal METH exposure, and 371 commonly changed DMCs between the two comparison groups also showed a significantly negative correlation and 86 annotated genes functionally enriched in the pathways of neurodevelopment and addiction. Key annotated genes included , , and , implicated in neurodevelopmental processes, were down-regulated in METH-METH group mice compared with the SAL-METH group. Taken together, we render novel insights into the epigenetic correlation of drug exposure and provide evidence for epigenetic characteristics that link maternal METH exposure to the intensity of the same drug-induced behavioral sensitization in adult offspring.
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http://dx.doi.org/10.3389/fphar.2022.940798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343784PMC
July 2022

Deep-Learning-Based Ultrasound Sound-Speed Tomography Reconstruction with Tikhonov Pseudo-Inverse Priori.

Ultrasound Med Biol 2022 Jul 31. Epub 2022 Jul 31.

Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Electronic address:

Ultrasound sound-speed tomography (USST) is a promising technology for breast imaging and breast cancer detection. Its reconstruction is a complex non-linear mapping from the projection data to the sound-speed image (SSI). The traditional reconstruction methods include mainly the ray-based methods and the waveform-based methods. The ray-based methods with linear approximation have low computational cost but low reconstruction quality; the full wave-based methods with the complex non-linear model have high quality but high cost. To achieve both high quality and low cost, we introduced traditional linear approximation as prior knowledge into a deep neural network and treated the complex non-linear mapping of USST reconstruction as a combination of linear mapping and non-linear mapping. In the proposed method, the linear mapping was seamlessly implemented with a fully connected layer and initialized using the Tikhonov pseudo-inverse matrix. The non-linear mapping was implemented using a U-shape Net (U-Net). Furthermore, we proposed the Tikhonov U-shape net (TU-Net), in which the linear mapping was done before the non-linear mapping, and the U-shape Tikhonov net (UT-Net), in which the non-linear mapping was done before the linear mapping. Moreover, we conducted simulations and experiments for evaluation. In the numerical simulation, the root-mean-squared error was 6.49 and 4.29 m/s for the UT-Net and TU-Net, the peak signal-to-noise ratio was 49.01 and 52.90 dB, the structural similarity was 0.9436 and 0.9761 and the reconstruction time was 10.8 and 11.3 ms, respectively. In this study, the SSIs obtained with the proposed methods exhibited high sound-speed accuracy. Both the UT-Net and the TU-Net achieved high quality and low computational cost.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2022.05.033DOI Listing
July 2022

LINC00665 knockdown confers sensitivity in irradiated non-small cell lung cancer cells through the miR-582-5p/UCHL3/AhR axis.

J Transl Med 2022 08 2;20(1):350. Epub 2022 Aug 2.

Department of Radiotherapy, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, West Huanhu Road, Tiyuanbei, Hexi District, Tianjin, 300060, People's Republic of China.

Background: The resistance to radiotherapy remains a major obstacle that limits the efficacy of radiotherapy in non-small cell lung cancer (NSCLC). This study aims to illustrate the molecular mechanism underlying the role of LINC00665 in the radiosensitivity of NSCLC, which involves ubiquitin C-terminal hydrolase L3 (UCHL3).

Methods And Results: The expression of UCHL3 was determined in clinical tissue samples collected from NSCLC patients and NSCLC cell lines. We found that UCHL3 overexpression occurred in both NSCLC tissues and cells, associated with poor prognosis in NSCLC patients. Mechanistically, UCHL3 stabilized aryl hydrocarbon receptor (AhR) protein through deubiquitination, thereby promoting PD-L1 expression. UCHL3 reduced the radiosensitivity of NSCLC cells by stabilizing AhR protein. Upstream microRNAs (miRNAs) and lncRNAs of UCHL3 were predicted by microarray profiling and validated by functional experiments. LINC00665 functioned as a sponge of miR-582-5p and thus up-regulated the expression of the miR-582-5p target UCHL3. Gain- and loss- of function assays were performed to assess the effects of LINC00665, UCHL3 and miR-582-5p on the in vitro cell malignant behaviors and immune escape as well as on the in vivo tumor growth. Silencing LINC00665 or overexpressing miR-582-5p enhanced the sensitivity of NSCLC cells to radiotherapy. LINC00665 augmented the immune escape of NSCLC cells in vitro and in vivo through stabilizing AhR protein via the miR-582-5p/UCHL3 axis.

Conclusions: Overall, LINC00665 reduced the radiosensitivity of NSCLC cells via stabilization of AhR through the miR-582-5p/UCHL3 axis.
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http://dx.doi.org/10.1186/s12967-022-03516-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344728PMC
August 2022

Bioinformatics analysis reveals potential biomarkers associated with the occurrence of intracranial aneurysms.

Sci Rep 2022 Aug 2;12(1):13282. Epub 2022 Aug 2.

Library, Qufu Normal University, Rizhao, Shandong, China.

To better understand the molecular mechanisms of intracranial aneurysm (IA) pathogenesis, we used gene coexpression networks to identify hub genes and functional pathways associated with IA onset. Two Gene Expression Omnibus (GEO) datasets encompassing intracranial aneurysm tissue samples and cerebral artery control samples were included. To discover functional pathways and potential biomarkers, weighted gene coexpression network analysis was employed. Next, single-gene gene set enrichment analysis was employed to investigate the putative biological roles of the chosen genes. We also used receiver operating characteristic analysis to confirm the diagnostic results. Finally, we used a rat model to confirm the hub genes in the module of interest. The module of interest, which was designated the green module and included 115 hub genes, was the key module that was most strongly and negatively associated with IA formation. According to gene set variation analysis results, 15 immune-related pathways were significantly activated in the IA group, whereas 7 metabolic pathways were suppressed. In two GEO datasets, SLC2A12 could distinguish IAs from control samples. Twenty-nine hub genes in the green module might be biomarkers for the occurrence of cerebral aneurysms. SLC2A12 expression was significantly downregulated in both human and rat IA tissue. In the present study, we identified 115 hub genes related to the pathogenesis of IA onset and deduced their potential roles in various molecular pathways; this new information may contribute to the diagnosis and treatment of IAs. By external validation, the SLC2A12 gene may play an important role. The molecular function of SLC2A12 in the process of IA occurrence can be further studied in a rat model.
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http://dx.doi.org/10.1038/s41598-022-17510-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345973PMC
August 2022

Distinct Role of Surface Hydroxyls in Single-Atom Pt/CeO Catalyst for Room-Temperature Formaldehyde Oxidation: Acid-Base Versus Redox.

JACS Au 2022 Jul 10;2(7):1651-1660. Epub 2022 Jun 10.

Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, Washington 99164, United States.

The development of highly efficient catalysts for room-temperature formaldehyde (HCHO) oxidation is of great interest for indoor air purification. In this work, it was found that the single-atom Pt/CeO catalyst exhibits a remarkable activity with complete removal of HCHO even at 288 K. Combining density functional theory calculations and DRIFTS experiments, it was revealed that the active OH site generated on CeO in the vicinity of Pt via steam treatment plays a key role in the oxidation of HCHO to formate and its further oxidation to CO. Such involvement of hydroxyls is fundamentally different from that of cofeeding water which dissociates on metal oxide and catalyzes the acid-base-related chemistry. This study provides an important implication for the design and synthesis of supported Pt catalysts with atom efficiency for a very important practical application-room-temperature HCHO oxidation.
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http://dx.doi.org/10.1021/jacsau.2c00215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327081PMC
July 2022

Targeting the splicing factor NONO inhibits GBM progression through GPX1 intron retention.

Theranostics 2022 11;12(12):5451-5469. Epub 2022 Jul 11.

Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012, China.

Splicing factors are essential for nascent pre-mRNA processing and critical in cancer progression, suggesting that proteins with splicing functions represent potential molecular targets for cancer therapy. Here, we investigate the role of splicing factors in glioblastoma multiforme (GBM) progression and the possibility of targeting them for the treatment of the disease. The TCGA and CGGA public databases were used to screen for differentially expressed mRNA splicing factors. Immunohistochemistry and qRT-PCR were used to analyze the expression of non-POU domain-containing octamer-binding protein (NONO), a Drosophila behavior human splicing (DBHS) protein. Knockdown/overexpression of NONO with siRNA and lentiviral expression constructs was used to examine cell growth, apoptosis, and invasion in GBM cells. RNA sequencing was used to identify potential downstream molecular targets of NONO. RIP-PCR and RNA pulldown were used to determine the interaction between NONO and pre-mRNA. JC-1 staining and the seahorse assay were performed to assess redox homeostasis. Expression of NONO was increased in GBM samples and associated with poor survival in patients ( = 0.04). Knockdown of NONO suppressed GBM growth, and overexpression of NONO promoted GBM tumorigenesis and . RNA sequencing-based transcriptomic profiling confirmed that knockdown of NONO in U251 and P3 cells resulted in global intron retention of pre-mRNA and led to abnormal splicing of specific pre-mRNAs for and . NONO bound to a consensus motif in the intron of pre-mRNA in association with another DBHS protein family member, PSPC1. Knockdown of NONO impaired tumor growth, invasion, and redox homeostasis through aberrant splicing of . Finally, Auranofin, a small molecule inhibitor of NONO, suppressed GBM tumor growth in an orthotopic xenograft model in mice. We demonstrated that intron retention was a critical alternative RNA splicing event to occur in GBM progression, and that NONO was a key regulator of mRNA splicing in GBM. Targeting NONO represents a novel, potential therapeutic strategy for GBM treatment.
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http://dx.doi.org/10.7150/thno.72248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330516PMC
August 2022

Synergetic Effect of Mo, Mg-Modified Sn-β Over Moderate-Temperature Conversion of Hexose to Alkyl Lactate.

Front Chem 2022 14;10:944552. Epub 2022 Jul 14.

College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.

The thermocatalytic conversion of hexose into valuable chemicals such as methyl lactate under mild conditions is very appealing. Here, we report that Mo, Mg co-modified Sn-β catalyst can effectively catalyze the transformation of glucose and fructose into alkyl lactate at moderate temperatures. A maximum yield of around 35% of methyl lactate was achieved from the conversion of glucose in methanol at 100°C over Sn-β catalyst modified with 3 wt% Mo and 0.5 wt% Mg. However, up to 82.8% yield of ethyl lactate was obtained in the case of fructose in ethanol upon the same catalytic condition, suggesting a significant solvent effect. The Mo species plays a key role to enable the retro-aldol condensation of fructose, in which the competing side reactions are significantly suppressed with the assistance of neighboring Mg species probably through a synergetic effect of Lewis acid-base.
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http://dx.doi.org/10.3389/fchem.2022.944552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329925PMC
July 2022

Hierarchical Heterostructure Engineering of Layered Double Hydroxides on Nickel Sulfides Heteronanowire Arrays as Efficient Cathode for Alkaline Aqueous Zinc Batteries.

Small 2022 Jul 30:e2202799. Epub 2022 Jul 30.

Guangzhou Key Laboratory of Sensing Materials & Devices, Center for Advanced Analytical Science, c/ o School of Chemistry and Chemical Engineering, Guangzhou University, Guangzhou, 510006, P. R. China.

Aqueous alkaline rechargeable nickel-zinc (Ni-Zn) batteries possess great potential for large-scale energy storage systems because of their high output voltage, cheap cost, and intrinsic safety. However, the practical applicability of Ni-Zn batteries has been limited by traditional Ni-based cathodes with low capacity and poor cycle stability. Rational design of electrode structure and composition is highly desired but still significantly challenging. Herein, uniform self-supported hierarchical heterostructure composites interacting NiCo-layered double hydroxide with 1D nickel sulfides heteronanowire rooted on Ni foam (NF\Ni S /[email protected]) are successfully developed by a hydrothermal sulfurization-electrodeposition process. The self-supported 3D hierarchical heterostructured composites nanoarray provides abundant reactive sites, rapid ion diffusion channels, and fast electron transfer routes, as well as strong structural stability. More significantly, the strong interfacial charge transfer between Ni S /NiS heteronanowire and NiCo-LDH effectively modifies the electronic structure of the composites and thereby improving the reaction kinetics. Consequently, the NF\Ni S /[email protected] electrode presents a superior capacity of 434.5 mAh g (1.73 mAh cm ) at 3 mA cm . In addition, the fabricated NF\Ni S /[email protected]//Zn battery can offer a maximal energy density and power density as large as 556.3 Wh kg and 26.3 kW kg , respectively, as well as an exceptional cycling performance.
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http://dx.doi.org/10.1002/smll.202202799DOI Listing
July 2022

Rapid analysis of components in Qizhiweitong tablets and plasma after oral administration in rats by UPLC-Q-TOF-MS/MS based on self-developed database.

Biomed Chromatogr 2022 Jul 28. Epub 2022 Jul 28.

College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China.

Qizhiweitong is a famous traditional Chinese prescription medicine. It has been used to treat various stomach disorders, such as functional dyspepsia, chronic gastritis, and intestinal stress syndrome for a long time and gives favorable therapeutic effects in clinical settings. However, its chemical composition and possible bioactive components are not completely known. In the present study, we used ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) and qualitatively analyzed the chemical composition of Qizhiweitong tablet extract and the absorbed prototype constituents along with corresponding metabolites in rat plasma following oral administration of Qizhiweitong tablet on the basis of our self-developed component database that was established accurately and rapidly. We detected a total of 119 compounds and 61 xenobiotics in the Qizhiweitong tablet, which included 32 prototypes and 28 metabolites. The results of the present study laid a solid foundation for quality marker screening and integrative pharmacology-based study on the Qizhiweitong tablet.
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http://dx.doi.org/10.1002/bmc.5460DOI Listing
July 2022

Analysis of the Anti-Tumour Effect of Xuefu Zhuyu Decoction Based on Network Pharmacology and Experimental Verification in .

Front Pharmacol 2022 12;13:922457. Epub 2022 Jul 12.

Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, China.

Tumours are among the most lethal diseases that heavily endanger human health globally. Xuefu Zhuyu Decoction (XFZYD) is a prescription used to treat blood-activating stasis. Although XFZYD has been shown to suppress migration and invasion of tumour cells, the active ingredients, potential targets, and underlying mechanism remain largely elusive. To identify the prospective ingredients and major targets of XFZYD against tumours, and evaluate the efficacy and potential molecular mechanisms of XFZYD extract on tumour growth and invasion. We predicted that XFZYD might act on 80 targets through 128 active components using the network pharmacology analysis method. In addition, we prepared an XFZYD aqueous extract and employed the Ras/ -induced tumour model to carry out experimental verification. XFZYD did not exhibit any side effects on development, viability, and fertility. Furthermore, XFZYD significantly impeded tumour size and invasion at moderate concentrations and suppressed the increased phosphorylation of JNK but strongly enhanced the expression of Caspase 3 in the Ras/ model. Finally, the mRNA level of the transcription complex AP-1 component was remarkably reduced. In contrast, the transcription of three pro-apoptotic genes was significantly increased when XFZYD was used to treat the tumour model. The study findings suggest that XFZYD may promote tumour cell apoptosis by activating caspase signalling to control primary growth and hinder tumour cell invasion by suppressing JNK/AP-1 signalling activity, thus providing a potential therapeutic strategy for XFZYD in the clinical treatment of cancer and other related diseases.
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http://dx.doi.org/10.3389/fphar.2022.922457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315317PMC
July 2022

, Encoding a Typical CC-NBS-LRR Protein, Confers Resistance to Southern Corn Rust in Maize.

Front Plant Sci 2022 12;13:951318. Epub 2022 Jul 12.

Maize Research Institute, Beijing Academy of Agriculture and Forestry Sciences, Beijing Key Laboratory of Maize DNA Fingerprinting and Molecular Breeding, Beijing, China.

Southern corn rust (SCR) caused by Underw. poses a major threat to maize production worldwide. The utilization of host SCR-resistance genes and the cultivation of resistant cultivars are the most effective, economical strategies for controlling SCR. Here, we identified and cloned a new SCR resistance gene, , from the elite maize inbred line Jing2416K. was found to encode a typical CC-NBS-LRR protein localized in both the nucleus and cytoplasm. This gene was constitutively expressed at all developmental stages and in all tissues examined, with the strongest expression detected in leaves at the mature stage. A transcriptome analysis provided further evidence that multiple defense systems were initiated in Jing2416K, including pathogen-associated molecular pattern-triggered immunity and effector-triggered immunity, reinforcement of cell walls, accumulation of antimicrobial compounds, and activation of phytohormone signaling pathways. Finally, we developed functional Kompetitive allele-specific PCR markers for using two conserved SNP sites and successfully applied these functional markers for the detection of and the cultivation of resistant maize cultivars, demonstrating their great potential utility in maize breeding.
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http://dx.doi.org/10.3389/fpls.2022.951318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317930PMC
July 2022

Two cases of intestinal perforation due to mesenteric artery embolism during extracorporeal membrane oxygenation and intra-aortic balloon pumping.

Clin Med (Lond) 2022 Jul;22(4):360-363

Affiliated Hangzhou First People's Hospital and Zhejiang University School of Medicine, Hangzhou, China

The patient in case 1 was a 50-year-old man who presented to the emergency department of the local hospital with chest pain and syncope for 3 hours due to acute myocardial infarction. He underwent cardiopulmonary resuscitation (CPR) followed by extracorporeal membrane oxygenation (ECMO), and intestinal perforation was detected on day 9. The patient in case 2 was a 58-year-old man who was admitted to the hospital with abdominal pain lasting for 3 days. He also required CPR and ECMO for cardiogenic shock, and intestinal perforation was identified on day 7 of ECMO. We believe that this case report will be important to alert clinicians to the possibility of this complication and to encourage early detection and intervention to improve prognosis. Conventionally, the gastrointestinal tract has received secondary attention in patients receiving ECMO support because the vital organs tend to be considered first. However, this case report illustrates the importance of monitoring gastrointestinal function in patients undergoing ECMO.
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http://dx.doi.org/10.7861/clinmed.2022-0162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345213PMC
July 2022

Extendable Multiple Nodes Recurrent Tracking Framework With RTU+.

IEEE Trans Image Process 2022 8;31:5257-5271. Epub 2022 Aug 8.

Recently, tracking-by-detection has become a popular paradigm in Multiple-object tracking (MOT) for its concise pipeline. Many current works first associate the detections to form track proposals and then score proposalns by manual functions to select the best. However, long-term tracking information is lost in this way due to detection failure or heavy occlusion. In this paper, the Extendable Multiple Nodes Tracking framework (EMNT) is introduced to model the association. Instead of detections, EMNT creates four basic types of nodes including correct, false, dummy and termination to generally model the tracking procedure. Further, we propose a General Recurrent Tracking Unit (RTU++) to score track proposals by capturing long-term information. In addition, we present an efficient generation method of simulated tracking data to overcome the dilemma of limited available data in MOT. The experiments show that our methods achieve state-of-the-art performance on MOT17, MOT20 and HiEve benchmarks. Meanwhile, RTU++ can be flexibly plugged into other trackers such as MHT, and bring significant improvements. The additional experiments on MOTS20 and CTMC-v1 also demonstrate the generalization ability of RTU++ trained by simulated data in various scenarios.
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http://dx.doi.org/10.1109/TIP.2022.3192706DOI Listing
August 2022

Deactylation by SIRT1 enables liquid-liquid phase separation of IRF3/IRF7 in innate antiviral immunity.

Nat Immunol 2022 Aug 25;23(8):1193-1207. Epub 2022 Jul 25.

International Biomed-X Research Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.

Innate antiviral immunity deteriorates with aging but how this occurs is not entirely clear. Here we identified SIRT1-mediated DNA-binding domain (DBD) deacetylation as a critical step for IRF3/7 activation that is inhibited during aging. Viral-stimulated IRF3 underwent liquid-liquid phase separation (LLPS) with interferon (IFN)-stimulated response element DNA and compartmentalized IRF7 in the nucleus, thereby stimulating type I IFN (IFN-I) expression. SIRT1 deficiency resulted in IRF3/IRF7 hyperacetylation in the DBD, which inhibited LLPS and innate immunity, resulting in increased viral load and mortality in mice. By developing a genetic code expansion orthogonal system, we demonstrated the presence of an acetyl moiety at specific IRF3/IRF7 DBD site/s abolish IRF3/IRF7 LLPS and IFN-I induction. SIRT1 agonists rescued SIRT1 activity in aged mice, restored IFN signaling and thus antagonized viral replication. These findings not only identify a mechanism by which SIRT1 regulates IFN production by affecting IRF3/IRF7 LLPS, but also provide information on the drivers of innate immunosenescence.
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http://dx.doi.org/10.1038/s41590-022-01269-0DOI Listing
August 2022

Patulin Detoxification by Recombinant Manganese Peroxidase from Expressed by .

Toxins (Basel) 2022 Jun 29;14(7). Epub 2022 Jun 29.

State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.

The fungal secondary metabolite patulin is a mycotoxin widespread in foods and beverages which poses a serious threat to human health. However, no enzyme was known to be able to degrade this mycotoxin. For the first time, we discovered that a manganese peroxidase (MnP) from can efficiently degrade patulin. The MnP gene was cloned into pPICZα(A) and then the recombinant plasmid was transformed into X-33. The recombinant strain produced extracellular manganese peroxidase with an activity of up to 3659.5 U/L. The manganese peroxidase MnP was able to rapidly degrade patulin, with hydroascladiol appearing as a main degradation product. Five mg/L of pure patulin were completely degraded within 5 h. Moreover, up to 95% of the toxin was eliminated in a simulated patulin-contaminated apple juice after 24 h. Using as a model, it was demonstrated that the deconstruction of patulin led to detoxification. Collectively, these traits make MnP an intriguing candidate useful in enzymatic detoxification of patulin in foods and beverages.
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http://dx.doi.org/10.3390/toxins14070440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324453PMC
June 2022

The potential of a nomogram combined PI-RADS v2.1 and contrast-enhanced ultrasound (CEUS) to reduce unnecessary biopsies in prostate cancer diagnostics.

Br J Radiol 2022 Jul 25:20220209. Epub 2022 Jul 25.

Center of Minimally Invasive Treatment for Tumor, Department of Medical Ultrasound, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Objectives: To develop a nomogram prediction model based on Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) and contrast-enhanced ultrasound (CEUS) for predicting prostate cancer (PCa) and clinically significant prostate cancer (csPCa) in males with prostate-specific antigen (PSA) 4-10 ng ml to avoid unnecessary biopsy.

Methods: A total of 490 patients who underwent prostate biopsy for PSA 4-10 ng ml were enrolled and randomly divided into a pilot cohort (70%) and a validation cohort (30%). Univariate and multivariate logistic regression models were constructed to select potential predictors of PCa and csPCa, and a nomogram was created. The area under receiver operating characteristic (ROC) curve (AUC) was calculated, and compared using DeLong's test. The diagnostic performance and unnecessary biopsy rate of the nomogram prediction model were also assessed. Hosmer-Lemeshow Goodness-of-fit test was employed to test for model fitness.

Results: The multivariate analysis revealed that features independently associated with PCa and csPCa were age, PI-RADS score and CEUS manifestations. Incorporating these factors, the nomogram achieved good discrimination performance of AUC 0.843 for PCa, 0.876 for csPCa in the pilot cohort, and 0.818 for PCa, 0.857 for csPCa in the validation cohort, respectively, and had well-fitted calibration curves. And the diagnostic performance of the nomogram was comparable to the model including all the parameters ( > 0.05). Besides, the nomogram prediction model yielded meaningful reduction in unnecessary biopsy rate (from 74.8 to 21.1% in PCa, and from 83.7 to 5.4% in csPCa).

Conclusions: The nomogram prediction model based on age, PI-RADS v2.1 and CEUS achieved an optimal prediction of PCa and csPCa. Using this model, the PCa risk for an individual patient can be estimated, which can lead to a rational biopsy choice.

Advances In Knowledge: This study gives an account of improving pre-biopsy risk stratification in males with "gray zone" PSA level through PI-RADS v2.1 and CEUS.
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http://dx.doi.org/10.1259/bjr.20220209DOI Listing
July 2022

Bioactivation and reactivity research advances - 2021 year in review.

Drug Metab Rev 2022 Aug 5:1-36. Epub 2022 Aug 5.

Department of Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, CA, USA.

This year's review on bioactivation and reactivity began as a part of the annual review on biotransformation and bioactivation led by Cyrus Khojasteh (see references). Increased contributions from experts in the field led to the development of a stand alone edition for the first time this year focused specifically on bioactivation and reactivity. Our objective for this review is to highlight and share articles which we deem influential and significant regarding the development of covalent inhibitors, mechanisms of reactive metabolite formation, enzyme inactivation, and drug safety. Based on the selected articles, we created two sections: (1) reactivity and enzyme inactivation, and (2) bioactivation mechanisms and safety (Table 1). Several biotransformation experts have contributed to this effort from academic and industry settings.[Table: see text].
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http://dx.doi.org/10.1080/03602532.2022.2097254DOI Listing
August 2022

A VGG attention vision transformer network for benign and malignant classification of breast ultrasound images.

Med Phys 2022 Jul 22. Epub 2022 Jul 22.

Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Purpose: Breast cancer is the most commonly occurring cancer worldwide. The ultrasound reflectivity imaging technique can be used to obtain breast ultrasound (BUS) images, which can be used to classify benign and malignant tumors. However, the classification is subjective and dependent on the experience and skill of operators and doctors. The automatic classification method can assist doctors and improve the objectivity, but current convolution neural network (CNN) is not good at learning global features and vision transformer (ViT) is not good at extraction local features. In this study, we proposed a visual geometry group attention ViT (VGGA-ViT) network to overcome their disadvantages.

Methods: In the proposed method, we used a CNN module to extract the local features and employed a ViT module to learn the global relationship among different regions and enhance the relevant local features. The CNN module was named the VGGA module. It was composed of a VGG backbone, a feature extraction fully connected layer, and a squeeze-and-excitation block. Both the VGG backbone and the ViT module were pretrained on the ImageNet dataset and retrained using BUS samples in this study. Two BUS datasets were employed for validation.

Results: Cross-validation was conducted on two BUS datasets. For the Dataset A, the proposed VGGA-ViT network achieved high accuracy (88.71 1.55%), recall (90.73 1.57%), specificity (85.58 3.35%), precision (90.77 1.98%), F1 score (90.73 1.24%), and Matthews correlation coefficient (MCC) (76.34 3.29%), which were better than those of all compared previous networks in this study. The Dataset B was used as a separate test set, the test results showed that the VGGA-ViT had highest accuracy (81.72 2.99%), recall (64.45 2.96%), specificity (90.28 3.51%), precision (77.08 7.21%), F1 score (70.11 4.25%), and MCC (57.64 6.88%).

Conclusions: In this study, we proposed the VGGA-ViT for the BUS classification, which was good at learning both local and global features. The proposed network achieved higher accuracy than the compared previous methods.
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http://dx.doi.org/10.1002/mp.15852DOI Listing
July 2022

Treatment of peripheral bronchopleural fistula with interventional negative pressure drainage.

Ther Adv Respir Dis 2022 Jan-Dec;16:17534666221111877

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe Road, Zhengzhou 450052, China.

Objectives: Bronchopleural fistula is a serious complication of pneumonectomy and lobectomy and results in a reduction in the quality of life of patients. This study aimed to evaluate the efficacy and safety of percutaneous drainage tube placement with continuous negative pressure drainage for the treatment of peripheral bronchopleural fistula.

Methods: Data of 16 patients with peripheral bronchopleural fistula were retrospectively analyzed. A percutaneous thoracic drainage tube was placed under fluoroscopy and connected with a negative pressure suction device. The drainage tube was removed when the residual cavity disappeared on computed tomography.

Results: All 16 patients underwent lobectomy, including 11 patients with lung cancer (68.8%), 4 patients with pulmonary infection (25.0%), and 1 patient with hemoptysis (6.3%). All patients underwent successful drainage tube placement on the first attempt with a technical success rate of 100%. No serious complications occurred during or after the procedure. The drainage tubes were adjusted 3.25 ± 2.24 times (range: 1-8 times). A total of 30 drainage tubes were used (average per patient, 1.88 ± 1.36 tubes). The cure time of 16 patients was 114.94 ± 101.08 days (range, 30-354 days). The median drainage tube indwelling duration was 87 days, and the 75th percentile was 117 days.

Conclusion: Interventional percutaneous thoracic drainage tube placement with continuous negative pressure drainage is an effective, safe, and feasible method for the treatment of peripheral bronchopleural fistula.
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http://dx.doi.org/10.1177/17534666221111877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297443PMC
July 2022

HIV protease inhibitor nelfinavir is a potent drug candidate against echinococcosis by targeting Ddi1-like protein.

EBioMedicine 2022 Jul 14;82:104177. Epub 2022 Jul 14.

State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, 730000, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009, China. Electronic address:

Background: Alveolar echinococcosis (AE), which is caused by larval Echinococcus multilocularis, is one of the world's most dangerous neglected diseases. Currently, no fully effective treatments are available to cure this disease.

Methods: In vitro protoscolicidal assay along with in vivo murine models was applied in repurposing drugs against AE. Genome-wide identification and homology-based modeling were used for predicting drug targets. RNAi, enzyme assay, and RNA-Seq analyses were utilized for investigating the roles in parasite survival and validations for the drug target.

Findings: We identified nelfinavir as the most effective HIV protease inhibitor against larval E. multilocularis. Once-daily oral administration of nelfinavir for 28 days resulted in a remarkable reduction in parasite infection in either immune-competent or immunocompromised mice. E. multilocularis DNA damage-inducible 1 protein (EmuDdi1) is predicted as a target candidate for nelfinavir. We proved that EmuDdi1 is essential for parasite survival and protein excretion and acts as a functionally active protease for this helminth. We found nelfinavir is able to inhibit the proteolytic activity of recombinant EmuDdi1 and block the EmuDdi1-related pathways for protein export. With other evidence of drug efficacy comparison, our results suggest that inhibition of EmuDdi1 is a mechanism by which this HIV proteinase inhibitor mediates its antiparasitic action on echinococcosis.

Interpretation: This study demonstrates that nelfinavir is a promising candidate for treating echinococcosis. This drug repurposing study proves that the widely prescribed drug for AIDS treatment is potent in combating E. multilocularis infection and thus provides valuable insights into the development of single-drug therapy for highly prevalent co-infection between HIV and helminth diseases.

Funding: This work was supported by the National Natural Science Foundation of China (31802179), the Natural Science Foundation of Gansu Province, China (No. 21JR7RA027), and the State Key Laboratory of Veterinary Etiological Biology (No. SKLVEB2021YQRC01).
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http://dx.doi.org/10.1016/j.ebiom.2022.104177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294487PMC
July 2022
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