Publications by authors named "Wei Chen"

11,222 Publications

  • Page 1 of 1

Parkinson's disease-risk protein TMEM175 is a proton-activated proton channel in lysosomes.

Cell 2022 Jun;185(13):2292-2308.e20

Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 4114 Biological Sciences Building (BSB), 1105 N. University Ave, Ann Arbor, MI 48109, USA. Electronic address:

Lysosomes require an acidic lumen between pH 4.5 and 5.0 for effective digestion of macromolecules. This pH optimum is maintained by proton influx produced by the V-ATPase and efflux through an unidentified "H leak" pathway. Here we show that TMEM175, a genetic risk factor for Parkinson's disease (PD), mediates the lysosomal H leak by acting as a proton-activated, proton-selective channel on the lysosomal membrane (LyPAP). Acidification beyond the normal range potently activated LyPAP to terminate further acidification of lysosomes. An endogenous polyunsaturated fatty acid and synthetic agonists also activated TMEM175 to trigger lysosomal proton release. TMEM175 deficiency caused lysosomal over-acidification, impaired proteolytic activity, and facilitated α-synuclein aggregation in vivo. Mutational and pH normalization analyses indicated that the channel's H conductance is essential for normal lysosome function. Thus, modulation of LyPAP by cellular cues may dynamically tune the pH optima of endosomes and lysosomes to regulate lysosomal degradation and PD pathology.
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http://dx.doi.org/10.1016/j.cell.2022.05.021DOI Listing
June 2022

The influence of blood donation before pregnancy on neonatal birth weight.

PLoS One 2022 24;17(6):e0269367. Epub 2022 Jun 24.

Department of Blood Transfusion, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China.

Objective: To evaluate the effect of blood donation before pregnancy on neonatal birth weight.

Methods: A total of 14996 women with singleton pregnancies at full-term in Ningbo Medical Center Lihuili Hospital and Ningbo Women's and Children's Hospital from November 2019 to November 2020 were enrolled in this study. Detailed records of whole blood donation before pregnancy were obtained through Alipay software. The records were classified into three groups: nondonors, low-frequency donors and high-frequency donors according to the total numbers of blood donations in the 3-year period before pregnancy. The demographics and clinical information of the enrolled participants and their fetuses were collected from electronic medical records (EMRs). The effect of blood donations in the 3-year period before pregnancy on neonatal birth weight was analyzed.

Results: There was no significant difference in neonatal birth weight among the three groups (P = 0.373). In line with this, there was no association between the number of blood donations in the 3-year period before pregnancy and neonatal birth weight (β = 14.5; 95% confidence interval [CI]: -3.9, 31.4; P = 0.094) in the bootstrapped multivariate linear regression analysis models, adjusted for maternal age, number of pregnancies, number of deliveries, gestational age, mode of delivery, years of education and blood type in pregnant women. Compared to the nondonors, the risk of fetal macrosomia was higher in both low-frequency donors and all donors (OR: 1.539, 95% CI: 1.058, 2.134, P = 0.016; OR: 1.454, 95% CI: 1.033, 1.952, P = 0.021, respectively), in the bootstrapped binary logistic regression analysis models after adjusting for the variables mentioned above.

Conclusion: Our study showed that maternal blood donation in the 3-year period before pregnancy may not lead to a reduction in neonatal birth weight, but may be associated with the incidence of fetal macrosomia.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0269367PLOS
June 2022

Single-Atom Ce-Modified α-FeO for Selective Catalytic Reduction of NO with NH.

Environ Sci Technol 2022 Jun 24. Epub 2022 Jun 24.

Jiangsu Key Laboratory of Vehicle Emissions Control, School of the Environment, Nanjing University, Nanjing 210093, P. R. China.

A single-atom Ce-modified α-FeO catalyst (FeCeO catalyst with 7% atomic percentage of Ce) was synthesized by a citric acid-assisted sol-gel method, which exhibited excellent performance for selective catalytic reduction of NO with NH (NH-SCR) over a wide operating temperature window. Remarkably, it maintained ∼93% NO conversion efficiency for 168 h in the presence of 200 ppm SO and 5 vol % HO at 250 °C. The structural characterizations suggested that the introduction of Ce leads to the generation of local Fe-O-Ce sites in the FeO matrix. Furthermore, it is critical to maintain the atomic dispersion of the Ce species to maximize the amounts of Fe-O-Ce sites in the Ce-doped FeO catalyst. The formation of CeO nanoparticles due to a high doping amount of Ce species leads to a decline in catalytic performance, indicating a size-dependent catalytic behavior. Density functional theory (DFT) calculation results indicate that the formation of oxygen vacancies in the Fe-O-Ce sites is more favorable than that in the Fe-O-Fe sites in the Ce-free α-FeO catalyst. The Fe-O-Ce sites can promote the oxidation of NO to NO on the FeCeO catalyst and further facilitate the reduction of NO by NH. In addition, the decomposition of NHHSO can occur at lower temperatures on the FeCeO catalyst containing atomically dispersed Ce species than on the α-FeO reference catalyst, resulting in the good SO/HO resistance ability in the NH-SCR reaction.
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http://dx.doi.org/10.1021/acs.est.2c02916DOI Listing
June 2022

Material parameters identification of 3D printed titanium alloy prosthesis stem based on response surface method.

Comput Methods Biomech Biomed Engin 2022 Jun 24:1-10. Epub 2022 Jun 24.

Department of Trauma Unit, Tianjin Hospital, China.

3D printed Titanium alloy is widely used as a material of artificial joints and its mechanical properties is a key factor for improving operation results. Because the elastic modulus of the 3 D printed titanium alloy specimen was related to the size of the metal blank. It is very difficult to identify mechanical parameters by traditional mechanics experiments. In this paper, according to the inverse analysis principle of the parameter estimation, a response surface methodology (RSM) was proposed to identify the mechanical parameters, based on finite element inverse analysis. The finite element models of femoral prosthesis stem were established in line with compression experiments. The material parameters were combined by central composite design (CCD), and the response surface (RS) models were constructed using a quadratic polynomial with cross terms and optimized using a genetic algorithm (GA). Finally, the best mechanical parameter combination of the femoral prosthesis was calculated. The calculated elastic modulus and Poisson's ratio of a 3 D printed titanium alloy femoral prosthesis stem were 109.07 GPa and 0.29, respectively, with the elastic modulus error being very small. The proposed method is effective and can be extended for the identification of mechanical parameters in other 3 D printed models.
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http://dx.doi.org/10.1080/10255842.2022.2089023DOI Listing
June 2022

Oxygen Vacancy-Mediated Selective C-N Coupling toward Electrocatalytic Urea Synthesis.

J Am Chem Soc 2022 Jun 24. Epub 2022 Jun 24.

State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, Advanced Catalytic Engineering Research Center of the Ministry of Education, Hunan University, Changsha, Hunan 410082, P. R. China.

The electrocatalytic C-N coupling for one-step urea synthesis under ambient conditions serves as the promising alternative to the traditional urea synthetic protocol. However, the hydrogenation of intermediate species hinders the efficient urea synthesis. Herein, the oxygen vacancy-enriched CeO was demonstrated as the efficient electrocatalyst with the stabilization of the crucial intermediate of *NO inserting into vacant sites, which is conducive to the subsequent C-N coupling process rather than protonation, whereas the poor selectivity of C-N coupling with protonation was observed on the vacancy-deficient catalyst. The oxygen vacancy-mediated selective C-N coupling was distinguished and validated by the sum frequency generation spectroscopy. The introduction of oxygen vacancies tailors the common catalyst carrier into an efficient electrocatalyst with a high urea yield rate of 943.6 mg h g, superior than that of partial noble-metal-based electrocatalysts. This work provides novel insights into the catalyst design and developments of coupling systems.
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http://dx.doi.org/10.1021/jacs.2c03452DOI Listing
June 2022

Immunogenicity and Safety of an Inactivated Enterovirus 71 Vaccine Administered Simultaneously with Hepatitis B Virus Vaccine, Group A Meningococcal Polysaccharide Vaccine, Measles-Rubella Combined Vaccine and Japanese Encephalitis Vaccine: A Multi-Center, Randomized, Controlled Clinical Trial in China.

Vaccines (Basel) 2022 Jun 2;10(6). Epub 2022 Jun 2.

Shandong Provincial Center for Disease Control and Prevention, Jinan 250014, China.

Background: The aim of this study was to investigate the immunogenicity and safety of the enterovirus 71 vaccine (EV71 vaccine) administered alone or simultaneously.

Methods: A multi-center, open-label, randomized controlled trial was performed involving 1080 healthy infants aged 6 months or 8 months from Shandong, Shanxi, Shaanxi, and Hunan provinces. These infants were divided into four simultaneous administration groups and EV71 vaccine separate administration group. Blood samples were collected from the infants before the first vaccination and after the completion of the vaccination. This trial was registered in the Clinical Trials Registry (NCT03519568).

Results: A total of 895 were included in the per-protocol analysis. The seroconversion rates of antibodies against EV71 in four simultaneous administration groups (98.44% (189/192), 94.57% (122/129), 99.47% (187/188) and 98.45% (190/193)) were non-inferior to EV71 vaccine separate administration group (97.93% [189/193]) respectively. Fever was the most common adverse event, the pairwise comparison tests showed no difference in the incidence rate of solicited, systemic or local adverse events. Three serious adverse events related to the vaccination were reported.

Conclusions: The evidence of immunogenicity and safety supports that the EV71 vaccine administered simultaneously with vaccines need to be administered during the same period of time recommended in China.
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http://dx.doi.org/10.3390/vaccines10060895DOI Listing
June 2022

Tuning Multicolor Emission of Manganese-Activated Gallogermanate Nanophosphors by Regulating Mn Ions Occupying Sites for Multiple Anti-Counterfeiting Application.

Nanomaterials (Basel) 2022 Jun 13;12(12). Epub 2022 Jun 13.

Department of Physics, The University of Texas at Arlington, Arlington, TX 76019-0059, USA.

The ability to manipulate the luminescent color, intensity and long lifetime of nanophosphors is important for anti-counterfeiting applications. Unfortunately, persistent luminescence materials with multimode luminescent features have rarely been reported, even though they are expected to be highly desirable in sophisticated anti-counterfeiting. Here, the luminescence properties of ZnGaGeO:Mn phosphors were tuned by using different preparation approaches, including a hydrothermal method and solid-state reaction approach combining with non-equivalent ion doping strategy. As a result, Mn-activated ZnGaGeO phosphors synthesized by a hydrothermal method demonstrate an enhanced red photoluminescence at 701 nm and a strong green luminescence with persistent luminescence and photostimulated luminescence at 540 nm. While Mn-activated ZnGaGeO phosphors synthesized by solid-state reactions combined with a hetero-valent doping approach only exhibit an enhanced single-band red emission. Keeping the synthetic method unchanged, the substitution of hetero-valent dopant ion Li into different sites is valid for spectral fine-tuning. A spectral tuning mechanism is also proposed. Mn-activated ZnGaGeO phosphors synthesized by a hydrothermal approach with multimodal luminescence is especially suitable for multiple anti-counterfeiting, multicolor display and other potential applications.
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http://dx.doi.org/10.3390/nano12122029DOI Listing
June 2022

Is Effective in Relieving Type 2 Diabetes and May Be Related to Its Dominant Core Genome and Gut Microbiota Modulation Capacity.

Nutrients 2022 Jun 15;14(12). Epub 2022 Jun 15.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

The prevalence of diabetes mellitus is increasing globally. Probiotics have been shown to be an effective intervention for diabetes. This study focused on the relieving effects and possible mechanisms of 16 strains of two dominant species ( and , which exist in the human gut at different life stages) on type 2 diabetes (T2D). The results indicated that more strains appeared to be superior in alleviating T2D symptoms than strains. This effect was closely related to the ability of to restore the homeostasis of the gut microbiota, increase the abundance of short-chain fatty acid-producing flora, and alleviate inflammation in mice with T2D. In addition, compared with , had a higher number of core genes, and these genes were more evolutionarily stable, including unique environmental tolerance, carbon and nitrogen utilization genes, and a blood sugar regulation gene, . This may be one of the reasons why is more likely to colonize in the adult gut and show a superior ability to relieve T2D. This study provides insights into future studies aimed at investigating probiotics for the treatment of metabolic diseases.
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http://dx.doi.org/10.3390/nu14122479DOI Listing
June 2022

Comparison of Selenium-Enriched , Selenium-Enriched Yeast, and Selenite for the Alleviation of DSS-Induced Colitis in Mice.

Nutrients 2022 Jun 12;14(12). Epub 2022 Jun 12.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Patients with inflammatory bowel disease (IBD) have been found to have decreased immune function. Selenium (Se) is an essential trace element that is beneficial for human health, which has a significant stimulating effect on immune function. We compared the effects of different Se forms on the alleviation of colitis in DSS-induced mice. Moreover, we also aimed to determine whether Se-enriched CCFM 1089 could be used as a new organic Se supplement. Different Se supplements (Se-enriched CCFM 1089, Se-enriched yeast and sodium selenite) were given to Se-deficient mice suffering from colitis. Se-enriched CCFM 1089, which is based on selenocysteine (SeCys), had similar effects in terms of reducing oxidative stress and inhibiting pro-inflammatory factors to Se-enriched yeast; however, selenase activity in the Se-enriched CCFM 1089-treated mice was higher than that in other treatment groups. In addition, Se-enriched CCFM 1089 could better protect the intestinal mucosa, which increased the expression of tight junction proteins (ZO-1 and occludin) in mice. Thus Se-enriched CCFM 1089 was shown to alleviate IBD, suggesting that it has potential as a good organic Se supplement.
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http://dx.doi.org/10.3390/nu14122433DOI Listing
June 2022

Detecting the Subtle Photo-Responsive Conformational Bistability of Monomeric Azobenzene Functionalized Keggin Polyoxometalates by Using Ion-Mobility Mass Spectrometry.

Molecules 2022 Jun 19;27(12). Epub 2022 Jun 19.

State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China.

Accurately characterizing the conformational variation of novel molecular assemblies is important but often ignored due to limited characterization methods. Herein, we reported the use of ion-mobility mass spectrometry (IMS/MS) to investigate the conformational changes of four azobenzene covalently functionalized Keggin hybrids (azo-Keggins, compounds -). The as-prepared azo-Keggins showed the general molecular formula of [CHN][SiWO(Si(CH)NH-CO(CH)O-CHN=NCH-R)] (R = H, = 0 (); R = NO, = 0 (); R = H, = 5 (); R = H, = 10 ()). The resultant azo-Keggins maintained stable monomeric states in the gas phase with intact molecular structures. Furthermore, the subtle photo-responsive trans-cis conformational variations of azo-Keggins were clearly revealed by the molecular shape-related collision cross-section value difference ranging from 2.44 Å to 6.91 Å. The longer the alkyl chains linkers were, the larger the conformational variation was. Moreover, for compounds and , higher stability in -conformation can be observed, while for compounds and , bistability can be achieved for both of them.
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http://dx.doi.org/10.3390/molecules27123927DOI Listing
June 2022

Landscape Composition and Soil Physical-Chemical Properties Drive the Assemblages of Bacteria and Fungi in Conventional Vegetable Fields.

Microorganisms 2022 Jun 12;10(6). Epub 2022 Jun 12.

State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, Institute of Applied Ecology, Fujian Agriculture and Forestry University, Fuzhou 350002, China.

The soil microbiome is crucial for improving the services and functioning of agroecosystems. Numerous studies have demonstrated the potential of soil physical-chemical properties in driving the belowground microbial assemblages in different agroecosystems. However, not much is known about the assemblage of bacteria and fungi in response to soil physical-chemical properties and the surrounding landscape composition in different vegetable fields of a highly intensive agricultural system. Here, we investigated the effects of soil physical-chemical properties and landscape composition on the community trends of bacteria and fungi in two different soil compartments (bulk and rhizospheric soils) of two different brassica crop types (Chinese cabbage and flower cabbage). The results revealed that bulk soil had a higher alpha diversity of both bacteria and fungi than rhizospheric soil. Each of the soil physical-chemical properties and landscape compositions contributed differently to driving the community structure of distinct bacterial and fungal taxa in both soil compartments and crop types. The higher proportions of forest, grassland, and cultivated land, along with the higher amount of soil calcium in flower cabbage fields, promote the assemblage of Gammaproteobacteria, Actinobacteria, Oxyophotobacteria, Agaricomycetes, and Eurotiomycetes. On the other hand, in Chinese cabbage fields, the increased amounts of iron, zinc, and manganese in the soil together with higher proportions of non-brassica crops in the surrounding landscape strongly support the assemblage of Deltaproteobacteria, Gemmatimonadetes, Bacilli, Clostridia, Alphaproteobacteria, an unknown bacterial species Subgroup-6, Mortierellomycetes, Rhizophlyctidomycetes, and Chytridiomycetes. The findings of this study provide the most comprehensive, comparative, and novel insights related to the bacterial and fungal responses in a highly intensive vegetable growing system for the improvement of the soil fertility and structure. These are important clues for the identification of key bacteria and fungi contributing to the plant-environment interactions and are of a practical significance for landscape-based ecological pest management.
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http://dx.doi.org/10.3390/microorganisms10061202DOI Listing
June 2022

Research on the Road Performance of Asphalt Mixtures Based on Infrared Thermography.

Materials (Basel) 2022 Jun 17;15(12). Epub 2022 Jun 17.

Science and Technology Innovation Center, Shandong Transportation Institute, Jinan 250102, China.

Temperature segregation during the paving of asphalt pavements is one of the causes of asphalt pavement distress. Therefore, controlling the paving temperature is crucial in the construction of asphalt pavements. To quickly evaluate the road performance of asphalt mixtures during paving, in this work, we used unmanned aerial vehicle infrared thermal imaging technology to monitor the construction work. By analyzing the temperature distribution at the paving site, and conducting laboratory tests, the relationship between the melt temperature, high-temperature stability, and water stability of the asphalt mix was assessed. The results showed that the optimal temperature measurement height for an unmanned aerial vehicle (UAV) with an infrared thermal imager was 7-8 m. By coring the representative temperature points on the construction site and then conducting a Hamburg wheel tracking (HWT) test, the test results were verified through the laboratory test results in order to establish a prediction model for the melt temperature and high-temperature stability of y = 10.73e + 1415.78, where the predictive model for the melt temperature and water was y = -19.18e + 98.03. The results showed that using laboratory tests combined with UAV infrared thermography could quickly and accurately predict the road performance of asphalt mixtures during paving. We hope that more extensive evaluations of the roadworthiness of asphalt mixtures using paving temperatures will provide reference recommendations in the future.
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http://dx.doi.org/10.3390/ma15124309DOI Listing
June 2022

SOD3 and IL-18 Predict the First Kidney Disease-Related Hospitalization or Death during the One-Year Follow-Up Period in Patients with End-Stage Renal Disease.

Antioxidants (Basel) 2022 Jun 18;11(6). Epub 2022 Jun 18.

Department of Life Sciences, Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan.

End-stage renal disease (ESRD) patients experience oxidative stress due to excess exogenous or endogenous oxidants and insufficient antioxidants. Hence, oxidative stress and inflammation cause endothelial damage, contributing to vascular dysfunction and atherosclerosis. Therefore, ESRD patients suffer more cardiovascular and hospitalization events than healthy people. This study aims to test the correlations between ROS, SOD3, IL-2, IL-6, and IL-18 and the first kidney disease-related hospitalization or death events in ESRD patients undergoing regular hemodialysis. A total of 212 participants was enrolled, including 45 normal healthy adults and 167 ESRD patients on regular dialysis. Blood samples from all participants were collected for ROS, SOD3, IL-2, IL-6, and IL-18 measurement at the beginning of the study, and every kidney disease-related admission or death was recorded for the next year. Multivariate analysis was conducted by fitting a linear regression model, logistic regression model, and Cox proportional hazards model to estimate the adjusted effects of risk factors, prognostic factors, or predictors on continuous, binary, and survival outcome data. The results showed that plasma SOD3 and serum IL-18 were two strong predictors of the first kidney disease-related hospitalization or death. In the Cox proportional hazards models (run in R), higher IL-18 concentration (>69.054 pg/mL) was associated with a hazard ratio of 3.376 for the first kidney disease-related hospitalization or death (95% CI: 1.2644 to 9.012), while log(SOD3) < 4.723 and dialysis clearance (Kt/V; 1.11 < value < 1.869) had a hazard ratio = 0.2730 (95% CI: 0.1133 to 0.6576) for reducing future kidney disease-related hospitalization or death. Other markers, including body mass index (BMI), transferrin saturation, total iron binding capacity, and sodium and alkaline phosphate, were also found to be significant in our study. These results reveal the new predictors SOD3 and IL-18 for the medical care of end-stage renal disease patients.
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http://dx.doi.org/10.3390/antiox11061198DOI Listing
June 2022

Enhanced removal of Cr(VI) from aqueous solutions by polymer-mediated nitrogen-rich reduced graphene oxide.

J Hazard Mater 2022 Aug 18;436:129184. Epub 2022 May 18.

School of Environment and Energy, South China University of Technology, Guangzhou, Guangdong 510006, China; The Key Laboratory of Pollution Control and Ecosystem Restoration in Industry Clusters of Ministry of Education, Guangzhou, Guangdong 510006, China. Electronic address:

The efficient removal of heavy metal by rationally designed carbon-based adsorbents is a key challenge in the field of water purification. Herein, we report a nitrogen-enriched lignosulfonate exfoliated graphene oxide (N-LEGO) for hexavalent chromium (Cr(VI)) removal from aqueous solution. The nitrogen content of N-LEGO reached 13.28%, and the ratio of N-bonding configurations (pyri-N:amine-N:pyrro-N:grap-N) was 2.3:1.6:1:2.3. For Cr(VI) with initial concentration of 70 mg L under pH= 2, the residuary concentration after treated by N-LEGO was close to 0.004 mg L, which meets the industrial wastewater discharge standard. The Cr(VI) adsorption behavior on N-LEGO can be fitted with the pseudo-second-order kinetics and Freundlich isotherm model well. The adsorption mechanism of Cr(VI) on N-LEGO includes anions electrostatic attraction, reduction and surface chelation. Density functional theory (DFT) simulations showed that N atoms doping was feasible and thermodynamically stable, meanwhile the N-doped system was easier to adsorb CrO than HCrO. The findings of this work can provide a new idea for the development of N-doped carbon-based adsorbents for the removal of highly toxic Cr(VI) from aqueous solutions.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129184DOI Listing
August 2022

Comprehensive benchmarking of CITE-seq versus DOGMA-seq single cell multimodal omics.

Genome Biol 2022 Jun 23;23(1):135. Epub 2022 Jun 23.

Department of Medicine, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA, 15261, USA.

The recently developed method TEA-seq and similar DOGMA-seq single cell trimodal omics assays provide unprecedented opportunities for understanding cell biology, but independent evaluation is lacking. We explore the utility of DOGMA-seq compared to the bimodal CITE-seq assay in activated and stimulated human peripheral blood T cells. We find that single cell trimodal omics measurements after digitonin (DIG) permeabilization were generally better than after an alternative "low-loss lysis" (LLL) permeabilization condition. Next, we find that DOGMA-seq with optimized DIG permeabilization and its ATAC library provides more information, although its mRNA and cell surface protein libraries have slightly inferior quality, compared to CITE-seq.
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http://dx.doi.org/10.1186/s13059-022-02698-8DOI Listing
June 2022

Very-low-density lipoprotein receptor-enhanced lipid metabolism in pancreatic stellate cells promotes pancreatic fibrosis.

Immunity 2022 Jun 18. Epub 2022 Jun 18.

Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Shanghai Pudong Hospital, Fudan University, Shanghai 201399, China. Electronic address:

Lipoprotein disorder is a common feature of chronic pancreatitis (CP); however, the relationship between lipoprotein disorder and pancreatic fibrotic environment is unclear. Here, we investigated the occurrence and mechanism of pancreatic stellate cell (PSC) activation by lipoprotein metabolites and the subsequent regulation of type 2 immune responses, as well as the driving force of fibrotic aggressiveness in CP. Single-cell RNA sequencing revealed the heterogeneity of PSCs and identified very-low-density lipoprotein receptor (VLDLR) PSCs that were characterized by a higher lipid metabolism. VLDLR promoted intracellular lipid accumulation, followed by interleukin-33 (IL-33) expression and release in PSCs. PSC-derived IL-33 strongly induced pancreatic group 2 innate lymphoid cells (ILC2s) to trigger a type 2 immune response accompanied by the activation of PSCs, eventually leading to fibrosis during pancreatitis. Our findings indicate that VLDLR-enhanced lipoprotein metabolism in PSCs promotes pancreatic fibrosis and highlight a dominant role of IL-33 in this pro-fibrotic cascade.
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http://dx.doi.org/10.1016/j.immuni.2022.06.001DOI Listing
June 2022

Insights into the Regulation of Rice Seed Storability by Seed Tissue-Specific Transcriptomic and Metabolic Profiling.

Plants (Basel) 2022 Jun 14;11(12). Epub 2022 Jun 14.

College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

Non-dormant seeds are continuously aging and deteriorating during storage, leading to declining seed vigor, which is a challenge for the rice seed industry. Improving the storability of seeds is of great significance to ensure the quality of rice and national food security. Through a set of chromosome segment substitution lines population constructed using rice NIP as donor parent and rice ZS97 as recurrent parent, we performed seed storability QTL analysis and selected four non-storable NILs to further investigate the storability regulatory mechanisms underlying it. The seeds were divided into four tissues, which were the embryo, endosperm, aleurone layer, and hull, and tissue-specific transcriptome and metabolome analyses were performed on them. By exploring the common differentially expressed genes and differentially accumulated metabolites, as well as the KEGG pathway of the four non-storable NILs, we revealed that the phenylpropanoid biosynthesis pathway and diterpenoid biosynthesis pathway played a central role in regulating seed storability. Integrated analysis pinpointed 12 candidate genes that may take part in seed storability. The comprehensive analysis disclosed the divergent and synergistic effect of different seed tissues in the regulation of rice storability.
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http://dx.doi.org/10.3390/plants11121570DOI Listing
June 2022

A randomized, placebo-controlled clinical trial of hydrogen/oxygen inhalation for non-alcoholic fatty liver disease.

J Cell Mol Med 2022 Jun 23. Epub 2022 Jun 23.

The Second Affiliated Hospital of Shandong First Medical University, Tai'an, China.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide with increasing incidence consistent with obesity, type 2 diabetes and cardiovascular diseases. No approved medication was currently available for NAFLD treatment. Molecular hydrogen (H ), an anti-oxidative, anti-inflammatory biomedical agent is proved to exhibit therapeutic and preventive effect in various diseases. The purpose of this study was to investigate the effect of hydrogen/oxygen inhalation on NAFLD subjects and explore the mechanism from the perspective of hepatocyte autophagy. We conducted a randomized, placebo-controlled clinical trial of 13-week hydrogen/oxygen inhalation (China Clinical Trial Registry [#ChiCTR-IIR-16009114]) including 43 subjects. We found that inhalation of hydrogen/oxygen improved serum lipid and liver enzymes. Significantly improved liver fat content detected by ultrasound and CT scans after hydrogen/oxygen inhalation was observed in moderate-severe cases. We also performed an animal experiment based on methionine and choline-deficient (MCD) diet-induced mice model to investigate effect of hydrogen on mouse NASH. Hydrogen/oxygen inhalation improved systemic inflammation and liver histology. Promoted autophagy was observed in mice inhaled hydrogen/oxygen and treatment with chloroquine blocked the beneficial effect of hydrogen. Moreover, molecular hydrogen inhibited lipid accumulation in AML-12 cells. Autophagy induced by palmitic acid (PA) incubation was further promoted by 20% hydrogen incubation. Addition of 3-methyladenine (3-MA) partially blocked the inhibitory effect of hydrogen on intracellular lipid accumulation. Collectively, hydrogen/oxygen inhalation alleviated NAFLD in moderate-severe patients. This protective effect of hydrogen was possibly by activating hepatic autophagy.
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http://dx.doi.org/10.1111/jcmm.17456DOI Listing
June 2022

Universal tumor screening for lynch syndrome on colorectal cancer biopsies impacts surgical treatment decisions.

Fam Cancer 2022 Jun 23. Epub 2022 Jun 23.

Department of Pathology, The Ohio State University Wexner Medical Center, Optometry Clinic and Health Science Faculty Office Building, 1664 Neil Avenue, Suite 6100, Columbus, OH, 43210, USA.

Universal tumor screening (UTS) for Lynch syndrome (LS) on colorectal cancer (CRC) can be performed on biopsies or resection specimens. The advantage of biopsies is the chance to provide preoperative genetic counseling/testing (GC/T) so patients diagnosed with LS can make informed decisions regarding resection extent. We evaluated utilization of UTS on biopsies, percentage of patients with deficient mismatch repair (dMMR) who underwent GC/T preoperatively, and whether surgical/treatment decisions were impacted. We performed a retrospective review of medical records to assess CRC cases with dMMR immunohistochemical staining from 1/1/2017 to 2/26/2021. 1144 CRC patients had UTS using MMR immunohistochemistry; 559 biopsies (48.9%) and 585 resections (51.1%). The main reason UTS was not performed on biopsy was it occurred outside our health system. 58 (5%) of CRCs were dMMR and did not have MLH1 promoter hypermethylation (if MLH1 and PMS2 absent). 28/58 (48.3%) of dMMR cases were diagnosed on biopsy. Of those 28, 14 (50%) eventually underwent GC/T, and 7 (25%) had GT results prior to surgery. One of the 7 had incomplete documentation of results affecting their treatment plan. Of the remaining 6 with complete documentation, 5 underwent surgery and one was treated with immunotherapy only. Three patients elected a more extensive surgery. 6/28 (21.4%) dMMR patients identified on biopsy made an informed surgical/treatment decision based on their dMMR status/LS diagnosis. When applied, UTS on biopsy followed by genetic counseling and testing informs surgical decision-making. Process and implementation strategies are in place to overcome challenges to more broadly optimize this approach.
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http://dx.doi.org/10.1007/s10689-022-00302-3DOI Listing
June 2022

Distributed State Estimation Over Wireless Sensor Networks With Energy Harvesting Sensors.

IEEE Trans Cybern 2022 Jun 22;PP. Epub 2022 Jun 22.

This article is concerned with the distributed state estimation problem over wireless sensor networks (WSNs), where each smart sensor is capable of harvesting energy from the external environment with a certain probability. The data transmission between neighboring nodes is dependent on the energy level of each sensor, and the internode communication is deemed as a failure when the current energy level is inadequate to guarantee the normal data transmission. Considering the intermittent information exchange over WSNs, a novel distributed state estimator is first constructed via introducing a set of indicator functions, and then the evolution of the probability distribution of energy level and its steady-state distribution is systematically discussed by resorting to the eigenvalue analysis approach and the mathematical induction. Furthermore, the optimal estimator gain is derived by minimizing the trace of the estimation error covariance under known communication sequences. In addition, the convergence of the minimized upper bound of the expected estimation error covariance is analyzed under any initial condition. Finally, an illustrative example regarding the target tracking problem is provided to verify the validity of the obtained theoretical results.
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http://dx.doi.org/10.1109/TCYB.2022.3179280DOI Listing
June 2022

Mass cytometry reveals immune atlas of urothelial carcinoma.

BMC Cancer 2022 Jun 20;22(1):677. Epub 2022 Jun 20.

Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, China.

Immunotherapy has emerged as a robust clinical strategy for cancer treatment. PD1/PD-L1 inhibitors have been used as second-line therapy for urothelial carcinoma due to the high tumor mutational burden. Despite the efficacy of the treatment is significant, the response rate is still poor. The tumor immune microenvironment plays a key role in the regulation of immunotherapeutic efficacy. However, a comprehensive understanding of the intricate microenvironment in clinical samples remains unclear. To obtain detailed systematic tumor immune profile, we performed an in-depth immunoassay on 12 human urothelial carcinoma tissue samples and 14 paratumor tissue samples using mass cytometry. Among the large number of cells assayed, we identified 71 T-cell phenotypes, 30 tumor-associated macrophage phenotypes. T cell marker expression profiles showed that almost all T cells in the tumor tissue were in a state of exhaustion. CD38 expression on tumor-associated macrophages (TAMs) was significantly higher than PDL1, and CD38 TAMs were closely associated with immunosuppression. CD38 may be a more suitable target for immunotherapy in urothelial carcinoma compared to PD1/PDL1. This single-cell analysis of clinical samples expands our insights into the immune microenvironment of urothelial carcinoma and reveals potential biomarkers and targets for immunotherapy development.
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http://dx.doi.org/10.1186/s12885-022-09788-7DOI Listing
June 2022

Deep Learning-Based Sensor Array: 3D Fluorescence Spectra of Gold Nanoclusters for Qualitative and Quantitative Analysis of Vitamin B Derivatives.

Anal Chem 2022 Jun 18. Epub 2022 Jun 18.

Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, School of Pharmacy, Fujian Medical University, Fuzhou 350004, China.

Vitamin B derivatives (VB6Ds) are of great importance for all living organisms to complete their physiological processes. However, their excess in the body can cause serious problems. What is more, the qualitative and quantitative analysis of different VB6Ds may present significant challenges due to the high similarity of their chemical structures. Also, the transfer of deep learning model from one task to a similar task needs to be present more in the fluorescence-based biosensor. Therefore, to address these problems, two deep learning models based on the intrinsic fingerprint of 3D fluorescence spectra have been developed to identify five VB6Ds. The accuracy ranges of a deep neural network (DNN) and a convolutional neural network (CNN) were 94.44-97.77% and 97.77-100%, respectively. After that, the developed models were transferred for quantitative analysis of the selected VB6Ds at a broad concentration range (1-100 μM). The determination coefficient () values of the test set for DNN and CNN were 93.28 and 97.01%, respectively, which also represents the outperformance of CNN over DNN. Therefore, our approach opens new avenues for qualitative and quantitative sensing of small molecules, which will enrich fields related to deep learning, analytical chemistry, and especially sensor array chemistry.
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http://dx.doi.org/10.1021/acs.analchem.2c00655DOI Listing
June 2022

Reversible Al Metal Anodes Enabled by Amorphization for Aqueous Aluminum Batteries.

J Am Chem Soc 2022 Jun 18. Epub 2022 Jun 18.

Materials Science and Engineering Program and Walker Department of Mechanical Engineering, Texas Materials Institute, The University of Texas at Austin, Austin, Texas 78712, United States.

Aqueous aluminum metal batteries (AMBs) are regarded as one of the most sustainable energy storage systems among post-lithium-ion candidates, which is attributable to their highest theoretical volumetric capacity, inherent safe operation, and low cost. Yet, the development of aqueous AMBs is plagued by the incapable aluminum plating in an aqueous solution and severe parasitic reactions, which results in the limited discharge voltage, thus making the development of aqueous AMBs unsuccessful so far. Here, we demonstrate that amorphization is an effective strategy to tackle these critical issues of a metallic Al anode by shifting the reduction potential for Al deposition. The amorphous aluminum (-Al) interfacial layer is triggered by an in situ lithium-ion alloying/dealloying process on a metallic Al substrate with low strength. Unveiled by experimental and theoretical investigations, the amorphous structure greatly lowers the Al nucleation energy barrier, which forces the Al deposition competitive to the electron-stealing hydrogen evolution reaction (HER). Simultaneously, the inhibited HER mitigates the passivation, promoting interfacial ion transfer kinetics and enabling steady aluminum plating/stripping for 800 h in the symmetric cell. The resultant multiple full cells using [email protected] anodes deliver approximately a 0.6 V increase in the discharge voltage plateau compared to that of bare Al-based cells, which far outperform all reported aqueous AMBs. In both symmetric cells and full cells, the excellent electrochemical performances are achieved in a noncorrosive, low-cost, and fluorine-free Al(SO) electrolyte, which is ecofriendly and can be easily adapted for sustainable large-scale applications. This work brings an intriguing picture of the design of metallic anodes for reversible and high-voltage AMBs.
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http://dx.doi.org/10.1021/jacs.2c04820DOI Listing
June 2022

Mussel-Inspired Microgel Encapsulated NLRP3 Inhibitor as a Synergistic Strategy Against Dry Eye.

Front Bioeng Biotechnol 2022 1;10:913648. Epub 2022 Jun 1.

Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, China.

The inflammatory response mediated by oxidative stress is the main pathogenesis of dry eye, but clinical observations have shown that scavenging oxygen-free radicals alone has limited therapeutic effect. Moreover, the unique anatomy and physiology of the ocular surface result in low bioavailability of drugs, and higher concentration is required to achieve the desired efficacy, which, however, may bring systemic side effects. These problems pose a challenge, but the revelation of the ROS-NLRP3-IL-1β signaling axis opens up new possibilities. In this investigation, an NLRP3 inhibitor was successfully encapsulated in polydopamine-based microgels and used for dry eye treatment. It was demonstrated that the well-designed microgels exhibited good biocompatibility, prolonged drug retention time on the ocular surface, and effective inhibition of corneal epithelial damage and cell apoptosis. In addition, due to the synergistic effect, the NLRP3 inhibitor-loaded microgels could exert enhanced oxygen radical scavenging and inflammation-inhibiting effects at a lower dose than monotherapy. These findings suggest that polydopamine-based microgels have advantages as ocular surface drug delivery platforms and have promising applications in oxidative damage-related inflammatory diseases in synergy with anti-inflammatory drugs.
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http://dx.doi.org/10.3389/fbioe.2022.913648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198461PMC
June 2022

Organoids From Mucinous Appendiceal Adenocarcinomas as High-Fidelity Models for Individual Therapy.

Front Med (Lausanne) 2022 2;9:829033. Epub 2022 Jun 2.

Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.

Background: Mucinous appendiceal adenocarcinoma (MAA) is a rare, heterogeneous disease. Patients with unrespectable mucinous appendiceal adenocarcinoma presenting with peritoneal spread are treated by intraperitoneal chemotherapy, hyperthermic intraperitoneal chemotherapy, systemic chemotherapy, or targeted therapy. However, there are no guidelines for efficacious drugs against mucinous appendiceal adenocarcinoma. Therefore, relevant high-fidelity models should be investigated to identify effective drugs for individual therapy.

Methods: Surgical tumor specimens were obtained from a mucinous appendiceal adenocarcinoma patient. The tissue was digested and organoid culture was established. H&E and immunohistochemistry staining as well as DNA sequencing was performed on tissue and organoid. The pathological characteristics and gene mutations of the organoid were compared to those of the original tumor. Drug sensitivity tests were performed on organoid and the patient clinical responds to chemotherapy and targeted therapy was compared.

Results: Organoids were successfully established and stably passaged. Pathological characteristics of organoids including H&E staining and expression of protein markers (CK20, CDX-2, STAB2, CD7, PAX8) were consistent to those of the original tumor. Moreover, the organoids carried the same gene mutations as the primary tumor. Sensitivity of the organoids to chemotherapeutic drugs and tyrosine kinase inhibitors included: 5-FU (IC 43.95 μM), Oxaliplatin (IC 23.49 μM), SN38 (IC 1.02 μM), Apatinib (IC 0.10 μM), Dasatinib (IC 2.27 μM), Docetaxel (IC 5.26 μM), Regorafenib (IC 18.90 μM), and Everolimus (IC 9.20 μM). The sensitivities of organoid to these drugs were comparable to those of the patient's clinical responses.

Conclusion: The mucinous appendiceal adenocarcinoma organoid model which retained the characteristics of the primary tumor was successfully established. Combined organoid-based drug screening and high throughput sequencing provided a promising way for mucinous appendiceal adenocarcinoma treatment.
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http://dx.doi.org/10.3389/fmed.2022.829033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201037PMC
June 2022

GZR18, a novel long-acting GLP-1 analog, demonstrated positive in vitro and in vivo pharmacokinetic and pharmacodynamic characteristics in animal models.

Eur J Pharmacol 2022 Jun 16;928:175107. Epub 2022 Jun 16.

Gan & Lee Pharmaceuticals, Beijing, China. Electronic address:

GZR18 is a novel analog of glucagon-like peptide-1 (GLP-1). This study evaluates the pharmacology, pharmacokinetics, and efficacy of GZR18, and its potential for the treatment of Type 2 diabetes mellitus (T2DM). In vitro pharmacology and activity of GZR18 were characterized by a binding assay of GZR18 using human serum albumin (HSA), an activation assay in human GLP-1 receptor-expressing cell lines, and its effect on glucose-stimulated insulin secretion (GSIS) in primary mice islets. Pharmacokinetic profiling was performed in Sprague Dawley rats and cynomolgus monkeys, and efficacy evaluated using GZR18 single or repeated doses in db/db mice. GZR18 showed similar binding affinity for HSA and GLP-1 receptor compared with semaglutide and liraglutide. GZR18 increased GSIS, which was confirmed by dynamic islet perifusion and fluorescence imaging using PKZnR-5 for real-time detection. In cynomolgus monkeys, the average GZR18 maximal concentration was 527 nmol L, the terminal half-life (T) was 61.3 h, and the time to maximum concentration was 14 h. Single-dose GZR18 lowered blood glucose levels and reduced body weight over 72 h in db/db mice. GZR18 successive administration (every three days for 33 days, i.e. 11 doses) lowered nonfasting and fasting blood glucose levels (p < 0.05 versus control) and glycated hemoglobin, following the 11th dose. Food and water consumption in db/db mice was lowered following repeated doses of GZR18 (p < 0.05 versus control), without a reduction in body weight. These results demonstrate the potential of GZR18 as a long-acting GLP-1 analog for the treatment of T2DM.
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http://dx.doi.org/10.1016/j.ejphar.2022.175107DOI Listing
June 2022

miR-107 attenuates sepsis-induced myocardial injury by targeting PTEN and activating the PI3K/AKT signaling pathway.

Cells Tissues Organs 2022 Jun 17. Epub 2022 Jun 17.

Sepsis is a public health problem worldwide. This study investigated the mechanism of miR-107 on sepsis-induced myocardial injury. Sepsis rat models were established by cecal ligation and puncture, and the cell model was established using lipopolysaccharide (LPS)-induced cardiomyocytes. Cardiac function indexes of rats were measured using echocardiography. Pathological changes in the rat myocardium were observed using histological staining. Expressions of miR-107 in the serum of rats and cardiomyocyte were detected after the treatment of miR-107 mimic or/and pcDNA3.1-PTEN, followed by assessment of cell cycle, proliferation, and apoptosis. Binding sites of miR-107 and PTEN were predicted. PTEN, PI3K, p-PI3K, AKT, and p-AKT expressions in LPS-induced cardiomyocytes were measured. miR-107 was significantly downregulated in the serum of CLP rats and LPS-induced cardiomyocytes. miR-107 overexpression remarkably improved cardiac function and histological changes, decreased inflammatory factors, and alleviated the sepsis-induced myocardial injury in rats. In LPS-induced cardiomyocytes, miR-107 overexpression increased cardiomyocyte proliferation, inhibited apoptosis, and enhanced the proportion of cardiomyocytes arrested in S and G2/M phases. miR-107 targeted PTEN. PTEN overexpression partially reversed the inhibition of miR-107 mimic on cardiomyocyte apoptosis. miR-107 overexpression activated the PI3K/AKT pathway by inhibiting PTEN. To conclude, miR-107 activates the PI3K/AKT pathway by inhibiting PTEN, thus attenuating sepsis-induced myocardial injury and LPS-induced cardiomyocyte apoptosis.
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http://dx.doi.org/10.1159/000525476DOI Listing
June 2022

Instrumental Texture Assessment of IDDSI Texture Levels for Dysphagia Management. Part 1: Thickened Fluids.

J Texture Stud 2022 Jun 19. Epub 2022 Jun 19.

School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China.

Thickened fluids are commonly used in the medical management of individuals who suffer from swallowing difficulty (known as dysphagia). International Dysphagia Diet Standardisation Initiative (IDDSI) developed a standardised international terminology and description for texture-modified foods and thickened fluids to allow dysphagia patients to receive the correct consistency of food/drink. Syringe flow test and fork drip test are suggested by IDDSI to identify the drink category (IDDSI Level 1 - 4). These practical methods are widely welcomed by carers and patients because of their simplicity. However, these methods are not most feasible for industrial applications, where objective measurements are required for industry for the purpose of quality control of such products. Therefore, our aim in this work was to develop quantitative and objective measurements that best describe IDDSI level category for use as an objective framework. Two measuring techniques, syringe flow test and fork drip test, recommended by IDDSI were evaluated in two different sets of experiment. Participants were recruited to categorise fluid samples of known texture parameters using syringe flow test and fork drip test techniques. The apparent stress measured from Ball-Back Extrusion (BBE) technique for each of the fluid category (IDDSI Level 1 - 4) were calculated. Bands of apparent stress for each of the fluid category were developed from two measuring techniques, syringe flow test and fork drip test. An inconsistency was observed between these two measuring techniques for IDDSI Level 3 fluid due to different dominating factors in the two tests. However, we proposed to combine the results from the two experiments to develop a quantitative range for each IDDSI Level as objective complements to the IDDSI Framework. Thickened fluid manufacturers are encouraged to follow the proposed guidelines presented once they are clinically validated and use them fine tune their products, thus enhancing the safety for individuals with dysphagia.
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http://dx.doi.org/10.1111/jtxs.12707DOI Listing
June 2022

Fecal microbiota transplantation for diseases: Therapeutic potential, methodology, risk management in clinical practice.

Life Sci 2022 Jun 15:120719. Epub 2022 Jun 15.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China.

Background: More than 95 % of human diseases may be related to the disturbance of gut microbes. As a treatment method that extensively regulates the gut microbes, fecal microbiota transplantation (FMT) has proven to be an effective therapy for some diseases, becoming a topic of interest among clinicians, patients and scientists.

Aim: To review the latest clinical research results of FMT in the treatment of various diseases and the methodology and risk management in clinical application.

Methods: Search PubMed and Web of Science for reliable research results of clinical treatment of FMT within 5-10 years, as well as application guidelines and risk management policies in different regions.

Results: As a measure of allogeneic/autologous microbiota transplantation, FMT has been used to treat a variety of diseases. By reviewing the clinical studies of FMT in gastrointestinal diseases, metabolic diseases, neurological diseases and malignant tumors, the various mechanisms in the treatment of diseases are summarized. Such as regulation of receptor microbiota composition, specific metabolites, phage function and immune response. In addition, potential risk factors, donor stool screening indicators, recipient self-specificity and possible prognostic marker molecules in the course of FMT treatment were generalized.

Conclusions: The potential regulatory mechanisms, risk factors and targets of FMT in gastrointestinal diseases, metabolic diseases, malignancies and neurological diseases were reviewed and proposed. It provides a theoretical basis for the establishment of a standardized treatment system for FMT and a breakthrough in treatment technology.
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http://dx.doi.org/10.1016/j.lfs.2022.120719DOI Listing
June 2022

Dual nicotinic acetylcholine receptor subunit gene knockouts reveal limits to functional redundancy.

Pestic Biochem Physiol 2022 Jun 11;184:105118. Epub 2022 May 11.

Bio21 Molecular Science and Biotechnology Institute, School of BioSciences, The University of Melbourne, Parkville 3010, Australia. Electronic address:

The nicotinic acetylcholine receptor (nAChR) subunit gene family consists of ten members in Drosophila melanogaster. The mature nAChR is a pentamer assembled from these subunits. Despite recent advances in the in vitro expression of some receptor subunit combinations (nAChR subtypes), the in vivo combinations and stoichiometry of these subtypes remains poorly defined. In addition, there are many potential nAChR signalling roles for different subtypes in insect behaviour, development and physiology. Prior work has shown that nAChR subunit mutants can display altered sleep and mating behaviour, disrupted hormone signalling and reduced locomotion, climbing ability and longevity. Teasing out the specific receptor subunits that are involved in these different functions is potentially made more difficult given that the structural similarity between members of gene families often means that there is a degree of functional redundancy. In order to circumvent this, we created a dual knockout strain for the Dα1 and Dβ2 nAChR subunit genes and examined four traits including insecticide resistance. These subunits had been previously implicated in the response to a neonicotinoid insecticide, imidacloprid. The use of the dual knockout revealed that Dα1 and Dβ2 subunits are involved in signalling that leads to the inflation of wings following adult emergence from the pupal case. The Dβ1 subunit had previously been implicated as a contributor to this function. The lack of a phenotype or low penetrance of the phenotype in the Dα1 and Dβ2 single mutants compared to the dual knockout suggests that these subunits are, to some extent, functionally redundant. We also observed stronger reductions in climbing ability and longevity in the dual knockout. Our findings demonstrate that a dual knockout approach to examining members of the nAChR subunit gene family may increase the power of genetic approaches linking individual subunits and combinations thereof to particular biological functions. This approach will be valuable as the nAChRs are so widely expressed in the insect brain that they are likely to have many functions that hereto remain undetected.
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http://dx.doi.org/10.1016/j.pestbp.2022.105118DOI Listing
June 2022
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