Publications by authors named "Bo Zhang"

5,475 Publications

  • Page 1 of 1

Azobenzene-Based Solar Thermal Fuels: A Review.

Nanomicro Lett 2022 Jun 29;14(1):138. Epub 2022 Jun 29.

School of Materials Science and Engineering, Tianjin University, Tianjin, 300350, People's Republic of China.

The energy storage mechanism of azobenzene is based on the transformation of molecular cis and trans isomerization, while NBD/QC, DHA/VHF, and fulvalene dimetal complexes realize the energy storage function by changing the molecular structure. Acting as "molecular batteries," they can exhibit excellent charging and discharging behavior by converting between trans and cis isomers or changing molecular structure upon absorption of ultraviolet light. Key properties determining the performance of STFs are stored energy, energy density, half-life, and solar energy conversion efficiency. This review is aiming to provide a comprehensive and authoritative overview on the recent advancements of azobenzene molecular photoswitch system in STFs fields, including derivatives and carbon nano-templates, which is emphasized for its attractive performance. Although the energy storage performance of Azo-STFs has already reached the level of commercial lithium batteries, the cycling capability and controllable release of energy still need to be further explored. For this, some potential solutions to the cycle performance are proposed, and the methods of azobenzene controllable energy release are summarized. Moreover, energy stored by STFs can be released in the form of mechanical energy, which in turn can also promote the release of thermal energy from STFs, implying that there could be a relationship between mechanical and thermal energy in Azo-STFs, providing a potential direction for further research on Azo-STFs.
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http://dx.doi.org/10.1007/s40820-022-00876-8DOI Listing
June 2022

Circ_0062582 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells in vitro by elevating SMAD5 expression through sponging miR-197-3p.

Cells Tissues Organs 2022 Jun 28. Epub 2022 Jun 28.

Circular RNAs (circRNAs) play crucial roles in many human diseases. However, the functions of circRNAs in osteoporosis (OP) are barely reported. In this study, we aimed to explore the function of circ_0062582 in osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. Circ_0062582 and SMAD5 were downregulated and miR-197-3p was upregulated in OP patients and increased in osteoblast medium (OM)-induced hBMSCs in vitro. Circ_0062582 knockdown inhibited the viability and osteogenic differentiation of hBMSCs. Circ_0062582 directly targeted miR-197-3p and miR-197-3p inhibition reversed the effects of circ_0062582 on hBMSC viability and osteogenic differentiation. SMAD5 was the target gene of miR-197-3p. SMAD5 overexpression promoted the viability and osteogenic differentiation of hBMSCs and attenuated miR-197-3p-mediated suppressive roles in hBMSC viability and osteogenic differentiation. In conclusion, circ_0062582 sponged miR-197-3p to elevate SMAD5 expression, thereby inducing hBMSC proliferation and osteogenic differentiation in vitro.
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http://dx.doi.org/10.1159/000525703DOI Listing
June 2022

Patatin-like phospholipase A-induced alterations in lipid metabolism and jasmonic acid production affect the heat tolerance of Gracilariopsis lemaneiformis.

Mar Environ Res 2022 Jun 20;179:105688. Epub 2022 Jun 20.

Key Laboratory of Marine Biotechnology of Zhejiang Province, School of Marine Sciences, Ningbo University, Ningbo, 315211, Zhejiang, China. Electronic address:

High temperatures seriously limit the growth and productivity of Gracilariopsis lemaneiformis. By hydrolyzing glycerolipids into lysophospholipids (LPs) and free fatty acids (FFAs), patatin-like phospholipase A (pPLA) plays an important role in stress responses. GlpPLA expression was up-regulated under heat stress, however, the regulation of pPLA in heat tolerance of G. lemaneiformis is unknown. In this study, G. lemaneiformis under heat stress was treated with bromoenololide (BEL), a chemical inhibitor of pPLA, to evaluate the cellular function of pPLA in this species. When pPLA was inhibited through BEL treatment, the sensitivity of G. lemaneiformis to heat stress increased and the biomass and maximum and effective quantum yield of photosystem II decreased. Moreover, BEL treatment resulted in a significant decrease in many lipid molecular species, all of which are mainly composed of 16C, 18C, and 20C fatty acids. Consistently, FFA levels and LPs contents in G. lemaneiformis under BEL treatment showed a significant decrease. The first step in the synthesis of jasmonic acid (JA) is the lipoxygenase (LOX)-mediated oxygenation of linolenic acid (C18:3). BEL treatment decreased JA and C18:3 accumulation and markedly downregulated the expression of GILOX under heat stress. Together, these results indicate that pPLA is closely related to the growth of G. lemaneiformis under heat stress, and pPLA is involved in the lipid metabolism and JA biosynthesis of G. lemaneiformis in response to heat stress. This research broadens the understanding of the heat stress adaptation mechanism of G. lemaneiformis.
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http://dx.doi.org/10.1016/j.marenvres.2022.105688DOI Listing
June 2022

Construction of a Tumor Immune Microenvironment-Related Prognostic Model in BRAF-Mutated Papillary Thyroid Cancer.

Front Endocrinol (Lausanne) 2022 8;13:895428. Epub 2022 Jun 8.

Department of Nuclear Medicine, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China.

BRAF mutation is a representative oncogenic mutation, with a frequency of 60% in papillary thyroid carcinoma (PTC), but the reasons for the poor prognosis and more aggressive course of BRAF-mutated PTC are controversial. Tumor immune microenvironment (TIME) is an essential factor permitting the development and progression of malignancy, but whether TIME participates in the prognosis of BRAF-mutated PTC has not yet been reported. The primary goal of the present study was to provide a comprehensive TIME-related prognostic model to increase the predictive accuracy of progression-free survival (PFS) in patients with BRAF-mutated PTC. In this study, we analyzed the mRNA-seq data and corresponding clinical data of PTC patients obtained from the TCGA database. By calculating the TIME scores (immune score, stromal score and ESTIMATE score), the BRAF mutation group (n=237) was dichotomized into the high- and low-score groups. By functional analysis of differentially expressed genes (DEGs) in different high/low score groups, we identified 2 key TIME-related genes, and , which affected PFS in BRAF-mutated PTC. A risk scoring system was developed by multivariate Cox analysis based on the abovementioned 2 TIME-related genes. Then, the BRAF-mutated cohort was divided into the high- and low-risk groups using the median risk score as a cutoff. A high risk score correlated positively with a higher expression level but negatively with PFS in BRAF-mutated PTC. Ultimately, a nomogram was constructed by combining risk score with clinical parameter (Tumor stage), and the areas under the ROC curve (AUCs) of the nomogram for predicting 1-, 3- and 5-year PFS were then calculated and found to be 0.694, 0.707 and 0.738, respectively, indicating the improved accuracy and clinical utility of the nomogram versus the risk score model in the BRAF-mutated PTC cohort. Moreover, we determined the associations between prognostic genes or risk score and immune cell infiltration by two-way ANOVA. In the high-risk score, high HTR3A expression, and high NIPAL4 expression groups, higher infiltration of immune cells was found. Collectively, these findings confirm that the nomogram is effective in predicting the outcome of BRAF-mutated PTC and will add a spatial dimension to the developing risk stratification system.
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http://dx.doi.org/10.3389/fendo.2022.895428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9215106PMC
June 2022

Correlation Between Ictal Signs and Anatomical Subgroups in Temporal Lobe Seizures: A Stereoelectroencephalography Study.

Front Neurol 2022 10;13:917079. Epub 2022 Jun 10.

Department of Neurosurgery, Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing Key Laboratory of Epilepsy Research, Sanbo Brain Hospital, Capital Medical University, Beijing, China.

Objective: Ictal semiology is a fundamental part of the presurgical evaluation of patients with temporal lobe epilepsy. We aimed to identify different anatomical and semiologic subgroups in temporal lobe seizures, and investigate the correlation between them.

Methods: We enrolled 93 patients for whom stereoelectroencephalography exploration indicated that the seizure-onset zone was within the temporal lobe. Ictal signs and concomitant stereoelectroencephalography changes were carefully reviewed and quantified, and then cluster analysis and the Kendall correlation test were used to associate ictal signs with the temporal structures of patients.

Results: Clustering analysis identified two main groups of temporal structures. Group 1 consisted of the medial temporal lobe structures and the temporal pole, which were divided into two subgroups. Group 1A included the hippocampal head, hippocampal body, and amygdala, and this subgroup correlated significantly with oroalimentary automatisms, feeling of fear, and epigastric auras. Group 1B included the hippocampal tail, temporal pole, and parahippocampal gyrus, and this subgroup correlated significantly with manual and oroalimentary automatisms. Group 2 consisted of the cortical structures of the temporal lobe and was also divided into two subgroups. Group 2A included the superior and middle temporal gyrus, correlated significantly with bilateral rictus/facial contraction, generalized tonic-clonic seizure, and manual automatisms. Group 2B included Heschl's gyrus, the inferior temporal gyrus, and the fusiform gyrus, and this subgroup correlated significantly with auditory auras, focal hypokinetics, unilateral upper and lower limbs tonic posture/clonic signs, head/eye deviation, unilateral versive signs, and generalized tonic-clonic seizure.

Significance: The temporal structures can be categorized according to the level at which each structure participates in seizures, and different anatomical subgroups can be correlated with different ictal signs. Identifying specific semiologic features can help us localize the epileptogenic zone and thus develop stereoelectroencephalography electrode implantation and surgical resection protocols for patients with temporal lobe epilepsy.
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http://dx.doi.org/10.3389/fneur.2022.917079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226566PMC
June 2022

Ectopic Colonization and Immune Landscapes of Periodontitis Microbiota in Germ-Free Mice With Streptozotocin-Induced Type 1 Diabetes Mellitus.

Front Microbiol 2022 10;13:889415. Epub 2022 Jun 10.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

A two-way relationship between diabetes and periodontitis has been discussed recently. Periodontitis microbiota might affect the immune homeostasis of diabetes, but the molecular mechanism of their interactions is still not clear. The aims of this study were to clarify the possible immune regulatory effects of periodontitis microbiota on diabetes and the correlation between immunomodulation and ectopic colonization. A model of germ-free mice with streptozotocin-induced type 1 diabetes mellitus (T1D), which was orally inoculated with mixed saliva samples for 2 weeks, was used in this study. Those mice were randomly divided into two groups, namely, SP (where the T1D mice were orally inoculated with mixed saliva samples from periodontitis patients) and SH (where the T1D mice were orally inoculated with mixed saliva samples from healthy subjects). Ectopic colonization of saliva microbiota was assessed using culture-dependent method and Sanger sequencing, and the composition of gut microbiota was analyzed using 16S rRNA gene sequencing. Changes in 15 types of immune cells and six cytokines either from the small intestine or spleen were detected by multicolor flow cytometry. The correlation between gut microbiota and immune cells was evaluated by redundancy analysis. Although periodontitis microbiota minorly colonized the lungs, spleens, and blood system, they predominantly colonized the gut, which was mainly invaded by . SH and SP differed in beta diversity of the gut bacterial community. Compared to SH, microbial alteration in small intestine occurred with an increase of , , , , and a decrease of in SP. More types of immune cells were disordered in the spleen than in the small intestine by periodontitis microbiota, mainly with a dramatical increase in the proportion of macrophages, plasmacytoid dendritic cells (pDCs), monocytes, group 3 innate lymphoid cells, CD4-CD8- T cells and Th17 cells, as well as a decline of αβT cells in SP. Cytokines of IFNγ, IL17, and IL22 produced by CD4 + T cells as well as IL22 produced by ILCs of small intestine rose in numbers, and the intestinal and splenic pDCs were positively regulated by gut bacterial community in SP. In conclusion, periodontitis microbiota invasion leads to ectopic colonization of the extra-oral sites and immune cells infiltration, which might cause local or systemic inflammation. Those cells are considered to act as a "bridge" between T1D and periodontitis.
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http://dx.doi.org/10.3389/fmicb.2022.889415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226645PMC
June 2022

Full-Length Transcriptomics Reveals Complex Molecular Mechanism of Salt Tolerance in L.

Front Plant Sci 2022 9;13:917338. Epub 2022 Jun 9.

Key Laboratory of Grassland Resources and Ecology of Western Arid Region, Ministry of Education, College of Grassland Science, Xinjiang Agricultural University, Urumqi, China.

L. (commonly known as smooth bromegrass) is a grass species with high nutritional value, great palatability, cold tolerance, and grazing resistance, which has been widely cultivated for pasture and sand fixation in northern and northwestern China. Salt stress is a main environmental factor limiting growth and production of smooth bromegrass. In this study, we performed PacBio Iso-Seq to construct the first full-length transcriptome database for smooth bromegrass under 300 mM NaCl treatment at different time points. Third-generation full-length transcriptome sequencing yielded 19.67 G polymerase read bases, which were assembled into 355,836 full-length transcripts with an average length of 2,542 bp. A total of 116,578 differentially expressed genes were obtained by comparing the results of third-generation sequencing and second-generation sequencing. GO and KEGG enrichment analyses revealed that multiple pathways were differently activated in leaves and roots. In particular, a number of genes participating in the molecular network of plant signal perception, signal transduction, transcription regulation, antioxidant defense, and ion regulation were affected by NaCl treatment. In particular, the CBL-CIPK, MAPK, ABA signaling network, and SOS core regulatory pathways of Ca signal transduction were activated to regulate salt stress response. In addition, the expression patterns of 10 salt-responsive genes were validated by quantitative real-time PCR, which were consistent with those detected by RNA-Seq. Our results reveal the molecular regulation of smooth bromegrass in response to salt stress, which are important for further investigation of critical salt responsive genes and molecular breeding of salt-tolerant smooth bromegrass.
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http://dx.doi.org/10.3389/fpls.2022.917338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219601PMC
June 2022

Preoperative duration of pain is associated with chronic opioid use after adult spinal deformity surgery.

Spine Deform 2022 Jun 24. Epub 2022 Jun 24.

Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, 601 North Caroline Street, JHOC 5241, Baltimore, MD, 21287, USA.

Purpose: Few studies have explored the association between preoperative patient-reported measures and chronic opioid use following adult spinal deformity (ASD) surgery. We sought to explore the association between preoperative duration of pain, as well as other patient-reported factors, and chronic opioid use after ASD surgery.

Methods: We retrospectively reviewed our U.S. academic tertiary care hospital's database of ASD patients. We included patients 18 years or older who underwent arthrodesis of four or more spinal levels from January 2008 to February 2018, with 2-year follow-up. The primary outcome variable was chronic opioid use, defined as opioid use at both 1 and 2 years postoperatively. We analyzed patient characteristics; duration of preoperative pain (<4 years or ≥4 years); radiculopathy; preoperative Scoliosis Research Society-22r (SRS-22r) score; Oswestry Disability Index (ODI) value; and surgical characteristics.

Results: Of 119 patients who met the inclusion criteria, 93 (78%) were women, and mean ± standard deviation age was 59 ± 13. Sixty patients (50%) reported preoperative opioid use, and 35 (29%) reported chronic opioid use. Preoperative opioid use was associated with higher odds of chronic use (adjusted odds ratio, 5.9; 95% confidence interval 1.6-21), as was preoperative pain duration of ≥4 years (adjusted odds ratio, 3.3; 95% confidence interval 1.1-9.8). Patient characteristics, surgical variables, ODI value, and SRS-22r score were not significantly associated with chronic postoperative opioid use.

Conclusion: Preoperative opioid use and duration of pain of ≥4 years were associated with higher odds of chronic opioid use after ASD surgery.

Level Of Evidence: III.
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http://dx.doi.org/10.1007/s43390-022-00531-7DOI Listing
June 2022

Bifunctional Phenol-enabled Sequential Polymerization Strategy for Printable Tough Hydrogels.

Macromol Rapid Commun 2022 Jun 24:e2200419. Epub 2022 Jun 24.

Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, 710069, China.

Hydrogels are promising material candidates in engineering soft robotics, mechanical sensors, biomimetic regenerative medicine, etc. However, developing multinetwork hydrogels with high mechanical properties and excellent printability is still challenging. Here, we report a bifunctional phenol-enabled sequential polymerization (BPSP) strategy to fabricate high-performance multinetwork hydrogels under the orthogonal catalysis of efficient ruthenium photochemistry. Benefiting from this bifunctional design, phenols can sequentially polymerize with typical monomers and themselves to fabricate various phenol-containing polymers (Ph-Ps) and Ph-Ps-based multinetwork tough hydrogels, respectively. The as-prepared hydrogels have maximum stress of 0.75 MPa and toughness of 2.2 MJ/m under the critical strain of 800%. These property parameters are a maximum of 16 times higher than that of the phenol-postmodified and phenol-free hydrogels. Moreover, the rapid coupling polymerization of phenols can shorten the gelation times of hydrogels to as low as ∼4 s, which enables its printable property for customizable applications. As a proof of concept, a 3D scaffold-like structure is optimized as highly sensitive mechanical sensors for detecting various human motions. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/marc.202200419DOI Listing
June 2022

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

Small 2022 Jun 24:e2201558. Epub 2022 Jun 24.

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

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

In Vitro and In Vivo Characterization of a New Strain of Mosquito Flavivirus Derived from .

Viruses 2022 Jun 14;14(6). Epub 2022 Jun 14.

Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.

Mosquito-specific flaviviruses comprise a group of insect-specific viruses with a single positive RNA, which can affect the duplication of mosquito-borne viruses and the life growth of mosquitoes, and which have the potential to be developed as a vaccine platform for mosquito-borne viruses. In this study, a strain of mosquito flavivirus (MFV) YN15-283-02 was detected in collected from Yunnan, China. The isolation of the purified MFV YN15-283-02 from cell culture failed, and the virus was then rescued by an infectious clone. To study the biological features of MFV YN15-283-02 in vitro and in vivo, electron microscopy, phylogenetic tree, and viral growth kinetic analyses were performed in both cell lines and mosquitoes. The rescued MFV (rMFV) YN15-283-02 duplicated and reached a peak in C6/36 cells at 6 d.p.i. with approximately 2 × 10 RNA copies/μL (RNA to cell ratio of 0.1), but without displaying a cytopathic effect. In addition, the infection rate for the rMFV in show a low level in both larvae (≤15%) and adult mosquitoes (≤12%).
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http://dx.doi.org/10.3390/v14061298DOI Listing
June 2022

Inhibition of -Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication.

Int J Mol Sci 2022 Jun 12;23(12). Epub 2022 Jun 12.

Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.

Cancer suppression through the inhibition of -acetyltransferase 10 (NAT10) by its specific inhibitor Remodelin has been demonstrated in a variety of human cancers. Here, we report the inhibitory effects of Remodelin on prostate cancer (PCa) cells and the possible associated mechanisms. The prostate cancer cell lines VCaP, LNCaP, PC3, and DU145 were used. The in vitro proliferation, migration, and invasion of cells were measured by a cell proliferation assay, colony formation, wound healing, and Transwell assays, respectively. In vivo tumor growth was analyzed by transplantation into nude mice. The inhibition of NAT10 by Remodelin not only suppressed growth, migration, and invasion in vitro, but also the in vivo cancer growth of prostate cancer cells. The involvement of NAT10 in DNA replication was assessed by EdU labeling, DNA spreading, iPOND, and ChIP-PCR assays. The inhibition of NAT10 by Remodelin slowed DNA replication. NAT10 was detected in the prereplication complex, and it could also bind to DNA replication origins. Furthermore, the interaction between NAT10 and CDC6 was analyzed by Co-IP. The altered expression of NAT10 was measured by immunofluorescence staining and Western blotting. Remodelin markedly reduced the levels of CDC6 and AR. The expression of NAT10 could be altered under either castration or noncastration conditions, and Remodelin still suppressed the growth of in vitro-induced castration-resistant prostate cancers. The analysis of a TCGA database revealed that the overexpression of NAT10, CDC6, and MCM7 in prostate cancers were correlated with the Gleason score and node metastasis. Our data demonstrated that Remodelin, an inhibitor of NAT10, effectively inhibits the growth of prostate cancer cells under either no castration or castration conditions, likely by impairing DNA replication.
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http://dx.doi.org/10.3390/ijms23126573DOI Listing
June 2022

Investigation of Synergistic Effects and Kinetics on Co-Pyrolysis of and Waste Tires.

Int J Environ Res Public Health 2022 Jun 9;19(12). Epub 2022 Jun 9.

Key Laboratory of Energy Thermal Conversion and Control of Ministry of Education, School of Energy and Environment, Southeast University, Nanjing 210096, China.

A thermogravimetric analysis is used to analyze the thermal kinetics and investigate the synergistic effects between (AP) and waste tires (WTS) in a temperature range of 50-900 °C under three heating rates (15, 25, and 35 °C/min). Two model-free methods (FWO and KAS) and a model-fitting method (CR) were applied to calculate the activation energy. Results revealed that heating rates had no significant effect on the pyrolysis operation. The addition of WTS improved the thermal degradation of the samples as the samples had more than one stage during the main reaction period. A promoting synergistic effect was found in the blend 75A25WT and obtained the lowest activation energy among all the blends without a catalyst, while the blend 50A50WT exhibited an inhibiting effect. On the other hand, the addition of HZSM-5 accelerated the reaction time and obtained the lowest activation energy among all the blends without a catalyst. Furthermore, ΔW of 75A25WT+C was the lowest, indicating that the blend with a catalyst exhibited the strongest synergistic effect. This research confirmed that the addition of WTS improved the thermal parameters of the samples and clarified the capacity of HZSM-5 to reduce the activation energy.
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http://dx.doi.org/10.3390/ijerph19127101DOI Listing
June 2022

Functional Identification of Porcine during Muscle Development.

Animals (Basel) 2022 Jun 11;12(12). Epub 2022 Jun 11.

National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.

is paternally expressed and is involved in metabolism switching, stem cell maintenance, cell proliferation, and differentiation. Porcine was identified in our previous study as a candidate gene that regulates muscle development. In the present study, we characterized expression in pigs, and the results showed that was highly expressed in the muscles of pigs. In-vitro cellular tests showed that promoted myoblast proliferation, migration, and muscular hypertrophy, and at the same time inhibited muscle degradation. The expression of myogenic and fusion markers and the formation of multinucleated myotubes were both upregulated in myoblasts with overexpression. levels in cultured myocytes were negatively correlated with the expression of key factors in the Notch pathway, suggesting that the suppression of Notch signaling pathways may mediate these processes. Collectively, our results suggest a biological function of as an enhancer of muscle development by the inhibition of Notch pathways.
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http://dx.doi.org/10.3390/ani12121523DOI Listing
June 2022

and inhibited oral squamous cell carcinomas by regulating genome stability.

Bioengineered 2022 Jun;13(6):14094-14106

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

Periodontitis is a risk factor for the development of oral squamous cell carcinomas (OSCC). Both DNA damage response (DDR) and activation of inflammasomes induced by the microbiome might play important roles in the development of tumors, in relation to genome stability of tumor cells. Herein, we explored whether periodontitis negative-associated bacteria ( and , namely called 'PNB'), which were highly abundant in healthy populations, could inhibit OSCC by promoting genome stability. Firstly, a murine SCC-7 tumor-bearing model that colonized with PNB was designed and used in this study. Then, cyclin D1 was detected by immunohistochemistry. Levels of DDR, NLRP3 inflammasomes and pro-inflammatory cytokines in tumors were detected by RT-qPCR or Western blot. Immune cells in spleens were detected by immunohistochemistry or immunofluorescence. Finally, the anti-cancer activity of PNB was assessed using CCK-8 assays and flow cystometry. Compared with the control, PNB decreased tumor weights from 0.77 ± 0.26 g to 0.42 ± 0.15 g and downregulated the expression of Cyclin D1. PNB activated the DDR by up-regulating γ-H2AX, p-ATR, and p-CHK1. PNB activated NLRP3 inflammasome-mediated pyroptosis via increases of NLRP3, gasdermin D, and mRNA levels of apoptosis-associated speck-like protein, Caspase-1. PNB suppressed the inflammatory response by down-regulating mRNA levels of NF-κΒ and IL-6 in tumors as well as the populations of CD4+ T cells and CD206+ immune cells in spleens. PNB inhibited proliferation and promoted cell death of HSC-3 cells. In conclusion, and showed a 'probiotic bacterial' potential to inhibit OSCC by regulating genome stability.
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http://dx.doi.org/10.1080/21655979.2022.2078556DOI Listing
June 2022

Bergamottin, a bioactive component of bergamot, inhibits SARS-CoV-2 infection in golden Syrian hamsters.

Antiviral Res 2022 Jun 19;204:105365. Epub 2022 Jun 19.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China; University of the Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused an ongoing pandemic, coronavirus disease-2019 (COVID-19), which has become a major global public health event. Antiviral compounds remain the predominant means of treating COVID-19. Here, we reported that bergamottin, a furanocoumarin originally found in bergamot, exhibited inhibitory activity against SARS-CoV-2 in vitro, ex vivo, and in vivo. Bergamottin interfered with multiple stages of virus life cycles, specifically blocking the SARS-CoV-2 spike-mediated membrane fusion and effectively reducing viral RNA synthesis. Oral delivery of bergamottin to golden Syrian hamsters at dosages of both 50 mg/kg and 75 mg/kg reduced the SARS-CoV-2 load in nasal turbinates and lung tissues. Pathological damage caused by viral infection was also ameliorated after bergamottin treatment. Overall, our study provides evidence of bergamottin as a promising natural compound, with broad-spectrum anti-coronavirus activity, that could be further developed in the fight against COVID-19 infection during the current pandemic.
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http://dx.doi.org/10.1016/j.antiviral.2022.105365DOI Listing
June 2022

Combined treatment with Rg1 and adipose-derived stem cells alleviates DSS-induced colitis in a mouse model.

Stem Cell Res Ther 2022 Jun 21;13(1):272. Epub 2022 Jun 21.

Colorectal Disease Center of Nanjing Hospital of Chinese Medicine, Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210022, China.

Background: Inflammatory bowel diseases, consisting of Crohn's disease and ulcerative colitis constitute chronic inflammatory conditions that may compromise the whole gastrointestinal tract as well as the colonic mucosa. Currently, there are no curative interventions for IBD, and all available treatments have side effects that limit their use. Adipose-derived stem cell (ADSC) treatment is a prospective treatment option for IBD. Previous findings indicated that ginsenoside (Rg1) dampened inflammatory diseases like colitis by inhibiting the binding of LPS to TLR4 on macrophages and restoring the Th17/Treg ratio. The purpose of this work was to investigate whether Rg1 can increase the influence of ADSC in a mouse model of colitis triggered by dextran sulfate sodium (DSS).

Methods: ADSC was intravenously inoculated into mice with DSS-triggered colitis, while Rg1 was delivered via oral gavage. Colon inflammation was assessed via body weight, colon length along with H&E staining. Serum cytokine levels were measured using ELISA. Besides, flow cytometry was adopted to determine the percentage, as well as FMI of immune cells in the spleen. The effects of simultaneous Rg1 and ADSC treatment on TLR4-MyD88 signaling were assessed via immunofluorescence.

Results: Rg1 and ADSC effectively alleviated the impacts of colon inflammation, weight loss, and colon length reduction along with histological score. Treatment with Rg1 and ADSC reduced serum levels of the proinflammatory cytokines, IL-1β, TNF-α, IL-6, IL-4, and IL-17A and upregulated the level of immunosuppressive cytokine, IL-10. Compared with ADSC or Rg1 alone, combined treatment with Rg1 and ADSC significantly improved the structure of microbial community. Additionally, treatment with Rg1 plus ADSC selectively elevated the level of splenic regulatory T (Treg) cells and downregulated the proportion of T helper type 17 (Th17) cells, indicating restoration of intestinal homeostasis. Besides, we established that the combination of ADSC + Rg1 restored immunological balance more effectively than either ADSC or Rg1 alone, illustrating that Rg1's modulatory function on the gut microbiota may boost the impact of ADSCs in restoration of the immune balance. ADSC combined with Rg1 might downregulate the expression of TLR4 and MyD88, thereby suppressing TLR4-MyD8 signaling. The immunofluorescence results also suggested that co-therapy with Rg-1 and ADSC may optimize treatment strategies of IBD.

Conclusions: Here, we find that the combination of Rg1 and ADSC alleviates DSS-induced colitis in a mouse model more efficiently than ADSC alone, indicating that Rg1 enhances the effect of ADSC against colitis.
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http://dx.doi.org/10.1186/s13287-022-02940-xDOI Listing
June 2022

The beneficial effects of square dance on musculoskeletal system in early postmenopausal Chinese women: a cross-sectional study.

BMC Womens Health 2022 06 21;22(1):247. Epub 2022 Jun 21.

Department of Orthopaedics, The Affiliated Hospital of Nantong University, Nantong City, Jiangsu Province, People's Republic of China.

Background: This study was set to investigate the correlation between square dance and musculoskeletal system of early postmenopausal Chinese women.

Methods: Chinese postmenopausal women, who had been without menstruation for 1-10 years from the onset of menopause were recruited from community centers for this study. A standardized structured face-to-face interview was performed to collect demographic information, life styles, personal medical history, diet and menstrual status. Subjects who had been practicing regular square dance without participated in other sports activities for more than 2 years and over 4 h per week (usually more than 45 min per time and more than 5 times per week) were assigned to square dance group. Those postmenopausal women who had not participated in regular exercises (no more than 0.5 h per week) were recruited as the sedentary control group. Bone mineral density (BMD) of spine, total hip and femoral neck was measured by using dual-energy X-ray absorptiometry. Lower limb muscle strength was measured for the non-dominant leg, body flexibility was measured by a simple trunk bend-and-reach test, and body balance was evaluated using a single-stance test for the non-dominant leg. Independent two-tailed Student's t-test was used for data analysis.

Results: 152 subjects from community centers were selected for this study and divided into square dance group (n = 74) and control group (n = 78). The square dance subjects had higher lumbar spine BMD (p = 0.01) and total hip BMD (p = 0.02) than control subjects, but there was no significant difference of femoral neck BMD (p = 0.48) between these two groups. Functional testing indicated that square dance subjects had higher lower limb muscle strength (p < 0.01) and longer single-stance time (p = 0.02) than the control subjects, but there was no significant difference in trunk bend-and-reach (p = 0.12) between these two groups.

Conclusion: Our results show that postmenopausal Chinese women can get beneficial effects, like higher BMD, stronger lower limb muscle and improved body balance ability on musculoskeletal system by participating in square dance regularly.
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http://dx.doi.org/10.1186/s12905-022-01832-9DOI Listing
June 2022

Refocus attention on HIV/AIDS: it was neglected during the COVID-19 pandemic.

Clin Microbiol Infect 2022 Jun 18. Epub 2022 Jun 18.

School of Public Health, Peking University, Beijing, China; Center for Intelligent Public Health, Institute for Artificial Intelligence, Peking University, Beijing, China; Center for Drug Abuse Control and Prevention, National Institute of Health Data Science, Peking University, Beijing, China; Peking University Clinical Research Institute, Peking University, Beijing, China. Electronic address:

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http://dx.doi.org/10.1016/j.cmi.2022.06.011DOI Listing
June 2022

PLGA Containing Human Adipose-Derived Stem Cell-Derived Extracellular Vesicles Accelerates the Repair of Alveolar Bone Defects via Transfer of CGRP.

Oxid Med Cell Longev 2022 11;2022:4815284. Epub 2022 Jun 11.

State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

Calcitonin gene-related peptide (CGRP) is an important neuropeptide expressed in the nerve fibers during bone repair. Here, we aimed to pinpoint the role of CGRP in the osteogenic differentiation property of human periodontal ligament stem cells (hPDLSCs) and the resultant repair of alveolar bone defect. The key factor related to the osteogenic differentiation of hPDLSCs was retrieved from the GEO database. After extraction from hADSCs (hADSC-EVs) and identification, EVs were subjected to coculture with hPDLSCs, in which the expression patterns of CGRP and osteogenic differentiation marker proteins (ALP, RUNX2, and OCN), as well as ALP activity, were detected. A novel cell-free tissue-engineered bone (TEB) comprised of PLGA/pDA and hADSC-EVs was implanted into the rats with alveolar bone defects to evaluate the repair of alveolar bone defects. CGRP was enriched in hADSC-EVs. hADSCs delivered CGRP to hPDLSCs through EVs, thereby promoting the osteogenic differentiation potential of hPDLSCs. The PLGA/pDA-EV scaffold released EVs slowly, and its implantation into the rat alveolar bone defect area significantly induced bone defect repair, which was reversed by further knockdown of CGRP. In conclusion, our newly discovered cell-free system consisted of hADSC-EVs, and PLGA/pDA scaffold shows promising function in repairing alveolar bone defects.
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http://dx.doi.org/10.1155/2022/4815284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9206573PMC
June 2022

Efficacy and Safety of rCCK96-104PE38 Targeted Drug in the General Surgical Treatment of Colon Cancer.

Biomed Res Int 2022 8;2022:7145606. Epub 2022 Jun 8.

North China University of Science and Technology Affiliated Hospital, Tangshan, 063000 Hebei, China.

To evaluate the clinical efficacy and safety of the rCCKPE38 targeted drug in patients with colon cancer in general surgery, data of 80 patients with colon cancer who were admitted to the hospital from April 2019 to July 2021 were selected and randomly divided into the treatment group and the control group, with 40 cases in each group. Patients in the treatment group were treated with the rCCKPE38 targeted drug, and those in the control group were treated with oxaliplatin. The treatment efficiency and incidence of adverse reactions were compared between the two groups. The inverse cholecystokinin (CCK) was fused with pseudomonas aeruginosa exotoxin (PE38 toxin) through the gene amplification technique to construct a prokaryotic expression vector. Then, the rCCKPE38 was purified by Ni-nitrilotriacetate (Ni-NTA) affinity chromatography, and the antitumor activity of rCCKPE38 was verified. The results showed that the amplified rCCKPE38 sequence was correct and the pET-28a prokaryotic expression system was adopted to successfully achieve active expression. The purified recombinant protein could induce the apoptosis of colon cancer cells in vitro and inhibit tumor growth in vivo. The total effective rate in the treatment group (80%, 32/40) was higher than that in the control group (60%, 24/40) ( < 0.05). To sum up, the recombinant toxin rCCKPE38 could not only specifically adsorb the colon cancer cells with high expression of CCK2R but also effectively inhibit tumor tissue growth and proliferation. Besides, the rCCKPE38 protein had a good anticancer effect that helped effectively reduce the incidence of adverse reactions in patients, which was worthy of promoting.
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http://dx.doi.org/10.1155/2022/7145606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200555PMC
June 2022

In vitro Antibacterial Activity and Resistance Prevention of Antimicrobial Combinations for Dihydropteroate Synthase-Carrying .

Infect Drug Resist 2022 13;15:3039-3046. Epub 2022 Jun 13.

Department of Pulmonary and Critical Care Medicine, Air Force Medical Center, PLA, Beijing, 100142, People's Republic of China.

Background: () is a multidrug-resistant gram-negative bacillus that is known to be an opportunistic pathogen, particularly in a hospital environment. The infection has a high morbidity and mortality. Sulfamethoxazole-trimethoprim (SXT) is the first-line agent recommended for its treatment. The global spread of dihydropteroate synthase () genes has resulted in an increased resistance rate. However, the appropriate therapy for infections caused by carrying has not yet been established.

Objective: Our study aimed to identify the optimal antibiotic combinations that could both show high antibacterial activity against carrying and the ability to prevent the emergence of resistance at clinical dosage regimens.

Methods: Time-killing experiments and mutant prevention concentration (MPC) experiments were conducted to evaluate the antibacterial effect and ability to prevent resistance to minocycline, tigecycline, moxifloxacin, and ticarcillin/clavulanic acid (T/K), both alone and in combination, at clinically relevant antimicrobial concentrations.

Results: Minocycline, tigecycline, and T/K all exhibited bacteriostatic activity to carrying . The combination of minocycline plus T/K and tigecycline plus T/K neither enhanced the bactericidal ability nor prevented drug-resistant mutations. Moxifloxacin, at 2 mg/L, showed good bactericidal activity to most , but bacterial regrowth at 24 h was observed in two strains. When combined with T/K, moxifloxacin showed good bactericidal activity in all moxifloxacin-sensitive strains. The concentrations of moxifloxacin alone were lower than most MPCs of the tested carrying strains. When combined with T/K, the mean steady-state concentrations (MSC) of moxifloxacin could prevent 70% of resistance, and the peak concentration (C) prevented 95% of resistance.

Conclusion: The combination of moxifloxacin and T/K can achieve a good in vitro bactericidal effect and prevent the emergence of resistance at clinical dosage regimens, and may be an optimal therapeutic strategy for infections, especially for vulnerable immunocompromised and critically ill patients.
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http://dx.doi.org/10.2147/IDR.S368338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205434PMC
June 2022

A New Scale for Predicting the Risk of In-hospital Mortality in Patients With Traumatic Spinal Cord Injury.

Front Neurol 2022 2;13:894273. Epub 2022 Jun 2.

Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.

Purpose: To analyze the relative factors influencing in-hospital mortality in patients with traumatic spinal cord injury (TSCI), and develop a score scale for predicting the risk of in-hospital mortality.

Method: We reviewed the medical records from 59 spine centers in mainland China from 1 January 2018 to 31 December 2018. The inclusion criteria were (1) confirmed diagnosis of TSCI, (2) hospitalization within 7 days of injury, and (3) affecting neurological level from C1 to L1. The exclusion criteria were (1) readmission, and (2) incomplete data. Included patients were classified into the survival and non-survival groups according to their status at discharge. Univariate and multivariate logistic regressions were performed to identify the factors related to in-hospital mortality in patients with TSCI. A new scale was developed, and the mortality rate in each risk group was calculated.

Results: Of the 3,176 participants, 23 (0.7%) died in the hospital, and most of them died from respiratory diseases (17/23, 73.9%). After univariate and multivariate logistic regression analysis, cervical spinal cord injury [odds ratio (OR) = 0.264, 95% confidence interval (CI): 0.076-0.917, = 0.036], abdominal visceral injury (OR = 3.778, 95% CI: 1.038-13.755, = 0.044), the American Spinal Injury Association (ASIA) score on admission (A: reference; B:OR = 0.326, 95% CI: 0.093-1.146, = 0.081; C:OR = 0.070, 95% CI: 0.016-0.308, < 0.001; D:OR = 0.069, 95% CI: 0.019-0.246, < 0.001), and surgery (OR = 0.341, 95% CI: 0.146-0.796, = 0.013) were significantly associated with in-hospital mortality. Scores for each of the four factors were derived according to mortality rates. The sum of the scores from all four factors was included in the scoring system and represented the risk of in-hospital mortality. The in-hospital mortality risk of the low-risk (0-3 points), moderate-risk (4-5 points), and high-risk groups (6-8 points) was 0.3, 2.7, and 9.7%, respectively ( < 0.001).

Conclusions: Cervical spinal cord injury, abdominal visceral injury, ASIA score on admission, and surgery were significantly associated with in-hospital mortality in patients with TSCI and stable condition. The scale system may be beneficial for clinical decision-making and for communicating relevant information to patients and their families.
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http://dx.doi.org/10.3389/fneur.2022.894273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204840PMC
June 2022

CD3D Is an Independent Prognostic Factor and Correlates With Immune Infiltration in Gastric Cancer.

Front Oncol 2022 1;12:913670. Epub 2022 Jun 1.

Department of Integrated Chinese and Western Medicine, Institute of Basic Medicine and Cancer (IBMC), The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Chinese Academy of Sciences, Hangzhou, China.

The protein encoded by CD3D is part of the T-cell receptor/CD3 complex (TCR/CD3 complex) and is involved in T-cell development and signal transduction. Previous studies have shown that CD3D is associated with prognosis and treatment response in breast, colorectal, and liver cancer. However, the expression and clinical significance of CD3D in gastric cancer are not clear. In this study, we collected 488 gastric cancer tissues and 430 paired adjacent tissues to perform tissue microarrays (TMAs). Then, immunohistochemical staining of CD3D, CD3, CD4, CD8 and PD-L1 was conducted to investigate the expression of CD3D in gastric cancer and the correlation between the expression of CD3D and tumor infiltrating lymphocytes (TILs) and PD-L1. The results showed that CD3D was highly expressed in gastric cancer tissues compared with paracancerous tissues (<0.000). Univariate and multivariate analyses showed that CD3D was an independent good prognostic factor for gastric cancer (=0.004, HR=0.677, 95%CI: 0.510-0.898 for univariate analyses; =0.046, HR=0.687, 95%CI: 0.474-0.994 for multivariate analyses). In addition, CD3D was negatively correlated with the tumor location, Borrmann type and distant metastasis (=0.012 for tumor location; =0.007 for Borrmann type; =0.027 for distant metastasis). In addition, the expression of CD3D was highly positively correlated with the expression of CD3, CD4, CD8, and PD-L1, and the combination of CD3D with CD3, CD4, CD8 and PD-L1 predicted the best prognosis (=0.043). In summary, CD3D may play an important regulatory role in the tumor immune microenvironment of gastric cancer and may serve as a potential indicator of prognosis and immunotherapy response.
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http://dx.doi.org/10.3389/fonc.2022.913670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198637PMC
June 2022

Outcomes of Endovascular Therapy in Young Patients with Acute Basilar Artery Occlusion: A Substudy of BASILAR Registry Study.

Neurol Ther 2022 Jun 16. Epub 2022 Jun 16.

Department of Neurology, Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, China.

Introduction: This study aimed to investigate clinical outcomes in young patients with basilar artery occlusion (BAO) receiving endovascular therapy (EVT).

Methods: Consecutive patients with BAO within 24 h who underwent EVT from the BASILAR Registry study were enrolled. We compared clinical outcomes of young patients (aged 18-55 years) with older patients (aged > 55 years) with stroke due to BAO at 90 days and 1 year after EVT. The primary and secondary outcomes were improvement in modified Rankin scale scores (mRS) at 90 days and either favorable (mRS 0-3) or mortality at 90 days, respectively.

Results: A total of 646 patients were included, of which 152 (23.53%) were aged 18-55 years. Dyslipidemia (42.11% vs. 30.36%, p = 0.007) and good collateral circulation (60.52% vs. 46.35%, p = 0.002) were more frequent in young patients than older. Stroke etiologies in young patients included large artery atherosclerosis (67.11%), cardioembolism (15.13%), and vessel dissection (5.26%). Young patients were associated with better prognosis (mRS: adjusted odds ratio (aOR) 1.73; 95% confidence interval [CI] 1.21-2.48; mRS 0-3: aOR 1.60; 95% CI 1.01-2.54; mortality: aOR 0.60; 95% CI 0.38-0.93) at 90 days. Baseline National Institutes of Health Stroke Scale (NIHSS) score, posterior circulation Alberta Stroke Program Early Computed Tomography Score (pc-ASPECTS), and sex were independent predictors of clinical outcomes of young patients at 90 days after EVT.

Conclusion: Young patients with BAO had better clinical outcomes after EVT than old patients. Predictors of clinical outcomes in young patients undergoing EVT included baseline NIHSS score, pc-ASPECTS, and sex.

Trial Registration: Clinical Trial Registration-URL: ChiCTR180001475 ( www.chictr.org.cn ).
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http://dx.doi.org/10.1007/s40120-022-00372-6DOI Listing
June 2022

Chronologically modified androgen receptor in recurrent castration-resistant prostate cancer and its therapeutic targeting.

Sci Transl Med 2022 Jun 15;14(649):eabg4132. Epub 2022 Jun 15.

Department of Surgery, Washington University in St. Louis, St. Louis, MO 63110, USA.

Resistance to second-generation androgen receptor (AR) antagonists such as enzalutamide is an inevitable consequence in patients with castration-resistant prostate cancer (CRPC). There are no effective therapeutic options for this recurrent disease. The expression of truncated AR variant 7 (AR-V7) has been suggested to be one mechanism of resistance; however, its low frequency in patients with CRPC does not explain the almost universal acquisition of resistance. We noted that the ability of AR to translocate to nucleus in an enzalutamide-rich environment opens up the possibility of a posttranslational modification in AR that is refractory to enzalutamide binding. Chemical proteomics in enzalutamide-resistant CRPC cells revealed acetylation at Lys in the zinc finger DNA binding domain of AR (acK609-AR) that not only allowed AR translocation but also galvanized a distinct global transcription program, conferring enzalutamide insensitivity. Mechanistically, acK609-AR was recruited to the and enhancers, up-regulating their transcription. ACK1 kinase-mediated AR Y267 phosphorylation was a prerequisite for AR K609 acetylation, which spawned positive feedback loops at both the transcriptional and posttranslational level that regenerated and sustained high AR and ACK1 expression. Consistent with these findings, oral and subcutaneous treatment with ACK1 small-molecule inhibitor, ()-9b, not only curbed AR Y267 phosphorylation and subsequent K609 acetylation but also compromised enzalutamide-resistant CRPC xenograft tumor growth in mice. Overall, these data uncover chronological modification events in AR that allows prostate cancer to evolve through progressive stages to reach the resilient recurrent CRPC stage, opening up a therapeutic vulnerability.
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http://dx.doi.org/10.1126/scitranslmed.abg4132DOI Listing
June 2022

Neuroligin-3 confines AMPA receptors into nanoclusters, thereby controlling synaptic strength at the calyx of Held synapses.

Sci Adv 2022 Jun 15;8(24):eabo4173. Epub 2022 Jun 15.

School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.

The subsynaptic organization of postsynaptic neurotransmitter receptors into nanoclusters that are aligned with presynaptic release sites is essential for the high fidelity of synaptic transmission. However, the mechanisms controlling the nanoscale organization of neurotransmitter receptors in vivo remain incompletely understood. Here, we deconstructed the role of neuroligin-3 (Nlgn3), a postsynaptic adhesion molecule linked to autism, in organizing AMPA-type glutamate receptors in the calyx of Held synapse. Deletion of lowered the amplitude and slowed the kinetics of AMPA receptor-mediated synaptic responses. Super-resolution microscopy revealed that, unexpectedly, these impairments in synaptic transmission were associated with an increase in the size of postsynaptic PSD-95 and AMPA receptor nanoclusters but a decrease of the densities in these clusters. Modeling showed that a dilution of AMPA receptors into larger nanocluster volumes decreases synaptic strength. Nlgn3, likely by binding to presynaptic neurexins, thus is a key organizer of AMPA receptor nanoclusters that likely acts via PSD-95 adaptors to optimize the fidelity of synaptic transmission.
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http://dx.doi.org/10.1126/sciadv.abo4173DOI Listing
June 2022

Biosynthesis of Sordarin Revealing a Diels-Alderase for the Formation of the Norbornene Skeleton.

Angew Chem Int Ed Engl 2022 Jun 14. Epub 2022 Jun 14.

Nanjing University, School of Life Science, CHINA.

Sordarin ( 1 ) is a fungal diterpene glycoside that displays potent antifungal bioactivity through inhibition of elongation factor 2. The structures of sordarin and related compounds are featured by a highly rearranged tetracyclic diterpene core. In this work we identified a concise pathway in the biosynthesis of sordarin. A diterpene cyclase (SdnA) generates the 5/8/5 cycloaraneosene framework, which was decorated by a set of P450s that catalyze a series of oxidations, including hydroxylation, desaturation, and C-C bond oxidative cleavage, to give a carboxylate intermediate with a terminal alkene and a cyclopentadiene moiety. A novel Diels-Alderase SdnG catalyzes an intramolecular Diels-Alder (IMDA) reaction on this intermediate to forge the sordarin core structure. The subsequent methyl hydroxylation and glycosylation completed the biosynthesis of sordarin. Our work disclosed a new strategy to the rearranged diterpene skeleton used by nature.
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http://dx.doi.org/10.1002/anie.202205577DOI Listing
June 2022

GA&HA-Modified Liposomes for Co-Delivery of Aprepitant and Curcumin to Inhibit Drug-Resistance and Metastasis of Hepatocellular Carcinoma.

Int J Nanomedicine 2022 7;17:2559-2575. Epub 2022 Jun 7.

School of Life Science and Technology, Weifang Medical University, Weifang, 261053, People's Republic of China.

Background: Tumor microenvironment (TME) plays a vital role in the development of hepatocellular carcinoma (HCC). Mounting evidence indicates that peripheral nerves could induce a shift from quiescent hepatic stellate cells (HSCs) to cancer-associated fibroblasts (CAFs) by secreting substance P (SP). The anti-tumor strategy by targeting "SP-HSCs-HCC" axis might be an effective therapy to inhibit tumor growth and metastasis.

Objective: In this study, we prepared novel liposomes (CUR-APR/HA&GA-LPs) modified with hyaluronic acid (HA) and glycyrrhetinic acid (GA) for co-delivery aprepitant (APR) and curcumin (CUR), in which APR was chosen to inhibit the activation of HSCs by blocking SP/neurokinin-1 receptor (NK-1R), and CUR was used to induce apoptosis of tumor cells.

Results: To mimic the TME, we established "SP+HSCs+HCC" co-cultured cell model in vitro. The results showed that CUR-APR/HA&GA-LPs could be taken up by CAFs and HCC simultaneously, and inhibit tumor cell migration. Meanwhile, the "SP+m-HSCs+HCC" co-implanted mice model was established to evaluate the anti-tumor effect in vivo. The results showed that CUR-APR/HA&GA-LPs could inhibit tumor proliferation and metastasis, and reduce extracellular matrix (ECM) deposition and tumor angiogenesis, indicating a superior anti-HCC effect.

Conclusion: Overall, the combination therapy based on HA&GA-LPs could be a potential nano-sized formulation for anti-HCC therapy.
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http://dx.doi.org/10.2147/IJN.S366180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188407PMC
June 2022

Enhancing production of hydrocarbon-rich bio-oil from biomass via catalytic fast pyrolysis coupled with advanced oxidation process pretreatment.

Bioresour Technol 2022 Jun 10;359:127450. Epub 2022 Jun 10.

Key Laboratory of Energy Thermal Conversion and Control of Ministry of Education, Southeast University, No.2 Sipailou, Xuanwu District, Nanjing, Jiangsu 210096, China.

This study aims to propose a method for upgrading biomass pyrolysis products based on the combination of sodium persulfate pretreatment and fast catalytic pyrolysis. Combined with the analysis of components and thermogravimetric analysis, the result showed that after pretreatment the biomass structure was gradually depolymerized, the contents of lignin, the reaction of activation energy and the crystallinity of cellulose decreased. Due to the destructive effect of persulfate radicals, in fast pyrolysis, the relative contents of acids and oxygen-containing substances decreased, and the relative content of phenols can significantly increase to 19.20%. The yield of aromatic hydrocarbons and total hydrocarbons had a high value under the catalytic pyrolysis in the best performance which amount of yield reached 28.66% and 33.72%, respectively. Sodium persulfate pretreatment was beneficial in the production of hydrocarbon-rich bio-oils and high-value chemicals since the radicals can effectively depolymerize lignin which promoted the process of pyrolysis.
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http://dx.doi.org/10.1016/j.biortech.2022.127450DOI Listing
June 2022
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