Publications by authors named "Shang Wang"

189 Publications

Minerals Determined a Special Ecological Niche and Selectively Enriched Microbial Species from Bulk Water Communities in Hot Springs.

Microorganisms 2021 May 10;9(5). Epub 2021 May 10.

State Key Laboratory of Biogeology and Environmental Geology, China University of Geosciences, Beijing 100083, China.

Minerals provide physical niches and supply nutrients or serve as electron donors/acceptors for microorganism survival and growth, and thus minerals and microbes co-evolved. Yet, little is known about how sediment minerals impact microbial community assembly in hot springs and to what extent mineralogical composition influences microbial community composition and diversity. Here the influences of minerals on thermophiles in Tengchong hot springs were revealed by network analysis of field samples, as well as in-situ microcosm experiments with minerals. A molecular ecological network was constructed based on high throughput sequencing data of 16S rRNA gene, with a combination of water geochemistry and sedimentary mineralogical compositions. Six modules were identified and this highly modular network structure represents the microbial preference to different abiotic factors, consequently resulting in niche partitioning in sedimentary communities in hot springs. Diverse mineralogical compositions generated special niches for microbial species. Subsequently, the in-situ microcosm experiments with four minerals (aragonite, albite, K-feldspar, and quartz) and spring water were conducted in a silicate-hosted alkaline spring (i.e., Gmq) and a carbonate-hosted neutral hot spring (i.e., Gxs) for 70 days. Different microbial preferences were observed among different mineral types (carbonate versus silicate). Aragonite microcosms in Gmq spring enriched archaeal genera Sulfophobococcus and Aeropyrum within the order Desulfurococcales by comparison with both in-situ water and silicate microcosms. Sulfophobococcus was also accumulated in Gxs aragonite microcosms, but the contribution to overall dissimilarity is much lower than that in Gmq spring. Besides, Caldimicrobium was a bacterial genus enriched in Gxs aragonite microcosms, in contrast to in-situ water and silicate microcosms, whereas Candidatus Kryptobacter and Thermus were more abundant in silicate microcosms. The differences in microbial accumulations among different mineral types in the same spring implied that mineral chemistry may exert extra deterministic selective pressure in drawing certain species from the bulk water communities, in addition to stochastic absorption on mineral surface. Taken together, our results highlight the special niche partitioning determined by mineralogical compositions and further confirm that minerals could be used as "fishing bait" to enrich certain rare microbial species.
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http://dx.doi.org/10.3390/microorganisms9051020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151621PMC
May 2021

Rationally designed protein cross-linked hydrogel for bone regeneration via synergistic release of magnesium and zinc ions.

Biomaterials 2021 Jul 12;274:120895. Epub 2021 May 12.

Department of Spine Surgery and Institute for Orthopaedic Research, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Jinan University Second College of Medicine, Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, Shenzhen, 518001, China. Electronic address:

The development of recombinant protein cross-linked injectable hydrogels with good mechanical strength and effective drug loading capacity for bone regeneration is extremely attractive and rarely reported. Here, we report the fabrication of a smart hydrogel delivery system by incorporating a rationally designed T4 lysozyme mutant (T4M) to mediate the localized delivery and synergistic release of Mg and Zn for bone repair. Apart from its intrinsic antibacterial properties, T4M bears abundant free amine groups on its surface to function as effective covalent crosslinkers to strengthen the hydrogel network as well as exhibits specific binding affinity to multivalent cations such as Zn. Moreover, the integrin receptor-binding Arg-Gly-Asp (RGD) sequence was introduced onto the C-terminus of T4 lysozyme to improve its cellular affinity and further facilitate rapid tissue regeneration. The final composite hydrogel displays excellent injectability, improved mechanical properties, antibacterial activity, and unique bioactivities. The effective loading of Mg/Zn in the hydrogels could mediate the sequential and sustained release of Mg and Zn, thereby resulting in synergistic enhancement on bone regeneration through modulation of the MAPK signaling pathway. We believe that the strategy proposed in this paper opens up a new route for developing protein cross-linked smart delivery systems for tissue regeneration.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120895DOI Listing
July 2021

Ovarian endometrioid carcinoma and clear cell carcinoma: A 21-year retrospective study.

J Ovarian Res 2021 May 4;14(1):63. Epub 2021 May 4.

Department of Obstetrics and Gynecology, Center of Gynecologic Oncology, Peking University People's Hospital, No. 11, South Avenue, Xi Zhi Men, Xicheng District, Beijing, 100044, China.

Objective: This study aimed to identify the clinical characteristics of Chinese patients with ovarian endometrioid carcinoma (EC) and clear cell carcinoma (CCC) and to assess the impact of concurrent endometriosis on this group.

Methods: The present study reviewed the medical records of patients who received initial treatment and a postoperative pathological diagnosis of EC or CCC at our center in China between 1998 and 2018.

Results: Of 211 patients, 73 had pure EC, and 91 had pure CCC, and the remaining 47 had mixed cancer. The proportion of EC and CCC remained stable over past 21 years. The proportion of EC declined with aging and the age of EC onset to incline to the young. And the age of CCC onset had two peaks, namely, 36 and 77 years. After review by the pathologist, the number of endometriosis cases found in the pathological section of the analysis increased to 114, accounting for 54% of patients. As the stage progressed, the appearance of endometriosis became increasingly scarce in pathological sections(p = 0.001). Compared with CCC, EC had a higher frequency of concurrent endometrial cancer (independent endometrial lesions) and estrogen and progesterone receptor expression(p = 0.000). And more patients were in premenopausal state in EC group(p = 0.040). In the pure group, multivariate analysis showed that correlation existed between relevance to endometriosis and worse outcomes(p = 0.041). In patients with mixed cancer, mixed endometrioid histology was associated with better survival than other subtypes, even with stage III or poorly differentiated tumors(p = 0.001).

Conclusions: CCC and EC which are common in ovarian cancer patients who have associated with endometriosis have distinct clinicopathological characteristics. Attention should be paid to ovarian cancer patients with a history of endometriosis and those with concurrent endometriosis in pathological sections.
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http://dx.doi.org/10.1186/s13048-021-00804-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094516PMC
May 2021

Evidence for the Involvement of the Chemosensory Protein AgosCSP5 in Resistance to Insecticides in the Cotton Aphid, .

Insects 2021 Apr 9;12(4). Epub 2021 Apr 9.

Biocontrol Engineering Laboratory of Crop Diseases and Pests of Gansu Province, Gansu Agricultural University, No. 1 Yingmen Village, Anning District, Lanzhou 730070, China.

It has been speculated that insect chemosensory proteins (CSPs) may have additional roles beyond olfaction. In this study, the phylogenetic and genomic analyses of the CSPs of the cotton aphid, , revealed the presence of gene gain-and-loss among different aphid field populations. Differential expressions of eight genes were demonstrated after treatments with insecticides of different modes of action. The expression of was significantly upregulated by the insecticide treatments in a dose-dependent manner. The flies overexpressing were significantly less susceptible to the insecticides, omethoate, imidacloprid and cypermethrin but not to deltamethrin and tau-fluvalinate, compared with control flies. The transgenic flies exhibited an LC resistance ratio of 2.6 to omethoate, compared with control flies. Likewise, the mortality of the transgenic flies to imidacloprid and cypermethrin was significantly lower than that of the control flies ( < 0.01). Homology modelling, molecular docking and dynamic simulation supported the interactions and revealed a higher stability of AgosCSP5/insecticide complexes than AgosCSP5/semiochemical complexes. Our study demonstrates for first time the in vivo evidence for the involvement of genes in insecticide resistance of crop insect pests and provides new insights of the newly discovered CSP-mediated insect resistance mechanism to insecticides.
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http://dx.doi.org/10.3390/insects12040335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070451PMC
April 2021

CDK7 blockade suppresses super-enhancer-associated oncogenes in bladder cancer.

Cell Oncol (Dordr) 2021 Apr 27. Epub 2021 Apr 27.

Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.

Purpose: Transcriptional addiction plays a pivotal role in maintaining the hallmarks of cancer cells. Thus, targeting super-enhancers (SEs), which modulate the transcriptional activity of oncogenes, has become an attractive strategy for cancer therapy. As yet, however, the molecular mechanisms of this process in bladder cancer (BC) remain to be elucidated. Here, we aimed to provide detailed information regarding the SE landscape in BC and to investigate new potential pharmaceutical targets for BC therapy.

Methods: We employed THZ1 as a potent and specific CDK7 inhibitor. In vitro and in vivo studies were carried out to investigate the anticancer and apoptosis-inducing effects of THZ1 on BC cells. Whole-transcriptome sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) were performed to investigate the mechanism and function of SE-linked oncogenic transcription in BC cells.

Results: We found that THZ1 serves as an effective and potent inhibitor with suppressive activity against BC cells. An integrative analysis of THZ1-sensitive and SE-associated oncogenes yielded potential new pharmaceutical targets, including DDIT4, B4GALT5, PSRC1 and MED22. Combination treatment with THZ1 and the DDIT4 inhibitor rapamycin effectively suppressed BC cell growth. In addition, we found that THZ1 and rapamycin sensitized BC cells to conventional chemotherapy.

Conclusions: Our data indicate that exploring BC gene regulatory mechanisms associated with SEs through integrating RNA-seq and ChIP-seq data improves our understanding of BC biology and provides a basis for innovative therapies.
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http://dx.doi.org/10.1007/s13402-021-00608-xDOI Listing
April 2021

New Model for Estimation of the Age at Onset in Spinocerebellar Ataxia Type 3.

Neurology 2021 Jun 23;96(23):e2885-e2895. Epub 2021 Apr 23.

From the Department of Neurology (L.P., Z.C., M.L., L.L., H.P., Y.S., Y.P., Q.D., S.W., G.Z., L.W., H.Y., L.H., Y.X., Z.T., N.W., Y.G., X.H., L.S., J.L., B.T., H.J.), Department of Pathology (C.W.), National Clinical Research Center for Geriatric Disorders (Z.C., L.S., B.T., H.J.), Xiangya Hospital, Central South University; Department of Neurology (Z.L.), The Second Xiangya Hospital, Central South University; Key Laboratory of Hunan Province in Neurodegenerative Disorders (Z.C., L.S., J.L., B.T., H.J.), Center for Medical Genetics School of Life Sciences (K.X., J.L., C.C.), Hunan Key Laboratory of Medical Genetics (K.X., J.L., C.C.), School of Computer Science and Engineering (R.Q.), and School of Basic Medical Science (H.J.), Central South University, Changsha, Hunan, China; Department of Neurology (T.K.), University of Bonn; and German Center for Neurodegenerative Diseases (DZNE) (T.K.), Bonn, Germany.

Objectives: The aim of this study was to develop an appropriate parametric survival model to predict patient's age at onset (AAO) for spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) populations from mainland China.

Methods: We compared the efficiency and performance of 6 parametric survival analysis methods (exponential, weibull, log-gaussian, gaussian, log-logistic, and logistic) based on cytosine-adenine-guanine (CAG) repeat length at to predict the probability of AAO in the largest cohort of patients with SCA3/MJD. A set of evaluation criteria, including -2 log-likelihood statistic, Akaike information criterion (AIC), bayesian information criterion (BIC), Nagelkerke R-squared (Nagelkerke R^2), and Cox-Snell residual plot, were used to identify the best model.

Results: Among these 6 parametric survival models, the logistic model had the lowest -2 log-likelihood (6,560.12), AIC (6,566.12), and BIC (6,566.14) and the highest value of Nagelkerke R^2 (0.54), with the closest graph to the bisector Cox-Snell residual graph. Therefore, the logistic survival model was the best fit to the studied data. Using the optimal logistic survival model, we indicated the age-specific probability distribution of AAO according to the CAG repeat size and current age.

Conclusions: We first demonstrated that the logistic survival model provided the best fit for AAO prediction in patients with SCA3/MJD from mainland China. This optimal model can be valuable in clinical and research. However, the rigorous clinical testing and practice of other independent cohorts are needed for its clinical application. A unified model across multiethnic cohorts is worth further exploration by identifying regional differences and significant modifiers in AAO determination.
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http://dx.doi.org/10.1212/WNL.0000000000012068DOI Listing
June 2021

Promising diagnostic and therapeutic circRNAs for skeletal and chondral disorders.

Int J Biol Sci 2021 7;17(5):1428-1439. Epub 2021 Apr 7.

Department of Spine Surgery and Institute for Orthopaedic Research, the 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University, the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen Key Laboratory of Reconstruction of Sports System, Shenzhen, 518055, China.

Circular RNAs (circRNAs) belong to a highly conserved subtype of non-coding RNAs, produced by the back-splicing of specific regions of pre-mRNA. CircRNAs have wide-ranging effects on eukaryotic physiology and pathology by acting as transcription regulators, miRNA sponges, protein sponges, and templates for translation. Skeletal and chondral disorders are the leading causes of pain and disability, especially for elders, affecting hundreds of millions of people worldwide. Plenty of evidence have shown that circRNAs are dysregulated and play vital roles in the occurrence and progression of skeletal and chondral disorders. Herein, we systematically summarize the emerging roles and underlying molecular mechanisms of hub circRNAs in the pathogenesis of several representative skeletal and chondral disorders. Our findings may provide further insight into the mechanistic details of the role of circRNA in bone or cartilage metabolism, and highlight the promising application of circRNAs in serving as potential diagnostic or therapeutic targets for the prevention and treatment of skeletal and chondral disorders.
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http://dx.doi.org/10.7150/ijbs.57887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040475PMC
April 2021

Two novel missense variants in SPTBN2 likely associated with spinocerebellar ataxia type 5.

Neurol Sci 2021 Apr 2. Epub 2021 Apr 2.

Department of Neurology, The Second Hospital of Shandong University, Jinan, 250033, Shandong, China.

Introduction: Spinocerebellar ataxias (SCAs) are a heterozygous group of neurodegenerative disorders. Spinocerebellar ataxia type 5 (SCA5) is a rare autosomal-dominant ataxia with pure cerebellum involvement. The clinical characteristics are limb and gait ataxia, trunk ataxia, sensory deficits, abnormal eye movement, dysarthria, and hyperactive tendon reflexes. Spectrin beta nonerythrocytic 2 gene (SPTBN2), coding β-III spectrin protein, was identified to be associated with SCA5. To date, more than 19 variants of SPTBN2 have been reported.

Methods: A family and an apparently sporadic patient with ataxia and cerebellar atrophy were recruited from Shandong Province (China). To discover the disease-causing variants, capillary electrophoresis and targeted next-generation sequencing were performed in the proband of the family and the sporadic patient. The candidate variants were verified by Sanger sequencing and analyzed by bioinformatics software.

Results: In our study, we verified two novel heterozygous variants in SPTBN2 in a SCA pedigree and a sporadic patient. The proband of the pedigree and her mother presented with walking instability and progressively getting worse. The sporadic patient suffered from slurred speech, walking instability, and drinking water choking cough. MRI examination of the proband and sporadic patient both displayed moderate cerebellar atrophy. The variants identified were traditionally conserved and predicted probably damaging and disease-causing by bioinformatics analysis.

Conclusion: We identified two novel heterozygous variants of SPTBN2 resulting in severe ataxia which further delineated the correlation between the genotype and phenotype of SCA5, and pathogenesis of variants in SPTBN2 should be further researched.
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http://dx.doi.org/10.1007/s10072-021-05204-3DOI Listing
April 2021

Propeptide in Lipase: New Insights into Its Mechanism of Activity and Substrate Selectivity by Computational Design.

J Agric Food Chem 2021 Apr 2;69(14):4263-4275. Epub 2021 Apr 2.

Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, PRC.

Most fungal lipases contain a propeptide, which is very important for their function and substrate selectivity. In the present study, lipase (RCL) was used as a research model to explore the mechanism of the propeptide of the lipase. Conventional molecular dynamics (MD) and metadynamics simulations were used to explore the mechanism by which the propeptide affects the activity of the lipase, which was subsequently verified by mutation experiments. MD simulations indicated that the propeptide had an inhibitory effect on the lid movement of RCL and found a key region (Val5-Thr10) on the propeptide. Subsequently, site-directed mutations were created in this region. The mutations enhanced the lipase catalytic efficiency to 700% and showed the potential for the propeptide to shift the substrate specificity of RCL. The specificity and activity of RCL mutants also had similar trends to wild-type RCL toward triglycerides with varying chain lengths. The mutual corroboration of simulation and site-directed mutagenesis results revealed the vital role of the key propeptide region in the catalytic activity and substrate specificity of the lipase.
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http://dx.doi.org/10.1021/acs.jafc.1c00721DOI Listing
April 2021

Generation of spinocerebellar ataxia type 3 patient-derived induced pluripotent stem cell line (CSUXHi005-A) from human urine epithelial cells.

Stem Cell Res 2021 May 17;53:102289. Epub 2021 Mar 17.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Diseases, Central South University, Changsha, Hunan, China; Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China; School of Basic Medical Science, Central South University, Changsha, Hunan, China. Electronic address:

Urine epithelial cells were harvested from a 32-year old female patient with spinocerebellar ataxia type 3 (SCA3) and reprogrammed into induced pluripotent stem cells (iPSCs) by non-integration system. The SCA3 derived iPSCs line, CSUXHi005-A, maintained 76 CAG expansions in the ATXN3 gene, was characterized by the expression of pluripotency markers and normal karyotype. The newly generated iPSCs retain the ability to differentiate into three germ layers by teratoma test, which provide an ideal tool for disease modeling, drug screening, and cellular therapy.
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http://dx.doi.org/10.1016/j.scr.2021.102289DOI Listing
May 2021

Efficacy of Longdan Xiegan Decoction on the Treatment of Eczema: A Systematic Review and Meta-Analysis.

Evid Based Complement Alternat Med 2021 18;2021:8836117. Epub 2021 Feb 18.

Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

Background: Longdan Xiegan decoction (LDXGD) has been widely used in the treatment of eczema. In recent years, randomized controlled trials (RCTs) of LDXGD for the treatment of eczema have gradually increased. Most of the results show that LDXGD is effective in treating eczema. However, whether these conclusions are reliable or not requires meta-analysis.

Objective: This study aimed to systematically evaluate the clinical efficacy of LDXGD in the treatment of eczema.

Materials And Methods: Seven electronic databases, including PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Chinese Biomedical Literature on Disc (CBM), China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Science and Technology Periodical Database (VIP) were systematically searched from their inception until January 2021. Risk of bias was assessed using criteria from the Cochrane Collaboration and meta-analysis was conducted on the screened literature data using Review Manage (RevMan 5.3). Then, to assess the quality of evidence, the GRADE criteria was adopted.

Results: 14 RCTs with 1080 participants were identified. Meta-analysis indicated that compared with western medicine (WM), the cure rate and the total effective rate of LDXGD in treating eczema were higher. Meanwhile, the recurrence rate and the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor (TNF-) after treatment were lower. The adverse reaction was reported in 5 out of 14 studies without significant statistical difference. According to GRADE criteria, the quality of evidence was low for all outcomes except for the cure rate (moderate-quality evidence) and the total effective rate (moderate-quality evidence).

Conclusion: The clinical efficacy of LDXGD in the treatment of eczema was more effective compared with the one of conventional WM alone. However, due to the limitation of the quality of the included studies, additional studies are required to further confirm these results.
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http://dx.doi.org/10.1155/2021/8836117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906809PMC
February 2021

Surgery decision conflict and its related factors among newly diagnosed early breast cancer patients in China: A cross-sectional study.

Nurs Open 2021 Feb 25. Epub 2021 Feb 25.

The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Aim: The aim of this study was to explore surgery decision conflict and its related factors among newly diagnosed early breast cancer patients in China.

Design: A cross-sectional survey study was conducted.

Methods: A total of 262 patients confronted with surgery decision-making were enrolled. The related factors were assessed with a demographic questionnaire, the Chinese version of the Decision Conflict Scale (DCS-C-16) and the Patient Participation Competence Scale (PPCS).

Results: Patients had a high level of decision conflict that was negatively correlated with the PPCS score. Age, marital status, living environment, education level, family income, cancer stage and the PPCS score were independent factors influencing decision conflict. Marital status, education level, cancer stage and participation competence were significant predictors of decision conflict. Patients who had higher participation competence were married, were well educated and had a lower cancer stage were likely to experience lower decision conflict.
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http://dx.doi.org/10.1002/nop2.791DOI Listing
February 2021

Temperature and microbial interactions drive the deterministic assembly processes in sediments of hot springs.

Sci Total Environ 2021 Jun 30;772:145465. Epub 2021 Jan 30.

CAS Key Laboratory for Environmental Biotechnology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences (CAS), Beijing 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100190, China.

Terrestrial geothermal ecosystems, as a representative of extreme environments, exhibit a variety of geochemical gradients, and their microbes are thought to be under high stress through environmental selection. However, it is still unclear how stochasticity and biotic interactions contribute to the microbial community assembly in hot springs. Here, we investigated the assembly processes and co-occurrence patterns of microbiota (i.e. bacteria and archaea) in both water and sediments sampled from fifteen hot springs in the Tengchong area, Southwestern of China, using 16S rRNA gene sequencing combined with multivariate ecological and statistical methods. These hot springs harbored more specialists than non-geothermal ecosystems, which are well-adapted to the extreme conditions, as shown by extremely high nearest-taxon index (NTI) and narrower niche width. Habitat differentiation led to the differences in microbial diversity, species-interactions, and community assembly between water and sediment communities. The sediment community showed stronger phylogenetic clustering and was primarily governed by heterogeneous selection, while undominated stochastic processes and dispersal limitation were the major assembly processes in the water community. Temperature and ferrous iron were the major factors mediating the balance of stochastic and deterministic assembly processes in sediment communities, as evidenced by how divergences in temperature and ferrous iron increased the proportion of determinism. Microbial interactions in sediments contributed to deterministic community assembly, as indicated by more complex associations and greater responsiveness to environmental change than water community. These findings uncover the ecological processes underlying microbial communities in hot springs, and provide potential insight into understanding the mechanism to maintain microbial diversity in extreme biospheres.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145465DOI Listing
June 2021

Seizure Onset Detection Using Empirical Mode Decomposition and Common Spatial Pattern.

IEEE Trans Neural Syst Rehabil Eng 2021 2;29:458-467. Epub 2021 Mar 2.

Automatic seizure onset detection plays an important role in epilepsy diagnosis. In this paper, a novel seizure onset detection method is proposed by combining empirical mode decomposition (EMD) of long-term scalp electroencephalogram (EEG) with common spatial pattern (CSP). First, wavelet transform (WT) and EMD are employed on EEG recordings respectively for filtering pre-processing and time-frequency decomposition. Then CSP is applied to reduce the dimension of multi-channel time-frequency representation, and the variance is extracted as the only feature. Afterwards, a support vector machine (SVM) group consisting of ten SVMs is served as a robust classifier. Finally, the post-processing is adopted to acquire a higher recognition rate and reduce the false detection rate. The results obtained from CHB-MIT database of 977 h scalp EEG recordings reveal that the proposed system can achieve a segment-based sensitivity of 97.34% with a specificity of 97.50% and an event-based sensitivity of 98.47% with a false detection rate of 0.63/h. This proposed detection system was also validated on a clinical scalp EEG database from the Second Hospital of Shandong University, and the system yielded a sensitivity of 93.67% and a specificity of 96.06%. At the event-based level, a sensitivity of 99.39% and a false detection rate of 0.64/h were obtained. Furthermore, this work showed that the CSP spatial filter was helpful to identify EEG channels involved in seizure onsets. These satisfactory results indicate that the proposed system may provide a reference for seizure onset detection in clinical applications.
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http://dx.doi.org/10.1109/TNSRE.2021.3055276DOI Listing
March 2021

A phenylalanine dynamic switch controls the interfacial activation of Rhizopus chinensis lipase.

Int J Biol Macromol 2021 Mar 18;173:1-12. Epub 2021 Jan 18.

Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, PR China. Electronic address:

The catalytic mechanism of most lipases involves a step called "interfacial activation" which significantly increases lipases activity beyond the critical micellar concentration (CMC) of substrate. In the present study, Rhizopus chinensis lipase (RCL) was used as a research model to explore the mechanism of lipase interfacial activation beyond the CMC. Molecular dynamic (MD) simulations indicated the open- and closed-lid transitions and revealed that Phe113 was the critical site for RCL activation by its dynamic flipping. Such putative switch affecting interfacial activation has not been reported in lipase so far. The function of Phe113 was subsequently verified by mutation experiments. The F113W mutant increases the lipase catalytic efficiency (1.9 s·μM) to 280% at the optimum temperature (40 °C) and pH 8.5 with the addition of 0.12 μg protein in the 200 μL reaction system. MD simulations indicated that the fast flipping rate from the closed to the open state, the high open state proportion, and the exposure of the catalytic triad are the main reasons for the lipase activation. The mutual corroboration of simulations and site-directed mutagenesis results revealed the vital role of Phe113 in the lipase activation.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.086DOI Listing
March 2021

Robust Underwater Adhesives Based on Dynamic Hydrophilic and Hydrophobic Moieties to Diverse Surfaces.

ACS Appl Mater Interfaces 2021 Jan 6;13(2):3435-3444. Epub 2021 Jan 6.

Department of Spine Surgery and Institute for Orthopaedic Research, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Jinan University Second College of Medicine, Shenzhen 518020, China.

Underwater adhesives (UAs) have promising applications in diverse areas. However, traditional UAs have several drawbacks such as weak and irreversible adhesion behaviors as well as poor performance in biological environments. To address these challenges, we engineered a novel synthetic adhesive based on dynamic hydrophilic and hydrophobic moieties, which shows very strong underwater adhesion strength (30-110 kPa) and debonding energy (20-100 J/m) to diverse substrates. Interestingly, the UAs could also be switched reversibly and repeatedly by the dynamic exchange of hydrophilic and hydrophobic moieties under alternating temperatures. We also demonstrate the versatile functions and practical value of the UAs for clinical applications as tissue sealants and hemostatic dressing in emergency rescue operations. This general and efficient strategy may be generalized to develop additional next generation UAs for many emerging technological and medical applications.
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http://dx.doi.org/10.1021/acsami.0c20186DOI Listing
January 2021

Ultrafast Parallel Micro-Gap Resistance Welding of an AuNi Microwire and Au Microlayer.

Micromachines (Basel) 2021 Jan 3;12(1). Epub 2021 Jan 3.

State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology, Harbin 150001, China.

Welding between an AuNi microwire and Au microlayer is of great importance for fabricating electrical contact structures for high precision inertial devices, satellite slip ring brushes, robots, etc. In this paper, the achievement of parallel micro-gap resistance welding (PMRW) with 200-μm AuNi microwires on a 3-μm Au layer was presented. The study on the orthogonal design of the experiment was carried out. The effect of the process parameters (welding current, welding time, and welding pressure) was discussed in reference to the morphologies and tensile force of the joint using range analysis. It is shown that too much or too little heat input will decrease the welding performance. A group of optimized process parameters (0.275 kA welding current, 3 ms welding time, and 28.7 N welding pressure) was obtained. During the welding process, the dynamic resistance of the whole welding system was measured, which can reflect the welding quality. Finite element simulation is utilized to calculate the welding temperature. The highest temperature was located in the center area of the AuNi microwire, reaching 1397.2 °C, which is higher than the melting point of AuNi. By contrast, the highest temperature for the pad was 826.47 °C (lower than the melting point of Au). Hence, under optimized process parameters, a transient interfacial reaction between the liquid AuNi microwire and solid Au pad occurred, and the strength of the welded joint reached 5.54 N.
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http://dx.doi.org/10.3390/mi12010051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824560PMC
January 2021

Microbial diversity accumulates in a downstream direction in the Three Gorges Reservoir.

J Environ Sci (China) 2021 Mar 28;101:156-167. Epub 2020 Aug 28.

CAS Key Laboratory of Environmental Biotechnology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. Electronic address:

Organic and inorganic materials migrate downstream and have important roles in regulating environmental health in the river networks. However, it remains unclear whether and how a mixture of materials (i.e., microbial species) from various upstream habitats contribute to microbial community coalescence upstream of a dam. Here we track the spatial variation in microbial abundance and diversity in the Three Gorges Reservoir based on quantitative PCR and 16S rRNA gene high-throughput sequencing data. We further quantitatively assess the relative contributions of microbial species from mainstem, its tributaries, and the surrounding riverbank soils to the area immediately upstream of the Three Gorges Dam (TGD). We found an increase of microbial diversity and the convergent microbial distribution pattern in areas immediately upstream of TGD, suggesting this area become a new confluence for microbial diversity immigrating from upstream. Indeed, the number of shared species increased from upstream to TGD but unique species decreased, indicating immigration of various sources of microbial species overwhelms local environmental conditions in structuring microbial community close to TGD. By quantifying the sources of microbial species close to TGD, we found little contribution from soils as compared to tributaries, especially for sites closer to TGD, suggesting tributary microbes have greater influence on microbial diversity and environmental health in the Three Gorges Reservoir. Collectively, our results suggest that tracking microbial geographic origin and evaluating accumulating effects of microbial diversity shed light on the ecological processes in microbial communities and provide information for regulating aquatic ecological health.
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http://dx.doi.org/10.1016/j.jes.2020.08.006DOI Listing
March 2021

Iron availability is a key factor for freshwater cyanobacterial survival against saline stress.

Environ Res 2021 03 15;194:110592. Epub 2020 Dec 15.

State Key Laboratory of Biogeosciences and Environmental Geology and Institute of Earth Sciences, China University of Geosciences, Beijing, 100083, China. Electronic address:

Estuaries are among the most productive ecosystems and dynamic environments on Earth. Varying salinity is the most important challenge for phytoplankton survival in estuaries. In order to investigate the role of iron nutrition on phytoplankton survival under salinity stress, a freshwater cyanobacterial strain was cultivated in media added with different proportions of seawater (measured with siderophore activities), and supplied with gel-immobilized ferrihydrite as iron source. Results showed that the strain grew well in media with 0% seawater supplied with ferrihydrite as iron source. Surprisingly, the biomasses in media with 50% seawater, with more newly excreted siderophore, were similar to those with 0% seawater, but better than those with 6.25%, 12.5% and 25% seawater. Smaller iron isotopic discriminations between the cyanobacterial cells associated iron and dissolved iron were observed in media with 0% and 50% seawater suggested that higher fractions of iron uptake from aqueous dissolved iron reservoir by these comparatively larger biomasses. In summary, this study proved that iron availability plays a key role in cyanobacterial survival under varying salinity stress, and suggested that siderophores introduced by seawater may accelerate iron dissolution, increase iron availability, and make cyanobacterial cells overcome the adverse effects of high-salinity, and indicated that siderophore excretion is a kind of survival strategy for phytoplankton in face of salinity stress.
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http://dx.doi.org/10.1016/j.envres.2020.110592DOI Listing
March 2021

Steeper spatial scaling patterns of subsoil microbiota are shaped by deterministic assembly process.

Mol Ecol 2021 02 26;30(4):1072-1085. Epub 2020 Dec 26.

CAS Key Laboratory for Environmental Biotechnology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences (CAS), Beijing, China.

Although many studies have investigated the spatial scaling of microbial communities living in surface soils, very little is known about the patterns within deeper strata, nor is the mechanism behind them. Here, we systematically assessed spatial scaling of prokaryotic biodiversity within three different strata (Upper: 0-20 cm, Middle: 20-40 cm, and Substratum: 40-100 cm) in a typical grassland by examining both distance-decay (DDRs) and species-area relationships (SARs), taxonomically and phylogenetically, as well as community assembly processes. Each layer exhibited significant biogeographic patterns in both DDR and SAR (p < .05), with taxonomic turnover rates higher than phylogenetic ones. Specifically, the spatial turnover rates, β and z values, respectively, ranged from 0.016 ± 0.005 to 0.023 ± 0.005 and 0.065 ± 0.002 to 0.077 ± 0.004 across soil strata, and both increased with depth. Moreover, the prokaryotic community in grassland soils assembled mainly according to deterministic rather than stochastic mechanisms. By using normalized stochasticity ratio (NST) based on null model, the relative importance of deterministic ratios increased from 48.0 to 63.3% from Upper to Substratum, meanwhile a phylogenetic based method revealed average βNTI also increased with depth, from -5.29 to 19.5. Using variation partitioning and distance approaches, both geographic distance and soil properties were found to strongly affect biodiversity structure, the proportions increasing with depth, but spatial distance was always the main underlying factor. These indicated increasingly deterministic proportions in accelerating turnover rates for spatial assembly of prokaryotic biodiversity. Our study provided new insights on biogeography in different strata, revealing importance of assembly patterns and mechanisms of prokaryote communities in below-surface soils.
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http://dx.doi.org/10.1111/mec.15777DOI Listing
February 2021

Engineering of a thermo-alkali-stable lipase from Rhizopus chinensis by rational design of a buried disulfide bond and combinatorial mutagenesis.

J Ind Microbiol Biotechnol 2020 Dec 18;47(12):1019-1030. Epub 2020 Oct 18.

Key Laboratory of Industrial Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, Jiangsu, China.

To improve the thermostability of the lipase (r27RCL) from Rhizopus chinensis through rational design, a newly introduced buried disulfide bond F223C/G247C was proved to be beneficial to thermostability. Interestingly, F223C/G247C was also found to improve the alkali tolerance of the lipase. Subsequently, six other thermostabilizing mutations from our previous work were integrated into the mutant F223C/G247C, leading to a thermo-alkali-stable mutant m32. Compared to the wild-type lipase, the associative effect of the beneficial mutations showed significant improvements on the thermostability of m32, with a 74.7-fold increase in half-life at 60 °C, a 21.2 °C higher [Formula: see text] value and a 10 °C elevation in optimum temperature. The mutated m32 was also found stable at pH 9.0-10.0. Furthermore, the molecular dynamics simulations of m32 indicated that its rigidity was enhanced due to the decreased solvent-accessible surface area, a newly formed salt bridge, and the increased ΔΔG values.
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http://dx.doi.org/10.1007/s10295-020-02324-1DOI Listing
December 2020

Toll-like receptor-2 gene knockout results in neurobehavioral dysfunctions and multiple brain structural and functional abnormalities in mice.

Brain Behav Immun 2021 01 16;91:257-266. Epub 2020 Oct 16.

Department of Neurology, Affiliated Hospital of Xuzhou Medical University, China; Institute of Neurological Diseases, Xuzhou Medical University, China. Electronic address:

Objective: Toll-like receptor-2 (TLR2), a member of TLR family, plays an important role in the induction and regulation of immune/inflammation. TLR2 gene knockout (TLR2KO) mice have been widely used for animal models of neurological diseases. Since there is close relationship between immune system and neurobehavioral functions, it is important to clarify the exact role of TLR2 defect itself in neurobehavioral functions. The present study aimed to investigate the effect of TLR2KO on neurobehavioral functions in mice and the mechanisms underlying the observed changes.

Methods: Male TLR2KO and wild type (WT) mice aged 3, 7, and 12 months were used for neurobehavioral testing and detection of protein expression by Western blot. Brain magnetic resonance imaging (MRI), electrophysiological recording, and Evans blue (EB) assay were applied to evaluate regional cerebral blood flow (rCBF), synaptic function, and blood-brain barrier (BBB) integrity in 12-month-old TLR2KO and age-matched WT mice.

Results: Compared to WT mice, TLR2KO mice showed decreased cognitive function and locomotor activity, as well as increased anxiety, which developed from middle age (before 7-month-old) to old age. In addition, significantly reduced regional cerebral blood flow (rCBF), inhibited long-term potentiation (LTP), and increased blood-brain barrier (BBB) permeability were observed in 12-month-old TLR2KO mice. Furthermore, compared with age-matched WT mice, significant reduction in protein levels of tight junction proteins (ZO-1, Occludin, and Claudin-5) and increased neurofilament protein (SMI32) were observed in 7 and 12-month-old TLR2KO mice, and that myelin basic protein (MBP) decreased in 12-month-old TLR2KO mice.

Conclusion: Our data demonstrated that TLR2 defect resulted in significantly observable neurobehavioral dysfunctions in mice starting from middle age, as well as multiple abnormalities in brain structure, function, and molecular metabolism.
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http://dx.doi.org/10.1016/j.bbi.2020.10.004DOI Listing
January 2021

Embryonic Mouse Cardiodynamic OCT Imaging.

J Cardiovasc Dev Dis 2020 Oct 4;7(4). Epub 2020 Oct 4.

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

The embryonic heart is an active and developing organ. Genetic studies in mouse models have generated great insight into normal heart development and congenital heart defects, and suggest mechanical forces such as heart contraction and blood flow to be implicated in cardiogenesis and disease. To explore this relationship and investigate the interplay between biomechanical forces and cardiac development, live dynamic cardiac imaging is essential. Cardiodynamic imaging with optical coherence tomography (OCT) is proving to be a unique approach to functional analysis of the embryonic mouse heart. Its compatibility with live culture systems, reagent-free contrast, cellular level resolution, and millimeter scale imaging depth make it capable of imaging the heart volumetrically and providing spatially resolved information on heart wall dynamics and blood flow. Here, we review the progress made in mouse embryonic cardiodynamic imaging with OCT, highlighting leaps in technology to overcome limitations in resolution and acquisition speed. We describe state-of-the-art functional OCT methods such as Doppler OCT and OCT angiography for blood flow imaging and quantification in the beating heart. As OCT is a continuously developing technology, we provide insight into the future developments of this area, toward the investigation of normal cardiogenesis and congenital heart defects.
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http://dx.doi.org/10.3390/jcdd7040042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712379PMC
October 2020

Prediction of the Age at Onset of Spinocerebellar Ataxia Type 3 with Machine Learning.

Mov Disord 2021 01 29;36(1):216-224. Epub 2020 Sep 29.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.

Background: In polyglutamine (polyQ) disease, the investigation of the prediction of a patient's age at onset (AAO) facilitates the development of disease-modifying intervention and underpins the delay of disease onset and progression. Few polyQ disease studies have evaluated AAO predicted by machine-learning algorithms and linear regression methods.

Objective: The objective of this study was to develop a machine-learning model for AAO prediction in the largest spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) population from mainland China.

Methods: In this observational study, we introduced an innovative approach by systematically comparing the performance of 7 machine-learning algorithms with linear regression to explore AAO prediction in SCA3/MJD using CAG expansions of 10 polyQ-related genes, sex, and parental origin.

Results: Similar prediction performance of testing set and training set in each models were identified and few overfitting of training data was observed. Overall, the machine-learning-based XGBoost model exhibited the most favorable performance in AAO prediction over the traditional linear regression method and other 6 machine-learning algorithms for the training set and testing set. The optimal XGBoost model achieved mean absolute error, root mean square error, and median absolute error of 5.56, 7.13, 4.15 years, respectively, in testing set 1, with mean absolute error (4.78 years), root mean square error (6.31 years), and median absolute error (3.59 years) in testing set 2.

Conclusion: Machine-learning algorithms can be used to predict AAO in patients with SCA3/MJD. The optimal XGBoost algorithm can provide a good reference for the establishment and optimization of prediction models for SCA3/MJD or other polyQ diseases. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28311DOI Listing
January 2021

Effect of increasing precipitation and warming on microbial community in Tibetan alpine steppe.

Environ Res 2020 10 18;189:109917. Epub 2020 Jul 18.

Key Laboratory of Alpine Ecology, Institute of Tibetan Plateau Research, Chinese Academy of Sciences, Beijing, 100101, China; Center for Excellence in Tibetan Plateau Earth Sciences, Chinese Academy of Sciences, Beijing, 100101, China. Electronic address:

Soil microorganisms play an important role in regulating the feedback of Alpine steppe ecosystems to future climate change. However, the interaction effect of warming and increasing precipitation on soil microorganisms remains unclear, in the face of an ongoing warmer and wetter climate on the Tibetan Plateau. In this study, we investigate the multi-factorial effects on soil microbial diversity, community structure, and microbial interactions in a three-year climate change experiment established in an Alpine steppe on the Tibetan Plateau, involving warming (+2 °C), +15% increasing precipitation and +30% increasing precipitation. Compared to warming, warming plus increasing precipitation alleviated the decrease in microbial diversity, and increased the dissimilarities in microbial community structures, largely influenced by water and substrate availability. We further observed differences in moisture increased the differences in microbial diversity and dissimilarities in microbial community structures across different precipitation levels under ambient temperature. Interestingly, warming plus increasing precipitation could create more ecological niches for microbial species to coexist but may lessen the strength of microbial interactions in contrast to increasing precipitation alone. Collectively, our findings indicate that microbial responses to future climate change in Alpine steppe soils will be more complex than those under single-climate-factor conditions.
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http://dx.doi.org/10.1016/j.envres.2020.109917DOI Listing
October 2020

Biallelic Intronic AAGGG Expansion of RFC1 is Related to Multiple System Atrophy.

Ann Neurol 2020 12 3;88(6):1132-1143. Epub 2020 Oct 3.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.

Objective: A recessive biallelic repeat expansion, (AAGGG) , in the RFC1 gene has been reported to be a frequent cause of late-onset ataxia. For cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), the recessive biallelic (AAGGG) genotype was present in ~92% of cases. This study aimed to examine whether the pentanucleotide repeat (PNR) was related to multiple system atrophy (MSA), which shares a spectrum of symptoms with CANVAS.

Methods: In this study, we screened the pathogenic (AAGGG) repeat and 5 other PNRs in 104 Chinese sporadic adult-onset ataxia of unknown aetiology (SAOA) patients, 282 MSA patients, and 203 unaffected individuals. Multiple molecular genetic tests were used, including long-range polymerase chain reaction (PCR), repeat-primed PCR (RP-PCR), Sanger sequencing, and Southern blot. Comprehensive clinical assessments were conducted, including neurological examination, neuroimaging, nerve electrophysiology, and examination of vestibular function.

Results: We identified biallelic (AAGGG) in 1 SAOA patient and 3 MSA patients. Additionally, 1 MSA patient had the (AAGGG) /(AAAGG) genotype with uncertain pathogenicity. We also described the carrier frequency for different PNRs in our cohorts. Furthermore, we summarized the distinct phenotypes of affected patients, suggesting that biallelic (AAGGG) in RFC1 could be associated with MSA and should be screened routinely in the MSA diagnostic workflow.

Interpretation: Our results expanded the clinical phenotypic spectrum of RFC1-related disorders and raised the possibility that MSA might share the same genetic background as CANVAS, which is crucial for re-evaluating the current CANVAS and MSA diagnostic criteria. ANN NEUROL 2020;88:1132-1143.
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http://dx.doi.org/10.1002/ana.25902DOI Listing
December 2020

Management of Gallstones and Acute Cholecystitis in Patients with Liver Cirrhosis: What Should We Consider When Performing Surgery?

Gut Liver 2020 Sep 15. Epub 2020 Sep 15.

Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.

Acute cholecystitis and several gallbladder stone-related conditions, such as impacted common bile duct stones, cholangitis, and biliary pancreatitis, are common medical conditions in daily practice. An early cholecystectomy or drainage procedure with delayed cholecystectomy is the current standard of treatment based on published clinical guidelines. Cirrhosis is not only a condition of chronically impaired hepatic function but also has systemic effects in patients. In cirrhotic individuals, several predisposing factors, including changes in the bile acid composition, increased nucleation of bile, and decreased motility of the gallbladder, contribute to the formation of biliary stones and the possibility of symptomatic cholelithiasis, which is an indication for surgical treatment. In addition to these predisposing factors for cholelithiasis, systemic effects and local anatomic consequences related to cirrhosis lead to anesthesiologic risks and perioperative complications in cirrhotic patients. Therefore, the treatment of the aforementioned biliary conditions in cirrhotic patients has become a challenging issue. In this review, we focus on cholecystectomy for cirrhotic patients and summarize the surgical indications, risk stratification, surgical procedures, and surgical outcomes specific to cirrhotic patients with symptomatic cholelithiasis.
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http://dx.doi.org/10.5009/gnl20052DOI Listing
September 2020

Expression and clinical significance of paired- related homeobox 1 and Smad2 in gastric cancer.

Eur J Cancer Prev 2021 Mar;30(2):154-160

Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou 730000, People's Republic of China.

Background: China has a high incidence rate and low survival rate of gastric cancer. Therefore, there is a great need to further identify novel oncogenes and clinically applicable molecular targets for the diagnosis and treatment of this disease.

Methods: Expressions of PRRX1, Smad2, epithelial phenotype marker E-cadherin, and interstitial phenotype vimentin protein in a sample of 64 gastric carcinoma and adjacent nontumorous tissues were detected by immunohistochemistry. Their relationship and correlations with clinicopathological features were analyzed.

Results: The positive rates of PRRX1, Smad2, E-cadherin, and vimentin protein in primary tumors were 60.94% (39/64), 59.38% (38/64), 34.38%(22/64), and 64.06% (41/64), respectively. A significant correlation was found among the expression of PRRX1, Smad2, E-cadherin, and vimentin (P < 0.05). Expression of the PRRX1, Smad2, and vimentin protein in gastric cancer tissue was correlated with Borrmann classification, lymph node-positive number, the degree of differentiation, depth of tumor invasion, and serum pepsinogen I (PGI) level (P < 0.05), but not with age, sex, serum carcinoembryonic antigen, serum CA199, or PGI/PGII (P > 0.05).

Conclusion: The positive rate of PRRX1 protein expression was positively correlated with the protein expression of Smad2 and vimentin, but negatively correlated with E-cadherin protein. PRRX1, Smad2, and vimentin proteins are associated with Borrmann type, lymph node positives, histologic grade, depth of tumor invasion, and serum PGI levels, all of which contribute to a poor prognosis for patients with gastric cancer.
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http://dx.doi.org/10.1097/CEJ.0000000000000619DOI Listing
March 2021

Relationship between PRRX1, circulating tumor cells, and clinicopathological parameter in patients with gastric cancer.

J BUON 2020 May-Jun;25(3):1455-1462

Department of Surgical Oncology, Gansu Province People's Hospital, Lanzhou 730000, China.

Purpose: Paired related homoeobox 1 (PRRX1) has been identified as a new epithelial-mesenchymal transition (EMT) inducer in gastric cancer and that PRRX1 upregulation is closely correlated with gastric cancer metastasis. In addition, circulating tumor cells (CTCs) play an important role in the process of gastric cancer's distant metastasis. Our study aimed to correlate Prrx1, CTCs and the clinicopathological parameters in primary gastric cancer patients.

Methods: Expressions of PRRX1 in a sample of 95 gastric carcinoma and adjacent nontumorous tissues were detected by immunohistochemistry. Then the integrated subtraction enrichment and immunostaining fluorescence in situ hybridization (SET-imFISH) platform were applied to detect and characterize CTCs in patients with gastric cancer. Finally, their correlations with clinicopathological parameters could be analyzed.

Results: The positive rate of PRRX1in gastric cancer was 56.84% and the rate was 36.84% in adjacent normal gastric mucosa, which was confirmed to be statistically significant. In the meantime, both the expression of PRRX1 and the positive rate of CTCs did not significantly correlate with age, gender or histologic type (p>0.05) but significantly related to tumor size, grade of differentiation, lymph node invasion, vascular invasion, metastasis status, depth of tumor invasion, lymph node metastasis and TNM stage (p<0.05). Besides, there was a close relationship between the PRRX1 of gastric cancer and the CTCs of peripheral blood specimens of cancer patients with the correlation coefficient 0.322.

Conclusion: Gastric cancer tissues showed that the level of PRRX1 expression was higher compared to the adjacent normal gastric mucosa. Both the expression of PRRX1 and the positive rate of CTCs significantly correlated with clinicopathological parameters. In addition, there was a positive correlation relationship between the PRRX1 of gastric cancer and the CTCs of peripheral blood specimens of cancer patients. These findings demonstrate that higher-level expression of PRRX1 in gastric cancer tissues increased the amount of CTCs in peripheral blood and facilitated the invasion and metastasis in patients with gastric cancer. Meanwhile, it gave some clues to clinical treatment. CTCs may contribute to promotion in diagnosis, therapy monitoring and prognosis of gastric cancer.
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February 2021

Live mechanistic assessment of localized cardiac pumping in mammalian tubular embryonic heart.

J Biomed Opt 2020 08;25(8):1-19

Baylor College of Medicine, United States.

Significance: Understanding how the valveless embryonic heart pumps blood is essential to elucidate biomechanical cues regulating cardiogenesis, which is important for the advancement of congenital heart defects research. However, methods capable of embryonic cardiac pumping analysis remain limited, and assessing this highly dynamic process in mammalian embryos is challenging. New approaches are critically needed to address this hurdle.

Aim: We report an imaging-based approach for functional assessment of localized pumping dynamics in the early tubular embryonic mouse heart.

Approach: Four-dimensional optical coherence tomography was used to obtain structural and Doppler hemodynamic imaging of the beating heart in live mouse embryos at embryonic day 9.25. The pumping assessment was performed based on the volumetric blood flow rate, flow resistance within the heart tube, and pressure gradient induced by heart wall movements. The relation between the blood flow, the pressure gradient, and the resistance to flow were evaluated through temporal analyses and Granger causality test.

Results: In the ventricles, our method revealed connections between the temporal profiles of pressure gradient and volumetric blood flow rate. Statistically significant causal relation from the pressure gradient to the blood flow was demonstrated. Our analysis also suggests that cardiac pumping in the early ventricles is a combination of suction and pushing. In contrast, in the outflow tract, where the conduction wave is slower than the blood flow, we did not find significant causal relation from pressure to flow, suggesting that, different from ventricular regions, the local active contraction of the outflow tract is unlikely to drive the flow in that region.

Conclusions: We present an imaging-based approach that enables localized assessment of pumping dynamics in the mouse tubular embryonic heart. This method creates a new opportunity for functional analysis of the pumping mechanism underlying the developing mammalian heart at early stages and could be useful for studying biomechanical changes in mutant embryonic hearts that model congenital heart defects.
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http://dx.doi.org/10.1117/1.JBO.25.8.086001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403774PMC
August 2020